Gây mê tại phòng mạch đã là công cụ trong sự phát triển của phẫu thuật ngoại trú. Các bác sĩ phẫu thuật răng hàm mặt nói riêng đã tối đa hóa lợi ích của phương pháp gây mê tại phòng mạch và đã đóng góp rất nhiều vào sự phát triển của nó. Các thủ tục phẫu thuật có thể được thực hiện tại văn phòng thay vì ở bệnh viện hoặc trung tâm phẫu thuật, điều này làm giảm nhu cầu về tài chính và thời gian cho bệnh nhân. Tương tự như vậy, chi phí gây mê tại phòng mạch thấp hơn đáng kể so với gây mê trong phòng mổ. Việc tuân thủ điều trị nha khoa ở cả trẻ em và người lớn có thể tăng lên đáng kể khi sử dụng phương pháp gây mê tĩnh mạch, giúp cải thiện sức khỏe răng miệng tổng thể của dân số nói chung. Các bác sĩ phẫu thuật răng hàm mặt đã là những người tiên phong trong việc gây mê tại phòng mạch. Nền tảng của họ về y học nội khoa và gây mê có được trong quá trình đào tạo nội trú khiến họ có đủ điều kiện duy nhất để tiến hành gây mê và thực hiện các thủ thuật phẫu thuật đồng thời. Từ những năm 2000 đến 2014, các bác sĩ phẫu thuật miệng được Công ty Bảo hiểm Quốc gia về Phẫu thuật Răng miệng và Răng hàm mặt (OMSNIC) chi trả đã thực hiện gây mê tại phòng mạch 42.792.419 lần. Trung bình, con số này tương đương với 666 lần quản lý cho mỗi bác sĩ phẫu thuật răng miệng mỗi năm. Trong số những lần sử dụng đó, 415 khiếu nại liên quan đến gây mê đã được báo cáo cho OMSNIC, bao gồm 121 trường hợp tử vong, tương đương với 1 trường hợp tử vong trong mỗi 353.657 lần sử dụng thuốc. Biên độ an toàn được các bác sĩ phẫu thuật răng miệng thiết lập trong việc sử dụng thuốc gây mê tại phòng mạch phần lớn có thể là do các nhà cung cấp nỗ lực thu thập và duy trì kiến thức chuyên sâu trong lĩnh vực y học và gây mê, đảm bảo lựa chọn bệnh nhân thận trọng và sử dụng thuốc gây mê tại phòng khám an toàn và hiệu quả kỹ thuật. Mục tiêu của cuốn sách này là hỗ trợ các nhà cung cấp duy trì nền tảng kiến thức của họ và lựa chọn đúng cách những bệnh nhân có thể gây mê an toàn trong môi trường văn phòng. Mỗi khi gặp bệnh nhân, nhà cung cấp dịch vụ phải có khả năng trả lời một loạt các câu hỏi: 1. Việc gây mê cho bệnh nhân này có thích hợp khi mắc các bệnh kèm theo không? Tại sao hoặc tại sao không? 2. Nếu bệnh nhân là một ứng cử viên sáng giá cho phương pháp gây mê tại phòng mạch, những nguyên tắc nào cần được xem xét trong quản lý chu phẫu bệnh nhân và sử dụng thuốc gây mê, dựa trên các bệnh đi kèm của bệnh nhân? 3. Nếu không có đầy đủ thông tin tại thời điểm tham vấn, cần thu thập thêm thông tin nào? Điều gì tạo nên công việc thích hợp cho các tình trạng bệnh đi kèm cụ thể? Những câu hỏi này, khi được cân nhắc và quan sát, là rất quan trọng trong việc đảm bảo việc sử dụng thuốc gây mê tại phòng mạch an toàn, hiệu quả và tránh các kết quả và biến chứng bất lợi không lường trước được. Cuốn sách này được tổ chức thành ba phần. Phần I bao gồm việc xem xét các nguyên tắc gây mê, bao gồm dược lý của các thuốc gây mê thường được sử dụng tại phòng khám, theo dõi bệnh nhân, đánh giá trước phẫu thuật, đường thở, gây tê tại chỗ, giảm đau và sử dụng kháng sinh hiệu quả. Phần II bao gồm các hệ thống cơ quan chính của cơ thể. Đối với mỗi hệ thống, một đánh giá ngắn gọn về giải phẫu và sinh lý học bình thường được đưa ra. Một số tình trạng bệnh đi kèm phổ biến ảnh hưởng đến các hệ thống này được xem xét, bao gồm cả sinh lý bệnh, chẩn đoán, xử trí và các cân nhắc liên quan đến gây mê. Mỗi chương, hoặc hệ thống cơ quan, có một trang bìa dạng tab để tham khảo nhanh. Trang bìa này liệt kê nội dung của chương và bao gồm các điều kiện đi kèm được thảo luận trong chương, với số trang. Phần III xem xét các nhóm bệnh nhân cần được xem xét đặc biệt trong việc sử dụng thuốc gây mê tại phòng khám. Các phụ lục bao gồm tài liệu thường xuyên được tham chiếu. Phụ lục A là một chỉ số thuốc tổng hợp phác thảo các nhóm thuốc thường được kê đơn để điều trị các bệnh kèm theo được thảo luận trong cuốn sách. Chỉ số này bao gồm các nhóm thuốc, cơ chế hoạt động, ví dụ về các loại thuốc thường được sử dụng trong nhóm, tác dụng phụ và những cân nhắc liên quan đến gây mê. Phụ lục B liệt kê các loại thuốc gây mê tại văn phòng thường được sử dụng và liều lượng điển hình của chúng. Cuối cùng, hỗ trợ sự sống cơ bản, hỗ trợ sự sống nâng cao về tim mạch và các thuật toán hỗ trợ sự sống nâng cao dành cho trẻ em được đưa vào Phụ lục C để tham khảo nhanh. Cuốn sách này không phải là sách giáo khoa chính. Các tác giả cho rằng tài liệu được tìm thấy ở đây là một bài đánh giá. Nó được dùng như một tài liệu tham khảo nhanh khi gặp bệnh nhân và những nguyên tắc này cần được xem xét lại. Ngoài ra, cuốn sách này không phải là một tài liệu tham khảo toàn diện. Nó không bao gồm mọi bệnh tật ảnh hưởng đến cơ thể con người. Thay vào đó, nó xem xét các điều kiện thường gặp. Bởi vì con người đang sống lâu hơn, với nhiều bệnh đi kèm hơn, việc sử dụng thuốc gây mê tại phòng mạch trở nên phức tạp hơn. Trọng tâm của cuốn sách này là hướng dẫn các học viên dọc theo cây quyết định khi họ gặp phải một bóng ma rộng
Anesthesia Considerations for the Oral and Maxillofacial Surgeon www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM ANESTHESIA CONSIDERATIONS for the Oral and Maxillofacial Surgeon Edited by Matthew Mizukawa, dmd Assistant Clinical Professor Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Private Practice Limited to Oral and Maxillofacial Surgery St George, Utah Samuel J McKenna, dds, md Professor and Chair Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Luis G Vega, dds Associate Professor and Residency Program Director Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Berlin, Barcelona, Chicago, Istanbul, London, Milan, Moscow, New Delhi, Paris, Prague, Sao Paulo, Seoul, Singapore, Tokyo, Warsaw www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM Library of Congress Cataloging-in-Publication Data Names: Mizukawa, Matthew, editor | McKenna, Samuel J., editor | Vega, Luis G., editor Title: Anesthesia considerations for the oral and maxillofacial surgeon / edited by Matthew Mizukawa, Samuel McKenna, Luis Vega Description: Hanover Park, IL : Quintessence Publishing Co Inc., [2017] | Includes bibliographical references and index Identifiers: LCCN 2017006580 (print) | LCCN 2017008471 (ebook) | ISBN 9780867157130 (spiral bound) | ISBN 9780867157581 () Subjects: | MESH: Oral Surgical Procedures | Anesthesia | Ambulatory Surgical Procedures | Intraoperative Complications prevention & control | Postoperative Complications prevention & control Classification: LCC RK510 (print) | LCC RK510 (ebook) | NLM WU 600 | DDC 617.9/676 dc23 LC record available at https://lccn.loc.gov/2017006580 97% © 2017 Quintessence Publishing Co, Inc Quintessence Publishing Co, Inc 4350 Chandler Drive Hanover Park, IL 60133 www.quintpub.com All rights reserved This book or any part thereof may not be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, or otherwise, without prior written permission of the publisher Editor: Bryn Grisham Design: Erica Neumann Production: Kaye Clemens Printed in China www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM CONTENTS Dedications viii reface ix P Contributors xi SECTION I: PRINCIPLES OF ANESTHESIA ADMINISTRATION 1 Basic Principles of Anesthesia 3 Patrick J Louis, Pamela J Sims, and Matthew Mizukawa 2 Pharmacology and Utility of Intravenous Anesthesia 15 Matthew Mizukawa 3 Pharmacology and Utility of Inhalation Anesthesia 31 Charles H Kates 4 Local Anesthesia Basics 39 James Bradford Lewallen, Paul G Sims, and Matthew Mizukawa 5 Prophylactic and Perioperative Antibiotics 49 Rick Shamo and David Shafer 6 Analgesia Considerations in Anesthesia 63 Sean M Young and H Daniel Clark 7 Postoperative Nausea and Vomiting 71 Danielle L Cruthirds, Pamela J Sims, and Patrick J Louis 8 Monitoring the Patient 81 Timothy M Orr and Matthew Mizukawa 9 Electrocardiography 91 Andrew E Wicke, Erik J Nielsen, and Scott Hoffman 10 Pre-anesthetic Patient Evaluation 113 Charles H Kates and Matthew Mizukawa 11 Management of Airway Urgencies and Emergencies 125 Luis G Vega, Paul Hinchey, Matthew Mizukawa, and Samuel J McKenna 12 Medical Emergencies 147 Samuel J McKenna and Nicholas Piemontesi 13 Aftermath of an Adverse Outcome or Complication 165 Lewis Estabrooks www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM SECTION II: ANESTHESIA AND COMORBID DISEASE 14 The Central Nervous System 175 Casey R Shepherd and Daniel L Orr II 15 The Cardiovascular System 197 Prem B Patel and Helen E Giannakopoulos 16 The Pulmonary System 219 Ravi Agarwal and George Obeid 17 The Digestive System 237 Ben Bailey and Jasjit K Dillon 18 The Renal System 251 Paul Hinchey and Luis G Vega 19 The Hepatic System 263 Emily King and Stuart Lieblich 20 The Endocrine System 277 Erica L Shook, A Thomas Indresano, and Matthew Mizukawa 21 The Musculoskeletal System 303 Andrew Cheung, Matthew Mizukawa, Lindsey Nagy, Travis Witherington, and Joshua Campbell 22 The Immune System 317 Steven Zambrano and Leslie R Halpern SECTION III: ANESTHESIA IN SPECIAL PATIENT GROUPS 23 Hematopathology and Coagulopathy 331 Robbie J Harris III, Matthew Mizukawa, and John Mizukawa 24 Malignancy 351 Matthew Myers, Gregory Romney, and Sudheer J Surpure 25 Geriatrics 361 Wayne H Dudley and Ryan M Dudley 26 Special Needs Populations 367 Pamela J Hughes and Mae Hyre 27 Pediatric Considerations 375 Brent DeLong, Adam S Pitts, and Matthew Mizukawa 28 Pregnancy 387 Steven I Kaltman and Trevor Johnson 29 Obesity and Obstructive Sleep Apnea 399 Salam O Salman and Jeffrey Dembo 30 Considerations for the Substance Abuse Patient 407 Julie Ann Smith www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM APPENDICES A Comprehensive Drug Index 421 A1 Addiction Aids 422 A2 α-Adrenergics 422 A3 Analgesics 422 A4 Antihypertensives 423 A5 Antidiabetics 425 A6 Antiasthmatics 426 A7 Anorexigenics 427 A8 Antiarrhythmics 427 A9 Anticholinesterase Inhibitors 428 A10 Muscle Relaxants 428 A11 Herbals 428 A12 Parkinson Disease Drugs 429 A13 GERD Drugs 429 A14 Thyroid Drugs 430 A15 CNS Stimulants 430 A16 CNS Depressants 430 A17 Heme-Related Agents 431 A18 Antiepileptics 432 A19 Antidepressants 435 A20 Antihistamines 436 A21 Vasopressors 436 A22 Antiemetics 438 B Commonly Used Drugs and Doses 439 C Algorithms 443 C1 Algorithm for Adult Cardiac Arrest 444 C2 Algorithm for Pediatric Cardiac Arrest 445 C3 Algorithm for Adult Bradycardia With a Pulse 446 C4 Algorithm for Pediatric Bradycardia With a Pulse and Poor Perfusion 447 C5 Algorithm for Adult Tachycardia With a Pulse 448 C6 Algorithm for Pediatric Tachycardia With a Pulse and Poor Perfusion 449 Index 451 www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM DEDICATIONS My deepest gratitude and love to my wife, Julie, and my children for supporting me in this project and sacrificing their time with me Thanks to my parents, John and Elaine, for raising me to reach for the stars Sincere recognition of my complete dependence on an Almighty God, who sustains me from day to day MM To Elaine, Will, and Anna, who have supported my career and the many nights and weekends in the hospital or at my desk Thank you for your unwavering love and support To the many Vanderbilt oral and maxillofacial surgery residents who have been an inspiration and a part of my life that I will always cherish SJM I want to thank my wife, Marina Without her unconditional support, my world would stop To my daughters, Eva and Elena, thanks for filling my life with love and laughter Drs Mizukawa and McKenna, your dedication and endless work have been the true fuel that has carried this project to fruition Thank you for allowing me to work with you Finally to my past, present, and future residents, this book is for you Thanks for your companionship during so many “surgical battles,” but more importantly, thank you for pushing me to be the best teacher I could be LGV viii www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM PREFACE Office-based anesthesia has been instrumental in the evolution of outpatient surgery Oral and maxillofacial surgeons in particular have maximized the benefits of office-based anesthesia and have contributed greatly to its evolution Surgical procedures can be performed in the office rather than in a hospital or surgical center, which reduces the financial and time demands on the patient Likewise, the cost of anesthesia administered in the office is considerably lower than that of anesthesia administered in an operating room Compliance with dental treatment in both the pediatric and adult populations can be substantially increased when intravenous anesthesia is utilized, which improves the overall dental health of the general population Oral and maxillofacial surgeons have been pioneers in office-based anesthesia administration Their background in internal medicine and anesthesia acquired during residency training makes them uniquely qualified to administer anesthesia and perform surgical procedures simultaneously Between the years 2000 and 2014, oral surgeons covered by the Oral and Maxillofacial Surgery National Insurance Company (OMSNIC) administered office-based anesthesia 42,792,419 times On average, this number equates to 666 administrations per oral surgeon per year Of those administrations, 415 anesthesia-related claims were reported to OMSNIC, including 121 deaths, which is equivalent to death in every 353,657 administrations The margin of safety established by oral surgeons in administering office-based anesthesia can largely be attributed to providers’ efforts to obtain and maintain deep knowledge in the fields of medicine and anesthesia, ensure prudent patient selection, and use safe and effective office-based anesthesia techniques The objective of this book is to assist providers in maintaining their knowledge base and properly selecting patients who can safely undergo anesthesia in the office setting Every time a patient is encountered, the provider must be able to answer a sequence of questions: Is it appropriate to anesthetize this patient in light of any comorbid diseases? Why or why not? If the patient is a good candidate for office-based anesthesia, what principles should be considered in the perioperative management of the patient and the administration of the anesthetic agent, in light of the patient’s comorbidities? If sufficient information is not available at the time of consultation, what additional information should be gathered? What constitutes the proper workup for specific comorbid conditions? These questions, when considered and observed, are critical in ensuring the safe, effective administration of office-based anesthesia and avoiding unforeseen adverse outcomes and complications This book is organized into three sections Section I contains a review of the principles of anesthesia, including the pharmacology of commonly used office-based anesthetic ix www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM agents, monitoring of the patient, preoperative evaluation, the airway, local anesthesia, analgesia, and effective use of antibiotics Section II comprises the major organ systems of the body For each system, a brief review of the normal anatomy and physiology is given Some common comorbid conditions that affect these systems are reviewed, including pathophysiology, diagnosis, management, and anesthesia-related considerations Each chapter, or organ system, has a tabbed cover page for quick reference This cover page lists the contents of the chapter and includes the comorbid conditions discussed in the chapter, with page numbers Section III reviews patient groups that warrant special consideration in the administration of office-based anesthesia The appendices cover frequently referenced material Appendix A is a comprehensive drug index that outlines the drug classes commonly prescribed to treat the comorbid diseases discussed in the book This index includes the drug classes, mechanisms of action, examples of commonly used drugs in the class, side effects, and anesthesia-related considerations Appendix B lists commonly used office-based anesthesia drugs and their typical dosages Finally, basic life support, advanced cardiovascular life support, and pediatric advanced life support algorithms are included in Appendix C for quick reference This book is not a primary textbook The authors presume that the material found herein is a review It is meant to serve as a quick reference when patients are encountered and these principles need review Also, this book is not a comprehensive reference It does not include every disease that affects the human body Rather, it reviews conditions that are commonly encountered Because humans are living longer, with more comorbid diseases, office-based anesthesia administration has become more complex The focus of this book is to guide practitioners along the decision tree as they encounter a wide spectrum of ages, diseases, and conditions and to strengthen the margin of safety of office-based anesthesia administration x www.ajlobby.com Mizukawa_FM.indd 10 6/22/17 10:15 AM CONTRIBUTORS Ravi Agarwal, dds Brent DeLong, dds Residency Program Director Department of Oral and Maxillofacial Surgery MedStar Washington Hospital Center Washington, District of Columbia Clinical Professor Department of Oral and Maxillofacial Surgery San Antonio Military Medical Center Wilford Hall Ambulatory Surgery Center Lackland Air Force Base San Antonio, Texas Ben Bailey, dmd Chief Resident Department of Oral and Maxillofacial Surgery School of Dentistry University of Washington Seattle, Washington Jeffrey Dembo, dds, ms Professor Emeritus Department of Oral and Maxillofacial Surgery College of Dentistry University of Kentucky Lexington, Kentucky Joshua Campbell, dds Assistant Professor Department of Oral and Maxillofacial Surgery University of Tennessee Medical Center Knoxville, Tennessee Jasjit K Dillon, dds, md, bds, fdsrcs Clinical Associate Professor Department of Oral and Maxillofacial Surgery School of Dentistry University of Washington Acting Chief of Service and Program Director Oral and Maxillofacial Surgery Clinic Harborview Medical Center Seattle, Washington Andrew Cheung, dds Gratis Clinical Assistant Professor Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Guest Lecturer Department of Oral and Maxillofacial Surgery Department of Hospital and General Dentistry University of Tennessee Medical Center Knoxville, Tennessee Private Practice Limited to Oral and Maxillofacial Surgery Oak Ridge and Crossville, Tennessee Ryan M Dudley, md Resident, Internal Medicine School of Medicine University of Nevada, Las Vegas Las Vegas, Nevada Wayne H Dudley, dds Private Practice Limited to Oral and Maxillofacial Surgery St George, Utah H Daniel Clark, dds, md Private Practice Limited to Oral and Maxillofacial Surgery Franklin, Tennessee Lewis Estabrooks, dmd, ms Associate Clinical Professor Department of Oral and Maxillofacial Surgery School of Dental Medicine Tufts University Boston, Massachusetts Danielle L Cruthirds, phd Associate Professor of Pharmaceutical Sciences Department of Pharmaceutical, Social and Administrative Sciences McWhorter School of Pharmacy Samford University Birmingham, Alabama xi www.ajlobby.com Mizukawa_FM.indd 11 6/22/17 10:15 AM Helen E Giannakopoulos, dds, md A Thomas Indresano, dmd Associate Professor of Oral and Maxillofacial Surgery/Pharmacology Director, Postdoctoral Oral and Maxillofacial Surgery Residency Program Penn Dental Medicine University of Pennsylvania Philadelphia, Pennsylvania Dr T Galt and Lee Dehaven Atwood Professor and Chair Department of Oral and Maxillofacial Surgery University of the Pacific Arthur A Dugoni School of Dentistry San Francisco, California Leslie R Halpern, md, dds, phd, mph Chief Resident Department of Surgery Department of Oral and Maxillofacial Surgery College of Dental Medicine Nova Southeastern University Broward Health Medical Center Fort Lauderdale, Florida Trevor Johnson, dmd Associate Professor, Program Director Department of Oral and Maxillofacial Surgery School of Dentistry Meharry Medical College Nashville, Tennessee Robbie J Harris III, dds Private Practice Limited to Oral and Maxillofacial Surgery Paducah, Kentucky Steven I Kaltman, dmd, md Professor and Chairman Department of Oral and Maxillofacial Surgery Dean of Hospital and Extramural Affairs College of Dental Medicine Nova Southeastern University Fort Lauderdale, Florida Paul Hinchey, dmd, md Resident Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Charles H Kates, dds, pa Clinical Associate Professor of Clinical Anesthesiology Clinical Associate Professor of Surgery Miller School of Medicine University of Miami Director of Anesthesia and Pain Management Division of Oral and Maxillofacial Surgery and Dentistry Department of Surgery University of Miami at Jackson Memorial Hospital Miami, Florida Private Practice Limited to Oral and Maxillofacial Surgery and Anesthesiology Aventura, Florida Scott Hoffman, md Retired Professor of Clinical Anesthesiology Department of Anesthesiology Vanderbilt University School of Medicine Vanderbilt University Hospital Nashville, Tennessee Pamela J Hughes, dds Associate Professor and Chair Department of Oral and Maxillofacial Surgery School of Dentistry Oregon Health & Science University Portland, Oregon Mae Hyre, dmd, md Emily King, dmd Oral and Maxillofacial Surgeon Facial Surgery Center Charleston Area Medical Center Private Practice Limited to Oral and Maxillofacial Surgery Charleston, West Virginia Resident Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee James Bradford Lewallen, dds, md, msc Private Practice Limited to Oral and Maxillofacial Surgery Franklin, Tennessee xii www.ajlobby.com Mizukawa_FM.indd 12 6/22/17 10:15 AM Stuart Lieblich, dmd Erik J Nielsen, dds Clinical Professor Division of Oral and Maxillofacial Surgery School of Dental Medicine University of Connecticut Farmington, Connecticut Private Practice Limited to Oral and Maxillofacial Surgery Avon, Connecticut Resident Department of Oral and Maxillofacial Surgery and Dentistry Vanderbilt University School of Medicine Nashville, Tennessee George Obeid, dds Chairman Department of Oral and Maxillofacial Surgery MedStar Washington Hospital Center Washington, District of Columbia Patrick J Louis, dds, md Professor and Residency Training Program Director Department of Oral and Maxillofacial Surgery School of Dentistry University of Alabama at Birmingham Birmingham, Alabama Daniel L Orr II, dds, ms (Anesthesiology), phd, jd, md Professor and Director of Oral and Maxillofacial Surgery and Anesthesiology School of Dental Medicine University of Nevada, Las Vegas Las Vegas, Nevada Clinical Professor of Surgery and Anesthesiology School of Medicine University of Nevada, Reno Reno, Nevada Samuel J McKenna, dds, md Professor and Chair Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee John Mizukawa, dds Timothy M Orr, dmd Chief Resident Department of Oral and Maxillofacial Surgery and Dentistry Vanderbilt University School of Medicine Nashville, Tennessee Anesthesiologist Austin, Texas Prem B Patel, dmd, md Private Practice Limited to Oral and Maxillofacial Surgery Chicago, Illinois Matthew Mizukawa, dmd Assistant Clinical Professor Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Private Practice Limited to Oral and Maxillofacial Surgery St George, Utah Nicholas Piemontesi, dmd, md Resident Department of Oral and Maxillofacial Surgery and Dentistry Vanderbilt University School of Medicine Nashville, Tennessee Matthew Myers, dmd Adam S Pitts, dds, md Chief Resident Department of Oral and Maxillofacial Surgery Banner University Medical Center University of Arizona College of Medicine Phoenix, Arizona Chairman, Department of Oral and Maxillofacial Surgery Tristar Centennial Medical Center Clinical Instructor Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Private Practice Limited to Oral and Maxillofacial Surgery Nashville, Tennessee Lindsey Nagy, dds Private Practice Limited to Oral and Maxillofacial Surgery Oak Ridge, Tennessee xiii www.ajlobby.com Mizukawa_FM.indd 13 6/22/17 10:15 AM Gregory Romney, dmd Julie Ann Smith, dds, md, mcr Private Practice Limited to Oral and Maxillofacial Surgery Mesa, Arizona Private Practice Limited to Oral and Maxillofacial Surgery Portland, Oregon Salam O Salman, md, dds Sudheer J Surpure, md, dds Associate Program Director and Assistant Professor Department of Oral and Maxillofacial Surgery College of Medicine University of Florida, Jacksonville Jacksonville, Florida Chief, Division of Oral and Maxillofacial Surgery Director, Oral and Maxillofacial Surgery Residency Program Oral and Maxillofacial Surgery Center Banner—University Medical Center Phoenix Clinical Assistant Professor Division of Oral and Maxillofacial Surgery Department of Surgery College of Medicine—Phoenix University of Arizona Phoenix, Arizona David Shafer, dmd Associate Professor, Chair, and Residency Program Director Department of Oral and Maxillofacial Surgery University of Connecticut School of Dental Medicine Farmington, Connecticut Luis G Vega, dds Associate Professor and Residency Program Director Department of Oral and Maxillofacial Surgery Vanderbilt University Medical Center Nashville, Tennessee Rick Shamo, dds, md Director of Oral and Maxillofacial Surgery Memorial Hospital of Sweetwater County Rock Springs, Wyoming Andrew E Wicke, dmd Casey R Shepherd, dmd, md Chief Resident Department of Oral and Maxillofacial Surgery and Dentistry Vanderbilt University School of Medicine Nashville, Tennessee Private Practice Limited to Oral and Maxillofacial Surgery Kalispell, Montana Erica L Shook, dds Maxillofacial Surgeon Kaiser Permanente Hospital Oakland Medical Center Oakland, California Travis Witherington, dds Pamela J Sims, pharmd, phd Sean M Young, dds, md Private Practice Limited to Oral and Maxillofacial Surgery Oak Ridge, Tennessee Professor of Pharmaceutical Sciences Department of Pharmaceutical, Social and Administrative Sciences McWhorter School of Pharmacy Samford University Birmingham, Alabama Private Practice Limited to Oral and Maxillofacial Surgery Franklin, Tennessee Steven Zambrano, dds Private Practice Limited to Oral and Maxillofacial Surgery Cordova, Tennessee Paul G Sims, dds Private Practice Limited to Oral and Maxillofacial Surgery Butte, Montana xiv www.ajlobby.com Mizukawa_FM.indd 14 6/22/17 10:15 AM I SECTION I SECTION PRINCIPLES OF ANESTHESIA ADMINISTRATION www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 7/17/17 12:25 PM SECTION I SECTION X SECTION X SECTION X www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 7/17/17 12:25 PM CHAPTER Basic Principles of Anesthesia Patrick J Louis, dds, md Pamela J Sims, pharmd, phd Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia The pharmacologic effects of drugs are determined by pharmacokinetic and pharmacodynamic principles Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of the drug Pharmacodynamics describes the interaction of the drug with the target receptor and the subsequent effect on an organ, tissue, or system Understanding the pharmacokinetic and pharmacodynamic properties of each anesthetic agent is essential to predict the patient’s response Pharmacokinetics When a drug is administered to a patient to produce a systemic effect, the drug undergoes four pharmacokinetic processes: absorption, distribution, metabolism, and excretion Absorption is the process of movement of the drug from the site of administration into the bloodstream Although many routes of administration are available, common routes utilized in office-based anesthesia include intravenous, oral, intramuscular, intraosseous, transmucosal, transcutaneous, inhaled, and intranasal If the drug is administered intravenously (directly into the bloodstream), the process of absorption and its potential variability is avoided Drugs administered by other routes of administration must be absorbed from the site of administration into the bloodstream Most drug absorption occurs by passive diffusion based on Fick’s law of diffusion: Flux = [K × A × D × (C1 − C2)] h where K is the partition coefficient; A, the surface area (diffusional area); D, the diffusion coefficient; C1, the extracellular concentration; C2, the intracellular concentration; and h, the thickness of the membrane (diffusional distance) Lipophilic drugs in their un-ionized form generally have higher partition and diffusion coefficients, which favors absorption Blood flow away from the absorption site maintains the concentration gradient and promotes drug absorption Thinner, well-perfused membranes (eg, vascular mucosa) favor absorption Additionally, the greater the surface area to which the drug is administered or exposed, the more absorption will occur The bioavailability of a drug, or the fraction of the dose administered that reaches systemic circulation, can vary among the nonintravenous routes of administration For example, when a drug is administered orally, only a fraction of the initial dose may survive the acid and digestive enzymes of the stomach and/or the first-pass metabolism across the gastric mucosa and the portal circulation from the duodenum through the liver Consequently, only a portion of the initial dose administered may reach the central nervous system to elicit an effect An advantage of oral dosing, however, is the ease of administration compared with more invasive routes, such as intramuscular, intraosseous, and intravenous Intramuscular administration and intraosseous administration are efficient because exposure of a drug to well-perfused muscle and bone tissue results in rapid absorption into the venous circulation These routes also avoid initial metabolism of the drug in the digestive system, so smaller doses are often required to achieve the same effect than would be required with oral administration Bronchial inhaled administration is rapid When drug is inhaled, it is absorbed into the pulmonary venous circulation and then transported to the left heart and subsequently to the systemic circulation, including the central nervous system Three main factors affect absorption of gases into the blood: relative solubility of the drug in blood and gas, cardiac output, and the gradient of alveolar partial pressure to venous partial pressure Solubility of the anesthetic agent is determined by the blood/gas partition coefficient This coefficient indicates the relative capacity of blood and gas to hold the drug For example, isoflurane has a blood/gas coefficient of 1.4, which means that, at equilibrium, blood holds 1.4 times the amount of isoflurane that gas does Desflurane has a blood/gas coefficient of 0.45, which means that, at equilibrium, more of the drug stays in the alveoli in the gas phase than enters the blood Cardiac output, defined as the product of heart rate and stroke volume, describes the movement of blood through the circulation Cardiac output is required to push blood through the pulmonary circulation to maintain the gradient of partial pressure required for absorption The more blood that passes through the pulmonary circulation, the more drug can be absorbed and carried back to the heart If stasis of blood occurs in the pulmonary circulation, the blood will become saturated and unable to absorb any more of the drug www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM Pharmacokinetics The gradient of alveolar and venous partial pressures of the drug also affects absorption This gradient is driven by delivery and unloading of the drug in brain, muscle, fat, and other tissues, creating a pressure difference Tissue uptake of the anesthetic agent is essential in creating this gradient Distribution describes the movement of a drug to and from the bloodstream and extravascular sites For most drugs, the site of action is outside the bloodstream For the drug to reach the site of action and elicit a pharmacologic response, it must distribute from the bloodstream through the capillary and other phospholipid bilayer membranes to the target tissue or organ Factors that influence distribution and extravascular migration of the drug include the size of the drug molecule, the degree of protein binding, the lipophilicity of the drug, and the pKa of the drug Drug molecules with small molecular weight generally diffuse passively across most biologic membranes Because general anesthetics, sedatives, and opioid analgesics elicit their pharmacologic effect in the central nervous system, they must penetrate the tight junctions of the highly lipophilic blood-brain barrier Small drug molecules that can squeeze between the tight junctions of blood vessels and the blood-brain barrier diffuse more readily into the central nervous system than larger drug molecules The binding of drugs to plasma proteins, such as albumin or α1-acid glycoprotein, limits drug distribution because of the size of the protein-drug complex In the case of drugs with lower protein binding, or as the protein binding of a drug decreases because of lower protein concentrations or displacement by other protein-bound drugs, a higher concentration of free drug is available to distribute extravascularly to peripheral sites Because the concentration of plasma proteins influences distribution, many elderly patients who have decreased serum protein concentrations can have increased free drug concentrations; therefore, for a drug to achieve the same effect in these patients as it would have in younger adult patients, a markedly lower dose may be required Lipophilicity, described by the octanol/water partition coefficient, promotes the movement of a drug across membranes, particularly lipophilic barriers, such as the blood-brain barrier Lipophilic drugs have a high affinity for fatty tissue, into which they distribute more slowly than they into highly perfused organs and tissues This high affinity for and slower distribution into fat creates a drug reservoir that results in redistribution of the drug into and out of the blood and central nervous system over time, which can prolong the drug’s action As determined by the Henderson-Hasselbalch equation, drugs in the un-ionized form favor movement across membranes Because many general anesthetic agents are basic, a pKa below or approaching 7.4 means that more of the drug will be un-ionized at physiologic pH For the barbiturate anesthetics and propofol, which are acidic, a pKa above or approaching 7.4 means that more of the drug will be un-ionized at physiologic pH Pharmacokinetic models view the body as compartments in relationship to the bloodstream The bloodstream and the organs and tissues that are immediately perfused are considered the central compartment The tissues and organs into which drugs distribute more slowly are considered peripheral compartments (Fig 1-1) In the two-compartment model, the distribution of drug to and from the blood and perfused tissues and organs results in a rapid decline in concentration in the bloodstream in the distribution phase, followed by a slower decline in drug concentration in the bloodstream caused by metabolism and excretion of the drug (the elimination phase) In the two-compartment model, the half-life of the drug in the distribution phase, α, is always much shorter than the half-life in the elimination phase, β, and is generally more predictive of the duration of the drug’s effects in the perfused organs, such as the central nervous system For drugs that subsequently distribute into less well-perfused tissues or organs, such as muscle or fat, the deeper peripheral compartment may be considered a third compartment Distribution of the drug into and out of this deeper peripheral compartment frequently creates a drug reservoir that can result in prolonged redistribution and effect of the drug The extent of distribution of the drug from the bloodstream to extravascular sites is described by the apparent volume of distribution, Vd Therefore, lipophilic drugs with a higher Vd are more extensively distributed outside the bloodstream than hydrophilic drugs with a smaller Vd are Because Vd is directly related to half-life, drugs with a larger Vd have a longer half-life, described in the equation t½ = 0.693Vd / Cl www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia ABSORPTION Drug administration P450 EXCRETION METABOLISM DISTRIBUTION Intravenous Fig 1-1 Diagram depicting the pharmacokinetic jour- ney of drugs from their site of administration to their ultimate clearance from the body Metabolism describes the conversion of active drug to inactive metabolites that can be excreted from the body Although some drugs are metabolized outside the liver, drug clearance is generally accomplished primarily by means of biotransformation or metabolism in the liver and excretion by the kidneys and to a lesser degree in bile The primary purpose of hepatic biotransformation is to produce polar metabolites that can be excreted by the kidneys Because general anesthetic agents, sedatives, and opioid analgesics are lipophilic molecules, they must be metabolized by the liver and undergo biotransformation into water-soluble metabolites that can be excreted by the kidneys or in bile Hepatic metabolic processes are classified as phase I or phase II Phase I consists of oxidative/reductive metabolic processes that generally produce polar metabolites that are excreted by the kidneys Cytochrome P450 enzymes, the largest group of phase I enzymes, are susceptible to induction and inhibition drug interactions, and their function decreases with aging Phase II consists of conjugative metabolic processes that are generally employed when phase I metabolism does not produce sufficiently polar metabolites Of the phase II processes, glucuronidation is of greatest relevance to the metabolism of general anesthetic agents, sedatives, and opioid analgesics because glucuronide metabolites often undergo biliary excretion and subsequently are enterohepatically recirculated from the gastrointestinal tract into the bloodstream Enterohepatic recirculation of glucuronide metabolites occurs when gastrointestinal flora cleave the glucuronide conjugate from the drug or drug metabolite molecule and the active drug or drug metabolite is reabsorbed from the gastrointestinal tract through the hepatic portal vein into systemic circulation The processes of enterohepatic recirculation of glucuronide metabolites and the redistribution of lipophilic drugs into and out of the central nervous system contribute to the variable and prolonged effects of several general anesthetic agents, sedatives, and opioid analgesics Renal excretion of polar metabolites of general anesthetic agents, sedatives, and opioid analgesics generally has little impact on their effect in patients If a renally excreted metabolite has pharmacologic activity, alterations in renal function can result in adverse effects www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM Pharmacokinetics Considerations of inhaled anesthetics For inhaled anesthetics, potency is described in terms of minimum alveolar concentration (MAC) The concentration of an inhaled anesthetic that prevents movement in response to surgical stimulation in 50% of patients is defined as the MAC of that anesthetic agent MACawake is a fraction of the MAC that indicates the alveolar concentration of anesthetic agent at which suppression of verbal response and memory formation is achieved Inhaled anesthetic agents behave as gases do, not as liquids As they distribute between tissues, or between blood and gas, equilibrium is reached when the partial pressure of anesthetic gas is equal in the two tissues or between the blood and gas At equilibrium, the concentrations differ because of differences in solubility in those tissues or physiologic environments, resulting in unique blood/gas, brain/blood, and fat/blood partition coefficients These ratios demonstrate that inhaled anesthetic agents are more soluble in some tissues, such as fat, than in others, such as blood, and that the different agents have a range of solubility within each tissue or physiologic environment (Table 1-1) For inhaled anesthetics that are not very soluble in blood or fat, such as nitrous oxide, equilibrium is achieved quickly For an agent that is more soluble in fat, such as halothane, equilibrium is achieved more slowly because fat represents a large anesthetic reservoir that is poorly perfused and therefore fills slowly Table 1-1 Properties of common inhaled anesthetic agents Partition coefficient Anesthetic agent MAC (vol %) MACawake Blood/gas Brain/blood Fat/blood Desflurane 2.4 0.45 1.3 27 Halothane 0.75 0.41 2.3 2.9 51 Isoflurane 1.2 0.4 1.4 2.6 45 105 60.0 0.47 1.1 0.6 0.65 1.7 Nitrous oxide Sevoflurane 2.3 48 An important consideration is the speed of anesthetic induction Anesthesia occurs when the partial pressure of the anesthetic agent in the brain is equal to or greater than the MAC of that anesthetic Because the brain is highly perfused, the partial pressure of the anesthetic in the brain becomes equal to the partial pressure in alveolar gas and blood within several minutes Therefore, anesthesia is achieved shortly after alveolar partial pressure reaches the MAC For anesthetic agents that are highly soluble in blood and other tissues, the partial pressure will rise more slowly This limitation on the speed of induction can be overcome by delivering higher inspired partial pressure of the anesthetic agent The elimination of an inhaled anesthetic mimics in reverse the process of uptake For anesthetic agents with low solubility in blood and tissue, recovery is independent of the duration of anesthetic administration and should mirror the speed of induction For anesthetic agents with high blood and tissue solubility, accumulation in the fat prevents blood and alveolar partial pressures from rapidly declining, and recovery depends on the duration of anesthetic administration Patients will be arousable when alveolar partial pressures reach MACawake Considerations of parenteral anesthetics Parenteral anesthetics are small lipophilic compounds that quickly partition into the highly perfused and lipophilic tissues of the central nervous system, where they rapidly produce anesthesia After a single intravenous bolus, anesthetic concentrations in the bloodstream decline rapidly as the anesthetic distributes into the central nervous system Anesthetic concentrations in the central nervous system then fall rapidly as the anesthetic redistributes from the central nervous system back into the blood, where it either is transported to and metabolized by the liver www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia or diffuses into viscera and muscle and subsequently into poorly perfused adipose tissue The termination of the anesthetic effect primarily results from redistribution of the anesthetic agent from the central nervous system, not metabolism Therefore, the duration of the anesthetic effect after a single dose often depends more on the distribution half-life (α) than on the elimination half-life (β) of the anesthetic agent After administration of multiple doses or prolonged infusion of a parenteral anesthetic agent, its lipophilic properties (resulting in its accumulation in fatty tissue) and elimination half-life (reflecting the metabolic clearance) are more predictive of the duration of effect The physicochemical and pharmacokinetic properties of common parenterally administered general anesthetic agents are provided in Table 1-2 Table 1-2 Properties of common parenterally administered general anesthetic agents Anesthetic agent Molecular weight (g/mol) Octanol/water partition coefficient Acidity/ alkalinity pKa Distribution half-life (min) Elimination half-life (h) Protein binding (%) Alfentanil 471 158 Base 7.5 3.8 1.6 92 Etomidate 244 1,000 Base 4.5 20.0 2.9 76 Ketamine 238 794 Base 7.45 11.0 3.0 27 Methohexital 284 63 Acid 8.7 5.6 3.9 73 Midazolam 326 4,677 Base 6.6 31.0 1.9 98 Propofol 178 7413 Acid 11.1 2.5 1.8 98 Remifentanil 413 25 Base 7.5 NM 0.13 92 Sufentanil 579 8,912 Base 8.9 1.4 2.7 93 Thiopental 264 580 Acid 7.4 4.6 12.1 85 NM, not measurable Clinical drug efficacy and safety The efficacy of a drug refers to its ability to elicit a specific physiologic effect Efficacy is generally expressed in terms of the maximum effect of a drug, compared with the maximum effect of another For example, if drug A elicits a greater effect than drug B does, despite the dose given, then drug A is said to have greater efficacy.1 The potency of intravenous anesthetic agents is more difficult to measure and is defined as the amount of a drug required to elicit a certain effect In comparing two anesthetic agents, if one agent produces the desired effect with 10 mg and the other agent requires 100 mg to produce the same effect, the first agent is more potent Potency can be easily illustrated in a typical dose-response curve (Fig 1-2) Fig 1-2 Dose-response curves demonstrating potency of two drugs Drug A is more potent than drug B because it achieves the desired response at a smaller dose Although the efficacy (maximum effect) of the two drugs is the same, the leftward shift of the doseresponse curve of drug A indicates greater potency www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM Pharmacodynamics The safety of drugs is expressed in terms of effective doses and lethal doses The median effective dose (ED50) is the free plasma concentration at equilibrium that produces a specific response in 50% of patients In anesthesia, the desired response is lack of response to surgical stimulation The median lethal dose (LD50) is the dose that results in death in 50% of patients The therapeutic index of a drug is equal to the ratio LD50:ED50; the greater the ratio, the safer the drug In other words, the greater the difference between ED50 and LD50, the less likely it is that administration of the drug at effective doses will result in death Pharmacodynamics Pharmacodynamics is defined as the study of the biochemical and physiologic effects of drugs and the mechanism of their actions, including the correlation of their action and effect with their chemical structure For a substance to produce an effect, it must bind to a receptor within the body Several types of receptors have naturally occurring ligands, or molecules that bind to them Drugs may be agonists or antagonists for these receptors, thereby producing effects within the body that influence the potency and efficacy of the drug Ligands A ligand is any molecule that binds to a receptor Ligands can be endogenous, such as antibodies, hormones, and neurotransmitters, or they can be exogenous, such as the vast spectrum of drugs available for therapeutic use Drugs can be classified as agonists, which have excitatory or inhibitory effects, or antagonists Agonistic drugs are designed to elicit effects similar to those of endogenous agonists, whereas antagonists are molecules that prevent an agonist from binding to a receptor, thus blocking its effect Antagonists can be further characterized as competitive or noncompetitive A competitive antagonist competes with an agonist and reversibly binds to a receptor A noncompetitive antagonist irreversibly binds to a receptor and permanently blocks the agonist action until new receptors can be generated At the neuromuscular junction, acetylcholine mediates muscle contraction by reversibly binding to the postsynaptic nicotinic acetylcholine receptor Atracurium (a non-depolarizing neuromuscular blocking drug) is an example of a competitive antagonist Botulinum toxin is an example of a noncompetitive antagonist Some drugs, classified as inverse agonist or superantagonist, decrease receptor response to less than that which occurs in the absence of the agonist This scenario can occur because some receptors are in an activated state in the absence of an agonist, creating a baseline effect.2 Receptors Receptors are present in the cell membrane and intracellularly Receptors in the cell membrane include membrane receptors, voltage-gated ion channels, and ligand-gated ion channels These receptors interact with water-soluble ligands that not readily cross the hydrophobic lipid bilayer Guanine nucleotide–binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of α, β, and γ subunits.3,4 The G protein–coupled receptor (GPCR) superfamily of proteins provide the primary mechanism by which cells detect changes in the external environment and present this information intracellularly.5 Binding of an extracellular agonist to a GPCR induces a change in conformation of the receptor The activated receptor promotes the exchange of bound guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the G protein α subunit GTP binding changes the conformation of switch regions within the α subunit, allowing the bound inactive trimeric G protein to be released from the receptor and to dissociate into an active α subunit (GTP-bound) and a β/γ dimer.6 The α subunit and the β/γ dimer then activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels These effectors regulate the intracellular concentrations of secondary messengers, including cyclic adenosine monophosphate (cAMP), diacylglycerol, and sodium and calcium cations.7 The result is a physiologic response caused by downstream regulation of gene transcription Hydrolysis of α subunit–bound GTP to GDP allows the α and β/γ subunits to reassociate and bind www.ajlobby.com Mizukawa_Chap_01.indd 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia to the receptor, terminating the signal.6 Stimuli to which GPCRs are known to respond include neurotransmitters, neuropeptides, light, gustatory compounds, odors, hormones, and glycoproteins Examples of GPCRs include (1) presynaptic α2-adrenergic receptors, which cause inhibition of voltage-dependent calcium channels and decrease the release of norepinephrine,8 and (2) opioid receptors, which prevent calcium influx into presynaptic terminals and reduce glutaminergic excitatory transmission.9 Voltage-gated ion channels are charged water-filled pores composed of several proteins that span the membrane Ion pairs between positive and negative charges help stabilize these channels Changes in membrane potential cause a conformational change in the central pore, with rearrangement of ion pairs that results in increased permeability of the ion specific to that channel Examples of voltage-gated channels include (1) voltage-gated sodium channels, which are responsible for depolarization and for creation and propagation of action potential; (2) voltage-gated potassium channels, which are responsible for repolarization; (3) voltage-gated calcium channels, which link muscle excitation with contraction and neuronal excitation with release of neurotransmitters; (4) hyperpolarization-activated cyclic nucleotide-gated channels, which are permeable to potassium and sodium and function as pacemaking channels in the heart; and (5) voltage-gated proton channels, which open with depolarization and are strongly pH sensitive, allowing protons to leave the cell.10 A ligand-gated ion channel is a combination of a receptor protein and an ion channel Binding of certain molecules to this ionotropic receptor directly alters the membrane potential by causing a conformational change in the channel protein This change results in the opening of the channel and flux of ions across the cell membrane Examples of ligand-gated ion channels include (1) anion-permeable γ-aminobutyric acid (GABAA) receptor, which causes intracellular flux of chloride ions, resulting in hyperpolarization of the membrane potential; (2) anion-permeable glycine receptor (GlyR), the activity of which is similar to that of GABAA receptor; (3) cation-permeable nicotinic acetylcholine receptor, which causes sodium and potassium influx, resulting in depolarization; (4) cation-permeable ionotropic glutamate-gated receptors, which cause sodium, potassium, and calcium flux, resulting in depolarization; and (5) two-pore-domain potassium channels, which cause potassium influx, resulting in hyperpolarization at the presynaptic and postsynaptic levels.10 Central Nervous System Regulation General anesthetics work by causing a decrease in central nervous system activity, reportedly as a result of stimulation of inhibitory neurotransmitters and inhibition of excitatory neurotransmitters This section gives a pertinent overview of this complex topic and presents the major modulators of the central nervous system, including inhibitory neurotransmitters, excitatory neurotransmitters, and intracellular signaling Inhibitory neurotransmitters γ-aminobutyric acid receptor GABA receptor is an inhibitory receptor found within the central nervous system The most abundant inhibitory neurotransmitter receptor in the brain, it is found in high concentrations in the thalamus and cerebral cortex It is a heteromeric transmembrane protein.11 The subtype that has been widely studied is the GABAA receptor The receptor is composed of five subunits Stimulation of the GABAA receptor allows for the flux of chloride ion through the ionophore, causing hyperpolarization and a decrease in excitatory neurotransmission.11 Binding sites for benzodiazepines, barbiturates, and neurosteroids have been identified.12,13 Volatile anesthetics and ethanol appear to bind at the neurosteroid site 10 www.ajlobby.com Mizukawa_Chap_01.indd 10 6/21/17 3:07 PM Central Nervous System Regulation Transient inhibitory postsynaptic currents (IPSCs) are generated by the stimulation of GABAergic receptors located in high concentration at the postsynaptic terminals of excitatory neurons GABAergic drugs, including general anesthetics, sedatives, and anxiolytics, enhance the blockade of fast excitatory impulses by the generation of IPSCs.14 GABAergic drugs also have other mechanisms of action, including potentiation of GABA, direct stimulation of the GABA receptor, and desensitization of non-postsynaptic receptors for GABA GABAergic drugs potentiate the binding of GABA to the GABA receptor by means of allosteric modulation of the GABA receptor that can increase the receptor’s affinity for GABA.15 Desensitization allows for prolonged binding Glycine Glycine is an inhibitory neurotransmitter Its receptor, GlyR, has five known subunits and is highly expressed in the spinal cord and brainstem Alanine, taurine, serine, and proline can bind to this receptor and cause inhibition but are less potent GlyR is blocked by the plant alkaloid strychnine, which in high concentrations can cause muscular contractions and tetany Glycine has properties similar to GABA, and binding of glycine to GlyR leads to an increase in the conductance of chlorine through glycine-gated channels, causing hyperpolarization of the neuronal membrane, which results in antagonism of other depolarization stimuli.16 The volatile anesthetics and ethanol have effects at this receptor.17 Of note, glycine has also been identified in the forebrain, where it has been shown to function as a co-agonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor.18,19 Epinephrine/norepinephrine The presynaptic α2-adrenergic receptor is present throughout the central nervous system Three subtypes of the α2 receptor have been identified The α2A receptor has been identified in high concentration in the locus ceruleus and brain stem.20 α2-adrenergic receptor agonist causes activation of potassium channels, allowing for efflux of potassium and inhibition of calcium entry into the calcium channels of neuronal cells and resulting in hyperpolarization of the neuronal membrane and decreased activity.21 Stimulation of the presynaptic α2A receptor demonstrates sedative-hypnotic and analgesic effects Dexmedetomidine is a highly selective and potent α2 agonist The primary site of action of α2-adrenergic receptor agonist is the locus ceruleus, not the cerebral cortex The unusual subcortical form of dexmedetomidine-induced sedation is characterized by an easy and quick arousal, resembling awakening from natural sleep.22 Potassium Two-pore-domain potassium channels, also known as potassium leak channels, are transmembrane potassiumselective ionic pores that are constitutively open at rest and are central to neural function.23 They are voltageindependent and are thought to provide background modulation of neuronal excitability.24 The TASK and TREK potassium leak channels serve to influence both resting membrane potential and the repolarization phase of the action potential Human TREK-1 is highly expressed in the brain, where it is particularly abundant in GABA-containing interneurons of the caudate nucleus and putamen TREK-1 is also expressed in the prefrontal cortex, hippocampus, hypothalamus, midbrain serotonergic neurons of the dorsal raphe nucleus, and sensory neurons of the dorsal root ganglia Activation of these TREK-1 channels by volatile anesthetics hyperpolarizes the membrane and suppresses the generation of action potential.25 11 www.ajlobby.com Mizukawa_Chap_01.indd 11 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia Opioid neuropeptides The identified opioid receptors and their endogenous opioid peptides have been well characterized Actions of exogenous agonists at these receptors include analgesia, depression of respiratory function, decreased gastrointestinal motility, and sedation Ketamine has been shown to interact with μ receptors and contribute to analgesia and respiratory depression The analgesic effects of nitrous oxide are attributable in part to the release of endogenous opioid peptides in the periaqueductal gray (Table 1-3) Table 1-3 Receptor-drug interactions Receptor Acetylcholine (nicotinic and muscarinic) Endogenous ligand Acetylcholine Location in central nervous system Mechanism of action Nicotinic subtype: brain, spinal cord, autonomic ganglia Mediates cation influx and membrane depolarization Muscarinic subtype: cerebral cortex, cerebellum, brainstem, hippocampus G protein–linked inhibition of adenylyl cyclase, stimulation of phospholipase C, or regulation of K+ channels Effect of drugs Effects blocked by inhaled anesthetics, intravenous anesthetics GABA GABA • Cerebral cortex • Thalamus • Reticular formation • Potentiates GABA • Provides direct stimulation of GABA receptor • Desensitizes GABA receptor • Generates IPSC • Mediates Cl− conductance with membrane hyperpolarization • Decreases probability of action potential firing by increasing frequency of channel opening and/or increasing mean channel opening time Effects enhanced by barbiturates, benzodiazepines, etomidate, ethanol, propofol, volatile anesthetics Glycine • Glycine • Alanine • Proline • Serine • Taurine • Brainstem • Spinal cord Mediates Cl− conductance with membrane hyperpolarization Effects enhanced by inhaled anesthetics K+ channels (TREK-1, TREK-2, TASK-1, TASK-2, TASK-3) Mediate K+ influx and membrane • ACh • Strongly expressed in spinal • Glutamate cord, dorsal root ganglia, hyperpolarization at presynaptic and • H+ corpus callosum, cerebellum, postsynaptic levels caudate nucleus/putamen • Norepinephrine • Moderately expressed in • Serotonin cerebral cortex, hippocampus, • Substance P hypothalamus NMDA • Glutamate • Aspartate Opioid receptors (μ, σ, κ, ε) • Brain • Peptides • Spinal cord • β-endorphin • Dynorphin • Leu-enkephalin • Met-enkephalin • Hippocampus • Medullary respiratory control center Effects enhanced by inhaled anesthetics Mediates Na+, K+, and Ca2+ conductance with membrane depolarization Effects blocked by ketamine, nitrous oxide, xenon, extracellular Mg2+ • Prevents Ca2+ influx into presynaptic terminal • Reduces glutaminergic excitatory transmission Effects enhanced by ketamine, nitrous oxide Presynaptic • Norepinephrine Increase receptor concentration • Activation inhibits voltage-dependent Ca2+ α2 -adrenergic • Epinephrine channels in the brainstem, locus ceruleus, • Decreases norepinephrine release (α2A , α2B, α2C ) and spinal cord • Decreases cellular cyclic guanosine monophosphate Effects enhanced by clonidine, dexmedetomidine, nitrous oxide 12 www.ajlobby.com Mizukawa_Chap_01.indd 12 6/21/17 3:07 PM Conclusion Excitatory neurotransmitters Glutamate Glutamate and aspartate are the main excitatory neurotransmitters in the central nervous system The three classes of glutamate receptors are NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainic acid.26 Stimulation of the NMDA receptor plays an extensive role in the memory and learning areas of the hippocampus These NMDA receptors are found in large concentrations in central respiratory control centers Activation of the NMDA receptor requires binding of glutamate or aspartate for activation For efficient opening of ion channels, the NMDA receptor requires the binding of glycine or D-serine as a co-agonist.27,28 The organization of the glutamate receptor subtypes suggests that they have both ionotropic and metabotropic receptor families.29 All glutamate receptors are highly permeable to sodium and potassium, and the NMDA receptor is also highly permeable to calcium.30 Binding of glutamate to the glutamate receptor will increase the probability of channel opening and enhance neurotransmission by increasing conductance of sodium and in some cases calcium Stimulation of these receptors causes fast excitatory postsynaptic currents NMDA receptor antagonists, such as ketamine and nitrous oxide, block this excitation.31 Metabotropic glutamate receptors provide another level of response through their links with the phosphoinositide and cyclic nucleotide (cAMP) second messenger systems.32 Metabotropic glutamate receptors are coupled to signal transduction pathways via G proteins, producing alterations in intracellular second messengers and generating slower synaptic responses Acetylcholine Nicotinic and muscarinic acetylcholine receptors (AChRs) are found throughout the body.33 Nicotinic AChRs are formed by the association of five subunits, each contributing to the pore lining AChRs can be divided into two main families: muscular and neuronal.33 Stimulation of the nicotinic and muscarinic AChRs is complex and can be inhibitory or excitatory.34–36 The AChR is a nonspecific cation channel and is activated in conscious awareness and rapid eye movement sleep Cholinergic defects of the central nervous system are associated with disturbances in conscious awareness, hallucinations, and some degenerative brain diseases.37 AChRs are inhibited by volatile and intravenous anesthetics.36 Ketamine is a strong inhibitor of nicotinic AChR Physostigmine, a cholinesterase inhibitor, raises the concentration of acetylcholine within the acetylcholine synaptic cleft and is used to treat delirium after general anesthesia Intracellular signaling Multiple anesthetics have been shown to affect G protein activation Halothane, isoflurane, enflurane, and sevoflurane all inhibit GTP–GDP exchange and enhance dissociation of one of the nonhydrolyzable GTP analogs GPCR agonists, such as μ opioid and α2-adrenergic receptors, can affect anesthetic sensitivity, reducing MAC Conclusion Knowledge of basic pharmacologic principles gives the clinician an understanding of the characteristics of anesthetic agents that make them suitable for use in clinical practice A deeper appreciation can be achieved through an understanding of the neurotransmitters and receptors in the central nervous system and how anesthetic agents interact with these receptors The overview of clinically relevant basic principles of anesthesia in this chapter provides the clinician with a foundation for the topics presented in later chapters of this book 13 www.ajlobby.com Mizukawa_Chap_01.indd 13 6/21/17 3:07 PM 1 • Basic Principles of Anesthesia References Griffin CE III, Kaye AM, Bueno FR, Kaye AD Benzodiazepine pharmacology and central nervous system-mediated effects Ochsner J 2013;13:214–223 20 Chiu TH, Chen MJ, Yang YR, Yang JJ, Tang FI Action of dexmedetomidine on rat locus coeruleus neurones: Intracellular recording in vitro Eur J Pharmacol 1995;285:261–268 Milano CA, Allen LF, Rockman HA, et al Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor Science 1994;264(5158):582–586 21 Khan ZP, Ferguson CN, Jones RM Alpha-2 and imidazoline receptor agonists: Their pharmacology and therapeutic role Anaesthesia 1999;54:146–165 Preininger AM, Hamm HE G protein signaling: Insights from new structures Sci STKE 2004;2004(218):re3 22 Arcangeli A, D’Alò C, Gaspari R Dexmedetomidine use in general anaesthesia Curr Drug Targets 2009;10:687–695 Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes DNA Res 2000;7:111–120 23 Lesage F Pharmacology of neuronal background potassium channels Neuropharmacology 2003;44:1–7 24 Franks NP General anaesthesia: From molecular targets to neuronal pathways of sleep and arousal Nat Rev Neurosci 2008;9:370–386 Gether U Uncovering molecular mechanisms involved in activation of G protein-coupled receptors Endocr Rev 2000;21:90–113 25 Westphalen RI, Krivitski M, Amarosa A, Guy N, Hemmings HC Jr Reduced inhibition of cortical glutamate and GABA release by halothane in mice lacking the K+ channel, TREK-1 Br J Pharmacol 2007;152:939–945 Svoboda P, Teisinger J, Novotný J, et al Biochemistry of transmembrane signaling mediated by trimeric G proteins Physiol Res 2004;53(suppl 1):S141–S152 Landry Y, Gies JP Heterotrimeric G proteins control diverse pathways of transmembrane signaling, a base for drug discovery Mini Rev Med Chem 2002;2:361–372 26 Dingledine R, Borges K, Bowie D, Traynelis SF The glutamate receptor ion channels Pharmacol Rev 1999;51:7–61 Qin K, Sethi PR, Lambert NA Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins FASEB J 2008;22:2920–2927 27 Chen PE, Geballe MT, Stansfeld PJ, et al Structural features of the glutamate binding site in recombinant NR1/NR2A N-methyl-D-aspartate receptors determined by site-directed mutagenesis and molecular modeling Mol Pharmacol 2005;67:1470–1484 Standifer KM, Pasternak GW G proteins and opioid receptor-mediated signalling Cell Signal 1997;9:237–248 28 Wolosker H D-serine regulation of NMDA receptor activity Sci STKE 2006;2006(356):pe41 10 Camerino DC, Tricarico D, Desaphy JF Ion channel pharmacology Neurotherapeutics 2007;4:184–198 29 Aramori I, Nakanishi S Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells Neuron 1992;8:757–765 11 Garcia PS, Kolesky SE, Jenkins A General anesthetic actions on GABA(A) receptors Curr Neuropharmacol 2010;8:2–9 30 Paoletti P, Neyton J NMDA receptor subunits: Function and pharmacology Curr Opin Pharmacol 2007;7:39–47 12 Study RE, Barker JL Diazepam and ( )-pentobarbital: Fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons Proc Natl Acad Sci U S A 1981;78:7180–7184 31 de Sousa SL, Dickinson R, Lieb WR, Franks NP Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon Anesthesiology 2000;92:1055–1066 13 Skolnick P, Moncada V, Barker JL, Paul SM Pentobarbital: Dual actions to increase brain benzodiazepine receptor affinity Science 1981;211(4489):1448–1450 32 Schoepp DD, Conn PJ Metabotropic glutamate receptors in brain function and pathology Trends Pharmacol Sci 1993;14:13–20 33 Vizi ES, Lendvai B Side effects of nondepolarizing muscle relaxants: Relationship to their antinicotinic and antimuscarinic actions Pharmacol Ther 1997;73:75–89 14 Maconochie DJ, Zempel JM, Steinbach JH How quickly can GABAA receptors open? Neuron 1994;12:61–71 15 Olsen RW, Li GD GABA(A) receptors as molecular targets of general anesthetics: Identification of binding sites provides clues to allosteric modulation Can J Anaesth 2011;58:206–215 34 Flood P, Ramirez-Latorre J, Role L Alpha beta neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected Anesthesiology 1997;86:859–865 16 Betz H, Becker CM The mammalian glycine receptor: Biology and structure of a neuronal chloride channel protein Neurochem Int 1988;13:137–146 35 Radcliffe KA, Dani JA Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission J Neurosci 1998;18:7075–7083 17 Sonner JM, Antognini JF, Dutton RC, et al Inhaled anesthetics and immobility: Mechanisms, mysteries, and minimum alveolar anesthetic concentration Anesth Analg 2003;97:718–740 36 Franks NP, Lieb WR Molecular and cellular mechanisms of general anaesthesia Nature 1994;367(6464):607–614 18 Furukawa H, Singh SK, Mancusso R, Gouaux E Subunit arrangement and function in NMDA receptors Nature 2005;438(7065):185–192 37 Ji D, Lape R, Dani JA Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity Neuron 2001; 31:131–141 19 Kleckner NW, Dingledine R Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes Science 1988;241(4867):835–837 14 www.ajlobby.com Mizukawa_Chap_01.indd 14 6/21/17 3:07 PM CHAPTER Pharmacology and Utility of Intravenous Anesthesia Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_02.indd 15 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia Anesthesia administered via an intravenous (IV) route is the mainstay of office-based anesthesia and is a reliable, safe mode of anesthesia care Myriad drugs are utilized in the office setting, all of which have unique pharmacologic characteristics and profiles Thorough knowledge of these characteristics and how they influence the utility or contraindication of these drugs is critical in safely and efficiently administering IV anesthesia in patients with comorbid disease This chapter reviews the classes of drugs used in IV anesthesia and includes the mechanism of action, dosing, time of onset, duration of effect, and pros and cons of commonly used drugs in each class The reader should keep in mind that these profiles assume a balanced technique including multiple IV agents, unless otherwise specified Three receptors in the body, when modulated by agents discussed in this chapter, produce the anesthetic effects of anxiolysis, sedation, hypnosis, amnesia, and analgesia These receptors are the γ-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), and α2-adrenergic receptors Opioids have no hypnotic or amnestic effects, but they provide analgesia and potentiate the effects of GABA agonists Benzodiazepines GABA is the chief inhibitory neurotransmitter of the central nervous system Benzodiazepines are GABA agonists and bind to the α and γ subunits of the anion-permeable GABA (GABAA) receptor This binding enhances the affinity of the GABA receptor to GABA, causing an influx of chloride ion intracellularly, hyperpolarizing the postsynaptic nerve, and inhibiting action potential formation The GABA α1 subunit accounts for the anticonvulsant, sedative, and amnestic effects, whereas the α2 subunit accounts for the anxiolytic and muscle relaxant effects.1 Three benzodiazepines are commonly used clinically: midazolam, diazepam, and lorazepam In office-based anesthesia, midazolam is the chief player because of its kinetic and safety profiles, and diazepam may have clinical relevance Lorazepam has no utility in office-based anesthesia Midazolam Midazolam (Versed, Roche) is the most widely used benzodiazepine in office-based anesthesia In a balanced technique, midazolam is dosed at 0.05 to 0.15 mg/kg, titrated to effect Its time of onset is approximately 30 to 60 seconds, and duration is approximately 20 to 30 minutes, depending on the dose Amnesia associated with midazolam tends to be more profound than amnesia associated with diazepam, which is a major advantage (Box 2-1) BOX 2-1 Midazolam: Pros and cons Cons • No analgesic effect • No antiemetic effect • Possible prolonged sedation resulting from its active metabolite, 1-hydroxymidazolam • Muscle relaxation including airway musculature; caution required when using high doses in patients with obstructive sleep apnea Pros • Sedation, amnesia, anxiolysis • Muscle relaxation • Anticonvulsant effect • Modest hemodynamic and respiratory effects • Oral, intramuscular, or nasal administration • Rarity of pain on injection because carrier does not contain propylene glycol 16 www.ajlobby.com Mizukawa_Chap_02.indd 16 6/20/17 10:27 AM Barbiturates Diazepam Diazepam (Valium, Roche) was widely used for IV anesthesia before the emergence of midazolam Diazepam can be used in a balanced technique with a dose of to 20 mg, which has a slightly slower time of onset than midazolam at 30 to 45 seconds and has a duration of 60 to 120 minutes, depending on the dose (Box 2-2) BOX 2-2 Diazepam: Pros and cons Cons • Airway reactivity: cough, laryngospasm, hiccough, tremors • Pain on injection, thrombophlebitis • Risk of seizure activity with prolonged, high doses2 Pros • Anxiolysis, amnesia (less than midazolam), sedation • Anticonvulsant effect • Long duration, which may be beneficial in long procedures Flumazenil Flumazenil (Romazicon, Roche) is a competitive antagonist of the GABA receptor Its affinity for the receptor is much higher than that of other benzodiazepines, such as midazolam and diazepam When it binds the receptor, flumazenil has minimal effect on the nerve and its transmission Flumazenil has no intrinsic ability to displace an agonist from the receptor, but rather exerts its effect by quickly binding the receptor after an agonist dissociates It can be used to reverse overdosing of any benzodiazepine In office-based anesthesia, it is generally given to reverse the effects of benzodiazepine after inadvertent overdosing or to counteract prolonged effects after the procedure is completed It is given in 0.2 mg IV doses every minutes, up to a 3-mg total dose, until the desired effect is achieved It has a rapid onset, with clinical manifestations occurring within approximately minute, and a short duration of approximately 30 minutes Patients should be monitored for at least 30 minutes after dosing to make sure resedation does not occur, particularly with longer-acting benzodiazepines (Box 2-3) BOX 2-3 Flumazenil: Pros and cons Cons • Need to monitor the patient for resedation for 30 minutes after last dose because of short duration • Lowered seizure threshold Pros • Ability to reverse sedation, respiratory depression, and amnesia resulting from benzodiazepines • Rapid onset, short duration Barbiturates Barbiturates are agonists for the GABAA receptor, although studies have also shown modulation of the NMDA receptor.1 Barbiturates bind to the GABA receptor and directly cause chloride ion influx, hyperpolarization of the nerve, and inhibition of transmission Barbiturates include thiobarbiturates and oxybarbiturates Methohexital is an oxybarbiturate that was widely used before the introduction of propofol A dose-dependent drop in blood pressure and an associated reflex tachycardia are often seen with administration of barbiturates Although these effects are typically tolerated well by healthy individuals, caution should be used in patients with hypovolemia or a compromised ability to compensate for this drop in blood pressure Apnea can occur with large doses of barbiturate, and dose-dependent respiratory depression is seen with smaller doses Barbiturates are contraindicated in patients with a diagnosis of acute intermittent porphyria 17 www.ajlobby.com Mizukawa_Chap_02.indd 17 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia Thiopental Thiopental was the main thiobarbiturate used in anesthesia and was also used in lethal injections, but it is not currently manufactured or available for use A 3- to 4-mg/kg dose will rapidly induce general anesthesia in 15 to 30 seconds and has a duration of approximately 20 to 30 minutes It has a weaker hypnotic effect than other agents and can potentiate or trigger status asthmaticus.1 Methohexital Methohexital succeeded thiopental as an IV anesthetic induction agent It has a very rapid onset, 10 to 30 seconds, with a 1- to 1.5-mg/kg induction dose Its duration is approximately to minutes, making it attractive for use in office-based anesthesia (Box 2-4) BOX 2-4 Methohexital: Pros and cons Cons • Airway reactivity: cough, laryngospasm, hiccough, tremors • Pain on injection, thrombophlebitis • Risk of seizure activity with prolonged, high doses2 Pros • Rapid onset • Short duration Propofol Propofol is an alkyl phenol that is currently the most widely used IV anesthetic induction agent Its mechanism of action is thought to be modulation of the β subunit of the GABAA receptor, causing hyperpolarization of the nerve Studies also show effects on the α and γ subunits, as well as some effect on the α2-adrenergic and NMDA receptors.1 An induction dose of mg/kg will produce unconsciousness in 20 to 30 seconds, with a duration of approximately to 10 minutes When propofol is used in a balanced IV technique, boluses of 20 to 30 mg can be administered incrementally until the desired level of anesthesia is achieved An infusion of 30 to 100 μg/kg per minute can be used, depending on the other medications used and the age and health of the patient It is a potent respiratory depressant and will cause apnea with an induction dose A dose-dependent 10% to 40% drop in blood pressure can be seen, with relatively little change in the heart rate because of the depressive effect on the heart and the baroreflex.1 It is highly lipid soluble and comes in a formulation with soybean oil, glycerol, and lecithin, a purified egg phospholipid Propofol has been shown to be safe in most patients with egg allergies because the allergen is usually albumin (yolk), not lecithin (egg white).2 Propofol is metabolized in the liver and, to a lesser degree, in the lungs, resulting in largely inactive metabolites that are excreted by the kidneys Propofol infusion syndrome, characterized by bradycardia, asystole, metabolic acidosis, rhabdomyolysis, hyperlipidemia, and enlarged liver, is extremely rare during short procedures in the office setting1 (Box 2-5) 18 www.ajlobby.com Mizukawa_Chap_02.indd 18 6/20/17 10:27 AM Ketamine BOX 2-5 Propofol: Pros and cons Pros • Rapid onset • Short duration • Blunted airway reactivity and cough reflex • Antiemetic effect • Ability to intubate without use of a paralytic • Anticonvulsant effect Cons • Need to use entire bottle within hours of opening because of concern for bacterial growth in lipid carrier • Pain on injection • Hypotension • Blunted reflex tachycardia resulting in possible compromise of cardiac output • Profound respiratory depression and/or apnea2 • Relaxation of airway musculature • Risk of propofol infusion syndrome • Myoclonus Ketamine Ketamine is a phencyclidine derivative that produces general anesthesia rapidly Its anesthetic effects are the result of inhibition of the NMDA receptor Its analgesic effects are thought to be the result of binding of opioid receptors Unlike many other IV agents used in anesthesia, it is a potent analgesic and causes minimal cardiovascular and respiratory depression (Box 2-6) Overall, its effects are largely sympathomimetic, except for an increase in secretions and salivation It is said to produce dissociative or cataleptic anesthesia, characterized by unconsciousness, eyes remaining open with nystagmus, and some preservation of protective reflexes, such as cough, swallowing, and corneal reflexes.1 These effects are the result of disruption of the afferent sensory stimulation of higher cortical centers in the brain A 2-mg/kg induction dose has an onset of 20 to 30 seconds and duration of 20 to 30 minutes However, when ketamine is used in a balanced technique, the dose may be decreased to 0.5 mg/kg and given in small boluses, similar to the administration of propofol Intramuscular dosing generally starts at a dose of to mg/ kg with a 5-minute onset and will last approximately 20 minutes, depending on the dose.4 BOX 2-6 Ketamine: Pros and cons Pros • Sedation, unconsciousness, analgesia, amnesia • Cardiovascular stability (increased blood pressure and heart rate can be attenuated with midazolam, propofol, and opioids) • Airway muscle tone, respiratory drive, and functional residual capacity maintained (respiratory depression seen when ketamine is given in high doses or with other respiratory depressants3) • Bronchodilation • Premedication with oral, intramuscular, or nasal administration • Lower risk of aspiration because of retention of cough and swallowing reflexes • Anticonvulsant Cons • Increased salivation resulting in predisposition to laryngospasm, which can be addressed with glycopyrrolate if clinically relevant • Emergence delirium (can be attenuated with concomitant dosing of midazolam and propofol); higher risk in patients with older age, female sex, and/or baseline psychoses1 • No reversal agent • Prolonged action resulting from active metabolite, norketamine • Malignant hyperthermia trigger • Contraindication in patients with neurologic trauma, intracranial lesions (because of increased intracranial pressure), glaucoma and/or recent ophthalmologic surgery (because of increased intraocular pressure); newborns; and patients with uncontrolled hypertension, coronary artery disease, and/or congestive heart failure • Postoperative nausea and vomiting 19 www.ajlobby.com Mizukawa_Chap_02.indd 19 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia Opioids Opioids are a class of drug characterized by the production of analgesia, but they have many other physiologic effects that must be appreciated by the anesthesia provider The effects of opioids are modulated by the μ, δ, and κ opioid receptors The μ receptor will cause analgesia, respiratory depression, gastroparesis, decreased gastrointestinal function, and sedation μ receptors can be classified as μ1, μ2, and μ3 receptors The δ receptor produces analgesia The κ receptor produces analgesia, decreased gastrointestinal motility, and sedation μ and κ receptors, found in the spinal cord and brain, provide analgesia by blocking afferent nociceptor impulse transmission from the spinal cord to the brain, as well as blocking pain centers in the brain Opioids, when administered alone, have little inotropism but can cause bradycardia by directly affecting the sinoatrial node.5 Because these effects are relatively weak, increased heart rate resulting from drops in blood pressure because of coadministration of drugs such as midazolam and propofol will trump the negative chronotropic effects of the opioids Opioids also produce a dose-dependent respiratory depression, mainly caused by the μ receptor This respiratory depression manifests as decreased ventilatory effort, blunting of ventilatory drive in response to hypercapnia, and blunting of the cough reflex The latter can be useful in a patient with a hyperactive airway Large doses of opioids can attenuate or prevent coughing resulting from substantial airway stimulation, such as endotracheal intubation or laryngeal mask airway placement Opioids are said to be cardioprotective and are widely used in cardiothoracic surgery because of their ability to attenuate the sympathetic response to surgical stimulation and pain.5 Decreased gastrointestinal motility and delayed gastric emptying may compromise the nil per os (NPO, no oral intake) status of patients who have taken preanesthetic opioids Patients who use opioids chronically may have clinically relevant volumes of gastric contents even after hours without oral intake Postoperative nausea and vomiting (PONV) is a common side effect of opioids because they directly stimulate the chemoreceptor trigger zone, resulting in nausea Coadministration of ondansetron, promethazine, propofol, dexamethasone, and/or other antiemetic agents can help prevent PONV Miosis, or pupillary constriction, can also occur with opioid administration It is caused by increased parasympathetic tone of the oculomotor nerve Meperidine can attenuate postoperative shivering, although other opioids not display this property Pruritus often occurs with opioid administration Although some opioids, such as morphine, codeine, and meperidine, have been shown to cause histamine release, non–histamine-releasing opioids are associated with pruritus as well It is not uncommon for patients to scratch their nose on induction of anesthesia after administration of fentanyl Interestingly, naloxone will alleviate the pruritus caused by opioids Relevant opioids in office-based outpatient anesthesia include fentanyl, remifentanil, and meperidine Fentanyl Fentanyl is the most widely used opioid in office-based anesthesia because of its pharmacologic profile and low cost At a dose of µg/kg, fentanyl has an onset of 20 to 30 seconds and duration of 20 to 30 minutes, which is congruent with the duration of many outpatient oral surgery procedures Though it has no intrinsic sedative or amnestic properties, it has a synergistic effect with midazolam and other sedatives/hypnotics when used in a balanced technique (Box 2-7) 20 www.ajlobby.com Mizukawa_Chap_02.indd 20 6/20/17 10:27 AM Opioids BOX 2-7 Fentanyl: Pros and cons Cons • Lack of sedative, anxiolytic, hypnotic, and amnestic properties • PONV • Respiratory depression • Rigid chest wall and ventilatory emergencies resulting from rapid administration of large doses (can be treated with naloxone or succinylcholine) Pros • Profound analgesia • Possible modest hypotension and dose-dependent bradycardia • Blunting of cough reflex and attenuation of hyperactive airway • Blunting of sympathetic response of surgical stimulation • No histamine release • Lower cost than remifentanil Remifentanil The opioid remifentanil is useful in IV anesthesia because of its ultra-short-acting properties It is usually administered via infusion at a rate of 0.05 to 0.1 µg/kg per minute for deep sedation and at a rate of 0.05 to µg/kg per minute for general anesthesia.6 It can be used in small bolus doses of 0.5 to µg/kg, titrated to effect, similar to the administration of fentanyl Remifentanil has a rapid onset and short duration Its metabolism by plasma esterases results in recovery within minutes of the termination of dosing or discontinuation of infusion, regardless of the duration of infusion (Box 2-8) BOX 2-8 Remifentanil: Pros and cons Cons • Lack of sedative, anxiolytic, hypnotic, and amnestic properties • PONV • Respiratory depression • Rigid chest wall and ventilatory emergencies resulting from rapid administration of large doses • Expensive cost Pros • Potency 10 times that of fentanyl • Short duration because of degradation by plasma esterases • Possible modest hypotension and dose-dependent bradycardia • Blunting of cough reflex and attenuation of hyperactive airway • Blunting of sympathetic response of surgical stimulation • No histamine release Meperidine Meperidine was the most widely used opioid before the introduction of fentanyl A dose of 0.5 to mg/kg, titrated to effect, has an onset of minutes and duration of 30 to 45 minutes Compared with fentanyl, it has substantial drawbacks Fentanyl is approximately 1,000 times more potent than meperidine Meperidine is chemically similar to atropine; therefore, although it is an antisialagogue, it produces tachycardia Meperidine is associated with histamine release and must be used with caution in asthmatic patients It has a very potent active metabolite, normeperidine, which is a central nervous system stimulant and can cause seizure activity Normeperidine can have adverse reactions with monoamine oxidase inhibitors and amphetamines, leading to seizures, agitation, cardiovascular collapse, and serotonin syndrome7 (Box 2-9) 21 www.ajlobby.com Mizukawa_Chap_02.indd 21 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia BOX 2-9 Meperidine: Pros and cons Pros • Analgesia • Decreased salivation and secretions • Management of postoperative shivering Cons • Lack of sedative, anxiolytic, hypnotic, and amnestic properties • Relatively weak analgesic effect • Possible tachycardia • Potent active metabolite, normeperidine, can prolong effects, especially in patients with liver and renal disease • Histamine release requiring caution in asthmatic patients • Central nervous system stimulation, resulting in lowered seizure threshold • Contraindication in patients who have used a monoamine oxidase inhibitor in the past 2–3 weeks • PONV Naloxone Naloxone is an opioid receptor antagonist Although it acts on all opioid receptor subtypes, it has the greatest affinity for the μ receptor, which is responsible for analgesia and respiratory depression Indications for its use include prolonged ventilatory depression, nausea, pruritus, and muscle rigidity associated with opioid use It is given in a 0.4-mg dose and has an onset of to minutes and duration of 30 to 45 minutes Administration can result in increased heart rate and blood pressure because of the reversal of analgesia and increased pain Depending on the initial dose of opioid, the duration of action of the opioid may exceed the duration of naloxone Therefore, patients should be monitored for at least 30 minutes after naloxone administration to ensure that respiratory depression does not recur (Box 2-10) BOX 2-10 Naloxone: Pros and cons Cons • Blocking of analgesic effect of opioid • Relatively short duration requires monitoring of patient for at least 30 after dosing to ensure that respiratory depression does not recur Pros • Rapid onset • Reversal of respiratory depression, nausea, pruritus, and muscle rigidity associated with opioid Etomidate Etomidate is a GABA receptor agonist It is dosed at 0.2 to 0.6 mg/kg for general anesthesia and 0.2 to 0.4 mg/kg for deep sedation, with an onset of 15 to 20 seconds and duration of 10 minutes Because of its ability to induce general anesthesia with minimal cardiovascular and ventilatory changes, it is useful in patients who cannot tolerate the drop in blood pressure that is routinely seen with administration of other general anesthetic agents, such as propofol and methohexital, or the elevation in blood pressure and heart rate that is seen with ketamine Because etomidate is associated with adrenal insufficiency after even a single dose, its use has declined rapidly A body of research investigating its use in procedural sedation, particularly in the emergency department, may strengthen the indication for its use in office-based anesthesia The emergency medicine literature has recently shown positive outcomes of the use of etomidate for procedural sedation in adults and children, with no substantial morbidity 22 www.ajlobby.com Mizukawa_Chap_02.indd 22 6/20/17 10:27 AM Dexmedetomidine or mortality.8,9 These studies showed a statistically significant drop in adrenal function for up to 12 hours after a single dose of etomidate, although the results of the adrenocorticotropic hormone stimulation test remained within a normal limit.10 Furthermore, these patients were not observed to have significant intraoperative or postoperative hypotension.9 A separate study investigating the postoperative effect of a single dose of etomidate in cardiothoracic surgery showed no evidence associating etomidate exposure with significant hypotension, prolonged mechanical ventilation, longer hospital stay, or mortality.11 Although etomidate could be better than other anesthetic agents for sedation of patients with substantial congestive heart failure or compromised cardiac reserve, such patients are poor candidates for in-office anesthesia and may be more safely treated in a surgical center or hospital operating room (Box 2-11) BOX 2-11 Etomidate: Pros and cons Pros • Rapid onset of sedation/hypnosis and amnesia • Minimal cardiovascular changes • Minimal decrease in ventilatory drive • Ability to induce and maintain general anesthesia or to be used in a balanced technique for procedural sedation/general anesthesia • No histamine release Cons • Possible seizure activity and/or myoclonus (can be avoided with premedication of fentanyl or midazolam)1,8 • Inhibition of the hypothalamic-pituitary-adrenal axis causing adrenal insufficiency for up to 12 hours (in healthy patients, a normal level of adrenal function is maintained)10 • PONV • Phlebitis Dexmedetomidine Dexmedetomidine, an α2-adrenergic receptor agonist, produces sedative, anxiolytic, and analgesic effects while minimizing respiratory depression.1 It has minimal amnestic effects Its mechanism of action is, in part, the result of hyperpolarization of presynaptic receptors in the sympathetic trunk, leading to decreased norepinephrine release and attenuation of the sympathetic stress response.2,6 Consequently, dexmedetomidine is associated with dose-dependent bradycardia and hypotension However, high bolus doses have been reported to lead to loss of α2 selectivity, and the α1 effects of vasoconstriction, increased blood pressure, and reflex bradycardia can occur, resolving in approximately 15 minutes.12 Dexmedetomidine also acts centrally within the spinal cord and locus ceruleus, resulting in its sedative, anxiolytic, and analgesic effects It helps reduce shivering and has antisialagogic effects (Box 2-12) BOX 2-12 Dexmedetomidine: Pros and cons Pros • Sedation, analgesia • Reduction of shivering • Limitation of tachycardia and hypertension • Sedation closely resembling physiologic sleep2 • Minimal effect on respiratory drive • Antisialagogue • Ability to reduce or treat emergence delirium • Possible reversal of effect by α2 antagonist, such as atipamezole (not FDA cleared for human use) Cons • No amnesia • Caution required in patients with heart block (because of bradycardia) and in patients with severe congestive heart failure • Easy arousal from sedation • Slower onset and longer duration compared with those of propofol 23 www.ajlobby.com Mizukawa_Chap_02.indd 23 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia Dexmedetomidine can be given slowly in small boluses of 0.25 to 0.5 µg/kg in divided doses to maintain anesthesia and preserve spontaneous ventilation in a balanced technique Dexmedetomidine can also be used as a sole IV anesthetic agent, which requires up to 10 times the sedation dose.1 It is recommended that dexmedetomidine be administered as a constant infusion rather than in boluses Many practitioners who use dexmedetomidine balance its infusion with additional agents, such as midazolam and fentanyl, in a balanced technique similar to that of propofol infusion An infusion rate of 0.5 to µg/kg per hour, in a balanced technique, can provide adequate anesthesia but may have a prolonged recovery period compared with that of propofol.2,13 The distribution half-life of dexmedetomidine is minutes, with a peak effect at approximately 15 minutes Dexmedetomidine can also be given as a premedication, 2.5 µg/kg intramuscularly 15 minutes preoperatively, producing anxiolysis and analgesia The buccal route utilizes dexmedetomidine as an oral rinse that is swished for 15 minutes before discarding The intranasal route also provides high bioavailability and predictable sedation and anxiolysis The minimum alveolar concentration of sevoflurane is reduced when to µg/kg of intranasal dexmedetomidine (100 µg/mL solution) is administered 45 minutes preoperatively.13 α2 antagonists, such as atipamezole, have been shown to reverse the cardiovascular and sedative effects of dexmedetomidine; however, their use is not cleared by the US Food and Drug Administration (FDA) Neuromuscular Blockers Neuromuscular blockers, or paralytics, are drugs that block the activation of skeletal muscle at the motor end plate Under normal conditions, the presynaptic nerve terminal releases acetylcholine into the synaptic cleft, where it binds to the nicotinic acetylcholine receptor of the motor end plate This receptor is a pentamer, with two α subunits, one β subunit, one δ subunit, and one ε subunit Transmission of an action potential from the motor nerve to the skeletal muscle fiber requires two molecules of acetylcholine binding to the two α subunits simultaneously, which opens the channel and results in depolarization and a new action potential in the muscle tissue The paralytic agents are classified, on the basis of their mechanism of action, as depolarizing agents or non-depolarizing agents For further review of neuromuscular physiology, see chapter 21 Depolarizing agents bind to the acetylcholine receptor, which will trigger muscle contraction This effect is manifested by the initial fasciculation of skeletal muscle However, whereas binding of acetylcholine lasts only milliseconds, binding of succinylcholine to the receptor is prolonged, preventing other nerve impulses from activating the muscle.1 Succinylcholine is the most widely used depolarizing agent because of its rapid onset and short duration of action It is ideal for use in office-based anesthesia, either for elective endotracheal intubation or for treatment of laryngospasm Non-depolarizing agents also bind with high affinity to the acetylcholine receptor in a competitive manner They are divided into two classes based on their chemical structure: benzyl isoquinolinium drugs and aminosteroid drugs Benzyl isoquinolinium drugs include atracurium, cisatracurium, mivacurium, and doxacurium Aminosteroids include vecuronium and rocuronium, among others.1 When neuromuscular blockade is needed in the office anesthesia setting, it is generally for the management of airway emergencies, such as laryngospasm, so rapid onset is desired Because of its rapid onset, rocuronium is the non-depolarizing agent most commonly used for rapid sequence intubation Many studies have compared succinylcholine and rocuronium for rapid sequence intubation A Cochrane study in 2008 reviewed 40 studies comparing the two agents and showed better intubating conditions with succinylcholine.14 However, more recent studies have shown no difference in intubating conditions between rocuronium and succinylcholine in both the intensive care setting and the prehospital setting.15,16 These studies deserve consideration by office-based anesthesia providers because intensive care and prehospital settings both include 24 www.ajlobby.com Mizukawa_Chap_02.indd 24 6/20/17 10:27 AM Neuromuscular Blockers complex patient populations and conditions in which intubation is challenging and not necessarily planned, such as in patients with severe bleeding, hemodynamic instability, or critical illness.15–17 In fact, one study in the United Kingdom demonstrated that rocuronium is emerging as the first-line agent for rapid sequence intubation in the prehospital setting because of its rapid onset and lack of the undesirable side effects of hyperkalemia and myalgia.16 Clinicians should consider the characteristics of both succinylcholine and rocuronium when deciding which agent to use Although both have a rapid onset of action, the onset of succinylcholine is faster (60 seconds with a dose of 0.5 to mg/kg) than that of rocuronium (90 seconds with a dose of 0.6 mg/kg) This discrepancy can be overcome by doubling the dose of rocuronium to 1.2 mg/kg, which brings its onset closer to 60 seconds However, this dose also increases the duration of action to 70 minutes.18 The duration of action—5 to 10 minutes for succinylcholine versus 35 to 50 minutes for rocuronium—is the main factor that sways most practitioners to keep succinylcholine as the first-line agent for rapid sequence intubation.14 Because succinylcholine and rocuronium are the most widely used neuromuscular blockers in office-based anesthesia, the discussion in this chapter is limited to these two agents and sugammadex Succinylcholine Succinylcholine is the most widely used depolarizing agent because of its rapid onset and ultrashort duration of action A dose of 0.5 to mg/kg will provide muscle relaxation within 60 seconds and last for to 10 minutes.1 In an emergency situation where IV access is not achievable, an intramuscular dose of to mg/kg can be given and will have an onset of action in to minutes.17 Its short duration of action is attributed to its metabolism by acetylcholinesterase in the synaptic cleft Although some office-based anesthesia providers routinely intubate their patients and thus use succinylcholine regularly, most reserve succinylcholine for use in airway emergencies, such as laryngospasm or airway unresponsive to suctioning and positive pressure ventilation, and/or for the purpose of achieving a deeper plane of anesthesia In these situations, an intubating dose of mg/kg may not be necessary, and a dose of 0.5 mg/kg may be sufficient and preferred Caution is required when redosing within minutes because succinylcholine stimulates muscarinic acetylcholine receptors in the cardiac sinus node, causing sinus bradycardia This response can occur with the initial dose as well Ventricular arrhythmias may also occur, likely because of a lowered threshold for arrhythmia in the ventricle, hyperkalemia, and increased catecholamine release.1 Hyperkalemia is a potentially serious side effect that can lead to arrhythmia Plasma concentrations of potassium can increase up to 0.5 mEq/L after administration of succinylcholine.1 This rise is the result of sodium rushing into muscle cells and potassium exiting the cells This degree of elevation of potassium is usually tolerated well by healthy individuals, but if signs or symptoms of hyperkalemia arise, it can be treated the same as any other hyperkalemic event, with administration of 10 units of insulin and an ampule of 50% dextrose Some neuromuscular disorders can exaggerate the hyperkalemic response to succinylcholine The mechanism is a compensatory increase in the number of acetylcholine receptors found outside the synaptic cleft of the muscle cells If the number of receptors increases, more potassium will escape from the cells Conditions that can have this effect include upper or lower motor neuron defects, prolonged chemical denervation, direct muscle trauma, severe burns, rhabdomyolysis, disuse atrophy, and severe infection.19 On the contrary, in patients with conditions in which the number of acetylcholine receptors in the synaptic cleft is decreased, such as myasthenia gravis, the dose of succinylcholine may need to be increased Contraindications to the use of succinylcholine include a history of arrhythmia, especially arrhythmia triggered by changes in plasma potassium level Because succinylcholine is thought to be a trigger for malignant hyperthermia, its use is contraindicated in any patient who has a personal or family history of malignant hyperthermia Caution is necessary when using succinylcholine in patients at high risk of developing substantial hyperkalemia, including the patient populations mentioned above (Box 2-13) 25 www.ajlobby.com Mizukawa_Chap_02.indd 25 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia BOX 2-13 Succinylcholine: Pros and cons Pros • Rapid onset (30–60 seconds) • Ultrashort duration (5–10 minutes) • Ability to counteract laryngospasm and enable endotracheal intubation quickly in emergent situations Cons • Arrhythmogenic effect • Potential increase in potassium concentration up to 0.5 mEq/L • Potential sinus bradycardia, particularly after redosing within a 5-minute interval • Myalgia • Malignant hyperthermia trigger • Need for refrigeration to prolong shelf life Rocuronium Rocuronium is the most widely used non-depolarizing agent when succinylcholine is contraindicated The normal intubating dose is 0.6 mg/kg, which will provide muscle relaxation in 90 to 120 seconds and last for 35 to 50 minutes As mentioned earlier, increasing the dose to 1.2 mg/kg achieves an onset of action similar to that of succinylcholine but also increases the duration of action from 35 minutes to 70 minutes Historically, the longer duration of action has discouraged practitioners from using rocuronium, especially in an airway emergency where the ability to intubate is questionable If rocuronium is given and intubation is not possible, patient ventilation must be controlled by the clinician until spontaneous ventilation returns If the patient’s airway cannot be managed for the duration of the muscle relaxation (35 to 50 minutes), the consequences can be disastrous However, in some reports, sugammadex almost instantly reversed the muscle relaxation of non-depolarizing agents such as rocuronium and vecuronium.20 Thus, sugammadex can serve as an effective safety net when a non-depolarizing agent is given, intubation is not possible, and mask ventilation with or without airway adjuncts is not possible Despite its long duration of action, rocuronium has substantial benefits It has no absolute contraindications, except a known allergy to rocuronium It does not carry the risk of hyperkalemia, and it can be safely given to patients with neuromuscular disorders and injury Myalgia is not seen with rocuronium It does not trigger malignant hyperthermia (Box 2-14) BOX 2-14 Rocuronium: Pros and cons Pros • Rapid onset (60–90 seconds) • Ability to use in rapid sequence intubation when airway emergencies occur • No arrhythmogenic effect • No hyperkalemia • No myalgia • No malignant hyperthermia • Ability to use sugammadex to reverse effects and counteract long duration Cons • Long duration (35–50 minutes) • Emergent surgical airway may be required if rocuronium is given, intubation is not achieved, and sugammadex is not available 26 www.ajlobby.com Mizukawa_Chap_02.indd 26 6/20/17 10:27 AM Glucocorticoids Sugammadex Sugammadex (Bridion, Merck) is used as a reversal agent for rocuronium and occasionally for reversal of vecuronium and pancuronium The FDA cleared its use in the United States on December 15, 2015 Its mechanism of action is selective binding to aminosteroid neuromuscular blocking agents, such as rocuronium and vecuronium, rendering them inactive to bind to the acetylcholine receptor This effect restores muscle contractility rapidly, with an average reversal time of 1.9 to 2.1 minutes after a 6-mg/kg dose and 1.5 to 1.8 minutes after an 8-mg/kg dose Sugammadex was found to be up to 17 times faster than neostigmine in reversing blockade after the reappearance of a second posttetanic count.18 When used in an airway emergency situation in which rocuronium is given to intubate the patient but attempts to intubate and ventilate fail, a dose of 16 mg/kg is recommended to reverse this deep level of neuromuscular blockade A 16-mg/kg dose of sugammadex given minutes after administration of rocuronium reversed the neuromuscular blockade within minutes and was found to reverse blockade more rapidly than the resolution of neuromuscular blockade seen with succinylcholine.21 Because the action does not involve the acetylcholine receptor or acetylcholine, the cholinergic side effects of cholinesterase inhibitors, such as bradycardia and hypotension, are not seen.22 The ability to reblock the neuromuscular junction with rocuronium if an airway emergency arises after sugammadex is dosed has been questioned Although redosing with rocuronium within 24 hours of the administration of sugammadex is not recommended, the administration of 1.2 mg/kg of rocuronium minutes after the administration of sugammadex was shown to produce neuromuscular blockade in approximately minutes.23 Obviously, a shorter time between sugammadex dosing and rocuronium redosing will result in a longer time to neuromuscular blockade (Box 2-15) BOX 2-15 Sugammadex: Pros and cons Pros • Rapid onset (approximately minutes with a 6-mg/kg dose) • Ability to reverse even deep levels of neuromuscular blockade • Ability to use for management of a failed rapid sequence intubation attempt where ventilation is not possible • No bradycardia or hypotension resulting from cholinesterase inhibition • Ability to use a dose of 1.2 mg/kg of rocuronium to achieve neuromuscular reblockade within approximately minutes in case of an airway emergency after sugammadex dosing Cons • FDA cleared only for reversal of rocuronium and vecuronium • Can affect the efficacy of oral contraceptives24 • Patient should be monitored because neuromuscular reblockade can occur if the duration of the neuromuscular blocking agent exceeds the duration of sugammadex Glucocorticoids Cortisol, an endogenous glucocorticoid, has been mimicked pharmacologically for use in the treatment of endocrinopathies, autoimmune disorders, and asthma and other inflammatory pulmonary conditions as well as for use in the perioperative period to control pain, swelling, and PONV While synthetic formulations take advantage of the ability of steroids to inhibit inflammation and the immune response, there are many other physiologic effects of steroids that can bring unintentional harm to patients with comorbid diseases if these effects are not appreciated 27 www.ajlobby.com Mizukawa_Chap_02.indd 27 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia Physiologic effects The physiologic effects of glucocorticoids are numerous and must be understood by any practitioner administering these drugs Corticosteroids inhibit inflammation by decreasing the production of prostaglandin and leukotriene, which are inflammatory mediators.25 This effect is thought to be the work of lipocortin-1 Steroids have also been shown to attenuate the expression of cyclooxygenase, further limiting prostaglandin and leukotriene function.26 Corticosteroids also inhibit the chemotaxis and migration of immune cells to the site of injury or insult Macrophages, eosinophils, and T lymphocytes are all inhibited to some degree by glucocorticoids Steroids can also cause leukocytosis and, specifically, an increase in circulating neutrophils This effect may be a result of decreased chemotaxis to extravascular sites and glucocorticoid-induced prolongation of the life span of neutrophils.26 Corticosteroids prime the cardiovascular system to catecholamines The increased sensitivity to catecholamines increases the body’s response to stress, making increased cardiac output available to meet the increased demand for oxygen and substrate The metabolic effects of glucocorticoids also prepare the body for the increased demands of stress In gluconeogenesis, a major effect of steroids, protein is catabolized to amino acids, which are then converted to glucose for energy use Adipose tissue is also accessed and broken down to fatty acids and in turn to glucose Glycogen stores are converted to glucose for consumption All of these processes result in relative hyperglycemia Glucocorticoids also inhibit osteoblast function and have been shown to be associated with euphoria, depression, lethargy, and psychosis Use in office-based anesthesia In office-based anesthesia, glucocorticoids are routinely used as steroid replacement in the perioperative period in patients with adrenal insufficiency, for the management of postoperative pain and swelling, and for the management of PONV They are also useful adjuncts in asthmatic patients The numerous formulations of synthetic glucocorticoids are generally equivalent in their anti-inflammatory efficacy but vary in potency and duration.27 Table 2-1 shows the relative potency and duration of specific glucocorticoids Table 2-1 Relative potency and duration of action of glucocorticoids* Formulation Short-acting Equivalent dose (mg) 25 20 Relative anti-inflammatory effect 0.8 Relative mineralcorticoid effects 0.8 Duration of action (h) 8–12 8–12 Methylprednisolone 0.5 12–36 Prednisolone 0.8 12–36 Prednisone 0.8 12–36 Triamcinolone 12–36 Betamethasone 0.6 30 36–54 Dexamethasone 0.75 30 36–54 Glucocorticoid Cortisone Hydrocortisone Intermediate-acting Long-acting *Adapted from Flynn and Hemel.24 28 www.ajlobby.com Mizukawa_Chap_02.indd 28 6/20/17 10:27 AM References Dexamethasone Dexamethasone is the most widely used steroid for the management of postoperative pain, swelling, and nausea (Box 2-16) It is generally dosed at to mg for adults Its duration is approximately 36 to 54 hours One study demonstrated a statistically significant difference in postoperative pain, swelling, and nausea after extraction of third molars when mg of dexamethasone was given preoperatively, compared with a placebo.28 Dexamethasone, like most glucocorticoids, has a delayed onset because of its mechanism of action Glucocorticoids bind to glucocorticoid receptors in the cytoplasm of cells This binding releases chaperone proteins from the receptor, making the receptor complex permeable into the nucleus, where it binds to DNA and affects transcription.26 Because of its side effect of hyperglycemia, the administration of dexamethasone to patients with diabetes is the subject of debate Although it is well documented that even single doses of dexamethasone given preoperatively will cause hyperglycemia in the postoperative period,29 the clinical relevance of this hyperglycemia, and its effect on surgical outcomes and perioperative morbidity and mortality, is not well documented It is generally understood that, despite a transient period of elevated blood glucose, a 4- to 8-mg dose can be safely given to a patient with well-controlled type diabetes Prudence should be used in administering dexamethasone to patients with poorly controlled diabetes Consultation with the patient’s primary care physician to review the most recent hemoglobin A1c level is useful in assessing recent glycemic control to determine whether dexamethasone is appropriate BOX 2-16 Dexamethasone: Pros and cons Cons • Possible itching around the perineum and genitals after rapid injection • Slower onset of action (30–60 minutes) • Transient hyperglycemia Pros • Reduced postoperative pain and swelling • Reduced PONV • Ability to use adjunctively in asthmatic patients • Duration of 36–54 hours Conclusion To a large degree, the safety of office-based anesthesia should be attributed to the wide array of drugs available for use Because each drug has characteristics that make it favorable in some patients but unfavorable in other patients, depending on their comorbid diseases, a thorough knowledge of these diseases as well as the physiologic effects of these drugs is critical to safely administer anesthesia Using a blanket regimen of anesthetic drugs for every patient is dangerous and should be avoided It is this tailoring of drugs to each individual patient, based on his/her medical conditions, that becomes the basis and foundation of the art of office-based anesthesia References Becker DE Pharmacodynamic considerations for moderate and deep sedation Anesth Prog 2012;59:28–42 Vuyk J, Sitsen E, Reekers M Intravenous anesthetics In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Saunders, 2014:821– 863 Fukuda K Opioid analgesics In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Saunders, 2014:864–914 Garcia P, Whalin MK, Sebel PS Intravenous anesthetics In: Hemmings HC Jr, Egan TD Pharmacology and Physiology for Anesthesia Philadelphia: Saunders, 2013:137–158 Giovannitti JA Jr Pharmacology of intravenous sedative/anesthetic medications used in oral surgery Oral Maxillofac Surg Clin North Am 2013;25:439–451 Treasure T, Bennett J Office-based anesthesia Oral Maxillofac Surg Clin North Am 2007;19:45–57 29 www.ajlobby.com Mizukawa_Chap_02.indd 29 6/20/17 10:27 AM 2 • Pharmacology and Utility of Intravenous Anesthesia 19 Martyn J, Richtsfeld M Succinylcholine-induced hyperkalemia in acquired pathologic states: Etiologic factors and molecular mechanisms Anesthesiology 2006;104:158–169 Haas DA Pharmacology of agents used for intravenous sedation Oral Maxillofac Surg Clin North Am 2001;13:75–84 Miner J, Danahy M, Moch A, Biros M Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department Ann Emerg Med 2007;49:15–22 20 Woloszczuk-Gębicka B, Zawadzka-Głos L, Lenarczyk J, Sitkowska BD, Rzewnicka I Two cases of the “cannot ventilate, cannot intubate” scenario in children in view of recent recommendations Anaesthesiol Intensive Ther 2014;46:88–91 Godwin SA, Burton JH, Gerardo CJ, et al; American College of Emergency Physicians Clinical policy: Procedural sedation and analgesia in the emergency department Ann Emerg Med 2014;63:247–258 10 Schenarts CL, Burton JH, Riker RR Adrenocortical dysfunction following etomidate induction in emergency department patients Acad Emerg Med 2001;8:1–7 21 de Boer HD, Driessen JJ, Marcus MA, Kerkkamp H, Heeringa M, Klimek M Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: A multicenter, dose-finding and safety study Anesthesiology 2007;107:239–244 11 Wagner CE, Bick JS, Johnson D, et al Etomidate use and postoperative outcomes among cardiac surgery patients Anesthesiology 2014;120:579–589 22 Abrishami A, Ho J, Wong J, Yin L, Chung F Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade Cochrane Database Syst Rev 2009;(4):CD007362 12 Virtanen R, Savola JM, Saano V, Nyman L Characterization of the selectivity, specificity and potency of medetomidine as an alpha-2 adrenergic agonist Euro J Pharmacol 1988;150:9–14 23 Cammu G, de Kam PJ, De Graeve K, et al Repeat dosing of rocuronium 1.2 mg kg-1 after reversal of neuromuscular block by sugammadex 4.0 mg kg-1 in anaesthetized healthy volunteers: A modelling-based pilot study Br J Anaesth 2010;105:487–492 13 Giovannitti J Jr, Thoms SM, Crawford JJ s-2 adrenergic receptor agonists: A review of current clinical applications Anesth Prog 2015;62:31–39 24 Flynn M, Hemel SK Adrenal cortical steroids In: Drug Facts and Comparisons 1997 St Louis: Wolters Kluwers Health, 1997;122–128 25 Becker DE Basic and clinical pharmacology of glucocorticosteroids Anesth Prog 2013;60:25–32 14 Perry JJ, Lee JS, Sillberg VA, Wells GA Rocuronium versus succinylcholine for rapid sequence induction intubation Cochrane Database Syst Rev 2008;(2):CD002788 [update 2015;(10):CD002788] 26 Barnes PJ Anti-inflammatory actions of glucocorticoids: Molecular mechanisms Clin Sci (Lond) 1998;94:557–572 15 Marsch SC, Steiner L, Bucher E, et al Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: A prospective, randomized controlled trial Crit Care 2011;15:R199 27 Shaikh S, Verma H, Yadav N, Jauhari M, Bullandgowda J Applications of steroid in clinical practice: A review ISRN Anesth 2012;2012:985495 16 Hartly EL, Alcock R Rocuronium versus suxamethonium: A survey of first-line muscle relaxant use in UK prehospital rapid sequence induction Prehosp Disaster Med 2015;30:184–186 28 Baxendale BR, Vater M, Lavery KM Dexamethasone reduces pain and swelling following extraction of third molars Anaesthesia 1993;48:961–964 17 Stollings JL, Diedrich DA, Oyen LJ, Brown DR Rapid-sequence intubation: A review of the process and considerations when choosing medications Ann Pharmacother 2014;48:62–76 29 Hans P, Vanthuyne A, Dewandre PY, Brichant JF, Bonhomme V Blood glucose concentration profile after 10 mg dexamethasone in nondiabetic and type diabetic patients undergoing abdominal surgery Br J Anaesth 2006;97:164–170 18 Naguib M, Lien CA, Meistelman C Pharmacology of neuromuscular blocking drugs In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Saunders, 2014:958–994 30 www.ajlobby.com Mizukawa_Chap_02.indd 30 6/20/17 10:27 AM CHAPTER Pharmacology and Utility of Inhalation Anesthesia Charles H Kates, dds, pa www.ajlobby.com Mizukawa_Chap_03.indd 31 6/20/17 10:27 AM 3 • Pharmacology and Utility of Inhalation Anesthesia Overview of Inhalation Anesthesia Over the last several decades, clinicians have moved away from the use of inhalation anesthesia and toward the use of total intravenous anesthesia in office-based oral and maxillofacial surgery This chapter reintroduces inhalation anesthesia as a viable alternative and adjunctive modality in modern office-based oral and maxillofacial surgery Advantages of inhalation anesthesia Inhalation anesthesia allows for maximum control of anesthetic depth with depression of glottic reflexes at low concentrations, thereby minimizing or eliminating the risk of laryngospasm Inhalation anesthesia provides unparalleled versatility as a primary or adjunctive anesthetic modality Patients are fully awake at discharge with no prolonged effects or possibility of silent airway obstruction or anesthetic relapse after they leave the clinician’s office Inhalation anesthesia results in little or no nausea or vomiting when properly administered, and adjunctive medications are rarely needed Disadvantages of inhalation anesthesia The primary disadvantages of inhalation anesthesia are cost and the need for an anesthesia circuit and vaporizers Sevoflurane costs approximately US $130 per bottle (250 mL) The anesthesia machine should be certified annually, and it should have a circle absorber that will allow for maximum economy and reduction of dehydration Because requirements vary from state to state, the practitioner should verify anesthesia machine certification requirements with the state board governing dental anesthesia In addition to the standard monitoring, monitoring of the fraction of inspired oxygen (FiO2) and continuous patient temperature monitoring are necessary The provider must be prepared to treat malignant hyperthermia, although the occurrence of this complication in dental offices is extremely rare Mechanism of action of inhaled anesthetics The mechanism of action of inhaled anesthetics remains poorly understood and cannot be explained by a single molecular mechanism Inhaled anesthetics not act on a single, universal target The potency of inhaled anesthetics correlates with lipid solubility and interactions with hydrophobic targets Inhalation anesthetics exert their action by binding to critical signaling proteins Briefly, ion channels associated with the neurotransmitters γ-aminobutyric acid (GABA), glycine, and N-methyl-D-aspartate (NMDA) are likely the molecular targets and site of action of inhaled anesthetics.1 Inhaled anesthetics enhance inhibitory synaptic transmission through presynaptic release of GABA and postsynaptic potentiation of GABA and glycine-mediated ion channels Inhaled anesthetics inhibit excitatory release of the neurotransmitter glutamate and inhibit glutamate receptors Inhaled anesthetics also inhibit postsynaptic excitatory NMDA and nicotinic acetylcholine receptors Nitrous Oxide Nitrous oxide (N2O) is used primarily as a sedative-analgesic agent or in combination with volatile inhaled anesthetics to decrease the minimum alveolar concentration (MAC) and the inhaled concentration of the volatile anesthetic In office-based oral and maxillofacial surgery, nitrous oxide is often used to supplement intravenous sedation The only modern anesthetic agent that is inorganic, nitrous oxide is colorless and odorless It is stored as a liquid The pressure in the tank is unrelated to the volume remaining in the cylinder The use of 65% nitrous oxide decreases the MAC of volatile anesthetics by 50%, and the MACs of each volatile anesthetic are additive 32 www.ajlobby.com Mizukawa_Chap_03.indd 32 6/20/17 10:27 AM Nitrous Oxide In adults, nitrous oxide attenuates the circulatory and respiratory effects of other volatile anesthetics In the so-called “second gas effect,” when nitrous oxide is added at high concentration, the rapid uptake will decrease the alveolar volume, increase the alveolar concentration of the volatile agent, and draw in more of the anesthetic mixture from the upper airway Cardiovascular effects With administration of nitrous oxide, the arterial blood pressure, cardiac output, and heart rate remain unchanged or increase slightly Nitrous oxide stimulates catecholamine release, and there is a slightly higher incidence of epinephrine-induced dysrhythmias compared with ether-based anesthetics such as sevoflurane and isoflurane Respiratory effects Tachypnea occurs as a result of decreased tidal volume Minimal change is seen in minute ventilation and resting arterial carbon dioxide (CO2) levels The hypoxic drive is markedly depressed by even small amounts of nitrous oxide Cerebral effects Nitrous oxide results in mild elevation of intracerebral pressure, increased cerebral blood volume and flow, and increased cerebral oxygen consumption It can be used for analgesia in minor procedures at levels below the MAC Neuromuscular effects Nitrous oxide does not cause notable muscle relaxation, although patients demonstrate skeletal muscle rigidity when it is used in high concentrations in hyperbaric chambers It is not associated with malignant hyperthermia Renal and hepatic effects Nitrous oxide decreases renal blood flow by increasing renal vascular resistance A drop in glomerular filtration rate and urinary output occurs Hepatic blood flow may decrease but does so to a lesser degree than when volatile agents are used Biotransformation and toxicity Nitrous oxide is mostly exhaled unchanged in form A small amount (less than 0.01%) diffuses through the skin It can cause bone marrow depression (by means of inhibition of vitamin B12-dependent enzymes) and can result in peripheral neuropathies It is teratogenic and must be avoided during the first and second trimesters of pregnancy Contraindications Nitrous oxide tends to diffuse into air-containing cavities more rapidly than the air diffuses out (nitrous oxide is 35 times more soluble in blood than nitrogen is) Nitrous oxide must be avoided in patients with air embolism, acute intestinal obstruction, intracranial air, pulmonary air cyst, intraocular air bubbles, tympanic membrane grafting, or recent eye surgery 33 www.ajlobby.com Mizukawa_Chap_03.indd 33 6/20/17 10:27 AM 3 • Pharmacology and Utility of Inhalation Anesthesia Isoflurane Isoflurane is a chemical isomer of enflurane It is nonflammable and has a pungent odor The main advantages of isoflurane are its cost and the ability to use it in older patients with controlled cardiac disease In the author’s experience, isoflurane is not the inhaled anesthetic of choice for use in robust individuals, such as athletes or young adults, or in hyperactive individuals, unless it is used in combination with adjunctive intravenous medications In some patients, it leaves a metallic taste in the mouth Cardiovascular effects Isoflurane causes minimal cardiac depression, and cardiac output is maintained Tachycardia sometimes occurs due to preservation of carotid baroreflexes and mild β-adrenergic stimulation An increase of inhaled concentration causes a reduction of arterial blood pressure because of a decrease in systemic vascular resistance and an increase in muscle blood flow Isoflurane increases coronary arterial blood flow Respiratory effects At low levels (0.1 MAC), isoflurane blunts the normal ventilatory response to hypoxia and hypercapnia Minute ventilation falls Isoflurane irritates upper airway reflexes and is a bronchodilator Cerebral effects Isoflurane increases cerebral blood flow and intracranial pressure Its effects are less pronounced than those of halothane or enflurane and are reversible with hyperventilation Hyperventilation is not required for the prevention of intracranial hypertension (as it is with halothane) Isoflurane reduces cerebral metabolic oxygen requirements At MAC, it produces an electrically silent electroencephalogram Brain protection is necessary during episodes of cerebral ischemia Neuromuscular effects Isoflurane relaxes skeletal muscles Renal and hepatic effects Isoflurane decreases renal blood flow, glomerular filtration rate, and urinary output Total hepatic blood flow is reduced Biotransformation and toxicity Isoflurane is metabolized to trifluoroacetic acid Its limited metabolism minimizes the risk of substantial hepatic dysfunction Contraindications No unique contraindications or drug interactions of isoflurane have been identified 34 www.ajlobby.com Mizukawa_Chap_03.indd 34 6/20/17 10:27 AM Desflurane Desflurane Desflurane has a chemical structure similar to that of isoflurane However, the slight difference in chemical structure results in physical properties of desflurane that are very different from those of isoflurane Its high vapor pressure requires the use of a heated, pressurized vaporizer Its uptake, distribution, and elimination are rapid, requiring tighter control of the anesthetic level The wake-up time is half that of isoflurane Desflurane is 25% as potent as other volatile agents It is pungent and irritating to breathe and can cause laryngospasm Because of its low blood gas partition coefficient, desflurane has very low solubility in blood and therefore results in very rapid induction and recovery Were it not for its pungent odor and tendency to cause laryngospasm, it might be ideal for use in office-based oral and maxillofacial surgery Unfortunately, it is very difficult to use with mask induction (which is essential for children and for some adults with special needs) Cardiovascular effects The cardiovascular effects of desflurane are similar to those of isoflurane Rapid increases in concentration lead to transient elevation in heart rate, arterial blood pressure, and catecholamine levels that are more pronounced than those seen with isoflurane Unlike isoflurane, desflurane does not increase coronary arterial blood flow Respiratory effects Desflurane causes a decrease in tidal volume and an increase in respiratory rate It causes an overall decrease in alveolar ventilation by producing a rise in resting arterial partial pressure of CO2 (Paco2) It depresses the ventilatory response to increasing Paco2 Desflurane can cause upper airway irritation, salivation, breath holding, coughing, and laryngospasm It should be used with caution for inhalation induction Cerebral effects Desflurane causes vasodilation of the cerebral vasculature It increases cerebral blood flow and intracranial pressure at normotension and normocapnia It causes a decline in the cerebral metabolic rate of oxygen and a decrease in cerebral oxygen consumption Neuromuscular effects Dose-dependent skeletal muscle relaxation is seen with desflurane Renal and hepatic effects Desflurane has no nephrotoxic effects Liver function tests are unaffected, and no hepatic injury occurs Biotransformation and toxicity Metabolism of desflurane is minimal At low flows, more extensive degradation by desiccated carbon dioxide absorbent can result in potentially clinically relevant levels of carbon monoxide Contraindications Desflurane is contraindicated in patients with severe hypovolemia, malignant hyperthermia, and/or intracranial hypertension 35 www.ajlobby.com Mizukawa_Chap_03.indd 35 6/20/17 10:27 AM 3 • Pharmacology and Utility of Inhalation Anesthesia Drug interactions Desflurane potentiates non-depolarizing muscle relaxants Sevoflurane Sevoflurane is currently the agent of choice for inhalation anesthesia in office-based oral and maxillofacial surgery It can be used easily for mask induction, inadvertent overdose can be managed easily, and it does not precipitate laryngospasm It can also be used for inhalational sedation at 0.25% to 0.5% inhaled concentrations Its primary disadvantages are cost and occasionally a stormy recovery Sevoflurane is nonpungent and has low blood solubility It is characterized by a rapid increase in alveolar anesthetic concentration, rapid emergence, and a rapid fall in alveolar anesthetic concentration Cardiovascular effects Sevoflurane mildly depresses cardiac contractility It causes a decrease in systemic vascular resistance (less than that seen with isoflurane or desflurane) Cardiac output is not well maintained with sevoflurane (the decrease is greater than that caused by isoflurane or desflurane) Respiratory effects Like isoflurane, sevoflurane depresses respiration Sevoflurane can reverse bronchospasm Cerebral effects Like isoflurane and desflurane, sevoflurane causes an increase in cerebral blood flow and intracranial pressure Cerebral metabolic requirements are decreased It impairs autoregulation in the brain Neuromuscular effects Sevoflurane causes muscle relaxation Hepatic effects Sevoflurane decreases blood flow in the portal vein and increases blood flow in the hepatic artery Biotransformation and toxicity Sevoflurane is metabolized by the liver microsomal enzyme P450 Soda lime can degrade sevoflurane, producing a nephrotoxic end product compound that has not been found to be clinically relevant.2 A new carbon dioxide absorbent (Amsorb; Armstrong Medical) does not produce this compound.1,3 Clinical Inhalation Anesthesia Techniques The action of an inhaled anesthetic agent is governed by its physical and pharmacologic properties, so the clinician should choose an agent that has a low solubility and MAC to achieve rapid induction, rapid recovery, and maximum 36 www.ajlobby.com Mizukawa_Chap_03.indd 36 6/20/17 10:27 AM Clinical Inhalation Anesthesia Techniques control of anesthetic depth In office-based oral and maxillofacial surgery, inhalation anesthesia can be used by itself or can be combined with intravenous modalities The one-breath technique with sevoflurane Premedicate the patient with 0.2 mg glycopyrrolate and a small amount of benzodiazepine while preoxygenating the patient with a non-rebreather mask Flood the breathing circuit with 8% sevoflurane and oxygen at a fresh gas flow of L/min Have the patient a forced exhalation Place a full face mask on the patient Have the patient a forced inhalation (Avoid mask leak.) Have the patient retain full lung inflation Expect unconsciousness within 15 to 30 seconds Maintain 6% to 8% sevoflurane for to minutes, or until induction is complete As a deeper level of anesthesia is reached, an oral or nasal airway may be required (Avoid mask leak.) 10 Establish the airway with one of the following modalities: • Open technique (nasal mask, nasal airway with connector) • Supraglottic device (laryngeal mask airway, King supraglottic airway, cuffed oropharyngeal airway) • Closed technique (eg, endotracheal intubation, which may require the use of a small amount of muscle relaxant) 11 Place an oropharyngeal barrier (open technique) or a throat pack (closed technique) 12 Reduce the concentration of sevoflurane to maintenance levels Balanced techniques Intravenous induction with inhalational maintenance Premedicate the patient with a small dose of benzodiazepine (which provides amnesia), glycopyrrolate (controls secretions, limits bradycardia), and, if needed, a narcotic of the clinician's choice Perform intravenous induction with the agent of choice Complete the induction with the inhaled agent Maintain anesthesia with inhaled agents of choice Inhalation anesthesia as an adjunct to intravenous sedation Sedate the patient in the usual fashion with one of the following combinations: • Benzodiazepine, propofol, narcotic • Ultra-short-acting narcotic, propofol, ketamine • Dexmedetomidine, benzodiazepine, narcotic • Any other drug combination of choice If the patient becomes uncooperative, add low-concentration sevoflurane (0.25% to 0.5% will usually suffice) Inhalation anesthesia as an adjunct to nitrous oxide sedation Administer nitrous oxide and oxygen in the usual fashion Add 0.25 to 0.5 MAC of sevoflurane before administering local anesthesia Inject the local anesthetic agent Maintain anesthesia with administration of nitrous oxide and oxygen Add 0.25 to 0.5 MAC of sevoflurane as needed (0.25% to 0.5%) 37 www.ajlobby.com Mizukawa_Chap_03.indd 37 6/20/17 10:27 AM 3 • Pharmacology and Utility of Inhalation Anesthesia Summary This chapter discusses how inhalation anesthetic techniques and modalities can be used in modern office-based oral and maxillofacial surgery The pharmacology and pertinent characteristics of inhaled anesthetics are reviewed and integrated with clinical applications References Dosch MP, Tharp D The Anesthesia Gas Machine Detroit: University of Detroit Mercy Graduate Program in Nurse Anesthesiology, 2016 http://healthprofessions.udmercy.edu/programs/crna/agm/ Revised March 2016 Accessed 19 May 2016 Gentz BA, Malan TP Jr Renal toxicity with sevoflurane: A storm in a tea cup? Drugs 2001;61:2155–2162 Rudolph U, Antkowiak B Molecular and neuronal substrates for general anaesthetics Nat Rev Neurosci 2004;5:709–720 38 www.ajlobby.com Mizukawa_Chap_03.indd 38 6/20/17 10:27 AM CHAPTER Local Anesthesia Basics James Bradford Lewallen, dds, md, msc Paul G Sims, dds Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_04.indd 39 6/20/17 10:27 AM 4 • Local Anesthesia Basics The two classes of local anesthetics are amino esters and amino amides They differ in the type of cross-linkage between the aromatic ring and the tertiary amine that forms the basic chemical structure of all local anesthetics In general, compared with amides, ester local anesthetics are metabolized more rapidly because of plasma cholinesterase metabolism and are more allergenic Amides undergo hepatic metabolism, resulting in longer half-lives; are less allergenic; and are the primary anesthetics used in clinical practice Amide anesthetics are commonly recognized by the two instances of the letter i in the name Clinically relevant amides include lidocaine, bupivacaine, mepivacaine, prilocaine, articaine, and ropivacaine (Table 4-1) Esters have one i in the name and include tetracaine, chloroprocaine, procaine, benzocaine, and cocaine Benzocaine and cocaine are primarily used for topical application Other common topical formulations helpful for intravenous catheter or laceration site anesthesia in children are EMLA (eutectic mixture of the local anesthetics lidocaine 2.5% and prilocaine 2.5%) and LET (lidocaine 4%, epinephrine 0.1%, and tetracaine 0.5%) Table 4-1 Clinically relevant amide local anesthetics Local anesthetic (%) Absolute maximum dose (mg) Pregnancy class 500 C Anesthetic Brand name(s) Articaine Septocaine Epinephrine 1:100,000 Bupivacaine Marcaine 0.5 Epinephrine 1:200,000 1.3 90 C Lidocaine Xylocaine None Epinephrine 1:50,000 Epinephrine 1:100,000 4.5 7 300 500 500 B • Carbocaine • Polocaine None 400 C Prilocaine Citanest Plain Citanest Forte 400 B Ropivacaine* Naropin 0.5 200 B Mepivacaine Vasoconstrictor Maximum dose1 (mg/kg) None Epinephrine 1:200,000 None *Not available in dental carpule Mechanism of Action Local anesthetics affect sodium ion channels in nerve fibers by preventing channel activation and mechanically blocking the passage of sodium These actions inhibit depolarization and impulse conduction Conduction begins at the nodes of Ranvier, the gaps in the myelin sheath that encircles the nerve axons These gaps give the anesthetic a point of entry into the axon (Fig 4-1) In the uncharged, basic form, local anesthetics can cross through the lipid-rich axon and gain access to the ion channel binding sites from the axoplasmic aspect of the nerve terminal Inside the nerve terminal, the anesthetic changes to the charged form through ionization, and the cationic form of the anesthetic attaches to the receptor site Binding is improved when the channel is in the activated or inactivated form and is decreased when channels are in the resting state, a characteristic known as frequency-dependent blockade.2 The small myelinated axons (Aγ and Aδ) are anesthetized first, the larger myelinated axons (Aα and Aβ) are anesthetized next, and unmyelinated axons (C fibers) are anesthetized last 40 www.ajlobby.com Mizukawa_Chap_04.indd 40 6/20/17 10:27 AM Mechanism of Action Fig 4-1 Local anesthesia mechanism of action The local anesthetic agent (LA) is introduced in charged form (LAH+) outside the nerve (1), changes to uncharged form for entry into the nerve (2), and recharges and binds to the intraneural aspect of the channel (3), resulting in a mechanical blockade of sodium passage (4) Note that in step 1, the pKa of the LA will determine how much of the drug is in the uncharged form As the pKa nears the physiologic pH of 7.4, a greater portion of the drug is in the uncharged form, which enters the lipid bilayer Thus, pKa affects the onset of action In step 2, lipophilicity dictates potency Highly lipophilic LA will readily cross the lipid bilayer In step 3, protein binding determines the duration of action As protein binding increases, the LA will have a longer duration of action due to prolonged binding to the sodium channel Myelin sheath Protein binding Blockage of sodium Needle Na+ LAH+ LAH+ pKa/pH of tissue LA LA Lipid solubility The action of local anesthetics is influenced by pKa, lipid solubility, protein binding, and vasoactivity (Tables 4-2 and 4-3) The pKa of a solution, which is the pH at which 50% of the drug is in its charged form and 50% is in its uncharged form, dictates the onset of action of a drug A local anesthetic exists in two forms: charged, or ionized, and uncharged, or nonionized Each has opposing chemical features The charged form is hydrophilic and tends to bind the protein channel, whereas the uncharged form is lipophilic and tends not to bind the protein channel but can more readily cross the lipid bilayer than the charged form can Assuming that the pH of tissue is 7.4, a local anesthetic with a pKa of 7.4 would have 50% of the drug in the charged, ionized form and 50% in the uncharged, nonionized form in tissue The pKa of most local anesthetics is > 7.4; therefore, > 50% of the drug is in the charged form A higher pKa means that a greater proportion of the drug is in the charged form, which does not enter the axon readily Conversely, a lower pKa means that a greater proportion of the drug is in the uncharged form, which is able to enter the axoplasmic space and bind the ion channel Thus, the onset of action is more rapid with a lower pKa For example, lidocaine, which has a pKa of 7.9, has a faster rate of onset than bupivacaine, which has a pKa of 8.1 Infection causes tissue acidity (lower pH), which increases ionization, thus resulting in the presence of more of the charged form of an anesthetic and slower uptake into nerves High volumes of an anesthetic of comparatively lower concentration in a confined tissue space can accelerate onset of anesthesia because of increased pressure for mass diffusion through adjacent tissue.3 Table 4-2 Factors affecting action of local anesthetics Factor Characteristic Affected Effect pKa Onset of action Low pKa = fast onset High pKa = slow onset Lipophilicity Potency Low lipophilicity = low potency High lipophilicity = high potency Protein binding Duration of action Low protein binding = decreased duration High protein binding = increased duration 41 www.ajlobby.com Mizukawa_Chap_04.indd 41 6/20/17 10:27 AM 4 • Local Anesthesia Basics Table 4-3 Characteristics of common local anesthetics Protein binding Relative vasodilatory value* Duration (min) Anesthetic pKa Lipid solubility Lidocaine 7.7 4.0 65 Lidocaine with epinephrine 7.7 4.0 65 60 180–300 Pulpal Soft tissue 5–10 60–120 Bupivacaine 8.1 NA 95 2.5 90–180 240–540 Mepivacaine 7.9 1.0 75 0.8 20–40 120–180 Prilocaine 7.7 1.5 55 0.5 10–60 90–240 Prilocaine with epinephrine 7.7 1.5 55 0.5 60–90 180–480 Articaine 7.8 95 60–75 180–360 Ropivacaine 8.1 94 NA 120–360 180–200 17 2.8 NA, not available *Relative vasodilatory value is the vasoactivity using lidocaine as reference value The potency of local anesthetics describes the amount of a drug required to evoke a response compared with the dose of another drug required to evoke the same degree of response Potency is dictated by lipophilicity Highly lipophilic drugs readily cross the lipid-rich nerve sheath, whereas less lipophilic drugs will require a higher dose to elicit the same response Bupivacaine and ropivacaine are the most potent injectable anesthetics, compared with lidocaine, mepivacaine, and prilocaine, which have near equal potency The lipophilicity of a local anesthetic also accounts for its ability to cross the blood-brain barrier and the placenta, which is pertinent in the consideration of contraindications or complications Lipid solubility also affects the duration of action of local anesthetics, although protein binding is more influential in determining this trait Because sodium channels are proteins, the affinity of a local anesthetic to bind the channels dictates the duration of its action A higher protein binding results in a longer duration of action For example, the protein binding of lidocaine is 65%, whereas that of bupivacaine is 95%, resulting in a longer duration of bupivacaine compared with that of lidocaine.3 Local anesthetics generally cause vasodilation at therapeutic doses and vasoconstriction at subtherapeutic doses Cocaine and the S(−) enantiomer of ropivacaine are vasoconstricting The more vasodilating the anesthetic, the shorter the duration of its effect, because dilated vasculature promotes anesthetic clearance The vasoconstricting effects of cocaine and ropivacaine are beneficial in hemostasis Vasoconstrictors such as epinephrine are added to slow the distribution of anesthetic away from target tissues In the United States, two vasoconstrictors are available in dental carpules Epinephrine is the most widely used and is available in dental carpules in concentrations of 1:100,000 and 1:200,000 Levonordefrin is available in a formulation with mepivacaine at a concentration of 1:20,000 Epinephrine and levonordefrin have only a few differences Epinephrine is an agonist of the α- and β-adrenergic receptors Thus, it will cause a dose-dependent increase in systemic vascular resistance and vasoconstriction, as well as an increase in chronotropy/inotropy of the myocardium Levonordefrin displays its main effects on the α-adrenergic receptors and minimally affects the β receptors Thus, local effects of vasoconstriction and hemostasis are seen, and systemic exposure will result in increased systemic vascular resistance and blood pressure However, the heart rate will theoretically remain stable, if not decrease, because of reflex bradycardia from the increased blood pressure and the lack of a β agonist to oppose that reflex 42 www.ajlobby.com Mizukawa_Chap_04.indd 42 6/20/17 10:27 AM Dosing Dosing Local anesthetic dosing is primarily a function of metabolism and elimination but is influenced by the method of delivery and by site-specific factors, such as infection Often, alterations in dosing are necessary in special patient groups, such as children, elderly patients, and patients with medical comorbidities Amide local anesthetics are primarily metabolized by the cytochrome P450–linked enzymes in the liver and eliminated by the kidneys Ester anesthetics undergo hydrolysis in the plasma by the enzyme pseudocholinesterase Plasma carboxylesterase contributes to the metabolism of the amide anesthetic articaine, resulting in partial extrahepatic metabolism With relatively normal prerenal metabolism, the expected excretion of unchanged drug ranges from 10% for cocaine to 3% for lidocaine Impairment of cardiac, liver, or renal function necessitates reductions in dosing Common comorbidities that may require dose reductions include congestive heart failure, hepatic cirrhosis, shock, and severe renal failure The common factor affecting dosing in these patients is the slowing or inhibition of metabolism and distribution Patients with atypical pseudocholinesterase, the enzyme required to hydrolyze ester anesthetics and succinylcholine, will have prolonged metabolism and are at higher risk of toxicity after administration of an ester anesthetic The incidence of atypical pseudocholinesterase is between in 3,200 and in 5,000.4 The prudent practitioner should individualize anesthetic dosing to the patient, while keeping absolute maximum values in mind Dosing requires a twofold consideration because of anesthetic and vasoconstrictor limits Age, comorbidities, and other factors affecting metabolism primarily influence anesthetic dosing, whereas cardiac health and the location of the injection are more important considerations in vasoconstrictor dosing Concentrations and dilutions of anesthetic and vasoconstrictor must be converted to milligrams per milliliter because the maximum dosing guidelines are given in milligrams per kilogram The percentage of an anesthetic solution is the number of grams of anesthetic per milliliter of fluid A 100% solution has gram, or 1,000 mg, of drug per mL of fluid Therefore, a 10% solution will have 100 mg/mL, and a 1% solution will have 10 mg/mL A 4% solution will have 40 mg/mL For vasoconstrictors, the concentration is expressed as a ratio A 1:1 ratio of vasoconstrictor means gram of vasoconstrictor per mL of solution Therefore, a 1:1,000 concentration will have g, or 1,000 mg, of vasoconstrictor per 1,000 mL of solution, or mg/mL A 1:100,000 concentration will have g, or 1,000 mg, per 100,000 mL, or 0.01 mg/mL A 1:200,000 concentration will have g, or 1,000 mg, per 200,000 mL, or 0.005 mg/mL If a carpule (1.7 mL) of lidocaine 2% with 1:100,000 epinephrine is given, a total of 34 mg of lidocaine (1.7 mL × 20 mg/mL of 2% solution) and 0.017 mg of epinephrine (1.7 mL × 0.01 mg/mL of 1:100,000 solution) is given The maximum recommended dose of epinephrine in patients without cardiac comorbidities is 0.2 mg (11 carpules of 1:100,000 epinephrine, with 1.7 mL in each carpule) In patients with cardiovascular disease, the maximum recommended dose of epinephrine in local anesthetics is 0.04 mg (two carpules) Tables 4-4 and 4-5 detail the concentrations of local anesthetic and vasoconstrictors Table 4-4 Local anesthetic dilutions and corresponding concentrations Table 4-5 Vasoconstrictor dilutions and corresponding concentrations Vasoconstrictor Local anesthetic Percentage Concentration Ratio Concentration based on ratio Concentration 100 g/mL (1,000 mg/mL) 1:1 g/1 mL or 1,000 mg/1 mL 1,000 mg/mL 40 mg/mL 1:1,000 1,000 mg/1,000 mL 30 mg/mL 1:50,000 1,000 mg/50,000 mL 0.02 mg/mL 20 mg/mL 1:100,000 1,000 mg/100,000 mL 0.01 mg/mL 10 mg/mL 1:200,000 1,000 mg/200,000 mL 0.005 mg/mL 0.5 mg/mL mg/mL 43 www.ajlobby.com Mizukawa_Chap_04.indd 43 6/20/17 10:27 AM 4 • Local Anesthesia Basics If multiple anesthetic agents are used, experts recommend using the lowest maximum dose value of the individual agents as the overall maximum dose for the combined anesthetics For example, when bupivacaine and lidocaine are used together, the recommended maximum dose would be 90 mg (1.3 mg/kg) of total anesthetic, which is the maximum recommended dose of bupivacaine.2 Despite this recommendation, greater doses of local anesthetic are often used For the extraction of all four third molars, providers often use two carpules (3.4 mL) of 0.5% bupivacaine and four carpules (6.8 mL) of 2% lidocaine The patient in this example will receive 153 mg of local anesthetic (17 mg of bupivacaine and 136 mg of lidocaine) Redosing of local anesthetic is often not necessary in most dental procedures because of their short procedure times If redosing is indicated, the clinician must be aware of the elimination half-life of the anesthetics used The elimination half-life of lidocaine is 1.5 to hours, meaning that in each 2-hour interval the concentration will be reduced 50%, and a negligible concentration (6.25%) will remain after hours, or four half-lives For comparison, the half-life of articaine is 30 minutes These estimations depend on clearance, volume, and distribution, which can vary in individual patients Infants with immature hepatic enzymes and adults with hepatic compromise should receive the lowest possible amount of anesthetic because the recommendations are not based on pediatric patients or patients with medical compromise Infant local dosing varies because infants have an increased cardiac output, leading to increased absorption; immaturity of plasma proteins, causing increased amounts of free local anesthetic in the plasma; and slower plasma clearance from immature hepatic enzymes (3.5 hours, compared with to 12 hours, for bupivacaine).3 The enzyme responsible for the metabolism of ropivacaine is not active until approximately age years.5 Other than ropivacaine metabolism, the pharmacology of local anesthetics in patients older than year is similar to that in adult patients In elderly patients, dosing is affected by alterations in hepatic and renal function Hepatic blood flow decreases by 10% per decade, enzymatic function is impaired, and albumin quantity is decreased Normal hepatic function permits a lidocaine half-life of 1.5 hours, whereas the half-life is hours in patients with hepatic impairment.6 Renal clearance is reduced because elderly patients have decreased renal blood flow (10% per decade in adult years) and decreased glomerular filtration, causing prolongation of metabolite elimination.7 In elderly patients who have impaired cardiac function or dysrhythmias, bupivacaine should be used cautiously because it is more cardiotoxic than comparable doses of lidocaine are Compared with lidocaine, an isomer of bupivacaine has an increased attraction to cardiac tissue and distributes more slowly away from cardiac sodium channels Opinions vary as to whether the presence of a vasoconstrictor permits higher dosing of anesthetic Lower dosing was historically recommended in solutions without a vasoconstrictor; however, other authors argue that this distinction is no longer valid.2 Practically, the availability of anesthetics without a vasoconstrictor provide an alternative to dose adjustments with lidocaine Pregnancy and lactation are not contraindications to the administration of local anesthetic As noted earlier, the lipophilicity of a local anesthetic allows it to cross the placenta Lidocaine, prilocaine, and ropivacaine are the only three local anesthetics that have a class B drug classification by the US Food and Drug Administration Scant literature has addressed the safety of local anesthetics during lactation, but judicious use is considered safe Epinephrine should be limited during breastfeeding because the amount excreted is unknown Techniques Regional blocks and local infiltration are used to provide anesthesia to oral and maxillofacial tissues General principles include use of a beveled needle, slow injection of anesthetic, and aspiration before injection Whereas infiltration can provide profound anesthetic in the maxillary bone, primarily in children, the thick bone of the mandible prevents adequate anesthesia with infiltration Regional blocks are intended to anesthetize the sensory branches of the trigeminal nerve 44 www.ajlobby.com Mizukawa_Chap_04.indd 44 6/20/17 10:27 AM Complications Regional blocks used in the maxilla include the posterior superior alveolar, infraorbital, greater palatine, nasopalatine, and maxillary nerve blocks Of note, the depth of penetration for successful posterior superior alveolar and infraorbital blocks in adults is 16 mm, or half the length of a long needle Needle insertion depth is 30 mm in either the high tuberosity or greater palatine approach to the maxillary nerve block Adjunctive injection techniques include the Gow-Gates, Akinosi (closed-mouth), intraosseous, periodontal ligament, and extraoral blocks The Gow-Gates block is useful if the inferior alveolar nerve block is not successful and can successfully anesthetize the inferior alveolar, lingual, mylohyoid, auriculotemporal, and buccal nerves A long needle is used to inject the anesthetic agent in a line from the intertragic notch to the contralateral corner of the mouth at an injection site just distal to the maxillary second molar If the maxillary third molar is in occlusion, the entry site is distal to that tooth The anesthetic is deposited after negative aspiration (2% average) and slight withdrawal after contact with the condylar neck For patients in maxillomandibular fixation or patients with trismus resulting from temporomandibular disorder or infection, the Akinosi block is useful Other than the buccal nerve, it affects the same distribution as the Gow-Gates block As in the Gow-Gates block, a long needle is used The needle is injected at the mucogingival line, parallel to the maxillary occlusal plane in the region of the second or third molar The needle is advanced laterally, and bone contact is not necessary With both the Gow-Gates and Akinosi blocks, the needle penetration depth is approximately 25 mm Intraosseous injections can be performed with commercially available intraosseous syringes and can provide anesthesia of structures distal to the injection site, although they are more commonly used to provide local anesthesia at the site of the injection In an oral surgery procedure in which flaps are used to expose bone, the provider can use a drill to access the medullary bone and inject the anesthetic directly into the cancellous space After closure of the flap, the injection window is covered, in contrast to the open tract left after techniques that involve injection through mucosa into bone The injection site is between teeth, mm apical to the gingival margin Therefore, special attention is required to avoid root damage Periodontal ligament injections are performed with a 27-gauge needle slipped into the depth of the gingival sulcus along the long axis of the tooth Resistance to injection should be felt, and the anesthetic should be delivered slowly so that it has time to infiltrate into the periodontal ligament Both the mandible and maxilla can be anesthetized with extraoral blocks This type of anesthesia is most commonly provided at the infraorbital site for infraorbital nerve distribution or through the sigmoid notch to anesthetize the inferior alveolar nerve.8 Common misconceptions related to anesthesia include that lip anesthesia is indicative of pulpal anesthesia, that accessory mylohyoid innervation is the most common reason for inferior alveolar nerve block failure,9,10 that buccal infiltration is not useful in the mandible,11 and that the speed of local administration is irrelevant to block success.12 Pulpal anesthesia of mandibular first molars is successful in 71% of attempts, and the addition of buccal infiltration of articaine can increase the success rate to 88% in patients without pulpitis.13 Research shows that when irreversible pulpitis is present, an inferior alveolar nerve block alone is successful only 19% to 56% of the time.12 Complications Administration of local anesthetic is commonplace for most dental providers Although frequent administration of local anesthetic leads to skill in delivery, complications are inevitable A hematoma can form in the infratemporal fossa after deep penetration or wandering of a needle during a posterior superior alveolar nerve block Damage to the posterior superior artery or pterygoid plexus is not uncommon with the use of this block, and subsequent hematoma can result in extraoral swelling Nicking the inferior alveolar artery with the needle bevel during administration of an inferior alveolar block can result in an intraoral hematoma, leading to pain and trismus Other causes of trismus after local injection include pain from injection in the short term, or local muscle damage from the needle and/or from myotoxic anesthetic solution 45 www.ajlobby.com Mizukawa_Chap_04.indd 45 6/20/17 10:27 AM 4 • Local Anesthesia Basics Nerve alteration can occur if the anesthetic needle gouges or lacerates the nerves in the area of injection This occurrence is usually signaled by a sensation during needle positioning similar to that of an electrical shock Lingual nerve damage is more common than inferior alveolar nerve injury (79% versus 21%), with temporary injury reports as high as 0.54% and permanent injury reports as high as 0.01%.14 The discomfort of neural gouging should be distinguished from pain on injection, which is frequently exacerbated by rapid injection of the acidic local solution Facial nerve paralysis can occur if the parotid capsule is violated with an inferior alveolar nerve block that ventures onto the posterior aspect of the ramus This occurrence is usually a transitory finding that resolves when the anesthesia wears off Neurotoxicity of local anesthetics increases with anesthetic concentrations Thus, the use of nerve blocks in 4% solutions is not advised, and permanent paresthesia has been reported.15 Cardiac complications, other than those resulting from overdose of anesthetic or vasoconstrictor, are typically caused by infiltration of the vascular system by small doses of vasoconstrictor Infiltration into the vasculature can cause tachycardia, hypertension, and alterations in cardiac rhythm Subsequent to the tachycardia and anxiety associated with an infiltration, a vasovagal event resulting in transient syncope may occur Ropivacaine is a good choice of longer-acting anesthetic in patients with preexisting cardiac disease because it contains no epinephrine It is less cardiotoxic than bupivacaine, and it can provide relative vasoconstriction in patients on anticoagulant medication, in whom the hemostatic effects of epinephrine are desired Overdose of prilocaine (maximum dose 6.0 mg/kg, or 400 mg), articaine, or benzocaine can result in methemoglobinemia Methemoglobinemia occurs when ferric forms of iron on hemoglobin bind oxygen tightly, preventing the release of oxygen to target tissue that normally occurs with the reduced, ferrous form of iron on hemoglobin O-toludine, a metabolite of prilocaine, can cause methemoglobinemia This condition can occur hours after local administration, and it can result in respiratory depression and cyanosis that is poorly responsive to oxygen administration because the administered oxygen cannot unload at the hypoxic tissues Treatment includes administration of intravenous methylene blue (1.5 mg/kg repeated every hours) or the slower-acting intravenous ascorbic acid Providers who use EMLA, which contains prilocaine, in small children should be aware of the risk of methemoglobinemia Allergic reactions to local anesthetics have a variety of inciting agents Historically, allergies were primarily caused by the ester anesthetics and their metabolite p-aminobenzoic acid The advent of amide anesthetics has drastically reduced the occurrence of allergies If an allergy to amide anesthetics is present, other amides can be used because cross-allergenicity is not a concern as it is with the ester class of drugs Other reported causes of allergic reactions to local anesthetics include methylparaben (a bacteriostatic agent used in multidose vials) and sodium bisulfite or metabisulfite (used as an antioxidant in dental cartridges containing a vasoconstrictor) A steroid-dependent asthmatic patient with a reported sulfite (not sulfa) allergy should receive plain local anesthetic if possible Many patients report allergies to local anesthetics, but prudent questioning usually reveals a vasoactive response to a vasoconstrictor Epinephrine infiltration leading to tachycardia, flushing, and near syncope is often interpreted by patients as an allergy Minor allergic responses may go undetected or result in local irritation, whereas serious allergic reactions can lead to anaphylaxis and death The management of this scenario is discussed in chapter 12, which addresses medical emergencies The central nervous system (CNS) and cardiovascular system are the most clinically relevant systems affected by local anesthetic toxicity (Box 4-1) Drugs such as lidocaine have therapeutic indications in the management of seizures and dysrhythmias Supratherapeutic doses of local anesthetic can have untoward effects The typical dose of two to eight carpules of local anesthetic equates to one-sixth to one-fourth of the toxic dose CNS symptoms occur before cardiovascular symptoms and can arise with levels of 4.5 µg/mL (blood levels after injections are approximately µg/mL) Excitation of nervous tissue precedes depression of function, which is followed by tonic-clonic seizures (at 7.5 µg/mL) and respiratory depression (at 10 µg/mL) The nervous effects of local anesthetics are mediated by depression of CNS inhibitory neurons and release of glutamate, both causing the initial excitation At levels of to 10 µg/mL, dysrhythmias can arise, and higher levels (> 10 µg/mL) lead to cardiac depression, vasodilation, and eventual cardiac arrest Specifically, local anesthetics affect the cardiac muscle by prolonging conduction time (increased PR interval and prolonged QRS interval), depressing intrinsic nodal pacing, and decreasing inotropy 46 www.ajlobby.com Mizukawa_Chap_04.indd 46 6/20/17 10:27 AM References BOX 4-1 Effects of local anesthetic toxicity on the CNS and cardiovascular system CNS • Lightheadedness/dizziness • Visual and auditory disturbance (tinnitus) • Disorientation/drowsiness • CNS excitation leading to shivering, muscular twitch, tremor, tonic-clonic convulsions (seizure) • CNS depression leading to respiratory depression Cardiovascular system • Conduction delays • Depressed chronotropy • Negative inotropy • Vasodilation • Calcium channel inhibition • Ventricular dysrhythmia CNS symptoms may be more likely in patients with obstructive sleep apnea than in other patients because elevated arterial partial pressure of carbon dioxide causes increased cerebral blood flow and increased levels of anesthetic delivery to the brain Hypercapnia and associated respiratory acidosis also inhibit plasma protein binding, prolonging the presence of free drug in the plasma and allowing the drug to travel to the brain Concomitant use of antacids, β blockers, cannabinoids, carbonic anhydrase inhibitors, inhaled anesthetics, serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants may increase the levels or effects of lidocaine with epinephrine In contrast, a decreased effect of lidocaine may occur with concomitant use of spironolactone.1 Signs that can alert the provider to anesthetic overdose can be confused with common signs seen during moderate and deep sedation, depending on the drugs used for anesthesia Agitation, slurred speech, nystagmus, perioral numbness, disorientation, and changes in heart and respiratory rate can all be caused by anesthetic drugs but should be considered warning signs in patients who have received high volumes of anesthetic Treatment includes termination of the procedure, use of basic life support/advanced cardiovascular life support protocols, administration of anticonvulsants, and involvement of emergency services In cases in which local anesthesia, primarily bupivacaine, causes life-threatening cardiovascular compromise, a rapid bolus of 20% intravenous fat emulsion 1.5 mL/kg followed by infusion of 0.25 mL/kg per minute for 10 minutes is recommended.16 Conclusion The proper use of local anesthesia is essential for safe and effective procedures in and around the oral cavity Local anesthesia can prevent or reduce the need for systemic medications to successfully complete procedures and promote patient cooperation Understanding local anesthetic mechanisms of action, various techniques for delivery, and potential complications gives the provider a knowledge base for judicious use in a variety of clinical situations References Malamed SF Handbook of Local Anesthesia, ed St Louis: Mosby, 2010 National Institutes of Health, US National Library of Medicine Pseudocholinesterase deficiency Genetics Home Reference http://ghr.nlm nih.gov/condition/pseudocholinesterase-deficiency Accessed 11 November 2016 Berde CB, Strichartz GR Local anesthetics In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:913–939 Dalens B Regional anesthesia in children In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:2519–2557 Wynn RL, Meiller TF, Crossley HL Drug Information Handbook for Dentistry, ed 22 Hudson, OH: Lexicomp, 2016 Stenson RE, Constantino RT, Harrison DC Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man Circulation 1971;43:205–211 47 www.ajlobby.com Mizukawa_Chap_04.indd 47 6/20/17 10:27 AM 4 • Local Anesthesia Basics 12 Reader A Taking the pain out of restorative dentistry and endodontics: Current thoughts and treatment options to help patients achieve profound anesthesia Endodontics: Colleagues for Excellence Winter 2009:1–8 Sieber F, Pauldine R Geriatric anesthesia In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:2261–2276 Moore PA, Cuddy MA, Cooke MR, Sokolowski CJ Periodontal ligament and intraosseous anesthetic injection techniques: Alternatives to mandibular nerve blocks J Am Dent Assoc 2011;142(suppl 3):13S–18S 13 Matthews R, Drum M, Reader A, Nusstein J, Beck M Articaine for supplemental, buccal mandibular infiltration anesthesia in patient with irreversible pulpitis J Endod 2009;35:343–346 14 Cummings DR, Yamashita DR, McAndrews JP Complications of local anesthesia used in oral and maxillofacial surgery Oral Maxillofac Surg Clin North Am 2011;23:369–377 Clark S, Reader A, Beck M, Meyers WJ Anesthetic efficacy of the mylohyoid nerve block and combination inferior alveolar nerve block/ mylohyoid nerve block Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:557–563 15 Haas DA, Lennon D A 21 year retrospective study of reports of paresthesia following local anesthetic administration J Can Dent Assoc 1995;61:319–320,323–326,329–330 10 Foster W, Drum M, Reader A, Beck M Anesthetic efficacy of buccal and lingual infiltrations of lidocaine following an inferior alveolar nerve block in mandibular posterior teeth Anesth Prog 2007;54:163–169 16 Weinberg G Lipid rescue resuscitation from local anaesthetic cardiac toxicity Toxicol Rev 2006;25:139–145 11 Meechan JG The use of the mandibular infiltration anesthetic technique in adults J Am Dent Assoc 2011;142(suppl 3):19S–24S 48 www.ajlobby.com Mizukawa_Chap_04.indd 48 6/20/17 10:27 AM CHAPTER Prophylactic and Perioperative Antibiotics Rick Shamo, dds, md David Shafer, dmd www.ajlobby.com Mizukawa_Chap_05.indd 49 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics It is difficult to overstate the effect that antibiotics have had on health care Accordingly, their importance to the oral and maxillofacial surgeon is without question These medications are critical to our current practices of infection management However, questions still exist regarding their indications and use when no infection is present at the time of treatment Surgical site infections can be frustrating for both patient and physician, and systemic infections can be life threatening For surgical procedures that carry a low risk of surgical site infection, adverse effects that can result from use of an antibiotic regimen may outweigh the benefits For noninvasive procedures, antibiotic prophylaxis is generally not recommended In the past, many practitioners advocated use of prophylactic antibiotics extending well into the postoperative period In most cases, the literature does not support this practice.1 To ensure a favorable risk-to-benefit ratio, it is important to adhere to current evidence-based antibiotic practices Certain patient characteristics increase the risk of postoperative infection (Box 5-1) Patients with head or neck cancer, for example, have numerous defined patient-specific risk factors.2–4 BOX 5-1 Risk factors for the development of postoperative infection • • • • • • • • • • • • Coincident remote site infections or colonization • Low body mass index (BMI) • Obesity > 20% ideal body weight • Diabetes mellitus • Poor nutritional status (anemia/ hypoalbuminemia) • Procedure duration • Extended hospital stay before surgery • Large volume of blood loss • Foreign body implants/prostheses Postoperative radiotherapy Cigarette smoking Systemic steroid use Extremes of age Alcohol consumption Drug abuse Tumor classification Neck dissection Reconstructive procedures Chemoradiotherapy Prior tracheotomy The purpose of antibiotic prophylaxis is not to sterilize the patient’s blood and tissues but to reduce the bacterial burden to levels that can be managed by the host immune system Studies have clearly demonstrated that bacteremia occurs during oral surgery procedures.5–10 However, the number of teeth extracted, the duration of the procedure, and the amount of blood loss not affect the incidence of bacteremia during the procedure Significant bacteremia has also been demonstrated to occur in conjunction with normal daily activities, such as chewing food or brushing teeth.11–14 Factors that can increase the incidence of bacteremia include periodontal, periapical, or pericoronal infections.15 Although no studies in humans have indicated that higher-magnitude bacteremia increases the likelihood of the development of complications such as infectious endocarditis,5 bacteremias used in animal studies to induce infectious endocarditis were markedly higher in magnitude than those resulting from typical dental procedures In fact, bacteremia that occurs as a result of dental procedures is generally of low magnitude, and bacteremia resulting from routine daily activities has been estimated to be several million times higher.5,16,17 For these reasons, many otherwise healthy patients are no longer given antibiotics before invasive oral surgery procedures even when such procedures are known to cause bacteremia In general, the decision whether to use antibiotic prophylaxis in a patient undergoing an invasive oral surgery procedure depends primarily on the patient’s risk factors1 and secondarily on the procedure itself In patients who are otherwise healthy, the decision depends primarily on the procedure itself Infectious Endocarditis Infectious endocarditis is a severe cardiac complication that can occur as a result of bacteremia Turbulent blood flow through the heart can potentially cause trauma and expose underlying tissue collagen Platelet and fibrin 50 www.ajlobby.com Mizukawa_Chap_05.indd 50 6/20/17 10:31 AM Infectious Endocarditis attachment to the exposed tissue collagen creates sterile vegetations, which can become infected with bacteria because the vegetation facilitates attachment of bacteria at that location Infectious endocarditis can result in fever, malaise, and fatigue in most patients and can cause other symptoms known to be associated with the condition, including Roth spots (retinal hemorrhages), new onset of heart murmur, Janeway lesions (lesions on the palms or soles), Osler nodes (painful raised lesions in the distal fingers), renal infarcts, and splinter hemorrhages Patients may also experience stroke or deep vein thrombosis and may require cardiac valve replacement.18 For many years, administration of antibiotic prophylaxis was common practice for any person thought to have even mild risk of endocarditis More recently, many studies have shown a poor cost-benefit ratio of antibiotic prophylaxis19 and have failed to demonstrate its efficacy in reducing the occurrence of endocarditis in patients at risk of the condition.20,21 The American Heart Association has periodically released recommendations for prophylaxis of at-risk patients as evidence has accumulated regarding the practice The most recent guidelines, issued in 2007,22 resulted in substantial changes to the previous guidelines from 1997 because the available evidence suggested the following23: Bacteremia was much more likely to occur as a result of routine daily activities than as a result of dental procedures Antibiotic prophylaxis was likely to prevent only a very small number of cases of infectious endocarditis in patients undergoing dental procedures The risk of antibiotic-associated adverse events was greater than any perceived benefit Maintenance of optimal oral health and hygiene is more important in the prevention of infectious endocarditis than antibiotic prophylaxis prior to dental procedures is The American Heart Association guidelines also further limited which populations should receive antibiotic prophylaxis (Box 5-2) Such patients should receive prophylaxis whenever the procedure involves penetration of oral mucosa or manipulation of gingival tissue or the periapical region The guidelines for prophylaxis can be found in Table 5-1 The 2007 guidelines also removed the antibiotic erythromycin from the prophylactic regimen In the United Kingdom, guidelines published in 2008 recommended cessation of routine antibiotic prophylaxis for both at-risk and generally healthy patients, citing a concern that continuing routine prophylaxis may actually lead to a net loss of life.24 Since that time, Dayer et al25 evaluated the relationship between the substantial reduction in prophylactic antibiotic use in the United Kingdom after the release of the guidelines and the incidence of endocarditis The study found that the rate of infectious endocarditis increased significantly from 2008 to 2013 for both low-risk and high-risk patients beyond projections based on the previous trend.25 Although this finding does not establish a causal relationship, further studies could lead to modification of the current UK recommendations BOX 5-2 Cardiac conditions requiring antibiotic prophylaxis before invasive dental procedures* • Prosthetic heart valve • History of infectious endocarditis • Certain congenital heart diseases –– Unrepaired cyanotic congenital heart disease, including placement of palliative shunts and conduits –– Congenital heart defect completely repaired with prosthetic material or device, whether placed by surgery or by catheter, during the first months after the repair procedure –– Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) • Valvulopathy in cardiac transplant patients *Adapted from American Heart Association 2007 guidelines.22 51 www.ajlobby.com Mizukawa_Chap_05.indd 51 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics Table 5-1 American Heart Association antibiotic prophylaxis regimens* Dose† Situation Antibiotic Adults Children Oral medication Amoxicillin 2g 50 mg/kg Patient unable to take oral medication Ampicillin Cefazolin or ceftriaxone g IM or IV g IM or IV 50 mg/kg IM or IV 50 mg/kg IM or IV Oral medication for patient allergic to penicillins or ampicillin Cephalexin Clindamycin Azithromycin or clarithromycin 2g 600 mg 500 mg 50 mg/kg 20 mg/kg 15 mg/kg Patient unable to take oral medication and allergic to penicillins or ampicillin Cefazolin or ceftriaxone g IM or IV 50 mg/kg IM or IV Clindamycin 600 mg IM or IV 20 mg/kg IM or IV IM, intramuscular; IV, intravenous *Adapted from American Heart Association 2007 guidelines.22 † Single dose administered 30–60 minutes before procedure General Principles of Effective Antibiotic Prophylaxis After it is determined that antibiotic prophylaxis is indicated, certain principles should be followed to maximize the benefit of prophylaxis while minimizing potential harm: Antibiotics should be selected to target the organisms most frequently associated with surgical site infections related to the particular procedure or anatomic location.26 Knowledge of the organisms most likely to cause infection is critical to selecting the narrowest spectrum antibiotic that will effectively prevent infection while minimizing substantial changes to the body’s healthy bacterial flora and the development of resistant strains A sufficient dose should be administered via the appropriate route to ensure blood and tissue concentration levels higher than the minimal inhibitory concentration for the predicted infection-causing organisms.26 To be effective, prophylactic antibiotics must be present in the tissues at three to four times the minimal inhibitory concentration.27 The antibiotic should be administered within an appropriate time frame Administration of most antibiotics is recommended within 60 minutes before incision.28,29 Doses administered more than hours before the procedure are unlikely to be effective.23,30 The exceptions are vancomycin and fluoroquinolones, which should be given approximately hours before incision because of the longer time required for administration of each dose.28 Appropriate blood and tissue antibiotic concentrations should be maintained throughout the duration of the surgical procedure If the duration of a procedure exceeds two half-lives of the antibiotic or if excessive blood loss occurs, a second dose should be given28,29 (Table 5-2) Table 5-2 Recommended dosing for antibiotic prophylaxis* Recommended Dose Antibiotic Adults Children Ampicillin-sulbactam g (ampicillin g, sulbactam g) 50 mg/kg of the ampicillin component Recommended Half-life in redosing interval adults with (from initiation normal renal of preoperative function, h dose), h 0.8–1.3 1.2–2.2 50 mg/kg 1–2 10 mg/kg 2–4 15 mg/kg (neonates weighing < 1,200 g should receive a single 7.5-mg/kg dose) 6–8 NA Cefazolin g (3 g for patients weighing ≥ 120 kg) 30 mg/kg Cefuroxime 1.5 g Clindamycin 900 mg Metronidazole 500 mg NA, not applicable *Adapted from Bratzler et al.29 52 www.ajlobby.com Mizukawa_Chap_05.indd 52 6/20/17 10:31 AM General Principles of Effective Antibiotic Prophylaxis Frequent familiarization with locally identified antimicrobial resistance patterns (antibiograms) is necessary Antibiotic efficacy varies from region to region as antibiotic resistance patterns emerge Over the past two decades, the organisms responsible for surgical site infections have changed substantially.29 Familiarity with the provider’s local antibiogram is essential to select antibiotics that cover resistant organisms The use of novel, broad-spectrum antibiotics for routine surgical prophylaxis should be avoided Development of antibiotic resistance has not been shown to occur with single doses of antibiotics.31 Nevertheless, novel, broad-spectrum antibiotics should be avoided when an infection is not already present to preserve these medications for use against resistant strains of bacteria The selection of the appropriate antibiotic for a particular patient and procedure is not a standardized process Multiple factors, including the type of procedure, the patient’s history of infection or colonization with resistant strains of bacteria, prior reactions or allergies to antibiotics, comorbidities affecting metabolism and excretion of antibiotics, and the cost and availability of antibiotics, can influence the decision These and other factors influencing each patient and situation must be carefully considered (Tables 5-3 and 5-4) Table 5-3 Recommendations from the American Academy of Orthopaedic Surgeons/American Dental Association clinical practice guideline for the prevention of orthopedic implant infection after dental procedures* Grade of Recommendation Recommendation The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures Limited Unable to recommend for or against the use of topical oral antimicrobials in patients with prosthetic joint implants or other orthopedic implants undergoing dental procedures Inconclusive In the absence of reliable evidence linking poor oral health to prosthetic joint infection, it is the opinion of the work group that patients with prosthetic joint implants or other orthopedic implants maintain appropriate oral hygiene Consensus *Adapted from the American Academy of Orthopaedic Surgeons and American Dental Association clinical practice guideline.32 Table 5-4 Intravenous antibiotic prophylaxis recommendations for head and neck surgery* Type of procedure Recommended agents Alternative agents in patients with 𝛃-lactam allergy Strength of evidence† Clean None None B Clean with placement of prosthesis Cefazolin, cefuroxime Clindamycin C Clean-contaminated cancer surgery Cefazolin + metronidazole, cefuroxime + metronidazole, ampicillin-sulbactam Clindamycin A Other clean-contaminated procedures Cefazolin + metronidazole, cefuroxime + metronidazole, ampicillin-sulbactam Clindamycin B *Adapted from Bratzler et al.29 A = Evidence from well-conducted randomized controlled clinical trials, a meta-analysis, or well-conducted cohort studies; B = Evidence from well-conducted case control studies, uncontrolled studies that are not well conducted, or conflicting evidence that tends to favor the recommendation; C = Expert opinion or data extrapolated from evidence for general principles and other procedures † Most antibiotics have well-known side effect profiles and potential adverse reactions To avoid undue harm, the benefits for administering the drug must clearly outweigh any risks Although a single prophylactic dose poses little risk of the development of bacterial resistance,31 the widespread use of multiple dose regimens poses a considerable threat to our ability to retain antibiotic efficacy in the future The risk of anaphylaxis also exists Although calculation of this risk secondary to the use of an antibiotic such as penicillin is difficult,21,33 some researchers have estimated approximately one mortality per 60,000 administrations,31,34 whereas others estimate the risk to be much 53 www.ajlobby.com Mizukawa_Chap_05.indd 53 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics higher.35–37 Another well-known risk of antibiotic prophylaxis is gastrointestinal disturbance leading to diarrhea and possible pseudomembranous colitis resulting from overgrowth of the native bacteria Clostridium difficile, which can lead to death.38 The risk of this complication increases when multiple antimicrobials are used Limiting antimicrobial use to single-dose prophylactic regimens decreases this risk.29 Antibiotic Use by Procedure Dentoalveolar surgery/third molar extractions With dentoalveolar surgery and third molar extractions in particular constituting a large component of the average oral surgery practice, it is not surprising that many studies have examined the role of antibiotics in this area The reported incidence of postoperative infection ranges from 1% to approximately 12%.39–44 The large number of patients undergoing these procedures means that oral and maxillofacial surgeons will frequently encounter such infections Although studies have demonstrated improved postoperative symptoms45–48 and decreased infection rates, particularly in patients with bony impaction of third molars,45,47 some of the studies have substantial weaknesses in design Most prospective, randomized, double-blinded, placebo-controlled studies have found no significant benefit in the use of antibiotics associated with dentoalveolar surgery.49–53 When infections occur, they are most often well circumscribed and self-limiting If intervention is required, a simple incision and drainage procedure along with therapeutic antibiotics is usually curative.54–57 For patients who meet the criteria for prophylaxis for infectious endocarditis, the American Heart Association antibiotic regimens should be followed Dental implant placement Numerous studies have supported the use of single-dose prophylactic antibiotics in conjunction with dental implant placement.58–60 A 2013 Cochrane review of available literature demonstrated that g of amoxicillin given orally hour before implant procedures significantly reduced the risk of early implant failure The practice of continued antibiotic use beyond the perioperative period was not well supported.61 For failing implants, there is no established antibiotic protocol However, infections cultured often contain the same bacteria as those found in periodontitis Similar to orthopedic implants, treatment often requires removal.62 Orthognathic surgery Studies in the current literature demonstrate surgical site infection in approximately 7% of patients undergoing orthognathic surgery.63,64 Although Peterson et al initially recommended against antibiotic prophylaxis on the basis of the results of a study in 1976,65 Peterson later advocated the use of antibiotics, estimating that their use could reduce the rate of infection in orthognathic surgery patients to approximately 1%.39 Multiple studies since that time have demonstrated the benefit of prophylactic administration of antibiotics.66–69 However, long-term use to reduce postoperative wound infection rates remains controversial.68–74 Both Danda and Ravi72 and Harrell and Shetty73 performed meta-analyses that demonstrated a significantly decreased rate of postoperative infection with an extended course of antibiotics Tan et al, however, found that postoperative intravenous administration of penicillin was no more effective than the oral form.70 The analysis of Danda and Ravi72 further suggests that the penicillin family of antibiotics may be the most effective in preventing infection, while Zijderveld et al66 found amoxicillin/clavulanate and cefuroxime to be equally effective Wahab et al found that patients who received three postoperative doses of amoxicillin in addition to the initial prophylactic dose had a statistically significant reduction in the rate of infection.75 Baqaina et al studied the potential benefit of a longer course of antibiotics and did not find a difference between 1-day or 5-day postoperative antibiotic use.76 Because of the lack of consensus on postoperative use of antibiotics, the authors of this chapter recommend that each practitioner carefully consider each procedure and the patient’s risk factors to determine the most appropriate regimen 54 www.ajlobby.com Mizukawa_Chap_05.indd 54 6/20/17 10:31 AM Patients Requiring Special Consideration Management of maxillofacial fractures Formulation of evidence-based guidelines regarding antibiotic use in patients with maxillofacial fractures is complicated by the fact that relatively few well-designed studies have examined this issue.77 According to general surgical prophylaxis practices, the wound classification would suggest that patients with open fractures that are considered contaminated or dirty should receive therapeutic rather than prophylactic antibiotics, whereas patients with closed fractures would be less likely to benefit from antibiotics The conclusions of the existing studies strongly support the use of prophylactic antibiotics in certain cases.78–80 In 1987, Chole and Yee found a significant decrease in wound infection in maxillofacial fracture patients who received g of cefazolin prophylactically and another 1-g dose hours later.79 Other studies using intravenous ceftriaxone and penicillin regimens have demonstrated similar results.79,81 Multiple studies have shown no benefit of longer dosing regimens.79–81 Zallen and Curry78 reported infection rates of 6.25% in patients receiving antibiotics and 50.33% in patients not receiving antibiotics, a finding that further supports the use of antibiotics in patients with fractures in tooth-bearing regions of the mandible When maxillofacial trauma surgical site infections occur, they are almost exclusively encountered in the mandibular ramus, body, and symphysis rather than in the maxilla, the zygoma, and the condylar region of the mandible.82 Of all mandibular fractures, those occurring in the third molar or angle region of the mandible are associated with the highest risk of infection The treatment modality also appears to play a role, with open treatment of fractures associated with a significant increase in infection rate.82,83 For patients with orbital floor fractures, antibiotic use is more controversial Although cases of infection have been reported in the literature,84 infection is relatively rare Despite the rarity of infection, in a survey by Courtney et al, 91% of respondents reported routine prescribing of antibiotics for patients with orbital fractures.85 The benefit of antibiotic prophylaxis in this case remains in question In terms of longer-term antibiotic use for orbital fractures, extended coverage beyond the perioperative period appears to provide no benefit.86 Similarly, no demonstrated benefit of extended antibiotic therapy has been found in patients with Le Fort and zygomatic fractures.87 Bone grafting Antibiotics are almost universally used in bone grafting protocols in the attempt to reduce graft failure resulting from infection Although few articles have specifically addressed this subject, a prospective, placebo-controlled, double blinded trial by Lindeboom and van den Akker in 2003 supported this practice, finding a statistically significant decrease in the infection rate in patients who received a single prophylactic dose of antibiotics.88 A follow-up study demonstrated no statistically significant difference between the use of penicillin and the use of clindamycin as the prophylactic agent.89 Patients Requiring Special Consideration Patients with prosthetic joints The question of whether prophylactic antibiotics should be used in patients with prosthetic joints has historically been vigorously debated among orthopedic surgeons and dental practitioners In the past, patients with joint prostheses were recommended to receive antibiotic prophylaxis for dental procedures for years after implantation of the prosthesis Citing a study that showed that no joint infections occurred in association with procedures lasting 45 minutes or less,90 some authors recommended that prophylaxis could be omitted when oral procedures were likely to be of short duration.91 The incidence of prosthetic joint infections related to oral bacteria has been shown to range from 0.04% to 0.07% of cases.92,93 These figures not demonstrate causality but rather an association The most recent collaborative recommendations of the American Academy of Orthopaedic Surgeons and the American 55 www.ajlobby.com Mizukawa_Chap_05.indd 55 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics Dental Association were released in 2012 (see Table 5-3) In this systematic review, the authors of the guideline found no direct evidence linking prosthetic infections to dental procedures As a result, the recommendation for routine prophylaxis was revoked, and the recommendation was made that providers make the decision for or against prophylaxis on a case-by-case basis.32,94 Patients with head or neck cancer Patients with head or neck cancer require careful consideration because infections can be particularly difficult to manage, and failure due to infection can be particularly devastating In patients with previous irradiation, compromised vascular supply to the area can impair healing as well as the body’s ability to fight infections in the affected area The literature clearly demonstrates that the rate of infection of clean wounds in head and neck surgery is very low (1% or less).85,95–97 Thus, the recommendation for an otherwise healthy patient is to forgo prophylaxis in straightforward, clean procedures However, procedures involving free flaps or immunocompromised patients may require antibiotics because of the potential for devastating graft loss resulting from infection This decision should be made after careful consideration of the procedure and the patient’s risk factors (Table 5-4) Clean-contaminated wounds have been demonstrated to have substantially higher rates of infection In these cases, Ancef (GlaxoSmithKline) with addition of another antibiotic such as metronidazole or gentamicin has been shown to have significantly lower infection rates compared with Ancef alone.95,98 Patients with osteonecrosis of the jaw Management of osteonecrosis of the jaw (ONJ) is a rapidly evolving field of study Antibiotics have been associated with a protective effect against the development of ONJ,99–102 and many studies have shown antibiotics to be an important part of prevention and treatment protocols in patients who are at risk of or have developed ONJ.99–105 In addition, some researchers advocate the use of chlorhexidine mouthrinse and/or hyperbaric oxygen therapy in conjunction with oral antibiotics to help treat or prevent ONJ.102,103,105–107 The current American Association of Oral and Maxillofacial Surgeons guidelines for patients with medication-related ONJ recommend the use of penicillin antibiotics in patients with stage 0, 2, or ONJ In patients who are allergic to penicillins, antibiotics that have been used with success include quinolones, metronidazole, clindamycin, doxycycline, and erythromycin.108,109 Diabetic patients A relatively vast body of knowledge is available regarding preoperative risk factors and management of diabetic patients in conjunction with major surgical procedures, including cardiothoracic and abdominal surgery The available literature clearly demonstrates that diabetic patients undergoing these types of procedures experience substantial immunocompromise and decreased wound healing ability, which worsens as the disease progresses and with poorer glycemic control.110 In this group of patients, postoperative glucose levels appear to be the most important factor affecting the development of infection-related complications.111–116 The rate of infection in diabetic patients is three times that of otherwise healthy adults, and this infection rate doubles in patients with poor postoperative glucose control.117 Conversely, patients with tight postoperative glucose control have demonstrated significantly improved perioperative outcomes.111,118 The evidence suggesting increased incidence of postoperative infection after oral surgery procedures and underlying the subsequent recommendations for prophylaxis is mostly anecdotal.119 Although studies have revealed an increased predisposition to odontogenic infections and oral candidiasis in diabetic patients,117 convincing findings to support the role of prophylactic antibiotics are not available Very few well-designed studies have evaluated the outcomes of oral surgical procedures in diabetic patients The existing studies of oral surgery in diabetic patients have not demonstrated a significant connection between glycemic control and postoperative healing.120,121 Well-designed studies need to be performed to better define the risk associated with oral surgery procedures and any benefit, or lack thereof, of antibiotic prophylaxis in diabetic patients.122,123 56 www.ajlobby.com Mizukawa_Chap_05.indd 56 6/20/17 10:31 AM References Patients with renal or hepatic failure Patients with renal or hepatic failure have a decreased ability to metabolize and excrete antibiotics These patients require special consideration regarding the type of antibiotic to use and possible dosage adjustment For patients with renal failure, the clinician must determine the patient’s glomerular filtration rate and adjust the antibiotic dose according to the drug manufacturer’s or pharmacist’s recommendations These recommendations are commonly found in most drug references For patients who have recently undergone renal transplantation, elective dental procedures are discouraged during the first months postoperatively.124 Patients requiring urgent dental care should receive antibiotic coverage because of the high risk and potentially devastating effects of infection Because of their altered metabolic activity, patients with hepatic failure require dosage reductions of antibiotics such as metronidazole, erythromycin, and clindamycin.125 HIV-positive patients Routine antibiotic prophylaxis for dentoaveolar procedures is not recommended for HIV-positive patients who demonstrate no signs of immunocompromise Participants in a workshop conducted in 2002 to determine treatment protocols for HIV-infected patients concluded that antibiotic prophylaxis was recommended in HIV-positive patients with signs of immunocompromise, such as CD4+ counts below 200 cells/µL HIV-positive patients should also be asked about symptoms and history of opportunistic infections The workshop participants further recommended prophylaxis for patients with neutrophil counts below 500 cells/µL because of the high infection rate associated with neutropenia.126 Patients on highly active antiretroviral therapy protocol without the previously mentioned signs of immunocompromise, who have lab values within normal limits and are otherwise healthy, not require antibiotic prophylaxis Some studies have found a higher rate of infection in HIV-positive patients undergoing open reduction internal fixation for mandible fractures In these patients, consideration of antibiotic prophylaxis is warranted.127 Summary For many years, the practice of antibiotic prophylaxis has been an important tool used for the benefit of patients undergoing surgical procedures Each patient and each situation provides a unique set of circumstances, requiring careful consideration prior to deciding whether or not prophylaxis is indicated and what regimen to use Because oral and maxillofacial surgery is a practice rather than simply a profession, our understanding of the appropriate use of such tools has improved over time as new information is shared and applied This process will undoubtedly continue as more information becomes available, informing future practices It is thus important that each practitioner stays current with this field of knowledge to consistently practice according to evidence-based principles References Hirakawa H, Hasegawa Y, Hanai N, Ozawa T, Hyodo I, Suzuki M Surgical site infection in clean-contaminated head and neck cancer surgery: Risk factors and prognosis Eur Arch Otorhinolaryngol 2013;270:1115–1123 Termine N, Panzarella V, Ciavarella D, et al Antibiotic prophylaxis in dentistry and oral surgery: Use and misuse Int Dent J 2009;59:263–270 Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR; Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee Guidelines for prevention of surgical site infection, 1999 Am J Infect Control 1999;27:97–132 Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P Dental bacteremia in children Pediatr Cardiol 1997;18:24–27 Roberts GJ, Jaffray EC, Spratt DA, et al Duration, prevalence and intensity of bacteraemia after dental extractions in children Heart 2006;92:1274–1277 Hayama M, Akahani S, Michiba T, Cho H, Yamamoto M, Mori T Significant factors for surgical site infection: Analysis of 203 head and neck surgeries [in Japanese] Nihon Jibiinkoka Gakkai Kaiho 2014;117:103–110 Debelian GJ, Olsen I, Tronstad L Bacteremia in conjunction with endodontic therapy Endod Dent Traumatol 1995;11:142–149 57 www.ajlobby.com Mizukawa_Chap_05.indd 57 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics 24 National Institute for Health and Care Excellence Prophylaxis against infective endocarditis: Antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures https://www.nice.org.uk/guidance/cg64 Published March 2008 Last updated September 2015 Accessed May 2016 King RC, Crawford JJ, Small EW Bacteremia following intraoral suture removal Oral Surg Oral Med Oral Pathol 1988;65:23–28 Guntheroth WG How important are dental procedures as a cause of infective endocarditis? Am J Cardiol 1984;54:797–801 10 Everett ED, Hirschmann JV Transient bacteremia and endocarditis prophylaxis A review Medicine (Baltimore) 1977;56:61–77 25 Dayer M, Jones S, Prendergast B, Baddour L, Lockhart P, Thornhill M Incidence of infective endocarditis in England, 2000–13: A secular trend, interrupted time-series analysis Lancet 2015;385:1219–1228 11 Bahrani-Mougeot FK, Paster BJ, Coleman S, Ashar J, Barbuto S, Lockhart PB Diverse and novel oral bacterial species in blood following dental procedures J Clin Microbiol 2008;46:2129–2132 26 Keegan M, Brown D Perioperative antibiotics and practice: Little things that make a big difference Anesthesiol Clin North America 2004;22:473–491 12 Hall G, Heimdahl A, Nord CE Bacteremia after oral surgery and antibiotic prophylaxis for endocarditis Clin Infect Dis 1999;29:1–8 13 Seymour RA, Lowry R, Whitworth JM, Martin MV Infective endocarditis, dentistry and antibiotic prophylaxis: Time for a rethink? Br Dent J 2000;189:610–616 27 Lieblich SE Postoperative prophylactic antibiotic treatment in third molar surgery—A necessity? [discussion] J Oral Maxillofac Surg 2004;62:9 14 Roberts GJ Dentists are innocent! “Everyday” bacteremia is the real culprit: A review and assessment of the evidence that dental surgical procedures are a principal cause of bacterial endocarditis in children Pediatr Cardiol 1999;20:317–325 28 File TM New guidelines for antimicrobial prophylaxis in surgery Infect Dis Clin Pract 2013;21:185–186 29 Bratzler DW, Dellinger EP, Olsen KM, et al Clinical practice guidelines for antimicrobial prophylaxis in surgery Am J Health Syst Pharm 2013;70:195–283 15 Takai S, Kuriyama T, Yanagisawa M, Nakagawa K, Karasawa T Incidence and bacteriology of bacteremia associated with various oral and maxillofacial surgical procedures Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:292–298 30 Burje JF The effective period of preventive antibiotic action in experimental incision and dermal lesions Surgery 1961;50:161–168 31 Tomás Carmona I, Diz Dios P, Scully C Efficacy of antibiotic prophylactic regimens for the prevention of bacterial endocarditis of oral origin J Dent Res 2007;86:1142–1159 16 Gould FK, Elliott TS, Foweraker J, et al Guidelines for the prevention of endocarditis: Report of the Working Party of the British Society for Antimicrobial Chemotherapy J Antimicrob Chemother 2006;57:1035–1042 32 American Academy of Orthopaedic Surgeons, American Dental Association Prevention of orthopaedic implant infection in patients undergoing dental procedures: Evidence-based guideline and evidence report http://www.ada.org/~/media/ADA/Member%20Center/FIles/ PUDP_guideline.ashx Published 2012 Accessed May 2016 17 Ashrafian H, Bogle RG Antimicrobial prophylaxis for endocarditis: Emotion or science? Heart 2007;93:5–6 18 Cunha B, D’Elia A, Pawar N, Schoch P Viridans streptococcal (Streptococcus intermedius) mitral valve subacute bacterial endocarditis (SBE) in a patient with mitral valve prolapse after a dental procedure: The importance of antibiotic prophylaxis Heart Lung 2010;39:64–72 33 Atkinson TP, Kaliner MA Anaphylaxis Med Clin North Am 1992;76:841–855 34 Finch R Chemoprophylaxis of infective endocarditis Scand J Infect Dis Suppl 1990;70:102–110 19 Oliver R, Roberts GJ, Hooper L, Worthington HV Antibiotics for the prophylaxis of bacterial endocarditis in dentistry Cochrane Database Syst Rev 2008;(4):CD003813 35 Bor DH, Himmelstein DU Endocarditis prophylaxis for patients with mitral valve prolapse: A quantitative analysis Am J Med 1984;76:711–717 20 Oliver R, Roberts GJ, Hooper L Penicillins for the prophylaxis of bacterial endocarditis in dentistry Cochrane Database Syst Rev 2004;(2):CD003813 36 Pallasch TJ A critical appraisal of antibiotic prophylaxis Int Dent J 1989;39:183–196 21 Pallasch TJ Antibiotic prophylaxis: Problems in paradise Dent Clin North Am 2003:47:665–679 37 Tzukert AA, Leviner E, Sela M Prevention of infective endocarditis: Not by antibiotics alone A 7-year follow-up of 90 dental patients Oral Surg Oral Med Oral Pathol 1986;62:385–388 22 Wilson W, Taubert KA, Gewitz M, et al Prevention of infective endocarditis: Guidelines from the American Heart Association: A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group Circulation 2007;116:1736–1754 [erratum 2007;116:e376–e377] 38 Levy DG, Stergachis A, McFarland LV, et al Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting Clin Ther 2000;22:91–102 39 Peterson L Antibiotic prophylaxis against wound infections in oral and maxillofacial surgery J Oral Maxillofac Surg 1990;48:617–620 40 Martin MV, Kanatas AN, Hardy P Antibiotic prophylaxis and third molar surgery Br Dent J 2005;198:327–330 23 Farbod F, Kanaan H, Farbod J Infective endocarditis and antibiotic prophylaxis prior to dental/oral procedures: Latest revision to the guidelines by the American Heart Association published April 2007 Int J Oral Maxillofac Surg 2009;38:626–631 41 Mitchell DA A controlled clinical trial of prophylactic tinidazole for chemoprophylaxis in third molar surgery Br Dent J 1986;160:284–286 42 Goldberg MH, Nemarich AN, Marco WP 2nd Complications after mandibular third molar surgery: A statistical analysis of 500 consecutive procedures in private practice J Am Dent Assoc 1985;111:277–279 58 www.ajlobby.com Mizukawa_Chap_05.indd 58 6/20/17 10:31 AM References 43 Chiapasco M, Cicco L, Marrone G Side effects and complications associated with third molar surgery Oral Surg Oral Med Oral Pathol 1993;76:412–420 60 Ata-Ali J, Ata-Ali F, Ata-Ali F Do antibiotics decrease implant failure and postoperative infections? A systematic review and meta-analysis Int J Oral Maxillofac Surg 2014;43:68–74 44 Piecuch J, Arzadon J, Lieblich S Prophylactic antibiotics for third molar surgery: A supportive opinion J Oral Maxillofac Surg 1995;53:53–60 61 Esposito M, Grusovin MG, Worthington HV Interventions for replacing missing teeth: Antibiotics at dental implant placement to prevent complications Cochrane Database Syst Rev 2013;(7);CD004152 45 Monaco G, Tavernese L, Agostini R, Marchetti C Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients J Oral Maxillofac Surg 2009;67:1467–1472 62 Pye AD, Lockhart DE, Dawson MP, Murray CA, Smith AJ A review of dental implants and infection J Hosp Infect 2009;72:104–110 63 Alpha C, O’Ryan F, Silva A, Poor D The incidence of postoperative wound healing problems following sagittal ramus osteotomies stabilized with miniplates and monocortical screws J Oral Maxillofac Surg 2006;64:659–668 46 Foy S, Shugars D, Phillips C, Marciani R, Conrad S, White R The impact of intravenous antibiotics on health-related quality of life outcomes and clinical recovery after third molar surgery J Oral Maxillofac Surg 2004;62:15–21 64 Barrier A, Breton P, Girard R, Dubost J, Bouletreau P Surgical site infections in orthognathic surgery and risk factors associated [in French] Rev Stomatol Chir Maxillofac 2009;110:127–134 47 Lacasa JM, Jiménez JA, Ferrás V, et al Prophylaxis versus pre-emptive treatment for infective and inflammatory complications of surgical third molar removal: A randomized, double-blind, placebo-controlled, clinical trial with sustained release amoxicillin/clavulanic acid (1000/62.5 mg) Int J Oral Maxillofac Surg 2007;36:321–327 65 Peterson L, Augusta G, Booth D Efficacy of antibiotic prophylaxis in intraoral orthognathic surgery J Oral Surg 1976;34:1088–1091 66 Zijderveld S, Smeele L, Kostense P, Tuinzing D Preoperative antibiotic prophylaxis in orthognathic surgery: A randomized, double-blind, and placebo-controlled clinical study J Oral Maxillofac Surg 1999;57:1403–1406 48 Ren Y, Malmstrom H Effectiveness of antibiotic prophylaxis in third molar surgery: A meta-analysis of randomized controlled clinical trials J Oral Maxillofac Surg 2007;65:1909–1921 67 Tan S, Lo J, Zwahlen R Perioperative antibiotic prophylaxis in orthognathic surgery: A systematic review and meta-analysis of clinical trials Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:19–27 49 Kaczmarzyk T, Wichlinski J, Stypulkowska J, Zaleska M, Panas M, Woron J Single-dose and multi-dose clindamycin therapy fails to demonstrate efficacy in preventing infectious and inflammatory complications in third molar surgery Int J Oral Maxillofac Surg 2007;36:417–422 68 Classen D, Evans R, Pestotnik S, Horn S, Menlove R, Burke J The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection N Engl J Med 1992;326:281–286 50 Kaczmarzyk T Abuse of antibiotic prophylaxis in third molar surgeries J Oral Maxillofac Surg 2009;67:2551–2552 69 Oomens MA, Verlinden CR, Goey Y, Forouzanfar T Prescribing antibiotic prophylaxis in orthognathic surgery: A systematic review Int J Oral Maxillofac Surg 2014;43:725–731 51 Ataoğlu H, Oz GY, Candirli C, Kiziloğlu D Routine antibiotic prophylaxis is not necessary during operations to remove third molars Br J Oral Maxillofac Surg 2008;46:133–135 52 Siddiqi A, Morkel JA, Zafar S Antibiotic prophylaxis in third molar surgery: A randomized double-blind placebo-controlled clinical trial using split-mouth technique Int J Oral Maxillofac Surg 2010;39:107–114 70 Tan S, Lo J, Zwahlen R Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial Int J Oral Maxillofac Surg 2011;40:1363–1368 53 Adde C, Soares M, Romano M, et al Clinical and surgical evaluation of the indication of postoperative antibiotic prescription in third molar surgery Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114(5, suppl):S26–S31 71 Danda A, Wahab A, Narayanan V, Siddareddi A Single-dose versus single-day antibiotic prophylaxis for orthognathic surgery: A prospective, randomized, double-blind clinical study J Oral Maxillofac Surg 2010;68:344–346 54 Hill M No benefit from prophylactic antibiotics in third molar surgery Evid Based Dent 2005;6:10 72 Danda A, Ravi P Effectiveness of postoperative antibiotics in orthognathic surgery: A meta-analysis J Oral Maxillofac Surg 2011;69:2650–2656 55 van Eeden SP, Butow K Post-operative sequelae of lower third molar removal: A literature review and pilot study on the effect of Covomycin D SADJ 2006;61:154–159 73 Harrell L, Shetty V Extended antibiotic therapy may reduce risk of infection following orthognathic surgery J Evid Based Dent Pract 2012;12:144–145 56 Halpern LR, Dodson TB Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery? J Oral Maxillofac Surg 2007;65:177–185 74 Bentley KC, Head TW, Aiello GA Antibiotic prophylaxis in orthognathic surgery: A 1-day versus 5-day regimen J Oral Maxillofac Surg 1999;57:226–230 57 Hedstrom L, Sjogren P Effect estimates and methodological quality of randomized controlled trials about prevention of alveolar osteitis following tooth extraction: A systematic review Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:8–15 75 Wahab P, Narayanan V, Nathan S, Madhulaxmi Antibiotic prophylaxis for bilateral sagittal split osteotomies: A randomized, double-blind clinical study Int J Oral Maxillofac Surg 2013;42:352–355 58 Sharaf B, Jandali-Rifai M, Susarla SM, Dodson TB Do perioperative antibiotics decrease implant failure? J Oral Maxillofac Surg 2011;69:2345–2350 76 Baqaina Z, Hydeb N, Patrikidouc A, Harris M Antibiotic prophylaxis for orthognathic surgery: A prospective, randomised clinical trial Br J Oral Maxillofac Surg 2004;42:506–510 59 Sharaf B, Dodson T Does the use of prophylactic antibiotics decrease implant failure? Oral Maxillofacial Surg Clin N Am 2011;23:547–550 77 Kyzas PA Use of antibiotics in the treatment of mandible fractures: A systematic review J Oral Maxillofac Surg 2011;69:1129–1145 59 www.ajlobby.com Mizukawa_Chap_05.indd 59 6/20/17 10:31 AM 5 • Prophylactic and Perioperative Antibiotics 95 Johnson JT, Schuller DE, Silver F, et al Antibiotic prophylaxis in highrisk head and neck surgery: One-day vs five-day therapy Otolaryngol Head Neck Surg 1986;95;554–557 78 Zallen RD, Curry JT A study of antibiotic usage in compound mandibular fractures J Oral Surg 1975;33:431–434 79 Chole R, Yee J Antibiotic prophylaxis for facial fractures A prospective, randomized clinical trial Arch Otolaryngol Head Neck Surg 1987;113:1055–1057 96 Avenia N, Sanguinetti A, Cirocchi R, et al Antibiotic prophylaxis in thyroid surgery: A preliminary multicentric Italian experience Ann Surg Innov Res 2009;3:10 80 Miles BA, Potter JK, Ellis E III The efficacy of postoperative antibiotic regimens in the open treatment of mandibular fractures: A prospective randomized trial J Oral Maxillofac Surg 2006;64:576–582 97 Johnson JT, Wagner RL Infection following uncontaminated head and neck surgery Arch Otolaryngol Head Neck Surg 1987;113:368–369 98 Robbins KT, Favrot S, Hanna D, Cole R Risk of wound infection in patients with head and neck cancer Head Neck 1990;12:143–148 81 Andreasen JO, Jensen SS, Schwartz O, Hillerup Y A systematic review of prophylactic antibiotics in the surgical treatment of maxillofacial fractures J Oral Maxillofac Surg 2006;64:1664–1668 99 Montefusco V, Gay F, Spina F, et al Antibiotic prophylaxis before dental procedures can reduce ONJ incidence Blood 2007;110:3613 82 Andreasen JO, Storgård Jensen S, Kofod T, Schwartz O, Hillerup S Open or closed repositioning of mandibular fractures: Is there a difference in healing outcome? A systematic review Dent Traumatol 2008;24:17–21 100 Montefusco V, Gay F, Spina F, et al Antibiotic prophylaxis before dental procedures may reduce the incidence of osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates Leuk Lymphoma 2008;49:2156–2162 83 Senel FC, Jessen GS, Melo MD, Obeid G Infection following treatment of mandible fractures: The role of immunosuppression and polysubstance abuse Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:38–42 101 López-Jornet P, Camacho-Alonso F, Martínez-Canovas A, Molina-Miđano F, Gómez-García F, Vicente-Ortega V Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: A study of the changes in the jaws J Oral Maxillofac Surg 2011;69:2488–2493 84 Goldfarb MS, Hoffman DS, Rosenberg S Orbital cellulitis and orbital fractures Ann Ophthalmol 1987;19:97–99,115 102 Dimopoulos M, Kastritis E, Bamia C, et al Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid Ann Oncol 2008;20:117–120 85 Weber RS, Callender DL Antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery Ann Otol Rhinol Laryngol 1992;101:16–20 86 Zix J, Schaller B, Iizuka T, Lieger O The role of postoperative prophylactic antibiotics in the treatment of facial fractures: A randomised, double-blind, placebo-controlled pilot clinical study Part 1: Orbital fractures in 62 patients Br J Oral Maxillofac Surg 2013;51:332–336 103 Ferlito S, Puzzo S, Liardo C Preventive protocol for tooth extractions in patients treated with zoledronate: A case series J Oral Maxillofac Surg 2001;69:e1–e4 104 Van den Wyngaert T, Claeys T, Huizing M, Vermorken J, Fossion E Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome Ann Oncol 2008;20:331–336 87 Soong PL, Schaller B, Zix J, Iizuka T, Mottini M, Lieger O The role of postoperative prophylactic antibiotics in the treatment of facial fractures: A randomised, double-blind, placebo-controlled pilot clinical study Part 3: Le Fort and zygomatic fractures in 94 patients Br J Oral Maxillofac Surg 2014;52:329–333 105 Lodi G, Sardella A, Salis A, Demarosi F, Tarozzi M, Carrassi A Tooth extraction in patients taking IV bisphosphonates: A preventive protocol and case series J Oral Maxillofac Surg 2010;68:107–110 88 Lindeboom JA, van den Akker HP A prospective placebo-controlled double-blind trial of antibiotic prophylaxis in intraoral bone grafting procedures: A pilot study Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:669–672 106 Hoefert S, Eufinger H Relevance of a prolonged preoperative antibiotic regime in the treatment of bisphosphonate-related osteonecrosis of the jaw J Oral Maxillofac Surg 2011;69:362–380 89 Lindeboom JA, Baas EM, Kroon FH Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: A prospective randomized study in bilateral mandibular sagittal ramus osteotomies Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:145–149 107 Freiberger JJ, Padilla-Burgos R, McGraw T, et al What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: A randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics J Oral Maxillofac Surg 2012;70:1573–1583 90 LaPorte DM, Waldman BJ, Mont MA, Hungerford DS Infections associated with dental procedures in total hip arthroplasty J Bone Joint Surg Br 1999;81:56–59 108 Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws— 2009 update J Oral Maxillofac Surg 2009;67:2–12 91 Curry S, Phillips H Joint arthroplasty, dental treatment, and antibiotics: A review J Arthroplasty 2002;17:111–113 109 Ruggiero SL, Dodson TB, Fantasia J, et al American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update J Oral Maxillofac Surg 2014;72:1938–1956 [errata 2015;73:1440 and 2015;73:1879] 92 Little JW Managing dental patients with joint prostheses J Am Dent Assoc 1994;125:1374–1381 93 Maderazo EG, Judson S, Pasternak H Late infections of total joint prostheses: A review and recommendations for prevention Clin Orthop 1988;229:131–142 110 Halkos ME, Lattouf OM, Puskas JD, et al Elevated preoperative hemoglobin A1c level is associated with reduced long-term survival after coronary artery bypass surgery Ann Thorac Surg 2008;86:1431–1437 94 Wahl M Antibiotic prophylaxis in artificial joint patients [comment] J Oral Maxillofac Surg 2010;68:949 60 www.ajlobby.com Mizukawa_Chap_05.indd 60 6/20/17 10:31 AM References 119 American Academy of Pediatric Dentistry Guideline on antibiotic prophylaxis for dental patients at risk for infection https://www.aapd.org/ media/Policies_Guidelines/G_AntiobioticProphylaxis.pdf Accessed 25 April 2017 111 Barasch A, Safford M, Litaker M, Gilbert G Risk factors for oral postoperative infection in patients with diabetes Spec Care Dentist 2008;28:159–166 112 Jacober SJ, Sowers JR An update on preoperative management of diabetes Arch Intern Med 1999;159:2405–2411 120 Aronovich S, Skope LW, Kelly JP, Kyriakides TC The relationship of glycemic control to the outcomes of dental extractions J Oral Maxillofac Surg 2010;68:2955–2961 113 Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery J Am Coll Cardiol 2002;40:418–423 121 Capuzzi P, Montebugnoli L, Vaccaro MA Extraction of impacted third molars: A longitudinal prospective study on factors that affect postoperative recovery Oral Surg Oral Med Oral Pathol 1994;77:341–343 114 Szabó Z, Håkanson E, Svedjeholm R Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting Ann Thorac Surg 2002;74:712–719 122 Bell G, Large D, Barclay S Oral health care in diabetes mellitus SADJ 2000;55:158–65 123 Ship J Diabetes and oral health: An overview J Am Dent Assoc 2003;134:4S–10S 115 Axelrod DA, Upchurch GR Jr, DeMonner S, et al Perioperative cardiovascular risk stratification of patients with diabetes who undergo elective major cardiovascular surgery J Vasc Surg 2002;35:894–901 124 Gudapati A, Ahmed P, Rada R Dental management of patients with renal failure Gen Dent 2002;50:508–510 116 Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events Circulation 2004;109:1497–1502 125 Ramu C, Padmanabhan TV Indications of antibiotic prophylaxis in dental practice—Review Asian Pac J Trop Biomed 2012;2:749–754 126 Shirlaw PJ, Chikte U, MacPhail L, Schmidt-Westhausen A, Croser D, Reichart P Oral and dental care and treatment protocols for the management of HIV-infected patients Oral Dis 2002;8(suppl 2):136–143 117 Ueta E, Osaki T, Yoneda K, Yamamoto T Prevalence of diabetes mellitus in odontogenic infections and oral candidiasis: An analysis of neutrophil suppression J Oral Pathol Med 1993;22:168–174 127 Schmidt B, Kearns G, Perrott D, Kaban LB Infection following treatment of mandibular fractures in human immunodeficiency virus seropositive patients J Oral Maxillofac Surg 1995;53:1134–1139 118 Van den Berghe G, Wouters P, Weekers F, et al Intensive insulin therapy in critically ill patients N Engl J Med 2001;345:1359–1367 61 www.ajlobby.com Mizukawa_Chap_05.indd 61 6/20/17 10:31 AM www.ajlobby.com Mizukawa_Chap_05.indd 62 6/20/17 10:31 AM CHAPTER Analgesia Considerations in Anesthesia Sean M Young, dds, md H Daniel Clark, dds, md www.ajlobby.com Mizukawa_Chap_06.indd 63 6/20/17 10:31 AM 6 • Analgesia Considerations in Anesthesia Patient comfort plays a substantial role in the overall patient experience of oral and maxillofacial surgery Patient satisfaction with minor oral surgery has been negatively correlated with pain felt during a procedure.1 Adequate analgesia is the foundation of patient comfort, and pain management must extend beyond prescribing appropriate postoperative analgesics The pain experience is influenced by preoperative, intraoperative, and postoperative factors Accordingly, the surgeon should take advantage of opportunities for pain management in the preoperative, intraoperative, and postoperative periods After a brief review of pain mechanisms, this chapter focuses on factors that affect pain perception and appropriate interventions to improve the overall patient experience Mechanisms of Pain Nociception refers to the processing of noxious stimuli that create the sensation of pain Four processes contribute to nociception: transduction, transmission, modulation, and perception Transduction refers to the initiation of an action potential in peripheral nociceptors Mechanical, chemical, and thermal tissue damage will cause the local release of mediators, including potassium, hydrogen ions, prostaglandins, and bradykinin, which in turn activate the action potential Other mediators, such as substance P, histamine, and serotonin, sensitize peripheral nociceptors in the damaged area, lowering the threshold for action potentials in adjacent nociceptors Transmission refers to the conduction of the electrical activity initiated by local tissue damage, from the nerve endings in the periphery to the cell bodies of afferent neurons in the dorsal root ganglion, up the spinal cord, and ultimately to the sensory cortex Perception takes place at the level of the sensory cortex A person’s pain perception is ultimately the result of cortical interpretation of stimuli that are processed and transmitted from peripheral nerve endings to the supraspinal level This interpretation is also affected by learned behavior and situation-specific anxiety or fear Modulation refers to the endogenous and exogenous mechanisms that inhibit noxious transmissions from reaching the sensory cortex Some of the endogenous mediators that modulate noxious stimuli are enkephalin, norepinephrine, and gamma-aminobutyric acid Analgesia is the inability to feel pain caused by noxious stimuli Analgesic drugs interfere with one or more of the nociceptive processes to reduce the overall experience of pain Preoperative Period When anesthetic options are discussed with patients during the preoperative consultation, it is important for the clinician to understand a patient’s tolerance for dental and surgical procedures, especially pertaining to fear or anxiety Identifying patient concerns will guide recommendations for local anesthesia, nitrous oxide sedation, intravenous (IV) sedation, or general anesthesia Postoperative pain level has been correlated with perioperative anxiety.2,3 Depending on the patient’s anxiety level, a practitioner may recommend a preoperative oral anxiolytic For patients undergoing IV sedation, oral premedication is rarely necessary In addition to selecting an appropriate anesthetic plan, the surgeon should provide a reasonable expectation for postoperative discomfort for a given procedure Many surgeons prefer a separate preoperative consultation visit before the day of the surgical procedure The authors of one study evaluated the effect of a separate consultation on levels of anxiety and found no statistically significant difference in anxiety levels compared with those of patients who underwent same-day consultation and procedure However, more than 90% of patients in the study group would choose a preoperative consultation again if given the option.4 In another study, patients who received detailed postoperative instructions reported less pain in the first 24 hours after third molar removal than patients who received open-ended instructions.5 Some practitioners recommend a preoperative analgesic, such as ibuprofen or naproxen, to prevent central sensitization by blocking the formation of prostaglandins Clinical data on preventive analgesia have been conflicting.6,7 A recent study suggests that this practice does not clinically reduce postoperative pain, facial swelling, trismus, or need for rescue analgesics when compared with postoperative administration.8 Preoperative IV ketorolac (a 64 www.ajlobby.com Mizukawa_Chap_06.indd 64 6/20/17 10:31 AM Intraoperative Period nonsteroidal anti-inflammatory drug [NSAID]) has been shown to reduce early postoperative pain in the first hours after third molar removal but did not reduce total opioid consumption in the first postoperative days.9 Steroids and antibiotics should also be considered as measures to prevent pain A single IV steroid dose before incision results in decreased pain during the first postoperative days compared with use of a placebo.10 Use of a preincision antibiotic before third molar removal, in addition to reducing the risk of wound infection, has resulted in less postoperative pain compared with use of no antibiotic.11,12 Intraoperative Period Analgesia during the intraoperative period requires effective anesthesia Local anesthesia is the foundation of a successful procedure, even in the sedated patient Profound local anesthesia blocks the conduction of nociceptive input from operative stimuli, thereby reducing the amounts of sedative medications during IV sedation Evidence suggests that local anesthetics attenuate the inflammatory response and associated postoperative pain.13,14 Local anesthesia, particularly that resulting from long-acting medications, such as bupivacaine, provides the patient with time to begin taking postoperative pain medications before elimination of local anesthesia Important concepts regarding technique, selection of appropriate local anesthetic drug, and potential complications are addressed in chapter Several classes of medication are commonly used in combination in the sedated patient Chapters and provide a detailed discussion of these medications, many of which contribute to effective analgesia In addition to a preoperative steroid and/or NSAID, nitrous oxide (N2O) may be used as part of a balanced anesthesia approach Nitrous oxide is ubiquitous in dentistry and is increasingly being used in the hospital setting, such as during maternal labor and minor pediatric procedures Nitrous oxide exhibits rapid onset and elimination, and it provides modest intraoperative analgesia A double-blinded study of pediatric patients undergoing minor procedures demonstrated 50% lower pain scores with nitrous oxide and oxygen than with nitrogen and oxygen.15 Nitrous oxide has also been shown to be more effective than oral midazolam in allowing IV access in children and adolescents with previous difficulties with IV access Patients receiving 50% nitrous oxide during IV line procedures experienced a shorter procedure time, an improved rate of IV access, and a better patient experience for children or adolescents.16 In the author’s clinical practice, nitrous oxide is used routinely in conjunction with IV sedation, both before IV access and throughout the procedure This approach has also reduced the total dose of the other medications used during IV sedation Opioids are an important part of a balanced anesthetic technique in IV sedation in outpatient oral and maxillofacial surgery Fentanyl is currently the most commonly used opioid analgesic because of its rapid onset of action and distribution into the central nervous system It is 100 times more potent than morphine but results in less histamine release, which reduces the incidence of itching that is commonly seen with morphine Its onset of action is to minutes because of its high fat solubility, and its duration is typically 30 to 45 minutes, making it an appropriate choice for the majority of outpatient procedures Nausea and vomiting are uncommon side effects Fentanyl is a respiratory and circulatory depressant, especially when used in conjunction with other sedatives Titration of fentanyl minimizes these risks The risk of glottis and chest wall rigidity is rare unless large boluses (≥5 µg/kg) are administered This potentially life-threatening complication is reversible with naloxone or succinylcholine Remifentanil is an alternative opioid used by some oral and maxillofacial surgeons who prefer a continuous infusion technique in combination with propofol Remifentanil is an ultra-short-acting opioid analgesic with unique pharmacodynamics, particularly rapid onset, easy titration, and context-sensitive half-life, which is independent of the duration of infusion Clinically, these properties translate into rapid onset and recovery, independent of procedure duration For surgeons who use an intermittent bolus technique, remifentanil’s rapid termination of effect offers limited advantage over fentanyl Because fentanyl is typically given as a one-time dose at the beginning of a procedure, it rarely results in extended postanesthesia recovery time A substantial cost barrier has limited the use of remifentanil in outpatient oral surgery Remifentanil is available only in powder form and must be used within 24 hours after being reconstituted, often resulting in drug waste In terms of analgesic properties, when fentanyl and 65 www.ajlobby.com Mizukawa_Chap_06.indd 65 6/20/17 10:31 AM 6 • Analgesia Considerations in Anesthesia remifentanil were compared in deep sedation procedures, no statistically significant difference was found in indicators of pain control, such as intraoperative heart rate.17 Ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits intrinsic analgesic properties Low-dose ketamine (0.15 to 1.0 mg/kg) is commonly used in balanced anesthetic techniques and has been shown to be opioid sparing.18 Benzodiazepines and propofol reduce the incidence of postoperative hallucinations and nightmares, both of which are known complications of ketamine A systematic review of IV ketamine confirms an increase in time to first analgesic use and decreased total opioid consumption in the postoperative period.19 The rapid onset of hypnosis and potent analgesic effect of ketamine allows the surgeon to administer local anesthesia without patient movement and to begin the procedure with minimal delay Clonidine and dexmedetomidine are centrally acting α2 adrenoreceptor agonists that have not yet been widely adopted in outpatient oral and maxillofacial surgery practices Both exhibit sedative and analgesic properties The analgesic effect is due to downregulation of afferent pain stimuli at the supraspinal level Clonidine is most often administered as a preoperative oral medication, with maximum sedative effect at 120 minutes It causes a dose-dependent reduction in heart rate and blood pressure, and the dose should be reduced in geriatric patients to avoid hypotension and oversedation Clonidine does not appear to have any effect on respiratory drive Dexmedetomidine, approved in 1999 for use in intensive care units for sedation and analgesia, has seen increased use in general anesthesia in the operating room setting It is typically titrated intravenously as a continuous infusion Cost is currently a substantial barrier to widespread use of dexmedetomidine Postoperative Period Despite efforts to minimize postoperative pain through preoperative and intraoperative interventions, postoperative analgesics are necessary for most patients undergoing outpatient oral surgery procedures This section reviews the common classes of medications used in current oral and maxillofacial surgery practices (Table 6-1) Often more than one analgesic is prescribed to achieve superior pain relief while minimizing potential side effects of the individual drugs This multimodal approach is especially useful when moderate to severe pain is expected Table 6-1 Analgesics commonly used in oral and maxillofacial surgery Medication class Common dosage Dosage schedule Maximum dosage Ibuprofen Naproxen Ketoprofen Ketorolac NSAID 400–800 mg 250–500 mg 50–100 mg 10 mg Orally every 4–6 h Orally every 12 h Orally every h Orally every 4–6 h 3,200 mg in 24 h 1,500 mg in 24 h 300 mg in 24 h 40 mg in 24 h Codeine Hydrocodone Oxycodone Opioid 15–60 mg 2.5–10 mg 5–15 mg Orally every 4–6 h 360 mg in 24 h 60 mg*† 60 mg*† Hydromorphone Opioid 2–8 mg Orally every 3–4 h Meperidine Opioid 50–150 mg Orally every 3–4 h Acetaminophen Other Tramadol Other Analgesic 325–1,000 mg Orally every 4–6 h 50–100 mg Orally every 4–6 h 48 mg*† 600 mg in 24 h 1,000 mg in h or 4,000 mg in 24 h Precautions • Avoid in third trimester of pregnancy • Caution required in patients with renal disease, coagulation disorders, asthma, or history of gastrointestinal bleeding Caution required in pediatric or elderly patients, patients with urethral stricture, and patients with biliary disease Caution required in patients with hypersensitivity to sulfites, urethral stricture, biliary disease, or seizure disorder Caution required in patients taking MAO inhibitors and patients with sickle cell disease • Caution required in patients with hepatic disease • Risk of methemoglobinemia 400 mg in 24 h • Caution required in elderly patients, patients (300 mg in patients with history of seizures, and patients with older than 75 y) psychiatric disorder • Risk of serotonin syndrome • Risk of Stevens-Johnson syndrome *Higher maximum daily dosage may be appropriate in patients with opiate tolerance † Maximum daily dosage may be limited by acetaminophen or ibuprofen content in opiate-combination medications 66 www.ajlobby.com Mizukawa_Chap_06.indd 66 6/20/17 10:31 AM Postoperative Period Nonsteroidal anti-inflammatory drugs NSAIDs (eg, aspirin, ibuprofen, naproxen) are a mainstay in postoperative pain management NSAIDs inhibit prostaglandin and thromboxane synthesis via inhibition of the cyclooxygenase (COX) enzyme (Fig 6-1) Most NSAIDs inhibit both the COX-1 and COX-2 isoenzymes Most NSAIDs undergo hepatic metabolism and are excreted in the urine Ibuprofen is most commonly selected because of its familiarity, low cost, widespread availability, and low risk profile in patients without substantial comorbid conditions NSAIDs are often prescribed in conjunction with an opioid-acetaminophen combination medication for relief of moderate to severe postoperative pain Ibuprofen has been shown to improve pain, swelling, jaw function, and return to normal diet after minor oral surgery.10 Ibuprofen was also associated with a 50% reduction in opioid requirement.10 Ibuprofen has also been shown to be superior to acetaminophen after removal of mandibular third molars.20 NSAIDs should be avoided in patients with asthma and in patients with certain cardiovascular, gastrointestinal, hepatic, and renal conditions, as well as during pregnancy, especially in the third trimester Cell damage Cell membrane PLA2 Arachidonic acid Cyclooxygense (COX) Lipoxygenase Leukotrienes Bronchoconstriction Histamine Vasodilation Pain PGs COX-1 PG COX-2 TXA2 • Gastric mucosa • Platelet function • Renal function • Vasoconstriction PG PC • Pain, inflammation • Platelet inhibition • Fever • Vasodilation • Renal function Fig 6-1 The role of arachidonic acid in the mediation of pain and swelling When cells sustain mechanical, chemical, or thermal injury, phospholipids in the cell membrane are cleaved by phospholipase A2 (PLA2), releasing arachidonic acid Arachidonic acid is further cleaved by lipoxygenase to make leukotrienes, or cyclooxygenase (COX-1) to produce prostaglandin (PG) and thromboxane A2 (TXA2), or cyclooxygenase (COX-2) to make PG and prostacyclin (PC) The physiologic responses of leukotrienes, PG, TXA2, and PC are shown Most NSAIDs inhibit both COX-1 and COX-2 Some selectively inhibit the COX-2 enzyme, reducing the gastrointestinal side effects of COX-1 inhibition Acetaminophen Acetaminophen, also known as paracetamol, is a mild nonsteroidal analgesic that exhibits minimal anti-inflammatory activity and is therefore not classified as an NSAID Although its mechanism of action is not completely understood, acetaminophen appears to selectively inhibit COX-2.21 Acetaminophen undergoes hepatic metabolism, and overdose of acetaminophen is the most common cause of acute liver failure in the United States Acetaminophen is often given in combination with opioids (hydrocodone or oxycodone), and patients should be cautioned about risk of acetaminophen toxicity with overuse For patients who cannot tolerate opioids, or in whom opioids are contraindicated, acetaminophen can be an effective alternative,22 although it is more effective when given in combination with ibuprofen.20 Acetaminophen should be avoided in patients who have severe liver disease or who consume alcoholic beverages daily 67 www.ajlobby.com Mizukawa_Chap_06.indd 67 6/20/17 10:31 AM 6 • Analgesia Considerations in Anesthesia Opioid and opioid-containing medications Opioid drugs act on endogenous opioid receptors to provide central analgesia A multitude of opioid analgesics are available Codeine derivatives (hydrocodone and oxycodone) are appropriate for management of acute postoperative pain In a survey conducted in 2013 of the opioid prescribing habits among oral and maxillofacial surgeons after third molar removal, nearly all respondents prescribed opioids; hydrocodone was prescribed most frequently (60%), followed by oxycodone and codeine Hydrocodone and oxycodone prescriptions were typically written for 20 or fewer 5-mg tablets A minority of respondents (22%) prescribed more than 20 tablets Two-thirds recommended adjunctive use of NSAIDs.23 These prescribing habits are generally in line with recommendations to prescribe smaller doses with higher frequency, and to limit the number of tablets to cover the expected duration of substantial pain Oral surgeons have a responsibility to minimize their contribution to opioid diversion and misuse Codeine is less commonly prescribed by oral and maxillofacial surgeons because it offers less predictable pain control Codeine is an inactive parent drug that is dependent on cytochrome P450 metabolism to form an active metabolite (morphine) It is relatively ineffective in up to 10% of the population, who are poor metabolizers of cytochrome P450 When prescribed in combination with acetaminophen, codeine is a Schedule III drug at the time of this printing As a result of the 2014 rescheduling of hydrocodone-containing products in the United States from Schedule III to Schedule II of the Controlled Substances Act, the reliance on codeine plus acetaminophen for postoperative pain management has increased because of the ability to phone a codeine-acetaminophen prescription to pharmacies.24 Oral morphine, hydromorphone, oxymorphone, and methadone are examples of opioid analgesics often prescribed in sustained-release and extended-release formulations, and are reserved for the management of chronic pain Immediate-release oral hydromorphone is a morphine derivative that is an appropriate alternative to codeine derivatives for patients requiring relief of moderate to severe pain Tramadol is an atypical opioid analgesic that has both opioid and serotonin-norepinephrine reuptake inhibitory effects Tramadol is a substrate for cytochrome P450 and thus has many drug interactions For these reasons, it is less commonly prescribed All opioid analgesics have similar side effect profiles Nausea and vomiting are common postoperative complaints that can be minimized by taking opioids with food Constipation is a problem with prolonged opioid use and is infrequently reported with short-term use after minor oral surgery Respiratory depression and somnolence are important side effects that patients and family members must be made aware of, particularly for patients who undergo deep sedation or general anesthesia Home monitoring is important to ensure patient safety Pain Management in Patients with Chronic Pain or Opioid Dependence Patients with a history of chronic pain, substance use disorders, or opioid dependence require special consideration These patients typically demonstrate increased opioid tolerance and decreased pain tolerance Preoperative consultation should be considered before surgical treatment for patients with chronic pain and for patients in methadone treatment programs Methadone is a long-lasting opioid analgesic used to treat individuals who are dependent on or addicted to opioids, individuals who are addicted to heroin, and individuals with chronic pain Because of the extremely addictive nature of these drugs and the withdrawal symptoms associated with them, people who are dependent on these drugs often cannot function in society as they try to quit Methadone is usually dosed once a day because of its long half-life, and its dose can be tapered to help ease the cessation efforts Intraoperatively, local and regional anesthesia with long-acting local anesthetics should be used whenever possible Postoperatively, nonopioid analgesics such as NSAIDs may be used solely or in combination with opioid medications Patients currently taking methadone or other long-acting opioids should resume their normal doses of these medications as soon as possible Short-acting opioid medications may be prescribed; however, an opioid agreement may be necessary to outline the expected time frame for providing these medications It may be prudent to have a responsible friend or 68 www.ajlobby.com Mizukawa_Chap_06.indd 68 6/20/17 10:31 AM References family member of the patient dispense or monitor the use of opioid pain medications The use of medications that have previously been problematic for the patient should be avoided.25 Summary In today’s outcome-focused health care environment, proper management of pain is critical to achieving desired patient comfort and satisfaction with surgical care Careful consideration should be given to managing pain at multiple points along the course of care including before, during, and after surgery References 13 Hollmann MW, Durieux ME Local anesthetics and the inflammatory response: A new therapeutic indication? Anesthesiology 2000;93:858–875 Muglali M, Komerik N Factors related to patients’ anxiety before and after oral surgery J Oral Maxillofac Surg 2008;66:870–877 Kain ZN, Mayes LC, Caldwell-Andrews AA, Karas DE, McClain BC Preoperative anxiety, postoperative pain, and behavioral recovery in young children undergoing surgery Pediatrics 2006;118:651–658 14 Gordon SM, Dionne RA, Brahim J, Jabir R, Dubner R Blockade of peripheral neuronal barrage reduces postoperative pain Pain 1997;70:209–215 Chieng YJ, Chan WC, Klainin-Yobas P, He HG Perioperative anxiety and postoperative pain in children and adolescents undergoing elective surgical procedures: A quantitative systematic review J Adv Nurs 2014;70:243–255 15 Reinoso-Barbero F, Pascual-Pascual SI, de Lucas R, et al Equimolar nitrous oxide/oxygen versus placebo for procedural pain in children: A randomized trial Pediatrics 2011;127:e1464–e1470 16 Ekbom K, Kalman S, Jakobsson J, Marcus C Efficient intravenous access without distress: A double-blind randomized study of midazolam and nitrous oxide in children and adolescents Arch Pediatr Adolesc Med 2011;165:785–791 van Wijk A, Lindeboom J The effect of a separate consultation on anxiety levels before third molar surgery Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:303–307 Vallerand WP, Vallerand AH, Heft M The effects of postoperative preparatory information on the clinical course following third molar extraction J Oral Maxillofac Surg 1994;52:1165–1170 17 Lacombe GF, Leake JL, Clokie CM, Haas DA Comparison of remifentanil with fentanyl for deep sedation in oral surgery J Oral Maxillofac Surg 2006;64:215–222 Dionne RA Suppression of dental pain by the preoperative administration of flurbiprofen Am J Med 1986;80(3, suppl A):41–49 18 Schmid RL, Sandler AN, Katz J Use and efficacy of low-dose ketamine in the management of acute postoperative pain: A review of current techniques and outcomes Pain 1999;82:111–125 Jung YS, Kim MK, Um YJ, Park HS, Lee EW, Kang JW The effects on postoperative oral surgery pain by varying NSAID administration times: Comparison on effect of preemptive analgesia Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:559–563 19 Laskowski K, Stirling A, McKay WP, Lim HJ A systematic review of intravenous ketamine for postoperative analgesia Can J Anaesth 2011;58:911–923 Aznar-Arasa L, Harutunian K, Figueiredo R, Valmaseda-Castellón E, Gay-Escoda C Effect of preoperative ibuprofen on pain and swelling after lower third molar removal: A randomized controlled trial Int J Oral Maxillofac Surg 2012;41:1005–1009 20 Bailey E, Worthington HV, van Wijk A, Yates JM, Coulthard P, Afzal Z Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth Cochrane Database Syst Rev 2013;(12):CD004624 Gutta R, Koehn CR, James LE Does ketorolac have a preemptive analgesic effect? A randomized, double-blind, control study J Oral Maxillofac Surg 2013;71:2029–2034 21 Hinz B, Cheremina O, Brune K Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man FASEB J 2008;22:383–390 10 Mehra P, Reebye U, Nadershah M, Cottrell D Efficacy of anti-inflammatory drugs in third molar surgery: A randomized clinical trial Int J Oral Maxillofac Surg 2013;42:835–842 22 Weil K, Hooper L, Afzal Z, et al Paracetamol for pain relief after surgical removal of lower wisdom teeth Cochrane Database Syst Rev 2007;(3):CD004487 11 Monaco G, Tavernese L, Agostini R, Marchetti C Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients J Oral Maxillofac Surg 2009;67:1467–1472 23 Mutlu I, Abubaker AO, Laskin DM Narcotic prescribing habits and other methods of pain control by oral and maxillofacial surgeons after impacted third molar removal J Oral Maxillofac Surg 2013;71:1500–1503 12 Lacasa JM, Jiménez JA, Ferrás V, et al Prophylaxis versus pre-emptive treatment for infective and inflammatory complications of surgical third molar removal: A randomized, double-blind, placebo-controlled, clinical trial with sustained release amoxicillin/clavulanic acid (1000/62.5 mg) Int J Oral Maxillofac Surg 2007;36:321–327 24 Peng PW, Tumber PS, Gourlay D Perioperative pain management of patients on methadone therapy Can J Anesth 2005;52:513–523 25 Seago S, Hayek A, Pruszynski J, Newman MG Change in prescription habits after federal rescheduling of hydrocodone combination products Proc (Bayl Univ Med Cent) 2016;29:268–270 69 www.ajlobby.com Mizukawa_Chap_06.indd 69 6/20/17 10:31 AM www.ajlobby.com Mizukawa_Chap_06.indd 70 6/20/17 10:31 AM CHAPTER Postoperative Nausea and Vomiting Danielle L Cruthirds, phd Pamela J Sims, pharmd, phd Patrick J Louis, dds, md www.ajlobby.com Mizukawa_Chap_07.indd 71 6/20/17 10:31 AM 7 • Postoperative Nausea and Vomiting A 20% to 30% incidence of postoperative nausea and vomiting (PONV) can be expected with the use of intravenous sedation and general anesthesia for oral and maxillofacial surgery procedures.1–3 Patients have rated severe nausea worse than postoperative pain.4 This chapter reviews the pathophysiology of nausea and vomiting, antiemetic interventions, and current therapies used for the prevention and management of PONV and postdischarge nausea and vomiting (PDNV) Pathophysiology The vomiting reflex appears to originate in the emetic or vomiting center located in the medulla Multiple sensory inputs, including the vagus nerve (cranial nerve X), the vestibular nerve (cranial nerve VIII), the limbic system, and the chemoreceptor trigger zone (CRTZ), are involved in this reflex.5 The vagus nerve relays sensory input, primarily via serotonin, from the mechanoreceptors and chemoreceptors in the gastrointestinal (GI) tract, respiratory tract, and cardiovascular system The vestibular nerve relays input from the auditory labyrinth via histamine and acetylcholine The limbic system appears to play a role in the learned response of anticipatory nausea and vomiting.6 The CRTZ is exposed to blood and cerebrospinal fluid and thus can react to substances in the blood Several neurotransmitters and neuromodulators, including serotonin, dopamine, histamine, acetylcholine, substance P, and adrenaline, trigger this area.7 The CRTZ identifies harmful substances and relays this information to the vomiting center The vomiting center then activates the efferent motor pathways initiating the vomiting response.8,9 The vomiting cascade is complex and includes multiple steps The cascade continues until the stimulus is no longer present.8 Risk Factors To determine a patient’s risk for PONV, the provider may use an assessment score Apfel et al10 developed a risk scoring system consisting of four predictors: female sex, history of motion sickness and/or PONV, nonsmoking status, and use of postoperative opioids When none, one, two, three, or four of these risk factors were present, the incidence of PONV was 10%, 21%, 39%, 61%, or 79%, respectively A patient’s risk of PONV depends on preoperative, intraoperative, and postoperative factors.5,10–13 These risk factors are summarized in Tables 7-1 to 7-3 Risk factors related to opioid use in oral surgery require a more detailed discussion and special consideration because of the physiologic effects of opioid use Opioids directly stimulate the area postrema, causing PONV, decreasing gastric and GI motility, prolonging gastric emptying time, and predisposing the patient to PONV by sensitizing the otic and vestibular areas to motion.5,14 Postoperative patient movement resulting in stimulation of endolymph in the inner ear appears to increase the frequency of opioid-induced emesis.14 Frequent changes in body position that occur in the ambulatory patient increase the frequency of opioid-induced emesis.14,15 PONV in outpatients often occurs after movement from the chair to a standing position, during ambulation, or during the car ride home.16 These dose-related effects may last for up to hours after opioid administration.16 72 www.ajlobby.com Mizukawa_Chap_07.indd 72 6/20/17 10:31 AM Antiemetic Interventions Table 7-1 Preoperative risk factors for PONV Risk factor Important considerations Age More common in children after y of age; risk peaks at age 11–14 y and decreases in adults with increasing age Sex After puberty, risk is two to three times higher in female patients than in male patients and is increased closer to menstruation Weight Increased in morbidly obese patients Gastric contents Increased with full stomach and fried or fatty foods History Increased threefold with history of PONV or motion sickness Table 7-2 Intraoperative risk factors for PONV Risk factor Type of procedure Important considerations Increased with presence of swallowed blood in the stomach after oral surgery Duration of procedure Increased with duration Type of anesthesia Increased with general anesthesia and premedication with opioids; nitrous oxide–induced central nervous system stimulation of the vomiting center, sympathetic nervous system, and peripheral pathways; interaction with opioid receptors Table 7-3 Postoperative risk factors for PONV Risk factor Important considerations Pain Major cause of PONV Hypotension Orthostatic hypotension can occur as a result of dehydration; risk increased with opioids (vasodilation) and phenothiazines (blockade of α-adrenergic receptors) Dehydration Children particularly susceptible Opioid analgesia Strong emetic effect Oral intake Increased risk in the presence of gastric contents Movement Movement from chair to standing, ambulation, or postoperative car transportation Antiemetic Interventions The antiemetic agents commonly used for the management of PONV include anticholinergics, antihistamines, phenothiazines, sedatives/anxiolytics, butyrophenones, dopamine receptor antagonists, serotonin receptor antagonists, corticosteroids, or a combination of these agents (Table 7-4) Drugs that may be effective prophylactic medication for PONV may be ineffective for the treatment of active vomiting No single antiemetic medication has been 100% effective for all patients4,5,11,13,14,17–19 (Table 7-5) 73 www.ajlobby.com Mizukawa_Chap_07.indd 73 6/20/17 10:31 AM 7 • Postoperative Nausea and Vomiting Table 7-4 Common antiemetic agents Class Anticholinergics Drug Name Dimenhydrinate (Dramamine [Prestige Brands]) Primary indication Important considerations Motion sickness, vertigo Paradoxic reactions, xerostomia; additive anticholinergic effects with opioids Antihistamines Scopolamine Hydroxyzine (Vistaril [Pfizer]; Atarax [GlaxoSmithKline]) Motion sickness, vertigo Xerostomia; additive anticholinergic effects with opioids Anxiolytic antihistamine Safest agent for prevention of anxiety-associated nausea and vomiting Phenothiazines Cyclizine Prochlorperazine (Compazine [GlaxoSmithKline]) Vertigo Nausea and vomiting Benzamides Promethazine Nausea and vomiting (Phenergan [Baxter]) Metoclopramide (Reglan [ANI]) Gastric-emptying agent Trimethobenzamide Nausea and vomiting (Tigan [Pfizer]) Butyrophenones Droperidol Nausea and vomiting Serotonin receptor antagonists* Ondansetron (Zofran [Novartis]) Nausea and vomiting Xerostomia; additive anticholinergic effects with opioids High incidence of adverse drug effects, hypotension, respiratory depression, additive with opioids; risk of extrapyramidal side effects; caution required in patients with dystonia; blocks desired effect of vasoconstrictors used in local anesthesia • More sedating, longer acting than prochlorperazine • Other considerations same as for prochlorperazine Few adverse side effects • Least expensive and safest agent for preventing and treating nausea and vomiting • Few adverse side effects • Adverse effects similar to phenothiazines; risk of QT interval prolongation • Can be used with caution due to adverse effects Most effective and safest agent for preventing and treating nausea and vomiting *5-HT3 receptor antagonists Table 7-5 Factors affecting choice and administration of antiemetic agents Goal Antiemetic Dosing Important considerations Reduce nausea caused by swallowing blood Metoclopramide 5–10 mg 30 before procedure; may repeat in 4–8 h if needed; ODT effective in 10–15 Do not use in patients with Parkinson disease Reduce nausea caused by anxiety Hydroxyzine 50–100 mg 30 before procedure Some sedation Prevent or treat nausea Trimethobenzamide 300 mg every 6–8 h as needed No significant considerations Prevent or treat nausea and vomiting Ondansetron Tablet: 4–8 mg every h as needed; ODT or film: mg every h as needed More expensive than other antiemetics ODT has faster onset of action and is an excellent option when patient cannot tolerate swallowed tablet ODT, oral disintegrating tablet Anticholinergics Anticholinergic drugs block the action of acetylcholine on the parasympathetic nervous system Most anticholinergic drugs interact with muscarinic cholinergic receptors in the brain, secretory glands, heart, and smooth muscle and are also called antimuscarinic agents.20 Belladonna alkaloids (eg, atropine, scopolamine) are easily absorbed from the GI tract, whereas quaternary anticholinergics (eg, glycopyrrolate) are poorly absorbed when administered orally.21 Some anticholinergics are injected preoperatively to aid in relaxation and to decrease secretions, such as saliva.5,11,13,14,19 Dimenhydrinate (Dramamine; Prestige Brands) is an anticholinergic commonly used in the treatment of motion sickness The benefit is due to the high concentration of H1 and muscarinic cholinergic receptors in the vestibular 74 www.ajlobby.com Mizukawa_Chap_07.indd 74 6/20/17 10:31 AM Antiemetic Interventions system Its use is contraindicated in children younger than years.22 Scopolamine can be given the evening before a procedure or immediately preoperatively.5,19 A muscarinic antagonist, it is a competitive antagonist of M1 receptors.14,19 If anticholinergic agents are used perioperatively to reduce saliva, they may be more helpful in reducing postoperative vomiting than in reducing nausea.14 If used concurrently with opioids, such as morphine, that possess emetic properties of a longer duration than the antiemetic properties of scopolamine, delayed PONV may occur.14 The potential disadvantages of the use of anticholinergics include sedation, blurred vision, mydriasis, dry mouth, memory loss, urinary retention, hallucinations, confusion, and disorientation.13,19 These effects can be additive with the anticholinergic effects of the opioids.14,17 Although additional sedation may be beneficial, patients should be carefully monitored for oversedation.15 To address the potential for delayed PONV, a transdermal delivery system (TDS) of scopolamine applied the night before the surgical procedure will provide drug administration for up to days.14 Apfel et al published a systematic review and meta-analysis of the use of scopolamine TDS.23 Scopolamine TDS was associated with a statistically significant reduction in risk for PONV during the first 24 hours after the start of anesthesia and was effective compared with a placebo in the prevention of PONV when treatment was initiated the night before or on the day of the surgical procedure.23 However, scopolamine TDS was associated with a higher prevalence of visual disturbances at 24 to 48 hours compared with a placebo.23 Because of the low incidence of adverse events and the lack of a statistically significant increase in recovery time, scopolamine TDS is recommended alone or in combination with other drugs, such as ondansetron, for prevention of PONV.24 In addition, it has the benefit of enhancing sedation and decreasing salivation Antihistamines Hydroxyzine (Vistaril [Pfizer], Atarax [GlaxoSmithKline]) is categorized as a first-generation piperazine.15,25 It is an H1 receptor inverse agonist with sedative, antiemetic, anticholinergic, and bronchodilating properties.15,25,26 The duration of action is to hours, and it has minimal circulatory and respiratory depressant effects.25,26 In doses up to 1.5 mg/kg, intravenous (IV) hydroxyzine caused a statistically significant increase in arterial partial pressure of oxygen and no increase in arterial partial pressure of carbon dioxide and/or pH for up to 60 minutes after administration.27 The sedative, antisialogogic, and antiemetic effects of hydroxyzine make it a good premedication when given in combination with opioids to supplement their analgesic effect.26 Hydroxyzine is further beneficial in that it lacks both antagonism and synergy with benzodiazepines and scopolamine, allowing either of these two agents to be used simultaneously or later in the procedure as needed A 100-mg intramuscular (IM) dose of hydroxyzine was shown to decrease the incidence of PONV more effectively than a 2.5-mg IM dose of droperidol.26 When given orally, hydroxyzine is rapidly absorbed, with an onset of action of 30 minutes and peak concentration and maximal clinical effectiveness in hours.15,25 Hydroxyzine is metabolized in the liver to the active metabolite cetirizine.21,25 The half-life of hydroxyzine is approximately 16 hours and is prolonged in older patients.25 Administration in elderly patients differs from administration in younger patients because consideration must be given to possible reduced elimination When hydroxyzine is administered concurrently with other sedative drugs, such as opioids, the dose should be reduced.21 Its use in oral sedation in combination with midazolam has been shown to be more efficacious than the use of midazolam alone.28 Cyclizine, primarily used for the management of motion sickness,21 has similar effectiveness to promethazine in preventing and treating PONV caused by opioids.14 Its primary mechanism of action may have direct effects on the labyrinthine apparatus and the CRTZ.21 It exerts a central anticholinergic action.25 The overall incidence of adverse effects is less frequent with cyclizine than with the phenothiazine antiemetics, with excess sedation being the most frequent adverse effect.29,30 Dopamine receptor antagonists The phenothiazines (eg, promethazine, prochlorperazine), benzamides (eg, metoclopramide, trimethobenzamide), and butyrophenones (eg, droperidol) are strong D2 receptor antagonists.14 75 www.ajlobby.com Mizukawa_Chap_07.indd 75 6/20/17 10:31 AM 7 • Postoperative Nausea and Vomiting Phenothiazines Historically, phenothiazines (promethazine, prochlorperazine) have been among the most widely used antiemetic medications.14 Phenothiazines exert a direct D2 receptor blocking effect in the CRTZ with moderate antihistaminic and anticholinergic actions and are especially effective in countering the effects of opioids on the CRTZ.14 They have no effect on gastric emptying.31 These drugs have α-adrenergic blocking activity and can cause profound hypotension when epinephrine is administered.32 Promethazine (Phenergan [Baxter]) is an effective prophylactic antiemetic that results in more sedation and a more prolonged recovery period than prochlorperazine.13,14 It is a first-generation histamine H1 receptor antagonist, competitively blocking histamine H1 receptors without blocking the secretion of histamine.25 Promethazine also acts as a moderate muscarinic antagonist.25 It displays strong sedation and moderate to strong extrapyramidal side effects with moderate autonomic effects.25 Promethazine has a half-life of 16 to 19 hours.33 In April 2006, the US Food and Drug Administration (FDA) alerted prescribers that promethazine should not be used in children younger than years of age because of the potential for fatal respiratory depression The FDA further advised caution when administering promethazine in any form to pediatric patients years of age and older.21,34 In addition, in 2009 the FDA required a boxed warning for promethazine injection to better communicate the risks of severe tissue injury associated with IV administration of this drug.21,35 Because of the potential for adverse events, promethazine should be used with caution as a prophylactic agent in patients at high risk of PONV When used to treat PONV, a dose of 6.25 mg in adult patients is as effective as higher doses.36,37 In patients in whom PONV prophylaxis with ondansetron was unsuccessful, the use of promethazine was significantly more effective than a repeat dose of ondansetron for the treatment of established PONV.36 Prochlorperazine (Compazine [GlaxoSmithKline]) blocks D2 receptors After intramuscular injection, antiemetic action is evident within 30 to 60 minutes and lasts for to hours.38 Oral administration results in a slower onset but a longer duration of action (6 hours).38 It is effective for the management of low to moderate nausea and can be administered both preoperatively and postoperatively.14 Prochlorperazine displays weak autonomic effects and moderate sedation It has a higher incidence of extrapyramidal symptoms, including akathisia, acute dystonia, pseudoparkinsonism, and tardive dyskinesia, compared with other D2 receptor antagonists.21,29,30,39,40 Higher doses display increased effectiveness, but its use is dose limited because of side effects, which include hypotension, restlessness, and sedation.21 Anticholinergic adverse effects of phenothiazines include dry mouth, urinary retention, tachycardia, and drowsiness.14 Furthermore, phenothiazines block α-adrenergic receptors, causing hypotension.21 When phenothiazines are combined with opioids, the sedative, anticholinergic, and hypotensive effects of phenothiazines are at least additive if not synergistic with the sedating, respiratory depressant, anticholinergic, and vasodilating effects of opioid analgesics.14 Because phenothiazines block α-adrenergic receptors,21 they can prevent the desired vasoconstriction result ing from agents commonly administered in combination with local anesthetics in dental procedures.32 Vaso con strictors confine the local anesthetic to the region around the site of injection, which reduces systemic effects and prolongs the duration of action In addition, the vasoconstrictor reduces bleeding As a result of the phenothiazine-induced α-adrenergic blockade, the β-adrenergic effects of the vasoconstrictors will predominate, resulting in the potential for hypotension and reflex tachycardia.32 Furthermore, the phenothiazine reversal of vasoconstriction can reduce the duration of effect of the local anesthetic.32 Benzamides Metoclopramide (Reglan [ANI]) serves as an antiemetic because of its antagonism of D2 receptors in the CRTZ in the central nervous system, in the GI tract, and in vomiting centers in the area postrema.41 This effect prevents the nausea and vomiting triggered by most stimuli Metoclopramide demonstrates mixed 5-HT3 receptor antagonism and 5-HT4 receptor agonism.41 At higher doses, 5-HT3 antagonist activity may contribute to its antiemetic 76 www.ajlobby.com Mizukawa_Chap_07.indd 76 6/20/17 10:31 AM Antiemetic Interventions effects Metoclopramide is not related to the phenothiazines and does not have antihistaminic properties As an antiemetic, metoclopramide is not overly effective, and its use is normally reserved for patients at low emetic risk Its most common use is in adjunct therapy with opioids to prevent PONV resulting from opioid use.42,43 It increases lower esophageal sphincter tone and promotes gastric emptying, which may prevent the delayed gastric emptying caused by opioid analgesics.41,43 Metoclopramide has a short duration of action (1 to hours) and therefore may not be effective for the management of PONV when administered before a procedure.21,42 However, it will promote gastric emptying during the procedure, which will reduce the potential for the accumulation of swallowed blood in the stomach.21,42,43 To achieve adequate plasma concentrations for antiemetic effectiveness, metoclopramide is best administered at the end of surgery, and it has a better antiemetic efficacy in the immediate postoperative period when administered to patients taking opioids for postoperative pain.14 Metoclopramide can be given IV or IM near the end of surgery and by mouth every to hours as needed.14 An orally disintegrating tablet (ODT) is available This dosage form dissolves on the tongue and has a faster onset of action than a swallowed tablet has.21 Metoclopramide has relatively few adverse effects when used in low doses and does not affect hemodynamic stability.44 Metoclopramide has a number of important drug interactions, so a complete medication list should be reviewed before administration.21,41,45 Trimethobenzamide (Tigan [Pfizer]) is a substituted benzamide similar to metoclopramide and therefore is a dopamine antagonist with possible weak 5-HT3 effects.46 Trimethobenzamide is thought to have effects on the CRTZ, although its specific mechanism of action is unknown.21 Side effects can include drowsiness, dizziness, headache, diarrhea, muscle cramps, and blurred vision.21 Trimethobenzamide can be given orally or by IM injection and has a mean half-life of to hours.21 Dose adjustment should be considered in elderly patients and in patients with renal impairment.47 Because trimethobenzamide has few side effects, it may be a good choice in the prevention and management of PONV It may be particularly useful as an alternative to promethazine in elderly patients and patients with Parkinson disease.48 Butyrophenones Droperidol, a butyrophenone, has a pharmacologic and antiemetic profile similar to that of phenothiazines.14 Droperidol is a strong D2 receptor antagonist that acts at the CRTZ and area postrema.14 The onset of antiemetic action of droperidol is slower than that of prochlorperazine, but the duration of effect is longer (as long as 24 hours after administration).44 Droperidol is an α-blocker, with the adverse effect of hypotension; an anticholinergic, with the adverse effect of sedation; and a dopamine antagonist, with adverse extrapyramidal symptoms.14 Furthermore, droperidol can cause prolongation of the corrected QT interval Droperidol should be used with caution as an antiemetic for management of PONV.49 Like phenothiazines, droperidol can prevent the desired vasoconstriction resulting from agents commonly found in combination with local anesthetics used in dental procedures.32 As a result of the droperidol-induced α-adrenergic blockade, the β-adrenergic effects of the vasoconstrictors will predominate, resulting in the potential for hypotension and reflex tachycardia.32 Furthermore, the droperidol-induced reversal of vasoconstriction can reduce the duration of effect of the local anesthetic.16 Serotonin receptor antagonists The serotonin 5-HT3 receptor is highly specific and selective for nausea and vomiting.14,50 The most commonly used protocols for the management of PONV include the use of 5-HT3 receptor antagonists alone or in combination with other agents.13 5-HT3 receptor antagonists selectively block 5-HT3 receptors in the periphery and brain (CRTZ).18 Stimulation of the 5-HT3 receptors has been shown to initiate the vomiting reflex.18 Peripheral 5-HT3 receptors are located in vagal nerve terminals that are linked to the vomiting center via the nucleus tractus solitarius.18 These drugs can block the initiation of the vomiting reflex caused by emetogenic stimuli.18 The antivomiting effect is greater than the antinausea effect of this class of drugs The overall adverse effect profile compares with other antiemetics.13,14 All 5-HT3 receptor antagonists have similar side effects that include headache, constipation, and dizziness.19 77 www.ajlobby.com Mizukawa_Chap_07.indd 77 6/20/17 10:31 AM 7 • Postoperative Nausea and Vomiting Although it was initially developed for the management of nausea and vomiting induced by chemotherapy and radiation therapy, ondansetron (Zofran [Novartis]) was the first 5-HT3 receptor antagonist evaluated and approved for the management of PONV.1 Ondansetron administered at a dose of mg IV at the end of surgery was found to be effective in preventing PONV and opioid-induced PONV.13,51–56 Although other 5-HT3 receptor antagonists are available, ondansetron has the lowest adverse effect profile.14 In contrast to the effects of phenothiazines, sedation and extrapyramidal symptoms are not typically seen.14 Unlike phenothiazines, the 5-HT3 receptor antagonists not reduce the effectiveness of vasoconstrictors used with local anesthesia or cause the associated drug interactions.14 Ondansetron is available as an oral tablet, ODT, or soluble film and for IV administration The IV route of administration requires smaller doses than are necessary for the oral (swallowed) route of administration because the IV route bypasses the liver and the first-pass effect.21 ODTs or soluble films are excellent options for nauseated patients because these dosage forms are designed to disintegrate and dissolve rapidly in the oral cavity, where they are at least partially absorbed Absorption in the oral cavity prevents exposure of drug to the stomach, thereby preventing the potential loss of drug available for absorption into circulation caused by vomiting and also preventing exposure of the orally absorbed drug to the first-pass effect.18 Therefore, doses given in the form of ODTs should be initially lower than doses given in the form of oral (swallowed) tablets Conclusion In outpatient oral and maxillofacial surgery, the use of strategies to reduce PONV and PDNV should be considered, especially in high-risk patients Preoperatively, patients who are at high risk of PONV, such as patients with a history of PONV or severe motion sickness, should receive prophylactic treatment, which could include the use of scopolamine TDS, hydroxyzine, trimethobenzamide, and/or ondansetron preoperatively The prophylactic use of a scopolamine patch has been shown to be effective in patients with a history of PONV, with a particular benefit in patients who experience PONV and PDNV with movement or in whom opioid-induced PONV is delayed.16 When used preoperatively, both scopolamine and hydroxyzine have the advantage of enhancing sedation.14 Trimethobenzamide is relatively inexpensive and has a low incidence of adverse effects Both ondansetron and metoclopramide have been shown to be more effective in preventing PONV when administered at the end of surgery than when administered at other times.14 In addition, metoclopramide may aid in GI emptying and decrease PONV related to the swallowing of blood The use of opioids should be minimized in patients at high risk for nausea and vomiting A 4-mg IV administration of ondansetron has been determined to be the optimally effective dose for the treatment of opioid-induced PONV.14 Because of their adverse effects, promethazine and droperidol should be used with caution in adults and older children Promethazine is contraindicated in patients younger than years Postoperatively, patients in whom ondansetron is unsuccessful should be reassessed, and a different agent should be used for rescue treatment Although many antiemetics are available, some have substantial adverse effects Knowledge of the pharmacology and the adverse effects of these drugs should guide the clinician in choosing the proper antiemetic 78 www.ajlobby.com Mizukawa_Chap_07.indd 78 6/20/17 10:31 AM References References 19 Kloth DD New pharmacologic findings for the treatment of PONV and PDNV Am J Health Syst Pharm 2009;66(1, suppl 1):S11–S18 Rodrigo MR, Campbell RC, Chow J, Tong CK, Hui E, Lueveswanij S Ondansetron for prevention of postoperative nausea and vomiting following minor surgery: A double-blind randomized study Anaesth Intensive Care 1994;22:576–579 20 McCarthy BG, Peroutka SJ Differentiation of the muscarinic cholinergic receptor subtypes in human cortex and pons: Implications for anti-motion sickness therapy Aviat Space Environ Med 1988;59:63–66 Rodrigo C, Campbell RC, Chow J, Tong A The effect of a 4mg preoperative intravenous dose of ondansetron in preventing nausea and vomiting after maxillofacial surgery J Oral Maxillofac Surg 1996;54:1171–1175 21 Facts & Comparisons eAnswers Wolters Kluwer website http://www wolterskluwercdi.com/facts-comparisons-online/ Accessed March 2017 Camu F, Lauwers MH, Verbessem D Incidence and aetiology of postoperative nausea and vomiting Eur J Anaesthesiol Suppl 1992;6:25–31 22 PubMed Health Dimenhydrinate (by injection) https://www.ncbi.nlm nih.gov/pubmedhealth/PMHT0009958/ Accessed March 2017 23 Apfel CC, Zhang K, George E, et al Transdermal scopolamine for the prevention of postoperative nausea and vomiting: A systematic review and meta-analysis Clin Ther 2010;32:1987–2002 [erratum 2010;32:2502] Macario A, Weinger M, Carney S, Kim A Which clinical anesthesia outcomes are important to avoid? The perspective of patients Anesth Analg 1999;89:652–658 Thompson HJ The management of post-operative nausea and vomiting J Adv Nurs 1999;29:1130–1136 24 Gan TJ, Sinha AC, Kovac AL, et al A randomized, double-blind, multicenter trial comparing transdermal scopolamine plus ondansetron to ondansetron alone for the prevention of postoperative nausea and vomiting in the outpatient setting Anesth Analg 2009;108:1498–1504 Sleisenger MH The Handbook of Nausea and Vomiting Boca Raton, FL: CRC, 1994 25 Skidgel RA, Kaplan AP, Erdös EG Histamine, bradykinin, and their antagonists In: Brunton LL, Chabner BA, Knollman BC Goodman & Gilman’s The Pharmacological Basis of Therapeutics, ed 12 New York: McGraw-Hill, 2011:911–936 Broomhead CJ Physiology of postoperative nausea and vomiting Br J Hosp Med 1995;53:327–330 Larson P, Halliburton P, DiJulio J Nausea, vomiting and retching In: Carrieri-Kohlman V, Lindsay AM, West CM Pathophysiological Phenomena in Nursing: Human Responses to Illness, ed Philadelphia: Saunders, 1993:371–394 26 McKenzie R, Wadhwa RK, Uy NT, et al Antiemetic effectiveness of intramuscular hydroxyzine compared with intramuscular droperidol Anesth Analg 1981;60:783–788 Wang SC, Borison HL The vomiting center: A critical experimental analysis Arch Neurol Psychiatry 1950;63:928–941 27 Zsigmond EK, Flynn K, Shively JG Effect of hydroxyzine and meperidine on arterial blood gases in healthy human volunteers J Clin Pharmacol 1989;29:85–90 10 Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N A simplified risk score for predicting postoperative nausea and vomiting: Conclusions from cross-validations between two centers Anesthesiology 1999;91:693–700 28 Shapira J, Kupietzky A, Kadari A, Fuks AB, Holan G Comparison of oral midazolam with and without hydroxyzine in the sedation of pediatric dental patients Pediatr Dent 2004;26:492–496 11 Kolodzie K, Apfel, C Nausea and vomiting after office-based anesthesia Curr Opin Anaesthesiol 2009;22:532–538 29 Dundee JW, Loan WB, Morrison JD A comparison of the efficacy of cyclizine and perphenazine in reducing the emetic effects of morphine and pethidine Br J Clin Pharmacol 1975;2:81–85 12 Alexander M, Krishnan B, Yuvraj V Prophylactic antiemetics in oral and maxillofacial surgery: A requiem? J Oral Maxillofac Surg 2010;67:1873–1877 30 Bellville JW, Howland WS, Bross ID Postoperative nausea and vomiting, III: Evaluation of the antiemetic drugs fluphenazine (prolixin) and promethazine (phenergan) and comparison with triflupromazine (vesprin) and cyclizine (marezine) J Am Med Assoc 1960;172:1488–1493 13 Gan TJ, Meyer TA, Apfel CC, et al; Society for Ambulatory Anesthesia Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting Anesth Analg 2007;105:1615–1628 31 Dundee JW, Moore J, Love WJ, Nicholl RM, Clarke RS Studies of drugs given before anesthesia, VI: The phenothiazine derivatives Br J Anaesth 1965;37:332–352 14 Kovac AL Prevention and treatment of postoperative nausea and vomiting Drugs 2000;59:213–243 32 Goulet J, Pérusse R, Turcotte JY Contraindications to vasoconstrictors in dentistry: Part III Pharmacologic interactions Oral Surg Oral Med Oral Pathol 1992;74:692–697 15 Malamed SF Sedation: A Guide to Patient Management, ed St Louis: Mosby, 2010 16 Dundee JW, Kirwan MK, Clarke RS Anesthesia and premedication as factors in postoperative vomiting Acta Anaesthesiol Scand 1965;9:223–231 33 RxList Promethazine HCl: Drug description http://www.rxlist.com/ promethazine-hcl-drug.htm Updated 13 June 2008 Accessed 10 June 2011 17 Perrott DH, Yuen JP, Andresen RV, Dodson TB Office-based ambulatory anesthesia: Outcomes of clinical practice of oral and maxillofacial surgeons J Oral Maxillofac Surg 2003;61:983–995 34 Freeman M Promethazine and respiratory depression Samford University Global Drug Information Service’s New Drug FAX Sheet 2006;11(23):1 18 Muchatuta NA, Paech MJ Management of postoperative nausea and vomiting: Focus on palonosetron Ther Clin Risk Manag 2009;5:21–34 35 Wensel TM New boxed warning for promethazine Samford University Global Drug Information Service’s New Drug FAX Sheet 2009;14(35):1–2 79 www.ajlobby.com Mizukawa_Chap_07.indd 79 6/20/17 10:31 AM 7 • Postoperative Nausea and Vomiting 36 Habib AS, Reuveni J, Taguchi A, White WD, Gan TJ A comparison of ondansetron with promethazine for treating postoperative nausea and vomiting in patients who received prophylaxis with ondansetron: A retrospective database analysis Anesth Analg 2007;104:548–551 46 Tigan Drugs.com website http://www.wolterskluwercdi.com/factscomparisons-online/ Accessed March 2017 37 Kazemi-Kjellberg F, Henzi I, Tramèr MR Treatment of established postoperative nausea and vomiting: A quantitative systematic review BMC Anesthesiol 2001;1:2 48 Ahlskog JE Trimethobenzamide in elderly patients Mayo Clin Proc 2004;79:829 47 Drugs.com Trimethobenzamide: Professional http://www.drugs.com/ pro/trimethobenzamide.html Accessed 10 June 2016 49 Alvarez PA, Pahissa J QT alterations in psychopharmacology: Proven candidates and suspects Curr Drug Saf 2010;5:97–104 38 Dillon GP Jr Clinical evaluation of promethazine for prevention of postoperative nausea and vomiting Am Pract Dig Treat 1957;8:1571–1575 39 Howat DD Anti-emetic drugs in anaesthesia: A double blind trial of two phenothiazine derivatives Anaesthesia 1960;15:289–297 50 Sanders-Bush E, Hazelwood L 5-Hydroxytryptamine (serotonin) and dopamine In: Brunton LL, Chabner BA, Knollman BC Goodman & Gilman’s The Pharmacological Basis of Therapeutics, ed 12 New York: McGraw-Hill, 2011:335–362 40 Gralla RJ, Osoba D, Kris MG, et al Recommendations for the use of antiemetics: Evidence-based clinical practice guidelines J Clin Oncol 1999;17:2971–2994 [errata 1999;17:3860 and 2000;18:3064] 51 Loeser EA, Bennett G, Stanley TH, Machin R Comparison of droperidol, haloperidol and prochlorperazine as postoperative anti-emetics Can Anaesth Soc J 1979;26:125–127 41 Sharkey KA, Wallace JL Treatment of disorders of bowel motility and water flux; anti-emetics; agents used in biliary and pancreatic disease In: Brunton LL, Chabner BA, Knollman BC Goodman & Gilman’s The Pharmacological Basis of Therapeutics, ed 12 New York: McGraw-Hill, 2011:1325–1326 52 Leeser J, Lip H Prevention of postoperative nausea and vomiting using ondansetron, a new, selective, 5-HT3-receptor antagonist Anesth Analg 1991;72:751–755 53 Kenny GN, Oates JD, Lesser J, et al Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: A dose ranging study Br J Anaesth 1992;68:466–470 42 Assaf RA, Clarke RS, Dundee JW, Samuel IO Studies of drugs given before anesthesia, XXIV: Metoclopramide with morphine and pethidine Br J Anaesth 1974;46:514–519 43 Bateman DN, Davies DS Pharmacokinetics of metoclopramide Lancet 1979;1(8108):166 54 McKenzie R, Kovac A, O’Connor T, et al Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery Anesthesiology 1993;78:21–28 44 Harrington RA, Hamilton CW, Brogden RM, Linkewich JA, Romankiewicz JA, Heel RC Metoclopramide: An updated review of its pharmacological properties and clinical use Drugs 1983;25:451–494 55 Scuderi P, Wetchler B, Sung YF, et al Treatment of postoperative nausea and vomiting after outpatient surgery with the 5-HT3 receptor antagonist ondansetron Anesthesiology 1993;78:15–20 45 PubMed Health Metoclopramide https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0001178 Accessed March 2017 56 Kovac AL, Pearman MH, Khalil SN, et al; S3A-379 Study Group Ondansetron prevents postoperative emesis in male outpatients J Clin Anesth 1996;8:644–651 80 www.ajlobby.com Mizukawa_Chap_07.indd 80 6/20/17 10:31 AM CHAPTER Monitoring the Patient Timothy M Orr, dmd Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_08.indd 81 6/21/17 3:15 PM 8 • Monitoring the Patient Vigilant monitoring of the patient under anesthesia is important to allow the clinician to assess the physiologic response to anesthesia and make minute-to-minute modifications in anesthesia delivery Monitoring during anesthesia includes the fundamental observations of level of consciousness, response to surgical stimulation, and ventilatory effort in addition to the measurement of physiologic parameters, such as breath sounds, respiratory rate, heart rate, blood pressure, hemoglobin oxygen saturation, end-tidal carbon dioxide (etCO2), cardiac electrical activity (electrocardiogram [ECG]), and temperature A thorough understanding of normal anatomy and physiology, the patient’s medical history, the pharmacology of drugs administered during anesthesia, and the mechanism of monitoring systems is essential to provide personalized, effective, and safe anesthesia Proper monitor selection, application, and interpretation allows detection of even small changes in a patient’s response to anesthesia and initiation of corrective action before larger, potentially life-threatening complications arise The anesthesia provider who focuses on maintaining smooth anesthesia while keeping the patient close to physiologic baseline generally experiences fewer postoperative anesthesia-related complications and less morbidity and mortality.1 Ensuring hemodynamic stability, end-organ oxygenation, and cardiovascular health is key to planning and executing successful anesthesia The monitoring systems discussed in this chapter are recommended; however, each clinician must rely on his or her training and comply with state dental and/or medical board laws for monitoring of patients under various levels of anesthesia Monitoring Requirements Although the requirements for patient monitoring during anesthesia are dictated by individual state dental and medical boards, the American Society of Anesthesiologists (ASA), the American Society of Dental Anesthesiologists, and the American Association of Oral and Maxillofacial Surgeons have issued recommendations for patient monitoring under moderate sedation and deep sedation/general anesthesia.2,3 These recommendations focus on ventilation, oxygenation, and circulation monitoring Ventilation and oxygenation should minimally be assessed by continuous etCO2 monitoring and pulse oximetry, respectively Additional means of monitoring ventilation include auscultation of breath sounds with a precordial or pretracheal stethoscope and observation of chest excursions Circulation should be monitored by means of blood pressure evaluation every minutes, continuous heart rate evaluation by ECG, and pulse oximetry The ASA recommends that every patient receiving anesthesia shall have his/her temperature monitored when clinically significant changes in body temperatures are intended, anticipated, or suspected.2 If an endotracheal tube or laryngeal mask airway is used, etCO2 and inspired oxygen concentration should be monitored Monitoring of patients under local anesthesia with one or more monitoring modality may be appropriate For example, a patient with a history of arrhythmia may benefit from ECG monitoring Patients with hypertension may benefit from blood pressure monitoring, especially if the patient has a history of poorly controlled hypertension Principles of Monitoring Monitoring in anesthesia is focused on evaluating adequate function of three major organ systems: the cardiovascular system, the pulmonary system, and the brain In addition, monitoring of temperature and neuromuscular function may be indicated Errors in anesthetic management can result from the interpretation of monitor data and from monitor malfunction This chapter discusses the monitoring modalities used in office-based anesthesia, their underlying principles, and possible circumstances in which monitor data may be misinterpreted 82 www.ajlobby.com Mizukawa_Chap_08.indd 82 6/21/17 3:15 PM Blood Pressure Monitoring Visual Assessment, Auditory Assessment, and Palpation Before the advent of modern monitoring devices, practitioners relied on the senses of sight, hearing, and touch to monitor a patient’s response to anesthesia These basic senses are still useful adjuncts in the delivery of ambulatory anesthesia In certain circumstances, visual assessment of the patient can be more accurate than capnography For example, if a patient tends toward mouth breathing, nasal cannula capnography may not detect etCO2 and may suggest apnea or airway obstruction Ventilatory effort, or lack thereof, and signs of airway obstruction, such as paradoxical chest movement, can be reliably visualized to either confirm or refute the capnographic data Auditory assessment is also useful because the astute practitioner can detect the absence of breath sounds and/or the signs of pending airway obstruction, such as stridor or wheezing Palpation is an indispensable tool For example, when the ECG suggests a possible dysrhythmia, palpation of the radial or carotid pulse can demonstrate a regular heart rate and normal rhythm, indicating possible lead placement error or lead dysfunction The hand can be placed discreetly on the patient’s chest to confirm chest rise Electrocardiography The ECG provides a continuous visual representation of the electrical activity of the heart ECG monitoring is particularly important in patients with a history of dysrhythmia Although cardiac complications are unlikely in the typically young and healthy population of patients who undergo ambulatory oral surgery, early detection of aberrations in cardiac rate and rhythm can enable prompt intervention and prevent deterioration into a poorly perfusing rhythm Electrocardiography is discussed in detail in chapter Blood Pressure Monitoring Blood pressure is the pressure generated by circulating blood Blood pressure is the product of cardiac output (CO) and peripheral vascular resistance (PVR): blood pressure = CO × PVR Recall that cardiac output is the product of heart rate (HR) and stroke volume (SV): CO = HR × SV The principal determinant of vascular resistance is vessel diameter Therefore, an increase in heart rate, stroke volume, and/or vasoconstriction will result in increased blood pressure In general, the stroke volume and heart rate contribute to the systolic blood pressure, whereas peripheral vascular resistance determines the diastolic blood pressure Blood pressure can be measured manually or with automated devices The manual method involves an aneroid manometer that is inflated around the upper arm until loss of arterial blood flow through the brachial artery occurs, confirmed with the absence of Korotkoff sounds through a stethoscope placed over the antecubital fossa.4 The pressure in the cuff is slowly released until the pulse or Korotkoff sounds return This pressure is noted as the systolic blood pressure The diastolic blood pressure is the pressure at which the Korotkoff sounds disappear as the pressure in the cuff continues to decrease Automated, or noninvasive, blood pressure monitors operate according to similar principles However, they utilize digital oscillometric monitors to measure the oscillating signals associated with arterial pressure changes during systole and diastole A cuff is inflated until arterial flow through the brachial artery is occluded The pressure is then incrementally released As flow returns, the arterial pressure produces oscillating signals The systolic blood pressure is the pressure at which the oscillating signal is first detected As cuff pressure continues to drop, the oscillating signal increases in magnitude until the maximum magnitude is reached, indicating mean arterial pressure The cuff pressure continues to decrease, and the oscillations eventually dissipate In automated monitoring, the diastolic blood pressure is calculated from the systolic blood pressure and mean arterial pressure.4 83 www.ajlobby.com Mizukawa_Chap_08.indd 83 6/21/17 3:15 PM 8 • Monitoring the Patient Continual monitoring of blood pressure is required for patients undergoing intravenous or inhalation anesthesia regardless of anesthetic depth Blood pressure monitoring allows the anesthesia provider to make educated assessments of the patient’s hydration, end-organ perfusion, and hemodynamic stability Anesthetics should be tailored to the individual patient because patients may be hypertensive, hypotensive, or normotensive In general, the blood pressure should be kept as close to baseline as possible Maintaining the baseline blood pressure may be challenging in certain patients because of factors such as anxiety, fear, dehydration, and the patient’s medications A temptation to lower the blood pressure of hypertensive patients to an ideal pressure of 120/80 can be dangerous because a blood pressure of 120/80 may not be sufficient to perfuse vital organs in an individual whose circulatory system has compensated for chronic hypertension This scenario underscores the importance of obtaining baseline vital signs at the consultation visit, where anxiety, fear, and dehydration are less of a factor and a true representative blood pressure can be obtained This blood pressure can serve as the goal to maintain during anesthesia The provider should develop a preoperative plan to control as many factors that may affect blood pressure as possible, including adequate hydration (within the constraints of oral intake restrictions), usual antihypertensives taken on schedule, and management of patient anxiety.1 Blood pressure monitors can give erroneous readings Factors to consider when monitoring blood pressure include the location of the blood pressure cuff, the size of the appendage (arm or leg) where blood pressure is measured, the size of the blood pressure cuff, the position of the patient, and proper placement of the cuff A properly sized blood pressure cuff is necessary to ensure an accurate reading As a general rule, the width of the cuff should be approximately 40% of the circumference of the patient’s arm An inappropriately sized cuff will give inaccurate data, with smaller cuffs giving higher readings and larger cuffs giving erroneously low readings In the case of arm blood pressure monitoring, the cuff must be placed correctly to occlude the brachial artery during measurement If the surgeon or assistant leans against the blood pressure cuff, the blood pressure reading will be inappropriately high Likewise, if the patient moves the appendage where the blood pressure is monitored, the reading may be erroneous Patient position also affects blood pressure; therefore, to be comparable, blood pressure measurements should be taken from the same extremity with the patient in the same position Pulse Oximetry By definition, oximetry is the measurement of oxygen Maintaining adequate oxygenation of arterial blood to support vital organ metabolism is paramount in anesthesia The partial pressure of oxygen in arterial blood (Pao2), which is the measure of oxygen dissolved in arterial blood, is approximately 75 to 100 mm Hg under normal conditions Oxyhemoglobin saturation (Sao2) describes the degree of hemoglobin oxygen saturation and is expressed as a percentage Although Pao2 is the most important indicator of oxygenation, measurement of Pao2 and Sao2 requires invasive sampling, such as arterial blood gas sampling.5 Pulse oximetry provides a continuous measurement of oxyhemoglobin saturation (Spo2) that approximates Sao2 without invasive sampling Although Spo2 does not equal Pao2, the oxyhemoglobin dissociation curve illustrates their relationship (Fig 8-1) The dissociation curve demonstrates that in order to maintain a satisfactory arterial oxygen level, Spo2 greater than 90% must be maintained (Spo2 of 90% corresponds with Pao2 of 60 mm Hg) One should also note that, on the curve, as Spo2 drops below 90%, Pao2 begins to drop precipitously Accordingly, it is good practice to maintain an Spo2 greater than 95% to stay away from the edge of this “cliff.”6 Additionally, most studies have shown a margin of error of approximately 2% to 3% Therefore, to maintain an actual Sao2 above 90%, Spo2 should be kept above 92% to 93%.5 Although occasional drops of 1% to 2% from baseline Spo2 readings may be acceptable in the course of a procedure requiring anesthesia, a progressive decline below 90% requires prompt intervention 84 www.ajlobby.com Mizukawa_Chap_08.indd 84 6/21/17 3:15 PM Pulse Oximetry Oxyhemoglobin saturation (%) 100 Normal oxygen affinity Increased oxygen affinity = oxygen loading • Increased pH • Decreased temperature • Decreased 2,3-diphosphoglycerate Decreased oxygen affinity = oxygen unloading • Decreased pH • Increased temperature • Increased 2,3-diphosphoglycerate 75 50 25 0 25 50 75 100 Oxygen pressure (mm Hg) Fig 8-1 An example of an oxyhemoglobin dissociation curve This diagram shows how cer- tain physiologic conditions such as pH, temperature, and 2,3-diphosphoglycerate can alter oxyhemoglobin saturation Note that a left shift of the curve indicates increased affinity of hemoglobin for oxygen, promoting oxygen loading onto the hemoglobin molecule Physiologic conditions causing a left shift are listed Under these conditions, at any given oxygen pressure (25 mm Hg in this figure), a left shift will result in an increased oxyhemoglobin saturation, relative to baseline conditions The converse can be noted with a right shift, which results in oxygen unloading and decreased oxyhemoglobin saturation Pulse oximetry measures oxyhemoglobin saturation by detecting different levels of hemoglobin species in arterial blood The four hemoglobin species present in blood are oxyhemoglobin (HbO2), reduced hemoglobin (Hb), methemoglobin (metHb), and carboxyhemoglobin (COHb) Because only trace amounts of metHb and COHb are present under normal conditions, the major contributors to pulse oximetry are HbO2 and Hb A pulse oximeter measures the oxygen saturation of these species of hemoglobin at the monitor site, usually a finger, toe, or earlobe (Fig 8-2) The pulse oximeter emits red light at a wavelength of 660 nm alternating with infrared light of wavelength 940 nm The light is transmitted through the tissue to a photodetector Because HbO2 absorbs red light well and Hb absorbs infrared light well, when these two light sources penetrate the vasculature and are absorbed at different ratios, the detector measures the difference in the amounts of red and infrared light transmitted during diastole and systole The monitor converts these data into a ratio of oxygenated hemoglobin and deoxygenated hemoglobin This ratio is then converted to Spo2 by the oximeter processor 85 www.ajlobby.com Mizukawa_Chap_08.indd 85 6/21/17 3:15 PM 8 • Monitoring the Patient Fig 8-2 Use of a pulse oximeter One of the biggest hurdles in pulse oximetry is differentiating light absorption by arterial blood from light absorption by other tissues, such as skin, soft tissue, and venous blood To account for absorbance by other tissues, the pulse oximeter operates on the basis of the assumption that only arterial blood pulsates and first determines the fluctuating component of absorbance for each wavelength of light The fluctuating signal, which can be seen on the pulse oximeter display, represents the increased absorbance of light during systole as the artery expands with a rush of blood The oximeter then determines the nonfluctuating component of absorption of each wavelength of light, which is assumed to be the absorbance by tissue other than arterial blood The so-called “ratio of ratios” (R) is calculated as follows: R = (F660/NF660)/(F940/NF940), where F and NF are the fluctuating and nonfluctuating components, respectively, of each wavelength of light (Fig 8-3) This ratio is then converted by the oximeter to the Spo2.4,5 Absorption due to pulsatile arterial blood Light absorption Absorption due to venous and capillary blood Muscle Absorption due to tissue Connective tissue Time Diode Fig 8-3 Pulse oximetry signals Many tissues absorb red light (660 nm) and infrared light (940 nm), including skin, connective tissue, muscle, as well as Hb and HbO2 in venous and arterial blood However, to isolate oxygen saturation in arterial blood, the pulse oximeter detects fluctuating signals of light absorbance, representing the ebb and flow of blood through the artery during diastole and systole These values are then incorporated into the “ratio of ratios,” along with absorption values from the nonfluctuating signal, to give the Spo2 86 www.ajlobby.com Mizukawa_Chap_08.indd 86 6/21/17 3:15 PM etCO2 Monitoring Erroneous Spo2 readings generally result from four sources: ambient light, low flow to the monitor site, patient movement, and presence of abnormal light absorbers in the blood.4 The oximeter cannot distinguish between light emitted from the monitor and light from other sources, such as ceiling lights This obstacle is overcome by applying three sequential samples of light In the first, the photodiode emits red light, which is naturally mixed with ambient light The second is infrared light mixed with ambient light The third is ambient light alone This sequence is repeated hundreds of times per second, enabling the monitor to cancel out ambient light data from the calculations.4 Low flow is a difficult problem because many comorbid conditions, such as diabetes and peripheral vascular disease, drastically reduce blood flow to extremities Weak pulsations result in low F:NF ratios, requiring amplification of the signals Consequently, background noise is also amplified, making the calculations less accurate This problem may be addressed simply by changing the location of the oximeter probe to an area of increased flow In some patients, it can be overcome to some extent by warming the hands, encouraging enhanced flow If hypotension seems to be a cause of the decreased flow, supporting blood pressure can help enhance flow Patient movement causes venous pulsations, which can be interpreted by the oximeter as a fluctuating signal and will lead to erroneous readings To overcome slight, brief movements, the monitor averages the data over time Thus, if the averaging period is lengthened, these movements will have less effect on the data.4 This averaging period, however, is responsible for the lag time between the occurrence of actual saturation changes and the corresponding change in display on the monitor The longer the averaging period, the longer the lag The presence of abnormal light absorbers in the blood will alter Spo2 readings For example, abnormally high levels of metHb, such as in patients with methemoglobinemia, will result in symmetrically increased absorbance of red and infrared light, driving the ratio of red to infrared light toward 1.0 and the Spo2 reading toward 85% COHb absorbs red light, but not infrared light, so conditions that cause abnormally high COHb, such as carbon monoxide poisoning or chronic smoking, may result in a falsely high Spo2 reading.2 Intravascular dyes also alter absorbance and will result in erroneous readings etCO2 Monitoring Ventilation is the process of exchanging air between the lungs and the environment Under normal conditions, it consists of inhalation of oxygen-rich air into the lungs and exhalation of carbon dioxide–rich air from the lungs Failure to ventilate can have substantial consequences Although oxygenation without ventilation is possible, ventilation is the normal means of oxygenating the pulmonary vasculature Hypercapnia will result from hypoventilation or apnea and can lead to respiratory acidosis Because expired carbon dioxide is the natural marker of ventilation, its measurement during the respiratory cycle reflects ventilatory activity Capnometry is the measurement of the partial pressure of carbon dioxide expired during a normal tidal volume, or etCO2 It is measured by sampling expired air and detecting partial pressures of carbon dioxide by infrared monitors The data are then displayed as a waveform and as a numeric etCO2 value A typical etCO2 waveform and abnormal waveforms that may be seen in office-based anesthesia are shown in Fig 8-4 87 www.ajlobby.com Mizukawa_Chap_08.indd 87 6/21/17 3:15 PM 8 • Monitoring the Patient Expiration Inhalation Pco2 45 40 α IV I Time 40 40 Time d mm Hg mm Hg b Time mm Hg c 40 e β II mm Hg a III mm Hg 40 mm Hg etCO2 Time Time 40 f Time Fig 8-4 Capnogram depicting a normal etCO2 waveform (a), as well as abnormal waveforms (b-f) (a) The normal waveform has four main phases Phase I represents the beginning of expiration Air from the anatomical dead space (nose, mouth, pharynx, and trachea), which has baseline levels of CO2, is sampled This baseline should be mm Hg Phase II is the expiratory upstroke when a mixture of alveolar gas and gas from anatomical dead space is sampled, showing a rapid increase in CO2 The transition from phase II to III is the a-angle, which approximates 90 degrees This angle represents ventilation and perfusion relationships, with angles exceeding 90 degrees indicating mismatches Phase III is the alveolar plateau, when sampling from well-ventilated areas of the lung transitions to sampling of poorly ventilated areas of the lung that have relatively higher concentrations of CO2 Later in the respiratory cycle, these higher concentrations of poorly ventilated areas account for the positive slope of phase III If all areas of the lung were equally ventilated and had equal concentrations of CO2, phase III would be nearly horizontal The measure of CO2 at the end of this tidal volume is the etCO2 measurement, which approximates 35–38 mm Hg The transition from phase III to IV (the inspiratory downstroke) is the b-angle Changes in this angle can represent rebreathing of exhaled gas, when angles exceeding 90 degrees are seen Note the mm Hg difference between partial pressure of carbon dioxide (Pco2) and etCO2 This is attributed to the dilution of alveolar gas with anatomical dead space, which is void of CO2 (b) Note that the slope of phase III is increased and the a-angle is increased This represents a delay in the flow of gas to the sampler from increased airway resistance, such as in airway obstruction or asthma and chronic obstructive pulmonary disease (c) The etCO2 is elevated, possibly due to either increased CO2 production, as in hypermetabolic conditions or malignant hyperthermia, or decreased ventilation as in hypoventilation (d) This capnogram shows hypopnea and insufficient ventilatory effort (e) Depiction of bradypnea Notice the increase of etCO2 with time, which is expected with low respiratory rates (f) Depiction of tachypnea Notice the decrease of etCO2 with time, which is expected with high respiratory rates Just as Spo2 can be used to estimate Pao2, etCo2 is an approximation of arterial partial pressure of carbon dioxide (Paco2) For example, an etCO2 of 35 to 38 mm Hg correlates with a Paco2 of approximately 40 mm Hg.6 The discrepancy of to mm Hg accounts for alveolar dead space.7 The etCO2 value is much more accurate in a closed airway with an endotracheal tube than in the office setting, where endotracheal tubes are less commonly used The etCO2 waveform display, however, is a useful real-time representation of a patient’s ventilatory status (Fig 8-5) 88 www.ajlobby.com Mizukawa_Chap_08.indd 88 6/21/17 3:15 PM Twitch Monitoring Fig 8-5 Example of an etCO2 waveform display Use of a precordial stethoscope, although largely replaced by capnography, can provide useful information, not only about ventilation, but also about the presence of abnormal breath sounds that may be a sign of a treatable condition, such as bronchospasm Temperature Monitoring Temperature monitoring is vital during anesthesia because patients can vary widely in their thermoregulation during a procedure Body temperature can also give subtle clues of potentially more serious issues that can arise, such as metabolic hyperthermic conditions (malignant hyperthermia and thyroid storm) and severe hypothermia Shortly after induction of anesthesia, body temperature begins to slowly drop as a result of convection, conduction, evaporation, and radiation This effect is especially notable in pediatric and elderly patients because their thermoregulatory mechanisms may not be fully functional and may require assistance from external heat sources Most general anesthetic agents cause vasodilation and redistribution of blood flow, which causes a further decrease in body temperature Effects of hypothermia include increased recovery time; shivering, which increases metabolic oxygen consumption and thus can lower systemic partial oxygen pressures; and impairment of coagulation and wound healing.2 Body temperature can be monitored externally or invasively In general, invasive temperature monitoring, such as rectal, esophageal, or nasal temperature measurement, provides a more accurate reading than external temperature monitoring does Most procedures requiring office-based anesthesia are performed with external temperature monitoring, which provides a reflection of temperature trends rather than accurate readings Twitch Monitoring Some anesthesia practitioners administer depolarizing or non-depolarizing muscle relaxants in the office setting These agents cause competitive blocking of the neuromuscular junction, preventing muscular contraction Although this type of blocking is rarely needed in a dental setting, it has a place in certain surgical procedures, depending on the procedure and the preferences of the surgeon, patient, and anesthesia provider In addition, the anesthesia provider should always have succinylcholine and, when the patient has a history of malignant hyperthermia, rocuronium for use in case an airway or medical emergency occurs and endotracheal intubation is required If neuromuscular blockers are used, appropriate monitoring is necessary 89 www.ajlobby.com Mizukawa_Chap_08.indd 89 6/21/17 3:15 PM 8 • Monitoring the Patient A twitch monitor (Fig 8-6) sends out a short electrical signal to two electrodes This stimulus causes a muscular contraction unless the neuromuscular junction is blocked As acetylcholine slowly increases in concentration at the junction, thus overtaking the neuromuscular blocker, muscular contractions begin to appear, weakly at first.8 Twitch monitoring can ensure that extubation does not occur before the patient has regained sufficient neuromuscular function for airway support and ventilation Careful note should be made of the level of blockage, the duration of action of the drug, and the time at which any potential reversal agents were used Fig 8-6 Photograph of a twitch monitor Conclusion Proper and effective patient monitoring is fundamental to providing safe anesthesia When monitoring is insufficient or improperly performed or interpreted, major morbidity and even mortality can occur This chapter reviews the basic principles of the myriad monitoring modalities so that the office-based anesthesia provider can ensure safe and efficient care to the patient Because technology is continually advancing, it is recommended to stay abreast of new and forthcoming as they emerge References Stoelting RK, Miller RD Basics of Anesthesia, ed London: Churchill Livingstone, 2007 Nitzan M, Romem A, Koppel R Pulse oximetry: Fundamentals and technology update Med Devices (Auckl) 2014;7:231–239 American Society of Anesthesiologists Standards for Basic Anesthetic Monitoring https://www.asahq.org/~/media/Sites/ASAHQ/Files/Public/Resources/standards-guidelines/standards-for-basic-anesthetic-monitoring.pdf Accessed March 2017 Becker DE, Casabianca AB Respiratory monitoring: Physiological and technical considerations Anesth Prog 2009;56:14–20 American Association of Oral and Maxillofacial Surgeons Parameters of Care: Clinical Practice Guidelines for Oral and Maxillofacial Surgery (AAOMS ParCare 2012) Chicago: American Association of Oral and Maxillofacial Surgeons, 2012 Connor CW Commonly used monitoring techniques In: Barash P, Cullen BF, Stoelting RK, Cahalan M, Stock MC (eds) Clinical Anesthesia, ed Philadelphia: Wolers Kluwer, 2013: 699–933 Kodali BS Capnography outside the operating rooms Anesthiology 2013;118:192–201 Szocik J, Barker SJ, Tremper KK Fundamental principles of monitoring instrumentation In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone, 2010: 1197–1227 90 www.ajlobby.com Mizukawa_Chap_08.indd 90 6/21/17 3:15 PM CHAPTER Electro cardiography Andrew E Wicke, dmd Erik J Nielsen, dds Scott Hoffman, md www.ajlobby.com Mizukawa_Chap_09.indd 91 6/20/17 10:32 AM 9 • Electrocardiography The electrocardiogram (ECG) is a recording of the surface electrical activity of the heart and is an effective way to monitor many attributes of the electrical activity of the heart during anesthesia When interpreting an ECG, the clinician may find it helpful to keep in mind the basic sequence and course of electrical conduction through cardiac tissue In a healthy patient, the sinoatrial (SA) node, located at the junction of the superior vena cava and the right atrium, is the origin of intrinsic electrical activity (Fig 9-1) The P wave represents atrial depolarization From the SA node, an electrical impulse proceeds through the crista terminalis, moves anteriorly toward the inferior portion of the right atrium, and arrives at the atrioventricular (AV) node, where the electrical impulse is temporarily delayed to allow adequate ventricular filling After ventricular diastole, the impulse propagates through the AV bundle (bundle of His) in the interventricular septum, which splits into right and left bundle branches In a normal heart, depolarization of the septum travels from right to left This direction may be reversed in patients with a conduction defect The terminal portions of the bundle branches are Purkinje fibers that course through the myocardium of the ventricles Synchronous depolarization of the ventricles during systole generates the QRS complex SA node Bundle of His Left bundle branch AV node Purkinje fibers Right bundle branch Fig 9-1 Structures involved in electrical conduction in the heart 92 www.ajlobby.com Mizukawa_Chap_09.indd 92 6/20/17 10:32 AM Elements of the ECG Elements of the ECG The ECG includes the following elements (Fig 9-2) RR interval square = 0.1 mV R P PR segment PR interval ST segment T U R P Q Q S QRS interval ST interval S QT interval square = 0.04 s Fig 9-2 Elements of the ECG RR interval The RR interval is the time between successive R waves Abnormalities in the RR interval are seen in patients with tachycardia, bradycardia, or dysrhythmias P wave The P wave represents atrial depolarization and originates in the SA node Abnormalities include increased amplitude or a peaked wave and can occur in patients with hypokalemia or hyperkalemia, right atrial enlargement, or pulmonary hypertension PR interval The PR interval is the time between the beginning of the P wave and the beginning of the QRS complex It represents the time of the electrical conductance through the AV node Measurement of the PR interval can provide an estimation of function of the AV node A prolonged PR interval can be seen in patients with AV node disease QRS interval The QRS interval represents the time of ventricle depolarization Widening of this interval can indicate conduction abnormalities in the bundle of His or branches of the bundle 93 www.ajlobby.com Mizukawa_Chap_09.indd 93 6/20/17 10:32 AM 9 • Electrocardiography ST segment The ST segment represents an isoelectric period prior to ventricular repolarization Elevation or depression of the ST segment may represent myocardial injury T wave The T wave represents ventricle repolarization A peaked T wave can be seen in patients with hyperkalemia A flattened T wave can be caused by hypokalemia or myocardial ischemia An inverted T wave can be caused by myocardial ischemia or left ventricular hypertrophy QT interval The QT interval represents the time between ventricle depolarization and repolarization It varies with the heart rate (average up to 420 milliseconds) QTc is a corrected QT interval time accounting for the variability of the heart rate A shortened or prolonged QT interval can be caused by electrolyte disturbances, drug effects, or tachyarrhythmias ECG Leads The surface electrical activity of the heart is evaluated using 10 electrodes arranged in standard configurations (Fig 9-3) Voltage differences from pairings of electrodes creates 12 leads that display surface electrical activity from different orientations A 12-lead ECG has three limb leads (I, II, III), three augmented leads (aVR, aVL, aVF), and six precordial leads (V1 through V6) Electrical impulses moving toward a lead yield a positive deflection Impulses moving away from a lead yield a negative deflection For example, an electrical impulse moving from the right arm electrode (RA) to the left arm electrode (LA) will produce a positive deflection in lead I This concept is described by the Einthoven triangle (Fig 9-4) With the electrical activity of the heart analyzed from 12 different orientations, the 12-lead ECG displays activity at all anatomical aspects of the heart, including the anterior walls, lateral walls, septal walls, and apex (Fig 9-5) RA LA RL LL RA V1 LA V2 V3 V4 V5 V6 RL LL b a Fig 9-3 Placement of 10 electrodes for 12-lead ECG (a) Four extremity electrodes: right arm (RA), left arm (LA), right leg (RL), and left leg (LL) Leads can be placed distally on the extremities or closer to the torso (b) Six chest electrodes 94 www.ajlobby.com Mizukawa_Chap_09.indd 94 6/20/17 10:32 AM ECG Monitoring Lead I: LA–RA RA LA Lead III: LL–LA Lead II: LL–RA Fig 9-4 Depiction of the Einthoven triangle, which describes the relationship of ECG limb leads and vectors of heart depolarization I aVR V1 aVL Anterior/septal wall: V1 and V2 V2 High lateral wall: I and aVL II Anterior V4 Inferior wall: II, III, aVF III aVF–] V3 Anterior V3 Low lateral V5 and V6 Fig 9-5 A 12-lead ECG displays electrical activity in the associated anatomical locations of the heart ECG Monitoring The purpose of ECG monitoring is to recognize changes in heart electrical activity in real time For ECG monitoring during anesthesia, either three electrodes (RA, LA, LL) or five electrodes (RA, RL, LA, LL, chest) are used Three electrodes permit monitoring of leads I, II, and III With five electrodes, a fourth, unipolar lead can be monitored, depending on the location of the chest lead (precordial positions V1 through V6) (Fig 9-6) For most ambulatory oral and maxillofacial surgery anesthesia purposes, three leads are monitored Importantly, three-lead monitoring has limitations For example, lead II of a three-lead system is most useful to detect ventricular dysrhythmias because the vector of lead II is most closely aligned with the vector of depolarization of the ventricles However, when a patient with coronary artery disease is monitored, it may be more beneficial to monitor lead V5 because this lead is better oriented to detect ischemic changes in the inferolateral aspect of the heart For example, lead V5 has 75% sensitivity for detecting ischemic changes, whereas lead II has 33% sensitivity Lead V5 can be simulated in a three-lead system by moving the LA lead to the V5 position with lead I selected at the monitor 95 www.ajlobby.com Mizukawa_Chap_09.indd 95 6/20/17 10:32 AM 9 • Electrocardiography RA LA RA LA Chest LL RL a LL b Fig 9-6 Electrode placement for three-lead (a) and five-lead (b) ECG monitoring ECG Interpretation The following ECG parameters should be evaluated: • Heart rate • Heart rhythm • Mean electrical (QRS) axis • QRS amplitude • ST segment The ECG tracing is displayed on a standardized background grid where time is measured on the horizontal axis, each small square is mm in length and represents 0.04 seconds, and each large square is mm in length and represents 0.2 seconds The amplitude of electrical activity is measured on the vertical axis Heart rate Heart rate is an important determinant of myocardial oxygen demand and cardiac function Many factors, including the sympathetic and parasympathetic nervous systems, affect heart rate Drugs with parasympathetic activity usually have a negative chronotropic effect Drugs with sympathetic activity usually have a positive chronotropic effect on the heart and increase the oxygen demand of the myocardium A normal heart rate is 60 to 100 beats per minute (bpm) A rate > 100 bpm represents sinus tachycardia, whereas a rate < 60 bpm represents sinus bradycardia Although ECG monitors provide a calculated rate, it is important to be able to quickly determine heart rate The “square counting” method is a simple way to assess the heart rate, especially with regular rates (Fig 9-7): • Locate an R wave on the tracing that is closest to a dark line • Locate the next R wave, and count how many large (5-mm) squares are in that RR segment • Assign each dark line a rate that corresponds to the sequence 300-150-100-75-60-50 • If the second R wave falls in the middle of a large box, the mean of the two adjacent numbers provides an estimate of the rate 96 www.ajlobby.com Mizukawa_Chap_09.indd 96 6/20/17 10:32 AM ECG Interpretation 300 Start here 150 100 75 60 50 Fig 9-7 Square-counting method of estimating heart rate The second R wave is closest to the 60-bpm dark line Therefore, the approximate heart rate is 66 bpm Heart rhythm Heart rhythm is the result of the periodicity of the heart’s electrical system Arrhythmias may be caused by abnormal automaticity (spontaneous firing of myocardial cells outside the sinus/AV node), conduction block (eg, AV block), or reentry conduction Dysrhythmias can be described according to their origin: supraventricular (atrial or nodal) or ventricular (Fig 9-8) The ECG representation of a rhythm disturbance will help determine the origin of the specific arrhythmia Dysrhythmias should be systematically evaluated as follows: • Rule out any artifact that may be contributing to an abnormal appearance of the ECG (eg, nearby electrical equipment interference, patient movement, electrode movement) • Assess the clinical scenario Does the patient have a history of arrhythmia? Consider the possibility that arrhythmia is the baseline • Assess the ventricular rate Is the rate regular or irregular? Is ventricular ectopy present? • Assess the P waves at leads II and V1 −− What is the rate and morphology? −− What is the relationship of P waves to QRS complexes? >> Confirm that every QRS complex is associated with a P wave >> Is there a 1:1 relationship? Lack of a 1:1 relationship could be a sign of an AV dissociation, such as an AV block • Assess the width of the QRS interval −− Is the QRS interval narrow (ie, < 0.12 seconds, or three small squares)? >> If so, then a supraventricular arrhythmia is most likely >> If not, then the QRS interval is wide, and either a ventricular arrhythmia or supraventricular arrhythmia with bundle branch block may be present • Assess the QRS mean electrical axis Has the axis changed substantially from the axis during the sinus rhythm? If so, the arrhythmia is most likely ventricular 97 www.ajlobby.com Mizukawa_Chap_09.indd 97 6/20/17 10:32 AM 9 • Electrocardiography Supraventricular Atrial Ventricular Nodal a b Fig 9-8 Supraventricular (a) and ventricular (b) types of dysrhythmia Normal sinus rhythm Characteristics of a normal sinus rhythm on an ECG tracing are as follows (Fig 9-9a): • Rate of 60 to 100 bpm • Regular P wave associated with each QRS complex • PR interval of 0.12 to 0.20 seconds • QRS interval of ≤ 0.10 seconds • Regular rhythm a Fig 9-9a Normal sinus rhythm 98 www.ajlobby.com Mizukawa_Chap_09.indd 98 6/20/17 10:32 AM ECG Interpretation Sinus dysrhythmias Atrial fibrillation. Characteristics of atrial fibrillation are as follows (Fig 9-9b): • Rapid atrial rate, which can be > 350 bpm • Variable ventricular rate; not all atrial contractions are conducted to the ventricles • P wave not visible • QRS interval normal or possibly widened, especially if a conduction delay is present • Irregularly irregular rhythm P wave missing, replaced by a fine wavy wave b Fig 9-9b Atrial fibrillation Atrial flutter. Characteristics of atrial flutter are as follows (Fig 9-9c): • Rapid atrial rate (250 to 350 bpm) • Variable ventricular rate; not all atrial contractions are conducted to the ventricles • P wave not visible; sawtooth waves may be observed between ventricular contractions • Normal QRS interval • Regular or irregularly irregular rhythm Sawtooth patterns in baseline c Fig 9-9c Atrial flutter 99 www.ajlobby.com Mizukawa_Chap_09.indd 99 6/20/17 10:33 AM 9 • Electrocardiography Supraventricular tachycardia. Characteristics of supraventricular tachycardia are as follows (Fig 9-9d): • Rapid rate (150 to 200 bpm) • P wave indistinguishable from T wave • Normal PR interval (0.12 second) • Normal QRS interval • Regular rhythm d Fig 9-9d Supraventricular tachycardia Premature atrial contraction. Characteristics of premature atrial contraction are as follows (Fig 9-9e): • Variable rate ranging from 50 to 100 bpm • Abnormal P wave because of ectopic origin • PR interval may be normal • Normal QRS interval • Irregular rhythm PAC e Fig 9-9e Premature atrial contraction (PAC) 100 www.ajlobby.com Mizukawa_Chap_09.indd 100 6/20/17 10:33 AM ECG Interpretation Sinus block. Characteristics of sinus block are as follows (Fig 9-9f): • Normal or slow rate • Normal configuration of P wave • Normal PR interval • Normal QRS interval • Irregular rhythm Paused (missed beat) f Fig 9-9f Sinus block Conduction disturbances First-degree AV block. Characteristics of first-degree AV block are as follows (Fig 9-9g): • Normal rate • Normal P wave • PR interval > 0.2 second • QRS interval normal, or wide if conduction is delayed at bundle branches • Regular rhythm Lengthened PR interval (> 0.2 sec) g Fig 9-9g First-degree AV block 101 www.ajlobby.com Mizukawa_Chap_09.indd 101 6/20/17 10:33 AM 9 • Electrocardiography Second-degree AV block, Mobitz type I (Wenckebach). Characteristics of second-degree AV block, Mobitz type I (also called Wenckebach block), are as follows (Fig 9-9h): • Normal or slow rate • Normal P wave • Progressive lengthening of the PR interval over several beats preceding a nonconducted P wave and dropped (ie, absent) QRS complex • Normal QRS complex that is periodically dropped • Irregular rhythm No QRS complex h Fig 9-9h Second-degree AV block, Mobitz type I Second-degree AV block, Mobitz type II. Characteristics of second-degree AV block, Mobitz type II, are as follows (Fig 9-9i) • Slow ventricular rate • Normal configuration of P wave with regular rate and intermittent nonconducted P wave • Normal PR interval that is constant in conducted beats • QRS interval sometimes normal, usually widened (if block is distal to the bundle of His) • Irregular rhythm if P waves and QRS complexes have a fixed relationship (eg, 2:1, 3:1) • Irregularly irregular rhythm if P waves and QRS complexes not have a fixed relationship No QRS complex No QRS complex i Fig 9-9i Second-degree AV block, Mobitz type II 102 www.ajlobby.com Mizukawa_Chap_09.indd 102 6/20/17 10:33 AM ECG Interpretation Third-degree AV block. Characteristics of third-degree AV block are as follows (Fig 9-9j): • Atrial rate may be normal • Variable ventricular rate • Normal configuration of P wave; the P wave is independent of the QRS complex because conduction to the ventricles does not occur • Narrow or wide QRS interval, depending on the location of the escape rhythm • PR interval not measurable • Regular rhythm j Fig 9-9j Third-degree AV block Ventricular dysrhythmias Premature ventricular contraction. Characteristics of premature ventricular contraction (PVC) are as follows (Fig 9-9k): • Normal rate • P wave absent or buried in the QRS complex • PR interval not measurable • QRS interval wide; usually > 0.12 second • Irregular rhythm k Fig 9-9k Premature ventricular contraction 103 www.ajlobby.com Mizukawa_Chap_09.indd 103 6/20/17 10:33 AM 9 • Electrocardiography Bigeminy. Bigeminy is the same as PVC except that every other QRS complex demonstrates PVC (Fig 9-9l) l Fig 9-9l Bigeminy Trigeminy. Trigeminy is the same as bigeminy except that every third QRS complex demonstrates PVC (Fig 9-9m) m Fig 9-9m Trigeminy 104 www.ajlobby.com Mizukawa_Chap_09.indd 104 6/20/17 10:33 AM ECG Interpretation Ventricular tachycardia. Characteristics of ventricular tachycardia are as follows (Fig 9-9n): • Rate 100 to > 200 bpm • P wave may be unidentifiable • PR interval not measurable • Widened QRS interval (> 0.12 seconds) • Regular rhythm n Fig 9-9n Ventricular tachycardia Ventricular fibrillation. Characteristics of ventricular fibrillation are as follows (Fig 9-9o): • No effective cardiac activity • P wave absent • QRS complex absent • Rhythm absent o Fig 9-9o Ventricular fibrillation 105 www.ajlobby.com Mizukawa_Chap_09.indd 105 6/20/17 10:33 AM 9 • Electrocardiography Asystole. Characteristics of asystole are as follows (Fig 9-9p): • No cardiac electrical activity • P wave usually absent • QRS complex absent • Rhythm absent p Fig 9-9p Asystole Right bundle branch block. Characteristics of right bundle branch block are as follows (Fig 9-10): • Normal rate • Normal P wave • Normal PR interval • Right ventricular depolarization delayed −− Early features of the QRS complex (left ventricular depolarization) are normal −− Later features of the QRS complex reflect the delay in right ventricular depolarization and electrical spread from the left ventricle to the right ventricle • QRS interval wide (> 0.12 second) −− QRS complex has two R wave peaks, R and R', in V1 through V3 (RSR') −− A wide S wave is seen in leads I, aVL, V5, and V6 • Regular rhythm • ST depression and T wave inversion in leads V1 through V3 106 www.ajlobby.com Mizukawa_Chap_09.indd 106 6/20/17 10:33 AM ECG Interpretation R1 R S V1 a I b S Fig 9-10 Right bundle branch block (a) Wide S wave in lead I (b) RSR' pattern in V1 Left bundle branch block. In left bundle branch block, impulses not travel down the left bundle in the ventricular septum As a result, impulses must first travel through the right ventricle before stimulating left ventricular contraction This scenario results in dyssynchrony of ventricular contraction Characteristics of left bundle branch block are as follows (Fig 9-11): • Normal rate • Normal P wave • Normal PR interval • Wide QRS interval • QRS complex notched (M-shaped) • Tall R waves in leads I, V5, and V6 • Q waves absent in leads I, V5, and V6 • Deep S waves in leads V1 through V3 107 www.ajlobby.com Mizukawa_Chap_09.indd 107 6/20/17 10:33 AM 9 • Electrocardiography aVL a U1 b Fig 9-11 Left bundle branch block (a) M-shaped QRS complex (b) Absence of Q wave in lead aVL Mean electrical (QRS) axis The mean electrical axis is the electrical vector of depolarization of the myocardium Changes in the electrical axis can be associated with clinically important cardiac disease The electrical axis is estimated from the mean QRS electrical vector In a normal heart, the axis is located in the sextant demarcated by vectors at −30 degrees to 90 degrees (Figs 9-12 and 9-13) Because of the reproducible spatial arrangement of ECG leads, the electrical axis can be calculated on the basis of features of the QRS complex in specific leads (see Fig 9-13) The process of estimating the QRS electrical axis begins with evaluation of leads I and II If positive QRS deflection is present in both leads, then the axis is normal Otherwise, the isoelectric method of estimation is used as follows: Identify the isoelectric QRS lead (in which QRS positive and negative deflection are equal) Identify the leads with the tallest R waves The electrical axis is the lead that is 90 degrees from the isoelectric lead and pointing to the other positive lead(s) 108 www.ajlobby.com Mizukawa_Chap_09.indd 108 6/20/17 10:33 AM ECG Interpretation –90º aVL aVR –30º +180º 0º III +90º I II aVF Fig 9-12 The normal electrical axis is between −30 and 90 de- Fig 9-13 Relationship of ECG leads to electrical axis of heart grees The large arrow represents the mean of the individual myocardial electrical vectors For example, the electrical axis in Fig 9-14 can be estimated using the isoelectric method First, lead I is identified as the isoelectric lead Next, the leads with the tallest R waves are identified; they are leads II and III Finally, lead aVF is 90 degrees from lead I and points to the positive leads (leads II and III) Therefore, the mean electrical QRS axis is 90 degrees An abnormal electrical axis may occur in the following circumstances: • Congenital heart malposition/rotation • Ventricular hypertrophy (vector will deviate toward hypertrophied ventricle) • Infarction (vector deviates away from injured tissue) • Conduction abnormalities (eg, right bundle branch block will cause the right ventricle to depolarize later than the left ventricle, displacing the axis rightward) I aVR II aVL III aVF Fig 9-14 Sample ECG tracing for estimation of the electrical axis using the isoelectric method 109 www.ajlobby.com Mizukawa_Chap_09.indd 109 6/20/17 10:33 AM 9 • Electrocardiography Hypertrophy Hypertrophy is usually the result of pressure overload (eg, hypertension, valvular disease, hypertrophic cardiomyopathy) Ventricular hypertrophy may cause the following ECG changes: • Left ventricular hypertrophy: −− Increased electrical predominance of the left ventricle over the right ventricle −− Sum of S wave in V1 and R wave in V5 or V6 is > 35 mm −− Leftward shift of the electrical axis • Right ventricular hypertrophy: −− Increased electrical predominance of the right ventricle over the left ventricle −− Tall R wave in the right ventricular leads: R positive deflection > the S negative deflection −− Rightward shift of the electrical axis (> 90 degrees) Identification of hypertrophic right or left ventricles on an ECG suggests structural cardiac disease that may increase the risk of future cardiovascular complications Infarction Cardiac ischemia occurs when myocardial oxygen demand exceeds oxygen supply Myocardial infarction refers to necrosis of myocardial tissue as a result of prolonged ischemia Both ischemia and infarction produce characteristic ECG changes (Fig 9-15): Infarction is characterized by ST segment elevation with tall positive T waves and is sometimes called ST-elevation myocardial infarction (STEMI) Infarction will be manifested in specific leads depending on the location of the infarction: • Anterior infarction results in ST elevation with abnormal Q waves in leads V1 through V4 Reciprocal ST depression may be seen in leads II, III, and aVF • Inferior infarction results in ST elevation with abnormal Q waves in lead II, III, and aVF Reciprocal ST depression may also be seen in the anterior or anterolateral leads (aVL, possibly I) • Lateral infarction results in ST elevation with abnormal Q waves in lead I and aVL Reciprocal ST depression may be seen in inferior leads • Posterior infarction may not result in ST elevation in any of the leads ST depression with tall R waves can occur in leads V1 and V2 I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 II Fig 9-15 Inferior myocardial infarction with ST elevation in leads II, III, and aVF and reciprocal ST depression and T wave inversion in lead aVL 110 www.ajlobby.com Mizukawa_Chap_09.indd 110 6/20/17 10:33 AM Cardiac Consultation Ischemia is characterized by ST depression (non–ST-segment elevation myocardial infarction, or NSTEMI) in leads V4 through V6, I, II, and aVL Other conditions that can result in ST depression include the following: • Posterior myocardial infarction (leads V1 through V3) • Reciprocal change in STEMI resulting in ST depression in the lead or leads opposite the lead or leads with ST elevation • Right or left bundle branch block Indications for preoperative ECG Preoperative risk assessment should include consideration of a patient’s functional status and exercise capacity The 2014 American College of Cardiology (ACC) and American Heart Association (AHA) Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery describes elevated risk procedures as those in which the patient has a 1% or greater risk of cardiac death or myocardial infarction The authors of the guideline advocate the use of a web-based risk calculator to estimate cardiac risk on an individual basis.1 The 2014 ACC/AHA guidelines1 recommend preoperative ECG evaluation in patients with established coronary artery disease, especially before higher-risk procedures, because the ECG provides prognostic information related to short-term and long-term morbidity and mortality and also serves as a baseline should subsequent perioperative ECGs be necessary Although preoperative identification of ECG abnormalities, such as arrhythmias, pathologic Q waves, left ventricular hypertrophy, bundle branch blocks, and other abnormalities, has some prognostic value, the prognostic relevance is unclear Furthermore, the ACC/AHA guidelines state that a standard age or risk factor cutoff has not been established However, if it is determined that a preoperative ECG is necessary, it should be obtained no more than months before the elective surgical procedure in the stable patient The 2014 ACC/AHA guidelines for preoperative ECG are summarized as follows1: Preoperative resting 12-lead ECG is reasonable for patients with known coronary heart disease, significant arrhythmia, peripheral arterial disease, cerebrovascular disease, or other significant structural heart disease, except for those undergoing low-risk surgery Preoperative resting 12-lead ECG may be considered for asymptomatic patients without known coronary heart disease, except for those undergoing low-risk surgery Routine preoperative resting 12-lead ECG is not useful for asymptomatic patients undergoing low-risk surgical procedures Cardiac Consultation Valuable information can be obtained from both the patient’s medical history and the current and previous ECG tracings If abnormalities are discovered on ECG, comparison with previous ECG tracings should be made If the changes on the current ECG are new and suggest ischemia, infarction, or change in rhythm, consultation with a cardiologist is prudent If the patient has had no changes in the past years but the earlier ECG tracing shows possible ischemia or infarction and the patient has not had medical follow-up since the time of the earlier ECG, consultation with a cardiologist is warranted 111 www.ajlobby.com Mizukawa_Chap_09.indd 111 6/20/17 10:33 AM 9 • Electrocardiography Conclusion The interpretation of the ECG is a valuable and judicious skill that is imperative to the care of all patients Understanding the basic anatomy and physiology of the heart’s electrical conduction is essential to interpretation of the ECG The more familiar the practitioner is with normal findings, the more obvious the abnormal findings become This ensures adequate medical intervention when appropriate for patients with abnormal ECG findings References and Recommended Reading Fleisher LA, Fleischmann KE, Auerbach AD, et al 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2014;64:e77–e137 Bennett J, Treasure T Office-based anesthesia Oral Maxillofac Surg Clin North Am 2007;19:45–57 Cadogan M, Nickson C (eds) Life in the Fast Lane website http://lifeinthefastlane.com/ Accessed March 2017 De Jong JSSG, Postema PG, Kreuger R ECGpedia website http://www ecgpedia.org Accessed March 2017 Little JW, Falace DF, Miller CS, Rhodus NL Cardiac arrhythmias In: Little and Falace’s Dental Management of the Medically Compromised Patient, ed St Louis: Elsevier, 2012:67–80 Medical Training and Simulation Practical Clinical Skills website http:// www.practicalclinicalskills.com/ Accessed March 2017 112 www.ajlobby.com Mizukawa_Chap_09.indd 112 6/20/17 10:33 AM CHAPTER 10 Pre-anesthetic Patient Evaluation Charles H Kates, dds, pa Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_10.indd 113 6/21/17 3:16 PM 10 • Pre-anesthetic Patient Evaluation The safety and efficiency of office-based anesthesia depend largely on the initial patient evaluation The clinician is responsible for the thorough and thoughtful evaluation of each patient before the delivery of anesthesia.1 The patient evaluation provides a basis of information for the clinician to determine the suitability of a patient for anesthesia and to develop a personalized anesthetic plan that takes into consideration comorbid medical conditions and a physical assessment of the patient The elements of the pre-anesthetic evaluation are as follows: Chief complaint/history of present illness Past medical history a Allergies b Medications c Surgical/anesthetic history Family history Social history Review of systems Focused physical examination a Vital signs b Overall impresssion of patient c Head, eyes, ears, nose, and throat d Cardiovascular system e Pulmonary system Review of imaging Review of pertinent laboratory tests Assessment 10 Anesthetic management plan For most American Society of Anesthesiologists (ASA) class I and II patients, this evaluation will be straightforward However, as a patient’s medical comorbidities become more complex, the pre-anesthetic evaluation takes on added importance because each comorbid condition must be assessed in the context of anesthetic selection and delivery The principal objective is not only to identify comorbid conditions but to assess the severity and degree of control of those conditions Anesthesia may be safer in a patient with moderate disease under optimal control by primary care and specialist physicians than in a patient with mild disease that is poorly controlled Failure to recognize even seemingly minute elements in the pre-anesthetic evaluation can result in serious complications and even death Nearly all elements of the pre-anesthetic evaluation have direct implications for anesthesia administration This chapter focuses on elements of the history and physical examination that have the most relevant and substantial impact on safe anesthetic delivery The findings of the pre-anesthetic evaluation should be used to determine whether a patient is an appropriate candidate for office-based anesthesia The pre-anesthetic workup may also prompt further evaluation or consultation with the patient’s primary care and/or specialist physicians to arrive at the safest anesthetic plan History The author of this chapter prefers a history-taking system that is both efficient and complete The time-honored method of simply handing the patient a form to fill out often produces the following results: • The patient does not know the answer to the questions and therefore answers “no.” • The patient does not appreciate the importance of the questions and therefore answers “no.” • The patient does not want to share the information and therefore answers “no.” 114 www.ajlobby.com Mizukawa_Chap_10.indd 114 6/21/17 3:16 PM History Instead, the author of this chapter prefers a one-on-one interview by a trained staff member, who understands the clinical relevance of the questions and is able to obtain a detailed history The practitioner then evaluates the patient and conducts a rapid but thorough review of the history, with emphasis on the “yes” notations, and further explores areas that are germane to anesthesia Regardless of the method of obtaining and documenting the history, the following elements of the history must always be explored: • Comorbid medical conditions (specific organ systems and diseases are addressed in subsequent chapters of this book) • Medications: over-the-counter, prescription, and herbal preparations • Tobacco, alcohol, and recreational and illicit drug use • Allergies, drug intolerances, and features of previous drug reactions (eg, rash, urticaria) • Anesthetic history: difficulties, adverse events, satisfaction with previous techniques • Review of systems with special attention to the endocrine system, cardiovascular system (including exercise capacity, discussed below), and pulmonary system • Obstructive sleep apnea (OSA): severity (eg, apnea-hypopnea index, need for continuous positive airway pressure [CPAP], CPAP pressure requirements) • Status of oral intake: hours of no clear liquids; hours of no breast milk; and hours of no solids, nonhuman milk, or formula In regard to a patient’s history of drug allergy, immunoglobulin E–mediated hypersensitivity reactions should be distinguished from intolerance to known side effects of the drug A history of rash, pruritus, urticaria, hypotension, and/ or bronchospasm indicate an allergic reaction (see chapter 12) Anaphylactoid (pseudoallergic) reactions have similar signs and symptoms and can be differentiated from true allergic reactions only by serum testing for specific antibodies The review of systems is helpful to systematically elicit the status of disease affecting any organ system The review of systems is performed in addition to the past medical history Although the review of systems should include all organ systems, the most important systems from the standpoint of anesthesia selection and delivery are the cardiovascular and pulmonary systems In reviewing the cardiovascular system, the clinician should be aware that a history of ischemic heart disease and/or heart failure has been found to be associated with cardiac complications after major noncardiac surgery.2 Although that finding is not directly applicable to office-based anesthesia, assessing the status of the patient with known ischemic heart disease and/or heart failure is of primary concern Frequency and severity of symptoms such as chest pain, dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, syncope, and palpitations, among others, can provide useful information on a patient’s current cardiac status.3,4 Patients with active cardiac conditions, including unstable angina, decompensated heart failure, substantial arrhythmias, or severe valvular disease, clearly are not suitable candidates for office-based anesthesia More subtle presentations of these underlying cardiac conditions require careful assessment and, preferably, the input of a medical specialist to determine a patient’s suitability for office-based anesthesia Other conditions associated with an increased risk of cardiac complications after noncardiac surgery include diabetes, history of cerebrovascular disease, and renal disease with a serum creatinine level > 2.0 mg/dL.5 Assessment of exercise capacity is a reliable predictor of future cardiac events and the patient’s ability to tolerate anesthesia Functional capacity can be expressed in metabolic equivalent (MET) units, with MET defined as the oxygen consumption of a 70 kg person at rest A 2-MET activity requires twice the metabolic energy expenditure of sitting quietly Physical activity of > MET is considered vigorous activity, whereas activity of < MET is considered light activity In general, good functional capacity is demonstrated by the ability to perform physical activity of > MET without symptoms.5 115 www.ajlobby.com Mizukawa_Chap_10.indd 115 6/21/17 3:16 PM 10 • Pre-anesthetic Patient Evaluation Examples of specific activity MET levels are as follows6: • Watching television: MET • Walking at mph on a flat surface or up one flight of stairs while holding a bag of groceries: MET • Stationary cycling, very light effort: 5.5 MET • Jogging: MET • Rope jumping: 10 MET Preoperative pulmonary evaluation and optimization improves patient outcomes The most important preoperative pulmonary conditions to consider include dyspnea, asthma, chronic obstructive pulmonary disease (COPD), OSA, and smoking Review of the pulmonary system is focused on determining the status of pre-existing pulmonary disease Symptoms of shortness of breath, chest tightness, dyspnea, wheezing, cough, sputum production, snoring, witnessed OSA, and need for supplemental oxygen should be explored Well-controlled asthma is not a risk factor for intraoperative or postoperative complications.7 However, patients with poorly controlled asthma and, in particular, wheezing at the time of anesthesia induction have a higher risk of perioperative complications.7 Before elective surgery, patients should be free of wheezes, cough, or dyspnea, and, if the patient uses home spirometry, peak expiratory flow should be 80% of the expected level or the patient’s personal best Well-controlled asthma is characterized by daytime symptoms occurring no more than twice weekly and nighttime symptoms occurring no more than twice monthly.8 Triggers of bronchospasm, such as exercise, allergens, stress, chemical irritants, and airway infections, should be noted and avoided.3 In contrast to well-controlled asthma, COPD increases the risk of perioperative pulmonary complications Patient stability can be assessed by the history of the patient’s response to bronchodilator therapy In most patients, COPD will be most effectively controlled preoperatively with a combination of long-acting bronchodilator therapy and inhaled corticosteroids A history of recent hospitalization for acute bronchospasm or COPD exacerbation should be carefully considered in the assessment of the patient with pulmonary disease The pre-anesthetic evaluation and discovery of comorbid medical problems is especially important in patients with a history of OSA During the pre-anesthetic assessment, patients should be questioned regarding snoring and excessive daytime sleepiness, which may suggest undiagnosed OSA A large neck circumference (> 17 inches for men, > 16 inches for women) predicts a greater risk of OSA.9 The STOP-BANG questionnaire is a validated screening tool to assist in identifying patients who may have OSA10 (Box 10-1) BOX 10-1 S T O P B A N G STOP-BANG questionnaire used to screen risk of OSA Snoring: Do you snore loudly (louder than talking or loud enough to be heard through closed doors)? Tiredness: Do you often feel tired, fatigued, or sleepy during daytime? Observed apnea: Has anyone observed you stop breathing during your sleep? Pressure: Do you have or are you being treated for high blood pressure? BMI > 35 kg/m2 Age > 50 y Neck circumference > 40 cm Gender: Male sex Low risk for OSA: Yes to fewer than three questions High risk for OSA: Yes to three or more questions High probability of moderate to severe OSA: Yes to five or more questions BMI, body mass index Mask ventilation, direct laryngoscopy, and endotracheal intubation are more difficult in patients with OSA than in other patients Depending on the severity of OSA, mask ventilation may be impossible in a patient with OSA who 116 www.ajlobby.com Mizukawa_Chap_10.indd 116 6/21/17 3:16 PM Airway Evaluation experiences an anatomical airway obstruction after the induction of anesthesia Severity of OSA can be estimated by CPAP use and pressure settings, results of polysomnography, and consultation with the patient’s primary care physician or sleep physician (See chapter 29.) Finally, it is important to recognize that patients with OSA have increased frequency of comorbidities, including diabetes, hypertension, stroke, arrhythmias, congestive heart failure, pulmonary hypertension, cardiomyopathy, coronary artery disease, and myocardial infarction.11 Physical Examination The pre-anesthetic physical evaluation should be a focused examination that minimally includes assessment of vital signs (heart rate, blood pressure, room air oxygen saturation, weight, body mass index [BMI]), airway, cardiac function, and pulmonary function Vital signs should be documented so that the practitioner can reference them during anesthesia When obtained during a consultation visit in the absence of fear, anxiety, and dehydration, they are more representative of the patient’s true baseline When addressing deviation of intraoperative vital signs, the surgeon should consider the consultation vital signs as a reference for therapy The cardiac examination should focus on cardiac function and delivery of oxygenated blood sufficient to meet the patient’s metabolic demands: • Auscultation of the heart can allow the surgeon to assess cardiac rate and rhythm Arrhythmias should be noted Additional heart sounds, such as S3 or S4 gallop, may indicate dysfunction or valvular pathology • Murmurs can be benign but may also indicate serious valvular disorders that may be associated with substantial cardiac dysfunction • Increased jugular venous pulsations with or without hepatojugular reflux and peripheral edema (pitting edema of the ankles) indicate right heart failure.3 • Rales and dullness at the lung bases indicate pleural effusions • Crackles in the lung fields may indicate pulmonary edema and left heart failure.3 • The pulmonary examination should focus on the ability to oxygenate blood and release carbon dioxide (ventilation): –– Lungs should be clear to auscultation in all fields bilaterally –– Wheezes and a prolonged expiratory phase can indicate asthma or obstructive disease –– Increased diameter of the chest, wheezing, and distant breath sounds can indicate COPD Airway Evaluation The American Society of Anesthesiologists has defined a difficult airway as “the clinical situation in which a conventionally trained anesthesiologist experiences difficulty with face-mask ventilation of the upper airway, difficulty with tracheal intubation, or both.”12 The “cannot ventilate, cannot intubate” scenario may be one of the most feared by anesthesia providers Obvious catastrophic consequences can happen very quickly if certain risk factors and signs are not appreciated Because adverse airway events are an important source of morbidity and mortality in office-based anesthesia, particular attention must be directed to the evaluation of the airway.13 The examination should particularly include a careful examination of pertinent anatomy that may influence airway management, including endotracheal intubation Risk factors for difficult airway management include the following12,14: Infections involving the masticator, lateral pharyngeal, and/or sublingual spaces • Oropharyngeal swelling • Restricted oral opening (< 30 mm) • Mallampati class or 117 www.ajlobby.com Mizukawa_Chap_10.indd 117 6/21/17 3:16 PM 10 • Pre-anesthetic Patient Evaluation • High arched or narrow palate • Facial hair • Male sex • Rheumatoid arthritis affecting the temporomandibular joint and/or cervical spine • Dentofacial deformities and congenital syndromes, such as Crouzon, Goldenhar, Pierre Robin, and Treacher Collins syndromes • Thyromental distance < finger breadths • Head and neck radiation therapy • Short, thick neck with limited mobility • Obesity • OSA • BMI > 30 kg/m2 • Distorted anatomy resulting from pathology (oropharyngeal masses), previous surgery, trauma, or other causes • Pregnancy In the pre-anesthetic airway evaluation, the surgeon should specifically assess the following possible airway management scenarios: Will it be possible to ventilate the patient by mask after induction? Will it be possible to utilize a supraglottic device if needed? Is endotracheal intubation possible with direct laryngoscopy? Can a surgical airway be rapidly and efficiently deployed if necessary? Mask fit The face mask must be sized to accommodate the patient’s facial form and guarantee a perfect seal when applied It is therefore incumbent on the surgeon to have a variety of masks available from sizes through The masks should be malleable to allow for custom form adjustment Oral and nasal airways of various sizes should be available and should be measured on the patient before induction of anesthesia/sedation The properly sized oral airway should be measured from the oral commissure to the earlobe (Fig 10-1) A properly sized nasal airway should be measured from the nostril to the earlobe (Fig 10-2) Fig 10-1 Oropharyngeal airway sizing Fig 10-2 Nasopharyngeal airway sizing 118 www.ajlobby.com Mizukawa_Chap_10.indd 118 6/21/17 3:16 PM Airway Evaluation Supraglottic devices The most popular supraglottic device for airway maintenance during anesthesia is the flexible laryngeal mask airway (LMA; Fig 10-3) It can be positioned to allow access to the surgical area while providing a quasi closed system allowing for ventilation pressure of up to 20 cm H2O, with reasonable protection against passive regurgitation Sizes of these devices are through 5, each of which is appropriate for patients of different size To allow insertion of the device, the patient must have adequate mandibular mobility, adequate interincisal distance, and normal intraoral and pharyngeal anatomy The LMA device does not work well in patients with a limited mouth opening, tori, or enlarged lingual and palatal tonsils Fig 10-3 Example of a flex laryngeal mask airway (LMA Flexible, Teleflex) used in oral and maxillofacial surgery This device allows the surgeon operating space while taking advantage of the properties of the laryngeal mask airway An emergency variant of the LMA is the I-Gel (Intersurgical) supraglottic airway device, which can be inserted in patients with limited mouth opening or other anomalies (Fig 10-4) It requires no cuff inflation and is somewhat rigid, allowing for rapid and easy placement Fig 10-4 The I-Gel supraglottic airway device 119 www.ajlobby.com Mizukawa_Chap_10.indd 119 6/21/17 3:16 PM 10 • Pre-anesthetic Patient Evaluation Endotracheal intubation It is the opinion of the authors that the traditional thyromental distance measurement is flawed and provides minimal information to the practioner The thyromental distance is the hypotenuse of the right triangle of Patil, and therefore, it depends on a head positioning at a right angle This does not provide addtional necessary airway relationships such as height of the larynx, mandibular space, and laryngeal tilt A better prognosticator of the ability to intubate using a standard laryngoscope is the 3-3-2 fit method Confirmation of adequate temporomandibular joint mobility is also essential The 3-3-2 rule consists of the following: • A three-finger interincisal opening (with the patient’s fingers used as the reference) (Fig 10-5a) • A three-finger distance from the chin to the mandible-neck junction (surgeon’s fingers) (Fig 10-5b) • A two-finger distance from the mandible-neck junction to the thyroid notch (surgeon’s fingers) (Fig 10-5c) a b Fig 10-5 (a) Evaluation of the interincisal distance (b) Evaluation of the second measurement of the 3-3-2 fit rule (c) Evaluation of the height of the larynx in relation to the base of the tongue, the third measurement of the 3-3-2 rule C Mobility of the temporomandibular joint is best examined by placing the middle fingers of both hands just anterior to the mandibular condyles Have the patient open the mouth as widely as possible, and note the forward translation of the condyles in the glenoid fossa (Fig 10-6) The presence of hinge-axis-only joint movement will indicate that little or no forward and downward movement of the jaw occurs on opening In this situation, glottal visualization with traditional direct laryngoscopy will not be possible However, other methods of visualization, such as video laryngoscopy, transillumination, fiberoptic laryngoscopy, or the use of other techniques and devices, will often be effective Importantly, however, access to such laryngoscopy adjuncts is often limited in the oral surgery office, requiring the surgeon to rely on traditional direct laryngoscopy 120 www.ajlobby.com Mizukawa_Chap_10.indd 120 6/21/17 3:16 PM Airway Evaluation Fig 10-6 Evaluation of mandibular condyle mobility The modified Mallampati classification is another method of predicting the likelihood of a difficult airway should intubation be necessary (Fig 10-7) It is assessed with the patient sitting upright with the mouth open and the tongue protruded, without phonation Alternatively, it can be evaluated without tongue protrusion The classification is as follows: • Class 1: visualization of the tonsils, uvula, and soft palate • Class 2: visualization of the upper portion of the tonsils and uvula • Class 3: visualization of the base of the uvula • Class 4: no visualization of the uvula Hard palate Pillar Soft palate Uvula Class Class Class Class Fig 10-7 The Mallampati classification In general, higher Mallampati scores (classes and 4) are associated with poorer visualization in direct laryngoscopy However, unanticipated difficult airways can sometimes occur in patients with lower Mallampati scores The author of this chapter holds the opinion that the Mallampati classification is flawed because it depends on soft tissue landmarks and does not take into account other anatomical relationships, such as laryngeal tilt (the so-called “posterior larynx”) Also, it is often poorly applied by using phonation and by incorrectly positioning the patient during examination Other physical findings, such as tori, oral tumors, or obesity, also can limit the ability to successfully use traditional direct laryngoscopy 121 www.ajlobby.com Mizukawa_Chap_10.indd 121 6/21/17 3:16 PM 10 • Pre-anesthetic Patient Evaluation Cervical mobility should be evaluated by having the patient rotate the head laterally and extend and flex the neck to evaluate the ability to achieve the “sniffing” position during direct laryngoscopy (Fig 10-8) Patients with degenerative or rheumatoid arthritis may have limited neck mobility, which can make intubation difficult Fig 10-8 Evaluation of cervical neck mobility Finally, tracheal mobility should be assessed by having the patient swallow and noting symmetrical vertical movement of the larynx Rotation of the larynx indicates restriction of normal movement Restriction of movement will compromise visualization of the larynx with a traditional laryngoscope Surgical airway management All oral surgery offices should have a protocol for management of the difficult airway (see chapter 11) When face-mask ventilation is inadequate, tracheal intubation is unsuccessful, and supraglottic airway ventilation does not maintain oxygenation, cricothyrotomy will be necessary To be prepared for this eventuality, the surgeon must assess the patient’s anterior neck anatomy as part of the pre-anesthetic physical examination For example, the location of the cricothyroid membrane should be assessed by means of palpation Other Assessments Other data, such as prior electrocardiograms, echocardiograms, cardiac catheterization data, pulmonary function tests, and laboratory data, can help the clinician determine whether a patient is an appropriate candidate for office-based anesthesia These data are usually readily available from the patient’s primary care or consultant physician Laboratory evaluations should be obtained if indicated by the history and/or physical examination but otherwise are unnecessary in routine office-based anesthesia 122 www.ajlobby.com Mizukawa_Chap_10.indd 122 6/21/17 3:16 PM References Summary The pre-anesthetic patient evaluation is critical in calculating anesthesia risk and avoiding anesthesia morbidity and mortality All patients, regardless of health, demand a thorough evaluation following the format outlined in this chapter When additional data is required to assess risk, primary care and other consultant specialists should be contacted This chapter also reviews a practical method for rapid airway assessment in order to enhance the safety of general anesthesia and sedation in the oral and maxillofacial surgery office The suggestions and techniques described in this chapter will also help practitioners to improve airway skills, thereby reducing anesthetic complications References Warner DO, Warner MA, Barnes RD, et al Perioperative respiratory complications in patients with asthma Anesthesiology 1996;85:460–467 American Association of Oral and Maxillofacial Surgeons Parameters of Care: Clinical Practice Guidelines for Oral and Maxillofacial Surgery (AAOMS ParCare 2012) Patient Assessment Chicago: American Association of Oral and Maxillofacial Surgeons, 2012 Sweitzer BJ, Smetana GW Identification and evaluation of the patient with lung disease Med Clin North Am 2009;93:1017–1030 Lee TH, Marcantonio ER, Mangione CM, et al Derivation and prospective validation of a simple index for prediction of cardiac risk of major non-cardiac surgery Circulation 1999;100:1043–1049 Katz I, Stradling J, Slutsky AS, Zamel N, Hoffstein V Do patients with obstructive sleep apnea have thick necks? Am Rev Respir Dis 1990;141:1228–1231 Agarwal R, Porter MH, Obeid G Common medical illnesses that affect anesthesia and their anesthetic management Oral Maxillofac Clin North Am 2013;25:407–438 10 Chung F, Yegneswaran B, Liao P, et al STOP questionnaire: A tool to screen patients for obstructive sleep apnea Anesthesiology 2008;108:812–821 Becker DE Preoperative medical evaluation: Part General principles and cardiovascular considerations Anesth Prog 2009;56:92–103 11 Caples SM, Gami AS, Somers VK Obstructive sleep apnea Ann Intern Med 2005;142:187–197 Fleisher LA, Beckman JA, Brown KA, et al ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: A report of the American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery Circulation 2007;116(17):e418–e499 [errata 2008;117(5):e154 and 2008;118(9):e143–e144 12 Apfelbaum JL, Hagberg CA, Caplan RA, et al; American Society of Anesthesiologists Task Force on Management of the Difficult Airway Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway Anesthesiology 2013;118:251–270 13 D’Eramo EM, Bontempi WJ, Howard JB Anesthesia morbidity and mortality experience among Massachusetts oral and maxillofacial surgeons J Oral Maxillofac Surg 2008;66:2421–2433 14 Phero JC, Rosenberg MB, Giovannitti JA Jr Adult airway evaluation in oral surgery Oral Maxillofac Surg Clin North Am 2013;25:385–399 Ainsworth BE, Haskell WL, Herrmann SD, et al 2011 Compendium of Physical Activities: A second update of codes and MET values Med Sci Sports Exerc 2011;43:1575–1581 123 www.ajlobby.com Mizukawa_Chap_10.indd 123 6/21/17 3:16 PM www.ajlobby.com Mizukawa_Chap_10.indd 124 6/21/17 3:16 PM CHAPTER 11 Management of Airway Urgencies and Emergencies Luis G Vega, dds Paul Hinchey, dmd, md Matthew Mizukawa, dmd Samuel J McKenna, dds, md www.ajlobby.com Mizukawa_Chap_11.indd 125 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Airway compromise is the most common mechanism of injury in patients undergoing office-based sedation or general anesthesia.1,2 Consequently, airway assessment is essential when formulating an anesthetic plan Airway assessment is performed with the goal of identifying known factors that could contribute to any difficulties in ventilating/intubating a patient The initial assessment consists of a focused history and physical examination, as shown in Box 11-1 and reviewed in chapter 10 The difficult airway represents a complex relationship between patient factors, the clinical setting, and the skills of the practitioner The American Society of Anesthesiologists (ASA) defines a difficult airway as a clinical situation in which a conventionally trained anesthesiologist experiences difficulty with face-mask ventilation, tracheal intubation, or both (Box 11-2).3 The typical office-based oral and maxillofacial surgery patient is not intubated; therefore, the ability to maintain a patent airway and adequate spontaneous ventilation or to ventilate with a bag valve mask (BVM) is of utmost importance The anesthesia provider must recognize that anesthesia has the potential to compromise air exchange (Box 11-3) and must be equipped with the necessary skills and equipment to maintain or rescue the airway.4,5 A dedicated airway rescue tray is recommended to maximize efficiency and organization during emergency airway situations The composition of a basic airway tray is described in Box 11-4 and shown in Fig 11-1 B OX 11-1 Airway assessment: Risk factors for difficult ventilation/intubation History • Airway difficulties with previous anesthetics • History of snoring or obstructive sleep apnea • Previous surgery on the airway • Obesity Physical examination • Mallampati airway classification score or (see Fig 10-7) • Thyromental distance < cm • Mandibular retrognathia • Interincisal opening < 30 mm • Short neck • Neck circumference > 17 cm • Enlarged tonsils • Limited neck mobility • Abnormal oropharyngeal/neck masses • Congenital, developmental, or acquired facial deformities B OX 11- • • • • • Difficult airways as defined i by the ASA Difficult face-mask or supraglottic airway ventilation Difficult supraglottic airway placement Difficult laryngoscopy Difficult tracheal intubation Failed intubation 126 www.ajlobby.com Mizukawa_Chap_11.indd 126 6/20/17 10:35 AM Management of Airway Urgencies and Emergencies B OX 11- Classification of respiratory or airway problems Obstructive • Supraglottic • Glottic • Subglottic Pathophysiologic • Hyperventilation • Hypoventilation • Apnea B OX 11- • • • • • • • • • • Contents of a basic airway rescue tray Nasopharyngeal and oropharyngeal airways Laryngeal mask airways Endotracheal tubes Laryngoscope with a selection of blades McGill forceps Flexible stylet Suction catheter BVM for positive pressure ventilation Tongue blades and water soluble lubricants Cricothyroid cannula Fig 11-1 Airway rescue tray 127 www.ajlobby.com Mizukawa_Chap_11.indd 127 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Supplemental Oxygen, Preoxygenation, and Oxygen Delivery Systems Supplemental oxygen is important when providing any level of sedation or general anesthesia A patient’s ability to maintain a peripheral oxygen saturation (Spo2) > 90% during anesthesia is often compromised by decreased tidal volume, decreased respiratory rate, and airway obstruction The principle of providing a higher fraction of inspired oxygen (FiO2) via supplemental oxygen optimizes hemoglobin saturation and delivery of oxygen to vital organs Basic principles of oxygen sources and supplemental oxygen delivery systems are briefly discussed in the following sections Oxygen sources in the office setting Any facility providing anesthesia must have an adequate oxygen source In larger facilities, or in facilities where oxygen is plumbed to be delivered throughout, oxygen is stored in steel H-cylinders These cylinders contain approximately 7,000 L of oxygen, whereas smaller, portable E-cylinders hold approximately 600 L of oxygen Even if H-cylinders provide oxygen for day-to-day use, it is recommended that at least one E-cylinder be reserved should the central oxygen system fail or in the case of an emergency in an area of the facility where central oxygen is not readily accessible The amount of gas in an oxygen cylinder is expressed in pounds per square inch (psi) A full E-cylinder, for example, will have approximately 2,200 psi of pressure, indicating approximately 600 L of oxygen.6 If the clinician is unsure if the volume of oxygen in a cylinder is sufficient to provide supplemental oxygen during anesthesia, the duration, expressed in minutes, that a certain pressure of oxygen will provide flow can be calculated using the following equation, where F is a conversion factor (0.3 for E-cylinders and 3.0 for H-cylinders)6: Flow time = (psi × F ) / flow rate (L/min) Preoxygenation Preoxygenation before administering office-based anesthesia should always be considered As mentioned previously, the patient may be hypopneic or apneic at times during anesthesia During these periods, when oxygen is not replenished into the alveoli from the environment, the patient is relying largely on the volume of oxygen in the functional residual capacity, or the volume of air in the lungs at the end of a normal tidal volume Preoxygenation replaces nitrogen from the functional residual capacity with oxygen, functionally “filling the storage tank.” This principle is supported by studies demonstrating that, in the setting of emergency department endotracheal intubation, preoxygenation with supplemental oxygen will substantially prolong the time before desaturation below 90% compared with just room air.7 A higher FiO2 can be expected to preoxygenate the lungs more rapidly than a lower FiO2 Airway adjuncts facilitate delivering a high FiO2 to the lungs (see section on airway management adjuncts) Another factor influencing the efficacy of preoxygenation is patient positioning Patients who are in a supine position preoxygenate less effectively, compared with those in a semirecumbent position.7 This finding is attributed to the increased difficulty in inflating the lungs while in a supine position, particularly for obese patients In addition, there is a tendency toward atelectasis of the alveoli in the dependent, posterior regions of the lungs, while the patient is supine, resulting in a ventilation-perfusion mismatch in which alveoli are perfused but not ventilated This mismatch decreases the absorption of oxygen into the pulmonary vasculature, as well as the volume of oxygen reserves that are so critical in an apneic event A healthy adult effectively preoxygenated with 90% to 100% oxygen for a sufficient amount of time can have up to L of oxygen stored in the lungs and the blood In this scenario, assuming mL/kg/min of oxygen consumption at rest, the average-sized adult can be apneic for approximately minutes before desaturation, compared with minute when preoxygenated with room air.7 Because preoxygenation in the office setting is typically performed with a nasal cannula, the FiO2 is expected to be approximately 32% at L/min flow, resulting in a considerably increased time to desaturation in an apneic event In the difficult airway scenario, the oxygen reserve provided by preoxygenation can be the difference between a satisfactory and a fatal outcome 128 www.ajlobby.com Mizukawa_Chap_11.indd 128 6/20/17 10:35 AM Supplemental Oxygen, Preoxygenation, and Oxygen Delivery Systems Oxygen delivery methods Supplemental oxygen can be delivered to the patient in a variety of ways The nasal cannula is ideal for oral surgery offices, as it will provide an adequate FiO2 while maintaining excellent access to the mouth and face The recommended nasal cannula flow rate is to L/min The FiO2 provided by a nasal cannula is a function of the flow rate and can be calculated with the following equation: FiO2 = 20 + (4 × flow rate in L/min) In this equation, 20 = baseline FiO2 of room air Therefore, FiO2 rises 4% for every L/min rise in flow rate.6 Another factor affecting the FiO2 of a nasal cannula is the inspiratory flow rate As peak inspiratory flow rates increase, a higher fraction of room air is inspired, diluting the oxygen inhaled from the cannula Nasal cannulas also have the ability to measure end-tidal CO2 (etCO2) The nasal hood is another means of delivering supplemental oxygen It is generally used when nitrous oxide is used It can be used for oxygen delivery alone, providing an FiO2 as high as 35% to 40% at a flow rate of L/min However, the bulk of the hood can compromise access to the oral cavity, especially the anterior maxilla Like the nasal cannula, nasal hoods are compatible with etCO2 sampling A number of face masks are used to deliver supplemental oxygen The standard face mask is connected to an oxygen source and can provide up to 60% FiO2 at a flow rate of 10 L/min.6 The mask has exhalation ports that clear exhaled air from the mask A minimum flow rate of L/min is required to clear exhaled air from the mask between breaths However, these ports also allow room air into the mask with inhalation Because room air mixes with the oxygen from the source during inhalation, the standard face mask is not capable of providing an FiO2 above 60%.8 A non-rebreather mask has a reservoir bag (with 600- to 1,000-mL capacity) for oxygen and one-way exhalation valves to maximize FiO2 A one-way valve is between the reservoir and the mask, preventing exhaled air from entering the reservoir, and another one-way exhalation port allows exhaled air to exit the mask but prevents room air from entering the mask on inhalation Thus, the FiO2 approaches 100% with a non-rebreather mask The drawback of any face mask is the inability to access the oral cavity and to deliver positive pressure ventilation When the patient’s own ventilatory effort is inadequate or when his or her airway is obstructed, positive pressure ventilation must be provided to ensure adequate movement of air The BVM is a face mask attached to a self-inflating bag, which, in turn, is attached to an oxygen reservoir A one-way valve prevents air flowing from the mask into the bag and from the bag into the reservoir Additionally, an air intake valve is adjacent to the reservoir that will allow room air to flow into the bag if the source has insufficient oxygen A safety valve also allows excess oxygen out of the reservoir bag if flow rates are excessive When squeezed, the bag produces positive pressure through the face mask, providing a theoretical FiO2 of 100% at high flow rates For a number of reasons, an FiO2 of 100% is usually not achieved For example, if the oxygen flow rate from the source is insufficient, some of the air that flows into the bag will be room air, decreasing the FiO2 Demand valve masks, such as the LSP Elder demand valve (Allied Healthcare), are also available These masks provide positive pressure via a face mask and high-pressure oxygen source This device can be very useful and convenient, as it does not require a reservoir bag It is relatively small in size, so it does not clutter the space around the patient as much as a BVM Also, the button triggering positive pressure is much closer to the mask and easier to trigger than squeezing the bag of a BVM Some demand valve masks have the trigger in a position such that, with a difficult airway, both hands can be on the mask and still trigger positive pressure ventilation The main drawback is that the positive pressure is generated by means of flow from the source If no flow is available due to an empty tank, the mask will not provide positive pressure The BVM will still provide positive pressure even without oxygen flow in an emergency situation It is recommended that every facility have a BVM 129 www.ajlobby.com Mizukawa_Chap_11.indd 129 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Airway Management Maneuvers The two most common techniques to open an obstructed airway are the head-tilt/chin-lift and jaw-thrust maneuvers Head tilt/chin lift This technique is used to restore the airway in cases of minor obstructions Normally, it is performed by pressing down on the patient’s forehead with one hand while pulling up on his or her chin with two to three fingers from the opposite hand (Fig 11-2) Fig 11-2 Head-tilt/chin-lift maneuver Jaw thrust This technique is used to restore the airway in cases of moderate to severe obstructions Generally, it is performed by standing behind the patient and placing your index and middle fingers in the area of the mandibular angles and pulling the patient’s mandible forward (Fig 11-3) a b Fig 11-3 (a and b) Two views of the jaw-thrust maneuver Airway Management Adjuncts If attempts to open the airway with manipulation of the mandible are unsuccessful, various airway adjuncts can be employed to restore airway patency.5,9–11 130 www.ajlobby.com Mizukawa_Chap_11.indd 130 6/20/17 10:35 AM Airway Management Adjuncts Nasopharyngeal airway Nasopharyngeal airways (NPAs), or nasal trumpets, are flexible silicone tubes that are inserted through the nostril and extended into the hypopharynx, preventing collapse of the oropharyngeal tissues against the posterior aspect of the pharynx They are available in various lengths and diameters The proper length NPA is selected by measuring from the patient’s earlobe to his or her nostril (Fig 11-4) The diameter should not be larger than the patient’s nostril After insertion, the tip of the NPA should extend beyond the soft palate and uvula The NPA has the advantage of being well tolerated in the conscious patient When properly positioned, the NPA can be used in conjunction with a BVM to more effectively ventilate the apneic and/or obstructed patient One disadvantage of NPAs is that they not always extend to the base of the tongue and not assist in maintaining patency of the airway inferior to the oropharynx, where most obstruction occurs Fig 11-4 Nasopharyngeal airway sizing Oropharyngeal airway Oropharyngeal airways (OPAs) are rigid plastic devices inserted through the mouth to the hypopharynx, preventing collapse of the tongue against the posterior portion of the pharynx The OPA is best inserted with the convex portion along the dorsal aspect of the tongue and, once fully inserted, rotated 180 degrees A consequence of the OPA is stimulation of the gag reflex; therefore, it will not be tolerated in the conscious patient As a result, it must be used in unconscious and unresponsive patients only Another disadvantage of the OPA includes worsening obstruction due to potential posterior displacement of the tongue if improperly placed OPAs come in two styles: (1) the Guedel, which has a lumen through which a suction catheter can be inserted to suction the hypopharynx, and (2) the Berman, which is designed like an I-beam in a cross section Similar to the NPA, a properly positioned OPA can be used in conjunction with a BVM to ventilate the nonbreathing and/or obstructed patient The proper size of an OPA is selected by measuring from the patient’s earlobe to the corner of his or her mouth (Fig 11-5) The flange should rest on the patient’s lips 131 www.ajlobby.com Mizukawa_Chap_11.indd 131 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Fig 11-5 Oropharyngeal airway sizing Laryngeal mask airway The laryngeal mask airway (LMA) is a supraglottic (ie, above the vocal cords) airway device that is shaped like a large endotracheal tube on the proximal end and connects to an elliptical mask on the distal end The LMA is designed to rest in the hypopharynx and cover the supraglottic structures However, because it is a supraglottic device, it is not considered a secure airway LMAs provide adequate protection from oral contents but are unable to prevent aspiration of gastric contents Several types of LMAs exist The proper size of the classic LMA is selected according to the weight of the patient (Table 11-1) Properly sized and appropriately positioned LMAs should provide an adequate seal up to 20 cm H20 The technique for placement of the LMA is outlined in Box 11-5.11 Table 11-1 Laryngeal mask airway sizes (classic type) Mask size B OX 11- Patient size Maximum cuff volume Neonates/infants up to kg up to mL 1½ Infants 5–10 kg up to mL Infants/Children 10–20 kg up to 10 mL 2½ Children 20–30 kg up to 14 mL Children 30–50 kg up to 20 mL Adults 50–70 kg up to 30 mL Adults 70–100 kg up to 40 mL Large adults > 100 kg up to 50 mL Placement of a laryngeal mask airway Select the proper size Check the LMA cuff for leaks Deflate the LMA cuff completely Apply water-soluble lubricant Hold the LMA like a pen at the junction between the tube and the mask Slide the LMA along and against the hard palate to avoid infolding of the tip Advance gently until resistance is met Inflate the cuff; if initial placement does not result in a good seal, reposition or attempt the next larger size Confirm proper position with end-tidal CO2 detector 132 www.ajlobby.com Mizukawa_Chap_11.indd 132 6/20/17 10:35 AM Airway Management Adjuncts The LMA has some shortcomings For example, it does not completely protect the trachea and lungs from aspiration The classic LMA also requires inflation of the cuff to provide an adequate seal and to permit positive pressure ventilation Not only is inflating the cuff an extra step, but if the cuff is damaged during insertion, the LMA is rendered useless The tip of the LMA can be malpositioned either anteriorly or posteriorly, compromising the seal around the glottis The LMA tube is soft and is easily obstructed if the patient bites the tube Finally, the LMA also has no capability for the passage of an orogastric tube if gastric distension has resulted during BVM ventilation efforts Over time, newer supraglottic devices, based on the classic LMA design, have emerged Table 11-2 provides a comparison of the features of three of these devices that overcome the shortfalls of the classic LMA.12 Table 11-2 Comparison of the classic LMA and other supraglottic devices LMA Gastric venting Inflatable cuff Rigid bite block Intubation access Reinforced tip No Yes No No No Classic Supreme Yes Yes Yes No No AuraGain (Ambu) Yes Yes Yes Yes Yes I-Gel (Intersurgical) Yes No Yes No Yes Endotracheal tubes The endotracheal tube is the gold standard for airway management as it provides a patent airway, protects the trachea from aspiration, and allows for efficient positive pressure ventilation Endotracheal tubes are sized based on the inside diameter of the tube (Table 11-3) Pediatric sizing is much more variable because of the wide range of body mass in children aged to 18 years A basic formula for estimating the endotracheal tube size for pediatric patients is: Tube size = ([Age in y] / 4) + Table 11-3 Endotracheal tube sizes Age (y) Weight (kg) Inner diameter (mm)* Depth at lip (cm)† Miller Macintosh 12 4.5 12 2 14 4.5 13 2 16 5.0 14 2 20 5.5 15 2 24 6.0 16 2 10 30 6.5 17 2 12 38 7.0 18 2, 2, 14 50 7.0 19 2, 3, 18 + Woman Man Any Any 7.0 8.0 20 21 2, 3, 2, 3, 3, *For pediatric patients, inner diameter is calculated as ([age in y] / 4) + † For pediatric patients, depth is calculated as ([age in y] / 2) + 12 Endotracheal tube placement is usually facilitated by direct laryngoscopy with a manual (eg, Macintosh or Miller) or video-enhanced laryngoscope Flexible stylets (bougies) and Magill forceps are employed to further facilitate endotracheal tube placement Confirmation of endotracheal positioning should be performed by auscultation of the lung fields and the epigastrium and confirmation of etCO2 The cuff of the endotracheal tube should be inflated once the position is confirmed The recommended pressure of the cuff is 20 to 30 cm H2O Pressure in excess of 20 to 30 cm H2O will compromise capillary flow of the tracheal mucosa 133 www.ajlobby.com Mizukawa_Chap_11.indd 133 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Emergency Surgical Airway Preventable deaths from airway problems in the oral surgery office setting are the result of one or more of the following circumstances: • Failure to recognize a compromised airway and the need for airway rescue • Failure to properly equip the office for airway rescue • Inadequate office personnel preparation and rehearsal for airway rescue • Failure or delay to establish a patent airway • Failure to recognize an incorrectly placed airway The loss of a patient’s ability to maintain sufficient spontaneous ventilation to support a hemoglobin oxygen saturation of at least 90% is associated with hypoxemia (arterial partial pressure of oxygen = 60 mm Hg) and must be managed with ventilation assistance or control, depending on the severity of the apnea This event is marked by loss of respiratory effort and a flat etCO2 waveform In the most common situation encountered in the surgical office, apnea will be short lived and, at most, temporary ventilatory assistance will be necessary with a BVM and supplemental oxygen In contrast, airway obstruction with or without ventilatory drive can cause a sudden and complete inability to ventilate and oxygenate a patient during the course of anesthetic administration This too will be marked by a flat etCO2 waveform If ventilatory drive is intact, obstruction will also be marked by respiratory effort with sternal retractions and use of accessory muscles Simple measures such a chin lift or jaw thrust will often overcome the obstruction and restore airway patency Airway adjuncts such as NPAs or OPAs may help overcome supraglottic airway obstruction If laryngospasm is suspected, deep oropharyngeal suctioning and positive pressure BVM ventilation should be attempted Succinylcholine should be promptly administered after failed BVM ventilation Regardless of the reason for compromised air exchange, if the Spo2 cannot be maintained at 90% or above with BVM assistance or control, cerebral hypoxia and worse, cerebral anoxia, will result This critical condition must be rapidly recognized and managed with endotracheal intubation If the trachea cannot be intubated, the surgeon must quickly secure a surgical airway Although an attempt at an alternate supraglottic airway might rescue a patient from progressive hypoxia, critical time may be lost in attempts to secure an alternate airway that would be more wisely spent initiating a surgical airway Examples of alternate supraglottic airways include LMA, laryngeal tube airway, multilumen esophageal airway, and others Use of a supraglottic device might be justified while a second staff member prepares the surgical airway supplies Surgical cricothyrotomy is the rescue surgical airway of choice in the failed adult airway It is an easier, safer, and quicker alternative to tracheostomy Cricothyrotomy is indicated whenever a patient cannot be oxygenated and cannot be intubated nasally or orally As noted previously, a supraglottic device may be attempted as a rescue measure while the staff prepares for cricothyrotomy In the usual oral surgery office setting, no contraindications to cricothyrotomy are presented However, cricothyrotomy is not recommended in children because of the greater risk of subglottic stenosis Although the safe age for cricothyrotomy in children is not known, cricothyrotomy is not recommended in children aged < 12 years The preferred surgical airway in children is transtracheal ventilation, discussed in the needle cricothyrotomy section 134 www.ajlobby.com Mizukawa_Chap_11.indd 134 6/20/17 10:35 AM Emergency Surgical Airway Surgical cricothyrotomy technique Performance of cricothyrotomy requires knowledge of the local surgical anatomy (Fig 11-6) Hyoid bone Thyrohyoid membrane Median thyrohyoid ligament Lateral thyrohyoid ligament Superior cornu of thyroid cartilage Laryngeal incisure Thyroid cartilage Superior laryngeal nerve and artery Oblique line Cricothyroid muscle Median cricothyroid ligament Conus elasticus Inferior cornu of thyroid cartilage Cricothyroid joint Cricoid cartilage Trachea Fig 11-6 Cricothyrotomy anatomy The cricothyroid membrane (median cricothyroid ligament) is bordered by thyroid cartilage above, cricoid cartilage below, and the cricothyroid muscles laterally The dimensions of the cricothyroid membrane is 20 to 30 mm horizontally and to 10 mm vertically The isthmus of the thyroid is usually situated at the junction of the cricoid cartilage and the first tracheal ring, below the site of tracheal entry for cricothyrotomy Of note, a pyramidal lobe of the thyroid gland may lie over the cricoid cartilage or the cricothyroid membrane and be subject to injury and bleeding with cricothyrotomy Notable vasculature in this area (Fig 11-7) is the midline anterior jugular vein and superior thyroid artery and veins The cricothyroid artery and vein course transversely across the cricothyroid membrane at the superior aspect of the membrane Hyoid bone Superior thyroid artery and vein Cricothyroid artery and vein Thyroid cartilage Cricothyroid membrane Cricoid cartilage Cricothyroid muscle Thyroid gland Internal jugular vein Tracheal rings Common carotid artery Fig 11-7 Vasculature of the cricothyroid region 135 www.ajlobby.com Mizukawa_Chap_11.indd 135 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies All instruments and supplies necessary for cricothyrotomy should be immediately available and assembled in a surgical airway rescue kit (Box 11-6) It is critical that office staff has hands-on familiarity with the airway rescue kit and that they have regular mock airway rescue exercises B OX 11- • • • • • • • Adult cricothyrotomy instruments/supplies No 11 scalpel bade Bougie Tracheal hook Curved hemostat and/or Trousseau dilator No 6.0 cuffed endotracheal tubes No 4, cuffed Shiley (Covidien) tracheostomy tube 10-mL syringe Before initiating cricothyrotomy, clinicians should palpate the the thyroid cartilage, cricoid cartilage, and intervening cricothyroid membrane The clinician’s thumb and middle finger are used to stabilize the thyroid cartilage and maintain reference to the midline of the neck, whereas the index finger palpates the cricothyroid space (Fig 11-8a) Extension of the patient’s neck will aid in the identification of these landmarks Fig 11-8a In standard surgical cricothyrotomy, the thyroid cartilage is straddled with the thumb and middle finger The cricothyroid space is palpated with the index finger If time permits, the anterior neck is sterilely prepped If the patient is conscious and time allows, infiltration with lidocaine with 1:100,000 epinephrine at the planned skin incision and cricothyroid membrane can be performed A number of cricothyrotomy techniques are available The standard technique uses a vertical skin incision and a transverse cricothyroid membrane incision (Figs 11-8b and 11-8c) If the anterior neck landmarks are difficult to identify (because of obesity, short neck, neck swelling, etc.), the vertical skin incision is preferred With the thyroid cartilage stabilized, a 2- to 3-cm vertical skin incision is made at the level of the cricothyroid membrane through the skin and subcutaneous tissue If the neck anatomy is easily palpable, the surgeon may omit the vertical incision and make a single horizontal incision The index finger can be used to dilate the incision, bluntly dissect the tissue down to the cricothyroid membrane, and confirm the location of the cricothyroid membrane A 1-cm horizontal incision is then made at the inferior (ie, below the course of the cricothyroid artery and vein) aspect of the cricothyroid membrane into the tracheal lumen (see Fig 11-8c) The tracheal lumen is confirmed with the index finger The opening can then be dilated with the index finger, a curved hemostat, or a Trousseau dilator (Fig 11-8d) A tracheal hook may also be inserted to elevate the thyroid cartilage (Fig 11-8e) To facilitate endotracheal placement of the endotracheal 136 www.ajlobby.com Mizukawa_Chap_11.indd 136 6/20/17 10:35 AM Emergency Surgical Airway tube, a bougie may be passed into the tracheal lumen to guide tube insertion A 6.0 endotracheal tube or small tracheostomy tube (Shiley no or 6) is passed over the bougie and inserted into the trachea with a twisting motion, after which the bougie is withdrawn (Fig 11-8f) Correct tube placement is confirmed with auscultation of bilateral symmetrical breath sounds, absence of gastric sounds, and, if possible, with detection of etCO2 The tube is then secured to the neck Pressure is applied to initially address inevitable bleeding Fig 11-8b A vertical incision is made through skin and deep cer- Fig 11-8c The trachea is entered with a transverse incision vical fascia through the cricothyroid membrane just above the cricoid cartilage to avoid the cricoid artery and/or vein Fig 11-8d The cricothyrotomy is dilated with the index finger, a Fig 11-8e A trachea hook may be placed to elevate and stabilize the thyroid cartilage hemostat, nasal speculum, or Trousseau trachea dilator (shown) Fig 11-8f A no endotracheal tube or tracheostomy tube (shown) is placed 137 www.ajlobby.com Mizukawa_Chap_11.indd 137 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies The standard surgical cricothyrotomy technique is summarized in Box 11-7 B OX 11-7 Surgical cricothyrotomy technique Position patient with hyperextension of his or her neck Prepare the patient’s skin and apply local anesthesia Stabilize the thyroid cartilage between the thumb and middle finger of your nondominant hand, and palpate the patient’s cricothyroid membrane with your index finger With your dominant hand, make a 3- to 4-cm midline vertical incision from the inferior portion of the thyroid cartilage to the inferior portion of the cricoid cartilage Make a horizontal incision over the cricothyroid membrane Use scissors or a hemostat to dilate the cricothyroid opening Place a pediatric uncuffed tracheostomy tube or a Shiley No tracheotomy tube Attach a bag or anesthesia circuit, and check for end-tidal CO2 Secure the tube to the patient’s skin An alternative to the standard cricothyrotomy is the so-called “four-step method.” This technique omits the vertical skin incision and consists of a single horizontal incision through the skin and cricothyroid membrane as follows: Palpate the cricothyroid membrane (see Fig 11-8a) Make a horizontal skin incision through both the skin and the cricothyroid membrane Place the tracheal hook to elevate the cricoid cartilage (see Fig 11-8e) Insert the endotracheal or tracheostomy tube This step can be modified by first inserting a bougie as a guide for endotracheal or tracheotomy tube insertion (see Fig 11-8f) Commercially available cricothyrotomy kits are available that use the Seldinger technique With this technique, an 18-gauge needle is inserted into the trachea, followed by a guide wire and a dilator-airway catheter The median time required for experienced clinicians to perform cricothyrotomy in unfixed cadavers is 73 seconds, whereas the median time required for inexperienced clinicians is 180 seconds.13 In a study using fixed cadavers, the mean time required to perform the standard cricothyrotomy was 133 seconds, and for the 4-step method, it was 43 seconds.14 Needle cricothyrotomy technique Needle cricothyrotomy (or jet ventilation) involves insertion of a large-bore needle through the cricothyroid membrane into the trachea to provide temporary supplemental oxygen until a definitive airway can be placed Needle cricothyrotomy provides time for tracheal intubation on an urgent rather than emergency basis After sterile preparation of the anterior part of the patient’s neck, the cricothyroid membrane is punctured with a 12- to 14-gauge (for adults) or 16- to 18-gauge (for children) intravenous (IV) catheter The needle is withdrawn, and the catheter is connected to a 15 L/min oxygen supply using a Y-connector or dedicated jet ventilation valve to provide intermittent oxygen insufflation Alternatively, a side hole is cut in the oxygen tubing that may be intermittently occluded and released to control the flow of oxygen into the IV catheter Oxygen is insufflated for second and then discontinued for seconds, providing brief bursts of supplemental oxygen This method will provide 30 to 45 minutes of oxygenation, buying critical time for securing a definitive airway, but it is limited by the accumulation of CO2 It must be used cautiously with suspected complete glottic obstruction, as barotrauma may occur Lower oxygen flow rates (5 to L/min) are recommended with complete glottic obstruction 138 www.ajlobby.com Mizukawa_Chap_11.indd 138 6/20/17 10:35 AM Ventilation/Airway Urgencies and Emergencies Complications Complication rates with cricothyrotomy vary greatly depending on the clinical scenario, the location of the procedure, and the clinician’s level of training and experience (Box 11-8) B OX 11- Complications of cricothyrotomy Early • Bleeding • Laceration thyroid, cricoid cartilage, trachea • Unintentional tracheostomy • Placement of endotracheal or tracheostomy tube in a false track (ie, extratracheal location) • Pneumothorax/pneumomediastinum • Subcutaneous emphysema • Perforation of posterior trachea • Tracheal transection • Laryngeal fracture • Recurrent laryngeal nerve injury • Vocal cord injury • Esophageal injury Late • Infection • Dysphonia • Laryngeal or tracheal stenosis The oral and maxillofacial surgeon is rarely exposed to situations that call for an emergency surgical airway However, when the surgeon is faced with the acute situation where the hypoxic patient cannot be ventilated or intubated, the surgical cricothyrotomy, accomplished rapidly and correctly, can be lifesaving Skill acquisition should include training with mannequins or cadavers for at least five attempts or until the cricothyrotomy time can be reduced to 40 seconds.15 Decay of acquired skills should be addressed with regular skill rehearsal In addition, the office surgical team should rehearse the treatment of patients who cannot be ventilated or intubated Ventilation/Airway Urgencies and Emergencies Hyperventilation Hyperventilation is defined as an increase in frequency or volume of ventilation The etiology of hyperventilation is usually multifactoral and includes both voluntary and involuntary ventilation controls Anxiety, hysteria, and/or post anesthesia dysphoria can result in hyperventilation and are under voluntary control The involuntary controls of respiration are mediated by peripheral chemoreceptors that are activated by hypoxemia and central chemoreceptors, which are in turn activated in the setting of hypercarbia Hyperventilation quickly results in hypocarbia and respiratory alkalosis, triggering cerebral vasoconstriction, hypocalcemia, and leftward shift of the oxyhemoglobin curve These physiologic changes lead to the clinical manifestations typically associated with hyperventilation, including peripheral sensory alterations/paresthesias, dizziness, confusion, visual impairment, tetany, carpopedal spasms, and seizures Treatment of the anxious, dysphoric hyperventilating patient includes verbal reassurance Anxiolytics may be helpful Patients can also be instructed to breath into a plastic bag Rebreathing expired CO2 will minimize hypocarbia and the symptoms associated with hyperventilation Hyperventilation in the absence of anxiety and/or dysphoria should raise the suspicion of hypoxia 139 www.ajlobby.com Mizukawa_Chap_11.indd 139 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies Hypoventilation/apnea Hypoventilation is defined as a decrease in frequency or volume of respirations Apnea is the complete absence of ventilation Both processes can lead to hypercapnia and hypoxemia It is well known that respiratory depression is an adverse effect of narcotics, benzodiazepines, barbiturates, and propofol Additionally, these drugs, in combination with antihistamines, antipsychotics, or illicit drugs, can intensify hypoventilation Management of hypoventilation/apnea depends on the level of sedation/anesthesia that is intended Apnea is a consequence of general anesthesia If a lighter plane of anesthesia is desired, patient stimulation might be required to incentivize breathing Positive pressure ventilation with or without airway adjuncts may be necessary to maintain oxygen levels until the patient is able to breathe spontaneously Drug reversal agents can also be used Supraglottic obstruction Airway obstruction is one of the most common anesthetic emergencies, and usually, the obstruction is supraglottic Obstruction may be partial or complete Partial obstruction is characterized by noisy breathing/stridor and exaggerated ventilatory effort Complete airway obstruction is associated with complete absence of breath sounds and exaggerated, paradoxical chest and abdominal movements The most common cause of a supraglottic obstruction is tongue muscle relaxation with subsequent posterior displacement and obstruction of the posterior pharynx Other causes of obstruction include aspiration of foreign bodies such as emesis, avulsed or fractured teeth, and surgical instruments Initial management of airway obstruction includes a chin-lift or jaw-thrust maneuver Additionally, grasping the tongue and pulling it forward with gauze, an instrument, or a suture can also open the airway If these maneuvers fail, airway adjuncts, such as OPA and NPA, should be used If these are ineffective, a supraglottic airway device should be attempted Should the device fail to establish airway patency, endotracheal intubation should be attempted Finally, if endotracheal intubation fails, a surgical airway must be immediately established With regard to foreign body obstruction, the Magill forceps with or without the aid of a laryngoscope should be used to retrieve the foreign body Emesis and aspiration Emesis in a sedated/anesthetized patient can lead to aspiration of gastric contents Liquid aspiration can result in partial or complete obstruction, laryngospasm, bronchospasm, hypoxemia, hypotension, and atelectasis, whereas aspiration of solid material can rapidly lead to obstruction, asphyxia, and death.1 Physical damage to the lung parenchyma due to the acidic nature of gastric content is another risk Obesity, history of a hiatal hernia, pregnancy, and gastroesophageal reflux disease increase the risk of aspiration Oral intake restrictions before anesthesia administration include no solids or milk products for hours and no clear liquids for hours before anesthesia However, other conditions warrant special considerations, as they tend toward gastroparesis and increased gastric emptying times These include diabetes mellitus, opioid use, and anxiety The management of vomiting or regurgitation in a sedated patient is demonstrated in Box 11-9.16 140 www.ajlobby.com Mizukawa_Chap_11.indd 140 6/20/17 10:35 AM Ventilation/Airway Urgencies and Emergencies B OX 11-9 Management of vomiting and aspiration in the sedated patient If emesis is observed and aspiration is suspected, activate EMS Respiratory consequences of aspiration can be rapid and fatal Place the patient in the Trendelenburg position This position uses gravity in keeping vomitus in the pharynx and away from the lungs Turn the patient so he or she is positioned with the right side down (the most likely location of debris will be the right mainstem of the bronchus) Considering the anatomy of the stomach, the right lateral decubitus position also promotes the gastric contents to remain toward the pylorus and away from the lower esophageal sphincter Suction/remove any debris from the oral cavity and hypopharynx Apply 100% oxygen via a face mask, and, if the patient shows signs of respiratory distress, use positive-pressure ventilation If the patient shows any signs of bronchospasm, manage it accordingly (see Box 11-11) Intubate the patient if signs of laryngospasm or respiratory failure are present Corticosteroid use in cases of aspiration are not indicated, and prophylactic use of antibiotics are not indicated in cases of aspiration unless the aspirate is purulent or if the patient develops signs of pneumonia EMS, emergency medical services Laryngospasm Laryngospasm (or glottic obstruction) is a protective mechanism in which the intrinsic muscles of the larynx adduct the vocal cords, thus preventing irritants such as saliva, blood, irrigant, aspirate, or solid material from entering the trachea The duration and intensity of a laryngospasm will vary with the stimulus and the depth of anesthesia Patients will exhibit paradoxical chest and abdominal movements if they are spontaneously breathing Partial or incomplete laryngospasm is characterized by a high-pitched stridor, whereas airway silence due to the total absence of air movement is encountered in complete laryngospasm Complete laryngospasm must be differentiated from apnea, complete supraglottic obstruction, and bronchospasm The consequences of laryngospasm include hypoxemia, bradycardia, and, ultimately, cardiac arrest In the breathing patient, complete obstruction may lead precipitously to negative pressure pulmonary edema as the patient attempts vigorous ventilatory effort against a closed glottis Prevention is the best management for laryngospasm An oropharyngeal screen to keep foreign material out of the airway, as well as proper suctioning techniques, should be routinely used in the patient undergoing deep sedation or general anesthesia When laryngospasm is suspected, management should be urgently but methodically initiated (Box 11-10).17 141 www.ajlobby.com Mizukawa_Chap_11.indd 141 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies B OX 11-10 Management of laryngospasm Stabilize the surgical site Use pharyngeal suction with a Yankauer suction tip Reposition the patient as follows: head tilt, chin lift, jaw thrust, and tongue traction If no break is observed, use positive pressure ventilation with 100% oxygen via a full face mask If no break is observed, deepen the anesthetic with a bolus of a hypnotic agent such as propofol If no break is observed, administer an IV dose of succinylcholine at 0.1 to mg/kg (10 to 20 mg) If a second dose is necessary, increase it to a full intubating dose of to mg/kg Consider IV atropine (0.5 mg) to prevent bradycardia when multiple doses of succinylcholine are used For the pediatric patient with no IV access, mg/kg of succinylcholine can be given intramuscularly and be expected to produce a rapid response If the patient has a history of malignant hyperthermia, or a family history of malignant hyperthermia, administer IV rocuronium, 0.6 to 12 mg/kg Intubate the patient or manually ventilate until the effects of the paralytic are gone Bronchospasm Bronchospasm is a reflex bronchiolar smooth muscle constriction and increased airway mucous production that can be centrally mediated or locally mediated in response to airway irritation Clinical manifestations include expiratory wheezing and an increase in airway resistance This problem is uncommon in the oral and maxillofacial surgery office–based anesthesia setting However, bronchospasm can prevent adequate ventilation, even with a definitive airway in place Common causes of bronchospasm include asthma, anaphylaxis, aspiration of gastric contents or a foreign body, and physical irritation of the upper airway Prevention includes identification of risk factors such as stress, obesity, recent exposure to respiratory triggers (eg, smoke, allergens, weather changes), recent upper respiratory infection, low socioeconomic status, gastroesophageal reflux disease, and physical airway stimulation (ie, cough) Management of acute bronchospasm includes β-adrenergic agonist bronchodilator therapy, including parenteral epinephrine, especially if an allergic trigger is suspected (Box 11-11) In the sedated patient, bronchodilator therapy may have to be administered in conjunction with a BVM device or endotracheal intubation Without prompt and effective bronchodilator therapy, severe hypoxemia and cardiorespiratory arrest ensues 142 www.ajlobby.com Mizukawa_Chap_11.indd 142 6/20/17 10:35 AM Summary B OX 11-11 Management of acute bronchospasm in a sedated or anesthetized patient If the patient shows signs of bronchospasm, such as hypoxemia, wheezing, and respiratory distress, administer 100% oxygen via a face mask Consider activating EMS Albuterol can be administered via the face mask, resolving mild bronchospasm If bronchospasm persists, give 0.3 to 0.5 mg of epinephrine (1:1,000 solution) subcutaneously If you suspect anaphylaxis due to hypotension, administer 10 to 20 µg of IV epinephrine, titrated to effect If the patient becomes hypoxemic, deepen the anesthetic and intubate If you cannot intubate, place an LMA or other supraglottic device Use positive pressure ventilation with 100% oxygen Consider albuterol via the endotracheal tube Continue epinephrine dosing as outlined above until EMS arrives If repeated doses of epinephrine are used, be prepared to manage both hypertension and arrhythmias associated with epinephrine In the spontaneously breathing patient with bronchospasm, carefully monitor respiratory effort With time, increased ventilator effort will lead to fatigue of the respiratory musculature and, ultimately, respiratory distress In this case, intubate the patient to maintain adequate ventilation and oxygenation EMS, emergency medical services Summary Maintaining a patent airway and adequate ventilation is paramount in an anesthetized patient A thorough knowledge of the airway anatomy is critical in troubleshooting airway problems The anesthesia provider must be familiar with all of the possible airway urgencies and emergencies that can occur and be able to correctly diagnose these problems when they occur Additionally, the provider must be able to effectively and efficiently manage the compromised airway In 2013, the American Society of Anesthesiologists updated its recommendations on management of the difficult airway.3 These recommendations include the difficult airway algorithm (Fig 11-9) Although this algorithm may not completely pertain to office-based anesthesia in that endotracheal intubation is not generally the primary means of airway management in this setting, it succinctly identifies a decision tree that the practitioner can follow when encountering a difficult airway situation The foundational principles of airway management outlined in this chapter can prevent moribidity and mortality from airway events associated with office-based anesthesia 143 www.ajlobby.com Mizukawa_Chap_11.indd 143 6/20/17 10:35 AM 11 • Management of Airway Urgencies and Emergencies American Society of Anesthesiologists DIFFICULT AIRWAY ALGORITHM Assess the likelihood and clinical impact of basic management problems: • Difficulty with patient cooperation or consent • Difficult mask ventilation • Difficult supraglottic airway placement • Difficult laryngoscopy • Difficult intubation • Difficult surgical airway access Actively pursue opportunities to deliver supplemental oxygen throughout the process of difficult airway management Consider the relative merits and feasibility of basic management choices: • Awake intubation versus intubation after induction of general anesthesia • Noninvasive technique versus invasive techniques for the initial approach to intubation • Video-assisted laryngoscopy as an initial approach to intubation • Preservation versus ablation of spontaneous ventilation Develop primary and alternative strategies: AWAKE INTUBATION INTUBATION AFTER INDUCTION OF GENERAL ANESTHESIA Invasive airway access Airway approached by noninvasive intubation ‡ Initial intubation attempts successful* Cancel case Consider feasibility of other options† FROM THIS POINT ONWARDS CONSIDER: Calling for help Returning to spontaneous ventilation Awakening the patient FAIL Succeed* Initial intubation attempts UNSUCCESSFUL Invasive airway access‡ FACE MASK VENTILATION ADEQUATE FACE MASK VENTILATION NOT ADEQUATE CONSIDER/ATTEMPT SGA SGA ADEQUATE* NONEMERGENCY PATHWAY Ventilation adequate, intubation unsuccessful IF BOTH FACE MASK AND SGA VENTILATION BECOME INADEQUATE Alternative approaches to intubation§ Successful intubation* FAIL after multiple attempts Invasive airway access*‡ Consider feasibility of other options† SGA NOT ADEQUATE OR NOT FEASIBLE EMERGENCY PATHWAY Ventilation not adequate, intubation unsuccessful Call for help Emergency noninvasive airway ventilation¶ Successful ventilation* FAIL Awaken the patient|| Emergency invasive airway access*† *Confirm ventilation, tracheal intubation, or SGA placement with exhaled carbon dioxide Other options include (but are not limited to): surgery utilizing face mask or SGA anesthesia (eg, LMA, ILMA, laryngeal tube), local anesthesia infiltration, or regional nerve blockade Pursuit of these options usually implies that mask ventilation will not be problematic Therefore, these options may be of limited value if this step in the algorithm has been reached via the Emergency Pathway || Invasive airway access includes surgical or percutaneous airway, jet ventilation, and retrograde intubation ¶ † ‡ Alternative difficult intubation approaches include (but are not limited to): video-assisted laryngoscopy, alternative laryngoscope blades, SGA (eg, LMA or ILMA) as an intubation conduit (with or without fiberoptic guidance), fiberoptic intubation, intubating stylet or tube changer, light wand, and blind oral or nasal intubation § Consider repreparation of the patient for awake intubation or canceling surgery Emergency noninvasive airway ventilation consists of an SGA Fig 11-9 American Society of Anesthesiologists’ difficult airway algorithm.3 SGA, supraglottic airway; ILMA, intubating LMA 144 www.ajlobby.com Mizukawa_Chap_11.indd 144 6/20/17 10:35 AM References References American Association of Oral and Maxillofacial Surgeons Office Anesthesia Evaluation Manual, ed Chicago: American Association of Oral and Maxillofacial Surgeons, 2012 Metzner J, Posner KL, Domino KB The risk and safety of anesthesia at remote locations: The US closed claims analysis Curr Opin Anaesth 2009;22:502–508 Apfelbaum JL, Hagberg CA, Caplan RA, et al; American Society of Anesthesiologists Task Force on Management of the Difficult Airway Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway Anesthesiology 2013;118:251–270 Watson CB Respiratory complications associated with anesthesia Anesthesiol Clin North America 2002;20:513–537 Anderson J, Klock PA Jr Airway management Anesthesiol Clin 2014;32:445–461 Becker DE, Rosenberg MB, Phero JC Essentials of airway management, oxygenation, and ventilation, part 1: Basic equipment and devices Anesthesia Prog 2014;61:78–83 Weingart SD, Levitan RM Preoxygenation and prevention of desaturation during emergency airway management Ann Emerg Med 2012;59:165–175.e1 Marino PL Oxygen therapy In: Marino PL Marino’s The ICU Book, ed Philadelphia: Lippincott Williams & Wilkins, 2014:427–446 10 Luba K, Cutter TW Supraglottic airway devices in the ambulatory setting Anesthesiol Clin 2010;28:295–314 11 Pollack CV Jr The laryngeal mask airway: A comprehensive review for the emergency physician J Emerg Med 2001;20:53–66 12 Becker DE, Rosenberg MB, Phero JC Essentials of airway management, oxygenation, and ventilation, part 2: Advanced airway devices: Supraglottic airways Anesthesia Prog 2014;61:113–118 13 Mutzbauer TS, Munz R, Helm M, Lampl LA, Herrmann M Emergency cricothyrotomy—Puncture or anatomical preparation? Peculiarities of two methods for emergency airway access demonstrated in a cadaver model [in German] Anaesthesist 2003;52:304–310 14 Holmes JF, Panacek ED, Sakles JC, Brofeldt BT Comparison of cricothyroidotomy techniques: Standard method versus rapid 4-step technique Ann Emerg Med 1998;32:442–446 15 Wong DT, Prabhu AJ, Coloma M, Imasogie N, Chung FF What is the minimum training required for successful cricothyroidotomy? A study in mannequins Anesthesiology 2003;98:349–353 16 Kluger MT, Visvanathan T, Myburgh JA, Westhorpe RN Crisis management during anaesthesia: Regurgitation, vomiting, and aspiration Qual Saf Health Care 2005;14:e4 17 Visvanathan T, Kluger MT, Webb RK, Westhorpe RN Crisis management during anaesthesia: Laryngospasm Qual Saf Health Care 2005;14:e3 Cooper RM Strengths and limitations of airway techniques Anesthesiol Clin 2015;33:241–255 145 www.ajlobby.com Mizukawa_Chap_11.indd 145 6/20/17 10:35 AM www.ajlobby.com Mizukawa_Chap_11.indd 146 6/20/17 10:35 AM CHAPTER 12 Medical Emergencies Samuel J McKenna, dds, md Nicholas Piemontesi, dmd, md www.ajlobby.com Mizukawa_Chap_12.indd 147 6/26/17 2:23 PM 12 • Medical Emergencies Office-based anesthesia has grown exponentially over the past decade, with approximately 10 million procedures performed yearly in the United States.1 There are many advantages to office-based surgery, including cost control; office-based surgery is preferred by patients over similar procedures performed in the hospital2; and office-based surgery is preferred by surgeons because of increased efficiency, consistency, and convenience.3 A prospective study of 34,191 American Society of Anesthesiologists class I or II patients undergoing oral and maxillofacial surgical procedures, with the surgeon being both the proceduralist and the primary anesthesia provider in 96% of cases, demonstrated a complication rate of 1.3%.4 In this study, 72% of the patients received deep sedation or general anesthesia Complications included vomiting during induction (0.1%), laryngospasm or bronchospasm (0.3%), cardiac dysrhythmia (0.1%), syncope (0.1%), prolonged recovery (0.2%), and peripheral vascular injury (0.2%) The rate of hospitalization was 5.8 per 100,000 procedures Oral and maxillofacial surgeons have pioneered safe office-based surgery/anesthesia and are highly aware of the critical elements of providing safe ambulatory anesthetic services These elements of safety include a careful pre-anesthetic assessment, personalized anesthetic care that takes patient expectations into account, consideration of the magnitude of the surgical procedure, and, most importantly, careful assessment and consideration of comorbid conditions In addition to the critical importance of the pre-anesthetic evaluation and thorough knowledge of the patient, it is imperative that the clinical staff be trained in the recognition and management of intraoperative and perioperative anesthetic medical sentinel events and emergencies Besides standard educational activities, clinical staff training should include regular medical emergency drills with clear and consistent staff assignments and responsibilities in the management of office medical emergencies This chapter discusses contemporary measures to manage life-threatening medical emergencies occurring in the office in the perioperative period Malignant Hyperthermia Pathophysiology Malignant hyperthermia is characterized by a hypermetabolic state involving skeletal muscle, precipitated by certain inhalational anesthetics (eg, halothane, isoflurane, sevoflurane, desflurane, enflurane) and depolarizing neuromuscular blocking agents (eg, succinylcholine) The incidence of malignant hyperthermia is in 100,000 anesthetic administrations.5 Malignant hyperthermia is an autosomal dominant disease commonly involving mutations in the ryanodine receptor gene (RYR1) In the presence of a precipitant, the abnormal RYR1 leads to sustained release of calcium from the sarcoplasmic reticulum Sustained intracellular calcium release leads to sustained muscle contractions, increased anaerobic and aerobic metabolism, heat generation, and, ultimately, muscle cell hypoxia and death Myocyte death leads to the release of intracellular products such as myoglobin and potassium.6 Diagnosis Early changes in physiologic parameters in patients with malignant hyperthermia (Box 12-1) include hypercarbia, tachypnea, sinus tachycardia, masseter muscle rigidity, and generalized muscle rigidity Late changes variably include electrocardiographic (ECG) changes related to hyperkalemia, ventricular arrhythmias, metabolic acidosis, hyperthermia, myoglobinuria, acute renal failure, and coagulopathy (secondary to disseminated intravascular coagulation) It is important to consider other conditions that may mimic malignant hyperthermia, including infection/ sepsis, use of drugs (stimulants), thyroid storm, inadequate anesthesia/analgesia, serotonin syndrome, neuroleptic malignant syndrome, iatrogenic hyperthermia, and pheochromocytoma.7 148 www.ajlobby.com Mizukawa_Chap_12.indd 148 6/26/17 2:23 PM Malignant Hyperthermia BOX 12-1 • • • • • • etCO2, Clinical features that suggest malignant hyperthermia Increased etCO2 level (> 55 mm Hg) Tachycardia Tachypnea Masseter muscle rigidity, generalized muscle rigidity ECG changes related to hyperkalemia Hyperthermia end-tidal carbon dioxide Management Management of malignant hyperthermia (Box 12-2) involves first notifying emergency medical services (EMS), discontinuing use of any triggering agents, and hyperventilating the patient with 100% oxygen Dantrolene, a muscle relaxant that inhibits additional calcium release, is administered Hyperthermia is addressed with cooling measures (ice application, chilled saline gastric lavage, etc) Treatment may include administration of sodium bicarbonate for the management of metabolic acidosis and hyperkalemia After normalization of end-tidal carbon dioxide (etCO2), tachycardia, hyperthermia, and acidosis, the patient’s urine output and renal function should be carefully monitored.8 BOX 12-2 Management of malignant hyperthermia8 Notify EMS For additional advice, contact the hotline of the Malignant Hyperthermia Association of the United States at 1-800-644-9737 (in United States) or 1-315-464-7079 (outside United States) Discontinue use of the triggering substance Hyperventilate with 100% oxygen at 10 L/min to remove volatile anesthetic agent and decrease etCO2 Administer intravenous (IV) dantrolene 2.5 mg/kg through a large-bore IV line Repeat every minutes until normalization of etCO2, decreased muscle rigidity, and/or reduction in heart rate occurs or total dose reaches 10 mg/kg Administer sodium bicarbonate to mEq/kg IV push over to 10 minutes to manage acidosis and alkalinize urine Start cooling the patient with cold saline infusion, ice application, and chilled saline gastric lavage when core temperature is > 39°C; stop cooling when core temperature is < 38°C Determine the degree of metabolic acidosis Obtain blood gas test results (venous or arterial) Administer sodium bicarbonate if the patient has base excess of more than −8 mEq/L (1 to mEq/kg; maximum dose 50 mEq) Correct hyperkalemia (blood potassium level > 5.9 mEq/L or hyperkalemia-related ECG changes present) with the following: a Furosemide: 0.5 to 1.0 mg/kg IV, maximum dose 20 mg b Sodium bicarbonate: to mEq/kg IV push over to 10 minutes; not give in the same IV line as calcium c Monitor glucose In adult patients, administer 10 units insulin IV push with 50 mL 50% dextrose In pediatric patients, administer 0.1 units insulin/kg IV push with mL/kg 50% dextrose d If ECG monitoring demonstrates a widened QRS complex, consider administering calcium chloride 500 to 1,000 mg (maximum dose 2,000 mg) via slow IV infusion over to minutes in adults; repeat after 10 minutes if ECG changes persist In pediatric patients, administer 10 to 20 mg/kg cont on next page 149 www.ajlobby.com Mizukawa_Chap_12.indd 149 6/26/17 2:23 PM 12 • Medical Emergencies B O X - (cont) Management of malignant hyperthermia8 Treat arrhythmias per ACLS protocol Calcium channel blockers are contraindicated during an acute malignant hyperthermia crisis Monitor the following: a Urine output: Place a Foley catheter; maintain at to mL/kg per hour b Temperature: Maintain at < 39°C c Blood gas: Normalize pH; optimize partial pressure of carbon dioxide and oxygen d Basic metabolic profile: Normalize e Glucose: Normalize f Creatine kinase: Assess every to 12 hours; alkalinize urine if creatine kinase is > 10,000 IU/L g Prothrombin time and partial thromboplastin time: Monitor for disseminated intravascular coagulation ACLS, advanced cardiovascular life support Bronchospasm Pathophysiology Bronchospasm is an increase in airway resistance caused by contraction of bronchial smooth muscle Bronchial smooth muscle tone is influenced by the parasympathetic nervous system through muscarinic receptors (increased tone) and sympathetic nervous system β2-adrenergic receptors (decreased tone) Histamine may also influence tone through histaminergic receptors Common risk factors for bronchospasm include recent respiratory tract infection, recent exacerbation of asthma or chronic obstructive pulmonary disease, tobacco use, and endotracheal intubation Asthmatic patients are especially at risk because they have reduced airway caliber at baseline, bronchial smooth muscle hypertrophy, and increased airway reactivity However, in many cases of bronchospasm, no known risk factors are present.9 The most common causes of bronchospasm during anesthesia are airway irritation (secretions, blood, and direct laryngoscopy), allergic reactions, problems with the endotracheal tube, and aspiration.10 Nonselective β-blockers may trigger bronchospasm through inhibition of β2 receptors Especially in patients at greater risk, bronchospasm may occur at any time, but it most commonly occurs during anesthetic induction and light anesthesia In the maintenance stages of anesthesia, allergic reaction to an administered drug is the most common cause of bronchospasm.10 Diagnosis Clinical manifestations of bronchospasm include dyspnea, tachypnea, expiratory wheezing, prolonged expiratory phase, small tidal volumes, increased work of breathing, hypoxemia, and hypercarbia The pathophysiology of severe bronchospasm includes V/Q mismatch, right ventricular overload, decreased venous return, and hypotension As a result, etCO2 will increase and oxygen saturation will decrease Prompt recognition and intervention is necessary to treat the airway obstruction and correct the hypoxemia Other causes of respiratory distress that should be considered include mechanical airway obstruction, tension pneumothorax, pulmonary edema, aspiration, and pulmonary embolism 150 www.ajlobby.com Mizukawa_Chap_12.indd 150 6/26/17 2:23 PM Bronchospasm Management Understanding patients at risk is instrumental in preventing acute bronchospasm For patients with a history of reactive airway disease, pre-emptive treatment with a bronchodilator, steroids, or both is prudent For patients with reactive airway disease who are not at baseline (cough, wheezing, increased sputum production, increased frequency of rescue bronchodilator use, nighttime bronchospasm, etc), it is prudent to delay elective surgery For those patients at baseline, the choice of anesthetic agent is less important than an appropriate depth of anesthesia and analgesia is.1 However, the use of agents with bronchodilatory properties (propofol, ketamine) is advisable If endotracheal intubation or laryngeal mask anesthesia is planned, inhalational agents are beneficial because of their bronchodilatory properties (sevoflurane is preferred) In contrast, desflurane should be avoided during induction because of its pungent smell and ability to cause bronchospasm, especially in children with asthma Prevention strategies are summarized in Box 12-3 BOX 12-3 Prevention strategies of bronchospasm Preoperative • Continue the patient’s usual home bronchospasm medications up to the time of surgery • Auscultate chest; ensure baseline air movement • Measure peak flow; peak flow should be at baseline • Pretreat the patient with albuterol or ipratropium via metered dose inhaler or nebulizer • Consider preoperative corticosteroids for patients with asthma and atopic history • Delay surgery if the patient has a worsening cough, active wheezing, increased sputum production, or increased frequency of bronchodilator use Intraoperative • Consider administering intravenous (IV) lidocaine (attenuates histaminemediated hyperactivity); consider use of laryngotracheal lidocaine if the use of an endotracheal tube is planned in adults (may precipitate laryngospasm or bronchospasm in asthmatic patients and children) • Ensure adequate depth of anesthesia/ analgesia • Ensure scrupulous protection of airway with an oropharyngeal screen and suctioning • Consider IV anesthetics with bronchodilator properties (ketamine, propofol) • Consider inhalational anesthetics • Avoid drugs that cause histamine release (morphine and meperidine) Management of bronchospasm (Box 12-4) includes bronchodilation, supplemental oxygen, and the use of agents to reduce airway inflammation Oxygen is administered with the use of a face mask The anesthesia may be deepened, preferably with the use of anesthetics with bronchodilatory properties (ketamine, propofol, or inhalational anesthetics) Inhaled bronchodilators, such as albuterol and ipratropium, are administered Their effectiveness will be limited by reduced delivery of the medication to constricted bronchioles and in the obtunded patient Alternatively, inhaled bronchodilators can be administered through a medication elbow adapter in a bag-mask circuit in the obtunded patient Prompt use of epinephrine can be lifesaving if the inhaled bronchodilator is ineffective or an allergic cause of the bronchospasm is suspected Intravenous (IV) magnesium sulfate has been shown to be effective in the management of recalcitrant bronchospasm Finally, if hypoxemia cannot be managed with these measures and positive pressure mask ventilation, emergent tracheal intubation is necessary A corticosteroid should also be administered to reduce airway inflammation, although it will not have an immediate effect IV lidocaine can also further blunt airway reactivity; however, it is primarily used for prevention before bronchospasm occurs 151 www.ajlobby.com Mizukawa_Chap_12.indd 151 6/26/17 2:23 PM 12 • Medical Emergencies BOX 12-4 Management of bronchospasm Administer 100% oxygen by face mask; titrate to achieve arterial saturation of oxygen > 90% Deepen anesthesia with the use of IV anesthetics with bronchodilator properties, such as ketamine or propofol (inhalational anesthetics can be used if they are available and ventilation is good) Use a bag valve mask to assist ventilation as needed Administer a bronchodilator: • Administer a bronchodilator via metered dose inhaler: –– Albuterol to puffs every 20 minutes; in pediatric patients, to puffs –– Ipratropium to puffs every 20 minutes • Or administer a nebulized bronchodilator: –– Albuterol 2.5 to mg every 20 minute and/or –– Ipratropium 500 µg every 20 to 30 minutes, three times (in patients weighing < 20 kg, use 250 àg) ã If the patient has insufficient air movement, poor effort, lack of response to inhaled bronchodilator, and/or allergic trigger, administer intramuscular (IM) epinephrine 0.3 mL (in pediatric patients, use 0.01mL/kg) 1:1,000 in the lateral thigh every to minutes • If the patient has a poor response to IM epinephrine and/or hypotension unresponsive to fluid administration, administer IV epinephrine 1:10,000 mL every to minutes • In patients with recalcitrant bronchospasm, administer magnesium sulfate 75 mg/kg over 20 minutes; in pediatric patients, administer 40 mg/kg over 20 minutes up to g • Indications for intubation are as follows: –– Worsening hypoxemia, increased work of breathing, altered mental state –– Respiratory/cardiac arrest • To facilitate intubation, sedate with ketamine to 2mg/kg or propofol 1.5 to mg/kg followed by succinylcholine to mg/kg • Administer lidocaine 1.5 mg/kg IV • Administer corticosteroids, such as methylprednisolone to mg/kg IV IV, intravenous Myocardial Ischemia and Infarction Pathophysiology Myocardial ischemia results from an imbalance between myocardial oxygen supply and demand Factors that contribute to ischemia include an increased myocardial oxygen demand, which can result from increased heart rate, contractility, preload, and/or afterload, and decreased myocardial oxygen supply resulting from decreased coronary blood flow and/or decreased blood oxygen content Typically, coronary artery disease (CAD) is present, and a fixed atherosclerotic stenosis impairs blood flow and oxygen supply to the myocardium During times of increased myocardial oxygen demand, such as with exercise or other increased sympathetic activity, ischemia may result, manifested by stable angina, which includes chest pain on exertion that improves with rest or nitroglycerin As the atherosclerotic lesion matures, it becomes vulnerable to rupture, exposing vessel intimal and medial thrombogenic substances to the bloodstream, leading to thrombus formation and partial or complete occlusion of the vessel lumen Ischemia occurring at rest without myocardial necrosis is unstable angina If myocardial necrosis occurs, the result is either non–ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI), depending on the degree of involvement of the myocardium Unstable angina, NSTEMI, and STEMI are the three manifestations of acute coronary syndrome (ACS) Because it can be difficult to distinguish between stable angina and the three ACS types, prompt and urgent therapy must be implemented whenever any of these conditions is suspected 152 www.ajlobby.com Mizukawa_Chap_12.indd 152 6/26/17 2:23 PM Myocardial Ischemia and Infarction Diagnosis Generally, the different manifestations of ACS can be distinguished by history, ECG assessment, and biochemical markers (ie, troponins) (Tables 12-1 and 12-2).5,13–15 Table 12-1 Comparison of stable angina and ACS Characteristic Stable angina ACS Pathophysiology • Increased oxygen demand • Fixed atherosclerotic lesion/decreased oxygen supply Decreased oxygen supply secondary to ruptured atherosclerotic plaque causing subtotal occlusion (ie, unstable angina, NSTEMI) or total occlusion (ie, STEMI)8 Clinical manifestation Chest pain/substernal pressure • Heaviness, squeezing, pressure, tightness • Duration 10 to 15 minutes • Gradual in onset • Relieved with rest or nitroglycerin • Can occur with or without radiation to neck, jaw, arms, or back (usually on left side) • Precipitated by stress, emotion, exertion11 • Less likely angina if pain is sharp or stabbing, positional or pleuritic, reproducible by palpation, and in a patient with no history of angina or myocardial infarction12 Typical angina* • Unstable angina/NSTEMI: angina with new onset, crescendo (increasing frequency, duration, or intensity), or occurrence at rest; usually lasts < 30 minutes • STEMI: angina at rest, intense substernal pressure sensation (“crushing”); usually lasts > 30 minutes • Usually does not resolve with rest or nitroglycerin • Associated symptoms: diaphoresis, dyspnea, nausea/ vomiting, lightheadedness, palpitations Physical examination No specific physical findings • New mitral regurgitation • Signs of heart failure: hypotension, crackles in lung fields, cool extremities, increased jugular venous pressure Diagnostic features • Stress test • History • ECG –– ST deviation (depression or elevation) –– T wave abnormalities: inversions, peaked –– Q waves late –– Arrhythmias: atrial fibrillation, ventricular fibrillation, ventricular tachycardia, new left bundle branch block • Cardiac enzymes: elevated troponins (NSTEMI and STEMI) *These findings may not be present In 20% of myocardial infarctions, the patient is asymptomatic or experiences atypical symptoms.11 Table 12-2 Differential diagnosis of chest pain Etiology Possible diagnoses Cardiac Aortic dissection, pericardial effusion, pericarditis Pulmonary Pulmonary embolism, pneumothorax Gastrointestinal Gastroesophageal reflux disease, esophageal spasm, esophageal rupture, gastritis, pancreatitis, hepatitis Musculoskeletal Costochondritis Psychiatric Anxiety Management Treatment of myocardial ischemia includes increasing myocardial oxygen supply, reducing myocardial oxygen demand, anticoagulation, administering platelet inhibitors, and implementing reperfusion therapy if indicated16 (Box 12-5) If a patient develops signs/symptoms of myocardial ischemia during anesthesia, ACS should be suspected, and the procedure should be aborted If ACS is suspected, emergency assistance needs to be promptly activated in anticipation of transfer to the nearest hospital for evaluation for revascularization therapy The surgeon 153 www.ajlobby.com Mizukawa_Chap_12.indd 153 6/26/17 2:23 PM 12 • Medical Emergencies should keep in mind that “time is muscle,” meaning that the benefits of reperfusion are highest when it is performed early Supplemental oxygen may limit ischemic myocardial injury and provide patient comfort Providing adequate analgesia with opioids (eg, morphine) improves the oxygen supply-demand imbalance by venodilation and reduces painful stimuli that may contribute to the sympathetic response of increased blood pressure, tachycardia, and myocardial contractility Hydromorphone is preferred in hypotensive patients because morphine is associated with an increased risk of histamine release that may contribute to further reductions in blood pressure Nitroglycerin is administered to reduce myocardial demand by reducing preload through venodilation but may also improve the demand-supply imbalance by reducing afterload through systemic arteriole dilation and improving coronary vessel perfusion through coronary dilation In patients with either stable angina or ACS, aspirin and β-blockers should be administered (unless contraindicated) Aspirin helps prevent propagation and de novo formation of coronary thrombi β-blockers attenuate stimulation of heart rate and contractility BOX 12-5 Management of intraoperative myocardial ischemia • Abort the surgical procedure • If the patient has stable angina with chest pain that is not relieved after 20 minutes or three doses of nitroglycerin, assume that the patient has ACS and activate EMS • Monitor vital signs, oxygen saturation, and cardiac monitors • Establish IV access • Administer 100% oxygen by face mask or nasal cannulae; maintain arterial saturation of oxygen > 90% • If the patient has unstable angina or if ACS is suspected, activate EMS for transport to the nearest facility for possible reperfusion therapy if the patient has any of the following: –– ECG findings of ischemia or arrhythmias –– Symptoms of ACS –– Hypotension (not explained by anesthesia) • Administer pharmacologic management as follows: –– Opioid analgesia: dilaudid 0.5 to 1.0 mg IV or morphine sulfate to mg IV initially, then to mg every to 15 minutes (avoid morphine sulfate if the patient is hypotensive) –– Nitroglycerin 0.4 mg sublingual every minutes for three doses >> Nitroglycerin is contraindicated in patients taking phosphodiesterase inhibitors or in patients with systolic blood pressure < 90 mm Hg; use with caution if ECG findings suggest inferior/posterior myocardial infarction >> If symptoms are relieved after one or two typical doses, assume stable angina Modify treatment to prevent recurrence (ensure adequate analgesia and sedation) –– Antiplatelet agent: aspirin 325 mg (without enteric coating), one tablet by mouth (crushed/chewed) Hypertensive Urgency/Emergency Pathophysiology and diagnosis Hypertension is defined as systolic blood pressure (SBP) > 140 mm Hg and diastolic blood pressure > 90 mm Hg Substantial end-organ complications, including myocardial ischemia, congestive heart failure, stroke, and renal failure, can arise from hypertension Hypertension can be either primary (essential) or secondary Primary hypertension is responsible for 90% to 95% of hypertension cases and is usually caused by a complex interplay between genetic and environmental factors that promote an increase in baseline systemic vascular resistance and cardiac output Less common causes include renal disease, renal artery stenosis, Cushing disorder, primary hyperaldosteronism, pheochromocytoma, hyperthyroidism, and pregnancy Hypertension can also be induced by medication (estrogen, stimulants, steroids) Poorly controlled or untreated hypertension has been shown to be associated with a higher incidence of labile perioperative blood pressure13 and intraoperative adverse events, such as myocardial ischemia and arrhythmia.14,15 154 www.ajlobby.com Mizukawa_Chap_12.indd 154 6/26/17 2:23 PM Hypertensive Urgency/Emergency Management Elective surgery should be postponed in patients with blood pressures greater than 170/110 to allow for blood pressure optimization with oral antihypertensive medications.17 Achieving normotension acutely before elective surgery is undesirable because of altered cerebral autoregulation In these patients, substantial reductions in blood pressure can compromise cerebral perfusion.18 Other important considerations in patients with hypertension are comorbidities such as CAD, left ventricular hypertrophy, ventricular dysfunction, cerebrovascular compromise, and chronic kidney disease Therefore, antihypertensive medications should not be withheld before surgery Further, in patients with a history of treated hypertension, endogenous catecholamines should be minimized with IV anesthesia and profound local anesthesia Exogenous catecholamines should also be limited with the prudent use of local anesthetic/vasoconstrictor combinations Anesthetic agents to avoid include ketamine, which is associated with an increased sympathetic response promoting elevations in blood pressure and tachycardia Patients with long-standing hypertension may have some degree of left ventricular hypertrophy and/or CAD, and perioperative hypertension may precipitate myocardial ischemia and/or ventricular dysfunction Marked elevation in blood pressure should be treated promptly Initially, reversible causes, such as pain, inadequate anxiolysis, hypoxia, and hypercarbia, should be addressed If pain is poorly controlled, additional local anesthesia and/or deepening of the level of anesthesia should be accomplished In the postoperative period, pain should be addressed with the judicious use of opioids and possibly readministration of local anesthesia For longer procedures, bladder distension should be considered and is an important source of perioperative hypertension If blood pressures greater than 180/110 persist, parenteral antihypertensive agents should be used (Box 12-6) The choice of agent depends on several factors, including heart rate, severity, baseline ventricular function, and presence of bronchospastic disease β-blockers are a good choice for patients with good ventricular function and elevated heart rate but are contraindicated in patients with bronchospastic disease If bronchospastic disease is present, calcium channel blockers are an acceptable alternative Hydralazine, a long-acting vasodilator, can cause a reflex tachycardia that may be undesirable in patients with a history of CAD BOX 12-6 Management of intraoperative hypertension Eliminate reversible causes of hypertension and ensure adequate analgesia and anxiolysis with the use of the following: • β-blockers –– Esmolol (β1-blocker) mg/kg over 30 seconds, then 150 µg/kg per minute infusion; may increase by 50 µg/kg per minute every minutes as needed (maximum 300 µg/kg per minute) –– Labetalol (α1-, β1-, and β2-blocker) 20 mg over minutes; may repeat every 10 minutes as needed (maximum 300 mg total dose) –– Calcium channel blocker: nicardipine mg/h; increase by 2.5 mg/h every to 15 minutes (maximum 15 mg/h) –– Angiotension-converting enzyme inhibitor: Enalaprilat 0.625 to 1.25 mg IV; may repeat once in hours • Vasodilators –– Nitroglycerin µg/min; increase µg/min every to minutes up to 20 µg/min –– Hydralazine 10 to 20 mg every to hours If a hypertensive urgency/emergency occurs, it is important to assess the patient for end-organ damage after recovery from anesthesia The patient should be assessed for chest pain, headaches, visual disturbances, and altered mental status Evidence of end-organ damage and/or ECG changes from baseline should prompt a transfer to a medical facility for a thorough evaluation Finally, in patients with long-standing hypertension, intraoperative hypotension also must be avoided These patients require higher cerebrovascular perfusion pressures secondary to altered autoregulation, and large reductions in blood pressure may be detrimental 155 www.ajlobby.com Mizukawa_Chap_12.indd 155 6/26/17 2:23 PM 12 • Medical Emergencies Hypoglycemia Pathophysiology and diagnosis Hypoglycemia is defined as blood glucose < 50 mg/dL in adults and < 40 mg/dL in children Perioperative hypoglycemia is most likely to occur in patients with diabetes who take insulin or oral hypoglycemics (sulfonylureas) and have fasted before surgery Patients at high risk include those with tight glycemic control, history of hypoglycemia, and/or labile blood glucose.19 Clinical manifestations of hypoglycemia are a result of increased sympathetic response and neuroglycopenia Activation of the sympathetic nervous system results in diaphoresis, tremors, anxiety, increased blood pressure, tachycardia, and palpitations Reduced glucose delivery to the central nervous system causes irritability, confusion, behavior changes, belligerence, headaches, weakness, drowsiness, and eventually seizures and coma Patients with long-standing diabetes and severe neuropathy may have hypoglycemia unawareness, resulting in a blunted sympathetic response to hypoglycemia These patients, as well as those taking β-blockers, may not experience any sympathetic symptoms but progress directly to neuroglycopenic symptoms, including seizures or coma.20 Anesthetics, analgesics, hypoglycemic unawareness, and β-blockade all can make recognition of perioperative hypoglycemia difficult Management The goal of anesthetic management in the patient with diabetes is to minimize interruptions in established regimens of glucose control It is always advisable to discuss management strategies with the patient’s diabetologist before the day of surgery In general, fasting in preparation for anesthesia should be minimized to that necessary for the safe administration of anesthesia Therefore, early morning surgery is preferable Short-acting insulin and sulfonylureas should not be administered on the morning of the surgical procedure It may be advisable to decrease the bedtime dose of insulin glargine the evening before surgery Blood glucose should be evaluated preoperatively and should be maintained between 100 and 200 mg/dL If blood glucose is > 150 mg/dL, non–dextrose-containing IV fluids should be used If blood glucose is < 150 mg/dL, the IV fluid should be 5% dextrose in water (D5W) If IV access is unavailable, intramuscular (IM) glucagon or an oral glucose source can be administered If the patient is sedated or obtunded, oral glucose sources should be avoided because of the risk of aspiration Intraoperative hypoglycemia will be difficult to detect depending on the level of sedation Blood glucose levels should be assessed hourly during anesthesia Dextrose may be added to or removed from the IV fluids for the management of blood glucose below or above 150 mg/dL, as described above If blood glucose falls below 70 mg/ dL, 15 g of IV glucose (30 mL of 50% dextrose) should be administered (Box 12-7) Each milliliter of 50% glucose will raise blood glucose mg/dL Evaluation of blood glucose should be repeated in 15 minutes to ensure that blood glucose is > 100 mg/dL Permanent neurologic sequelae can result from extended periods of hypoglycemia; therefore, intraoperative hypoglycemia must be assiduously recognized and managed Intraoperative hyperglycemia should not be treated unless blood glucose is > 300 mg/dL Blood glucose > 300 mg/dL may be treated with insulin aspart using a 1:50 sliding scale starting at 150 mg/dL Additional insulin blood sugar correction should not be made for hours.21 BOX 12-7 Management of perioperative hypoglycemia If blood glucose is < 70 mg/dL, treat with the following: 30 mL of 50% dextrose IV or glucagon 0.5 to mg IM or SC IV fluids: D5W Reassess blood glucose in 15 minutes to verify blood glucose > 100 mg/dL SC, subcutaneous 156 www.ajlobby.com Mizukawa_Chap_12.indd 156 6/26/17 2:23 PM Anaphylaxis Anaphylaxis Pathophysiology and diagnosis Anaphylaxis is an acute, potentially fatal, multi–organ system event caused by the sudden degranulation of mediators from mast cells and basophils Anaphylaxis has immunoglobulin E (IgE)-mediated and IgE-independent (anaphylactoid) forms that are clinically indistinguishable Inflammatory mediators, including histamine, leukotrienes, kinins, and platelet-activating factor, result in vasodilation, vascular permeability, smooth muscle spasm in the respiratory and gastrointestinal tracts, increased mucus production, increased bronchial smooth muscle tone, and airway edema Anaphylaxis typically involves at least two organ systems, with cutaneous and respiratory symptoms being the most common Cutaneous findings typically appear first and include pruritus, erythema, urticaria, and angioedema Bronchospasm, laryngeal edema, and cardiovascular collapse mandate early recognition and management of anaphylaxis (Table 12-3) Anaphylaxis in the ambulatory surgery setting usually is caused by medications, including antibiotics (especially β-lactam antibiotics), propofol (because of allergy to egg and soy products), nonsteroidal anti-inflammatory drugs, and local anesthetics (reaction to metabisulfite preservative) Table 12-3 Clinical manifestations of anaphylaxis System Signs/symptoms Cutaneous Pruritus, erythema, urticarial, angioedema Respiratory Nasal congestion, rhinorrhea, dyspnea, wheezing, cough, shortness of breath, stridor if laryngeal edema Gastrointestinal Dysphagia, nausea/vomiting, abdominal pain, diarrhea Cardiovascular* Hypotension, chest pain, syncope, arrhythmias, shock *Can occur without other signs/symptoms of anaphylaxis Management Management first includes implementing basic life support and notifying EMS (Box 12-8) Epinephrine is administered to bronchodilate and constrict blood vessels (by means of its β2 and α1 agonist properties, respectively) and sustain blood pressure Therapy should also include histamine H1 and H2 blockers, steroids, and IV fluids Prompt and liberal use of epinephrine is lifesaving An epinephrine infusion may be required to sustain continued drops in blood pressure An epinephrine infusion can be given with mg epinephrine in 1,000 mL normal saline (1 µg/mL) infused at a starting rate of mL/min, increased to 10 mL/min (10 µg/min) as required In children, a starting infusion of 0.1 µg/kg per minute is recommended In adults, if an epinephrine infusion is not immediately available, a 30- to 50-µg (0.3 to 0.5 mL of 1:10,000 dilution) bolus of epinephrine should be carefully administered.22 Patients who have experienced an anaphylactic reaction should be transported to a hospital for monitoring when stable Increased secretions, bronchospasm, and laryngospasm may necessitate intubation 157 www.ajlobby.com Mizukawa_Chap_12.indd 157 6/26/17 2:23 PM 12 • Medical Emergencies BOX 12-8 Management of anaphylaxis If the patient has skin symptoms without respiratory symptoms: • Monitor the patient for respiratory/cardiovascular compromise • If a drug infusion is in progress, stop the infusion • Administer normal saline 500 mL/h and monitor blood pressure • Administer diphenhydramine 50 mg in patients < 65 years of age or 25 mg in patients > 65 years of age IV over to minutes • Administer hydrocortisone 100 mg IV or dexamethasone to 10 mg IV or methylprednisolone to mg/kg IV If the patient has respiratory and/or cardiovascular symptoms: • If a drug infusion is in progress, stop the infusion • Notify EMS • Administer normal saline 500 mL/h • Administer oxygen L/min via nasal cannula • Administer epinephrine as follows: –– IM: 0.2 to 0.5 mL (in pediatric patients, use 0.01 mg/kg) 1:1,000 in the anterolateral thigh Repeat every to 15 minutes for management of persistent respiratory/ cardiovascular symptoms –– If the patient has a poor response to IM epinephrine, administer mg epinephrine in 1,000 mg normal saline (1 µg/mL) at mL/min, titrated to blood pressure effect (maximum 10 mL/min) –– If the patient has recalcitrant symptoms or hypotension or if no infusion is available, administer an IV bolus of 0.3 to 0.5 mL of 1:10,000 epinephrine (100 µg/mL) • Administer albuterol 2.5 mg via nebulizer or to puffs (2 to puffs in children) via metered dose inhaler as needed for the management of bronchospasm • Administer diphenhydramine (H1 blocker) 50 mg (in patients age 12 to 64 years) or 25 mg (in patients age > 65 years or to 12 years) IV over to minutes • Administer ranitidine (H2 blocker) 50 mg IV (2 to mg/kg in pediatric patients) • Administer hydrocortisone 100 mg IV or dexamethasone to 10 mg IV or methylprednisolone to mg/kg IV Adrenal Insufficiency Pathophysiology Adrenal insufficiency can be primary, secondary, or tertiary Primary adrenal insufficiency can result from autoimmune disease, adrenal infarction, malignancy, or infection Secondary adrenal insufficiency results from any process that affects the pituitary and interferes with release of adrenocorticotropic hormone (ACTH) Tertiary adrenal insufficiency results from any process that interferes with the synthesis or release of corticotropin-releasing hormone (CRH) Chronic corticosteroid administration is the most common cause of tertiary adrenal insufficiency Exogenous corticosteroids not only inhibit CRH synthesis and secretion but also block the ACTH secretagogue action of CRH on the anterior pituitary ACTH is an important stimulant and growth factor for the adrenal glands Without adequate levels of ACTH, atrophy of the adrenal gland occurs, rendering the gland incapable of producing sufficient cortisol under periods of physiologic stress A patient with adrenal insufficiency may require corticosteroid supplementation during periods of physiologic stress to avert an adrenal crisis Clinical manifestations of an adrenal crisis include altered mental status, fever, abdominal pain, nausea/vomiting, orthostatic hypotension, and hypovolemia that can lead to shock unresponsive to resuscitation During outpatient anesthesia, hypotension may be the only clinical indicator of adrenal insufficiency 158 www.ajlobby.com Mizukawa_Chap_12.indd 158 6/26/17 2:23 PM Adrenal Insufficiency Diagnosis Clinically important suppression of the hypothalamic-pituitary-adrenal (HPA) axis will not result from any dose of corticosteroid taken for < weeks, a daily prednisone equivalent dose < mg taken in the morning, or < 10 mg prednisone taken every other day At the other extreme, prednisone 20 mg/day taken for > weeks causes HPA suppression Furthermore, any patient with cushingoid signs or symptoms should be considered to have adrenal suppression.23 Patients who take the prednisone equivalent of mg or more, who take less than the prednisone equivalent of mg in the evenings, or who have taken a suppressive corticosteroid dose in the past year may have HPA suppression and should undergo evaluation of the HPA axis Similarly, children using inhaled corticosteroids for > weeks within months of surgery may also be at risk of adrenal suppression and should undergo HPA evaluation.24 Low morning cortisol and low ACTH are consistent with tertiary adrenal insufficiency If the early morning serum cortisol value is > 10 µg/dL, clinically important HPA suppression is not likely Conversely, an early morning serum cortisol value < µg/dL likely reflects adrenal insufficiency For morning cortisol values between these two extremes, dynamic HPA testing is indicated Dynamic testing consists of IV or IM administration of high-dose synthetic ACTH (cosyntropin) with measurement of serum cortisol just before administration of ACTH and 30 and 60 minutes after administration of ACTH A stimulated serum cortisol value of > 18 to 20 µg/dL reflects a normal adrenal gland response to stimulation, typical of secondary or tertiary adrenal insufficiency However, depending on the extent of adrenal gland atrophy, patients with tertiary adrenal insufficiency, such as that resulting from chronic corticosteroid use, may have a sluggish response to ACTH administration Management Normal secretion of cortisol is approximately to 10 mg/day, with increases to 50 mg/day in response to minor surgery or illness25 and 75 to 100 mg/day in response to major surgery.26 Cortisol secretion > 200 mg/day in the first 24 hours, seen in patients who experience trauma, is rare after surgery In patients with primary adrenal insufficiency or HPA axis suppression, supplemental corticosteroid may be necessary to prevent adrenal crisis (Box 12-9) BOX 12-9 Perioperative corticosteroid dosing in patients with adrenal insufficiency or HPA axis suppression • Minor surgery/local anesthesia: hydrocortisone 25 mg (one dose) • Moderate stress: hydrocortisone 50 mg preoperatively, then 25 mg every hours for 24 hours • Major stress: hydrocortisone 100 mg preoperatively, then 50 mg every hours for 24 hours In patients with adrenal insufficiency and unexplained intraoperative hypotension and reflex tachycardia, adrenal crisis should be suspected, and EMS should be notified Management includes fluid resuscitation and steroid administration (Box 12-10) Etomidate should be avoided in patients at risk of adrenal suppression and adrenal crisis Etomidate inhibits steroid synthesis and may precipitate an adrenal crisis.27 159 www.ajlobby.com Mizukawa_Chap_12.indd 159 6/26/17 2:23 PM 12 • Medical Emergencies BOX 12-10 Management of adrenal crisis Notify EMS Administer to 10 L oxygen by face mask or nasal cannula Administer corticosteroid: dexamethasone to 10 mg IV every 12 hours (preferred if undiagnosed adrenal insufficiency is suspected) or hydrocortisone 100 mg IV, then 50 mg every hours Perform volume resuscitation with to L of normal saline (use D5W if the patient has hypoglycemia) • If the patient is unresponsive to fluid resuscitation, administer phenylephrine 100 µg IV or ephedrine µg IV Perioperative Hypotension Management of perioperative hypotension depends on the etiology Common causes of hypotension in an ambulatory oral surgery setting include vasovagal syncope, effects of anesthesia, and hypovolemia Other less common cardiac sources include arrhythmias and heart failure Other conditions that can mimic hypotension by causing confusion and altered mental status, such as adrenal crisis or hypoglycemia, need to be considered as well Except when it occurs in conjunction with an acute cardiac event, intraoperative hypotension should initially be addressed with fluid administration (Box 12-11) The dose of anesthetic agent may also be decreased as long as adequate anesthesia depth for the procedure is maintained If hypotension continues after these interventions, the use of pressors, such as ephedrine or phenylephrine, should be considered.28 BOX 12-11 Management of intraoperative hypotension Administer fluid bolus Adjust the anesthetic dose Administer ephedrine or phenylephrine • Administer ephedrine (β agonist; causes norepinephrine release) to 25 mg IV every to 10 minutes up to 150 mg • Administer phenylephrine (an α-adrenergic agonist) 100 µg (0.1 mg/mL) IV every 10 to 15 minutes (clinician should watch for reflex bradycardia) Vasovagal Syncope Pathophysiology and diagnosis Vasovagal syncope is a common medical emergency seen in the dental and oral surgery setting It is described as a loss of consciousness accompanied by bradycardia and hypotension evoked by a stressful trigger Common predisposing events include strong emotional or orthostatic events, noxious stimuli, fear, prolonged standing, and heat The pathogenesis is characterized by increased vagal tone leading to cardioinhibition (bradycardia) and/or sympathetic inhibition (vasodilation), which results in cerebral hypoperfusion and subsequently loss of consciousness.10 Prodromal symptoms may be present and can include nausea/vomiting, pallor, and diaphoresis When syncope is accompanied by these symptoms and a typical trigger (before initiation of IV access or dental blocks), vasovagal syncope should be highly suspected The differential diagnosis includes other causes of syncope, such as arrhythmias, seizures, and hypoglycemia 160 www.ajlobby.com Mizukawa_Chap_12.indd 160 6/26/17 2:23 PM Hyperventilation Management Management of vasovagal syncope first and foremost includes evaluation of airway, breathing, and circulation and support of respiration if necessary (Box 12-12) Oxygen is administered by nasal cannula The patient is then placed into the Trendelenburg position to increase cerebral blood flow Cardiac monitors and vital signs may reveal bradycardia, which can be treated with IV atropine If hypotension is present, a bolus of isotonic fluids may be administered If hypotension is refractory to fluids and atropine, IV phenylephrine may be used Additionally, the patient’s blood glucose level should be tested to rule out hypoglycemia Comfort measures, such as the use of cold compresses to the forehead and a cooling fan, are also helpful Spirits of ammonia or alcohol swabs may promote patient arousal as needed BOX 12-12 Management of vasovagal syncope Evaluation of airway, breathing, and circulation and provide support of respiration if necessary Administer oxygen and monitor vital signs, blood glucose, and three-lead ECG Place patient in the Trendelenburg position Obtain IV access and administer a bolus of isotonic fluid Administer atropine as needed if the patient has more than transient bradycardia Administer phenylephrine as needed if the patient has hypotension refractory to the IV fluid bolus Hyperventilation Pathophysiology and diagnosis During periods of exceptional anxiety, possibly associated with panic disorder, a patient’s minute ventilation may transiently increase beyond the level appropriate to meet metabolic needs This occurrence is often referred to as hyperventilation syndrome Although an uncommon occurrence, hyperventilation in the setting of office-based anesthesia is usually associated with IV sedation and an anxious, upset, and often dysphoric patient Adolescent female patients, in particular, seem more often to be susceptible to this event, in the author’s experience Although hyperventilation is often thought to be the culmination of a period of anxiety, possibly panic, and drug-induced dysphoria, the psychologic manifestation may actually be the result of hyperventilation Rapid, shallow breathing, in particular, is associated with panic disorder and ot her neuroses Affected patients may also report chest pain, dyspnea, lightheadedness, and dizziness A number of physiologic events, particularly hypocapnia and respiratory alkalemia, occur with hyperventilation These events, in turn, result in cerebral vasoconstriction and a decrease in cerebral blood flow In fact, for every mm Hg drop in arterial partial pressure of carbon dioxide (Paco2), a 2% reduction in cerebral blood flow occurs.29 Decreased cerebral blood flow may explain the neurologic symptoms of headache, lightheadedness, and extremity paresthesia.29 It has been proposed that alkalemia also leads to a decrease in ionized calcium, which may contribute to cutaneous paresthesia and tetany, even progressing to carpopedal spasm.30 Alkalemia also shifts the oxyhemoglobin dissociation curve leftward, increasing hemoglobin oxygen affinity and decreasing the release of oxygen at the tissue level The decrease in tissue oxygenation, along with local vasoconstriction may contribute to the symptoms of paresthesia and tetany In the presence of hyperventilation and dyspnea, other conditions that need to be considered include ACS, hypoglycemia, bronchospasm, congestive heart failure, seizures, arrhythmias, thyroid storm, pulmonary embolism, and pneumothorax 161 www.ajlobby.com Mizukawa_Chap_12.indd 161 6/26/17 2:23 PM 12 • Medical Emergencies Management The acute management of hyperventilation is directed toward increasing Paco2 while maintaining adequate oxygenation (Box 12-13) Reassuring the patient by explaining the symptoms and coaching the patient to breathe with slow, deliberate breaths may be helpful in establishing a more normal respiratory rate and tidal volume Unfortunately, coaching of a dysphoric, sedated patient may not be effective The classic remedy of having the patient breathe into a paper bag can recycle expired carbon dioxide back into the lungs and improve Paco2, but care must be taken to avoid hypoxemia The level of anesthesia can be carefully deepened if doing so will adequately address the dysphoria Patients prone to hyperventilation syndrome are likely best managed with a deep or general anesthetic BOX 12-13 Management of hyperventilation syndrome Consider other causes of hyperventilation Reassure and calm patient, explain symptoms, coach patient on breathing to control rate and tidal volume Use a rebreathing bag to increase Paco2 (avoid hypoxemia) Consider a cautious increase in anesthetic depth Summary The safe administration of office-based anesthesia requires an understanding of a patient’s co-morbid medical conditions as well as a personalized anesthetic plan that takes into consideration co-morbid conditions and the anesthetic needs of the patient Despite these preparations, medical emergencies arise, and it is imperative that the surgeon be comfortable initiating treatment for a number of life-threatening medical emergencies The surgical office staff should be knowledgeable and, through frequent drills, well-rehearsed in management of office medical emergencies References Kurrek MM, Twersky RS Office-based anesthesia: How to start an office-based practice Anesthesiol Clin 2010;28:353–367 Bartamian M, Meyer DR Site of service, anesthesia and postoperative practice patterns for oculoplastic and orbital surgeries Ophthalmology 1996;103:1628–1633 Byrd HS, Barton FE, Orenstein HH, et al Safety and efficacy in an accredited outpatient plastic surgery facility: A review of 5316 consecutive cases Plast Reconstr Surg 2003;112:636–641 Malignant Hyperthermia Association of the United States Managing an MH Crisis: Emergency Treatment for an Acute MH Event http:// www.mhaus.org/healthcare-professionals/managing-a-crisis Accessed January 2015 Atlee JL Bronchospasm In: Atlee JL Complications in Anesthesia, ed Philadelphia: Saunders, 2007:189–192 10 Westhorpe RN, Ludbrook GL, Helps SC Crisis management during anaesthesia: Bronchospasm. Qual Saf Health Care 2005;14:e7 Perrott DH, Yuen JP, Andresen RV, Dodson TB Office-based ambulatory anesthesia: Outcomes of clinical practice of oral and maxillofacial surgeons J Oral Maxillofac Surg 2003;61:983–995 11 Swap CJ, Nagurney JT Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes. JAMA 2005;294:2623–2629 [erratum 2006;295:2250] Brady JE, Sun LS, Rosenberg H, Li G Prevalence of malignant hyperthermia due to anesthesia in New York State, 2001-2005 Anesth Analg 2009;109:1162–1166 12 Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L Acute chest pain in the emergency room: Identification and examination of low-risk patients Arch Intern Med 1985;145:65–69 Butterworth JF, Mackey DC, Wasnick JD Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill Education, 2014:1183–1192 13 Goldman L, Caldera DL Risks of general anesthesia and elective operation in the hypertensive patient Anesthesiology 1979;50:285–292 Atlee JL Malignant hyperthermia In: Atlee JL Complications in Anesthesia, ed Philadelphia: Saunders, 2007:654–656 14 Prys-Roberts C Anaesthesia and hypertension Br J Anaesth 1984;56:711–724 162 www.ajlobby.com Mizukawa_Chap_12.indd 162 6/26/17 2:24 PM References 15 Kheterpal S, O’Reilly M, Englesbe MJ, et al Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery Anesthesiology 2009;110:58–66 16 Anderson JL, Adams CD, Antman EM, et al; American College of Cardiology, American Heart Association Task Force on Practice Guidelines, American College of Emergency Physicians, et al ACC/ AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/ Non–ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50(7):e1–e157 [erratum 2008;51:974] 17 Fleisher LA Preoperative evaluation of the patient with hypertension JAMA 2002;287:2043–2046 18 Stoelting RK, Miller RD Basics of Anesthesia, ed London: Churchill Livingstone, 2007 19 Joshi GP, Chung F, Vann MA, et al Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery Anesth Analg 2010;111:1378–1387 20 Cryer PE The barrier of hypoglycemia in diabetes Diabetes 2008;57:3169–3176 22 Campbell RL, Li JT, Nicklas RA, Sadosty AT; Members of the Joint Task Force; Practice Parameter Workgroup Emergency department diagnosis and treatment of anaphylaxis: A practice parameter Ann Allergy Asthma Immunol 2014;113:599–608 23 Hamrahian AH, Roman S, Milan S The surgical patient taking glucocorticoids UpToDate http://www.uptodate.com/contents/the-surgical-patient-taking-glucocorticoids Last updated 23 September 2014 Accessed 13 May 2016 24 Libworth BJ Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis Arch Intern Med 1999;159:941–955 25 Lamberts SW, Bruining HA, de Jong FH Corticosteroid therapy in severe illness N Engl J Med 1997;337:1285–1292 26 Chernow B, Alexander HR, Smallridge RC, et al Hormonal responses to graded surgical stress Arch Intern Med 1987;147:1273–1278 27 Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D Inhibition of adrenal steroidogenesis by the anesthetic etomidate N Engl J Med 1984;310:1415–1421 28 American Association of Oral and Maxillofacial Surgery Protocols for Emergencies http://www.aaoms.org/practice-resources/anesthesia/ anesthesia-resources/office-anesthesia-evaluation-manual-sample-forms Accessed June 2015 29 Raichle ME, Plum F Hyperventilation and cerebral blood flow Stroke 1972;3:566–575 30 Kerr WJ, Gliebe PA, Dalton JW Physical phenomena associated with anxiety states: The hyperventilation syndrome Cal West Med 1938;48:12–16 21 McKenna SJ Dental management of patients with diabetes Dent Clin North Am 2006;50:591–606 163 www.ajlobby.com Mizukawa_Chap_12.indd 163 6/26/17 2:24 PM www.ajlobby.com Mizukawa_Chap_12.indd 164 6/26/17 2:24 PM CHAPTER 13 Aftermath of an Adverse Outcome or Complication Lewis Estabrooks, dmd, ms www.ajlobby.com Mizukawa_Chap_13.indd 165 6/20/17 10:38 AM 13 • Aftermath of an Adverse Outcome or Complication Most clinicians enter the health care profession because of an inherent desire to help people However, not every patient responds as we desire, and some may even experience unanticipated or adverse outcomes Most adverse events in anesthesia can be prevented with (1) a complete and thoughtful review of comorbid conditions and other patient characteristics that may affect the safe and effective delivery of office-based anesthesia and (2) use of a personalized anesthetic strategy As clinicians, we recognize the value in analyzing adverse outcomes related to anesthesia We try to apply what is learned from the analysis of such events to improve ourselves, our systems, and future outcomes Far too often, we second-guess ourselves and focus on the “what ifs.” Because we hold ourselves to high standards, we may feel responsible for any adverse event, even when the event was unavoidable Yet, at times, providers make clinical judgment errors that may lead to an injury or poor result When an error occurs, not only is the patient a victim, but, in most cases, the doctor becomes a victim as well This chapter discusses the litigation process following an adverse event and how to cope with the emotional trauma that an oral and maxillofacial surgeon may experience after a simple adverse event or a devastating catastrophe The Oral and Maxillofacial Surgery National Insurance Company (OMSNIC) is the leading professional liability insurance carrier for oral and maxillofacial surgeons With an estimated 80% of the available market share, OMSNIC insures, on average, 4,590 oral and maxillofacial surgeons The OMSNIC morbidity and mortality data from 2000 through 2014 provide anesthetic procedure counts and claim activity as reported to OMSNIC during this time frame (unpublished data, 2015) The report accounts for 64,259 exposures or policies at risk, with more than 42 million office-based anesthetic administrations during this 14-year period Of these administrations, 71% were general anesthesia and 29% were sedation anesthesia An analysis shows that the average oral and maxillofacial surgeon performs 666 in-office anesthetic procedures each year, which would total 19,980 in-office anesthetic administrations over a 30-year period of practice Of the claims reported to OMSNIC from 2000 through 2014, 121 cases involved in-office anesthesia-related death From these data, it can be extrapolated that the average in-office mortality rate is death per 353,657 anesthetic administrations Considering this mortality rate, an oral and maxillofacial surgeon practicing for 30 years has approximately a in 18 chance of experiencing patient death related to office-based anesthesia One could conclude from these data that anesthesia administered in the oral surgery office setting is extremely safe This safety record has been the result of self-imposed guidelines and office inspections advanced by the American Association of Oral and Maxillofacial Surgeons Many of these guidelines have been enacted into state regulations for office-based anesthesia permits Not all adverse anesthesia events are the result of poor treatment Many oral and maxillofacial surgeons have saved patients’ lives with rapid diagnosis and treatment of a life-threatening event in their office For example, a patient has an acute heart attack in the waiting room before seeing the doctor The staff and doctor use their medical emergency management skills to stabilize and prepare the patient for transport to the hospital As a result, the patient survives The doctor and staff usually receive no public recognition for such lifesaving acts However, if the same patient experienced a heart attack in the course of office-based anesthesia, the actions of the professional team would be scrutinized publicly by the press, the licensing authority, and the legal community In general, the public expects that any patient who enters an oral surgery office for treatment will leave without complications Patients and families not consider the possibility that a life-threatening adverse event may occur In some cases, an adverse event may necessitate that a patient be transported to the hospital for further evaluation and treatment (Box 13-1) 166 www.ajlobby.com Mizukawa_Chap_13.indd 166 6/20/17 10:38 AM Aftermath of an Adverse Outcome or Complication BOX 13-1 • • • • • • • • • • • • Adverse events that may necessitate hospital transport Respiratory distress Cardiac arrest or developing acute coronary syndrome/myocardial infarction Allergic reactions Pulmonary embolism Hypotension Swelling resulting from ACE inhibitor Seizures Paradoxical anesthetic drug reaction Stroke Hypertension Congestive heart failure Delayed emergence ACE, angiotensin-converting enzyme If an adverse event occurs, the oral and maxillofacial surgeon may become a defendant in a lawsuit Anyone may file a lawsuit for any reason When a medical malpractice lawsuit is filed, usually several allegations are entered in the complaint (Box 13-2) Because a severe complication or the death of a patient is a catastrophic event, the relevance of other associated complications may be overlooked These complications may include the following: • Phlebitis • Falls • Nerve injuries resulting from needle sticks or positioning • Administration of drugs by nonlicensed personnel • Contamination of supplies or medications BOX 13-2 • • • • • • • • • • Common themes of allegations in anesthesia-related death claims Loss of adequate oxygenation Delay in instituting proper resuscitation Failure of patient to respond Judgment on location for a procedure Judgment on level of anesthesia Delay in recognition of the event Failure to appropriately resuscitate Inadequate preoperative history Judgment on drug selection Inadequate assistance Regardless of the treatment administered or outcome in these situations, the oral and maxillofacial surgeon may face litigation It may be several years after the incident before a claim is made Therefore, the surgeon’s response to the adverse event and the clinical record are critical to the defense 167 www.ajlobby.com Mizukawa_Chap_13.indd 167 6/20/17 10:38 AM 13 • Aftermath of an Adverse Outcome or Complication Documentation Is Your Best Defense In my experience, I have never met anyone who wished to have documented less after an adverse event However, documentation begins before an adverse event occurs Plaintiffs’ attorneys usually review the medical records before deciding to file a malpractice lawsuit If the records clearly document the surgeon’s clinical findings, the subsequent treatment, and, ultimately, the resuscitation efforts, such detailed records may deter a plaintiff’s attorney from filing a lawsuit, or, if a lawsuit is filed, such records will substantiate that appropriate care was provided In malpractice litigation resulting from an untoward anesthesia outcome, the oral and maxillofacial surgeon’s anesthesia record may be held to the standard of an anesthesia record used in a hospital operating room setting The oral and maxillofacial surgeon’s office-based anesthesia record should include contemporaneous time-stamped documentation of medications administered and vital signs Similarly, the documentation should include time-based records of any patient resuscitation The following steps will assist in your defense: • Maintain complete, original documentation of the patient’s history, informed consent, and treatment along with contemporaneous anesthesia and emergency resuscitation records • Keep your original records, and send only copies with the emergency medical services (EMS) to the hospital and to anyone else who requests the records After the event, you may remember important information that, because of the chaos of the event, was not recorded Always confer with your attorney before entering an addendum to the patient’s office record • Never alter the records or falsify facts Any altering of events is almost always discovered by the plaintiff’s counsel during depositions A perception of fabrication or alteration will cause you to lose credibility If that happens, no matter how defensible your actions are, you will not be believed by a professional licensing board or jury Preparing for Adverse Events Regular, organized patient rescue drills will support a culture of safety and preparedness that will prove valuable should a patient require critical rescue measures Offices in states that require anesthesia permits have regulatory guidelines and training requirements that must be assiduously observed The office staff will only be as good as their training; therefore, frequent patient emergency management training and practice are necessary OMSNIC offers a complimentary educational series for oral and maxillofacial surgeons and staff on the management of medical emergencies in the oral and maxillofacial surgeon’s office Managing an emergency effectively is a true team effort, and the best outcomes are achieved only with practice Responding to an Adverse Event The following actions are recommended if an anesthetic adverse event occurs • Manage the event appropriately in your office −− Treat the patient in accordance with appropriate algorithms −− Request help early from associates and notify EMS −− Designate a scribe to maintain a time-based record of medications and rescue interventions −− Assign a staff member to bring the family members into a private area before the arrival of EMS Explain that the patient experienced an unexpected event and is being transported to the hospital for further evaluation and treatment 168 www.ajlobby.com Mizukawa_Chap_13.indd 168 6/20/17 10:38 AM Responding to an Adverse Event • Arrange transportation of the patient to the hospital −− If permitted by EMS personnel, accompany the patient to the hospital If you are a solo practitioner, you may not be able to leave the office (eg, if other patients are recovering from anesthesia) −− Print out records from all monitors before they are disconnected −− Copy all records to be sent to the hospital −− Contact the emergency room physician at the receiving hospital and give a report before the patient arrives −− Have a staff member offer to drive the family members to the hospital −− Consider canceling remaining appointments and procedures if the emotional state of the surgeon and/ or staff may detract from normal office operations −− Arrange to meet at the hospital with the attending physicians, patient, and family members −− Be aware that expression of empathy is appropriate, but discussions with the patient and family regarding the cause of the event will generally have to wait for further evaluations, review of events, and so forth −− Respect the family’s wishes regarding your ongoing involvement as a concerned clinician, as a treating clinician, or in any other capacity • Contact your professional liability insurance carrier −− It is important to provide timely notification to your professional liability carrier of any adverse event, regardless of the perceived risk of legal action −− After an anesthetic adverse event, your professional liability carrier may assign a local attorney to assist you • Place your trust in the insurance carrier’s claim analyst and, if assigned, the defense attorney −− Follow their advice in the aftermath of the adverse event −− Do not alter any patient records Reporting to dental and medical licensing boards State professional licensing boards usually require notification by the surgeon when a patient is transported to the hospital from your office and if a patient you have treated expires within a defined period of time Timely reporting with accurate documentation not only is required but can minimize future problems It is recommended that legal counsel assist you in the reporting process Emotion and conjecture need to be separated from the facts In some cases, a hearing before a professional licensing board may be required Professional licensing boards have a duty to protect the public They also have the authority to discipline a clinician even to the extent of recommending revocation of an anesthesia permit or professional licensure Therefore, such hearings are a difficult and stressful process for the clinician Communicating with the patient’s family In my experience speaking with surgeons after a patient’s death, I have found that one of their first interests is the family of the patient They want to know how to discuss what has happened and show their concern Although I advise them to first confer with their attorney, an expression of sympathy is always helpful to both the grieving family and the surgeon In the first days after the event, autopsy and toxicology results are not known Therefore, the clinician should refrain from speculation regarding the cause or causes of the adverse event It is not uncommon for a family member of the deceased to blame the surgeon, complicating further a very difficult situation for the clinician A request by the surgeon for permission from the family to attend the funeral service demonstrates concern for the family and respect for the deceased patient 169 www.ajlobby.com Mizukawa_Chap_13.indd 169 6/20/17 10:38 AM 13 • Aftermath of an Adverse Outcome or Complication The Litigation Process An adverse event may lead to the filing of a malpractice lawsuit Litigation for an adverse event, regardless of the magnitude of the event, can be a stressful, demoralizing, and frustrating process because clinicians usually are not familiar with the adversarial nature of litigation The litigation process can leave surgeons feeling that they have been “put through the ringer” because their character, ethics, morals, and credibility have been challenged Because our patients rely on our expertise, we must place ourselves in the hands of professionals who can help protect us and look out for our best interest Working with your attorney and liability carrier Your defense attorney and professional liability carrier will assist you in the litigation process Ideally, you will have already made your professional liability carrier aware of the event by the time a lawsuit is filed Although you play an active role in the defense process, myriad people support and contribute to the successful handling of any malpractice claim Your liability insurance carrier’s claim analyst will handle the day-to-day aspects of your claim and assist you through the entire process A local defense attorney will be assigned to assist with your defense The defense attorney will the following: • Represent you in all legal aspects of the case • Likely take statements early in the process from all involved in the adverse event • Advise you on how to handle the local media if they approach you • Meet with you and your staff and advise you on communicating any information regarding the adverse event As clinicians, we have a natural tendency to discuss an adverse event to present our observations and professional opinion regarding the event However, you will be advised not to discuss the case with anyone This recommendation includes partners who were not present, referring clinicians, interested neighbors, and the staff The rationale for this advice is that the plaintiff’s attorney will eventually ask if you discussed the case with anyone and ask what you said The attorney may then question the person with whom you spoke If a discrepancy is found in what you and your confidant have said, the opposing attorney will attempt to discredit you A plaintiff’s attorney may also use those statements against you or take them out of context Participating in your defense Although skilled and devoted professionals are in place to assist you through the litigation process, your active participation in the defense process is required to obtain an optimal outcome When speaking with the claim analyst and your attorney, you should be honest and forthcoming with all information related to the claim Litigation often involves a flurry of activity, followed by long periods of little or no activity, during which time the lawyers gather records, review them, and submit them to consulting experts You will need to take time away from your practice to meet with your defense attorney and participate in activities such as depositions, jury selection, and even the trial itself At times, and even with the best defense team, this process can be frustrating 170 www.ajlobby.com Mizukawa_Chap_13.indd 170 6/20/17 10:38 AM Summary Emotional Impact on the Surgeon and Staff Oral and maxillofacial surgeons generally not deal with death on a routine basis Therefore, in addition to the effect of the adverse event on a patient and family, the aftermath of an anesthetic death event can be overwhelming for the surgeon and staff The surgeon and staff will often take the death of a patient personally and experience many of the grieving and psychologic challenges attributed to a personal loss Clinicians have resigned from practice after such events Other clinicians have committed suicide The surgeon may become the “other victim” as a result of perceived personal guilt, pressure from the family of the deceased, and, of course, the fear of disciplinary action by professional boards and legal retribution—all of which can affect family finances and the surgeon’s future I always advise surgeons to seek professional counseling for assistance during this stressful period if they are so inclined A valuable resource is the Physician Litigation Stress Resource Center (http://physicianlitigationstress.org), a website designed for health care practitioners involved in medical malpractice litigation It offers valuable resources to assist in managing the stressors associated with the claim and litigation experience Office staff may be emotionally distraught after an adverse event Staff should not be subject to blame in response to the surgeon’s struggle to come to terms with his or her personal emotions Rather, after any patient rescue scenario, it is important for the office team to debrief and acknowledge the collective efforts of the team on the patient’s behalf This process can occur in the absence of a clear understanding of mechanism of the adverse event In less complex rescue situations in which an adverse event has occurred without the death of a patient, it is beneficial for the surgeon and staff to analyze the adverse event and critique the team’s response After a death, the team should debrief, but speculation on the cause and possible mechanisms should be avoided Summary Although all surgeons hope never to have to experience the loss of a patient, unfavorable outcomes can occur even with excellent care By means of frequent training and simulated office emergencies, you can proactively prepare yourself and your staff for emergency situations that may occur If an untoward event happens, you will be prepared to respond and provide essential care for the patient If necessary, you will be in a better position to assist in your defense by providing accurate records to support your care and treatment of the patient who has experienced an anesthesia-related adverse event 171 www.ajlobby.com Mizukawa_Chap_13.indd 171 6/20/17 10:38 AM www.ajlobby.com Mizukawa_Chap_13.indd 172 6/20/17 10:38 AM II ANESTHESIA AND COMORBID DISEASE SECTION II SECTION www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 173 7/17/17 12:25 PM SECTION X SECTION II SECTION X SECTION X www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 174 7/17/17 12:25 PM CNS CHAPTER 14 The Central Nervous System Casey R Shepherd, dmd, md Daniel L Orr II, dds, ms (Anesthesiology), phd, jd, md www.ajlobby.com Mizukawa_Chapter_Openers.indd 175 6/21/17 3:24 PM CNS CHAPTER 14 The Central Nervous System Normal Anatomy and Physiology 177 Metabolic Disorders 179 Neurodegenerative/Demyelinating Disorders 182 Cerebrovascular Accident 185 Structural 188 Psychiatric Disorders 191 www.ajlobby.com Mizukawa_Chapter_Openers.indd 176 6/21/17 3:24 PM Normal Anatomy and Physiology The concepts of normal central nervous system (CNS) anatomy and physiology are integral to understanding the neuropharmacologic effects of anesthetic agents in patients with CNS conditions This chapter focuses on the relevant pathophysiology, diagnosis, management, and anesthetic considerations of metabolic, neurodegenerative, cerebrovascular, structural, and psychiatric diseases of the CNS Normal Anatomy and Physiology Anatomically, the CNS consists of the brain and the spinal cord The brain is divided into the cerebrum, the brainstem, and the cerebellum The cerebral cortex is the largest portion of the human brain and comprises two separate symmetric hemispheres joined caudally at their base by the corpus callosum The cerebral cortex is responsible for higher functions of memory, motor function, sensory perception, and cognitive thought Each hemisphere is divided by distinct fissures into four lobes (frontal, temporal, parietal, and occipital), each with a specific purpose and function The hypothalamus and the thalamus lie beneath the cerebral cortex The thalamus acts as a sensory relay station, connecting the peripheral nervous system to the cerebral hemispheres It also participates in functions of wakefulness and consciousness The hypothalamus is involved primarily in primitive perceptions and functions, such as hunger, thirst, sexual behavior, and sleep It also contributes to the regulation of hormone secretion from the pituitary gland The brainstem consists of the medulla, the pons, and the midbrain and is responsible for many primitive functions essential for survival The medulla primarily regulates homeostatic functions, such as blood pressure, cardiac rhythm, and breathing The pons is involved with coordinating eye and facial movements, facial sensation, hearing, and balance The midbrain is an important locale for automatic ocular motion and other specific functions of the visual and auditory systems The cerebellum maintains posture, balance, and muscular tone It also is involved in the fine-tuning of motor activity and the ability to perform rapid, repetitive, and coordinated motor functions.1 The spinal cord is an ovoid bundle of nervous tissue connecting the brain to the peripheral nervous system It is approximately 43 to 45 cm in length in adults and extends from the caudal medulla at the level of the foramen magnum to the level of the L1-2 intervertebral space Its primary functions are efferent motor transmission, afferent sensory conduction, and spinal reflex control.1 The brain is contained within the bony cranium, whereas the spinal cord is protected by the vertebrae of the spinal column Both the brain and the spinal cord are further protected by three layers of meninges, which, from the outermost to the innermost layer, are the dura mater, arachnoid mater, and pia mater Between these layers are several clinically important anatomical spaces, including the epidural, subdural, and subarachnoid spaces In particular, the subarachnoid space is notable because it contains cerebrospinal fluid (CSF), which is produced in the ventricular system of the brain and provides a cushion and basic immunologic protection to the brain and spinal cord CSF is also important in the autoregulation of cerebral blood flow.1 Anesthetic agents may have important effects on cerebral blood flow, metabolism, the properties of CSF, and intracranial pressure (ICP) Cerebral blood flow The adult human brain accounts for approximately 2% of total body weight but approximately 20% of total body oxygen utilization Accordingly, the brain receives 12% to 15% of total cardiac output (750 mL/min in adults) Cerebral blood flow (CBF) varies from 10 to 300 mL/100 g per minute, depending on metabolic activity The cerebral metabolic rate (CMR), a measure of cerebral oxygen consumption, increases with increased cerebral electrical activity In the absence of substantial oxygen reserves and because of the high oxygen demands of the brain, unconsciousness occurs in seconds with any interruption in cerebral blood flow If blood flow is not established within to minutes, irreversible cellular damage will occur.2 Different regions of the brain are more or less sensitive to hypoxia An important concept in the discussion of CBF is cerebral perfusion pressure (CPP), which is defined as the difference between mean arterial pressure (MAP) and ICP The association between CPP and ICP is important because increases in ICP > 30 mm Hg can decrease CPP and CBF The brain tolerates a range of blood pressure 177 www.ajlobby.com Mizukawa_Chap_14.indd 177 6/20/17 10:40 AM 14 • The Central Nervous System without compromising CBF CBF is autoregulated through a vascular smooth muscle response to changes in CPP The response is characterized by cerebral arterial constriction when CPP is increased and arterial dilation when CPP is decreased In normal individuals, CBF remains nearly constant if MAP remains between 50 and 150 mm Hg Beyond these limits, CBF becomes pressure dependent Specifically, after cerebral vessels are maximally dilated or constricted, autoregulation ceases, and CBF has a direct linear relationship to CPP Because ICP is normally < 10 mm Hg, CPP is primarily a function of MAP Increases in ICP can have a profound effect on cerebral perfusion According to the Monro-Kellie doctrine, the intracranial compartment is incompressible and therefore has a fixed volume Accordingly, any increase in the volume of one of its constituents (80% brain, 12% blood, 8% CSF) will lead to an increase in ICP unless an equal decrease in volume of another intracranial component occurs Common causes of increased ICP include parenchymal brain edema, intracranial hypertension, hydrocephalus, intracranial hemorrhage, venous thrombosis, increased venous pressure, tumors, and abscesses Normally, small changes in any constituent are compensated for by other components (eg, displacement of CSF from cranial to spinal compartments, increase in CSF absorption, decrease in CSF production, and decrease in total cerebral venous blood volume) However, after a threshold is reached, the elastic properties of the intracranial compartment are exhausted, and ICP rises exponentially The body attempts to compensate for decreased CPP by increasing MAP, but eventually compensatory mechanisms fail and ischemia results.2–4 Other factors affecting CBF include respiratory gas tensions, temperature, and blood viscosity The partial pressures of arterial carbon dioxide (Paco2) and oxygen (Pao2) are the most important extrinsic influences on CBF Paco2 is the most influential of the two gas tensions Mediated by the pH of the CSF, CBF increases approximately to mL/100 g per minute for each mm Hg increase in Paco2 Hyperventilation, which lowers Paco2, is therefore an effective method of rapidly reducing CBF and ICP Severe hypoxemia (Pao2 < 50 mm Hg) increases CBF substantially.2 As expected, hypothermia decreases and hyperthermia increases cerebral oxygen consumption and CBF Finally, CBF is increased with decreased blood viscosity (eg, anemia) and decreased with increased blood viscosity (eg, polycythemia).2 Apart from cerebral oxygen utilization, another important metabolic consideration is brain glucose consumption Nervous tissue cells depend on a continuous supply of glucose as their primary energy source Therefore, acute hypoglycemia can be harmful to the brain Blood-brain barrier The blood-brain barrier is a vascular barrier formed by tight junctions between cerebral vascular endothelial cells This barrier is lipid soluble but restricts substances with large molecular weights or substances that are ionized Accordingly, carbon dioxide, oxygen, water, and lipid-soluble substances freely cross the blood-brain barrier, whereas ions, proteins, and other substances with large molecular weight are restricted Conditions such as severe hypertension, tumors, trauma, stroke, infection, severe hypercapnia/hypoxia, and sustained seizure activity can compromise the blood-brain barrier.2 Effects of anesthetic agents The specific effects on the CNS of all anesthetic agents used alone or in combination are beyond the scope of this chapter In general, inhalational anesthetics decrease CMR When used with an intravenous anesthetic agent, nitrous oxide has minimal effects on CBF, CMR, and ICP Cerebral blood flow is increased by inhalational anesthetics through vasodilation and reduced by intravenous anesthetics With the exception of ketamine, intravenous anesthetics decrease CMR and CBF or have little effect on these physiologic parameters 178 www.ajlobby.com Mizukawa_Chap_14.indd 178 6/20/17 10:40 AM Porphyria Opioids generally have minimal effect on CMR and CBF unless hypercapnia results from respiratory depression Etomidate decreases CMR and CBF It is also associated with myoclonic activity and should be avoided in patients with seizure disorder Propofol reduces CMR and CBF Dystonic movements can be observed with propofol, although it raises the seizure threshold and is well suited for use in patients with seizure disorder Benzodiazepines lower CMR and CBF but to a lesser extent than etomidate and propofol Like propofol, benzodiazepines also raise the seizure threshold Ketamine is the only intravenous anesthetic agent that dilates the cerebral vasculature and increases CBF Because of the simultaneous CNS stimulatory and depressant actions of ketamine, it does not change the total CMR Ketamine can impair absorption of CSF, which in combination with increased CBF increases ICP As an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine may afford some protective effect against cerebral cell death and the resulting brain damage The reversal agents naloxone and flumazenil can reverse the beneficial reductions in CMR and CBF and should be used cautiously when these effects are desired Metabolic Disorders Porphyria Pathophysiology and diagnosis Porphyria is a rare group of inherited or acquired disorders characterized by enzymatic defects in heme biosynthesis Manifestations of the disease are a result of decreased heme production, increased accumulation of porphyrins in tissue, or increased δ-aminolevulinic acid (dALA) synthetase activity Porphyrias are classified according to three characteristics: (1) site of abnormal porphyrin production (hepatic versus erythropoietic), (2) acute or nonacute presentation, and (3) pattern of enzyme deficiency in heme production5 (Box 14-1) Hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, plumboporphyria), with the exception of porphyria cutanea tarda, tend to have predominantly neurologic signs and symptoms, whereas erythropoeitic porphyrias (uroporphyria, protoporphyria) result in skin involvement/sensitivity Acute porphyric attacks occur in only four types of porphyria: acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and dALA dehydratase deficiency porphyria (plumboporphyria).5–7 BOX 14-1 Classification of porphyrias Hepatic nonacute • Familial porphyria cutanea tarda • Acquired porphyria cutanea tarda Hepatic acute • Acute intermittent porphyria • Hereditary coproporphyria • Variegate porphyria • dALA dehydratase deficiency porphyria (plumboporphyria) Erythropoietic • Uroporphyria • Protoporphyria 179 www.ajlobby.com Mizukawa_Chap_14.indd 179 6/20/17 10:40 AM 14 • The Central Nervous System When an acute attack is triggered, the most common signs and symptoms include severe abdominal pain, vomiting, anxiety, confusion, hysteria, peripheral neuropathy (motor more frequently than sensory), hypertension, tachycardia, dehydration, red/purple urine, and electrolyte disturbances, such as hyponatremia, hypokalemia, hypochloremia, and hypocalcemia5,8 (Box 14-2) BOX 14-2 Clinical features of acute intermittent porphyria Cerebral involvement • Altered mental status • Confusion/hysteria • Anxiety/depression • Psychosis • Seizures • Coma Autonomic neuropathy • Abdominal pain • Vomiting • Tachycardia • Hypertension • Postural hypotension Peripheral neuropathy • Paresis/paralysis • Flaccid quadriplegia • Respiratory paralysis Laboratory pathology • Dark urine • Hyponatremia • Hypokalemia • Hypochloremia • Hypomagnesemia • SIADH • Leukocytosis Bulbar involvement • Cranial nerve dysfunction • Dysphagia • Dysphonia • Respiratory dysfunction Hypothalamic involvement • SIADH • Pyrexia SIADH, syndrome of inappropriate antidiuretic hormone Management Treatment of an acute porphyric crisis consists of reversing factors that increase dALA synthetase activity, withdrawing offending drugs, treating symptoms, and monitoring the patient Treatment includes hydration, electrolyte monitoring, administration of 10% dextrose (20 g/h), use of propranolol, treatment of underlying infection (if present), and administration of heme compound (hematin or heme arginate), cimetidine, antiemetics, and opioid analgesics Triggering drugs should be avoided during the treatment of symptoms resulting from an acute attack.5 After an acute porphyric crisis, emphasis should be placed on treatment of ongoing symptoms, such as pain, nausea, vomiting, hypoglycemia, and dehydration To avoid future attacks, an attempt should be made to determine the triggering drug Patients should be counseled to limit fasting, unnecessary dieting, alcohol, illegal drugs, smoking, excessive sun exposure, and emotional stress if possible After their first episode of porphyric crisis, patients should consult their primary care physician for diagnostic workup 180 www.ajlobby.com Mizukawa_Chap_14.indd 180 6/20/17 10:40 AM Porphyria Anesthetic considerations Factors that can precipitate an acute porphyric crisis include fasting/dehydration, infection, psychologic stress, physiologic hormone variation (eg, menstruation, pregnancy), excessive alcohol intake, and triggering drugs Although many commonly used drugs have been shown to display unsafe or unclear effects in patients with porphyria (Table 14-1), the most clinically relevant triggering drugs to avoid in the outpatient oral and maxillofacial surgery setting include barbiturates, etomidate, ketorolac, and hydralazine.5,8,9 Diazepam and ketamine should be used with caution because their effect on patients with porphyria is unclear.5 Table 14-1 Use of drugs during anesthesia in patients with porphyria Use in patients with porphyria Type of drug Intravenous agents Volatile agents Safe Unsafe • Midazolam • Propofol • Barbiturates • Etomidate Nitrous oxide Enflurane Unclear • Diazepam • Ketamine • Isoflurane • Sevoflurane • Desflurane Neuromuscular blockers • Succinylcholine • Vecuronium • Rocuronium – Atracurium Opioids • Morphine • Fentanyl • Dilaudid – Sufentanil Anticholinesterases Neostigmine – – Local anesthetics • Bupivacaine • Procaine – Cardiovascular • Atenolol • Labetalol • α-methyldopa • Hydralazine – Other • Glucose loading • Anticonvulsants • Scopolamine • Atropine • Droperidol • Promethazine • Chloral hydrate • Diphenhydramine • Cimetidine • Steroids • Oral contraceptives • Griseofulvin • Ketorolac – Lidocaine –, lack of known information in the specified category 181 www.ajlobby.com Mizukawa_Chap_14.indd 181 6/20/17 10:40 AM 14 • The Central Nervous System Neurodegenerative/Demyelinating Disorders Neurodegenerative disorders represent a diverse group of disease states that typically involve neuronal malfunction or loss within specific anatomic regions.3 For the purposes of this chapter, the most common and clinically relevant conditions, including Alzheimer disease, Parkinson disease, and multiple sclerosis, will be discussed Alzheimer Disease Pathophysiology and diagnosis Alzheimer disease is a chronic neurodegenerative disorder characterized by progressive cognitive impairment as well as memory loss, apraxia, aphasia, and agnosia It is the most common cause of dementia in patients older than 65 years and the fourth most common cause of disease-related death in the same population Though the cause of Alzheimer disease is still poorly understood, it is thought to be largely genetic in etiology Pathophysiologic hypotheses include decreased acetylcholine, extracellular amyloid deposits, and tau protein abnormalities with consequent neurofibrillary tangles Diagnosis is clinical and based predominantly on history and behavioral observations.3 Management No cure currently exists for Alzheimer disease, and treatment focuses on managing symptoms Pharmacologic options include cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine.3 However, even with treatment, the prognosis for patients with Alzheimer disease is poor Anesthetic considerations Anesthetic considerations in patients with Alzheimer disease include adequate preoperative education, use of short-acting agents, and avoidance of drug interactions Patients with Alzheimer disease, as well as other patients with dementia, are often confused and uncooperative in the immediate preoperative period Their attention span is limited, and they often ask the same questions multiple times with progressive agitation The provider should attempt to answer each question and reorient/reeducate the patient when possible Patience is essential.10 It is often helpful to have a familiar caregiver present during the pre-anesthetic and recovery phases of care The median effective dose of intravenous anesthetics is reduced in patients with Alzheimer disease because of the geriatric distribution of the disease Geriatric patients show increased volumes of distribution, decreased renal clearance, and reduced hepatic metabolism.11 Accordingly, shorter-acting anesthetic agents are preferred because they allow a more rapid return to baseline mental status.3 Anticholinergic medications should be avoided in patients with Alzheimer disease because these medications may exacerbate cognitive decline Common medications with anticholinergic activity include amitriptyline, atropine, clozapine, chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine.12 If an anticholinergic medication is necessary, glycopyrrolate is preferable because it does not cross the blood-brain barrier.10 The effects of succinylcholine are prolonged in patients with Alzheimer disease who take cholinesterase inhibitors These same patients show relative resistance to the non-depolarizing paralytics.3 182 www.ajlobby.com Mizukawa_Chap_14.indd 182 6/20/17 10:40 AM Parkinson Disease Parkinson Disease Pathophysiology and diagnosis Parkinson disease is a neurodegenerative disorder of unknown cause that affects approximately 1% of the population older than 60 years.2,13 Histopathologically, it is characterized by loss of dopaminergic fibers in the substantia nigra of the basal ganglia As a result, regional dopamine concentrations are depleted, resulting in diminished dopamine inhibition in the extrapyramidal motor system and consequent unopposed stimulation by acetylcholine.3 Classic signs of parkinsonism include the following: • Skeletal muscle tremor: resting tremor, “pill-rolling” tremor • Rigidity: cogwheel or lead-pipe rigidity, loss of arm swing, loss of head rotation when turning body • Bradykinesia: slow movement, difficulty initiating and executing movements • Postural instability: forward-flexed posture, festinating gait • Other: masklike facies, micrographia, hypophonia, dysphagia Management Treatment of Parkinson disease is targeted at increasing the concentration of dopamine in the basal ganglia and decreasing the neuronal effects of unopposed acetylcholine Levodopa, a dopamine precursor, is the most effective treatment of Parkinson disease It is typically combined with the decarboxylase inhibitor carbidopa to decrease the peripheral conversion of levodopa to dopamine and maximize the amount available to enter the CNS through the blood-brain barrier.13 Catechol-O-methyltransferase inhibitors, such as entacapone and tolcapone, are also used to prevent decarboxylation of levodopa in the peripheral circulation.2 Other antiparkinsonism drugs include amantadine, an antiviral agent, and selegiline, a type B monoamine oxidase inhibitor Anesthetic considerations Anesthetic considerations in the patient with Parkinson disease include the following: • Establishment of intravenous access may be challenging because of resting tremor • Levodopa therapy should be continued as usual The medication’s short half-life dictates continued routine administration to prevent withdrawal • Medications with antidopaminergic activity should be avoided Common antidopaminergic drugs include haloperidol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amoxapine, clomipramine, trimipramine, metoclopramide, droperidol, and domperidone.2–4 • Ketamine should be used with caution because it can cause cardiac irritability, exaggerated sympathetic nervous system responses, and arrhythmias.2 • Excessive salivation requires thorough suctioning of the posterior oropharynx to prevent accumulation of saliva and consequent laryngospasm 183 www.ajlobby.com Mizukawa_Chap_14.indd 183 6/20/17 10:40 AM 14 • The Central Nervous System Multiple Sclerosis Pathophysiology and diagnosis Multiple sclerosis is characterized by demyelination at multiple random sites within the brain and spinal cord Typically, the diagnosis requires the presence of two or more attacks associated with demyelinating lesions separated by both time and space In other words, patients will have two or more lesions found in separate parts of the CNS on separate occasions Although the cause is unknown, an autoimmune etiology initiated by a viral insult is largely accepted.2 Caucasian women between 20 and 40 years of age are primarily affected, with a geographic distribution favoring northern latitudes and areas of low sunlight The disease is characterized by alternating periods of attack and remission and is subcategorized according to these patterns (relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing)14,15 (Fig 14-1) The symptoms depend on the location of the lesions but often include sensory disturbances, motor weakness, and visual problems Fig 14-1 Progression of multiple sclerosis subtypes (a) Progressiverelapsing multiple sclerosis is characterized by steady increase in disability after onset with intermittent attacks (b) Secondary progressive multiple sclerosis is initially similar to relapsing-remitting multiple sclerosis but then results in increasing disability without periods of remission (c) Primary progressive multiple sclerosis is characterized by steady increase in disability without attacks (d) Relapsing-remitting multiple sclerosis causes unpredictable attacks, which may or may not leave permanent deficits, followed by periods of remission.14 a Increasing disability b c d Time 184 www.ajlobby.com Mizukawa_Chap_14.indd 184 6/20/17 10:40 AM Stroke Management Treatment is based on symptoms Common medications include diazepam, dantrolene, and baclofen to treat spasticity; bethanechol and other anticholinergics to treat urinary retention; and carbamazepine, phenytoin, or antidepressants to treat dysesthesias Glucocorticoids have been shown to be effective in decreasing the severity and duration of acute attacks, but little evidence supports their effect on long-term recovery Plasmapheresis is considered in patients who are unable to tolerate high-dose steroids In addition, glatiramer and interferon β have been shown to reduce the frequency of relapse by up to 30%.2 Anesthetic considerations Anesthetic considerations in patients with multiple sclerosis include the following: • Elective surgery should be avoided during relapse if possible The stress of anesthesia and surgery may lead to an attack • If a procedure is necessary, the process of obtaining consent should address the possibility that the procedure may trigger an attack and/or worsen existing symptoms • Increases in patient body temperature should be minimized Demyelinated fibers are extremely sensitive to temperature increases; an increase of as little as 0.5°C may completely block conduction.4 Cerebrovascular Accident Stroke Pathophysiology and diagnosis Cerebrovascular accident (CVA), or stroke, is defined as a sudden neurologic deficit resulting from ischemia (88% of cases) or hemorrhage (12% of cases) within the brain16,17 (Table 14-2) Stroke is the third leading cause of death in the United States and the leading cause of major disability Women have lower stroke rates than men until age 75 years Stroke rates are highest after age 75 years.3 185 www.ajlobby.com Mizukawa_Chap_14.indd 185 6/20/17 10:40 AM 14 • The Central Nervous System Table 14-2 Stroke subtypes Type of stroke Ischemic stroke Hemorrhagic stroke Subtype Risk factors Onset Signs and symptoms Hypoperfusion • Hypotension • Hemorrhage • Myocardial infarction Thromboembolism Sudden • Ischemic heart disease • Valvular heart disease • Peripheral vascular disease • Dilated cardiomyopathy • Hyperlipidemia • Atrial fibrillation • Diabetes mellitus • Caucasian race • Smoking • Male sex Headache Thrombosis • Often preceded by • Ischemic heart disease transient ischemic • Peripheral vascular disease attack • Hypertension • Fluctuating • Hyperlipidemia • Polycythemia • Diabetes mellitus • Caucasian race • Smoking • Male sex Headache Subarachnoid hemorrhage • Often none • Hypertension • Coagulopathy • Drugs* • Trauma • Ruptured aneurysm • Sudden • Often during exertion • Headache • Vomiting • Transient loss of consciousness Intracerebral hemorrhage • Hypertension • Coagulopathy • Drugs* • Trauma • African American race Gradual • Headache • Vomiting • Decreased consciousness • Seizures Parallels systemic disorder • Hypotension • Low urine output • Pallor • Diaphoresis *Include anticoagulants, antiplatelets, and thrombolytics The most common risk factors for CVA include hypertension, atrial fibrillation, diabetes mellitus, obesity, hypercholesterolemia, oral contraceptive use, and cigarette smoking Consistent hypertension has been demonstrated to be the major risk factor in the development of both hemorrhagic and atherosclerotic CVA The risk of the development of an acute CVA is estimated to increase by 30% for every 10 mm Hg elevation in systolic blood pressure above 160 mm Hg.18 Warning signs of acute stroke evolution include sudden onset of any of the following16: • Unilateral numbness or weakness of the face, arm, or leg • Confusion, difficulty speaking or understanding • Difficulty walking, dizziness, loss of balance or coordination • Difficulty seeing in one or both eyes • Severe headache with no known cause 186 www.ajlobby.com Mizukawa_Chap_14.indd 186 6/20/17 10:40 AM Stroke Management Acute signs of stroke represent a medical emergency If signs or symptoms arise, the emergency response system should be activated immediately The main goals of management of acute stroke are to ensure medical stability, reverse conditions contributing to the problem, identify the type of stroke, and determine if patients with acute ischemic stroke are candidates for thrombolytic therapy Management of acute ischemic stroke is as follows: • Use intravenous tissue thromboplastin activator in patients who meet criteria and in whom treatment can be initiated within 3.0 to 4.5 hours of symptom onset Prognosis depends on the time elapsed from the onset of symptoms to thrombolytic intervention.3 • Maintain adequate blood pressure Rapid lowering of blood pressure can impair cerebral perfusion and worsen ischemic injury Permissive hypertension should not exceed 185/110 mm Hg.19 • Maintain normothermia with antipyretics and cooling blankets as necessary • Initiate antithrombotic therapy within 48 hours • Initiate deep vein thrombosis/pulmonary embolism prophylaxis • Patients should have no oral intake because of the risk of dysphagia and aspiration pneumonia • Glucose should be monitored Both hyperglycemia and hypoglycemia should be avoided.19 • Transfer the patient to the neurologic intensive care unit if possible Management of acute hemorrhagic stroke is as follows: • Discontinue and reverse all anticoagulants and/or antiplatelet drugs if possible • The target MAP for intracranial hemorrhage without increased ICP is 110 mm Hg If increased ICP is present, the ICP should be monitored and MAPs titrated to maintain CPP between 60 and 80 mm Hg.19–21 • Raising the head of the bed 30 degrees and short-term hyperventilation can help decrease ICP • Maintain normothermia with antipyretics and cooling blankets as necessary • Avoid hypervolemia and hypotonic fluids because they increase cerebral edema • Patients should have no oral intake because of the risk of dysphagia and consequent aspiration pneumonia • Glucose should be monitored Both hyperglycemia and hypoglycemia should be avoided.21 • Use pneumatic compression devices for deep vein thrombosis/pulmonary embolism prophylaxis beginning the day of hospital admission.21 • Initial monitoring and management should take place in an intensive care unit or dedicated stroke unit.2 Anesthetic considerations Preoperative anesthetic considerations in the patient with stroke history and/or stroke risk include the following: • Patients at high risk should be identified17 (see Table 14-2) −− The patient should be considered ASA class II if patient had a CVA > months earlier and has no evidence of residual neurologic deficit −− The patient should be considered ASA class III if patient had a CVA > months earlier and has some degree of neurologic deficit −− The patient should be considered ASA class IV if patient had a CVA < months earlier or if substantial residual deficit remains.16 • Elective procedures should be postponed if the risk of stroke is substantial and the proper treatment has not been instituted to decrease the risk (anticoagulation, carotid endarterectomy, etc).22 • If proper risk reduction treatment has been instituted and the stroke occurred > months earlier, elective surgery is permissible The surgeon should confer with the patient’s primary care physician and/or neurologist.22 187 www.ajlobby.com Mizukawa_Chap_14.indd 187 6/20/17 10:40 AM 14 • The Central Nervous System Perioperative anesthetic considerations in the patient with stroke history and/or stroke risk include the following steps: • Obtain baseline vital signs • Minimize hypertension • Take care not to decrease blood pressure substantially from baseline (> 15%), especially in patients with carotid bruit, known carotid artery stenosis, or vertebrobasilar insufficiency • Limit epinephrine in local anesthetics to 40 µg (two carpules of local anesthetic with 1:100,000 epinephrine) • Vital signs should be measured periodically (every minutes) after administration of local anesthetics • Stress reduction strategies (eg, short appointments, effective pain control, management of apprehension) should be prioritized to minimize endogenous catecholamine release Sedation is beneficial because it provides anxiolysis and analgesia.23 Structural Disorders Seizure Disorder Pathophysiology and diagnosis The term seizure refers to a paroxysmal alteration in neurologic function caused by a synchronous, rhythmic depolarization of brain cortical neurons.4 Epileptic seizures are classified as partial or generalized Partial seizures may be simple (ie, without impairment of consciousness) or complex (ie, with impairment of consciousness) Generalized seizures may be nonconvulsive (also called absence) or convulsive.24 In general, seizures can result from numerous etiologies, including discontinuation of sedative-hypnotic drugs or alcohol, discontinuation of antiepileptic drugs, drug abuse (narcotics, cocaine, amphetamines), uremia, traumatic injury, neoplasms, infection, congenital malformations, birth injuries, electrolyte disturbances, blood in the ventricles, hypoxia, vascular disease, vascular accidents, or idiopathic etiologies.4 A seizure will occur in 6% to 10% of people younger than 70 years at some point during their lifetime Among patients who have had a seizure, 50% to 70% never have another However, 70% of people who have had two or more seizures have a defined epileptic focus and require antiepileptic medication.4,25 Management Older antiepileptic drugs, such as phenytoin, valproic acid, carbamazepine, ethosuximide, and phenobarbital, are now used less frequently because of their side effects Newer drugs, such as gabapentin, pregabalin, lamotrigine, topiramate, levetiracetam, and oxcarbazepine, are becoming more popular because of their efficacy, side effect profiles, and decreased interaction with other drugs4,25,26 (Box 14-3) 188 www.ajlobby.com Mizukawa_Chap_14.indd 188 6/20/17 10:40 AM Seizure Disorder BOX 14-3 Uncommon serious side effects of common antiepileptic drugs Carbamazepine • Agranulocytosis • Aplastic anemia • SJS/TEN • Hepatic failure • Dermatitis • Serum sickness • Pancreatitis • Lupus Ethosuximide • Agranulocytosis • SJS/TEN • Aplastic anemia • Hepatic failure • Dermatitis • Serum sickness Gabapentin • Multiorgan hypersensitivity Lamotrigine • SJS/TEN • Multiorgan hypersensitivity • Aseptic meningitis Levetiracetam • SJS/TEN • Pancytopenia • Psychosis Pregabalin • Angioedema • Hypersensitivity reactions • Rhabdomyolysis Oxcarbazepine • SJS/TEN • Multiorgan hypersensitivity • Agranulocytosis • Pancytopenia • Leukopenia Topiramate • Acute myopia and glaucoma • Kidney stones • Oligohidrosis and hyperthermia (primarily occurs in children) Phenytoin • Agranulocytosis • SJS/TEN • Aplastic anemia • Hepatic failure • Dermatitis • Serum sickness • Adenopathy • Pseudolymphoma • Neuropathy • Ataxia • Lupus • Hirsutism Valproate • Agranulocytosis • SJS/TEN • Aplastic anemia • Hepatic failure • Dermatitis • Serum sickness • Pancreatitis • Polycystic ovary syndrome SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis Anesthetic considerations Preoperatively, the clinician should consider hospital-based procedures for patients with questionable seizure control, including new seizure diagnosis, recent medication changes, vagal nerve stimulators, and history of status epilepticus.27 It is important that antiepileptic drugs be continued in the therapeutic range.25,28,29 Low antiepileptic drug levels are one of the leading causes of seizures in patients with epilepsy.30 In the perioperative setting, drugs that lower the seizure threshold should be avoided in the epileptic patient, especially in combination with one another31 (Box 14-4) Local anesthesia should be used judiciously because overdose of local anesthetic agents can suppress inhibitory neurons and increase seizure activity Although benzodiazepines are safe to use, reversal with flumazenil should be limited to emergencies because it is known to elicit seizures in patients with epilepsy.32–34 Opioids such as fentanyl and morphine are safe to administer but should be given with caution because they may become convulsant at higher doses.27,35 Meperidine should be avoided entirely, particularly in patients who have concurrent renal insufficiency, because it produces an epileptogenic metabolite, normeperidine.36 Propofol and many barbiturates appear to raise the seizure threshold and are therefore excellent anesthetic choices in the outpatient setting.27 Methohexital, however, appears to have the least protective effect and should be used with caution because it can activate epileptic foci.3 Ketamine increases the seizure threshold at doses used for sedation but may be convulsant at lower doses.37 Perioperative use of intravenous fluids containing glucose should be considered in order to prevent hypoglycemia-induced seizure activity In the event of status epilepticus (a single seizure lasting > minutes, or a series of seizures in which consciousness is not recovered), one of four pharmacotherapies may be employed: benzodiazepines, phenytoin/fosphenytoin, barbiturates, or propofol.25,27–29 189 www.ajlobby.com Mizukawa_Chap_14.indd 189 6/20/17 10:40 AM 14 • The Central Nervous System BOX 14-4 Common drugs reported to induce seizures Analgesics • Fentanyl • Meperidine • Propoxyphene • Tramadol Antipsychotics • Chlorpromazine • Haloperidol • Prochlorperazine • Thioridazine Antibiotics • Ampicillin • Cephalosporins • Imipenem • Isoniazid • Metronidazole • Penicillin Respiratory agents • Aminophylline • Theophylline Antidepressants • Amitriptyline • Bupropion • Nortriptyline Local anesthetics • Bupivacaine • Lidocaine • Procaine General anesthetics • Enflurane • Ketamine • Methohexital Others • Alcohol • Amphetamines • Anticholinergics • Antihistamines • Atenolol • Baclofen • Cyclosporine • Flumazenil • Hyperbaric oxygen • Iodinated contrast agents • Insulin • Lithium • Methylphenidate • Methylxanthines • Ondansetron • Tacrolimus Sympathomimetics • Ephedrine • Phenylpropanolamine • Terbutaline SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis Neoplasm Pathophysiology and diagnosis Primary CNS tumors are an uncommon and diverse group of neoplasms that can arise from virtually any cell type within the CNS Common tumor types include astrocytoma, oligodendroglioma, ependymoma, meningioma, pituitary adenoma, and acoustic neuroma Intracranial tumors may also result from metastasis of other malignancies Diagnosis of CNS lesions is generally based on magnetic resonance imaging (MRI) Both primary and metastatic tumors can cause either generalized or focal signs/symptoms38 (Box 14-5) Generalized symptoms result from mass effect within the cranium and consequent increased ICP Supratentorial tumors are more common in adults than in children and typically cause headache, seizures, or new neurologic deficits Infratentorial tumors are more common in children than in adults and typically cause obstructive hydrocephalus and ataxia.3 BOX 14-5 Signs and symptoms of CNS neoplasms Focal • Seizures • Weakness • Sensory deficits • Aphasia • Visual spatial dysfunction Generalized • Headaches • Seizures • Nausea/vomiting • Depressed level of consciousness • Neurocognitive dysfunction 190 www.ajlobby.com Mizukawa_Chap_14.indd 190 6/20/17 10:40 AM Psychiatric Disorders Management Management of CNS neoplasms may include surgery, chemotherapy, and/or radiation therapy, depending on the nature of the neoplasm Anesthetic considerations Anesthetic considerations in the patient with an intracranial mass revolve around the presence and/or potential increase of ICP.3 Symptoms of increased ICP include nausea, vomiting, and altered level of consciousness Objective signs include mydriasis, decreased reactivity of pupils to light, papilledema, bradycardia, systemic hypertension, and breathing disturbances A midline shift > 0.5 cm on computed tomography or MRI is also suggestive of increased ICP Patients with increased ICP may be extremely sensitive to opioids and sedatives CNS depression promotes hypoventilatory hypercapnia with consequent further increases in ICP In addition, drug-induced sedation can mask alterations in the level of consciousness that normally would accompany intracranial hypertension.3 Sedatives should therefore be used with caution Ketamine increases ICP and is contraindicated in patients with lesions that occupy intracranial space Propofol decreases ICP and is therefore an excellent alternative.3,39,40 Psychiatric Disorders Pathophysiology and diagnosis Although the spectrum of psychiatric disease is extensive, the most common disorders include mood disorders (eg, depression, anxiety, bipolar disorder), psychotic disorders, and personality disorders Pathophysiologically, these conditions are caused by dysregulation of monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine Psychiatric disorders are present in approximately 30% of patients requiring outpatient anesthesia and surgery in the United States Furthermore, 50% of these patients take or have recently taken medication for the psychiatric disorder Accordingly, the most important preoperative consideration for patients with psychiatric disorders is understanding each patient’s specific drug therapy and its associated side effect profile.4,27 Common medication classes used in the treatment of psychiatric disorders include antidepressants, mood-stabilizing agents, and antipsychotics Management Antidepressants Selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin at presynaptic membranes and are used in the treatment of depression and most mood disorders They have virtually no adrenergic, cholinergic, or histaminergic activity and therefore few side effects When present, observed side effects include agitation, headache, insomnia, nausea, diarrhea, dry mouth, and sexual dysfunction.2,3 Serotonin syndrome, a drug-induced hyperthermic condition, is a potentially life-threatening reaction resulting from elevated levels of serotonin (Table 14-3) It is caused by the interaction of drugs that affect the production, release, or metabolism of serotonin3,41–43 (Box 14-6) 191 www.ajlobby.com Mizukawa_Chap_14.indd 191 6/20/17 10:40 AM 14 • The Central Nervous System Table 14-3 Comparison of drug-induced hyperthermic syndromes Syndrome Onset Causative drugs Features Treatment Malignant hyperthermia Minutes • Succinylcholine • Inhalational anesthetics • Muscle rigidity • Hypercarbia • Hypertension • Dantrolene • Supportive care (ie, cardiopulmonary support, cooling, hydration, and correction of acidosis as needed) Neuroleptic malignant syndrome 24-72 h Antipsychotics • Muscle rigidity • Tachycardia • Hypertension • Stupor or coma • Rhabdomyolysis • Bradykinesia • Bromocriptine • Dantrolene • Supportive care (ie, cardiopulmonary support, cooling, hydration, agitation control, and correction of acidosis as needed) Serotonin syndrome Up to 12 h • SSRIs • MAOIs • Atypical antidepressants • Clonus • Hyperreflexia • Agitation • Delirium • Possible muscle rigidity • Cyproheptadine • Discontinue triggering agent • Supportive care (ie, cardiopulmonary support, cooling, hydration, and agitation control) Cyclic antidepressant overdose Up to h TCAs • Hypotension • Stupor or coma • Wide-complex dysrhythmias • No rigidity • Serum alkalinization • Magnesium MAOIs, monoamine oxidase inhibitors; TCAs, tricyclic antidepressants BOX 14-6 • • • • • • Common drugs associated with serotonin syndrome Atypical antidepressants Dextromethorphan Ecstasy Fentanyl Ginseng Linezolid • • • • • • Lithium LSD MAOIs Meperidine Metoclopramide Ondansetron • • • • • • SSRIs St John’s wort Sumatriptan TCAs Tramadol Valproate LSD, lysergic acid diethylamide; MAOIs, monoamine oxidase inhibitors; TCAs, tricyclic antidepressants Tricyclic antidepressants (TCAs) block the reuptake of norepinephrine and serotonin and are used for the treatment of depression, chronic pain, and obsessive-compulsive disorders Side effects of TCAs include anticholinergic effects (dry mouth, blurred vision, prolonged gastric emptying, and urinary retention), postural hypotension, and cardiac effects (tachycardia, T-wave flattening or inversion, and prolongation of PR, QRS, and QT intervals).2,3 Monoamine oxidase inhibitors (MAOIs) block the oxidative deamination of catecholamines They are useful in treating depression accompanied by panic attacks Side effects of MAOIs include orthostatic hypotension, agitation, tremor, seizures, muscle spasms, urinary retention, paresthesias, and jaundice Hypertensive crisis may also develop with the ingestion of tyramine-containing foods.2 Serotonin syndrome may develop with concomitant use of SSRIs.2,3 Mood-stabilizing agents Lithium and lamotrigine are mood-stabilizing agents used in patients with bipolar disorder and mania Side effects of lithium include cognitive dysfunction, weight gain, tremor, reversible T-wave changes, leukocytosis, hypothyroidism, and vasopressin-resistant diabetes insipidus Notable side effects of lamotrigine include Stevens-Johnson syndrome, toxic epidermal necrolysis, and leukopenia.2,3 192 www.ajlobby.com Mizukawa_Chap_14.indd 192 6/20/17 10:40 AM Psychiatric Disorders Antipsychotics Antipsychotics are predominantly dopamine receptor antagonists and are used primarily in the treatment of schizophrenia and mood disorders with psychotic features Dopamine blockade affects four separate dopamine pathways in the brain: the mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular pathways Mesolimbic dopamine blockade is effective in treating the so-called “positive symptoms of psychosis,” including hallucinations, delusions, and disorganized speech and behavior In contrast, dopamine blockade in the mesocortical pathway exacerbates the existing depression of dopamine activity that results in the so-called “negative symptoms of psychosis,” such as attention deficit, asociality, anhedonia, avolition, and alogia (poverty of speech) Finally, blockade in the nigrostriatal pathway leads to extrapyramidal side effects, and blockade in the tuberoinfundibular pathway leads to hyperprolactinemia Extrapyramidal side effects include acute dystonia, akathisia, parkinsonism, and tardive dyskinesia First-generation (typical) neuroleptics have a higher incidence of extrapyramidal side effects and hyperprolactinemia than second-generation (atypical) neuroleptics have Both typical and atypical neuroleptics also have variable antagonism to H1 histaminergic receptors (causing weight gain, sedation), M1 muscarinic receptors (causing orthostasis, reflex tachycardia), and α1 receptors (causing blurry vision, dry mouth, urinary retention, constipation, delirium) Other notable side effects of neuroleptics include QT interval prolongation, sedation, and the potential for life-threatening neuroleptic malignant syndrome3 (see Table 14-3) Anesthetic considerations Preoperative anesthetic considerations in patients with psychiatric disorders include the following: • Preoperative interviews should be conducted to ascertain the following aspects of the patient’s history27: −− How long has the patient been on medication? −− Has the patient recently switched medications? −− Does the patient take the medication as scheduled? −− Does the patient have any history of side effects while on the medication? −− Has the patient noticed any interactions with other medications? −− Does the medication cause drowsiness or sedation? • Patients who have been taking TCAs and MAOIs should be queried to determine any history of palpitations, known arrhythmias, or orthostatic hypotension/syncopal episodes If any of these factors are present, these patients may require an electrocardiogram and medical clearance before sedation Perioperative anesthetic considerations in patients with psychiatric disorders include the following steps: • Titrate anesthetic agents slowly because most psychopharmacotherapeutic agents produce some level of sedation at baseline and can have synergistic effects with sedatives • Exercise caution with propofol Evidence suggests that chronic SSRIs and/or TCAs may potentiate the effects of propofol on norepinephrine and serotonin reuptake at the synapse, thus propagating its systemic effects and causing disproportionate interaction.44 • Avoid the use of local anesthetics containing epinephrine in patients taking MAOIs • Avoid ketamine, ephedrine, and meperidine in patients taking TCAs and MAOIs • Avoid ketamine in patients taking antipsychotics because antipsychotics tend to decrease the seizure threshold.2 • Avoid antiemetics with dopamine antagonism (droperidol, metoclopramide, prochlorperazine) in patients taking antipsychotics because their use in this scenario can result in extrapyramidal symptoms, QT interval prolongation, or even neuroleptic malignant syndrome • Avoid serotonin-increasing medications in patients already taking SSRIs because their use in this scenario can lead to serotonin syndrome43 (see Box 14-6) 193 www.ajlobby.com Mizukawa_Chap_14.indd 193 8/10/17 9:34 AM 14 • The Central Nervous System Conclusion An understanding of normal CNS anatomy and physiology as well as the neuropharmacology of anesthetic agents is fundamental in identifying anesthetic considerations in patients with CNS disease Equally important is an understanding of the pathophysiology, diagnosis, and typical management protocols of the diseases themselves Armed with the knowledge of both normal CNS function and pathologic change, the provider will be better equipped to tailor the anesthetic and safely provide patient care References 17 Caplan LR Diagnosis and treatment of ischemic stroke JAMA 1991;266:2413–2418 American Association of Neurological Surgeons Anatomy of the Brain http://www.aans.org/Patient%20Information/Conditions%20and %20Treatments/Anatomy%20of%20the%20Brain.aspx Published in 2006 Accessed 20 May 2016 18 Mackay J, Mensah G The Atlas of Heart Disease and Stroke Geneva: World Health Organization Press, 2004 Morgan GE Jr, Mikhail MS, Murray MJ Anesthesia for patients with neurologic & psychiatric disease In: Morgan GE Jr, Mikhail MS, Murray MJ (eds) Clinical Anesthesiology, ed New York: McGraw-Hill, 2006:647–661 19 Jauch EC, Saver JL, Adams HP, et al Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association Stroke 2013;44:870–947 Pasternak JJ, Lanier WL Jr Diseases affecting the brain In: Hines RL, Marschall KE (eds) Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Elsevier Saunders, 2012:218–254 20 Manno EM, Atkinson JL, Fulgham JR, Wijdicks EF Emerging medical and surgical management strategies in the evaluation and treatment of intracerebral hemorrhage Mayo Clin Proc 2005;80:420–433 Roizen MF, Fleisher LA Anesthetic implications in concurrent disease In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:1067–1149 21 Hemphill JC III, Greenberg SM, Anderson CS, et al Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the American Heart Association/ American Stroke Association Stroke 2015;46:2032–2060 Jensen NF, Fiddler DS, Striepe V Anesthetic considerations in porphyrias Anesth Analg 1995;80:591–599 Moore MR, McColl K, Remington C, Goldberg A Disorders of Porphyrin Metabolism New York: Plenum Medical, 1987 Meissner PN, Harrison GG, Hift RJ Propofol as an i.v anaesthetic induction agent in variegate porphyria Br J Anaesth 1991;66:60–65 Taddeini L, Watson CJ The clinical porphyrias Semin Hematol 1968;5:335–369 Harrison GG, Meissner PN, Hift RJ Anaesthesia for the porphyric patient Anaesthesia 1993;48:417–421 22 Fonseca RJ Preoperative evaluation In: Fonseca RJ, Marciani M, Turvey T Oral and Maxillofacial Surgery, ed Philadelphia: Elsevier Saunders, 2009:1–21 23 Reed KL The physically compromised patient In: Malamed SF Sedation: A Guide to Patient Management, ed St Louis: Mosby Elsevier, 2010:546–550 24 Chang BS, Lowenstein DH Epilepsy N Engl J Med 2003; 349:1257–1266 25 Drugs for epilepsy Treat Guidel Med Lett 2013;11(126):9–18 10 Fernandez CR, Fields A, Richards T, Kaye AD Anesthetic considerations in patients with Alzheimer’s disease J Clin Anesth 2003;15:52–58 26 UpToDate Rare but serious side effects of antiseizure drugs http:// www.uptodate.com/contents/image?imageKey=NEURO/78896 Accessed 17 September 2014 11 Muravchick S Anaesthesia for the aging patient Can J Anaesth 1993;40(5, pt 2):R63–R73 27 Agarwal R, Porter MH, Obeid G Common medical illnesses that affect anesthesia and their anesthetic management Oral Maxillofac Surg Clin North Am 2013;25:407–438 12 Carrière I, Fourrier-Reglat A, Dartigues JF, et al Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study Arch Intern Med 2009;169:1317–1324 28 Roberts R Differential diagnosis of sleep disorders, non-epileptic attacks and epileptic attacks Curr Opin Neurol 1998;11:135–139 14 Lublin FD, Reingold SC Defining the clinical course of multiple sclerosis: Results of an international survey Neurology 1996;46:907–911 29 Shaner DM, McCurdy SA, Herring MO, Gabor AJ Treatment of status epilepticus: A prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin Neurology 1988;38:202–207 15 Compston A, Coles A Multiple sclerosis Lancet 2008; 372(9648):1502–1517 30 Knake S, Hamer HM, Rosenow F Status epilepticus: A critical review Epilepsy Behav 2009;15:10–14 16 Malamed SF The medically compromised patient In: Malamed SF Sedation: A Guide to Patient Management, ed St Louis: Mosby, 2010:519–545 31 Eisenschenk S, Gilmore RL Seizures associated with nonneurologic medical conditions In: Wyllie E, Gupta A, Lachhwani DK (eds) The Treatment of Epilepsy: Principles and Practice, ed Philadelphia: Lippincott Williams & Wilkins, 2006:571–584 13 Shaikh SI, Verma H Parkinson’s disease and anaesthesia Indian J Anaesth 2011;55:228–234 194 www.ajlobby.com Mizukawa_Chap_14.indd 194 6/20/17 10:40 AM References 32 Dhir A, Rogawski MA Role of neurosteroids in the anticonvulsant activity of midazolam Br J Pharmacol 2012;165:2684–2691 33 Auta J, Costa E, Davis JM, Guidotti A Imidazenil: An antagonist of the sedative but not the anticonvulsant action of diazepam Neuropharmacology 2005;49:425–429 39 Reves JG, Glass P, Lubarsky DA, McEvoy MD, Martinez-Ruiz R Intravenous anesthetics In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:719–768 40 Shapiro H Intracranial hypertension: Therapeutic and anesthetic considerations Anesthesiology 1975;43:445–471 34 Yi J, Torres J, Azner Y, Vaidya P, Schiavi A, Reti IM Flumazenil pretreatment in benzodiazepine-free patients: A novel method for managing declining ECT seizure quality J ECT 2012;28:185–189 41 Ward MC, Garlow S Mood and anxiety disorders In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS (eds) Principles and Practice of Hospital Medicine New York: McGraw-Hill, 2012:1875–1889 35 Czuczwar SJ, Frey HH Effect of morphine and morphine-like analgesics on susceptibility to seizures in mice Neuropharmacology 1986;25:465–469 42 Schellander R, Donnerer J Antidepressants: Clinically relevant drug interactions to be considered Pharmacology 2010;86:203–215 36 Butterfield KJ, Bennett JD, Dembo JB Outpatient anesthesia In: Miloro M, Ghali GE, Larsen P, Waite P (eds) Peterson’s Principles of Oral & Maxillofacial Surgery, ed Shelton, CT: People’s Medical, 2012:63–94 37 Myslobodsky MS, Golovchinsky V, Mintz M Ketamine: Convulsant or anti-convulsant? Pharmacol Biochem Behav 1981;14:27–33 43 Boyer EW, Shannon M The serotonin syndrome N Engl J Med 2005;352:1112–1120 [errata 2007;356:2437 and 2009;361:1714] 44 Zhao Y, Sun L Antidepressants modulate the in vitro inhibitory effects of propofol and ketamine on norepinephrine and serotonin transporter function J Clin Neurosci 2008;15:1264–1269 38 Michaud D, Schiff D, Batchelor T Incidence of primary brain tumors http://www.uptodate.com/contents/incidence-of-primary-brain-tumors?source=machineLearning&search=%20intracranial+tumor&selectedTitle=2~150§ionRank=1&anchor=H3#H13 Accessed March 2017 195 www.ajlobby.com Mizukawa_Chap_14.indd 195 6/20/17 10:40 AM www.ajlobby.com Mizukawa_Chap_14.indd 196 6/20/17 10:40 AM Cardiovascular CHAPTER 15 The Cardiovascular System Prem B Patel, dmd, md Helen E Giannakopoulos, dds, md www.ajlobby.com Mizukawa_Chapter_Openers.indd 197 6/21/17 3:24 PM Cardiovascular CHAPTER 15 The Cardiovascular System Normal Anatomy and Physiology 199 Cardiac Cycle 200 Congestive Heart Failure 202 Hypertension 205 Ischemic Heart Disease 209 Valvular Heart Disease 211 Congenital Heart Disease 214 www.ajlobby.com Mizukawa_Chapter_Openers.indd 198 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology Pericardium The heart is separated from the rest of the thoracic viscera by the pericardium The pericardial sac normally contains to 30 mL of fluid, which lubricates the heart and permits it to contract with minimal friction Heart and great vessels General characteristics The heart wall consists of three layers: the inner endocardium, the middle myocardium, and the outer epicardium The right border of the heart is formed by the right atrium The left border is formed primarily by the left ventricle The inferior border is formed primarily by the right ventricle and part of the left ventricle The superior border is formed primarily by the great vessels The apex of the superior border lies in the left fifth intercostal space slightly medial to the nipple line and is useful clinically for determination of the left border of the heart and for auscultation of the mitral valve Chambers The heart functions as a pump and consists of four chambers: the right and left atria and the right and left ventricles The right atrium is larger than the left atrium, but its walls are thinner The right atrium receives deoxygenated blood via the inferior and superior vena cava The left atrium is the most posterior of the four chambers and receives oxygenated blood from four pulmonary veins The right ventricle makes up the major portion of the anterior surface of the heart and pumps blood through the pulmonary arteries into the pulmonary circulation The left ventricle, which is longer and more conically shaped than the right ventricle, pumps blood into the aorta Its wall is usually twice as thick as that of the right ventricle because it performs more work than the right ventricle Valves Valves are present between each atrium and ventricle (atrioventricular valves) and between the ventricles and the great vessels of the heart (semilunar valves) to ensure unidirectional blood flow through the heart The tricuspid valve separates the right atrium and right ventricle, and the mitral valve separates the left atrium and left ventricle The pulmonary valve is located between the right ventricle and the pulmonary artery, and the aortic valve is located between the left ventricle and aorta Coronary arteries The right and left coronary arteries equally supply blood to the heart The right coronary artery travels in the coronary sulcus to reach the posterior surface of the heart, where it anastomoses with the circumflex branch of the left coronary artery In its course it gives off the conus artery, which travels to the right ventricle outflow tract, and the atrial branch, which supplies the sinoatrial (SA) node through the SA nodal artery As the right coronary artery continues in the atrioventricular groove, it gives off, with some variation, the marginal branch, which supplies most of the anterior wall of the right ventricle; an atrioventricular nodal artery; and a posterior interventricular (posterior descending) artery that anastomoses with the anterior interventricular (anterior descending) artery, a branch of the left coronary artery The left coronary artery divides into a circumflex branch, which passes posteriorly to anastomose with the right coronary artery on the posterior aspect of the heart, and an anterior interventricular (anterior descending) branch Sometimes the SA nodal artery is a branch of the left coronary artery 199 www.ajlobby.com Mizukawa_Chap_15.indd 199 6/20/17 10:41 AM 15 • The Cardiovascular System The interventricular branches of the left coronary artery supply the anterior two-thirds of the interventricular septum and thus the bundle branches of the cardiac conducting system Branches of the right coronary artery supply the posterior one-third of the interventricular septum Cardiac veins The cardiac veins accompany the coronary arteries and their branches The coronary sinus is the major drainage vessel of the heart It is located at the posterior aspect of the heart in the atrioventricular groove and drains into the right atrium The great, middle, and small cardiac veins, the oblique vein of the left atrium, and the posterior vein of the left ventricle are the principal veins draining into the coronary sinus Conduction system The heartbeat originates in a specialized cardiac conduction system Impulses originate in the SA node, travel radially throughout the atria, converge onto the atrioventricular node, continue to the atrioventricular bundle (bundle of His) and to its right and left bundle branches, and arrive at the Purkinje fibers (subendocardial branches), which allow impulses to be conveyed throughout the ventricular walls Some parts of the conduction system and, under abnormal conditions, portions of the myocardium are capable of spontaneous discharge However, the SA node, which typically is the cardiac pacemaker, normally fires most rapidly, with depolarization spreading to the other regions before other areas discharge Therefore, in the normal heart, the rate of discharge of the SA node determines the rate Heart sounds Two sounds are normally heard with a stethoscope during each cardiac cycle The first is a low, slightly prolonged “lub” caused by vibrations resulting from the sudden closure of the mitral and tricuspid valves at the start of ventricular systole The second is a shorter, high-pitched “dub” caused by vibrations associated with closure of the aortic and pulmonary valves just after the end of ventricular systole The interval between aortic and pulmonary valve closure during inspiration is frequently long enough for the second sound to have an aortic component followed by a pulmonary component (physiologic splitting of the second sound) A soft, low-pitched third sound is heard approximately one-third of the way through diastole in many normal young adults in their 20s or 30s, and is probably due to vibrations that occur with rapid ventricular filling A third heart sound in middle-aged or older adults is a sign of heart failure A rare fourth heart sound, heard just before the first heart sound, is caused by forceful atrial contraction in the presence of a stiff or hypertrophic ventricle It is associated with conditions such as long-standing hypertension, aortic stenosis, restrictive cardiomyopathy, and myocardial fibrosis after myocardial infarction Cardiac Cycle The cardiac cycle consists of diastole (ventricular relaxation and filling) and systole (ventricular contraction and emptying) The right heart is the pump for the pulmonary circuit, and the left heart is the pump for the systemic circuit The orderly depolarization process triggers a wave of contraction that spreads throughout the myocardium In single muscle fibers, contraction starts just after depolarization and lasts until approximately 50 milliseconds after repolarization is completed Atrial systole starts after the P wave of an electrocardiogram (ECG), and ventricular systole starts at the end of the R wave and ends just after the T wave The contraction produces sequential changes in pressures, causing blood to flow through the heart chambers and great vessels 200 www.ajlobby.com Mizukawa_Chap_15.indd 200 6/20/17 10:41 AM Cardiac Cycle Mechanical events Late diastole Late in diastole, the mitral and tricuspid valves between the atria and ventricles are open, and the aortic and pulmonary valves are closed Blood fills the atria and ventricles As the ventricles become distended, the rate of filling declines, and the cusps of the atrioventricular valves drift toward the closed position Atrial systole Approximately 70% of ventricular filling occurs passively during diastole In atrial systole, atrial contraction propels additional blood into the ventricles The atrial muscle surrounding the orifices of the superior and inferior vena cava contracts, narrowing the pulmonary vein orifices Ventricular systole At the beginning of ventricular systole, the mitral and tricuspid valves close Intraventricular pressure quickly rises This isovolumetric ventricular contraction lasts approximately 0.05 seconds, until the pressures in the left and right ventricles exceed the pressures in the aorta and pulmonary artery, causing the aortic and pulmonary valves to open When the aortic and pulmonary valves open, the phase of ventricular ejection begins Ejection is rapid at first and slows as systole progresses The intraventricular pressure rises to a maximum, then declines before ventricular systole ends Peak left ventricular pressure is approximately 120 mm Hg, and peak right ventricular pressure is approximately 25 mm Hg or less The amount of blood ejected by each ventricle per stroke at rest is 70 to 90 mL The end diastolic volume is approximately 130 mL, so approximately 50 mL of blood remains in each ventricle at the end of systole (end-systolic ventricular volume) The ejection fraction (EF) is the percentage of the end-diastolic volume that is ejected with each stroke and is normally approximately 65% The EF is a valuable index of ventricular function Early diastole After the ventricular muscle is fully contracted, the already falling ventricular pressures drop more rapidly This period lasts approximately 0.04 seconds It ends when the momentum of ejected blood is overcome and the aortic and pulmonary valves close After the valves are closed, pressure continues to drop rapidly during the period of isovolumetric ventricular relaxation Atrial pressure continues to rise after the end of ventricular systole until the atrioventricular valves open, permitting the ventricles to fill Filling is rapid at first and slows as the next cardiac contraction approaches Cardiac output Stroke volume (SV) is the amount of blood pumped out of each ventricle per beat and is approximately 70 mL from each ventricle The output of the heart (left or right ventricle) per minute during systole is the cardiac output Cardiac output equals the product of the SV and the heart rate (HR) Average cardiac output is 5.6 L/min for a resting supine man and 4.9 L/min for a resting supine woman Variations in cardiac output can result from changes in the SV or the HR When the strength of contraction increases, more of the blood that normally remains in the ventricles is expelled Therefore, the EF increases, and the end-systolic ventricular blood volume falls Factors that increase the strength of cardiac contraction are said to be positively inotropic; those that decrease it are said to be negatively inotropic The HR is controlled primarily by the autonomic innervation Sympathetic stimulation increases the HR, whereas parasympathetic stimulation decreases the HR Positive chronotropes increase the HR; negative chronotropes decrease the HR The force of contraction of cardiac muscle depends on preload and afterload Preload is the end diastolic pressure that stretches the right or left ventricle of the heart to its greatest extent under variable physiologic de201 www.ajlobby.com Mizukawa_Chap_15.indd 201 6/20/17 10:41 AM 15 • The Cardiovascular System mands Preload is theoretically described as the initial stretching of the cardiac myocyte before contraction, or the sarcomere length at the end of diastole Because the sarcomere length cannot be measured in vivo, parameters such as ventricular end-diastolic volume or pressure are used to measure preload Afterload is the tension that develops in the wall of the ventricles during ejection The greater the aortic/pulmonary pressures, the greater the afterload The pressure in the ventricles must be greater than the pressure in the aorta and in the pulmonary artery to open the aortic and pulmonary valves, respectively Myocardial muscle fiber tension and thus afterload is also increased in the presence of a dilated ventricle Echocardiography Wall motion and other aspects of cardiac function can be evaluated with echocardiography In echocardiography, ultrasonic waves are emitted from a transducer that also functions as a receiver to detect waves deflected back from parts of the heart When combined with Doppler techniques, echocardiography can be used to measure the velocity and volume of flow through the valves Congestive Heart Failure Pathophysiology and diagnosis Heart failure is a structural or functional disorder that impairs the ability of the ventricles to fill or eject blood The term congestive heart failure (CHF) describes the symptoms of circulatory congestion (pulmonary edema and/ or peripheral edema) Heart failure may be classified as left sided or right sided, high output or low output, acute or chronic, and compensated or decompensated The underlying etiology must be identified because it will often influence the choice of therapy As noted, cardiac output equals the product of the SV and the HR The SV is influenced by three factors: preload, contractility, and afterload Cardiac function may be inadequate as a result of alterations in any of these parameters In most patients, the primary problem is depression of cardiac contractility caused either by a loss of functional muscle, as in myocardial infarction, or by processes diffusely affecting the myocardium However, the heart may fail because preload is excessively elevated, such as in valvular regurgitation, or when afterload is excessive, such as in aortic stenosis or severe hypertension Pump function may also be inadequate because of an abnormal HR Whereas the normal heart can tolerate wide variations in preload, afterload, and HR, the diseased heart often has limited reserve for such alterations Finally, cardiac pump function may be above normal but nonetheless inadequate when metabolic demands or requirements for blood flow are excessive This situation is termed high-output failure It is a relatively rare type of heart failure but tends to be treatable Causes of high-output heart failure include thyrotoxicosis, beriberi (thiamine deficiency), severe anemia, arteriovenous shunting, and Paget disease Causes of heart failure are summarized in Box 15-1 BOX 15-1 Causes of heart failure Cardiac • Ischemia • Cardiomyopathy (toxic, metabolic, infiltrative, infectious, or idiopathic) • Valvular heart disease (eg, aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation) • Restrictive heart disease (pericardial or myocardial) • Congenital heart disease • Electrical abnormalities Noncardiac • Hypertension • Pulmonary embolus • High-output states 202 www.ajlobby.com Mizukawa_Chap_15.indd 202 6/20/17 10:41 AM Congestive Heart Failure Exertional dyspnea and fatigue are the most likely chief complaints of patients with CHF Dyspnea that is most prevalent in the supine position, particularly paroxysmal nocturnal dyspnea, which often occurs during the early hours of sleep, is strongly suggestive of CHF Nocturia, coughing, wheezing, right upper quadrant pain, anorexia, nausea, vomiting, and palpitations may be prominent complaints Cardiac palpation may reveal an expanded impulse area in patients with left ventricular hypertrophy Auscultation reveals a protodiastolic rhythm (S3) or an S4 secondary to forceful atrial contraction Pulmonary examination often reveals rales, most prominently located at the lung bases Other signs include jugular venous distention (JVD), hepatomegaly, splenomegaly, and peripheral edema Patients with a history of JVD, pulmonary edema, and/or S3 gallop rhythm are considered to be in a decompensated state Cardiac output is markedly reduced in these patients Severe ventilation-perfusion mismatch and hypoxemia may be present secondary to pulmonary edema and pleural effusions Patients with stable, hemodynamically compensated heart failure may have signs of diminished reserve, such as orthopnea, cardiomegaly, basilar rales, and decreased exercise tolerance, but JVD, pulmonary edema, and S3 gallop are not present A chest radiograph many demonstrate an enlarged heart (cardiomegaly), increased vascular markings from pulmonary vascular congestion, and pleural effusions The ECG is often nonspecific, although 70% to 90% of patients may demonstrate ventricular or supraventricular dysrhythmias Echocardiography can be used to evaluate chamber size, wall motion, valvular function, left ventricular wall thickness, and cardiac output Radionuclide angiography provides a fairly reproducible and precise assessment of left ventricular EF Laboratory tests, including complete blood count, metabolic panel, arterial blood gas test, liver function tests, and coagulation studies (prothrombin time or partial thromboplastin time, international normalized ratio [INR]), should be evaluated.1 Many patients with CHF are hyponatremic because of activation of the vasopressin system Treatment with diuretics and aldosterone activation may lead to hypokalemia and hypomagnesemia Hypocalcemia and hypophosphatemia are often present.1 Prerenal azotemia can occur as a result of renal injury from hypoperfusion or other comorbidities, such as hypertension and diabetes mellitus Hepatic congestion may lead to elevated bilirubin levels, prothrombin time, and liver function test results.1 Arterial blood gas testing often demonstrates hypoxemia and metabolic acidosis resulting from pulmonary congestion and poor organ perfusion.1 The diagnosis of CHF is summarized in Box 15-2 BOX 15-2 Summary of diagnosis of CHF • Left ventricle failure: exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, pulmonary rales, gallop rhythm, and pulmonary venous congestion • Right ventricle failure: elevated venous pressure, hepatomegaly, and dependent edema • Both: combination of above The status of patients with CHF can be classified on the basis of either symptoms and lifestyle impairment or severity of cardiac dysfunction The New York Heart Association classification is used to assess symptomatic limitations of heart failure and response to therapy (Box 15-3) Evaluation of left ventricular chamber size and left ventricular EF is used to estimate the degree of cardiac dysfunction Exercise testing with measurement of gas exchange also has been used to assess the severity of failure on the basis of peak exercise capacity.2 BOX 15-3 • • • • New York Heart Association functional classification Class I: ordinary physical activity does not cause symptoms Class II: ordinary physical activity results in symptoms Class III: less than ordinary physical activity results in symptoms Class IV: symptoms occur at rest 203 www.ajlobby.com Mizukawa_Chap_15.indd 203 6/20/17 10:41 AM 15 • The Cardiovascular System Management Reversible underlying conditions should be treated first These conditions include ischemic left ventricular dysfunction, thyrotoxicosis, myxedema, valvular lesions, intracardiac shunts, arrhythmias, and alcohol-induced or drug-induced myocardial depression.3 Otherwise, treatment strategies may be divided into pharmacologic and nonpharmacologic approaches Nonpharmacologic treatment includes diet, exercise, and appropriate rest.4 Patients should restrict salt intake to g daily.4 Alterations in lifestyle reduce the need for medication.4 Diuretics are used when patients with heart failure exhibit signs or symptoms of circulatory congestion.5 In patients with mild fluid retention, thiazide diuretics, such as hydrochlorothiazide, are often used Patients with more severe heart failure are treated with loop diuretics, such as furosemide Addition of a second diuretic, such as metolazone, may be effective in patients with symptoms that are resistant to loop diuretics alone Angiotensin-converting enzyme (ACE) inhibitors are effective therapy for CHF A combination of the vasodilators hydralazine and isosorbide dinitrate also has been shown to be effective in improving exercise tolerance and life span Calcium channel blockers may produce favorable hemodynamic responses but negative inotropic effects These agents are used in patients with concurrent myocardial ischemia β-blockers may produce favorable long-term effects on symptoms and left ventricle function when gradually titrated Patients with acutely decompensated heart failure are treated with the goal of restoring hemodynamics to baseline Resolution of pulmonary edema, decreased or eliminated oxygen requirements, improved tolerance of physical activity, and improvement of metabolic and electrolyte disturbances are goals of therapy Anesthetic considerations With advances in the management of CHF, it is now not unusual for patients with well-compensated heart failure to undergo routine oral surgical services The combined cardiopulmonary dysfunction of heart failure predisposes the patient to intraoperative hypoxemia, hypotension, metabolic acidosis, pulmonary edema, and arrhythmias In a prospective study of 1,001 patients undergoing noncardiac surgery, those who demonstrated S3 or JVD preoperatively had approximately a 20-fold increase in the risk of postoperative mortality compared with patients without these risk factors.6 Patients with pulmonary edema had a 14-fold increase in risk, and patients with pulmonary rales or cardiomegaly had a 5-fold increase in risk.6 The initial preoperative assessment should include determination of the cause of the heart failure, evaluation of current and baseline signs and symptoms, and recording of the current medication regimen.7 The initial evaluation should reveal whether the patient is in a decompensated state In patients with decompensated heart failure, elective procedures should be postponed.7 The choice of anesthetic agent is based on the patient’s status, the planned surgical procedure, and the surgeon’s experience and preference.7 The goal should be to maintain cardiac output and organ perfusion during anesthesia The surgeon should confer with the patient’s cardiologist in the process of selecting the most appropriate anesthetic Barbiturates and propofol generally produce the most profound depression of cardiac function and blood pressure Administration of ketamine (N-methyl-D-aspartate [NMDA] receptor agonist) may result in elevated cardiac output and blood pressure secondary to increased sympathetic activity Cardiovascular side effects are mild when benzodiazepines are given but become more pronounced when benzodiazepines are administered in combination with opioids Opioids are usually well tolerated by patients with decreased cardiac reserve Slower administration, smaller doses, and administration by infusion generally result in less dramatic alterations of blood pressure and myocardial function than other means of administration Patients with poorly compensated or uncompensated CHF who must undergo oral surgery will be most safely treated in an operating room setting Further, patients with poorly compensated CHF tolerate general anesthesia poorly and should be treated, if possible, with a moderate sedation protocol 204 www.ajlobby.com Mizukawa_Chap_15.indd 204 6/20/17 10:41 AM Hypertension Hypertension Pathophysiology and diagnosis Hypertension is a disorder of arterial pressure regulation in which the systemic arterial pressure is abnormally sustained at an elevated level (systolic blood pressure [SBP] ≥ 140 mm Hg or diastolic blood pressure [DBP] ≥ 90 mm Hg; see Table 15-1) Hypertension is a syndrome encompassing dysregulation of systemic vascular resistance (SVR), dysregulation of sodium and body fluid metabolism, and abnormal tissue fibrosis The mechanisms that normally prevent hypertension become dysregulated: the baroreceptor reflex becomes reset at a higher level, pressure natriuresis does not function appropriately to alter sodium excretion and urine flow, and the renin-angiotensin-aldosterone system is defective The prevalence of hypertension in the United States is increasing; according to the Centers for Disease Control and Prevention, about 75 million American adults (29%of the population) have high blood pressure Table 15-1 Classification of blood pressure in adults Classification Blood pressure (mm Hg) Normal SBP < 120 and DBP < 80 Prehypertension SBP 120–139 or DBP 80–89 Stage hypertension SBP 140–159 or DBP 90–99 Stage hypertension SBP 160–179 or DBP 100–119 Hypertensive urgency/emergency SBP > 180 or DBP > 120 The mean arterial pressure (MAP) describes the average blood pressure during a single cardiac cycle The MAP is considered to be the perfusion pressure seen by organs in the body MAP > 60 mm Hg is enough to sustain the organs of the average person The MAP is determined by cardiac output (CO; the product of the HR and the SV) and SVR, and it can be approximated using the more easily measured SBP and DBP: MAP = (2 × DBP) + SBP OR MAP = ( 2/3 × DBP) + (1/3 × SBP) For most patients with hypertension, CO is in the normal range; thus the MAP is elevated because of abnormally increased SVR Hypertension can be classified as primary (essential) or secondary and as benign or malignant (hypertensive urgency/emergency); see Tables 15-2 and 15-3 Primary hypertension, the most prevalent form, has no clearly definable cause; rather, it is a multifactorial process Primary hypertension can be further divided into resistance hypertension and compliance hypertension Resistance hypertension affects mostly young and middle-aged adults, is due to increased SVR, and includes elevated MAP, SBP, and DBP Compliance hypertension primarily affects elderly patients who have decreased vessel compliance (“stiff pipes”) and is characterized by SBP elevation and increased pulse pressure (pulse pressure = SBP – DBP) Secondary hypertension is caused by alteration of the regulatory mechanisms of arterial pressure (which can result from disorders of the renal, adrenal, endocrine, or central nervous system; drugs; alcohol; or other causes) 205 www.ajlobby.com Mizukawa_Chap_15.indd 205 6/20/17 10:41 AM 15 • The Cardiovascular System Table 15-2 Classification of hypertension: Primary vs secondary Type of hypertension Factor Primary (essential) Secondary Frequency 90%–95% of patients Etiology 5%–10% of patients • Identifiable underlying cause • No identifiable cause • Multifactorial etiology including heredity, behavior, environment (stress, diet, salt intake, etc) • Most often renal or adrenal cause Table 15-3 Classification of hypertension: Benign vs malignant Type of hypertension Factor Frequency Benign 95% of patients Malignant 5% of patients Blood pressure (mm Hg) SBP ≥ 140 or DBP ≥ 90 SBP ≥ 180 or DBP ≥ 120 Clinical symptoms None (until late in course) • Likely clinically symptomatic • Urgency if no evidence of organ damage is present • Emergency if evidence of organ damage is present; can be lethal if not treated rapidly and adequately Hypertension is diagnosed on the basis of accurate measurements of blood pressure with the patient properly prepared and positioned Hypertension, along with diabetes, high cholesterol, smoking, and old age, is considered a risk factor for coronary artery disease (CAD) In men, the risk for CAD increases starting around age 45 In women, the risk for CAD increases starting around age 55 Several screening and diagnostic tests (drug screening, 24-hour urinary metanephrine and aldosterone levels, renal Doppler ultrasonography, sleep study, thyroid-stimulating hormone level, dexamethasone suppression test, CT angiography, etc) can help identify causes of secondary hypertension and may be indicated Hypertension is rarely accompanied by any symptoms and hence sometimes is called the “silent killer.” Symptoms, when present, may include headache, tinnitus, vertigo, lightheadedness, malaise, and altered vision Physical findings in patients with hypertension may include obesity, carotid bruit, S4 heart sound (due to left ventricular hypertrophy), increased pulse pressure, and retinopathy (papilledema, retinal hemorrhages and exudates) In hypertensive emergency, patients can have a variety of symptoms and signs, including chest pain, arrhythmias, dyspnea, headaches, tinnitus, dizziness, weakness, tingling, altered mental status, vomiting, papilledema, failing vision, increased intracranial pressure, hematuria, proteinuria, and acute renal failure Hypertension over time can have detrimental consequences, including cardiac dysfunction, accelerated arterial disease, and renal dysfunction The left ventricle must generate increased systolic pressures, leading to left ventricular hypertrophy and unfavorably altering diastolic compliance Arteries are subject to increased stress, leading to accelerated atherosclerosis and thereby increasing the frequency of myocardial infarction, stroke, and the development of aneurysms Arteriolar destruction by sustained pressures is particularly pronounced in the kidneys, which can cause renal failure and further exacerbate the hypertension Along with diabetes mellitus, hypertension is one of the leading causes of chronic renal failure Management The ultimate goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality Keeping blood pressure to a target goal of lower than 140/90 is associated with a decrease in cardiovascular disease complications.8 In patients with hypertension and diabetes mellitus or renal disease, the goal is to keep blood pressure lower than 130/80.9,10 First-line treatment of primary hypertension consists of diet and lifestyle modifications with sodium restriction, DASH (Dietary Approaches to Stop Hypertension) diet, physical activity and exercise, weight loss, alcohol reduction, and reduction of psychologic stress.11 Effective lifestyle and diet modification may lower 206 www.ajlobby.com Mizukawa_Chap_15.indd 206 6/20/17 10:41 AM Hypertension blood pressure as much as an individual antihypertensive drug would (Box 15-4) However, for many patients, drug therapy is often necessary BOX 15-4 • • • • • Lifestyle modifications to prevent and manage hypertension Weight reduction (maintain normal body weight, body mass index 18.5–24.9 kg/m2) DASH diet (rich in fruits, vegetables, low-fat dairy) Dietary sodium reduction (< 2.4 g sodium per day) Physical activity (30 minutes per day, most days of the week) Moderation of alcohol (limit of two drinks per day for men and one drink per day for women) Antihypertensive medications can be divided into several classes, with many drugs in each class (Table 15-4) Certain classes are preferred in certain scenarios (heart failure, post–myocardial infarction, high risk of CAD, diabetes mellitus, chronic kidney disease, recurrent stroke prevention) Treatment of secondary hypertension is focused on treating the underlying cause Appropriate drug therapy decreases the incidence of CHF and stroke Management of hypertension can also have a beneficial impact on the development and progression of CAD Hypertensive patients should be treated as if they have CAD if any two CAD risk factors are present (hypertension, smoking, diabetes, elevated cholesterol, or elderly age) The longer the patient has hypertension, the higher the risk of end-organ damage Table 15-4 Oral antihypertensive drugs Class Drugs Thiazide diuretics Chlorothiazide, chlorthalidone, hydrochlorothiazide, polythiazide, indapamide, metolazone Loop diuretics Bumetanide, furosemide, torsemide Potassium-sparing diuretics Amiloride, triamterene Aldosterone receptor antagonists Eplerenone, spironolactone ACE inhibitors Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril Calcium channel blockers (nondihydropyridine) Diltiazem, verapamil Calcium channel blockers (dihydropyridine) Amlodipine, felodipine, isradipine, nicardipine, nifedipine, nisoldipine Angiotensin II receptor blockers Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan β-blockers Atenolol, betaxolol, bisoprolol, metoprolol, nadolol, propranolol, timolol Combined α- and β-blockers Carvedilol, labetalol α1-blockers Doxazosin, prazosin, terazosin Central α2 agonists and other centrally acting drugs Clonidine, methyldopa, reserpine, guanfacine Direct vasodilators Hydralazine, minoxidil Hypertension associated with the acute onset of end-organ damage, such as encephalopathy, acute pulmonary edema, or aortic dissection, is a hypertensive emergency Hypertensive emergencies require prompt and careful management A variety of parenteral agents are available for management of a hypertensive emergency, generally in the setting of an emergency department These agents include sodium nitroprusside, nitroglycerin, calcium channel blockers, and adrenergic blockers such as labetalol and esmolol In general, the blood pressure should not be reduced by more than 25% to 30% in the first several hours to minimize the possible complication of cerebral and/or myocardial ischemia 207 www.ajlobby.com Mizukawa_Chap_15.indd 207 6/20/17 10:41 AM 15 • The Cardiovascular System A hypertensive urgency differs from a hypertensive emergency by the absence of end-organ damage symptoms Hypertensive urgencies are preferably managed with oral agents such as furosemide (if the patient has volume overload), captopril (6.25 to 12.5 mg), or clonidine (0.2 mg); see chapter 12 Anesthetic considerations Patients with hypertension and cardiac disease require careful perioperative blood pressure control Preoperative, intraoperative, and postoperative hemodynamic and autonomic control are necessary to prevent associated cardiac morbidity and mortality Patients with hypertension should undergo a preoperative assessment of the nature of the hypertension-associated organ dysfunction, current drug therapy, and adequacy of blood pressure control.12 Appropriate intraoperative monitoring and blood pressure control, anesthetic selection, and anticipation of blood pressure changes that can result from painful intraoperative stimulation and emergence are all important considerations in the anesthetic management of patients with hypertension.13 Despite the erroneous belief that minor surgery causes minor stress, patients who undergo even minor outpatient procedures commonly have sympathetic stimulation resulting in perioperative hypertension Evidence of worsening hypertension and associated end-organ dysfunction (CHF, CAD, cerebral ischemia, renal dysfunction) should be evaluated Antihypertensive drugs should be continued throughout the perioperative period In particular, antihypertensive medication should not be withheld preoperatively Withholding antihypertensive medications may lead to withdrawal phenomena and increase complication rates Prophylactic cardiac risk reduction therapy with β-blockers or clonidine in patients with CAD, peripheral vascular disease (PVD), or two CAD risk factors reduces the risk of perioperative death.14,15 Perioperative therapy with β-blockers for at least days preoperatively, continued for 30 days postoperatively, reduces the risk of cardiac morbidity and death in 90% of patients at risk.14 Consultation with the patient’s cardiologist is recommended for high-risk patients Intraoperative monitoring should include ECG, blood pressure, HR, pulse oximetry, and end-tidal carbon dioxide Blood pressure should be measured frequently, at least every minutes The ECG should be assessed for evidence of myocardial ischemia In the hypertensive patient with CAD, tachycardia and fluctuations in systemic blood pressure should be avoided Control of the HR is the most critical element for preventing cardiac morbidity and death HRs above 120 beats per minute increase mortality rate Any anesthetic agent is acceptable in patients with hypertension if it is used with appropriate dosing and careful monitoring Combinations of midazolam and fentanyl are frequently used because of their limited hemodynamic effects Ketamine is rarely used in hypertensive patients because it can increase systemic blood pressure and cause tachycardia, which can lead to myocardial ischemia An excessive concentration or dose of anesthetics can result in hypotension, which may precipitate cerebral and/or myocardial ischemia in the chronically hypertensive patient Changes in surgical stimulation, poor pain control, and emergence may lead to changes in blood pressure and HR Appropriate and adequate use of local anesthesia is very effective and can minimize hemodynamic fluctuation Several studies have demonstrated that local anesthetics with epinephrine are safe and have few, if any, hemodynamic consequences in patients with cardiovascular disease; however, caution is still advised.16 By improving the effectiveness of local anesthesia, vasoconstrictors can decrease the magnitude of endogenous catecholamine release that may result from inadequate pain control.16 An epinephrine dose of 0.036 to 0.054 mg (two to three carpules of 1:100,000 solution) appears to be tolerated in most patients with hypertension and cardiovascular disease.17 Elective procedures should be deferred in patients with hypertensive urgency or end-organ symptoms If emergency oral surgery is necessary in this scenario, the patient’s blood pressure should be initially managed in consultation with the patient’s physician Surgery may be performed in a setting where ongoing blood pressure control can be optimized with a carefully titrated anesthetic and the additional use of parenteral antihypertensive medications as needed With adequate management of the blood pressure, epinephrine may be used conservatively to improve the effectiveness of local anesthesia 208 www.ajlobby.com Mizukawa_Chap_15.indd 208 6/20/17 10:41 AM Ischemic Heart Disease Ischemic Heart Disease Pathophysiology and diagnosis Ischemic heart disease (IHD) results from an imbalance in myocardial oxygen demand and supply Ischemia may therefore occur with reduced blood supply (eg, coronary artery obstruction, tachycardia causing shortened diastole, decreased cardiac output) and/or increased myocardial demand (eg, increased work load, hypertrophy) CAD is the most common type of heart disease and cause of myocardial infarctions, with more than 5.4 million people diagnosed with CAD each year in the United States More than 550,000 deaths per year in the United States are attributable to CAD, making CAD the leading cause of death in both men and women The causes of CAD include atherosclerosis, embolism, coronary artery spasm (Prinzmetal angina), and congenital abnormalities Atherosclerosis is the most important cause of CAD because it limits blood flow to the heart, leading to ischemia and potentially infarction The most common symptoms of IHD are dyspnea on exertion, fatigue, angina, orthopnea, paroxysmal nocturnal dyspnea, dizziness, and fainting Patients can remain asymptomatic despite having 50% to 70% stenosis of a major coronary artery The evaluation of IHD includes noninvasive and invasive tests, such as ECG, cardiac enzyme tests, Holter monitoring, exercise and nuclear stress tests, echocardiography, cardiac catheterization, and angiography Clinical consequences of myocardial ischemia include silent ischemia, stable angina, Prinzmetal angina, and acute coronary syndrome (ie, unstable angina, non–ST-elevation myocardial infarction [NSTEMI], ST-elevation myocardial infarction [STEMI]) Silent ischemia occurs without symptoms because myocardial cells are abnormal yet continue to function Stable angina is chronic, demand-related transient cardiac pain caused when metabolic needs (eg, exercise, stress) exceed blood supply because of a stable, fixed obstructive plaque Prinzmetal angina, also called variant angina, is cardiac pain occurring at rest or sleep because of coronary artery vasospasm Acute coronary syndrome is more serious and is caused by acute plaque changes Unstable angina is supply-related chest pain that varies in frequency and duration NSTEMI is a myocardial infarction with positive cardiac markers without ST elevation on ECG STEMI is a myocardial infarction with positive cardiac markers and ST elevation on ECG Management Prevention and management of IHD includes control of risk factors, such as hypertension, diabetes mellitus, poor diet, smoking, dyslipidemia, and sedentary lifestyle Management of IHD also includes pharmacotherapy and/or revascularization procedures with the goal of improving myocardial oxygen delivery and decreasing myocardial oxygen requirements Revascularization procedures include coronary angioplasty, coronary stenting, and coronary artery bypass grafting Acute coronary syndrome is a medical emergency that is managed using advanced cardiovascular life support protocol and proper referral for evaluation for revascularization Although a complete discussion of drug therapy for IHD is beyond the scope of this chapter, drug therapy includes a variety of medications to decrease oxygen demand and increase oxygen supply to the myocardium Pharmacologic agents that are used to reduce oxygen demand include nitrates (vasodilators), β-blockers (negative inotropes, negative chronotropes), and calcium channel blockers (vasodilators, negative inotropes) The pharmacologic agents used to improve blood supply include antiplatelet agents (eg, aspirin, clopidogrel, glycoprotein IIb/ IIIa receptor inhibitors) and anticoagulants (eg, heparin, direct thrombin inhibitors, factor Xa inhibitors) Patients who have had bare metal stents placed may require or more months of antiplatelet therapy.18 Patients with drug-eluting stents require antiplatelet therapy for year or more.19 Patients should be considered to have CAD if at least two CAD risk factors are present (hypertension, smoking, diabetes mellitus, elevated cholesterol level, or elderly age); see Box 15-5 209 www.ajlobby.com Mizukawa_Chap_15.indd 209 6/20/17 10:41 AM 15 • The Cardiovascular System BOX 15-5 • • • • • CAD risk factors Hypertension Diabetes Hyperlipidemia with cholesterol level > 240 mg/dL Smoking Age ≥ 60 years Anesthetic considerations Patients with CAD who undergo anesthesia for noncardiac surgery have increased morbidity and mortality rates Elective surgeries are usually delayed for at least months after myocardial infarction and months after revascularization surgery Consultation with the patient’s cardiologist for collaborative management is appropriate, especially in patients with CHF, aortic stenosis, intracoronary stents with the use of platelet inhibitors, and new or unstable angina symptoms The routine preoperative cardiac evaluation includes a thorough history of exercise tolerance, assessment of cardiac symptoms, and ECG Particular attention should be paid to new angina, change in anginal pattern, unstable angina, recent myocardial infarction, CHF, and aortic stenosis Patients with PVD will likely also have CAD Approximately 50% of patients with evidence of PVD will have more than 50% stenosis of one or more coronary arteries even in the absence of angina pectoris and in the presence of normal ECG Invasive preoperative testing does not add appreciably to the information provided by the history, physical examination, and ECG for predicting adverse outcomes.20 The pre-anesthetic ECG should be evaluated for evidence of myocardial ischemia, prior myocardial infarction, cardiac hypertrophy, abnormal cardiac rhythm or conduction disturbances, and electrolyte abnormalities Limited exercise tolerance in the absence of pulmonary disease, inability to lay flat, awakening from sleep with angina or shortness of breath, and angina at rest or with minimal exertion are all evidence of substantial cardiac disease If a patient can climb two to three flights of stairs without symptoms, cardiac reserve is probably adequate Angina is considered stable when no change in precipitating factors, frequency, or duration has occurred for at least 60 days Preoperative evidence of impaired left ventricle function includes a history of prior myocardial infarction, CHF, EF < 40%, left ventricular end-diastolic pressure > 18 mm Hg, cardiac index < L/min/m2, and areas of ventricular dyskinesia Cardiac medications should be continued throughout the perioperative period, especially β-blockers, which, when taken days preoperatively and 30 days postoperatively, substantially reduce the risk of cardiac morbidity.14 All patients with known CAD, known PVD, or two risk factors for CAD should receive a perioperative β-blocker unless a specific contraindication is present.9 Daily atenolol 25 mg taken orally is an appropriate β-blocker for this purpose The optimum time to start the use of a β-blocker is at the time of identification of the risk Medical or cardiac consultation can be requested, although the most common recommendation is to start the use of a β-blocker Anxiolytic medications, such as benzodiazepines, can effectively reduce anxiety and catecholamine release, thereby lessening HR increases and reducing myocardial oxygen consumption Opioids are beneficial, not only as an adjunct to sedation, but to help minimize painful stimulation and avoid tachycardia Propofol may be used if necessary, but hypotension should be avoided Ketamine should be avoided in patients with CAD because of its associated increases in HR and SBP, both of which increase myocardial oxygen demand Intraoperative anesthetic management includes modulation of sympathetic nervous system responses and rigorous control of hemodynamics Maintaining HR and blood pressure within 20% of the awake values is recommended Hypertension and hypotension should be avoided to maintain a favorable balance between myocardial oxygen demand and myocardial oxygen delivery An increased HR is more likely to produce signs of myocardial infarction than hypertension is Tachycardia increases myocardial oxygen demand but also decreases duration of 210 www.ajlobby.com Mizukawa_Chap_15.indd 210 6/20/17 10:41 AM Valvular Heart Disease diastole, thereby decreasing coronary perfusion Hypertension also increases myocardial oxygen demand; however, hypertension increases coronary perfusion despite the presence of atherosclerotic coronary arteries Adequate use of local anesthesia can be effective and can minimize hemodynamic fluctuation With a sufficient level of local anesthesia, vasoconstrictors can be cautiously used and can lower the risk of endogenous catecholamine release that may result from inadequate pain control.16 As noted previously, an epinephrine dose of 0.036 to 0.054 mg (two to three carpules of 1:100,000 solution) appears to be tolerated in most patients with hypertension and cardiovascular disease, and the benefits of the vasoconstrictor likely outweigh the potential risks.17 Valvular Heart Disease Pathophysiology and diagnosis Valvular heart disease may affect one or more of the four heart valves The most frequently encountered forms of valvular heart disease result in pressure overload (valvular stenosis) or volume overload (valvular regurgitation/insufficiency) The net effect of valvular disease is interference with forward blood flow from the heart into the systemic circulation Valvular heart disease may be congenital or acquired The aortic and mitral valves are most commonly affected The severity of valvular stenosis is reflected by pressure gradient across the valve and the effective valve orifice area The severity of valvular insufficiency is reflected in the magnitude of regurgitant backflow The most valuable diagnostic test for valvular disease is echocardiography Chest radiography and ECG can demonstrate certain valvular disease findings (chamber enlargement, left ventricular hypertrophy, calcification) Cardiac catheterization may be performed and can assist in diagnosis before surgery Symptoms of valvular disease include heart failure symptoms, palpitations, angina, and syncope Signs of valvular disease include specific heart murmurs, physical findings associated with CHF, and dysrhythmias (Table 15-5) Table 15-5 Heart auscultation sounds indicating valvular disease Condition Type of murmur Mitral stenosis Diastolic Description Low-pitched middiastolic rumbling murmur after an opening snap at apex Mitral regurgitation Systolic Holosystolic murmur at apex radiating to axilla Aortic stenosis Systolic Crescendo-decrescendo harsh murmur at left sternal border radiating to carotids Aortic regurgitation Diastolic Decrescendo high-pitched murmur at upper sternum Mitral valve prolapse Systolic Midsystolic click followed by late systolic murmur at apex; accentuated by Valsalva maneuver and standing; diminished with squatting Mitral stenosis Mitral stenosis leads to a progressive decrease in the mitral valve orifice, causing mechanical obstruction of left ventricle diastolic filling This obstruction produces increased pressures in the left atrium and pulmonary vasculature Over time, the left atrium becomes dilated and can predispose the patient to atrial fibrillation Mitral stenosis is commonly the result of fusion of mitral valve leaflets during the healing process after acute rheumatic carditis; however, symptoms develop many years later 211 www.ajlobby.com Mizukawa_Chap_15.indd 211 6/20/17 10:41 AM 15 • The Cardiovascular System Mitral regurgitation/insufficiency Mitral regurgitation is caused by an incompetent mitral valve, leading to left atrial volume overload and decreased left ventricle forward stroke volume due to the regurgitant backflow Acute mitral regurgitation can be caused by infective endocarditis or papillary muscle rupture or dysfunction Chronic mitral regurgitation can be caused by dilated cardiomyopathy (from ischemia, myocardial infarction, infections), rheumatic fever, Marfan syndrome, and other causes Aortic stenosis Aortic stenosis leads to a progressive decrease in the aortic valve orifice, causing mechanical obstruction of left ventricle forward SV This obstruction leads to increased left ventricle systolic pressures The classic triad of symptoms of aortic stenosis is chest pain, heart failure, and syncope Aortic stenosis usually results from progressive calcification of the valve with age, calcification of a congenitally abnormal (usually bicuspid) valve, or rheumatic fever Symptoms occur after a long latency period The incidence of sudden death is increased in patients with aortic stenosis Classification of the severity of aortic stenosis is shown in Table 15-6 Table 15-6 Classification of aortic stenosis Severity Mean pressure gradient (mm Hg) Aortic valve area (cm2) Mild < 25 > 1.5 Moderate 25–40 1.0–1.5 Severe 41–70 0.6–0.9 Critical > 70 < 0.6 Aortic regurgitation/insufficiency Aortic regurgitation is caused by an incompetent aortic valve, leading to decreased forward left ventricle SV due to regurgitant backflow from the aorta into the left ventricle Acute aortic regurgitation is most often the result of infective endocarditis, trauma, or dissection of a thoracic aortic aneurysm Chronic aortic regurgitation is usually caused by prior rheumatic fever but can be caused by many other chronic diseases Over time, aortic regurgitation can lead to left ventricular hypertrophy and left ventricular dilation Coronary perfusion can be compromised because of the decreased aortic diastolic pressure in addition to the increased myocardial oxygen demand secondary to left ventricular hypertrophy Mitral valve prolapse Mitral valve prolapse (MVP) is caused by an abnormality of the mitral valve support structure leading to prolapse of the valve into the left atrium during left ventricle systole The incidence of MVP increases with musculoskeletal abnormalities, including Marfan syndrome, pectus excavatum, and kyphoscoliosis Most patients are asymptomatic; however, MVP is the most common cause of pure mitral regurgitation Sudden death is extremely rare in patients with MVP Other potential complications of MVP include infective endocarditis, transient ischemic attacks, and cardiac dysrhythmias Management Valvular heart disease is initially managed medically but, depending on the severity, may require valve repair or replacement Medical management includes the management of hypertension, angina, and heart failure and possible anticoagulation therapy to manage atrial fibrillation Surgical treatment for valvular heart disease may be indicated 212 www.ajlobby.com Mizukawa_Chap_15.indd 212 6/20/17 10:41 AM Valvular Heart Disease depending on the severity, symptoms, and progression of the disease and the failure of medical management Surgical options include valvuloplasty (percutaneous balloon catheter dilation), valvulotomy (commissurotomy), valve repair (annuloplasty, removal of redundant leaflet segments, and resuspension), or valve replacement (with a biologic or mechanical valve) Mechanical valve recipients will require lifelong anticoagulation therapy Anesthetic considerations The selection of anesthetic drugs for patients with valvular disease is based on the effects of drug-induced changes in HR, SV, SVR, and pulmonary vascular resistance Patients with valvular disease can be more susceptible to the ventilatory depressant effects of sedative drugs Supplemental oxygen may increase the margin of safety Nitrous oxide can increase pulmonary vascular resistance; however, this increase is not sufficiently great to justify avoiding this drug in all patients with valvular disease.21 Ketamine should be avoided in patients with valvular heart disease when tachycardia is not desired, especially in patients with mitral stenosis, aortic stenosis, or MVP Addition of a narcotic to the anesthetic regimen can minimize sympathetic nervous stimulation and decrease alterations in HR Cardiac medications should be continued throughout the perioperative period The management of chronic anticoagulation therapy and use of antiplatelet agents should be discussed with the cardiologist For routine oral surgical procedures, clopidogrel does not need to be stopped, and in patients with a drug-eluting stent, antiplatelet therapy should never be stopped without the approval of the cardiologist Similarly, warfarin therapy does not need to be stopped for routine oral surgical procedures in patients with INR < Perioperative management considerations should be discussed with the patient’s cardiologist, especially for patients with aortic stenosis Medications to treat cardiac dysrhythmias (eg, lidocaine, amiodarone, metoprolol, esmolol) should be available, along with a cardiac defibrillator Hospital-based care should be considered for patients with substantial valvular disease An operating room setting with anesthesia staff may be necessary for high-risk patients (Table 15-7) Table 15-7 Anesthetic considerations in patients with valvular heart disease Condition Anesthetic considerations Mitral stenosis • Avoid tachycardia • Carefully titrate intravenous fluids to avoid volume overload • Avoid hypoxemia or hypoventilation, which can exacerbate pulmonary hypertension and evoke heart failure • Avoid sudden decreases in SVR Mitral regurgitation or aortic regurgitation • Avoid sudden decreases in HR and SVR • Avoid decreases in left ventricle SV • Allow mild increases in HR and mild decreases in SVR, which can increase cardiac output • Carefully titrate intravenous fluids to ensure adequate venous return and optimize forward left ventricle SV Aortic stenosis • Avoid extreme bradycardia and tachycardia (bradycardia can lead to overdistention of left ventricle; tachycardia can lead to myocardial ischemia because of decreased coronary blood flow and increased myocardial oxygen demand) • Avoid sudden decreases in SVR • Maintain normal sinus rhythm to ensure optimal left ventricle diastolic filling and SV • Confer with cardiologist • Consider treatment in a hospital setting with anesthesia staff; note that the patient may require intra-arterial pressure monitoring with avoidance of hypotension • Ensure prompt availability of a cardiac defibrillator (because external cardiac compressions are unlikely to generate an adequate SV across a stenotic valve) Mitral valve prolapse • Avoid tachycardia • Avoid sudden decreases in SVR • Optimize intravenous fluids to ensure adequate venous return • Perform surgery with the patient in a more reclined position (which helps to minimize cardiac emptying) 213 www.ajlobby.com Mizukawa_Chap_15.indd 213 6/20/17 10:41 AM 15 • The Cardiovascular System Congenital Heart Disease Congenital lesions account for approximately 2% of heart disease in adults Only the most common conditions are discussed here Pulmonary Stenosis Pathophysiology and diagnosis Stenosis of the pulmonary valve or infundibulum increases the resistance to outflow, raises the right ventricular pressure, and limits pulmonary blood flow In the absence of associated shunts, arterial oxygen saturation is normal, but severe stenosis causes peripheral cyanosis by reducing cardiac output Patients with mild pulmonary stenosis are asymptomatic Moderate to severe stenosis may cause dyspnea on exertion, syncope, chest pain, and eventually right ventricular failure Severe stenosis is associated with sudden death and can cause heart failure as early as the second or third decade of life On ECG, right axis deviation or right ventricular hypertrophy is noted Peaked P waves show evidence of right atrial overload On chest radiographs, heart size may be normal, the right ventricle and atrium may be prominent, or gross cardiac enlargement may be observed, depending on the severity Management Symptomatic patients or those with evidence of right ventricular hypertrophy usually require treatment Percutaneous balloon valvuloplasty is usually the treatment of choice.22 Surgical treatment can be performed; it has 2% to 4% mortality and an excellent long-term result in most cases.22 Coarctation of the Aorta Pathophysiology and diagnosis Coarctation of the aorta consists of localized narrowing of the aortic arch just distal to the origin of the left subclavian artery A bicuspid aortic valve is present in 25% of cases Blood pressure is elevated in the aorta and its branches proximal to the coarctation and is decreased distally Collateral circulation develops through the intercostal arteries and the branches of the subclavian arteries Infants with this condition may have severe heart failure Children and adults are usually asymptomatic but have hypertension Femoral pulsations are weak and are delayed in comparison with brachial pulsations The ECG usually shows left ventricular hypertrophy Chest radiography shows scalloping of the ribs due to enlarged collateral intercostal arteries, dilation of the left subclavian artery, poststenotic aortic dilation, and left ventricular enlargement Measurement of the gradient across the lesion by catheterization and aortography are the primary methods of diagnosis Magnetic resonance imaging (MRI) is a useful imaging adjunct, and Doppler ultrasound can be helpful in estimating the severity of the obstruction Management Resection of the coarctated site has a surgical mortality of 1% to 4% In patients 20 years of age or younger, coarctations should be resected In patients under 40 years of age, surgery is advisable if the patient has refractory hypertension or substantial left ventricular hypertrophy The surgical mortality rate rises considerably in patients older than 50 years Balloon angioplasty of the stenosis has been accomplished successfully, but aortic tears have been 214 www.ajlobby.com Mizukawa_Chap_15.indd 214 6/20/17 10:41 AM Patent Ductus Arteriosus described.23 Approximately one-fourth of patients who undergo surgical correction continue to have hypertension years after surgery, resulting in the complications associated with hypertension Atrial Septal Defect Pathophysiology and diagnosis In patients with an atrial septal defect, oxygenated blood from the left atrium passes into the right atrium, increasing right ventricular output and pulmonary blood flow Most patients with small or moderate defects are asymptomatic In patients with large shunts, exertional dyspnea or cardiac failure may develop, most commonly in the fourth decade of life or later Prominent right ventricular and pulmonary artery pulsations are readily visible and palpable On ECG, right axis deviation or right ventricular hypertrophy may be present Incomplete or complete right bundle branch block is present in nearly all patients with atrial septal defect Chest radiography shows large pulmonary arteries, increased pulmonary vascularity, an enlarged right atrium and ventricle, and a small aortic knob Echocardiography can demonstrate right ventricular volume overload with a large right ventricle and atrium, and sometimes it can reveal the defect itself A transesophageal ECG is helpful when the transthoracic ECG quality is not optimal Radionuclide flow studies can quantify left-to-right shunting MRI can elucidate the anatomy Cardiac catheterization remains the definitive diagnostic method because it can demonstrate an increase in oxygen saturation between the vena cava and the right ventricle resulting from the admixture of oxygenated blood from the left atrium, can quantify the shunt, and can allow the clinician to measure pulmonary vascular resistance Right and left ventricular contrast angiography may demonstrate associated valvular abnormalities or anomalous pulmonary venous drainage Management Small atrial septal defects not require surgery.24 The surgical mortality rate is low (< 1%) in patients under age 45 years who not have heart failure and who have systolic pulmonary pressures < 60 mm Hg.24 Patent Ductus Arteriosus Pathophysiology and diagnosis In patients with patent ductus arteriosus, the embryonic ductus arteriosus fails to close normally and persists as a shunt connecting the left pulmonary artery and aorta, usually near the origin of the left subclavian artery The defect is a form of arteriovenous fistula and increases the work of the left ventricle Patients have no symptoms unless left ventricular failure or pulmonary hypertension develops The heart is of normal size or slightly enlarged The pulse pressure is wide, and the diastolic pressure is low ECG may result in a normal tracing or may demonstrate left ventricular hypertrophy, depending on the magnitude of the shunting On chest radiography, the heart may be normal in size and contour, or left ventricular and left atrial enlargement may be observed The pulmonary artery, aorta, and left atrium are prominent Echocardiography allows the left ventricular and atrial size to be quantified MRI can demonstrate the abnormality The magnitude of the shunt can also be determined by radionuclide flow studies Cardiac catheterization can be performed to establish the presence and severity of left-to-right shunting and to determine whether pulmonary hypertension is present Angiography can be performed to define the anatomy 215 www.ajlobby.com Mizukawa_Chap_15.indd 215 6/20/17 10:41 AM 15 • The Cardiovascular System Management Surgical ligation of the patent ductus arteriosus can be accomplished with excellent results in patients with uncomplicated patent ductus arteriosus.25 Closure is recommended for children or adults with symptoms or large shunts.25 Ventricular Septal Defect Pathophysiology and diagnosis In patients with ventricular septal defect, a persistent opening in the upper interventricular septum permits blood to pass from the high-pressure left ventricle to the low-pressure right ventricle The resulting pathophysiology depends on the size of the defect and the magnitude of left-to-right shunting Large defects are associated with early left ventricular failure Chronic but moderate left-to-right shunts may lead to pulmonary vascular disease and right-sided heart failure Many ventricular defects close spontaneously in early childhood The clinical features of ventricular septal defect depend on the size of the defect and the presence or absence of raised pulmonary vascular resistance The ECG many be normal or may show right, left, or biventricular hypertrophy, depending on the size of the defect and the pulmonary vascular resistance In patients with large shunts, the right or left ventricle or both, the left atrium, and the pulmonary arteries are enlarged, and pulmonary vascularity is increased on the chest radiograph Echocardiography can demonstrate chamber size and may demonstrate the defect Doppler ultrasound can enable qualitative assessment of the magnitude of shunting and the pulmonary artery pressure MRI can often depict the defect Radionuclide flow studies can quantify the ratio of pulmonary to systemic flow Cardiac catheterization permits definitive diagnosis of all but the most trivial defects and permits measurement of pulmonary vascular resistance Management Small shunts in asymptomatic patients not require surgery Defects causing large shunts should be repaired to prevent irreversible pulmonary vascular disease or heart failure Some defects close spontaneously, and surgery should be deferred until late childhood unless the defect causes severe impairment Anesthetic considerations Providing optimal sedation and analgesia in infants and children with congenital heart defects can be difficult Depending on the age of the patient and the hemodynamic effects of the congenital defect, these patients may be most safely treated in an operating room setting Traditional sedative agents can have a negative effect on respiratory drive, and in many cases these patients are pre-emptively intubated to avoid potential apnea and cardiovascular compromise Furthermore, because of these potential adverse effects on ventilation, anesthetic agents are sometimes used at a lower dose, resulting in incomplete sedation Dexmedetomidine (α2-adrenergic receptor agonist) has been successfully used to provide sedation and analgesia in children after cardiac surgery; however, its use as the primary agent during invasive procedures in infants and toddlers with heart disease has not been studied.26 Dexmedetomidine also has minimal respiratory side effects Both propofol and dexmedetomidine provide effective procedural sedation, but propofol results in more hemodynamic and respiratory effects, including tachycardia, decreased mean MAP, and hypoxemia.27 These problems were not noted in patients receiving dexmedetomidine.27 These effects may be of clinical consequence in patients with cyanotic congenital heart disease in whom a decrease in MAP may increase right-to-left shunting The combination of dexmedetomidine and ketamine (NMDA receptor agonist) may prevent emergence phenomena and salivation, which can occur with ketamine alone.28 216 www.ajlobby.com Mizukawa_Chap_15.indd 216 6/20/17 10:41 AM References Conclusion Successful and safe treatment of patients with cardiovascular diseases that result from disruption of the normal conduction system and cardiac function relies on a thorough understanding of the anatomy and physiology of the cardiovascular system Furthermore, anesthetic considerations, including the choice of appropriate surgical arena and pharmacologic management, should be made References Patel RB, Secemsky EA Clinical features of heart failure and acute coronary syndromes Clin Lab Med 2014;34:15–30 Stevenson LW, Perloff JK The limited reliability of physical signs for estimating hemodynamics in chronic heart failure JAMA 1989;261:884–888 Yancy CW, Jessup M, Bozkurt B, et al 2013 ACCF/AHA guideline for the management of heart failure: Executive summary A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines Circulation 2013;128:1810–1852 Arroll B, Doughty R, Andersen V Investigation and management of congestive heart failure BMJ 2010;341:c3657 Rousch GC, Kaur R, Ernst ME Diuretics: A review and update J Cardiovasc Pharmacol Ther 2014;19:5–13 Goldman L, Caldera DL, Nussbaum SR, et al Cardiac risk factors and complications of non-cardiac surgery Medicine (Baltimore) 1978;57:357–370 McCallion J, Krenis LJ Preoperative cardiac evaluation Am Fam Physician 1992;45:1723–1732 Hansson L, Zanchetti A, Carruthers SG, et al; HOT Study Group Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial Lancet 1998;351:1755–1762 Arauz-Pacheco C, Parrott MA, Raskin P; American Diabetes Association Treatment of hypertension in adults with diabetes Diabetes Care 2003;26(suppl 1):80–82 10 National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification Am J Kidney Dis 2002;39(2, suppl 1):S1–S266 11 Merai R, Siegel C, Rakotz M, et al CDC grand rounds: A public health approach to detect and control hypertension MMWR Morb Mortal Wkly Rep 2016;65:1261–1264 12 National Institutes of Health; National Heart, Lung, and Blood Institute The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (NIH Publication No 04-5230) Washington, DC: US Deptartment of Health and Human Services, 2004 13 Miller RD, Pardo MC Jr Basics of Anesthesia, ed Philadelphia: Elsevier Saunders, 2011 14 Mangano DT, Layug EL, Wallace A, Tateo I; Multicenter Study of Perioperative Ischemia Research Group Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery N Engl J Med 1996;335:1713–1720 15 Wallace AW, Galindez D, Salahieh A, et al Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery Anesthesiology 2004;101:284–293 16 Niwa H, Sugimura M, Satoh Y, Tanimoto A Cardiovascular response to epinephrine-containing local anesthesia in patients with cardiovascular disease Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:610–616 17 Rhodus NL, Little JW Dental management of the patient with cardiac arrhythmias: An update Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:659–668 18 Nuttall GA, Brown MJ, Stombaugh JW, et al Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention Anesthesiology 2008;109:588–595 19 Rabbits JA, Nuttall GA, Brown MJ, et al Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents Anesthesiology 2008;109:596–604 20 Mangano DT, Goldman L Preoperative assessment of patients with known or suspected coronary artery disease N Engl J Med 1995;333:1750–1756 21 Hilgenberg JC, McCammon RL, Stoelting RK Pulmonary and systemic vascular responses to nitrous oxide in patients with mitral stenosis and pulmonary hypertension Anesth Analg 1980;59:323–326 22 Chen CR, Cheng TO, Huang T, et al Percutaneous balloon valvuloplasty for pulmonic stenosis in adolescents and adults N Engl J Med 1996;335:21–25 23 Yetman AT, Nykanen D, McCrindle BW, et al Balloon angioplasty of recurrent coarctation: A 12-year review J Am Coll Cardiol 1997;30:811–816 24 Konstantinides S, Geibel A, Olschewski M, et al A comparison of surgical and medical therapy for the atrial septal defects in adults N Engl J Med 1995;333:469–473 25 Clyman RI Surgical ligation of the patent ductus arteriosus: Treatment or morbidity? J Pediatr 2012;161:583–584 26 Chrysostomou C, Di Filippo S, Manrique AM, et al Use of dexmedetomidine in children after cardiac and thoracic surgery Pediatr Crit Care Med 2006;7:126–131 27 Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging Anesth Analg 2006;103:63–67 28 Levänen J, Mäkelä ML, Scheinin H Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium Anesthesiology 1995;82:1117–1125 217 www.ajlobby.com Mizukawa_Chap_15.indd 217 6/20/17 10:41 AM www.ajlobby.com Mizukawa_Chap_15.indd 218 6/20/17 10:41 AM The Pulmonary System Pulmonary CHAPTER 16 Ravi Agarwal, dds George Obeid, dds www.ajlobby.com Mizukawa_Chapter_Openers.indd 219 6/21/17 3:24 PM Pulmonary CHAPTER 16 The Pulmonary System Normal Anatomy and Physiology 221 Asthma 225 Chronic Obstructive Pulmonary Disease 229 Acute Respiratory Infection 232 Restrictive Lung Diseases 233 www.ajlobby.com Mizukawa_Chapter_Openers.indd 220 6/21/17 3:24 PM Normal Anatomy and Physiology The pulmonary system has many functions in addition to ventilation and oxygenation Other functions include performing gas exchange, maintaining acid-base balance, filtering blood clots/gas bubbles, serving as a blood reservoir, producing angiotensin-converting enzyme, producing immunoglobulin A to protect against respiratory infections, and participating in drug metabolism Normal Anatomy and Physiology The pulmonary system consists of two lungs surrounded by pleura within the rib cage The apex of the lung is smaller than the base to allow entry of the trachea, esophagus, and blood vessels into the mediastinum The base of the lung is larger than the apex and is formed mostly by the diaphragm, which is the principal pulmonary muscle The diaphragm accounts for three-fourths of the movement in the chest wall; the remainder is from the accessory intercostal muscles The sternocleidomastoid, scalene, and pectoral muscles can also be recruited to help in inspiration Expiration is generally passive but can be facilitated by the abdominal musculature.1 Ventilation begins with passage of air through the upper airways, which consist of the mouth, nose, pharynx, larynx, and trachea The upper airways humidify, warm, and filter the inspired air, protecting the lower airways The tracheobronchial tree conducts air to and from the alveoli (Fig 16-1) Generally, the cartilaginous airways (trachea, main stem, and small bronchi) and the terminal bronchioles (which have no cartilage support) lack alveoli and not participate in gas exchange The remainder of the distal airways (respiratory bronchioles, alveolar ducts, and alveolar sacs) are the principal elements in gas exchange Branching starts from the trachea, and each successive division divides into two smaller branches It is estimated that the airways divide 23 times With each division, the mean diameter of the airway decreases Trachea Left and right main bronchi Conducting airway Lobar bronchi Segmental bronchi Carina Bronchioles Respiratory airway Terminal bronchiole Respiratory bronchioles Alveolar ducts Alveolar sac Alveoli Fig 16-1 The tracheobronchial tree Histologically, most of the upper airways, the trachea, and the bronchi are lined with respiratory ciliated pseudostratified columnar epithelium, which contains numerous mucus-producing goblet cells A transition occurs from ciliated columnar epithelium in the bronchi to ciliated cuboidal epithelium in the bronchioles The cilia are synchronized to help clear mucus and move debris toward the throat to be swallowed In the terminal bronchioles, the epithelial layer transitions to nonciliated cuboidal cells with almost no goblet cells Within these terminal bronchioles are specialized secretory cells, known as Clara cells, which produce surfactant to protect the epithelial linings Finally, the alveolar epithelium becomes thin and squamous, consisting of two types of specialized cells Type 221 www.ajlobby.com Mizukawa_Chap_16.indd 221 6/20/17 10:42 AM 16 • The Pulmonary System pneumocytes are squamous cells that participate in gas exchange Type II pneumocytes produce surfactant and have the ability to produce new epithelial cells.1 The connective tissues within the airways vary in content with progression from the trachea to the terminal bronchioles Typically, the connective tissue layers contain elastic fibers, variable amounts of seromucous secretory glands, smooth muscles, and supporting cartilage The tracheal and bronchial connective tissues contain numerous seromucous secretory glands Supporting the connective tissues in the trachea are C-shaped rings of hyaline cartilage that are connected by the smooth trachealis muscle The bronchi have plates of cartilage rather than rings Starting in the bronchi, a circumferential layer of smooth muscle encircles the epithelium In the transition from the bronchi to the bronchioles, the cartilage and secretory glands decrease, and the smooth muscle layer becomes more prominent, playing a major role in supporting the bronchiole diameter The alveoli not have a substantial submucosal layer, thus providing a thin blood-air barrier The control mechanisms of smooth muscles in the airway provide important airway resistance and affect the role of pharmacologic agents in treatment These smooth muscles can extend to the terminal bronchioles and are influenced by both parasympathetic and sympathetic nerves Other nonadrenergic and noncholinergic mechanisms also affect smooth muscle tone; however, they are less important for this overview The parasympathetic fibers located on the vagus nerve mediate baseline airway tone and control smooth muscle contraction When stimulated, these fibers can initiate bronchoconstriction In addition, parasympathetic activation of submucosal glands and blood vessels causes mucus secretion and vasodilation, respectively Therefore, the release of histamine, as seen in patients with asthma, can increase the afferent vagal activity, leading to reflex bronchoconstriction and mucus secretion The parasympathetic control targets muscarinic receptors found on the postjunctional smooth muscles In addition to these postjunctional receptors on the smooth muscle itself, prejunctional muscarinic receptors inhibit the release of acetylcholine, leading to bronchodilation.1 An example of an anticholinergic used in the treatment of obstructive lung diseases is ipratropium Adrenergic receptors are also found in bronchial smooth muscle and allow for sympathetic control through α and β receptors The β2 subtype has the most substantial effect on airway smooth muscle responsiveness.1 Stimulation of these β2 receptors causes relaxation of these smooth muscles, leading to bronchodilation Albuterol is an example of a β2 agonist used in the treatment of acute asthma Pulmonary hemodynamics The lungs have two types of circulation: pulmonary and bronchial The bronchial circulation stems from systemic circulation to provide metabolic supply to the airways proximal to the terminal bronchioles The terminal bronchioles receive blood supply from the pulmonary circulation and the diffusion from alveolar gas The arterial supply to the remainder of the proximal airways is from the aorta or upper intercostal vessels, and the venous blood drains to the azygos, hemiazygos, or intercostal veins The pulmonary circulation receives the output of the right heart via the pulmonary artery, which accounts for 10% to 20% of total blood volume Each lung receives branches of the artery, which pass the deoxygenated blood into the pulmonary capillaries for oxygenation and for release of carbon dioxide (CO2) The oxygenated blood is then returned from each lung to the left heart via the two pulmonary veins The pulmonary system has the same flow rate as the systemic circulation However, the blood pressure within the pulmonary circulation is approximately one-sixth of the systemic blood pressure.2 As a result, the pulmonary vasculature has thinner vessel walls and less smooth muscle Because the pulmonary capillaries have low pressure, the blood flow is affected by gravity and alveolar size For example, when a person is standing, the apex of the lung will have less flow than the basal lung has Another regulator of pulmonary vascular tone is the alveolar concentration of oxygen (Cao2) During times of hypoxia, the pulmonary vasculature will vasoconstrict to redistribute the blood to better-ventilated regions in the lung.2 222 www.ajlobby.com Mizukawa_Chap_16.indd 222 6/20/17 10:42 AM Normal Anatomy and Physiology Ventilation control Ventilation is affected by controllers in the central nervous system, central and peripheral sensors, and effector mechanisms involving the upper airway and muscles.2 The medulla is the main controller of ventilation, controlling the basic ventilatory rhythm The pons modifies ventilatory activity via two centers The apneustic center terminates inspiration, and the pneumotaxic center controls breathing patterns in response to afferent stimuli The cerebral cortex controls voluntary ventilation Central chemoreceptors in the medulla respond to changes in both CO2 and pH Because the blood-brain barrier has free diffusion of CO2, it has a direct effect on the amount of circulating hydrogen ions (H+).1 For example, an increase in H+ concentration within the cerebrospinal fluid stimulates ventilation Generally, the central chemoreceptors that respond to CO2 are more sensitive than the peripheral chemoreceptors are However, unlike the peripheral chemoreceptors, the central receptors not respond to hypoxemia Additionally, at high partial pressure of CO2 (Paco2) levels (> 70 mm Hg), CO2 can act as a respiratory depressant Peripheral chemoreceptors are mostly found in the carotid body and the aortic body These receptors respond mostly to oxygen tension.1 In times of low oxygen tension (eg, acute blood loss), peripheral chemoreceptors will stimulate ventilation, whereas a decreased hemoglobin concentration, as in anemia, has no influence on ventilation The individual response to hypoxia varies widely, and sensitivity decreases with increasing age and life in high altitudes Generally, drugs used in sedation and anesthesia depress the normal responses to hypoxia, hypercapnia, and acidosis The phrenic nerve innervates the diaphragm The phrenic nerve arises from nerve roots C3, C4, and C5 Cervical cord injuries above C5 result in the loss of spontaneous respiration The tracheobronchial tree has innervations from the vagus nerve for parasympathetic bronchoconstriction and mucus production The sympathetic innervations that mediate bronchodilation arise from T1 through T4 Gas exchange Oxygen accounts for 21% of room air and has a partial pressure of 150 mm Hg at sea level It is important to remember that the partial pressure of oxygen varies with humidity After air enters the alveolus, it is mixed with residual alveolar gas, which consists mostly of CO2 The difference between the alveolar oxygen and arterial oxygen concentrations is important for effective ventilation The difference between the alveolar and the arterial oxygen concentrations, known as the A-a gradient, is approximately 15 mm Hg The arterial oxygen concentration is a clinical measurement, typically obtained through arterial blood gas (ABG) analysis The alveolar oxygen tension is calculated by using the alveolar gas law: Pao2 = FiO2 × (Patm – PH2O) – Paco2/RQ, where FiO2 is the fraction of inspired oxygen, Patm is atmospheric pressure, PH2O is the vapor pressure of water at body temperature, RQ is the respiratory quotient, and Paco2 is the arterial CO2 tension.2 On the basis of the alveolar gas law, one can see that the addition of supplemental oxygen to increase the FiO2 can maintain saturation even in times of hypoventilation (increased Paco2) Supplemental oxygen via a nasal cannula increases the FiO2 approximately 3% with each additional liter per minute increment Thus, L of oxygen via nasal cannula, commonly used during intravenous sedation, provides an FiO2 of approximately 27% The average alveolar oxygen tension at sea level is 105 mm Hg Because the oxygen tension of the venous blood entering the lungs is low (approximately 40 mm Hg), a large concentration gradient drives oxygen diffusion across the alveolar membranes Ideally, this blood, having passed through the lungs, should have an oxygen tension equal to that in the alveolus However, arterial blood analysis rarely shows arterial oxygen tension equal to the calculated alveolar oxygen tension This A-a gradient is typically due to venous admixture, which is influenced by variables including ventilation/perfusion mismatch, right-to-left shunting, and oxygen diffusion abnormalities The A-a gradient is important in the diagnosis of hypoxemia.1 Causes of hypoxemia either increase the A-a gradient or prevent it from changing The gas exchange of CO2 differs from that of oxygen CO2 has higher blood solubility and diffuses 20 times faster than oxygen does Thus, the gradient between arterial CO2 and alveolar CO2 is minimal, estimated to be mm Hg In the clinical setting, alveolar CO2 concentration can be measured using end-tidal gas analysis Because 223 www.ajlobby.com Mizukawa_Chap_16.indd 223 6/20/17 10:42 AM 16 • The Pulmonary System the alveolar-arterial gradient of CO2 is low, end-tidal measurements are a good indicator of arterial CO2 concentrations, with normal arterial CO2 tension estimated to be 40 mm Hg A major concern during anesthesia is the development of hypercapnia, which may be caused by either hypoventilation or increased CO2 production Acute hypercapnia causes pulmonary vasoconstriction, resulting in compromised right heart function, and an increase in heart rate and stroke volume that, despite the myocardial depressant effect of hypercapnia, leads to increased blood pressure This hypertensive effect is attenuated by a decrease in peripheral vascular resistance The neurologic effects of hypercapnia include increased cerebral blood flow and intracranial pressure, depressed level of consciousness, agitation, and decreased seizure threshold Finally, hypercapnia leads to a rightward shift of the oxygen-hemoglobin dissociation curve with enhanced tissue oxygen offloading.2 Lung volumes Understanding lung volumes is an important tool in the assessment of diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (Fig 16-2).1 One important pulmonary function test is spirometry, which helps estimate various lung volumes and lung capacities Although a detailed discussion is beyond the scope of this chapter, some basic definitions and utilities are discussed here 6.0 Volume (L) Inspiratory reserve volume 3.0 2.5 Inspiratory capacity Vital capacity Total lung capacity Tidal volume Expiratory reserve volume 1.5 Functional residual capacity Residual volume Fig 16-2 Representation of lung volumes used in spirometry The total lung capacity is the total volume of gases at maximal inspiration The vital capacity is the maximum volume that can be exhaled after maximum inspiration, normally 60 to 70 mL/kg The lung cannot be emptied completely, and the remaining volume after maximal exhalation is the residual volume Tidal volume is the amount of air moved during normal ventilation.1 After a tidal volume breath, the remaining volume is the functional residual capacity (FRC), approximately 1.7 to 3.5 L Many factors affect FRC, including age, body size, posture, obesity, sex, and pulmonary diseases For example, obesity increases abdominal pressure, leading to a reduced FRC During anesthesia, a patient with reduced FRC will have a lower threshold for desaturation during a period of apnea An important marker of airflow limitation that is used clinically to measure obstruction is the ratio of forced expiratory volume in second (FEV1) to forced vital capacity (FVC) FEV1 is the volume of air exhaled in the first second of a forced expiration, whereas FVC is the total volume of air expired during a forced expiration An individual with normal pulmonary function should be able to exhale 80% of vital capacity in second (FEV1/FVC ≥ 80%) Decreases in this ratio are associated with reversible causes of airflow limitation (eg, asthma) and irreversible airflow limitation (eg, COPD).1 224 www.ajlobby.com Mizukawa_Chap_16.indd 224 6/20/17 10:42 AM Asthma Oxygen transport Oxygen is carried in the blood in two forms: (1) dissolved in plasma or (2) bound to hemoglobin More than 98% of oxygen is reversibly bound to hemoglobin Hemoglobin, a protein found in red blood cells, is considered the primary vehicle for oxygen transport Each hemoglobin molecule can carry four oxygen molecules Hemoglobin saturation is the amount of oxygen bound as a percentage of its total oxygen binding ability In clinical practice, peripheral oxygen saturation (Spo2) is measured by pulse oximetry, which estimates the percentage of hemoglobin bound by oxygen The remaining 2% of oxygen in the arterial system is dissolved within the blood Generally, oxygen has low solubility in blood, manifest by the small amounts freely dissolved in the blood at normal partial pressures However, the amount of dissolved oxygen can increase substantially when a patient is given 100% oxygen to breathe or during hyperbaric oxygen treatment The amount of oxygen dissolved in blood accounts for the arterial partial pressure of oxygen (Pao2) Hemoglobin binds or releases oxygen in relation to the prevailing Pao2 For example, in the lungs, the oxygen tension is high, and hemoglobin acquires oxygen In peripheral tissues, where the oxygen tension is low, hemoglobin releases oxygen from its bound state This relationship is illustrated by the oxygen-hemoglobin dissociation curve (see Fig 8-1) A number of factors can alter the affinity of hemoglobin for oxygen and shift the oxygen-hemoglobin dissociation curve, as shown in Fig 8-1.1 This curve may shift to the left or to the right, depending on factors such as changes in temperature, acidity, CO2 levels, and 2,3-diphosphoglycerate levels A leftward shift increases the affinity of hemoglobin for oxygen, whereas a shift to the right reduces the affinity of hemoglobin for oxygen For more details, refer to chapter 23 Asthma Pathophysiology and diagnosis Asthma is a pulmonary disease characterized by airway inflammation and bronchiole smooth muscle hypertrophy and reactivity leading to episodic expiratory airflow obstruction Asthma has an estimated prevalence of 6% to 7% in the US population, and it can affect people of all ages.3 Signs and symptoms of asthma include episodic attacks of wheezing, coughing (productive or nonproductive), dyspnea, and chest tightness Acute exacerbations of asthma are typically short-lived, usually lasting minutes to hours, but can be life-threatening, as in status asthmaticus, which is a severe asthma attack that does not respond to standard treatments The exact cause of asthma is unknown but is thought to be genetic or environmental.3 The greatest risk factor is atopy; however, asthma can be seen in patients with other allergic diseases, such as rhinitis, urticaria, and eczema Symptoms of asthma may be exacerbated by a variety of triggers.4 Extrinsic triggers of asthma are environmental allergens, such as inhalants (eg, animal dander, dust, pollen), irritants (eg, smoke, chemicals), or drugs Intrinsic triggers are factors not related to allergies, such as exercise, strong emotions, stress, and/or menstrual cycles Symptoms can occur during the day or during sleep The pathophysiology of an asthma attack involves inflammatory mediators and overactivity of the parasympathetic nervous system Inflammatory mediators released by activated mast cells include histamine, bradykinin, leukotrienes, and prostaglandins, resulting in bronchoconstriction, mucosal edema, and increased secretions.5 The parasympathetic nervous system is also activated, increasing bronchiole vagal tone and leading to bronchoconstriction No consensus has been reached on a diagnostic classification system for asthma Asthma can be intermittent or persistent, with the persistent form further classified as mild, moderate, or severe.3 No single diagnostic test exists, and a clinical diagnosis of asthma is based on symptoms When asthma is suspected, spirometry aids in confirming the diagnosis (Table 16-1).6 One important measurement in spirometry is FEV1 The clinical measurement is then compared with a predicted value for the individual and aids in classifying the severity of obstruction 225 www.ajlobby.com Mizukawa_Chap_16.indd 225 6/20/17 10:42 AM 16 • The Pulmonary System Table 16-1 Asthma classification based on severity* Severity Factor Intermittent Mild persistent Moderate persistent Severe persistent Symptoms ≤ 2 d/wk > 2 d/wk but not daily Daily Throughout the day Nighttime awakenings ≤ 2 times/mo or times/mo > 1 time/wk but not nightly Often times/wk Rescue inhaler use ≤ 2 d/wk > 2 d/wk but not daily Daily Several times per day Limitation of daily activities None Minor limitation Some limitation Extreme limitation Pulmonary function • FEV1 > 80% predicted • FEV1/FVC normal • FEV1 > 80% predicted • FEV1/FVC normal • FEV1 > 60% predicted • FEV1/FVC reduced 5% • FEV1 5% *Modified from National Asthma Education and Prevention Program.6 Management Because no cure is available, treatment of asthma is based on preventing and controlling bronchial inflammation The treatment of asthma has two components The first component of treatment is bronchodilation Many patients often use inhaled β-adrenergic agonists or inhaled anticholinergics to relax bronchial smooth muscles One of the most common short-acting rescue inhalers is albuterol; others include levo-albuterol and ipratropium Patients with more persistent disease are placed on long-acting β2 agonists (eg, salmeterol or formoterol) or anticholinergics (eg, tiotropium) The second component of asthma treatment is to control airway inflammation and irritability This goal can be accomplished with the use of inhaled steroids, such as beclomethasone or fluticasone These medications are effective in chronic treatment of the disease and provide some bronchodilator effects Systemic steroids are typically reserved for use in short intervals for the treatment of acute bronchospasm The leukotriene receptor antagonists (montelukast, zafirlukast, and zileuton) are another class of drugs used to control airway inflammation These drugs are primarily used for maintenance, especially in individuals with allergy-induced asthma (Table 16-2) 226 www.ajlobby.com Mizukawa_Chap_16.indd 226 6/20/17 10:42 AM Asthma Table 16-2 Common medications used in the treatment of asthma Drug class Examples Mechanism of action Potential adverse effects Inhaled corticosteroids • Beclomethasone (Qvar, Teva) • Mometasone (Asmanex, Merck) • Flunisolide (Aerospan HFA, Meda) • Fluticasone (Flovent, GSK) • Budesonide (Pulmicort, AstraZeneca) • Ciclesonide (Alvesco, Sunovion) • Triamcinolone • Decreases airway inflammation • Decreases airway hyperresponsiveness Dysphonia, myopathy of laryngeal muscles, oropharyngeal candidiasis Oral corticosteroids • Methylprednisone (Medrol, Pfizer) • Prednisone • Decreases airway inflammation • Decreases airway hyperresponsiveness Dysphonia, myopathy of laryngeal muscles, oropharyngeal candidiasis Cromolyns • Cromolyn sodium nebulizer • Nedocromil • Inhibits release of mediators from mast cells • Stabilizes mast cell membranes Local throat irritation, cough Leukotriene modifiers • Zafirlukast (Accolate, AstraZeneca) • Montelukast (Singulair, Merck) • Zileuton (Zyflo, Chiesi) Inhibits 5-lipoxygenase, reducing synthesis of leukotrienes Minimal Short-acting β-adrenergic agonists • Albuterol (Proventil [Merck], Ventolin [GSK]) • Metaproterenol • Levalbuterol (Xopenex sulfate, Sunovion) • Pirbuterol • Isoproterenol (Isuprel, Valeant) • Terbutaline Stimulates β2 receptors on tracheobronchial tree Tachycardia, tremors, dysrhythmias, hypokalemia Long-acting β-adrenergic agonists • Salmeterol (Serevent, GSK) • Formoterol (Perforomist, Mylan) Stimulates β2 receptors on tracheobronchial tree Tachycardia, tremors, dysrhythmias, hypokalemia Anticholinergics • Ipratropium (Atrovent, Boehringer Ingelheim) • Tiotropium (Spiriva, Boehringer Ingelheim) Decreases vagal tone by blocking muscarinic receptors in airway smooth muscle Dry mouth, cough, blurred vision Oral methylxanthines • Theophylline (Elixophyllin [Forest Labs], Theochron [Nostrum Labs]) • Oxtriphylline (Choledyl[Warner/Chilcott]) • Inhibits phosphodiesterase • Increases cyclic adenosine monophosphate • Releases endogenous catecholamines Nervousness, nausea, vomiting, insomnia, irritability, dysrhythmias, anorexia, headache Combination drugs • Ipratropium and albuterol (Combivent, Boehringer Ingelheim) • Fluticasone and salmeterol (Advair, GSK) • Budesonide and formoterol (Symbicort, AstraZeneca) • Mometasone and formoterol (Dulera, Merck) See specific mechanism of action for each drug See specific drug interactions for each drug Anti-IgE • Omalizumab (Xolair, Genentech/Novartis) Inhibits binding of IgE molecules to the high-affinity IgE receptors on mast cells and basophils Anaphylaxis IgE, immunoglobulin E 227 www.ajlobby.com Mizukawa_Chap_16.indd 227 6/20/17 10:42 AM 16 • The Pulmonary System Anesthetic considerations Preoperative evaluation is needed to determine the severity of the disease and its control with medications A symptom questionnaire can be helpful to assess the severity of disease (Box 16-1) Well-controlled asthma does not appear to be a risk factor for intraoperative pulmonary complications.7 Poorly controlled disease is usually associated with recent emergency department visits and/or hospitalizations, increased use of rescue inhalers, or recent flare-ups requiring oral corticosteroids A preoperative physical examination should include auscultation of the lungs to elucidate any wheezing and assessment of the use of accessory muscles, which may suggest active disease.8 BOX 16-1 • • • • • Preoperative characteristics for evaluation in patients with asthma • • • • • Age of onset Triggers Allergies Number of hospitalizations Frequency of emergency visits Need for endotracheal intubation Cough and sputum characteristics Current medications Frequency of rescue inhaler use Previous surgical and anesthetic history Pulmonary function tests can be reviewed because they may assist the practitioner in assessing the severity and diagnosis of asthma, but they often not change the management in open-airway office-based anesthesia.9 Occasionally, patients with asthma use a peak flow meter to monitor their disease For these patients, assessing and comparing the preanesthetic peak flow with baseline performance may be useful in recognizing any recent asthmatic flare-ups and any lingering disease The peak expiratory flows should ideally be > 80% of the predicted value or the patient’s personal best before elective surgery.7 Generally, all home medications should be continued in the preoperative and perioperative period.10 On the day of surgery, the patient should be assessed for any evidence of wheezing If bronchospasm is a concern, the patient should receive short-acting β-agonist bronchodilator treatment Office-based anesthesia and surgery should be deferred if a patient does not respond to bronchodilator therapy With regard to the selection of an anesthetic agent, propofol has beneficial bronchodilation properties.11 Ketamine, although a smooth muscle relaxant, has a tendency to increase secretions.8,11 Increased secretions can be addressed with the preoperative administration of glycopyrrolate, an anticholinergic; however, it can increase the viscosity of airway secretions.12 Drugs to avoid include any medication that induces histamine release, such as morphine and meperidine.13 Typically, these patients well with open-airway anesthetics; however, if a more secured airway is necessary, one can consider a supraglottic airway, such as a laryngeal mask airway, to prevent airway stimulation.12 End-tidal CO2 monitoring is required, and the use of a precordial stethoscope enhances early detection of bronchospasm During anesthesia, the practitioner should be aware that asthmatic patients have a more reactive airway than other patients have, and the major implication is intraoperative acute bronchospasm.10 Although the incidence of bronchospasm during anesthesia is low, this complication can be difficult to manage and can result in brain injury or death The risk of acute bronchospasm in asthmatic patients continues during emergence from anesthesia Acute bronchospasm can be precipitated by debris within the airway, such as blood, gauze, irrigants, and particles It is crucial to ensure the use of appropriate measures, such as good suction, surgical illumination, proper use of throat packs, and a surgical team trained to manage bronchospasm should it occur.14 (See chapter 12 for management of bronchospasm.) 228 www.ajlobby.com Mizukawa_Chap_16.indd 228 6/20/17 10:42 AM Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Pathophysiology and diagnosis COPD, which includes emphysema and chronic bronchitis, is largely related to smoking and is hallmarked by chronic productive cough, sputum production, dyspnea, and abnormal lung function3 (Table 16-3) COPD is characterized by chronic inflammation, destruction of lung parenchyma, and risk of respiratory infections Similar to asthma, COPD is an obstructive phenomenon seen in the loss of elastic recoil of the lungs and the increased airway resistance However, COPD differs from asthma in that the chemical mediators in COPD lead to permanent, irreversible damage, whereas the effects of asthma may be reversible.15 Risk factors for the development of COPD include smoking, respiratory infections, occupational exposure to dusts (eg, coal, gold, textiles), and genetic factors, such as α-1 antitrypsin deficiency The three most important symptoms of COPD are chronic cough, sputum, and dyspnea The Global Initiative for Chronic Obstructive Lung Disease, an international organization that focuses on prevention and treatment of COPD, advocates the use of spirometry for the diagnosis of COPD According to this criterion, postbronchodilator FEV1/FRC < 70% confirms the presence of the obstructive phenomenon.12 COPD is then further classified on the basis of the patient’s response to bronchodilator therapy compared with the predicted FEV1/FRC Table 16-3 Characteristics of COPD* Type of COPD Factor Chronic bronchitis Emphysema Appearance/nickname “Blue bloater” “Pink puffer” Dyspnea Mild, late in disease Severe, early in disease Cough Frequent, early in disease Less frequent, occurring with exertion Sputum Copious Scant Infections Common Occasional Respiratory insufficiency Repeated Terminal Cor pulmonale Common Rare, terminal Hematocrit Elevated Normal Elastic recoil Normal Decreased Chest radiographs Increased lung markings, prominent vessels, large heart Hyperinflation Airway resistance Increased Normal to slight increase Often elevated (> 40 mm Hg) Usually normal (< 40 mm Hg) Paco2 *Modified from Little et al Chronic bronchitis is caused by hyperplasia of mucus-producing glands, goblet cell metaplasia, and chronic inflammation around the bronchi These processes lead to excessive mucus production, chronic cough with sputum, and airway obstruction Impairment of ciliary function results in a predisposition to frequent respiratory infection Bronchitis, unlike emphysema, tends not to cause pulmonary capillary bed damage The chronic obstruction leads to increased residual lung volumes, which may create a barrel-chested appearance In these patients, a substantial ventilation-perfusion mismatch leads to CO2 retention, hypoxemia, and polycythemia Patients with COPD and chronic bronchitis are sometimes referred to as “blue bloaters.”3 Emphysema results in destruction of the airways distal to the terminal bronchioles Destruction of the pulmonary capillary bed decreases the surface area available for oxygen exchange Ventilation of underperfused lung tissue leads to ventilation-perfusion mismatch; however, the mismatch is generally less severe than that seen in patients with chronic bronchitis In an attempt to maintain normal CO2 levels, compensatory hyperventilation oc- 229 www.ajlobby.com Mizukawa_Chap_16.indd 229 6/20/17 10:42 AM 16 • The Pulmonary System curs These patients are typically thin, often have distant breath sounds, and may show hyperlucency on chest radiographs Because of these changes, these patients are sometimes called “pink puffers.”3 COPD creates an environment of insufficient oxygen delivery In response to the inadequate oxygen within the alveoli, the body compensates by constricting the pulmonary vasculature in an effort to direct blood flow to more oxygenated parts of the lung Long-term hypoxia and vasoconstriction lead to pulmonary hypertension, which then creates a substantial strain on the right heart, culminating in cor pulmonale.15 The chest radiographic findings in patients with COPD include hyperinflation and, in patients with cor pulmonale, enlargement of the heart shadow Acute exacerbation of COPD is associated with increased cough and sputum production, which may be purulent, and increased dyspnea During this period, patients may require hospitalization, antibiotics, bronchodilators, and corticosteroids Even after adequate treatment, these patients are at high risk of repeat development of pulmonary complications; therefore, elective procedures under anesthesia require careful consideration.11 One of the leading causes of COPD is cigarette smoking Smoking cessation can reduce carboxyhemoglobin levels and reduce airway inflammation Smoking increases the risk of perioperative cardiac and pulmonary complications (Box 16-2).12 Abstinence from smoking can reduce these complications; however, no established guidelines or data are available to determine the ideal time to stop smoking preoperatively Generally, abstinence at least weeks before the procedure is thought to maximize the beneficial effects of smoking cessation.16 Even weeks of smoking cessation results in improvement in mucociliary function and possibly a reduced rate of perioperative complications The controversy surrounding smoking cessation is in the immediate preoperative period (24 to 48 hours) In this time frame, smoking cessation reduces carboxyhemoglobin levels; however, the risk of perioperative complications may increase because of sputum production and airway hyperreactivity.12 With patients who smoke, one concern in open-airway anesthesia is laryngospasm Although abstinence can provide some benefit as early as 12 hours after stopping, the time at which the perioperative risks dissipate in patients who smoke remains controversial BOX 16-2 • • • • • • • • Cardiac and respiratory effects of smoking* Represents a major risk factor for cardiovascular disease and chronic pulmonary disease Increases carbon monoxide, which competes with oxygen for delivery Leads to coronary vasoconstriction and increased myocardial work Decreases exercise tolerance Serves as a direct irritant, resulting in hyperreactive airways Decreases mucociliary clearance Decreases respiratory immune function Increases risk of in-hospital mortality and likelihood of admission to intensive care unit *Modified from Al-Ruzzeh and Kurup.12 Management Because no cure is available, the best treatment of COPD is prevention After diagnosis, the management is primarily symptomatic, with a goal of slowing the progression of the disease.15 Home oxygen is often utilized, especially in patients with chronic hypoxemia with Pao2 90% as measured by pulse oximetry.13 However, because patients with advanced disease tend to adapt to the chronic hypercarbia and rely on arterial oxygen levels to trigger respiratory drive (hypoxemic drive), excessive inspired oxygen concentration can lead to bradypnea, especially during anesthesia Opioids should be used cautiously because central nervous system depression can reduce the hypercapnic respiratory drive and cause prolonged ventilatory depression.12 In patients with severe disease, the surgeon should consider minimal conscious sedation with the use of medications such as midazolam along with profound local anesthesia Acute Respiratory Infection Pathophysiology and diagnosis Uncomplicated upper respiratory infection (URI) is common and usually viral in nature Common symptoms of uncomplicated URI include rhinitis, clear rhinorrhea, nasal congestion, and sore throat Fever is not common in adults with URI Purulent nasal secretions may occur in the absence of a bacterial infection Acute bacterial rhinosinusitis is an uncommon complication of URI Other complications of URI include lower respiratory tract infection marked by fever and productive cough, asthma, and otitis media Airway hypersensitivity after URI increases the risk of perioperative pulmonary complications during anesthesia, including excessive coughing, breath holding, laryngospasm, bronchospasm, atelectasis, postoperative stridor, pneumonia, and oxygen desaturation.8 The risk of a pulmonary complication is highest during acute infection; however, it remains elevatedfor up to weeks after resolution of symptoms Management Most cases of uncomplicated URI or the “common cold” not typically require antibiotic therapy because their etiology is viral Patients often treat their symptoms with over-the-counter medications, which often include a combination of analgesics, decongestants, antihistamines, antitussives, and/or mucolytics Because certain decongestants can elevate blood pressure, they should be used with caution in patients with hypertension If the patient has been diagnosed with a bacterial infection, the use of antibiotics is appropriate, and often the choice of drug is directed toward upper respiratory flora 232 www.ajlobby.com Mizukawa_Chap_16.indd 232 6/20/17 10:42 AM Restrictive Lung Diseases Anesthetic considerations In pediatric patients, the risk of respiratory complications associated with anesthesia is increased in the presence of URI.17 Generally, elective ambulatory procedures should be delayed in the presence of obvious symptoms of URI, such as rhinitis, cough, and/or fever In children, elective anesthesia should ideally be deferred for weeks after URI However, this delay may be impractical because the child is at risk of acquiring another URI and may have an acute dental problem that requires earlier intervention Patients with an uncomplicated URI who are asymptomatic for to weeks can be safely anesthetized.8 However, the provider must use good judgment and experience in the decision-making process when considering sedation of a patient recovering from URI Each patient should be assessed individually, and the provider should have a low threshold to cancel a procedure if the risks of anesthesia clearly outweigh the benefits The goal is to minimize secretions and avoid airway stimulation Before the fasting period in preparation for anesthesia, the patient should be well hydrated to help clear secretions and prevent mucous plugging The use of an anticholinergic, such as glycopyrrolate or atropine, can be considered to help decrease secretions However, this strategy has not necessarily been shown to decrease perioperative risk.18 Preoperative bronchodilators given 10 to 30 minutes before the onset of the anesthetic may reduce the incidence of bronchospasm and perioperative pulmonary events.17 In general, outpatient anesthesia should be administered with an open-airway technique to avoid airway stimulation resulting from the use of laryngeal mask airway or endotracheal tubes Restrictive Lung Diseases Pathophysiology and diagnosis Restrictive lung diseases (RLDs) are groups of pathologies that generally decrease lung volumes, reduce lung compliance, and restrict lung expansion These diseases are divided into extrinsic (extrapulmonary) or intrinsic (parenchymal) and can be either acute or chronic in nature.12 Unlike obstructive lung disease, RLDs not affect expiratory airflow, and airway resistance is normal even though the total lung capacity is reduced.15 Reduced gas exchange or reduced FRC can occur, leading to desaturation after normal activities such as exercise Acute intrinsic RLDs typically have acute onset and last days to weeks Often, patients with these conditions are seen acutely within the hospital setting, and often the management of the patient is within the inpatient or operating room setting Examples of acute intrinsic RLDs are pulmonary edema (cardiogenic or noncardiogenic), acute respiratory distress syndrome, alveolar hemorrhage, and aspiration pneumonitis Elective procedures for these patients should be delayed until the disease process has resolved and the patient’s condition is optimized Some examples of chronic intrinsic RLDs include idiopathic fibrotic disease, connective tissue diseases, sarcoidosis, or disease-related fibrosis, such as rheumatoid arthritis Chronic extrinsic RLDs are most often seen in patients with disorders of the chest wall, sternum, or mediastinum (Box 16-3) These diseases can compress the lungs, thus decreasing lung volumes and increasing the work of breathing One of the most common chronic extrinsic RLDs seen in the oral and maxillofacial surgery practice is obesity Obesity is an epidemic with substantial comorbidities, including cardiovascular, pulmonary, and metabolic diseases Obesity currently is best measured in terms of body mass index (BMI), which is calculated as weight in kilograms divided by height in meters squared (Table 16-5) 233 www.ajlobby.com Mizukawa_Chap_16.indd 233 6/20/17 10:42 AM 16 • The Pulmonary System BOX 16-3 Causes of chronic extrinsic RLD Deformities of the vertebral column • Scoliosis (lateral curvature with rotation of the spinal column) • Kyphosis (anterior flexion of the vertebral column) Deformities of the sternum • Pectus excavatum (inward concavity of the lower sternum) • Pectus carinatum (outward protuberance of the upper, middle, or lower sternum) Deformities of the pleura and mediastinum • Pleural effusions • Pneumothorax • Pleural fibrosis • Mediastinal mass/tumors Neurogenic disorders • Spinal cord transection • Muscular dystrophy • Guillain-Barré syndrome • Amyotrophic lateral sclerosis • Paralysis of diaphragm Restriction of lower thorax/upper abdomen • Obesity • Hernia • Ascites Table 16-5 World Health Organization international classification of BMI Category BMI range (kg/m2) 40 Because of the increased abdominal fat in obese patients, the FRC is reduced, leading to short desaturation times Obese patients also are at higher risk of pulmonary aspiration than other patients because of gastric reflux associated with either increased intragastric pressures or the increased prevalence of hiatal hernia.9 Management Management of RLDs depends on the specific diagnosis, which is based on clinical, radiographic, and histologic workups Many chronic intrinsic RLDs require the use of corticosteroids, immunosuppressive agents, and/or cytotoxic agents Some patients with intrinsic RLDs may benefit from supplemental oxygen therapy Advanced lung disease may require lung transplantation Patients with extrinsic RLDs, including disorders of the chest wall, may have had corrective surgery Obese patients can improve lung function through weight reduction and management of any nocturnal hypoventilation or obstructive sleep apnea (OSA) 234 www.ajlobby.com Mizukawa_Chap_16.indd 234 6/20/17 10:42 AM References Anesthetic considerations Most patients with RLDs are treated by pulmonary medicine specialists In many patients who have RLD, routine spirometry will show reduced capacities Hypoxemia may be present because of a ventilation/perfusion mismatch Preoperative workup for patients with RLD should include a cardiac workup because many patients with RLD can develop pulmonary hypertension, leading to cor pulmonale.12 A thorough review of systems should include symptoms of chest pain, shortness of breath, sleeping position, exertional dyspnea, fatigue, peripheral edema, and other symptoms Because RLDs encompass a variety of pathologies, a thorough assessment of other organ systems should also be completed For example, the risk of pulmonary aspiration in an obese patient should be assessed by means of evaluation for symptoms of gastroesophageal reflux disease, which can include coughing, the inability to lie flat, and heartburn Many patients with RLD, especially obese patients, are at risk of OSA If OSA is suspected or the STOP-BANG questionnaire (see Box 10-1) suggests high risk, sedation should be avoided, and the patient should undergo a formal assessment including polysomnography and workup by a sleep medicine physician.19 Alternatively, the surgical procedure can be performed with local anesthesia only, if feasible Many of these patients are at high risk of difficult mask ventilation and difficult intubation The surgeon should perform a thorough airway examination to determine whether the patient has a short neck, large tongue, small mouth, large tonsils, and/or excessive palatal soft tissues If the patient has been deemed an appropriate candidate for in-office sedation after consultation with the patient’s pulmonologist, it is important to limit any medications that can cause respiratory depression or pharyngeal collapse Patients with RLD have poor pulmonary reserves and can become hypoxic quickly If possible, the surgeon should use only moderate sedation with anesthetics such as midazolam or dexmedetomidine and should limit the use of opioids because of the potential for respiratory depression For obese patients, the anesthetic dose can be determined on the basis of either the total body weight or the ideal body weight For example, the recommendation for midazolam is to use the total body weight However, for opioids and propofol, the dosages should be adjusted to ideal body weight (defined as 110 lb plus lb for every inch above feet).12 Conclusion Respiratory illnesses continue to be major diseases that effect anesthetic management of oral surgery patients In general, patients with respiratory diseases can be safely sedated with the appropriate preoperative workup Most patients should continue their home regimens without interruptions with adjunctive use of home inhalers on the morning of surgery References Butterworth JF, Morgan G, Wasnick J, Maged M, Mackey DC, Priebe H-J Respiratory physiology & anesthesia In: Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill, 2013:487–526 Woods BD, Sladen RN Perioperative considerations for the patient with asthma and bronchospasm Br J Anaesth 2009;103(suppl 1):i57–i65 Feiner J Clinical cardiac and pulmonary physiology In: Miller RD, Pardo MC Jr (eds) Basics of Anesthesia, ed Philadelphia: Elsevier Saunders, 2011:50–65 National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Bethesda, MD: National Heart, Lung, and Blood Institute, 2007 Little JW, Falace DA, Miller CS, Rhodus NL Pulmonary disease In: Dental Management of the Medically Compromised Patient, ed St Louis: Mosby, 2012:94–118 Sweitzer BJ, Smetana GW Identification and evaluation of the patient with lung disease Anesthesiol Clin 2009;27:673–686 Dones F, Foresta G, Russotto V Update on perioperative management of the child with asthma Pediatr Rep 2012;4(2):e19 Steinbacher DM, Glick M The dental patient with asthma An update and oral health considerations J Am Dent Assoc 2001;132:1229–1239 Agarwal R, Porter MH, Obeid G Common medical illnesses that affect anesthesia and their anesthetic management Oral Maxillofac Surg Clin North Am 2013;25:407–438 235 www.ajlobby.com Mizukawa_Chap_16.indd 235 6/20/17 10:42 AM 16 • The Pulmonary System 10 Applegate R, Lauer R, Lenart J, Gatling J, Vadi M The perioperative management of asthma J Allergy Ther 2013;S11:1–7 11 Bigatello LM, Srinivasa V Chronic pulmonary disease In: Miller R, Pardo MC Jr (eds) Basics of Anesthesia, ed Philadelphia: Elsevier Saunders, 2011:430–447 12 Al-Ruzzeh S, Kurup V Respiratory diseases In: Hines RL, Marschall KE (eds) Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Elsevier Saunders, 2012:181–217 13 Becker DE Preoperative medical evaluation: Part 2: Pulmonary, endocrine, renal, and miscellaneous considerations Anesth Prog 2009;56(4):135–144 14 Gesek DJ Jr Respiratory anesthetic emergencies in oral and maxillofacial surgery Oral Maxillofac Surg Clin North Am 2013;25:479–486 15 Butterworth JF, Morgan G, Wasnick J, Maged M, Mackey DC, Priebe H-J Anesthesia for patients with respiratory disease In: Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill, 2013:527–544 16 Ali RY, Reminick MS Perioperative management of patients who have pulmonary disease Oral Maxillofac Surg Clin North Am 2006;18:81–94 17 Tait AR, Malviya S, Voepel-Lewis T, Munro HM, Seiwert M, Pandit UA Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections Anesthesiology 2001;95:299–306 18 Tait AR, Burke C, Voepel-Lewis T, Chiravuri D, Wagner D, Malviya S Glycopyrrolate does not reduce the incidence of perioperative adverse event in children with upper respiratory tract infections Anesth Analg 2007;104:265–270 19 Joshi GP, Ankichetty SP, Gan TJ, Chung F Society for Ambulatory Anesthesia consensus statement on preoperative selection of adult patients with obstructive sleep apnea scheduled for ambulatory surgery Anesth Analg 2012;115:1060–1068 236 www.ajlobby.com Mizukawa_Chap_16.indd 236 6/20/17 10:42 AM CHAPTER 17 Digestive The Digestive System Ben Bailey, dmd Jasjit K Dillon, dds, md, bds, fdsrcs www.ajlobby.com Mizukawa_Chapter_Openers.indd 237 6/21/17 3:24 PM CHAPTER 17 Digestive The Digestive System Normal Anatomy and Physiology 239 Gastroesophageal Reflux Disease 241 Peptic Ulcer Disease 243 Ulcerative Colitis 245 Crohn Disease 247 www.ajlobby.com Mizukawa_Chapter_Openers.indd 238 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology The digestive system consists of the gastrointestinal (GI) tract and several associated digestive organs The primary function of the GI tract is the conversion of physiologically external dietary intake into chemical forms that can be appropriately absorbed.1 It extends from the oral cavity to the anus The primary structures of the GI tract are the oral cavity, pharynx, esophagus, stomach, small intestine, large intestine, and rectum/anus (Table 17-1) The digestive organs associated with the GI tract include the salivary glands, liver, gallbladder, and pancreas, which secrete digestive fluids and enzymes into the lumen of the GI tract With the exception of the oral cavity and pharynx, the digestive tract has a generally uniform fundamental structure, with modifications at various levels to accommodate regional functional specialization From the outer aspect toward the lumen, this structure consists of four layers: the adventitia, the muscle layer, the submucosa, and the mucosa.2 Table 17-1 Major structures of the GI tract Component Physiologic function Anatomic structures/enzymatic activity Pathologic considerations Oral cavity and salivary glands •• Mastication •• Speech •• Early digestion •• Submandibular glands—secrete serous/mucous saliva •• Parotid glands—secrete serous saliva, amylase •• Sublingual glands—secrete mucous saliva •• Salivary amylase—contributes to carbohydrate metabolism Crohn disease Esophagus Propulsion •• Upper esophageal sphincter—prevents aspiration •• Lower esophageal sphincter—prevents retrograde movement of gastric contents •• GERD •• Barrett esophagus •• Crohn disease Stomach •• Storage of ingested •• Chief cells (fundus)—secrete pepsinogen food •• Parietal cells (fundus)—secrete intrinsic factor and hydrochloric acid •• Production of chyme •• G cells (antrum/duodenum)—release gastrin •• Enterochromaffin-like cells—release histamine •• Peptic ulcer disease •• Crohn disease Small intestine •• Digestion •• Nutrient absorption •• Duodenum •• Jejunum •• Ileum •• Peptic ulcer disease (duodenum) •• Crohn disease Large intestine Absorption of water and residual nutrients •• Cecum •• Colon (ascending, transverse, descending, sigmoid) •• Rectum •• Ulcerative colitis •• Crohn disease GERD, gastroesophageal disease Oral cavity The oral cavity is the entrance to the digestive system Its primary functions are mastication and speech Anatomically it can be divided into the vestibule, which is the recess between the lips/cheeks and teeth, and the oral cavity proper The oral cavity proper is bounded anteriorly by the dentition, laterally by the dentition and the cheeks, superiorly and posteriorly by the hard and soft palates, and inferiorly by the floor of the mouth It receives saliva from the salivary glands and, in coordination with the action of the tongue, forms food boluses, which are passed to the pharynx during deglutition.3 Salivary glands Saliva contains lubricating glycoproteins, electrolytes, and buffers It moistens food to allow bolus formation The three major salivary glands—the parotid, sublingual, and submandibular glands—are paired bilaterally The submandibular glands lie along the medial aspect of the mandible and produce saliva that contains both serous and 239 www.ajlobby.com Mizukawa_Chap_17.indd 239 6/20/17 10:42 AM 17 • The Digestive System mucous components This saliva enters the mouth through the bilateral Wharton ducts, which are found on either side of the lingual frenum The parotid glands produce solely serous saliva, which is rich in salivary amylase and is secreted into the oral cavity through the Stensen ducts in the area of the maxillary second molars Salivary amylase initiates the process of digestion of complex carbohydrates The sublingual glands are found in the superior aspect of the floor of the mouth and produce mucus-rich saliva that enters the mouth through multiple ducts near the lingual frenum Salivary output is modulated primarily by parasympathetic input and increases in response to the psychologic anticipation of food and also in response to the salivary reflex, which increases salivation when material is present in the oral cavity.4 Pharynx The pharynx is an anatomical space through which food and air both pass From superior to inferior, it consists of the nasopharynx, the oropharynx, and the laryngopharynx Its associated musculature pushes boluses of food from the oropharynx into the esophagus, while simultaneously closing the nasopharynx via elevation of the soft palate and protecting the larynx by elevating it against the epiglottis.4 Esophagus The esophagus is a muscular tube that extends an average of 25 cm from the pharynx through the thorax to terminate in the stomach During deglutition it facilitates the passage of bolus material via peristaltic movements of the muscle layer At the superior and inferior extents, it is bounded by the upper and lower esophageal sphincters, respectively The upper esophageal sphincter serves to prevent aspiration of esophageal contents The lower esophageal sphincter prevents gastric content from entering the esophagus in a retrograde fashion These esophageal sphincters not have a distinct anatomical basis The sphincter function consists of localized contraction of the muscular layer of the esophagus In the case of the lower esophageal sphincter, the diaphragmatic contraction that occurs where the esophagus passes through the muscular portion of the diaphragm also contributes to the sphincter function.2 In healthy patients, the esophageal mucosal epithelium is of the nonkeratinized, stratified squamous type and is lubricated by the secretion of mucus from submucosal esophageal glands.4 Stomach The stomach receives food boluses from the esophagus through the lower esophageal sphincter It is an approximately J-shaped muscular sac that stores ingested food and is involved in chemical and mechanical breakdown of food It produces a viscous combination of gastric juice and partially digested foods known as chyme, which passes through the pyloric sphincter into the proximal duodenum The gastric epithelium produces large amounts of protective alkaline mucus to prevent its own degradation by its acidic and enzymatic contents The gastric fundus contains the physiologically important parietal and chief cells Chief cells secrete the zymogen pepsinogen, whereas parietal cells produce intrinsic factor (necessary for absorption of vitamin B12) and hydrochloric acid This gastric acid initiates protein digestion by converting pepsinogen to its active proteolytic form, pepsin It also denatures proteins and has direct antibacterial action The secretion of hydrochloric acid involves the production of carbonic acid from water and carbon dioxide, which dissociates into protons and bicarbonate ions The bicarbonate moves to the blood stream via a countertransport process that moves chloride ions into the parietal cells The hydrogen ions are actively transported across the parietal cell luminal membrane by proton pumps into the gastric glands, and their associated chloride ions cross the membrane by carrier-mediated diffusion.4 Parietal cell secretion of gastric acid is controlled by an array of neural and local factors The primary neural factor is parasympathetic stimulation by input from the vagus nerve Local factors include gastrin, which is a peptide hormone released by G cells in the antrum and duodenum Gastrin stimulates enterochromaffin-like cells to release histamine, which binds to the H2 histamine receptor subclass on the parietal cells, promoting hydrochloric acid secretion.5 Defense of the gastric mucosa from the gastric contents is coordinated primarily by release of prostaglandins The prostaglandins increase blood flow 240 www.ajlobby.com Mizukawa_Chap_17.indd 240 6/20/17 10:42 AM Gastroesophageal Reflux Disease to the gastric mucosa, protecting it by increasing the local pH, bicarbonate secretion, and mucus secretion Prostaglandins also directly decrease gastric acid secretion.6 Small intestine The small intestine (also called the small bowel ), which is approximately m in length, serves as the primary region of digestion and absorption It receives pancreatic and hepatic digestive enzymes via the common bile and pancreatic ducts These enzymes are combined with the chyme received from the stomach Beginning at the stomach, the three regions of the small intestine are the duodenum, the jejunum, and the ileum Large intestine The large intestine (also called the large bowel ) consists of the cecum, the colon, and the rectum It begins at the ileocecal valve, which opens into the pouchlike cecum The large intestine is larger in diameter and shorter in length than the small intestine Its functions are the absorption of water and residual nutrients, and the storage of feces before defecation Resident bacteria produce several important nutrients, including vitamin K, which are subsequently absorbed Grossly, the colon can be divided into ascending, transverse, descending, and sigmoid regions The muscular layer of the large intestine is divided into three longitudinal bands called the teniae coli, the tone of which causes the formation of haustra coli, which are partial compartments of the colon that permit localized expansion of the lumen The terminal segment of the large intestine is the rectum, a storage region from which feces are expelled through the anal orifice during defecation.4 Gastroesophageal Reflux Disease Pathophysiology and diagnosis Gastroesophageal reflux disease (GERD) is defined as consisting of the complications associated with reflux or retrograde movement of gastric contents into the esophagus and extraesophageal regions of the larynx, oral cavity, or lungs GERD may occur with or without endoscopically identifiable erosive effects.7 The primary factor underlying the pathophysiology of GERD is failure of the antireflux mechanisms of the GI tract, which may occur as a result of low tone of the lower esophageal sphincter, anatomical defects of the lower esophageal sphincter, or impaired motility of the GI tract Hiatal hernia, in which the gastroesophageal junction migrates superiorly through the diaphragm into the lower mediastinum, is common in GERD patients.8 Although some degree of gastric content regurgitation into the esophagus is physiologic, in patients with GERD the increased exposure can be associated with discomfort, erosive esophagitis, Barrett esophagus, and esophageal carcinoma.9 Diagnosis can be based on the presence of typical symptoms of heartburn Diagnosis by means of upper endoscopy is useful in patients in whom alarm symptoms such as dysphagia or possible noncardiac chest pain would pose a high risk of complications, particularly in elderly patients.7 Management of disease Lifestyle modification and medical therapy are the mainstays of management of GERD, although surgical interventions are occasionally indicated Weight loss is recommended for overweight patients and patients with recent weight gain For patients with nocturnal symptoms, elevation of the head of the bed during sleep is recommended Selective elimination of foods associated with aggravation of symptoms is recommended, although no evidence is available to support the routine elimination of commonly suspect items such as chocolate, coffee, and spicy foods Routine medical management consists of proton-pump inhibitor (PPI) therapy, which decreases secretion of gastric acid Initial PPI courses are usually of limited duration, but PPI therapy may be extended to maintenance dosing in 241 www.ajlobby.com Mizukawa_Chap_17.indd 241 6/20/17 10:42 AM 17 • The Digestive System patients with persistent symptoms and in patients with complications of GERD such as erosive esophagitis or Barrett esophagus Histamine H2-receptor antagonists are an option for maintenance therapy In patients with impaired gastric motility that contributes to the etiology, prokinetic therapy may be considered (Box 17-1) Surgical therapy such as gastric bypass can be as effective as medical therapy in some patients.7 BOX 17-1 Medications for management of GERD (by drug category) Prokinetic agents • Metoclopramide Proton-pump inhibitors • Omeprazole • Lansoprazole • Esomeprazole • Pantoprazole • Rabeprazole Histamine H2-receptor antagonists • Ranitidine • Famotidine • Cimetidine • Nizatidine Antacids (rarely prescribed) • CaCO3 • Mg(OH)2 • Al(OH)3 • MgCO3 i Pulmonary aspiration of gastric contents during surgical anesthesia, known as Mendelson syndrome, is a catastrophic, although extremely rare, complication The incidence of aspiration of gastric contents during anesthesia in situations excluding severe trauma is low for adults and children, ranging from 2.3 to 10.2 per 10,000.10 Patients with GERD may be at increased risk of aspiration of gastric contents during procedures performed with sedation and anesthesia If a patient is on drug therapy for the management of GERD, the drug should be continued on the day of the procedure Many patients have a GERD diagnosis resulting from application of nonstandard diagnostic criteria (eg, self-diagnosis); if symptoms are mild and rare, these patients can be treated in the same manner as healthy patients would be In patients with consistently severe and frequent symptoms, special consideration is warranted to minimize risk of aspiration, such as by protecting the airway during anesthesia by avoiding laryngeal mask airways in favor of endotracheal intubation.11 If concern for aspiration is sufficiently high, rapid sequence or awake intubation may be indicated.12 Agents commonly used perioperatively or during sedation, including glycopyrrolate, opioids, propofol, and possibly nitrous oxide, may further reduce lower esophageal sphincter tone; practitioners should be mindful of this effect when balancing the benefits of each agent against the risk of aspiration pneumonitis in patients with GERD Premedication with histamine H2-receptor antagonists, PPIs, prokinetic agents, and antacids may be considered to minimize the severity of potential pneumonitis in patients at risk of aspiration (Box 17-2).13 BOX 17-2 Perioperative considerations in patients with GERD • Continue home GERD medications perioperatively • If symptoms are severe/frequent, for general anesthesia, avoid laryngeal mask airways and consider rapid sequence or awake intubation • If symptoms are severe/frequent, for sedation or general anesthesia, avoid or minimize use of glycopyrrolate, opioids, propofol, and possibly nitrous oxide • Consider premedication with histamine H2-receptor antagonists, PPIs, prokinetic agents, and antacids 242 www.ajlobby.com Mizukawa_Chap_17.indd 242 6/20/17 10:42 AM Peptic Ulcer Disease Peptic Ulcer Disease Pathophysiology and diagnosis i Peptic ulcer disease (PUD) encompasses gastric and duodenal ulcers of multiple etiologies An ulcer is defined as a disruption that reaches the muscular layer of the GI tract.6 The pathogenesis fundamentally depends on an imbalance between the protective mucosal barrier factors and the erosive elements of gastric acids and enzymes The most prevalent causative factors are Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs), although some patients have a third type of PUD that is not attributed to NSAIDs or H pylori.14 H pylori, which colonizes the gastric mucous layer, has in recent decades been found to be associated with PUD Although the precise mechanism through which H pylori colonization contributes to ulcer formation is unclear, it is hypothesized to promote disruption in the protective hydrophobicity of the mucosal barrier, allowing increased back diffusion of gastric acid.6 NSAIDs contribute to ulcer formation through direct cytotoxicity and indirect systemic effects Direct cytotoxicity is considered less important causatively than the indirect effects are The chief indirect effect of NSAIDs in increasing susceptibility to ulceration is the reduction of prostaglandin synthesis Prostaglandins, which are produced by the cyclooxygenase enzymes COX-1 and COX-2, are inhibited in varying ratios by different NSAIDs COX-1 inhibition is associated with impaired mucosal defense secondary to decreased blood flow, decreased mucus production, and decreased bicarbonate secretion; it can also exacerbate possible bleeding by impairing platelet aggregation and clot formation COX-2 inhibition can impair healing of ulcers by reducing angiogenesis.6 The typical symptom pattern consists of epigastric pain that is relieved by eating.13 However, PUD associated with long-term NSAID use that has not been complicated by bleeding or perforation is commonly asymptomatic A definitive diagnosis can be established with the use of endoscopy, to identify loss of mucosal integrity, and concomitant biopsy Biopsy specimens are analyzed with histologic examination, culture, polymerase chain reaction, and rapid urease testing.15 In symptomatic patients, a presumptive diagnosis can be determined noninvasively by testing for H pylori.14 Noninvasive tests, which are also useful in demonstrating posttreatment eradication, include the urea breath test and the stool antigen test.15 Management of disease Management of chronic PUD depends largely on the underlying etiology PUD associated with H pylori can be managed with the use of antisecretory medications that reduce gastric acidity or with antibiotic eradication of the pathogen (Box 17-3) In patients with PUD associated with H pylori in whom bleeding has occurred, antibiotic-based eradication is superior in preventing recurrent bleeding episodes Eradication or lack of reinfection should be confirmed after antibiotic treatment because susceptibility of H pylori to antibiotic regimens varies widely.16 The prevalence of PUD associated with NSAID use, including low-dose aspirin therapy, is increasing, whereas the prevalence of PUD associated with H pylori is decreasing.17 In NSAID-related PUD, the benefits of continuing NSAID treatment need to be balanced against the risks of further PUD complications Some patient groups, such as those with rheumatoid arthritis or with recently placed cardiac stents, may benefit from continued NSAID treatment They may use PPIs and histamine H2-receptor antagonists to mitigate the ulcerative effects of NSAIDS, or switch from a nonselective NSAID to a COX-2 selective one.18 The synthetic prostaglandin E1 analog misoprostol, which increases mucosal perfusion and bicarbonate secretion, thereby mitigating NSAID-induced mucosal injury, can also be used.13 Acute GI bleeding associated with PUD is a medical emergency and manifests as hematemesis or melena.19 Emergent treatment involves hemodynamic assessment and resuscitation, followed by endoscopic evaluation and possible vascular obliteration in conjunction with the use of intravenous PPIs.20 243 www.ajlobby.com Mizukawa_Chap_17.indd 243 6/20/17 10:42 AM 17 • The Digestive System BOX 17-3 Medications for management of PUD (by drug category) Prostaglandin analogs • Misoprostol Proton-pump inhibitors • Omeprazole • Lansoprazole • Esomeprazole • Pantoprazole • Rabeprazole Histamine H2-receptor antagonists • Ranitidine • Famotidine • Cimetidine • Nizatidine Antacids (rarely prescribed) • CaCO3 • Mg(OH)2 • Al(OH)3 • MgCO3 Anesthetic considerations Avoidance of aggravating factors such as the use of NSAIDs (including ibuprofen, ketorolac, and aspirin) is central to the anesthetic management of patients with PUD (Box 17-4) Complications of PUD include hemorrhage, perforation, and gastric outlet obstruction (GOO) Hemorrhage and perforation are the most severe and most common complications of PUD To minimize mortality, these complications should be recognized promptly as emergencies Patients with GOO can present with progressive intolerance of oral feeding, nausea, vomiting, weight loss, and the physiologic derangements associated with these symptoms.21 GOO is the least common complication of PUD, representing approximately 3% of complications requiring hospitalization.22 It is characterized by mechanical obstruction of the gastric outlet secondary to edema in the acute case or scarring and outlet stenosis in the chronic case For the purposes of anesthetic planning, patients with GOO should be considered to have elevated gastric content levels even after a standard preoperative period of no oral intake and therefore to be at increased risk of aspiration.13 BOX 17-4 Perioperative considerations in patients With PUD • Avoid NSAIDs • Focus examination and history on signs and symptoms of hemorrhage, perforation, and gastric outlet obstruction • Consider longer preoperative period of no oral intake or rapid sequence induction if general anesthesia is necessary 244 www.ajlobby.com Mizukawa_Chap_17.indd 244 6/20/17 10:42 AM Ulcerative Colitis Ulcerative Colitis Pathophysiology and diagnosis Inflammatory bowel disease consists of two primary entities: ulcerative colitis and Crohn disease Ulcerative colitis is an immunologically mediated inflammatory disease of the colon, of idiopathic origin, found in individuals with predisposing genetic factors that are mediated by environmental/dietary factors.23 The mucosal inflammation causes erosions that can progress to ulcerations, which may in turn give rise to substantial bleeding (Figs 17-1 to 17-3) No definitive criterion has been established for diagnosis of ulcerative colitis; clinical, laboratory, endoscopic, and histologic features all may be considered Hallmarks include bloody diarrhea of at least 1-month duration (with negative stool cultures) coupled with rectal mucosal inflammation that extends proximally to varying degrees Laboratory findings commonly include iron deficiency anemia, anti–goblet cell antibodies, or atypical/perinuclear antineutrophil cytoplasmic antibodies.25 Fig 17-1 Photomicrograph demonstrating pathologic histology in colonic tissue resected from a patient with ulcerative colitis The mucosa (M) is severely inflamed, but the inflammation is not transmural (involving the entire wall of the colon) as it would be in patients with Crohn disease The muscularis propria (MP) is devoid of inflammation (Courtesy of Dr Maria Westerhoff, Seattle, Washington.) Fig 17-2 Endoscopic image of colon demonstrating ulcerative colitis The patient has contiguous circumferential inflammation of the colon with erythema, granularity, friability, and mucopurulent exudate (Courtesy of Dr Timothy L Zisman, Seattle, Washington.) U U a PP b Fig 17-3 Inflammation in patients with ulcerative colitis occurs continuously with proximal extension from the rectum (a, shaded area) and without transmural involvement (b) Patterns of ulceration (U) can give rise to pseudopolyps (P) (Courtesy of Arjan Dillon, Seattle, Washington, modified with permission from Kumar et al.24) 245 www.ajlobby.com Mizukawa_Chap_17.indd 245 6/20/17 10:42 AM 17 • The Digestive System Management of disease The natural disease course is characterized by periods of exacerbation and remission of symptoms Management focuses on efforts to induce remission of the mucosal inflammation medically through the use of corticosteroids, aminosalicylates, biologic agents, and, in severe cases, immunosuppressants (Box 17-5) If medical management is insufficient, severe disease may require surgical treatment, usually consisting of partial or total colectomy, for definitive management.23 BOX 17-5 Medications for management of ulcerative colitis (by drug category) Corticosteroids • Prednisone • Prednisolone • Methylprednisolone • Budesonide Biologic agents • Infliximab • Natalizumab • Adalimumab • Etanercept Immunosuppressants • Azathioprine • 6-Mercaptopurine Aminosalicylates • Mesalazine • Sulfasalazine Anesthetic considerations Toxic megacolon is a severe, life-threatening complication of ulcerative colitis (and other inflammatory and infectious bowel diseases) characterized by colonic dilatation and systemic toxicity Although the etiology of toxic megacolon is unclear, factors impairing intestinal motility, such as the use of opiates, anticholinergics, and antidiarrheals, have been suggested to exacerbate the condition Avoidance of these factors is recommended.26 In general, inflammatory bowel disease does not influence the choice of anesthetic agent However, several of the medications used for management may have minor effects on the required minimum alveolar concentration of inhaled anesthetics or on the efficacy of non-depolarizing paralytic agents.27 Inflammatory autoimmune diseases such as ulcerative colitis and Crohn disease are common indications for glucocorticoid therapy; regimens vary, and a detailed preoperative history regarding these medications is critical to identify and plan for prevention of iatrogenic adrenal insufficiency Insufficiency is increasingly likely as dosages and treatment duration increase and may last several months after discontinuation of the drugs Oral and maxillofacial surgical procedures performed with the patient under anesthesia in the clinic setting are considered minor procedures, and in patients with or without suspected adrenal suppression, the risk of insufficiency is usually managed with administration of the patient’s usual morning steroid dose.28 However, if adrenal suppression is suspected and moderate or deep sedation is planned, the usual morning steroid dose should be doubled, or, alternatively, a stress dose of hydrocortisone may be given at the time of administration of the anesthesia (Box 17-6) Acute adrenal insufficiency is an emergency It is characterized by fever, abdominal pain, hypovolemia, and hypotension, and can lead to shock and death.29 BOX 17-6 Perioperative considerations in patients with ulcerative colitis • When possible, avoid the use of opiates, anticholinergics (eg, glycopyrrolate, atropine), and antidiarrheals (eg, loperamide) • Focus history on glucocorticoid use and consider stress dosing of hydrocortisone when indicated 246 www.ajlobby.com Mizukawa_Chap_17.indd 246 6/20/17 10:42 AM Crohn Disease Crohn Disease Pathophysiology and diagnosis Crohn disease is an inflammatory disease of the GI tract that may extend from the mouth to the anus It commonly consists of discontinuous areas of mucosal involvement (skip lesions) Crohn disease most often occurs in the distal antrum and duodenum Typical symptoms include diarrhea, abdominal pain, fever, and weight loss In patients with severe disease, strictures and fistulae can arise Although the etiology is uncertain, environmental, microbiologic, and genetic factors are thought to contribute to the immunologic dysregulation that underlies the condition.30 Although many nonspecific laboratory measures of inflammation, such as C-reactive protein level, erythrocyte sedimentation rate, fecal calprotectin level, and lactoferrin level, are used as markers of inflammation, no specific test is available to detect Crohn disease GI infection must be ruled out in making the diagnosis In patients with an appropriate history, computed tomography imaging and ileocolonoscopy in conjunction with histopathologically demonstrated inflammation are the usual bases for establishment of a diagnosis of Crohn disease31 (Figs 17-4 to 17-6) × Fig 17-4 Photomicrograph demonstrating pathologic histology in a colonic biopsy specimen from a patient with Crohn disease Granuloma (x) is a finding associated with Crohn disease but not with ulcerative colitis (Courtesy of Dr Maria Westerhoff, Seattle, Washington.) a Fig 17-5 Endoscopic image demonstrating the colon of a pa- tient with Crohn disease Deep ulcerations lead to narrowing of the lumen and architectural distortion of the colon with a cobblestone appearance (Courtesy of Dr Timothy L Zisman, Seattle, Washington.) b Fig 17-6 In patients with Crohn disease, inflammation occurs as discontinuous skip lesions (a, shaded areas) with potential transmural involvement (b) (Courtesy of Arjan Dillon, Seattle, Washington, modified with permission from Kumar et al.24) 247 www.ajlobby.com Mizukawa_Chap_17.indd 247 6/20/17 10:42 AM 17 • The Digestive System Management of disease The clinical course of Crohn disease is characterized by periods of exacerbation and remission of inflammation and associated symptoms The primary goals of treatment are to induce remission by promoting mucosal healing and to palliate symptoms The mainstay of treatment is the use of corticosteroids and/or immunosuppressants such as azathioprine or 6-mercaptopurine In patients with mild disease, some clinicians prefer to initiate therapy with 5-aminosalicylates before administering corticosteroids Increased infection risk is a common side effect of these medications32 (Box 17-7) Surgical treatment, consisting of resection of affected portions of the GI tract, is undertaken only as a last resort In contrast to the surgical management of ulcerative colitis, resection in patients with Crohn disease is only palliative, not curative, and repeat surgical procedures are common.13 BOX 17-7 Medications for management of Crohn disease (by drug category) Corticosteroids • Prednisone • Prednisolone • Methylprednisolone • Budesonide Biologic agents • Infliximab • Natalizumab • Adalimumab • Etanercept Immunosuppressants • Azathioprine • 6-Mercaptopurine Aminosalicylates • Mesalazine • Sulfasalazine Anesthetic considerations Chronic micronutrient and macronutrient deficiencies are common because of reduced nutritional intake and also malabsorption secondary to active disease or surgical resection Because malnutrition, particularly of protein energy, can impair surgical wound healing, an assessment of nutritional status is warranted in these patients.33 Depending on the areas affected by disease or resection, micronutrient deficiencies may include vitamin B12, zinc, magnesium, phosphorus, potassium, and the fat-soluble vitamins (A, D, E, and K) Chronic diarrhea is also associated with fluid volume disturbances.34 Depending on the severity of the disease and the degree of progression, preoperative assessment of electrolyte levels and fluid status may be necessary to avoid complications such as hypotension and cardiac arrhythmia Anemia is common in patients with chronic disease In patients with Crohn disease and an extensive history of medical interventions, peripheral intravenous access may be challenging and should be considered preoperatively In general, the presence of inflammatory bowel disease does not influence the choice of anesthetic agent (Box 17-8) If bowel obstruction is a concern in a patient with Crohn disease, the use of nitrous oxide should be avoided.35 Several medications used for management of Crohn disease may have a minimal effect on the minimum alveolar concentration of inhaled anesthetics and on the efficacy of non-depolarizing paralytic agents.27 As noted, in patients in whom supraphysiologic doses of corticosteroids are administered chronically, adrenal suppression should be suspected, and, depending on the anticipated physiologic stress with anesthesia, stress dosing of corticosteroid should be provided to reduce the risk of adrenal crisis 248 www.ajlobby.com Mizukawa_Chap_17.indd 248 6/20/17 10:42 AM References BOX 17-8 Perioperative considerations in patients with Crohn disease • Focus assessment on nutritional, electrolyte, and fluid statuses and replenish as indicated • Focus history on glucocorticoid use and consider stress dosing of corticosteroid when indicated • Plan for challenging intravenous access • Avoid the use of nitrous oxide when bowel obstruction is a concern Summary A comprehensive understanding of anatomy and physiology forms the foundation for safe and efficient anesthetic management of surgical patients with comorbid GI diseases Careful attention to disease status, as evidenced by history, physical examination, and current medication use will guide the anesthetist’s perioperative management, including the selection of anesthetic and surgical settings Where ambiguity exists, consultation with the patient’s medical providers is indicated to develop interdisciplinary management strategies regarding the optimization of physiologic status References Johnstone C, Hendry C, Farley A, McLafferty E The digestive system: Part Nurs Stand 2014;28:37–45 Waugh A, Grant A Ross and Wilson Anatomy and Physiology in Health and Illness, ed 11 Edinburgh: Churchill Livingstone Elsevier, 2010 Norton NS Netter’s Head and Neck Anatomy for Dentistry, ed Philadelphia: Elsevier Saunders, 2011 Martini FH, Nath JL, Bartholomew EF Fundamentals of Anatomy & Physiology, ed 10 San Francisco: Pearson Education, 2014 Waldum HL, Hauso Ø, Fossmark R The regulation of gastric acid secretion: Clinical perspectives Acta Physiol (Oxf) 2014;210:239–256 Wallace JL Prostaglandins, NSAIDs, and gastric mucosal protection: Why doesn’t the stomach digest itself? Physiol Rev 2008;88:1547–1565 Katz PO, Gerson LB, Vela MF Guidelines for the diagnosis and management of gastroesophageal reflux disease Am J Gastroenterol 2013;108:308–328 Fuchs KH, Babic B, Breithaupt W, et al EAES recommendations for the management of gastroesophageal reflux disease Surg Endosc 2014;28:1753–1773 Boeckxstaens GE, Rohof WO Pathophysiology of gastroesophageal reflux disease Gastroenterol Clin North Am 2014;43:15–25 10 Ng A, Smith G Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice Anesth Analg 2001;93:494–513 11 Butterworth JF, Mackey DC, Wasnick JD Preoperative assessment, premedication, & perioperative documentation In: Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw Hill, 2013:295–307 12 Roizen MF, Fleisher LA Anesthetic implications of concurrent diseases In Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:1067–1150 13 Hines RL, Marschall KE Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Elsevier Saunders, 2012 14 Malfertheiner P, Chart FK, McColl KE Peptic ulcer disease Lancet 2009;374:1449–1461 15 Garza-González E, Perez-Perez GI, Maldonado-Garza HJ, Bosques-Padilla FJ A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication World J Gastroenterol 2014;20:1438–1449 16 Gisbert JP, Khorrami S, Carballo F, Calvet X, Gené E, Dominguez-Muñoz JE H pylori eradication therapy vs antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer Cochrane Database Syst Rev 2010;(2):CD004062 17 Musumba C, Jorgensen A, Sutton L, et al The relative contribution of NSAIDs and Helicobacter pylori to the aetiology of endoscopicallydiagnosed peptic ulcer disease: Observations from a tertiary referral hospital in the UK between 2005 and 2010 Aliment Pharmacol Ther 2012;36:48–56 18 Tang RS, Chan FK Therapeutic management of recurrent peptic ulcer disease Drugs 2012;72:1605–1616 19 Neumann I, Letelier LM, Rada G, et al Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding Cochrane Database Syst Rev 2013;(6):CD007999 20 Laine L, Jensen DM Management of patients with ulcer bleeding Am J Gastroenterol 2012;107:345–360 249 www.ajlobby.com Mizukawa_Chap_17.indd 249 6/20/17 10:42 AM 17 • The Digestive System 21 Endo S, Takiguchi S, Miyazaki Y, et al Efficacy of endoscopic gastroduodenal stenting for gastric outlet obstruction due to unresectable advanced gastric cancer: A prospective multicenter study J Surg Oncol 2014;109:208–212 22 Wang YR, Richter JE, Dempsey DT Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006 Ann Surg 2010;251:51–58 29 Butterworth JF, Mackey DC, Wasnick JD Anesthesia for patients with endocrine disease In: Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw Hill, 2013:727–746 30 Thoreson R, Cullen JJ Pathophysiology of inflammatory bowel disease: An overview Surg Clin North Am 2007;87:575–585 31 Cheifetz AS Management of active Crohn disease JAMA 2013;309:2150–2158 23 Stewart MJ, Kutcher M, Storr M, Seow CH Interventions for maintenance of mucosal healing in ulcerative colitis Cochrane Database Syst Rev 2014;(2):CD010998 32 Stewart MJ , Garg SK, Seow CH, Storr M Interventions for induction and maintenance of mucosal healing in Crohn’s disease [protocol] Cochrane Database Syst Rev 2012;(10):CD010141 24 Kumar V, Abbas AK, Aster JC Robbins Basic Pathology, ed Philadelphia: Elsevier Saunders, 2012 33 Donnellan CF, Yann LH, Lal S Nutritional management of Crohn’s disease Therap Adv Gastroenterol 2013;6:231–242 25 Conrad K, Roggenbuck D, Laass MW Diagnosis and classification of ulcerative colitis Autoimmun Rev 2014;13:463–466 34 Nagelhout JJ, Plaus KL Gastrointestinal system: Inflammatory bowel disease In: Handbook of Anesthesia, ed Maryland Heights: Elsevier Saunders, 2014:103–106 26 Autenrieth DM, Baumgart DC Toxic megacolon Inflamm Bowel Dis 2012;18:584–591 27 Miller RD, Pardo MC Basics of Anesthesia, ed Philadelphia: Elsevier Saunders, 2011 35 Fleisher LA, Roizen MF Essence of Anesthesia Practice, ed Philadelphia: Elsevier Saunders, 2011 28 Hamlin NP, Wong CJ The Perioperative Medicine Consult Handbook New York: Springer, 2013 250 www.ajlobby.com Mizukawa_Chap_17.indd 250 6/20/17 10:42 AM CHAPTER 18 The Renal System Renal Paul Hinchey, dmd, md Luis G Vega, dds www.ajlobby.com Mizukawa_Chapter_Openers.indd 251 6/21/17 3:24 PM CHAPTER 18 The Renal System Normal Anatomy and Physiology 253 Acute Kidney Disease 254 Renal Chronic Kidney Disease and End-Stage Renal Disease 255 Hepatorenal Syndrome 259 Fluid and Electrolyte Disturbances 260 www.ajlobby.com Mizukawa_Chapter_Openers.indd 252 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology The kidneys receive up to one-fourth of a person’s cardiac output They are responsible for the regulation of salt and water balances, toxin and metabolite elimination, electrolyte and acid-base homeostasis, and hormone production.1 The kidneys comprise more than million functional subunits known as nephrons The structure of the nephron consists of the juxtaglomerular apparatus, the Bowman capsule, the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct Each of these anatomic units plays a specific role in maintaining appropriate hemodynamics The juxtaglomerular apparatus lies between the afferent arteriole and the distal tubule The main purpose of the juxtaglomerular apparatus is the secretion of renin Renin is an enzyme that participates in the renin-angiotensin-aldosterone system Hypovolemic states, such as those that can occur with low blood pressure, low effective circulating volume, or excessive sodium loss, serve as triggers for the release of renin Renin is responsible for the conversion of angiotensinogen to angiotensin I Angiotensin I is then transformed into angiotensin II via angiotensin-converting enzyme (ACE), which is found in the kidneys as well as in the lungs Angiotensin II is a powerful vasoconstrictor of the efferent arteriole within the glomerulus This vasoconstriction subsequently increases the glomerular filtration fraction, leading to enhanced sodium absorption Angiotensin II also stimulates the release of aldosterone from the adrenal cortex This hormone acts on the loop of Henle, the distal convoluted tubule, and the collecting duct by increasing sodium absorption The net effect of increasing sodium absorption is the passive absorption of water, thereby increasing circulatory volume The proximal end of the nephron is known as the Bowman capsule and is the location where ultrafiltration of the blood is first performed The glomerular capillaries are located within the capsule One afferent arteriole and one efferent arteriole make up a glomerulus The interface between the endothelial cells of the glomerulus and the epithelial cells of the Bowman capsule serves as the gateway for the filtrate to enter the tubular network The tubular network is a highly selective entity that prevents the passage of proteins on the basis of both molecular size and charge The proximal convoluted tubule is involved in the reabsorption of most sodium, glucose, water, chloride, and potassium as well as the secretion of numerous anions The loop of Henle consists of the thin descending limb, the thin ascending limb, and the thick ascending limb Its main purpose is to create a concentration gradient within the medulla The thin descending limb is permeable to water and essentially serves as a conduit for transport of the filtrate from the proximal convoluted tubule in the cortex into the renal medulla The ascending portion of the loop of Henle is responsible for maintaining a hypertonic medullary environment that is created through active transport of sodium into the medullary interstitium Because the ascending limbs are impermeable to water, the result is the flow of a hypotonic fluid into the distal convoluted tubule This portion of the nephron participates minimally in sodium reabsorption and does not substantially alter the nature of the tubular fluid The collecting duct spans both cortical and medullary components of the kidney and ultimately connects with the ureters Within the cortical portion of the collecting tubule, hormones such as aldosterone act on specialized cells that mediate sodium reabsorption and engage in acid-base regulation The medullary portion of the collecting tubule is the site of action of antidiuretic hormone Antidiuretic hormone inserts water channel proteins called aquaporins into the cell membranes of the collecting tubule cells, thus making the duct permeable to water This action results in concentration of the urine and is most helpful during states of dehydration Another critical function of the kidneys with marked pertinence to anesthesia is the production and secretion of erythropoietin (EPO) EPO is a glycoprotein produced by the peritubular cells of the renal cortex in response to hypoxemia These cells secrete EPO into circulation, where it is ultimately transported to the bone marrow EPO triggers increased erythrocyte proliferation and differentiation to compensate for the lack of circulating oxygen The obvious pathophysiologic effects of EPO deficiency associated with chronic kidney disease (CKD) are discussed later in the chapter 253 www.ajlobby.com Mizukawa_Chap_18.indd 253 6/20/17 10:43 AM 18 • The Renal System Acute Kidney Disease Pathophysiology and diagnosis Acute kidney disease is an umbrella term that describes conditions that rapidly affect kidney structure and function One of the most clinically relevant acute kidney diseases is acute kidney injury (AKI), which is defined as an abrupt loss in renal function as evidenced by increased serum creatinine levels or reduced urine output In an attempt to standardize the definition and staging of AKI, the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria were formulated These five categories represent progressive decline in kidney function The RIFLE criteria have been modified by the Acute Kidney Injury Network (AKIN) and the Kidney Disease: Improving Global Outcomes (KDIGO) group to provide staging classification systems based on increases in serum creatinine and/or decreases in patient urine output.2 The major causes of AKI can be classified into three main categories: prerenal azotemia, intrinsic azotemia, and postrenal azotemia Azotemia refers to the accumulation of elevated levels of nitrogen-containing compounds within the blood Most cases of AKI are attributable to prerenal causes Hypotension and hypovolemia represent two major etiologies of prerenal azotemia These conditions lead to decreased blood flow to the kidneys, which can result in ischemia-reperfusion injury The patient populations most susceptible to the development of prerenal azotemia are elderly patients, patients with congestive heart failure, and patients with renal vascular disease Intrinsic azotemia is caused most often by acute tubular necrosis but can occur with acute glomerulonephritis and interstitial nephritis Acute tubular necrosis has numerous causes but is mainly due to renal ischemia, nephrotoxic drugs (eg, nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics), and radiographic contrast dyes Postrenal azotemia is caused by obstruction of the outflow urinary tracts, as seen in patients with nephrolithiasis or benign prostatic hypertrophy Management of disease The goal of treatment of AKI is to prevent further kidney injury and correct any water, electrolyte, or acid-base imbalances It is also vitally important to determine the underlying etiology of AKI Hypovolemic states can result from excessive bleeding, reduced oral intake, or excessive fluid loss Renal blood flow should be maintained to prevent any further renal damage Fluid resuscitation provides rapid correction of hypotension and hypovolemia Numerous studies suggest that lactated Ringer solution is the fluid of choice because of its physiologically appropriate electrolyte composition Other proposed treatments for the management of AKI, including vasopressors, diuretics, and dialysis, have varying support in the literature.3 Anesthetic considerations One of the most important aspects of the management of acute kidney disease for the practicing oral and maxillofacial surgeon is the recognition of the possibility of acute kidney disease before surgery This recognition is most practically accomplished by means of a thorough history and physical examination Patients will often have recent screening laboratory studies, including complete blood count, basic metabolic panel, urine analysis, and/or urine electrolyte analysis A simple analysis of these studies could suggest the etiology of AKI Pertinent aspects of the patient’s history, including cardiac status, recent illnesses causing vomiting and diarrhea, and/or newly prescribed medications that may be nephrotoxic, are all risk factors for the development of AKI in the postoperative period A patient’s overall fluid status is assessed by examining the mucous membranes (dry versus wet) in conjunction with the patient’s preoperative vital signs Tachycardia may indicate hypovolemia and can be elucidated by obtaining a set of orthostatic vital signs.4 Acute kidney diseases can have a number of different etiologies, many of which can be life threatening In the outpatient oral and maxillofacial surgery setting, it is best to avoid elective surgery in patients who have AKI because of the increased risk that the AKI will worsen after a surgical procedure The cause of the patient’s kidney injury must be determined with the help of a primary care physician or kidney specialist If surgery 254 www.ajlobby.com Mizukawa_Chap_18.indd 254 6/20/17 10:43 AM Chronic Kidney Disease and End-Stage Renal Disease is absolutely necessary, the main anesthetic considerations involve the maintenance of the patient’s systemic blood pressure and cardiac output To avoid further injury to the renal system, it is important to avoid hypotension, hypovolemia, hypoxia, and any exposure to nephrotoxic agents.2 Chronic Kidney Disease and End-Stage Renal Disease Pathophysiology and diagnosis CKD is a global problem with incidence and prevalence rising at alarming rates In the United States, the two biggest factors contributing to this rapid progression are the growing diabetes mellitus and hypertension epidemics The National Kidney Foundation defines CKD as structural or functional kidney abnormalities with or without a decrease in the glomerular filtration rate (GFR) for ≥ months CKD is manifested in either pathologic kidney abnormalities or markers of kidney damage revealed in blood testing, urine testing, or imaging CKD can also be defined as GFR < 60 mL/min for ≥ months In a system similar to the previously described staging of acute renal injuries, CKD is classified according to the degree of glomerular filtration dysfunction The stage of CKD progresses with every 15 mL/min decrease in GFR below 90 mL/min The ultimate outcome of CKD is gradual loss of kidney function with eventual development of end-stage renal disease (ESRD) and increased overall risk of cardiovascular disease.5,6 The complications stemming from CKD and ESRD are numerous and include uremic syndrome, anemia, electrolyte and fluid imbalances, bleeding abnormalities, and severe cardiovascular effects Uremic syndrome is an umbrella term describing the neurologic, muscular, gastrointestinal, endocrine, metabolic, pulmonary, cardiovascular, and many other manifestations of chronic renal failure Clinical examples include anorexia, peripheral neuropathies, decrease in mental acuity, fatigue, and platelet dysfunctions Uremic syndrome manifests after the kidney fails to clear nitrogenous organic waste products, such as urea.7 Typically, these symptoms not manifest until the GFR falls below 25 to 30 mL/min Normally functioning kidneys make EPO, the major hormone of erythrocyte production This hormone regulates the manufacturing of erythrocytes by interacting with specific EPO receptors on bone marrow erythroid progenitors and is especially active when oxygen delivery levels decrease because of a reduction in the number of erythrocytes in circulation.8 Without adequate EPO production, patients are unable to respond appropriately to an anemic condition and subsequently become symptomatic Symptoms often include excessive fatigue, tachycardia, shortness of breath/exercise intolerance, generalized weakness, dizziness, and inability to concentrate The main treatments include iron supplementation, use of EPO-stimulating agents, and blood transfusions These interventions, however, are not without risk Red blood cell transfusions should be avoided when possible because of the risks, albeit low, of transfusion errors, volume overload, hyperkalemia, citrate toxicity, coagulopathy, infection transmission, and human leukocyte antigen (HLA) sensitization HLA sensitization has been associated with a delay in renal transplantation and an increased risk of renal graft loss due to the presence of previously formed HLA antibodies in patients who have previously undergone transfusion.9 Electrolyte and fluid imbalances are another consequence of CKD and are addressed later in the chapter As CKD progresses toward ESRD, the accumulation of uremic waste products interferes with platelet function and can cause serious bleeding ESRD is the clinical endpoint of CKD; however, unlike CKD, it is not strictly defined by a level of GFR dysfunction Rather, it is defined by the requirement of renal replacement therapy through dialysis or renal transplantation The most common clinical indications for dialysis include fluid overload, hyperkalemia, severe acidosis, metabolic encephalopathy, pericarditis, coagulopathy, refractory gastrointestinal symptoms, and drug toxicity.10 ESRD is a pervasive medical condition that affects nearly every organ system in the human body These patients tend to be immunocompromised at baseline and thus have an increased susceptibility to infection They also have increased surgical morbidity and mortality rates, thereby necessitating a thorough perioperative evaluation before any surgical procedures.4 Perioperative complications of ESRD include hyperkalemia, bleeding, cardiovascular dysfunction, hypertension and hypotension, congestive heart failure, ischemia, sepsis, and graft thrombosis.11 255 www.ajlobby.com Mizukawa_Chap_18.indd 255 6/20/17 10:43 AM 18 • The Renal System Management of disease The diagnosis, evaluation, management, and treatment of CKD and ESRD are extremely complicated and challenging Appropriate treatment of these patients requires the coordination of physicians, specialists, and other health care providers The overarching goals of management include (1) discovering and treating the specific causes of the kidney disease, (2) addressing any reversible conditions or factors that may be damaging kidney function, (3) prescribing renal protective agents such as ACE inhibitors and angiotensin II receptor blockers to slow the progression of kidney disease, (4) avoiding drugs that are nephrotoxic and appropriately adjusting levels of drugs that rely on kidney metabolism and/or excretion, (5) addressing the endocrine and metabolic consequences of diminished kidney function, (6) treating cardiovascular disease and its risk factors, and (7) preparing the patient for dialysis to remove waste and excess water from the blood and to correct electrolyte imbalance.12 Anesthetic considerations To safely use outpatient anesthesia in patients with CKD, the surgeon must have a firm understanding of the patient’s preoperative renal function status This requirement is best accomplished by collaborating with the patient’s primary care physician or nephrologist before any surgical procedures Most anesthetic drugs employed in the outpatient setting rely to varying degrees on renal excretion for proper elimination As a result, dosages must be adjusted to prevent dangerous accumulation of the drug and its metabolites Accumulation of nitrogen-containing waste products within the blood can interfere with the pharmacologic actions of anesthetic drugs and can cause decreased protein binding resulting in increased free drug concentrations, increased penetration of anesthetic agents into the brain, or synergistic interaction with retained toxins.12 Renal dysfunction influences the metabolic pathways of the liver, thus indirectly influencing drug metabolism The drug metabolism in the liver consists of phase and phase reactions CKD slows the reactions in both phases and results in increased serum drug concentrations.13 Propofol Propofol is a sedative-hypnotic agent commonly administered intravenously in the outpatient setting by oral and maxillofacial surgeons Although propofol has profound effects on the cardiovascular and respiratory systems, it has little effect on renal system physiology Propofol metabolism results in inactive metabolites that are excreted in the urine Chronic renal failure does not affect clearance of the parent drug and therefore does not require adjustment in these patients.12,14 Benzodiazepines Benzodiazepines are another important group of anesthetic agents that surgeons employ to achieve sedation, anxiolysis, and anterograde amnesia in the office setting These drugs are predominantly metabolized by the liver The metabolites of benzodiazepines are excreted mostly in the urine The most active metabolite of midazolam, α1-hydroxymidazolam, has substantial depressant effects in the central nervous system (CNS) and will accumulate in patients with advanced CKD or ESRD because of the prolonged half-life of its active metabolites Similarly, diazepam is a long-acting benzodiazepine whose liver metabolism results in the active metabolites desmethyldiazepam and oxazepam Consequently, in patients with CKD and renal failure, diazepam dosing should be reduced to avoid untoward effects of excessive sedation Lorazepam is another long-acting benzodiazepine that forms inactive metabolites after liver glucuronidation No renal dosing adjustments are necessary in patients with CKD.12,14,15 Recommendations for benzodiazepine dosing are as follows: • Midazolam and diazepam require a 50% reduction in dose when the GFR is < 10 mL/min, the patient is on hemodialysis, or the patient is on continuous ambulatory peritoneal dialysis No dosing adjustments are necessary for patients on continuous renal replacement therapy.8,11 256 www.ajlobby.com Mizukawa_Chap_18.indd 256 6/20/17 10:43 AM Chronic Kidney Disease and End-Stage Renal Disease • Lorazepam does not require dosing adjustment in patients with CKD or ESRD • The use of oral benzodiazepines for preoperative anxiolysis is not recommended because of the inability to appropriately titrate dosages and the increased propensity for oversedation Barbiturates With the development of newer anesthetic drugs, barbiturates such as methohexital have become less common in the induction of anesthesia and sedation in the outpatient setting Because of the possibility of drug shortages and the need for anesthetic versatility, the practitioner should be familiar with a wide variety of anesthetic modalities Barbiturates tend to decrease renal blood flow and GFR, which is an unsatisfactory consequence in patients who have compromised renal function at baseline.12 Barbiturates are also highly protein bound in the plasma In patients with CKD or ESRD, decreased circulating protein levels prevent binding of barbiturates, thus resulting in increased free circulation of the drug Uremia further decreases barbiturates’ protein binding ability via competitive inhibition with nitrogenous waste products.16,17 Opioids Opioids are crucial for providing adequate analgesia in patients before, during, and after oral and maxillofacial surgery procedures Renal dysfunction affects the absorption (reducing gastric emptying), distribution (decreasing plasma protein binding via competition with nitrogenous waste products and decreasing overall circulating plasma proteins), metabolism (influencing efficiency of liver metabolic enzymes), and elimination (decreasing the GFR, tubular secretion, and reabsorption) of opioids in these patients.18 The following is a list of opioids commonly used by oral and maxillofacial surgeons in outpatient anesthesia and recommendations for their use in patients with renal dysfunction • Morphine is metabolized by the liver into three metabolites, with the majority of the metabolites being morphine 3-glucuronide and morphine 6-glucuronide These potent metabolites, especially morphine 6-glucuronide, are actively secreted by the kidney; therefore, when renal dysfunction is present, they can accumulate, resulting in the potential for prolonged narcosis, seizures, and respiratory depression.10,18 If the patient’s GFR is > 50 mL/min, no dosing adjustment is necessary If the GFR is 10 to 50 mL/min, the dose should be decreased to 75% of the usual dose If the GFR is < 10 mL/min or the patient is on hemodialysis, continuous ambulatory peritoneal dialysis, or continuous renal replacement therapy, the dose should be decreased to 50% of the usual dose.8 • Fentanyl is metabolized by the liver primarily to norfentanyl, which is inactive and nontoxic Because of these properties, fentanyl is one of the safest opioids to use in patients with CKD or ESRD.10,18 If the patient’s GFR is > 50 mL/min, no dosing adjustment is necessary If the GFR is 10 to 50 mL/min or the patient is on continuous renal replacement therapy, the dose should be decreased to 75% of the usual dose If the GFR is < 10 mL/min or the patient is on hemodialysis or continuous ambulatory peritoneal dialysis, the dose should be decreased to 50% of the usual dose.8 • Remifentanil is metabolized independently of renal and hepatic mechanisms by rapid ester hydrolysis in erythrocytes and tissue cells Its metabolite is active but at a fraction of the potency of the parent drug and therefore is not clinically relevant Sufentanil and alfentanil are opioids with activity between that of fentanyl and remifentanil and are typically used in cardiac or prolonged surgical procedures requiring general anesthesia.12,19 These fentanyl derivatives form inactive metabolites after liver metabolism Patients with renal dysfunction not require dosing adjustments for remifentanil, sufentanil, or alfentanil • Hydromorphone is metabolized by the liver into the metabolite hydromorphone-3-glucuronide (H3G) and its derivatives, which are renally excreted H3G has neuroexcitatory properties and can accumulate in patients on hemodialysis or patients whose GFR is severely diminished (< 30 mL/min).18,19 Therefore, it should be used with caution in patients with renal dysfunction 257 www.ajlobby.com Mizukawa_Chap_18.indd 257 6/20/17 10:43 AM 18 • The Renal System • Meperidine is metabolized by the liver into the active metabolite normeperidine, which accumulates in renal dysfunction states Normeperidine has CNS excitatory effects that can result in serious CNS toxicity manifested as intractable myoclonus and/or seizure activity.12,18 Meperidine is not recommended for anesthetic use in patients on hemodialysis, continuous ambulatory peritoneal dialysis, or continuous renal replacement therapy If the patient’s GFR is > 50 mL/min, no dosing adjustment is necessary If the GFR is 10 to 50 mL/min, 75% of the usual dose is recommended If the GFR is < 10 mL/min, 50% of the usual dose is recommended.8 Ketamine Ketamine is metabolized by the liver into the metabolite norketamine, which has 20% to 30% of the activity of the parent compound.20 Little is known regarding the implications of norketamine accumulation in patients with renal dysfunction Ketamine is a cardiovascular stimulant and should be used cautiously in patients with CKD or ESRD, who may be hypertensive at baseline Anticholinergic agents Anticholinergic agents are utilized by oral and maxillofacial surgeons to combat bradycardia caused by muscle relaxation reversal with acetylcholinesterase medications as well as for their antisialagogue and antinauseant properties The most commonly used agents include atropine, glycopyrrolate, and scopolamine Atropine and glycopyrrolate both depend on the kidneys for proper elimination, with 30% to 50% of atropine excreted unchanged in the urine The CNS side effects of anticholinergic medications, especially in those patients administered scopolamine, can be amplified in the setting of azotemia In patients with renal dysfunction, premedication doses of atropine and glycopyrrolate not require adjustment However, when multiple doses are required, reduced dosing should be considered because of the potential for accumulation of the active metabolites of these drugs.12,13,19,21 Antiemetic medications Antiemetic medications are useful adjuncts to address the prevalent complaint of postoperative nausea and vomiting after outpatient oral surgical procedures Common antiemetic medications employed by oral and maxillofacial surgeons include the phenothiazines (eg, promethazine), butyrophenones (eg, droperidol), and 5-hydroxytryptamine antagonists (eg, ondansetron) Recommendations for dosing are as follows: • Promethazine is metabolized by the liver into inactive metabolites, which are excreted in urine and bile Promethazine does not require dosing or interval adjustments in patients with CKD or ESRD.8 • Droperidol is metabolized in the liver, with approximately 10% excreted unchanged in the urine When it is used in a small clinical dose (< 2.5 mg), active metabolite accumulation is unlikely in patients with CKD or ESRD.10 • Ondansetron is metabolized by the liver into relatively inactive metabolites, which are excreted in urine Ondansetron does not require dosing or interval adjustments in patients with CKD or ESRD.8 Nitrous oxide Nitrous oxide is a colorless, odorless gas often used by oral and maxillofacial surgeons for anxiolysis and mild sedation for oral surgical procedures Nitrous oxide should be used with caution in patients with CKD or ESRD who have severe anemia (hemoglobin level < g/dL); specifically, its use needs to be limited to 50% concentration to increase arterial oxygen content.10 258 www.ajlobby.com Mizukawa_Chap_18.indd 258 6/20/17 10:43 AM Hepatorenal Syndrome Hepatorenal Syndrome Pathophysiology and diagnosis Hepatorenal syndrome (HRS) is a form of functional renal failure that occurs in patients with concurrent liver disease Typically these patients have either acute or chronic liver disease, advanced liver failure, and portal hypertension.22,23 The two forms of HRS are delineated primarily by the rapidity of onset of renal dysfunction HRS type is the more serious condition and is defined as at least a doubling in serum creatinine level to > 2.5 mg/dL (or a 50% reduction in creatinine clearance) in ≤ weeks HRS type is considered less severe and has a less rapid onset with ascites refractory to diuretics Median survival rates differ greatly, with type patients having a median survival of weeks and type patients having a median survival of approximately to months In this syndrome, severe liver pathology causes a cascade of vascular hemodynamic changes that result in renal failure without an appreciable change in renal histology The main hemodynamic changes include substantial renal vasoconstriction, peripheral arteriolar vasodilation, impaired renal perfusion, and a low GFR.24 The major diagnostic criteria defined by the International Club of Ascites include (1) the presence of cirrhosis and ascites, (2) serum creatinine level > 1.5 mg/dL, (3) no improvement in serum creatinine level after at least 48 hours of diuretic withdrawal and volume expansion with albumin, (4) absence of shock, (5) no concurrent or recent treatment with nephrotoxic drugs, and (6) the absence of parenchymal kidney disease Clinically, these patients typically have the stigmata of advanced liver disease, such as jaundice, spider angiomas, splenomegaly, ascites, lower extremity edema, hepatic encephalopathy, tachycardia, and oliguria.25 Management of disease The goal of management in patients with HRS is the restoration of intravascular fluid volume, with the ultimate recommended treatment being liver transplantation Restoration of intravascular fluid volume is accomplished by various therapies, including discontinuation of diuretic medications in patients with evidence of cirrhosis and renal failure Vasoconstrictors (eg, terlipressin, α-adrenergic agonists) cause constriction within the gastrointestinal circulation, thereby improving renal perfusion Albumin improves the effective circulating arterial volume without contributing to ascites When vasoconstrictors are used in conjunction with albumin, the efficacy of the medications increases, and overall prognosis of HRS patients greatly improves Renal replacement therapy and albumin dialysis provide renal detoxification and liver detoxification, respectively The transjugular intrahepatic portosystemic shunt (TIPS) procedure connects the portal and hepatic veins, which reduces portal pressures, increases systemic circulatory volume, increases GFR, and suppresses the activity of the vasoconstrictor systems, thus restoring proper renal circulation Liver transplantation, which is the definitive therapy, restores liver function and normalizes both the portal circulation and the systemic circulation.26,27 Anesthetic considerations Patients with HRS are medically complex and are not candidates for outpatient anesthesia in the typical office setting If emergent care is needed, local anesthesia is an option only after conference with the patient’s physician.28 259 www.ajlobby.com Mizukawa_Chap_18.indd 259 6/20/17 10:43 AM 18 • The Renal System Fluid and Electrolyte Disturbances Pathophysiology and diagnosis Fluid and electrolyte disturbances are common in patients with kidney disease or ESRD As previously discussed, the proper functioning of the renal system is crucial to maintain proper salt and water balances as well as electrolyte and acid-base homeostasis These patients are susceptible to widely fluctuating intravascular fluid volumes, hyperkalemia, hypermagnesemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and hypoalbuminemia The principal systemic manifestations of renal dysfunction result from fluid overload, dehydration, hyperkalemia, and metabolic acidosis Extracellular fluid overload is caused by the retention of water and sodium within the vasculature This retention has important effects in the cardiovascular and pulmonary systems, such as systemic arterial hypertension, congestive heart failure, and pulmonary edema On the opposite end of the spectrum, intravascular volume depletion and hypovolemia occurs in patients who have had excessive amounts of fluid removed in dialysis By comparing the patient’s predialysis and postdialysis weights with the weight at the time of presentation, an accurate assessment of the patient’s overall volume status can be made The patient’s dialysis schedule must be obtained to determine the appropriate timing for surgery Clinical signs and symptoms of hyperkalemia include muscle weakness, ascending paralysis, nausea, and vomiting Cardiac manifestations of hyperkalemia are observed on the electrocardiogram (ECG) as distinct, characteristic changes These changes typically progress from symmetrically peaked T waves to widening of the QRS complex to the absence of P waves with eventual sine wave formation If treatment is not initiated, this arrhythmia progresses to ventricular fibrillation and eventual asystole Anesthetic considerations For patients with CKD or ESRD who are being considered for elective surgery in the outpatient setting, a thorough preoperative evaluation consisting of an in-depth recent history and physical examination with particular focus on any associated comorbidities, assessment of overall fluid status, and assessment of recent electrolyte values and coagulation studies is prudent Patients should also be examined for arteriovenous fistulas that are used for dialysis access in order to avoid placement of blood pressure cuffs and initiation of intravenous access at those sites.27 In patients with ESRD, dialysis should be performed on the days before and after the surgical procedure to maximize the likelihood of a euvolemic state and achieve normal electrolyte concentrations.27 Dialysis patients will ideally have a dry stable weight, which, if known, can help the practitioner determine if the patient is currently in a hypervolemic or hypovolemic state Judicious use of fluids is recommended to avoid the consequences of fluid overload, namely hypertension and pulmonary edema The patient’s volume status at the time of presentation helps guide fluid management during the surgical procedure Because lactated Ringer solution contains potassium, its use should be avoided to minimize the risk of hyperkalemia Normal saline (0.9% sodium chloride) or 5% dextrose are the preferred intravenous fluids.11,27 Elective surgery is contraindicated in patients whose potassium levels are > 5.5 mEq/L because tissue trauma and cell injury during surgery could increase values to dangerous levels.3 If ECG changes are seen on the monitor, the patient should be treated for hyperkalemia Treatment includes the following stepwise approach: Stabilize the cardiac membrane with 10 mL (1 ampule) of 10% intravenous calcium gluconate or mL of 10% calcium chloride solution Shift potassium intracellularly with 10 units of insulin and 50 g of glucose and administration of β agonists (20 mg nebulized albuterol in mL normal saline) Enhance the elimination of potassium with 80 to 240 mg of furosemide if the patient has some residual kidney function If the patient has minimal kidney reserve, 20 g of sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals) dissolved in 100 mL of 20% sorbitol can be administered orally Emergent hemodialysis is required if the patient remains symptomatic.29 260 www.ajlobby.com Mizukawa_Chap_18.indd 260 6/20/17 10:43 AM References Conclusion Kidney disease patients are medically complex patients who require a thorough preoperative medical assessment prior to the administration of anesthesia In the outpatient oral and maxillofacial surgery setting, elective surgery should be avoided in patients with acute kidney disease until a clear etiology for their kidney injury is determined Practitioners should be familiar with the appropriate anesthetic management of patients with CKD or ESRD Most drugs discussed require dose reduction as the severity of renal dysfunction increases A healthy working relationship between a patient’s primary care physician, nephrologist, and oral and maxillofacial surgeon facilitates treatment and ensures that the appropriate anesthetic plan is employed on an individual case basis References Hemmings HC Jr, Egan TD Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application Philadelphia: Elsevier Saunders, 2013 Fleisher LA Anesthesia and Uncommon Diseases, ed Philadelphia: Elsevier Saunders, 2012 Hines RL, Marschall KE Handbook for Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Elsevier Saunders, 2013 Carrasco LR, Chou JC Perioperative management of patients with renal disease Oral Maxillofac Surg Clin North Am 2006;18:203–212 Bope ET, Kellerman RD Conn’s Current Therapy 2014 Philadelphia: Elsevier Saunders, 2013 National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification Am J Kidney Dis 2002:39(2, suppl):S1–S266 Himmelfarb J, Sayegh MH Chronic Kidney Disease, Dialysis, and Transplantation, ed Philadelphia: Elsevier Saunders, 2010 Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM Brenner and Rector’s The Kidney, ed Philadelphia: Elsevier Saunders, 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group KDIGO clinical practice guideline for anemia in chronic kidney disease Kidney Int 2012;2(suppl):279–335 16 Stoelting RK, Hillier SC Pharmacology and Physiology in Anesthetic Practice, ed Philadelphia: Lippincott Williams & Wilkins, 2005 17 Goldstein NE, Morrison RS Evidence-Based Practice of Palliative Medicine Philadelphia: Elsevier Saunders, 2013 18 Ganzberg SI Pharmacology of outpatient anesthesia medications In: Miloro M, Ghali GE, Larsen P, Waite P (eds) Peterson’s Principles of Oral and Maxillofacial Surgery, ed Shelton, CT: People’s Medical Publishing House-USA, 2012:43–62 19 Reves JG, Glass P, Lubarsky DA, McEvoy MD, Martinez-Ruiz R Intravenous anesthetics In: Miller RD (ed) Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2010:719–768 20 Newman MF, Fleisher LA, Fink MP Perioperative Medicine: Managing for Outcome Philadelphia: Elsevier Saunders, 2008 21 Atlee JL Complications in Anesthesia, ed Philadelphia: Elsevier Saunders, 2007 22 Floege J, Johnson RJ, Feehally J Comprehensive Clinical Nephrology, ed Philadelphia: Elsevier Saunders, 2015 23 Dhillon A Hepatorenal syndrome In: Vincent JL, Abraham E, Moore FA, Kochanek PM, Fink MP Textbook of Critical Care, ed Philadelphia: Elsevier Saunders, 2011:752–756 24 Ferri FF Ferri’s Clinical Advisor 2015 Philadelphia: Elsevier Mosby, 2015 10 Morgan GE Jr, Mikhail MS, Murray MJ Anesthesia for patients with renal disease In: Morgan GE Jr, Mikhail MS, Murray MJ Clinical Anesthesiology, ed New York: McGraw-Hill, 2006:742–756 25 Pépin MN, Ginès P Management of hepatorenal syndrome In: Wilcox CS (ed) Therapy in Nephrology and Hypertension, ed Philadelphia: Elsevier Saunders, 2008:47–57 11 Merli GJ, Weitz HH Medical Management of the Surgical Patient, ed Philadelphia: Elsevier Saunders, 2008 26 Fabrizi F, Aghemo A, Messa P Hepatorenal syndrome and novel advances in its management Kidney Blood Press Res 2013;37:588–601 12 Gilbert SJ, Weiner DE National Kidney Foundation Primer on Kidney Diseases, ed Philadelphia: Elsevier Saunders, 2014 13 Hassan Y, Al-Ramahi R, Abd Aziz N, Ghazali R Drug use and dosing in chronic kidney disease Ann Acad Med Singapore 2009;38:1095–1103 14 Murray MJ, Harrison BA, Mueller JT, Rose SH, Wass CT, Wedel DJ Faust’s Anesthesiology Review, ed Philadelphia: Elsevier Saunders, 2015 15 Devlin JW, Roberts RJ Pharmacology of commonly used analgesics and sedatives in the ICU: Benzodiazepines, propofol, and opioids Anesthesiol Clin 2011;29:576–585 27 Agarwal R, Porter MH, Obeid G Common medical illnesses that affect anesthesia and their anesthetic management Oral Maxillofac Surg Clin North Am 2013;25:407–438 28 Sood MM, Sood AR, Richardson R Emergency management and commonly encountered outpatient scenarios in patients with hyperkalemia Mayo Clin Proc 2007;82:1553–1561 29 Holt NF Renal disease In: Hines RL, Marschall KE (eds) Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Elsevier Saunders, 2012:334–356 261 www.ajlobby.com Mizukawa_Chap_18.indd 261 6/20/17 10:43 AM www.ajlobby.com Mizukawa_Chap_18.indd 262 6/20/17 10:43 AM CHAPTER 19 The Hepatic System Hepatic Emily King, dmd Stuart Lieblich, dmd www.ajlobby.com Mizukawa_Chapter_Openers.indd 263 6/21/17 3:24 PM CHAPTER 19 The Hepatic System Normal Anatomy and Physiology 265 Hepatitis 266 Hepatic Cirrhosis and Liver Failure 270 www.ajlobby.com Mizukawa_Chapter_Openers.indd 264 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology The liver is the largest organ in the body It is located in the upper right quadrant of the abdominal cavity underneath the diaphragm The liver is divided into left and right lobes by the falciform ligament The right lobe has two additional smaller lobes on its inferior surface, the caudate and quadrate lobes The liver is held in place by several ligamentous attachments to the surrounding peritoneum, upper intestinal organs, diaphragm, and vessels.1 The liver has a dual blood supply Most of the blood supply comes from the portal vein, which contains nutrient-rich blood from the stomach, intestines, spleen, and pancreas The rest of the blood supply comes from the hepatic artery, which supplies oxygen-rich blood to the organ The portal vein is a low-resistance vessel, allowing for greater flow levels after absorption of a meal and allowing the liver to serve as a large circulatory reservoir.1 The liver can be divided into functional units called liver acini Each acinus contains a portal vein and hepatic artery peripherally that drain through sinusoids into the hepatic vein centrally All of the lobes of the liver are functionally identical, and the liver contains approximately 100,000 acini.1 The liver is composed of numerous cell types Most liver cells are hepatocytes, which serve as the major metabolic cells of the liver Other cell types include Kupffer, stellate, endothelial, and bile ductular cells, which all serve specialized functions Kupffer cells are of the macrophage lineage and serve an important role in host defense.1 Stellate cells have contractile function and store lipids Endothelial cells in the liver are specialized to have large fenestrae allowing the passage of macromolecules and lipoproteins, thus allowing hepatocytes to be exposed to most substances in circulation.2 The apical end of the hepatocytes allows secretion of bile into the bile ducts The functions of hepatocytes include the creation of most serum proteins, such as albumin and most coagulation factors The functions performed by the liver are numerous, and loss of these functions is incompatible with life The liver synthesizes amino acids and regulates nutrients such as glucose, glycogen, lipids, and cholesterol It is involved in the metabolism of lipophilic compounds and the production of bile to allow for excretion of these lipophilic products.1 Because the liver is an important site for the metabolism and regulation of carbohydrates, it plays a major role in the regulation of blood glucose levels The liver is the body’s major site of glycogen storage and gluconeogenesis, and it buffers blood glucose levels in times of fasting or in the postprandial period.1 Hepatocytes manage ingested and circulating lipids both by degradation of fatty acids for energy and by synthesis of fats to be stored in adipose tissue They also synthesize lipoproteins, such as cholesterol, and phospholipids, which are an integral part of all cell membranes Hepatocytes manage the degradation of ammonia, a central nervous system toxin, into urea, which is then excreted by the kidneys In addition to the physical detoxifying properties of the Kupffer cells, the liver possesses the ability to biochemically detoxify ingested substances through the function of hepatocytes that express high levels of cytochrome P450.2 Hepatocytes metabolize ingested drugs by oxidation and then esterification Finally, the liver is the site of degradation of most of the steroid hormones circulating through the body Multiple tests are available to assess liver function (Table 19-1) Usually, multiple tests are necessary to provide a meaningful assessment For instance, an elevated aspartate transaminase (AST) level could indicate liver damage or a myocardial infarction because the enzyme is found in both hepatic and cardiac tissues; however, an additional elevated alanine aminotransferase (ALT) level would be more indicative of liver damage because this enzyme is more specific to the liver 265 www.ajlobby.com Mizukawa_Chap_19.indd 265 6/20/17 10:44 AM 19 • The Hepatic System Table 19-1 Common liver function tests* Test Description Clinical relevance Normal range ALT Enzyme most specific to the liver • May indicate damage to liver or bile duct system • Levels can be elevated with certain drugs (for instance cholesterol medications) 34–45 IU/L Albumin Plasma protein made by the liver • Decreased production or loss in urine • May result in edema through loss of intravascular oncotic pressure 3.5–5.3 g/dL ALP Enzymes concentrated in the liver, bile ducts, and bone • May indicate bile duct obstruction or liver disease (also elevated in patients with bone disease) 25–85 IU/L AST Enzyme in liver, kidneys, brain, skeletal muscle, heart, and red blood cells • May indicate cell damage, such as that resulting from hepatitis, myocardial infarction, etc 6–40 IU/L Direct bilirubin Produced by the conjugation of bilirubin by the liver • Normal levels indicate a problem upstream of the liver: hemolytic anemia • Elevated levels suggest problems with the liver or bile duct system 0.1–0.4 mg/dL INR Measurement of prothrombin time; used to assess the extrinsic pathway of coagulation • May indicate liver damage leading to decreased production of clotting factors • May result in bleeding problems 0.9–1.1 (2–3.5 in patients on warfarin therapy) Total bilirubin Unconjugated and conjugated bilirubin, a breakdown product of heme May indicate liver damage, hemolytic anemia, or bile duct obstruction 0.1–1.0 mg/dL ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate transaminase; INR, international normalized ratio *Data modified from Ramsay.3 Hepatitis Pathophysiology and diagnosis Hepatitis refers to swelling and inflammation of the liver accompanied by inflammatory cell infiltrate in the liver tissues.4 The term most commonly refers to viral infection of the liver but can also refer to damage from autoimmune diseases, systemic conditions such as hemachromatosis, and drugs or toxins such as acetaminophen Although a few other viruses, such as Epstein-Barr virus and yellow fever virus, can cause hepatitis, it is overwhelmingly caused by a group of five viruses: hepatitis A, B, C, D, and E.4 Despite being molecularly different, all five hepatitis viruses cause clinically similar illnesses including jaundice, fever, and malaise.5 Hepatitis can range from subclinical to fulminant and can range from a self-clearing infection to a chronic infection Hepatitis A Hepatitis A is a member of the Picornaviridae family of RNA viruses The virus is transmitted by a fecal-oral route and is often associated with food/water contamination The virus has an incubation period of approximately weeks and is self-clearing in days to weeks.5 Diagnosis is made by serum testing for immunoglobulin G (IgG) antibodies to the virus IgG antibodies to the virus develop in infected individuals and likely confer lifelong immunity to reinfection by all strains of hepatitis A.4 Hepatitis B Hepatitis B is a member of the Hepadnaviridae family of DNA viruses It is unique among DNA viruses in that it uses reverse transcription for replication, a method common in retroviruses.5 The hepatitis B virus (HBV) is a blood-borne virus transferred through sharing of body fluids in sexual contact, illicit drug use, or fetal-maternal contact HBV has 266 www.ajlobby.com Mizukawa_Chap_19.indd 266 6/20/17 10:44 AM Hepatitis an incubation period of approximately 60 to 90 days and usually involves an asymptomatic or limited infection that is typically more severe and prolonged than hepatitis A infection is.5 Symptomatic infection may involve a serum sickness with rash and arthritis in addition to the standard symptoms of liver inflammation.5 In 3.5 2.8–3.5 60% of cases.12 In cirrhosis, portal hypertension is due to increased resistance to blood flow through the sinusoids of a fibrosed liver as well as vasodilation in the splanchnic vascular bed resulting in hyperdynamic splanchnic circulation.4 The increase in splanchnic circulation is thought to be due to an increase in the release of nitric oxide stimulated by reduced bacterial clearance.12 As a result, the heart rate and cardiac output increase, but blood pressure and systemic vascular resistance decrease, leading to functional hypovolemia As the condition progresses, the autonomic system cannot easily compensate for changes in fluid volumes, such as those resulting from dehydration or hemorrhage.13 Portal hypertension also causes perceived hypovolemia by altering the renin-angiotensin-aldosterone system in the kidneys that leads to sodium retention, further contributing to formation of ascites and edema.12 Patients with ascites, which is defined as fluid collection in the peritoneal cavity, may accumulate to liters of fluid in their abdominal cavity before noticing the abnormality Gastroesophageal varices are another serious complication of cirrhosis secondary to portal hypertension Portosystemic shunting is a method by which the circulatory system decreases pressure in the portal system through the development of venous bypasses in areas where the systemic circulation and portal circulation meet.4 This shunting occurs in a few locations, but the most relevant is gastroesophageal varices because they can cause massive bleeding in one-third of patients Each episode of gastroesophageal bleeding carries a 30% mortality rate.12 Other conditions secondary to portal hypertension include splenomegaly and hypersplenism Splenomegaly alone typically does not require treatment; however, hypersplenism can lead to significant thrombocytopenia and leukopenia Finally, patients with repeated liver damage are at risk of hepatocellular carcinoma Liver failure Hepatic failure can occur acutely and is sometimes described as fulminant hepatic failure or as the end result of chronic damage Liver failure requires a loss of 80% to 90% of liver function At that point, the liver no longer performs its vital functions, and without a liver transplant, the patient has a very poor prognosis because homeostasis is no longer maintained.4 Acute liver failure is defined as liver disease that occurs acutely and leads to encephalopathy within 26 weeks Acute causes of liver failure include fulminant viral hepatitis infection and drug-induced or toxin-induced hepatic necrosis In the United States, acetaminophen overdose accounts for approximately 50% of fulminant liver failure cases.4 Liver failure due to chronic disease is the end point of cirrhosis As discussed previously, causes of cirrhosis include alcoholic liver disease, chronic hepatitis infection, and nonalcoholic fatty liver disease Regardless of the cause of hepatic failure, the clinical features are the same Physical findings almost always include jaundice, fetor hepaticus (musty body odor), palmar erythema, spider angiomas, and peripheral edema Jaundice and scleral icterus are a result of the failure of the liver to conjugate bilirubin to be excreted in the bile Bilirubin levels > 3 mg/dL result in jaundice.3 Fetor hepaticus is a result of portosystemic shunting, which releases sulfur-containing compounds created by gastrointestinal bacteria into the systemic circulation.4 Spider angiomas and palmar erythema are caused by excess estrogens, which are usually broken down in the liver, circulating in the blood and leading to vasodilation of arterioles in the skin Additional findings resulting from hyperestrogenemia include hypogonadism and gynecomastia in men Peripheral edema is caused by hypoalbuminemia, which de271 www.ajlobby.com Mizukawa_Chap_19.indd 271 6/20/17 10:44 AM 19 • The Hepatic System creases plasma oncotic pressure Patients with liver failure are at high risk of encephalopathy, which results in an alteration in consciousness that can range from minor changes in behavior to marked changes in mental status Untreated, hepatic encephalopathy can lead to death from cerebral herniation Hepatic encephalopathy can occur when the liver, due to vascular shunting, does not remove neurotoxins from metabolism Elevated ammonia levels are associated with hepatic encephalopathy.4 Treatment of hepatic encephalopathy includes removal of nitrogenous products in the gut with the use of lactulose, and the condition is reversible.12 Hepatorenal syndrome and hepatopulmonary syndrome occur more often in patients with severe chronic liver disease than in patients with acute or fulminant liver failure Hepatopulmonary syndrome is defined by hypoxemia and intrapulmonary vascular dilation The exact cause of hepatopulmonary syndrome is not known, but vasodilation of the pulmonary capillary beds leads to a ventilation/perfusion mismatch resulting in hypoxemia.12 Patients may have decreased oxygen saturation and an exacerbation of dyspnea while rising from a supine position.4 Hepatorenal syndrome can occur secondary to changes in circulation in chronic liver disease, leading to decreased renal blood flow and kidney damage Patients will have kidney failure with no obvious cause other than a coexisting severe hepatic disease This condition will develop in approximately 8% of individuals with cirrhosis and ascites, and the only cure is liver transplantation.12 (For additional information on hepatorenal syndrome, see chapter 18.) Management of disease The management of cirrhosis is typically aimed at removing or treating the offending agent (eg, alcohol or hepatitis viruses) and then treating the sequelae of cirrhosis, such as ascites and gastroesophageal varices As noted, depending on the degree of fluid accumulation, treatment of ascites can involve sodium restriction, the use of diuretics such as spironolactone and furosemide, or repeated paracentesis.12 Because spontaneous bacterial peritonitis, which has a 25% mortality rate,12 is a serious complication of ascites, diagnostic paracentesis is always performed initially to characterize the fluid collection Bleeding from gastroesophageal varices can be catastrophic, and as noted, each episode of gastroesophageal bleeding carries a 30% mortality rate.12 Treatment involves nonselective β-blocker therapy or variceal band ligation Splenomegaly alone typically does not require treatment; however, hypersplenism can lead to thrombocytopenia and leukopenia Patients with cirrhosis require surveillance for hepatocellular carcinoma at regular intervals The only cure for liver failure is a liver transplant As in patients with cirrhosis, the management of end-stage liver disease is aimed at the treatment of symptoms while the patient awaits a liver transplant Treatment of hepatic encephalopathy is aimed at removing nitrogenous products in the gut with lactulose or rifaximin.12 The treatment of hepatorenal syndrome is aimed at preserving kidney function with medical management, such as the use of albumin and splanchnic vasopressors, or surgical procedures, such as transjugular intrahepatic portosystemic shunt (TIPS) procedures, in anticipation of liver transplant, which is the only definitive treatment.13 Hepatopulmonary syndrome is treated symptomatically, although, again, the definitive treatment is liver transplantation Management of patients with cirrhosis and liver failure requires special consideration because the disease comes with myriad associated conditions A medical consultation should be obtained to determine the degree of cirrhosis or liver failure and whether the patient has compensated or decompensated liver disease Patients with decompensated liver disease often have additional complications, and elective surgery is generally contraindicated.14 The oral and maxillofacial surgeon may be called on to treat a patient with decompensated cirrhosis because these patients often require dental extractions to meet dental clearance prior to being listed for liver transplant Coagulation factors may be affected in even moderate stages of liver dysfunction Substantial liver disease must be present for clotting abnormalities to be observed clinically because most clotting factors require only 25% of normal levels for adequate clot formation14; therefore, this concern is most likely in patients with more advanced cases of cirrhosis An INR test should be ordered to assess the coagulation pathway The surgeon should obtain historic INR values and a value on the day of the planned procedure, and it is advisable to have local hemostatic agents available in the office As with patients on oral anticoagulation therapy, an INR between and is an optimal range for treatment.15 Differential tests, such as complete blood count, should be ordered to assess for thrombocytopenia and leukopenia due to hypersplenism Platelet transfusion is typically indicated for a platelet count < 50 272 www.ajlobby.com Mizukawa_Chap_19.indd 272 6/20/17 10:44 AM Cirrhosis and Liver Failure x 109/L.16 Clotting ability and thrombocytopenia in patients with liver failure is a serious concern and may preclude treatment of these patients in an outpatient setting Caution should be exercised when administering fluids to patients with portal hypertension and gastroesophageal varices because they already have an increased circulatory volume, and it is easy to cause fluid overload The altered circulation puts patients at a greater risk of hypotension because the ability to compensate for changes in body fluid level is compromised.14 Ascites can also complicate circulation problems by interfering with venous return when patients are supine Secondary restrictive lung disease may develop in patients with ascites as a result of upward pressure on the diaphragm, particularly when the patient is in the supine position This condition can result in hypoxemia, which would be a relative contraindication for sedation This same concern for hypoxemia exists in patients with hepatopulmonary syndrome.4 Additional care should be taken if intubation of a patient with gastroesophageal varicose becomes necessary There are reports of gastroesophageal rupture when accidental esophageal intubation has occurred.17 The triggers of gastroesophageal varicose are still not well understood, but there is the potential for rupture of varicose with increase in blood pressure.17 Patients with cirrhosis are often immunocompromised because of the loss of activity of the Kupffer cells, which detoxify bacteria and toxins entering through the gastrointestinal tract It is important to quickly treat infection in these patients, keeping in mind that preferred antibiotic choices may be altered Patients with hepatic hypofunction may experience hypoglycemia during fasting periods because of loss of the liver’s metabolic functions It is prudent to test blood glucose in these patients, particularly in periods of oral intake restriction before outpatient office-based sedation/anesthesia Anesthetic considerations Patients with liver disease are at a greater risk of anesthetic complications than patients with normal liver function are When prescribing or administering medications to patients with varying degrees of liver damage, the surgeon must consider whether the drug in question can cause acute liver damage, worsen chronic liver damage, precipitate or worsen renal failure, or induce gastrointestinal bleeding Decreased liver function can also lead to prolonged duration and/or a higher circulatory level of anesthetic medications metabolized in the liver Several factors affect the pharmacokinetics of drugs in patients with liver dysfunction; for example, hypoalbuminemia may result in increased amount of drug circulating in an unbound form and an increased volume of distribution.10 The increased volume of distribution tends to result in delayed onset and prolonged duration of the medications Increases in unbound fraction may result in an amplified drug effect Ascites may have also negative effects on drug distribution, bioavailability, and elimination half-life.10 Decreased cytochrome P450 enzymes delay metabolism and clearance The decrease in hepatic blood can result in an increase in bioavailability and serum drug concentrations.10 Assessment of liver function through the Child-Turcotte-Pugh classification system (see Table 19-2) may provide guidance for modifications of drug dosages As described previously, class A (mild risk) is or points, class B (moderate risk) is to points, and class C (severe risk) is ≥ 10 points In patients with mild liver dysfunction, minimal dose adjustment is necessary, whereas in patients with substantial liver dysfunction, dosages might be reduced by 50%, and some drugs must be avoided altogether Local anesthetics In patients with substantial liver dysfunction, the half-life of local anesthetics is prolonged The liver metabolizes the amide family of local anesthetics, which includes many commonly used anesthetics, such as lidocaine, bupivacaine, and mepivacaine Articaine, which is classified as an amide, is metabolized in the liver as well as in the blood by plasma cholinesterase For this reason, articaine may be a preferable anesthetic in patients with liver dysfunction 273 www.ajlobby.com Mizukawa_Chap_19.indd 273 6/20/17 10:44 AM 19 • The Hepatic System Sedative drugs Some of the most commonly used sedative drugs in the outpatient setting, including midazolam, fentanyl, meperidine, and propofol, are metabolized by the liver Administration of intravenous drugs may include a normal initial dose, but because of altered hepatic clearance, caution is necessary when subsequent doses are provided.10 The anesthesia provider needs to anticipate the prolonged action, particularly of the benzodiazepines, and the toxic levels that can accumulate Repeated dosing of drugs such as diazepam or midazolam can lead to unpredictable action The pharmacodynamics of fentanyl is thought to be unaltered in patients with cirrhosis; however, elimination may be prolonged in patients with advanced liver disease.14 Remifentanil rapidly undergoes hydrolysis, and clearance and elimination are unaltered even in advanced liver disease Meperidine has been shown to have an up to 50% reduction in clearance in patients with cirrhosis and should be avoided.14 Propofol is thought to be safe to use in patients with liver dysfunction because of its rapid onset and short duration of action Many studies have examined the use of propofol during endoscopy in patients with cirrhosis and have shown that it is safe to use with adequate patient monitoring.10 When drugs are administered intravenously, care should be taken to administer fluids cautiously because these patients are prone to fluid overload A 50% dose reduction should be considered when drugs are administered orally Most oral sedatives have a high hepatic extraction ratio (first-pass metabolism), which is bypassed in the patient with liver disease because of shunting of portal blood to the central circulation As a result, these drugs display faster onset, increased profundity, and increased duration of action Meperidine, morphine, and midazolam are known to have a twofold increase in bioavailability after oral administration in patients with cirrhosis.18 Nitrous oxide is considered safe to use in patients with hepatic dysfunction because it does not undergo metabolism in the liver Other inhalational agents vary in the amount of hepatic metabolism (5% of sevoflurane versus 0.2% of desflurane), although hepatic disease is not a contraindication to the use of either sevoflurane or desflurane.11 Antibiotics Many antibiotics commonly used in dentistry, such as penicillins and cephalosporins, are either excreted or metabolized by the kidneys and thus are generally safe to use in patients with hepatic dysfunction Some concern may arise in patients with cirrhosis when β-lactam antibiotics are considered because they can cause leukopenia.10 Fluoroquinolones, which are commonly used to treat bacterial peritonitis in patients with cirrhosis, have been found to be safe.10 Aminoglycosides, vancomycin, and macrolide antibiotics, including clindamycin, should be avoided in patients with cirrhosis Analgesics Acetaminophen is a drug commonly associated with liver damage when taken in high doses and should be avoided in patients with liver failure Patients should be counseled to avoid acetaminophen in over-the-counter medications as well NSAIDs may be a better choice for pain relief in these patients because they mostly involve renal excretion, although concerns of hepatorenal syndrome, underlying renal damage, and increased risk of gastrointestinal bleeding should be addressed Narcotic pain medications such as hydrocodone and oxycodone are commonly prescribed to patients in combination with acetaminophen It may be prudent to prescribe narcotic pain medications that are not coupled with acetaminophen in patients with liver dysfunction When hydrocodone or oxycodone is prescribed, the dose should be reduced to prevent accumulation and prolonged duration of action.10 274 www.ajlobby.com Mizukawa_Chap_19.indd 274 6/20/17 10:44 AM References Conclusion The oral and maxillofacial surgeon will undoubtedly encounter patients with liver dysfunction in the out-patient setting As described in this chapter, there are a great number of conditions associated with liver disease that require special consideration It is crucial to determine the severity of liver dysfunction prior to planning any elective out-patient procedures because some patients are more appropriately treated in a hospital setting Lastly, it is imperative to remember that many drugs prescribed by oral surgeons or used for sedation in the out-patient setting are metabolized by the liver and will be affected by liver dysfunction References 10 Lewis JH, Stine JG Review article: Prescribing medications in patients with cirrhosis—A practical guide Aliment Pharmacol Ther 2013;37:1132–1156 Barrett KE, Barman S, Boitano S, Brooks H Transport and metabolic functions of the liver In: Barrett KE, Barman SM, Boitano S, Brooks HL Ganong’s Review of Medical Physiology, ed 24 New York: McGraw-Hill, 2012:509–518 11 Behne M, Wilke HJ, Harder S Clinical pharmacokinetics of sevoflurane Clin Pharmacokinet 1999;36:13–26 Ghany M, Hoofnagle JH Approach to the patient with liver disease In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (eds) Harrison’s Principles of Internal Medicine, ed 18 New York: McGraw-Hill, 2012:2520–2526 12 Bacon BR Cirrhosis and its complications In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J (eds) Harrison’s Principles of Internal Medicine, ed 18 New York: McGraw-Hill, 2012:2592–2602 Ramsay M Hepatic physiology & anesthesia In: Butterworth JF, Mackey DC, Wasnick JD (eds) Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill, 2013:691–706 13 Liou IW Management of end-stage liver disease Med Clin North Am 2014;98:119–152 Theise N Liver and gallbladder In: Kumar V, Abbas AK, Aster JC (eds) Robbins and Cotran Pathologic Basis of Disease, ed Philadelphia: Elsevier Saunders, 2015:821–881 14 Rothenburg DM, O’Connor CJ, Tuman KJ Anesthesia and the hepatobiliary system In: Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s Anesthesia, ed Philadelphia: Elsevier Saunders, 2015:2244–2261 Dienstag JL Acute viral hepatitis In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (eds) Harrison’s Principles of Internal Medicine, ed 18 New York: McGraw-Hill, 2012:2537–2557 15 Perry DJ, Noakes TJ, Helliwell PS Guidelines for the management of patients on oral anticoagulants requiring dental surgery Br Dent J 2007;203:389–393 Dienstag JL Chronic hepatitis In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (eds) Harrison’s Principles of Internal Medicine, ed 18 New York: McGraw-Hill, 2012:2567–2588 Centers for Disease Control and Prevention (CDC) Interpretation of Hepatitis B Serologic Test Results http://www.cdc.gov/hepatitis/hbv/ pdfs/serologicchartv8.pdf Accessed June 2016 16 American Society of Anesthesiologists Task Force on Perioperative Blood Management Practice guidelines for perioperative blood management: An updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management* Anesthesiology 2015;122:241–275 Centers for Disease Control and Prevention (CDC) Testing for HCV infection: An update of guidance for clinicians and laboratorians MMWR Morb Mortal Wkly Rep 2013;62:362–365 17 Kuschner WG Massive esophageal variceal hemorrhage triggered by complicated endotracheal intubation J Emerg Med 2000; 18:317–322 Gutierrez JA, Lawitz EJ, Poordad F Interferon-free, direct-acting antiviral therapy for chronic hepatitis C J Viral Hepat 2015;22:861–870 18 Bass NM, Williams RL Guide to drug dosage in hepatic disease Clin Pharmacokinet 1988;15:396–420 275 www.ajlobby.com Mizukawa_Chap_19.indd 275 6/20/17 10:44 AM www.ajlobby.com Mizukawa_Chap_19.indd 276 6/20/17 10:44 AM CHAPTER 20 The Endocrine System Endocrine Erica L Shook, dds A Thomas Indresano, dmd Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chapter_Openers.indd 277 6/21/17 3:24 PM CHAPTER 20 The Endocrine System Normal Anatomy and Physiology 279 Diabetes Mellitus 287 Hypoglycemia 291 Hyperthyroidism 293 Hypothyroidism 295 Hypercortisolism (Cushing Syndrome) 297 Endocrine Hypocortisolism (Adrenal Insufficiency) 299 www.ajlobby.com Mizukawa_Chapter_Openers.indd 278 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology The endocrine system is a collection of glands that secrete hormones into the circulatory system to act on distant tissues The endocrine glands include the hypothalamus, pituitary, pineal, pancreas, gonads, thyroid, parathyroid, and adrenal (Fig 20-1) Endocrine secretory cells can also be found in the kidney, liver, gastrointestinal tract, brown and white adipose tissue, placenta, and heart Dopamine Ne AD GH H uro H RH H TR G nR H CR Hypothalamus Somatostation hyp op hys is Ox yto cin T SH PRL X LH &F GH Kidneys SH H2O retention Cortisol Mammary glands Testes Ovaries Liver T3/T Thyroid Lactation Metabolism Heat regulation Endothelial cells Von Willebrand factor Oxytocin Stress response ADH X ADH Adrenal Posterior Pituitary ADH ACTH Anterior Pituitary Vasoconstriction Contraction of uterus • Testosterone • Development of pubertal features • Spermatogenesis • Ovulation • Development of pubertal features • Estradiol • Progesterone Chondrocytes Skeletal growth Fig 20-1 Endocrine overview ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; CRH, corticotropin-releasing hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GHRH, growth hormone–releasing hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; PRL, prolactin; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TSH, thyroidstimulating hormone It is via release of hormones that these endocrine glands/secretory cells are able to provide coordination between tissues and organs in response to physiologic and environmental demands placed on the body Hormones are classified according to five major classes: amino acid derivatives, small neuropeptides, large proteins, steroid hormones, and vitamin derivatives Protein hormones act at cell-surface membrane receptors, whereas steroid hormones are lipid soluble and thus able to pass through the cell membrane and interact with intracellular nuclear receptors.1 Hypothalamus The hypothalamus is located superior to the pituitary gland, with the median eminence serving as the functional link between the two The superior hypophyseal artery branches off of the internal carotid artery to form a vascular plexus termed the hypophyseal-portal circulation (or the hypothalamic-pituitary portal system), which serves to carry the peptide-releasing factors produced by the hypothalamus to their site of action in the anterior pituitary.2 The interactions between the hypothalamus and pituitary gland demonstrate the brain-endocrine interplay re- 279 www.ajlobby.com Mizukawa_Chap_20.indd 279 6/20/17 10:44 AM 20 • The Endocrine System Table 20-1 Summary of endocrine glands and hormones Gland Hormone Anterior pituitary Target gland/tissue FSH Gonads LH ACTH TSH PRL GH Gonads Adrenal gland Thyroid gland Ovaries, mammary glands Liver, adipose tissue Posterior pituitary* Arginine vasopressin, aka antidiuretic hormone Oxytocin Kidney Gonads Hypothalamus Corticotropin-releasing hormone Thyrotropin-releasing hormone Gonadotropin-releasing hormone Growth hormone–releasing hormone Somatostatin Anterior pituitary Anterior pituitary Anterior pituitary Anterior pituitary Stomach, pancreas, anterior pituitary Dopamine Anterior pituitary Melatonin Melatonin receptors throughout the body Liver, skeletal muscle, adipose tissue Liver, adipose tissue Pineal gland Pancreas β-islet cells Insulin α-cells Glucagon δ-islet cells Somatostatin Pancreatic polypeptide Stomach, pancreas, anterior pituitary Pancreas Estrogen Progesterone Testosterone Ovary, breast, uterus Uterus, breast Androgen receptors throughout body Follicular cells T4 and T3 Nearly all cells of the body Parafollicular cells Calcitonin Intestines, bone, kidney Parathyroid hormone Intestines, bone, kidney Gonads Thyroid gland Parathyroid gland Adrenal glands Cortex Cortisol Medulla Zona glomerulosa Zona fasciculata Aldosterone Kidney Most cells of the body Zona reticularis Adrenal androgens (androgen precursors) Androgen receptors throughout the body Catecholamines: epinephrine, norepinephrine, and dopamine Nearly all cells of the body ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GI, gastrointestinal; LH, luteinizing hormone; PRL, prolactin; TSH, thyroid-stimulating hormone; T3, triiodothyronine; T4, thyroxine *Hormones are produced in the hypothalamus but are secreted by the posterior pituitary ferred to as neuroendocrinology Hormones produced by the hypothalamus include: thyrotropin-releasing hormone, gonadotropin-releasing hormone, corticotropin-releasing hormone, growth hormone–releasing hormone, somatostatin, dopamine, oxytocin, and vasopressin (Table 20-1) Although produced by the hypothalamus, oxytocin and vasopressin travel via the hypothalamic magnocellular neurons to the posterior pituitary, where they are released into the circulation (see the following section, “Pituitary gland” ).3 280 www.ajlobby.com Mizukawa_Chap_20.indd 280 6/20/17 10:44 AM Normal Anatomy and Physiology Effect Female ovaries: regulates ovarian estrogen synthesis and induces follicular growth; male testicles: plays a role in spermatozoa development in concert with testosterone Female ovaries: induces cholesterol availability for ovarian steroidogenesis; male testicles: induces intratesticular testosterone synthesis Maintains adrenal gland function and induces adrenal steroidogenesis Stimulates the production and release of thyroid hormone Ovaries: secretion of estrogen and progesterone; mammary glands: controls milk production (lactation) Mediates growth and metabolic functions Regulates water homeostasis and osmolality of body fluids Induces uterine contraction during parturition and activates milk ejection in nursing women Stimulates pituitary release of ACTH Stimulates pituitary release of TSH Stimulates pituitary release of LH and FSH Stimulates pituitary release of GH Inhibits the movement of nutrients from the GI tract into the circulation by increasing gastric emptying time, decreasing gastric acid and gastrin production, inhibiting pancreatic enzyme secretion, and decreasing splanchnic blood flow; inhibits release of GH, TSH, and PRL from pituitary Inhibits release of prolactin from pituitary Regulates circadian rhythms and the reproductive axis, including gonadotropin secretion and the timing/onset of puberty Ultimately promotes storage of glucose into cells; liver: promotes glycogen synthesis and storage as well as inhibiting glycogenolysis, ketogenesis, and gluconeogenesis; muscle: promotes protein and glycogen synthesis; adipose tissue: promotes triglyceride storage Acts opposite of insulin—stimulates the breakdown of stored glycogen, activates gluconeogenesis, and promotes ketogenesis and lipolysis Inhibits the movement of nutrients from the GI tract into the circulation by increasing gastric emptying time, decreasing gastric acid and gastrin production, inhibiting pancreatic enzyme secretion, and decreasing splanchnic blood flow; inhibits release of GH, TSH, and PRL from pituitary Plays a role in self-regulating pancreatic secretion Stimulates development and maintenance of female reproductive organs and regulates menstrual cycle Prepares uterus for pregnancy and mammary glands for lactation Stimulates development of male reproductive organs, sperm production, and protein anabolism Controls metabolic processes in all cells—increases basal metabolic rate, increases heart rate and contractility, increases sympathetic effects, promotes gut motility, stimulates bone turnover, increases hepatic gluconeogenesis and glycogenolysis, increases intestinal glucose absorption, increases cholesterol synthesis and degradation, and increases lipolysis, as well as plays a critical role in tissue growth and brain maturation Regulates extracellular calcium (decreases serum calcium); intestines: inhibits calcium absorption bone: inhibits osteoclasts and stimulates osteoblasts; kidney: inhibits calcium reabsorption Regulates extracellular calcium (increases serum calcium); bone: stimulates bone resorption and release of calcium; kidney: stimulates reabsorption of calcium, inhibits phosphate transport, and increases production of activated vitamin D, which enhances absorption of calcium in the intestines via calbindin Regulates extracellular volume and blood pressure (part of renin-angiotensin-aldosterone system; controls potassium homeostasis) Released in response to stress: induces insulin resistance, increases blood glucose concentrations at the expense of protein and lipid catabolism, inhibits osteoblasts, increases blood pressure, suppresses immunologic and inflammatory responses Converted peripherally to more potent androgens—stimulates development of male reproductive organs, sperm production, and protein anabolism Causes the sympathetic flight-or-fight response: increases heart rate and blood pressure, bronchial dilation, vasoconstriction, pupillary dilation, and increased metabolism Pituitary gland The pituitary gland weighs approximately 600 mg and is located in the sella turcica (ie, “the Turkish saddle”) of the sphenoid bone inferior to the hypothalamus It is commonly divided into two main components: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis) The adenohypophysis/anterior pituitary 281 www.ajlobby.com Mizukawa_Chap_20.indd 281 6/20/17 10:44 AM 20 • The Endocrine System is of ectodermal origin, arising from Rathke pouch, whereas the neurohypophyis/posterior pituitary is of neural origin.2 Hormones produced and secreted by the anterior pituitary include: follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, and growth hormone (GH) Hormones secreted by the posterior pituitary (although produced in the hypothalamus) include: arginine vasopressin (also known as antidiuretic hormone) and oxytocin (see Table 20-1) Pineal gland The pineal gland can be found in the roof of the posterior portion of the third ventricle.3 It is composed of two cell types: pinealocytes and interstitial cells It is the principal source of melatonin (see Table 20-1), which plays significant roles in the regulation of circadian rhythms and the reproductive axis, including gonadotropin secretion and the timing/onset of puberty The pineal gland receives light-encoded information via a polysynaptic pathway originating in the retina and traveling along the retinohypothalamic tract, intrahypothalamic projections, preganglionic sympathetic neurons of the intermediolateral cell column of the thoracic spinal cord, and finally, to postganglionic neurons in the superior cervical ganglion, which provide noradrenergic innervation of the pineal gland.2 Pancreas The pancreas is located in the abdominal cavity behind the stomach and consists of both exocrine and endocrine components Blood is supplied to the posterior lobe by the superior mesenteric artery and to the remainder of the gland by the celiac artery.3 The endocrine secretory cells of the pancreas are called the islets of Langerhans The exocrine component serves as the major digestive gland of the body by secreting digestive enzymes into the small intestine, whereas the endocrine component serves as the source of insulin, glucagon, somatostatin, and pancreatic polypeptide (see Fig 20-2 and Table 20-1) Hypoglycemia Glucagon Liver Pancreas Glucose Glycogen Fatty acid + glycerol Muscle Adipose Fat Amino acids Protein + glycogen Insulin Hyperglycemia Fig 20-2 The role of the pancreas in glucose regulation In response to hyperglycemia, the pancreas releases insulin, which acts on the liver, adipose tissue, and muscle In the liver, glucose is stored as glycogen In adipose tissue, glucose is stored as fatty acids In muscle, glucose is stored as glycogen In response to hypoglycemia, the pancreas releases glucagon In the liver, glucagon promotes glycogenolysis, releasing glucose into the blood In adipose tissue, fat stores are broken down to fatty acids and glycerol and further converted to glucose via gluconeogenesis In muscle tissue, protein is broken down to amino acids, which are also converted to glucose via gluconeogenesis Insulin and glucagon have opposing physiologic effects In response to hyperglycemia, insulin is secreted by β-cells and acts on the liver, muscle, and adipose tissue to promote glucose storage In the liver, it promotes 282 www.ajlobby.com Mizukawa_Chap_20.indd 282 6/20/17 10:44 AM Normal Anatomy and Physiology glycogen synthesis In muscle and adipose tissue, insulin promotes a shift of glucose into cells and storage as glycogen and triglyceride, respectively In response to hypoglycemia, glucagon is secreted by α-cells and has an overall effect of glucose liberation into the circulation In the liver, it promotes glycogenolysis, which breaks down glycogen stores into glucose It also promotes gluconeogenesis in the liver and renal cortex, which is the process of producing glucose from various precursors, including fatty acids (adipose) and amino acids (muscle).3 Somatostatin is released by δ-cells and exerts inhibitory effects in circulation It inhibits growth hormone and thyroid-stimulating hormone from the anterior pituitary It also exerts inhibitory effects on the digestive system, slowing gastric emptying and decreasing blood flow to the gut It also inhibits release of insulin and glucagon, as well as other digestive enzymes in the gut.3 Gonads The gonads refer to the ovaries in females and testicles in males The ovaries are located in the posterior lateral pelvic wall and are suspended by three associated ligaments The testicles descend during development to their final location within the scrotum Hormones produced by the ovaries include estradiol and progesterone The testicles produce the hormones testosterone, dihydrotestosterone, and estradiol (see Table 20-1) These steroid sex hormones are responsible for the development and maintenance of the genital systems, the initiation of puberty, the onset of secondary sexual characteristics, as well as the regulation of ovulation and menstruation in females and the libido and potency in males.3 Thyroid gland The thyroid gland is the largest purely endocrine organ in the body, weighing approximately 15 to 20 grams in the average adult It is located in the neck, anterior to the trachea and inferior to the thyroid cartilage It consists of two lobes connected by an isthmus, with each lobe measuring approximately cm thick, cm wide, and cm long The thyroid gland originates as a thickening of epithelium at the foramen cecum in the pharyngeal floor, from which it descends along the thyroglossal duct Vascularity is provided by the superior thyroid artery, arising from the external carotid artery, and the inferior thyroid artery, arising from the subclavian artery.2 The thyroid gland produces and secretes thyroxine (T4), triiodothyronine (T3), and calcitonin (see Table 20-1) Upon stimulation by TSH from the anterior pituitary, the follicular cells of the thyroid gland produce T4 and T3 in an approximate ratio of 80–90:10–20 and release them into the circulation T4 acts largely as a prohormone and is converted to T3, which is to 10 times more potent and active than T4 Once in the circulation, both T3 and T4 are immediately bound by various plasma proteins, leaving approximately 0.3% and 0.03%, respectively, free in the plasma to elicit a physiologic response The physiologic effects of the thyroid gland include elevation of the basal metabolic rate, increased inotropy/chronotropy of the myocardium, and promotion of brain maturation and overall growth in children.2 Calcitonin is produced in the parafollicular cells of the thyroid gland and is released into the circulation in response to hypercalcemia It decreases serum calcium levels by promoting osteoblast function and incorporation of calcium back into reservoirs of bone tissue It also decreases calcium absorption in the gut and decreases calcium reabsorption in the kidneys Parathyroid glands The parathyroid glands are located adjacent to the thyroid gland, on the posterior aspect (Fig 20-3) Usually, individuals have four glands, although 12% to 15% of individuals have five Each gland weighs, on average, 40 mg These glands secrete parathyroid hormone (PTH), which plays a key role in regulating extracellular calcium concentration (see Table 20-1) PTH opposes calcitonin in its physiologic effects It promotes osteoclast activity in bone, releasing 283 www.ajlobby.com Mizukawa_Chap_20.indd 283 6/20/17 10:44 AM 20 • The Endocrine System calcium into the circulation It also increases the production of the active form of vitamin D (1,25-dihydroxy vitamin D), which in turn promotes absorption of calcium into the gut and ultimately into the circulation PTH also promotes reabsorption of calcium in the kidneys Parathyroid glands – Hypocalcemia + PTH release Bone Intestine Increase in calcium absorption Kidney Release of calcium into bloodstream via osteoclast function • Calcium reabsorbtion • Activation of Vitamin D Increase calcium concentration in the bloodstream Fig 20-3 Regulation of calcium levels via parathyroid hormone (PTH) PTH is released in response to low calcium levels, and acts on three organ systems It promotes intestinal absorption of calcium in the gut It activates osteoclasts, which resorb bone and release calcium from the bone structure It also promotes calcium reabsorption in the kidneys and activates vitamin D, which also increases calcium levels in the serum Note that elevated calcium levels trigger a negative feedback loop on the parathyroid glands, inhibiting release of PTH Adrenal glands The adrenal glands are located in the retroperitoneum, superior or medial to the kidneys (Fig 20-4) They have a combined weight of to 10 g and consist of the outer cortex and inner medulla The cortex has three zones: an outer zona glomerulosa, a zona fasciculata, and an inner zona reticularis The cortex is very vascular; the adrenal gland receives its main arterial supply from branches of the inferior phrenic artery, renal arteries, and the aorta Venous drainage is via the posterior aspect of the vena cava for the right adrenal gland and via the left renal vein for the left adrenal gland.3 Three main types of hormones are produced by the adrenal cortex: glucocorticoids (cortisol), mineralocorticoids (aldosterone), and sex steroids (mainly androgen precursors) The adrenal medulla produces the catecholamines epinephrine, norepinephrine, and dopamine (see Table 20-1).4 284 www.ajlobby.com Mizukawa_Chap_20.indd 284 6/20/17 10:44 AM Normal Anatomy and Physiology Zona Zona Zona Zona reticularis Zona glomerulosa Zona glomerulosa reticularis fasciculata Capsule fasciculata Capsule Adrenalmedulla medulla Adrenal Adrenalcortex cortex Adrenal Capsule Capsule a b Detailofofadrenal adrenalcortex cortex Detail Fig 20-4 (a) Anatomy of adrenal glands (b) The zones of the adrenal cortex Aldosterone is released by the zona glomerulosa and exerts its actions on the distal tubules to promote reabsorption of sodium and water, maintaining blood volume and pressure It is secreted in response to renin release by the juxtaglomerular cells of the kidneys in the presence of hypotension Cortisol is the stress hormone and is released by the zona fasciculata in response to physiologic stress, including surgery It has many physiologic effects: • Energy It provides adequate glucose to meet the demand of increased metabolism in the setting of stress by promoting gluconeogenesis and glycogenolysis Proteolysis and lipolysis are enhanced to provide substrate for gluconeogenesis in the liver • Control of blood flow Cortisol also primes the cardiovascular system in times of stress and is required for catecholamine action on the vasculature and the heart In addition, it promotes erythropoiesis to meet the increased oxygen demands during stress • Immune modulation It has a profound inhibitory effect on the immune system, in particular, the T-cell mediated response Chemotaxis of leukocytes and neutrophils to the wound is inhibited Wound healing is decreased due to a compromised activity of fibroblasts Bone healing is also compromised • Anti-inflammatory Cortisol inhibits the activity of phospholipase A2, which is the key enzyme in the synthesis of prostaglandins, leukotrienes, and thromboxanes from arachidonic acid These inflammatory mediators cause the classical symptoms of rubor (redness), dolor (pain), tumor (swelling), and calor (heat) Thus, inhibition of these mediators can reduce morbidity associated with injury and surgery The zona reticularis produces dehydroepiandrosterone (DHEA) sulfate, or DHEAS, the 3-sulfoconjugate of DHEA DHEAS is carried to peripheral tissues via the systemic circulation, where it is converted to DHEA DHEA, along with androstenedione, are converted to either testosterone or estrogen This production is a small fraction of the total production of these hormones, as the majority of testosterone and estrogen are produced in the testes and ovaries, respectively The catecholamines produced by the adrenal medulla include epinephrine and norepinephrine, in a ratio of 80:20, respectively Dopamine is a precursor to norepinephrine and, like norepinephrine, exerts many of its effects as a neurotransmitter The catecholamines mediate the fight-or-flight response to stress in two main ways: • Control of blood flow The catecholamines activate both α1- and β1-adrenergic receptors, causing vasoconstriction and positive inotropy and chronotropy, respectively This process maintains cardiac output and increases perfusion of vital organs in the setting of increased demand They also cause constriction of the splanchnic vessels, shunting blood flow away from the gut, and dilation of skeletal muscle, promoting blood flow and oxygen delivery Epinephrine also has a bronchodilatory effect, increasing oxygen absorption in the lungs and availability in the systemic circulation 285 www.ajlobby.com Mizukawa_Chap_20.indd 285 6/20/17 10:44 AM 20 • The Endocrine System • Energy Epinephrine also provides substrate for energy metabolism by promoting glycogenolysis and gluconeogenesis from muscle and adipose tissue via the β2 receptor Energy demand is also reduced by visceral smooth muscles, such as the gastrointestinal tract, to provide energy to skeletal muscle, cardiac muscle, and the brain.4 Major endocrine axes and pathways Hormone secretion and blood concentration is tightly regulated by a variety of factors, including feedback mechanisms (both negative and positive) and circadian rhythms Endocrine pathways/axes are often used to describe hormone actions in a simplified manner See the schematic representation of common axes in Fig 20-5 a b c d Fig 20-5 The hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-thyroid (HPT), and male and female hypothalamicpituitary-gonad (HPG) axes CRH, corticotropin-releasing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropinreleasing hormone; LH, luteinizing hormone; TRH, thyrotropin-releasing hormone 286 www.ajlobby.com Mizukawa_Chap_20.indd 286 6/20/17 10:44 AM Diabetes Mellitus Diabetes Mellitus Pathophysiology and diagnosis Diabetes mellitus is the most common endocrinopathy in the United States; 90% of patients with diabetes mellitus have type and 10% have type 1.5 Type diabetes mellitus is an autoimmune disease that causes destruction of pancreatic β-cells (insulin-producing cells) and thus a deficiency in insulin These patients are often diagnosed early in life and require exogenous insulin for survival, or they will develop ketoacidosis.6 Type diabetes mellitus is characterized by insulin resistance and abnormal β-cell function; type diabetes mellitus is often associated with obesity.5 Symptoms of diabetes mellitus include: polyphagia, polydipsia, polyuria, fatigue, and unexplained weight loss (Box 20-1).6 Acute hyperglycemia causes impaired wound healing, dehydration, increased risk of infection, and hyperviscosity with thrombogenesis.7 Delayed wound healing can be seen in diabetic patients with a blood glucose level greater than 250 mg/dL (even in the absence of end-organ damage) as a result of impaired granulocyte phagocytosis, chemotaxis, and bacterial killing, as well as impaired collagen and procollagen synthesis, capillary growth, and fibroblast proliferation.8 Chronic hyperglycemia is associated with end-organ damage, including nephropathy, peripheral neuropathy, retinopathy, dyslipidemia, cardiovascular/cerebrovascular/peripheral vascular diseases, diabetic ketoacidosis (mostly in patients with type 1), and hyperglycemic hyperosmolar syndrome (mostly in patients with type 2).6 BOX 20-1 • • • • • • • • Symptoms of hyperglycemia Polyphagia Polydipsia Polyuria Fatigue Unexplained weight loss Impaired wound healing Dehydration Increased risk of infection • • • • • • • • Hyperviscosity with thrombogenesis Nephropathy Neuropathy Retinopathy Dyslipidemia Vascular disease Diabetic ketoacidosis (type 1) Hyperglycemic hyperosmolar syndrome (type 2) Diagnosis of diabetes mellitus is made with one of the following: fasting blood glucose level > 126 mg/dL, hemoglobin A1c level > 6.5%, 2-hour plasma glucose level > 200 mg/dL after a 75-g oral glucose tolerance test, or symptoms of hyperglycemia with a random glucose level > 200 mg/dL.7 Management Type diabetes mellitus is managed with hypoglycemic agents (Table 20-2), and, on occasion, insulin Type diabetes mellitus is managed with exogenous insulin (Table 20-3) Proponents of tight glycemic control aim for blood glucose levels of 80 to 110 mg/dL for non–critically ill patients, although such tight glycemic control can increase the risk of hypoglycemia Thus, some aim for a less stringent target of < 140 mg/dL in non–critically ill patients For critically ill patients, the advised glucose target is 140 to 180 mg/dL.10 287 www.ajlobby.com Mizukawa_Chap_20.indd 287 6/20/17 10:44 AM 20 • The Endocrine System Table 20-2 Common noninsulin antidiabetic medications* Drug class Mechanism of action Half-life (h) Biguanides • Metformin Medication Decrease hepatic gluconeogenesis, increase insulin sensitivity 6–18 Sulfonylureas • Chlorpropamide • Tolbutamide • Glimepiride • Glipizide • Glyburide Stimulate insulin secretion, decrease insulin resistance 2–10 Meglitinides • Repaglinide • Nateglinide Stimulate pancreatic insulin secretion Thiazolidinediones • Rosiglitazone • Pioglitazone • Acarbose • Miglitol Regulate carbohydrate and lipid metabolism, reduce insulin resistance and hepatic glucose production 3–8 Reduce intestinal absorption of ingested glucose 2–4 Dipeptidyl peptidase-4 inhibitors • Sitagliptin • Saxagliptin Reduce breakdown of gastrointestinal hormones (incretins), enhance insulin secretion, decrease glucagon 8–14 Noninsulin injectables • Exenatide • Pramlintide Suppress glucagon secretion and hepatic glucose production, suppress appetite, delay gastric emptying 6–10 2–4 α-glucosidase inhibitors *Data from Agarwal et al6 and Joshi et al.9 Table 20-3 Common insulin medications* Drug class Medication Rapid-acting • Lispro • Aspart • Glulisine Short-acting Regular Intermediate-acting Onset Duration (h) 5–15 4–6 30–60 6–8 • Neutral protamine hagedorn • Zinc insulin • Extended zinc insulin 2–4 h 2–4 h 6–10 h 4–10 4–10 10–16 Long-acting (peakless) • Glargine • Detemir 2–4 h 20–24 Mixed insulins NPH/regular • Novolin 70/30 • Humulin 70/30 • Humulin 50/50 30–90 10–16 Aspart protamine/Aspart • Novolog mix 70/30 5–15 10–16 Lispro protamine/Lispro • Humalog 75/25 • Humalog 50/50 5–15 10–12 *Data from Agarwal et al6 and Joshi et al.9 288 www.ajlobby.com Mizukawa_Chap_20.indd 288 6/20/17 10:44 AM Diabetes Mellitus Anesthetic considerations Preoperative evaluation should include an assessment of medications, hospitalizations, hypoglycemic events, end-organ damage, and glycemic control Glycemic control can be evaluated by checking blood glucose levels and hemoglobin A1c A hemoglobin A1c level of ≤ 6.5% indicates well-controlled diabetes mellitus.11 A preoperative blood glucose level < 70 mg/dL indicates an increased risk of hypoglycemia, whereas a level > 250 mg/dL indicates a patient who has poorly controlled diabetes mellitus and who has increased risk of poor wound healing and vascular compromise.8 Diabetic patients should also be evaluated for limited joint mobility caused by glycosylation of proteins within the joints, as limited neck mobility can compromise the ability to intubate patients An easy way to test for joint mobility is to ask patients to hold the palms of their hands together (ie, in a prayer sign) and to assess if they are able to touch their fingers and palms fully together; inability to so suggests joint rigidity In diabetic patients, the clinician should also be aware of the increased risks of aspiration due to gastroparesis and silent ischemia (angina without chest pain).6 To minimize the disruption to their usual diabetic control regimen and glycemic control, diabetic patients should be scheduled for morning appointments and often require adjustments to their diabetic medications Perioperative management should include avoiding hypoglycemia and marked hyperglycemia Intraoperatively, blood glucose should be checked every to hours10; more frequent checks may be indicated in patients with other comorbidites, such as renal insufficiency Target blood glucose levels to maintain intraoperatively are between 80 and 200 mg/dL.5 For patients at risk for hypoglycemia, the practitioner may consider using a 5% dextrose solution for intravenous (IV) fluids to avoid a catabolic state Otherwise, normal saline is a good alternative Lactated Ringer solution is best avoided in patients with poorly controlled diabetes mellitus because of concern of hepatic conversion of lactate to glucose.6 Should hypoglycemia occur (blood glucose level < 50 mg/dL), the patient should be given glucose immediately (see section, “Hypoglycemia”) For marked hyperglycemia, insulin can be administered Hyperglycemia may be associated with the medical emergency diabetic ketoacidosis (DKA), which manifests with symptoms such as nausea, vomiting, polydipsia, polyuria, abdominal pain, Kussmaul respirations (deep, gasping, labored), altered level of consciousness, and possible coma Patients in DKA will be acidotic, dehydrated, hyperglycemic, and have ketones in their blood and urine Treatment requires hospitalization and includes: IV fluids, insulin, management of any underlying causes (ie, infection), and close observation Although administration of steroids should be done cautiously in diabetic patients, if dexamethasone is desired for anti-emetic and anti-inflammatory effects, it can be given as long as the practitioner is prepared to manage the subsequent elevation in the patient’s blood glucose level over the next hours.6 Regarding dosage, mg has been found to provide a sufficient anti-emetic effect while resulting in a smaller elevation of blood glucose levels than a dosage of mg.12 Postoperatively, patients should be encouraged to resume an oral diet as soon as possible and, once a normal diet is resumed, the patient should restart their normal diabetic medication regimen If the patient is unable to resume a normal diet soon after the surgical procedure, they should modify their diabetic medication under the advisement of their primary care physician until they are able to resume a normal diet (Box 20-2).1 289 www.ajlobby.com Mizukawa_Chap_20.indd 289 6/20/17 10:44 AM 20 • The Endocrine System BOX 20-2 Management of diabetic patients for ambulatory surgery* Preoperative assessment • Type and dose of antidiabetic therapy • Blood glucose and/or hemoglobin A1c level • Assess for end-organ damage • Hypoglycemia occurrences: frequency, manifestations, blood glucose level at which symptoms occur • Hospitalizations related to diabetic complications • Assess patient’s ability to monitor his or her blood glucose level and manage diabetes • Check joint rigidity (prayer test) to assess for limited neck range of motion • Schedule morning appointments • Remember increased risk of silent ischemia • Remember increased risk of aspiration due to gastroparesis Management of antidiabetic medications • Oral antidiabetic and noninsulin injectable therapy –– Hold on the day of the surgical procedure until a normal diet is resumed • Insulin –– Day before the surgical procedure °° No change in basal insulin regimen (unless the patient has a history of hypoglycemia) –– Day of surgical procedure °° Insulin pump: no change °° Long-acting insulin: 75%–100% of morning dose °° Intermediate-acting insulin and fixed-combination insulin: 50%–75% of morning dose °° Short-acting and rapid-acting insulin: hold morning dose Intraoperative management • IV fluids –– In general, use normal saline and keep the patient well hydrated (hyperglycemia and NPO status causes hypovolemia) –– If concerned for hypoglycemia, use 5% dextrose solution –– Avoid lactated Ringer solution in patients with poorly controlled diabetes (hepatic conversion of lactate to glucose) • Check blood glucose level every hour –– Suggested blood glucose target perioperatively is 80–200 mg/dL –– Manage hypo/hyperglycemia accordingly: °° Hypoglycemia: administer oral glucose and/or IV dextrose and/or IM/IV glucagon † °° Hyperglycemia: administer subcutaneous rapid-acting insulin analogs Postoperative management • Consider antibiotics for patients with poorly controlled diabetes (increased risk of infection and delayed wound healing) • Encourage the patient to resume a normal diet as soon as possible • Once the patient is on a normal diet, he or she can resume an antidiabetic medication regimen • If the patient is unable to resume a normal diet on the day of the surgical procedure, antidiabetic medications should be adjusted under the advisement of the patient’s primary care physician NPO, nil per OS (nothing by mouth); IM, intramuscularly *Data from Agarwal et al6 and Joshi et al.9 † Typically, unit of insulin will lower blood glucose levels by ~25–30 mg/dL.5 If DKA is suspected, transfer the patient to the hospital for further management (IV fluids, insulin, management of underlying cause, and close observation) 290 www.ajlobby.com Mizukawa_Chap_20.indd 290 6/20/17 10:44 AM Hypoglycemia Hypoglycemia Pathophysiology and diagnosis Whipple’s triad describes the three criteria used to define hypoglycemia: (1) symptoms consistent with hypoglycemia, (2) a measured low blood glucose level (< 50 mg/dL in adults; < 40 mg/dL in children13), and (3) relief of symptoms when the blood glucose level is normalized Symptoms of hypoglycemia can vary from mild disorientation and lethargy to unconsciousness, seizure, or, rarely, death (Box 20-3) Hypoglycemia is most commonly caused by diabetic medications or insufficient carbohydrate intake, but many other causes are possible (Box 20-4).1 BOX 20-3 Symptoms of hypoglycemia* Mild stage • Diminished cerebral function • Altered mood/lethargic • Hunger • Nausea BOX 20-4 Moderate stage • Sweating • Tachycardia • Piloerection • Anxiety • Delirium • Uncooperativeness • Cold and wet skin Severe stage • Unconsciousness • Seizure • Death Causes of hypoglycemia in adults* In diabetic patients, hypoglycemia is most commonly caused by an excessive insulin dose and/or inadequate carbohydrate intake Other causes include: Ill or medicated individual • Drugs –– Insulin or insulin secretagogue –– Alcohol –– Others • Critical illness –– Hepatic, renal, or cardiac failure –– Sepsis –– Inanition • Hormone deficiency –– Cortisol –– Glucagon and epinephrine (in insulin-deficient diabetic patients) • Non–islet cell tumor Seemingly well individual • Endogenous hyperinsulinism –– Insulinoma (insulin-secreting tumor of the pancreas) –– Functional β-cell disorders (nesidioblastosis) °° Noninsulinoma pancreatogenous hypoglycemia syndrome °° Post–gastric bypass hypoglycemia –– Insulin autoimmune hypoglycemia °° Antibody to insulin °° Antibody to insulin receptor °° Insulin secretagogue °° Other • Accidental, surreptitious, or malicious hypoglycemia *Data from Cryer et al.14 291 www.ajlobby.com Mizukawa_Chap_20.indd 291 8/10/17 9:35 AM 20 • The Endocrine System Management Hypoglycemia is an acute problem and must be managed urgently Administration of glucose should be performed promptly when hypoglycemia is suspected; one should not delay the administration of a glucose agent to obtain a blood glucose reading, as the risk of acute hypoglycemia is greater than that of acute hyperglycemia A blood glucose level can be measured at the time of glucose agent administration or soon thereafter Conscious patients should be administered oral glucose in the form of glucose tablets/gel, juice, regular soda, candy, honey, or sugar Once their glucose level has increased to a value no longer indicative of acute hypoglycemia, patients should be encouraged to consume a more complex carbohydrate and protein food to sustain their blood glucose level For patients who not respond to oral glucose treatment or who have loss of consciousness, intramuscular (IM)/IV glucagon (0.025 to 0.1 mg/kg up to mg) and/or IV dextrose (1 mL/kg up to 50 mL for 50% dextrose; 10 mL/kg up to 500 mL for dextrose 5% in water [D5W]) should be administered IM/IV glucagon has an onset of action within approximately 10 to 20 minutes and a peak response within 30 to 60 minutes IV dextrose solution usually shows a response within minutes (Boxes 20-5 and 20-6).11 BOX 20-5 Management of hypoglycemia: Conscious patient Recognize problem (altered consciousness) Discontinue treatment Position the patient comfortably Check ABCs; assess and perform basic life support as needed Administer O2 Monitor vital signs every minutes Measure blood glucose level if equipment is available Administer oral glucose (eg, glucose tablets/gel, juice, soda) Reassess clinical symptoms and blood glucose level If patient responds appropriately: • Encourage consumption of complex carbohydrate with protein • Discharge patient when he or she has recovered If patient does not respond to oral glucose: • Administer IM/IV glucagon or IV dextrose ABCs, airway, breathing, circulation 292 www.ajlobby.com Mizukawa_Chap_20.indd 292 6/20/17 10:44 AM Hyperthyroidism BOX 20-6 Management of hypoglycemia: Unconscious patient* Recognize the problem (unresponsive) Discontinue treatment Position the patient in the supine position Check ABCs; assess and perform basic life support as needed Administer O2 Monitor vital signs every minutes Measure blood glucose level if equipment is available Administer carbohydrates: –– IM/IV glucagon: 0.025–0.1mg/kg up to mg –– IV 50% dextrose solution: mL/kg up to 50 mL –– IV D5W: 10 mL/kg up to 500 mL –– Transmucosal glucose syrup or rectal honey or syrup Reassess clinical symptoms and blood glucose level If patient responds appropriately: • Encourage consumption of a complex carbohydrate with protein • Discharge the patient when he or she has recovered or consider transfer to emergency department Activate EMS if consciousness is not restored ABCs, airway, breathing, circulation; EMS, emergency medical services *Data from Malamed.11 Anesthetic considerations For detailed considerations, see the previous section, “Diabetes Mellitus,” as most hypoglycemia cases occur in diabetic patients In general, it is advised to schedule patients for morning appointments, check a blood glucose level preoperatively (the patient has higher risk of developing hypoglycemia if his or her blood glucose level is < 70 mg/dL), recognize the signs and symptoms of hypoglycemia, and manage the condition promptly when indicated Hyperthyroidism Pathophysiology and diagnosis The most common cause of hyperthyroidism is Graves disease, which is an autoimmune disorder with circulating antibodies that mimic the effects of thyroid-stimulating hormone, thus causing an excessive production of thyroid hormones Other causes of hyperthyroidism include multinodular goiter, thyroid adenoma, and excessive exogenous thyroid hormones.15 The incidence of hyperthyroidism in the United States is between 0.05% and 1.3% overall, and up to 3% in patients aged 80 years and older.6 Signs and symptoms include: weight loss, heat intolerance, palpitations, cardiac arrhythmias, exophthalmos, thyroid enlargement, and profound hypertens ion (Box 20-7).7,16 Diagnosis is confirmed by blood tests showing decreased levels of TSH and elevated levels of T3 and T4 293 www.ajlobby.com Mizukawa_Chap_20.indd 293 6/20/17 10:44 AM 20 • The Endocrine System BOX 20-7 Hyperthyroidism: Signs and symptoms • Weight loss with increased appetite • Heat intolerance • Palpitations • Exophthalmos • Thyroid enlargement • Tachycardia • Increased cardiac output • Profound hypertension • Cardiac arrhythmias (sinus tachycardia, atrial fibrillation) • Nervousness • Fatigue • Weakness • Excessive sweating • Dyspnea • Diarrhea • Insomnia • • • • • • • • Poor concentration Oligomenorrhea Hair loss Warm, moist skin Hyperkinesis Lid lag Emotional liability Hyperactive tendon reflexes Management Management options for hyperthyroidism include radioactive iodine, surgery (thyroidectomy), or antithyroid drugs such as methimazole, propylthiouracil, or inorganic iodide β-blocker therapy is also used to manage sympathetic symptoms Patients who undergo radioactive iodine therapy or surgery can develop hypothyroidism, depending on the extent of gland removal and/or destruction.6 Anesthetic considerations Preoperative evaluation should include a thorough discussion of the patient’s thyroid disorder Patients with untreated, uncontrolled, or recently diagnosed thyroid disease are not candidates for outpatient sedation.17 Patients with goiter have increased potential for airway obstruction and increased difficulty with intubation.6 For patients with arrhythmias (atrial fibrillation or sinus tachycardia), an electrocardiogram (ECG) and medical clearance should be obtained, as it can indicate refractory hyperthyroidism For patients who are well controlled (ie, have been euthyroid for at least to weeks) and who are followed closely by their physician, laboratory tests are not usually necessary, but, if in doubt, medical consultation and/or laboratory evaluation (including free T3, free T4, and TSH) is recommended Patients taking antithyroid medications and/or β-blockers should take their medications as scheduled.6 Intraoperatively, excessive adrenergic signs should be managed with β-blocker therapy (propranolol, esmolol, metoprolol, or atenolol) and cessation of surgery For patients with exophthalmos, it is advised to use eye protection Hypotension can be managed with IV fluids, decreased level of anesthesia, and/or phenylephrine as needed Anticholinergic medications including atropine and glycopyrrolate should be avoided, as should sympathetic nervous system stimulants, including ketamine, ephedrine, and IV epinephrine Nitrous oxide, opioids, and benzodiazepines are considered safe to use.7 Thyroid storm is a life-threatening exacerbation of hyperthyroidism that can occur anytime in the perioperative period, although it most commonly occurs intraoperatively or within the first 48 hours after the operation.5 It is a hypermetabolic state induced by excessive free thyroid hormones Mortality rates are reported at 10% to 75% Symptoms include hyperpyrexia (up to 41.1°C or 106°F), tachycardia, extreme anxiety, delirium, and prolonged recovery.5,6 Differential diagnosis should include malignant hyperthermia, neuroleptic malignant syndrome, and pheochromocytoma Patients require monitoring in a critical care unit and treatment with thioamides, β-blockers (goal heart rate of < 90 beats per minute), and antipyretics or external cooling measures (Box 20-8).5 294 www.ajlobby.com Mizukawa_Chap_20.indd 294 6/20/17 10:44 AM Hypothyroidism BOX 20-8 Management of hyperthyroid patients for ambulatory surgery* Preoperative assessment • Patient should be euthyroid for at least to weeks • If the patient is euthyroid for > to weeks and closely followed by his or her primary care physician, no laboratory tests are required • But, if in doubt, a medical consultation and/or laboratory evaluation (including free T3, free T4, and TSH) is recommended Management of antithyroid medications • Antithyroid medications and β-blockers should be continued as scheduled Intraoperative management • Avoid anticholinergic medications (atropine, glycopyrrolate) • Avoid sympathetic nervous system stimulants (ketamine, ephedrine, epinephrine) • Safe to use: nitrous oxide, opioids, and benzodiazepines • Hypotension can be managed with IV fluids, decreased level of anesthesia, and/or phenylephrine Thyroid storm (life-threatening thyrotoxicosis) • Possible causes: surgery, trauma, infection, stress, abrupt cessation of antithyroid medications, inadequately managed thyrotoxicosis, or exposure to exogenous iodine • Symptoms: hyperpyrexia, tachycardia, extreme anxiety, delirium, and prolonged recovery • Management: β-blockers, antipyretics and/or external cooling measures, antithyroid medications (PTU per orogastric tube or per rectum), corticosteroids, fluid resuscitation, monitoring in critical care unit PTU, propylthiouracil *Data from Agarwal et al6 and Njoku.10 Hypothyroidism Pathophysiology and diagnosis Hypothyroidism affects approximately 10% of adults aged 65 years and older and is more prevalent in females.6 Primary hypothyroidism accounts for 95% of all cases, which is characterized by low thyroid hormone levels (free T4) and normal or increased TSH levels Causes of primary hypothyroidism include autoimmune disease (Hashimoto thyroiditis), surgical thyroid resection, and radioiodine therapy Lithium, amiodarone, iron, and cholestyramine have also been found to induce hypothyroidism.5 Hypothyroidism can also be a result of secondary hypothyroidism due to a dysfunctional pituitary axis.6 Symptoms include fatigue, cold intolerance, lethargy, and weight gain (Box 20-9) 295 www.ajlobby.com Mizukawa_Chap_20.indd 295 6/20/17 10:44 AM 20 • The Endocrine System BOX 20-9 • • • • • • • • • • Signs and symptoms of hypothyroidism* • • • • • • • • • • Weight gain Cold intolerance Fatigue Sleepiness Deepening/hoarseness of voice Muscle aches Bradycardia Dry skin Coarse and/or brittle hair Edema (especially periorbital) Impaired memory and/or concentration Decreased stroke volume Decreased cardiac output Increased peripheral vascular resistance Impaired baroreceptor function Decreased maximal breathing capacity Decreased renal excretion Headache Anorexia Depression *Data from Agarwal et al.6 Management Hypothyroidism is preferably managed with the thyroid medication levothyroxine.5 Another medication that can be used is liotrix Anesthetic considerations Similar to hyperthyroidism, preoperative assessment should include a complete discussion of the patient’s thyroid disorder, and patients should be euthyroid before proceeding with outpatient sedation.17 Patients who have been euthyroid for at least to weeks and who are followed closely by their physician usually not require laboratory tests.6 However, if the status of the patient’s thyroid condition is uncertain, a medical consultation with the patient’s primary care physician and/or laboratory tests (including TSH and free T4) is recommended.18 Elective surgery should be delayed in cases of uncontrolled disease Patients should continue their medication dosing schedule, including morning doses, on the day of the surgical procedure.6 Perioperative management includes taking caution when administering anesthetics Hypothyroid patients have decreased gastric emptying and may have some degree of decrease in cardiac reserves The presence of a neck goiter can make airway access difficult Hypotension seems to react best to ephedrine, epinephrine, or dopamine, as opposed to a pure α-agonist Hypothyroid patients have increased sensitivity to anesthetics, and careful titration should be done to avoid oversedation.7 Opioids and local anesthetics can be used, but with the understanding that the overdose thresholds may be decreased.18 Medications to avoid include ketamine, atropine, and other medications that can increase the demand on the heart (Box 20-10).6 296 www.ajlobby.com Mizukawa_Chap_20.indd 296 6/20/17 10:44 AM Hypercortisolism (Cushing Syndrome) B O X - 0 Management of hypothyroid patients for ambulatory surgery* Preoperative assessment • The patient should be euthyroid for at least to weeks • If the patient has been euthyroid for > to weeks and closely followed by his or her primary care physician, no laboratory tests are required • But, if in doubt, a medical consultation and/or laboratory evaluation (including free T4 and TSH) is recommended Management of thyroid medications • Thyroid medication should be continued as scheduled Intraoperative management • Titrate local anesthetics and opioids carefully because of increased sensitivity and lower overdose thresholds • Avoid sympathetic nervous system stimulants (ketamine, ephedrine, epinephrine) *Data from Agarwal et al6 and Njoku.10 Hypercortisolism (Cushing Syndrome) Pathophysiology and diagnosis Cushing syndrome describes hypercortisolism from either an adrenal tumor or hyperplasia, ectopic ACTH from neoplasms, or exogenous steroid or ACTH administration Clinical manifestations of hypercortisolism include: central obesity, buffalo hump, moon face, osteoporosis, glucose intolerance, hirsutism, hypertension, and electrolyte imbalances (eg, hypokalemia, hypernatremia, metabolic alkalosis) (Box 20-11) Diagnosis is made by means of a dexamethasone suppression test and a free urinary cortisol measurement.18 B OX -11 Signs • • • • • • • and symptoms of hypercortisolism* Central obesity Moon face Buffalo hump Osteoporosis Glucose intolerance Hirsutism Hypertension • • • • • • • Electrolyte imbalances Hypokalemia Hypernatremia Metabolic alkalosis Diabetes Myopathy Easy bruising (although normal coagulation profile) *Data from Stoelting and Miller15 and the American Association of Oral and Maxillofacial Surgeons.18 Administration of exogenous glucocorticosteroids results in secondary adrenal insufficiency due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis Thus, when these patients are exposed to stress (ie, a surgical procedure), they will have impaired ability to produce cortisol in response.6 Patients who have taken 20 mg or more per day of prednisone for more than weeks in the past year are assumed to have adrenal suppression; < mg per day of prednisone for any length of time does not cause any significant HPA suppression; doses between and 20 mg per day may cause HPA suppression.7 For patients with HPA suppression, surgical stress can trigger adrenal crisis (see hypocortisolism section) 297 www.ajlobby.com Mizukawa_Chap_20.indd 297 6/20/17 10:44 AM 20 • The Endocrine System Management Management of hypercortisolism depends on the underlying etiologic processes and may require surgery of the pituitary or adrenal gland lesions, radiation of the pituitary, or the discontinued use of corticosteroids.18 Anesthetic considerations Preoperative evaluation requires a determination of the underlying etiologic processes If the patient is taking corticosteroids, the clinician must know why they are being taken as well as which steroid is being taken at what dose and duration The underlying disease must be evaluated to determine stability.6 An ECG and electrolyte and glucose levels should be obtained preoperatively given common findings of electrolyte imbalances, diabetes mellitus, hypertension, and risk of arrhythmias in these patients.15 Intraoperative management concerns focus on determining the amount of stress the patient is to experience and a consideration of the amount of HPA suppression the patient likely has Given that the risk and negative side effects of short-term glucocorticosteroid use at the recommended doses is low when compared with the severity of adrenal crisis, many support the strategy of administering perioperative steroid coverage by doubling the morning dose on the day of the surgical procedure.6 If any questions arise, the patient’s primary care physician should be consulted Postoperatively, the clinician may want to consider antibiotic administration given the risk of impaired wound healing and infection in these patients (Box 20-12) BOX 20-12 Management of hypercortisolism patients for ambulatory surgery* Preoperative assessment • Determine the underlying etiologic process and stability of that disease process • Determine if the patient is taking steroids, and if so, which one, dose, and duration • Check preoperative ECG, electrolytes, and blood glucose levels • Consider medical consult to discuss HPA suppression risk relative to planned surgical stress to determine perioperative steroid coverage requirements Intraoperative management • Consider perioperative steroid coverage: the commonly followed regimen is to double the morning dose on the day of the surgical procedure for patients with HPA suppression who will experience surgical stress • Use stress reduction techniques, including pain control with local anesthesia and analgesics Postoperative management • Consider the use of antibiotics given the risk of impaired wound healing and infection *Data from Agarwal et al6 and Stoelting and Miller.15 298 www.ajlobby.com Mizukawa_Chap_20.indd 298 6/20/17 10:44 AM Hypocortisolism (Adrenal Insufficiency) Hypocortisolism (Adrenal Insufficiency) Pathophysiology and diagnosis Primary adrenocortical insufficiency, or primary adrenal insufficiency, is called Addison disease The incidence is estimated to be between 0.3 and case per 100,000 people worldwide, occurring equally in both sexes and in all age groups.11 The most common cause of Addison disease is autoimmune adrenalitis Other causes of adrenal insufficiency include adrenal dysgenesis, impaired steroidogenesis, and corticosteroid withdrawal Clinical manifestations include fatigue, anorexia, hypoglycemia, nausea/vomiting, postural dizziness, hyperpigmentation, hypotension, tachycardia, perspiration, electrolyte disturbances, and anemia (Box 20-13).2 Diagnosis of hypoadrenalism is made on the basis of a low cortisol level, low fasting blood glucose level, hyperkalemia, hyponatremia, ACTH stimulation test, and radiographs.18 B O X - Signs • • • • • • • and symptoms of hypocortisolism* • • • • • • Fatigue Anorexia Hyperpigmentation Hypoglycemia Nausea/vomiting/diarrhea Postural dizziness Hypotension Tachycardia Perspiration Electrolyte disturbances Hyponatremia Hyperkalemia Anemia *Data from Kronenberg et al.2 Acute adrenal insufficiency results when the body is unable to have a sufficient cortisol response to stress, which can occur as a result of secondary adrenal insufficiency from exogenous steroid use or primary adrenal insufficiency Acute adrenal insufficiency is a true medical emergency Signs and symptoms include progressively severe mental confusion, extreme fatigue/lethargy, hyperkalemia, hypotension, hypoglycemia, intense pain in the abdomen/legs/lower back, progressive deterioration of the cardiovascular system, and loss of consciousness It may lead to death due to peripheral vascular collapse and ventricular asystole.11 Management Patients with primary adrenal insufficiency require administration of exogenous corticosteroids for the duration of their life Usual dosing is 20 mg of exogenous cortisol (hydrocortisone) daily.11 Anesthetic considerations Perioperative management of patients with adrenal insufficiency is similar to that of patients with Cushing syndrome During preoperative assessment, the clinician must determine which steroid the patient is taking, as well as dose and duration An ECG as well as electrolytes and blood glucose levels should be checked preoperatively.15 Perioperative management should include stress reduction protocols, including local anesthesia and analgesic administration Perioperative steroid coverage may be considered; the commonly followed regimen is to double the morning dose of exogenous steroid on the day of the surgical procedure Medical consultation may be warranted to determine appropriate perioperative steroid coverage requirements Etomidate should be avoided in patients with adrenal insufficiency due to its inhibition of steroid synthesis.5 Antibiotic therapy may be considered because of impaired wound healing in these patients (Box 20-14) 299 www.ajlobby.com Mizukawa_Chap_20.indd 299 6/20/17 10:44 AM 20 • The Endocrine System Management of hypocortisolism patients for ambulatory surgery* BOX 20-14 Preoperative assessment • Determine steroid management: type, dose, duration • Check preoperative ECG, electrolytes, and blood glucose levels • Consider a medical consultation to discuss perioperative steroid coverage requirements Intraoperative management • Consider perioperative steroid coverage: the commonly followed regimen is to double the morning dose on day of the surgical procedure • Use stress reduction techniques, including pain control with local anesthesia and analgesics Postoperative management • Consider the use of antibiotics given the risk of impaired wound healing and infection *Data from Agarwal et al6 and Stoelting and Miller.15 Should a patient develop acute adrenal insufficiency, they should be positioned in the supine position, and corticosteroids (4 mg of dexamethasone or 100 mg of hydrocortisone), dextrose, and IV fluids should be promptly administered Vital signs should be closely monitored (every minutes) and supplemental oxygen should be given It is advised to contact the patient’s primary care physician or activate emergency medical services (EMS) for patients with loss of consciousness (Box 20-15).11 B O X - Management of acute adrenal insufficiency* 1. Recognize the problem (see signs and symptoms) 2. Discontinue treatment 3. Position the patient in the supine position 4. Check ABCs; assess and perform basic life support as needed 5. Administer O2 6. Monitor vital signs every minutes 7. Administer steroids: –– mg dexamethasone IV or 100 mg hydrocortisone (Solu-Cortef [Pfizer]) IV 8. Administer IV fluids: –– L of 5% dextrose 9. Reassess clinical symptoms and blood glucose level 10. Manage hypoglycemia as needed Activate EMS if patient loses consciousness ABCs, airway, breathing, circulation *Data from Malamed.11 300 www.ajlobby.com Mizukawa_Chap_20.indd 300 6/20/17 10:44 AM References References 11 Malamed SF Medical Emergencies in the Dental Office, ed St Louis: Mosby, 2007 Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J Harrison’s Principles of Internal Medicine, ed 18 New York: McGraw-Hill, 2012 Gardner DG, Shoback D Greenspan’s Basic and Clinical Endocrinology, ed New York: McGraw-Hill, 2007 12 Chen H, Sippel RS, O’Dorisio MS, et al North American Neuroendocrine Tumor Society (NANETS) The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: Pheochromocytoma, paraganglioma, and medullary thyroid cancer Pancreas 2010;39:775–778 White BA, Porterfield SP The adrenal gland In: White BA, Porterfield SP Endocrine and Reproductive Physiology, ed St Louis: Mosby, 2013:147–176 13 Sperling MA Hypoglycemia In: Behrman RE, Kliegman RM, Jenson HB (eds) Nelson Textbook of Pediatrics, ed 17 Philadelphia: Saunders, 2003:505–518 Kohl BA, Schwartz S How to manage perioperative endocrine insufficiency Anesthesiol Clin 2010;28:139–155 14 Cryer PE, Axelrod L, Grossman AB, et al Endocrine Society Evaluation and management of adult hypoglycemic disorders: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2009;94:709–728 Kronenberg HM, Melmed S, Polonsky KS, Larsen PR Williams Textbook of Endocrinology, ed 11 Philadelphia: Saunders, 2007 Agarwal R, Porter MH, Obeid G Common medical illnesses that affect anesthesia and their anesthetic management Oral Maxillofac Surg Clin North Am 2013;25:407–438 15 Stoelting RK, Miller RD Basics of Anesthesia, ed London: Churchill Livingstone, 2006 Wall RT III Endocrine disease In: Hines RL, Marschall KE (eds) Stoelting’s Anesthesia and Co-existing Disease, ed Philadelphia: Saunders, 2012:376–406 16 Skugor M, Fleseriu M Hypothyroidism and hyperthyroidism In: Carey WD (ed) Cleveland Clinic: Current Clinical Medicine, ed Philadelphia: Saunders, 2010:416–419 Van Norman GA Preoperative assessment of common diseases in the outpatient setting Anesthesiol Clin North Am 1996;14:631–654 17 Murkin JM Anesthesia and hypothyroidism: A review of thyroxine physiology, pharmacology, and anesthetic implications Anesth Analg 1982;61:371–383 Joshi GP, Chung F, Vann MA, et al Society for Ambulatory Anesthesia Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery Anesth Analg 2010;111:1378–1387 18 American Association of Oral and Maxillofacial Surgeons Parameters of Care: Clinical Practice Guidelines for Oral and Maxillofacial Surgery (AAOMS ParCare 2012) Chicago: AAOMS, 2012 10 Njoku MJ Patients with chronic endocrine disease Med Clin North Am 2013;97:1123–1137 301 www.ajlobby.com Mizukawa_Chap_20.indd 301 6/20/17 10:44 AM www.ajlobby.com Mizukawa_Chap_20.indd 302 6/20/17 10:44 AM CHAPTER 21 The Musculoskeletal System Musculoskeletal Andrew Cheung, dds Matthew Mizukawa, dmd Lindsey Nagy, dds Travis Witherington, dds Joshua Campbell, dds www.ajlobby.com Mizukawa_Chapter_Openers.indd 303 7/11/17 12:20 PM CHAPTER 21 The Musculoskeletal System Normal Anatomy and Physiology 305 Scleroderma 307 Muscular Dystrophy 310 Myasthenia Gravis 312 Musculoskeletal Marfan Syndrome 315 www.ajlobby.com Mizukawa_Chapter_Openers.indd 304 7/11/17 12:20 PM Normal Anatomy and Physiology Musculoskeletal diseases have a wide variety of causes, ranging from autoimmune destruction of tissue to genetically determined defects in muscle membrane protein to pharmacologically induced alterations in calcium metabolism In some cases, the origin of the disease is unknown Musculoskeletal defects may reside in the neuromuscular junction, the muscle infrastructure, or the skeletal support structures A thorough knowledge of the normal anatomy and the nature of these defects are important in recognizing the anesthesia implications associated with musculoskeletal disease Although myriad diseases affect the musculoskeletal system, this chapter will review conditions that have salient anesthesia considerations Normal Anatomy and Physiology Motor unit Somatic musculature is broadly classified into skeletal and smooth variants based on anatomical and functional roles Skeletal muscle is under voluntary control, and smooth muscle is found in most internal organs except the heart Skeletal muscle is innervated by myelinated efferent motor nerve fibers (α motor neurons) These fastconducting somatic fibers arise from cell bodies located in the anterior or ventral horn of the spinal cord gray matter (Fig 21-1) Sensory neuron To brain Painful stimulus Dorsal root ganglion Spinal cord Biceps Motor neuron Triceps Fig 21-1 The pain reflex When the finger encounters a painful stimulus, an action potential is sent down the afferent sensory neuron to the spinal cord There it synapses with an excitatory interneuron that subsequently synapses with the efferent motor neuron to the bicep muscle, causing contraction and withdrawal of the hand from the stimulus It also synapses with an inhibitory interneuron that blocks the action of the tricep muscle, allowing the withdrawal of the hand The motor nerve axon exits through the spinal cord ventral root and travels uninterrupted to the muscle through a mixed peripheral nerve Inputs to the motor nerve cell body are both excitatory and inhibitory The inputs include neurons from the brain, neurons from other spinal cord segments, and afferent neurons from various sensory receptors.1 A motor neuron fires an action potential when the sum of the excitatory and inhibitory inputs depolarizes the nerve cell body to its critical threshold potential Threshold depolarization of the cell body produces local electrical currents that spread to adjoining regions of the nerve membrane, leading to further depolarization and action potential propagation down the axon 305 www.ajlobby.com Mizukawa_Chap_21.indd 305 6/20/17 10:47 AM 21 • The Musculoskeletal System As the nerve approaches the muscle tissue, it divides into branches that end on individual muscle cells, called muscle fibers A single motor neuron and all the muscle fibers it innervates are collectively called a motor unit1 (Fig 21-2) Motor neurons Nucleus Muscle fibers Myofibrils Fig 21-2 A single motor neuron and its innervation to the muscle fibers When a motor nerve fires, all of the fibers within a single motor unit contract simultaneously Motor units exhibit considerable variability, with each unit typically containing between 100 and 200 muscle fibers However, the motor unit may contain as few as two muscle fibers for fine, delicate movements or as many as 1,000 for coarse movements Larger motor units have larger nerve cell bodies and greater axon diameters than smaller units Neuromuscular junction Motor neurons that innervate skeletal muscle originate in the anterior (ventral) horn of the spinal cord As the nerve impulse reaches the terminal of the motor nerve, voltage-gated calcium channels open and allow calcium to enter the terminal This event triggers vesicles filled with acetylcholine (ACh) to undergo exocytosis, releasing ACh into the synaptic cleft of the motor end plate Nicotinic ACh receptors (AChRs) are embedded in the lipid bilayer of the presynaptic nerve terminal, serving as a positive feedback mechanism As ACh binds to the presynaptic receptors, more ACh is synthesized and released Nicotinic receptors are also found postsynaptically in the membrane of the motor end plate, propagating the electrical activity from the motor neuron to the muscle This transmission requires both α-subunits of the receptor to bind to ACh The AChR is an ion channel that conducts sodium and calcium into the cell and potassium out, resulting in an excitatory potential When enough AChRs are activated to depolarize the motor end plate to its threshold, an action potential is propagated along the muscle, and contraction is seen Binding of ACh to AChR is very brief, approximately millisecond, and then ACh dissociates from the receptor and is released back into the synaptic cleft Acetylcholinesterase (AChE), also known as “true” cholinesterase, which is found in close proximity to the postsynaptic nicotinic receptors, extends into the synaptic cleft to metabolize ACh to choline and acetate As ACh is metabolized, the motor end plate repolarizes, and the muscle cell becomes ready for another release of ACh from the nerve terminal The choline is transported back into the nerve terminal, where it is used to resynthesize ACh (Fig 21-3) 306 www.ajlobby.com Mizukawa_Chap_21.indd 306 6/20/17 10:47 AM Scleroderma Presynaptic neuron Action potential Ca2+ Ca2+ Nerve terminal Voltage-gated Ca2+ Cytoplasm Synaptic vesicles Synaptic cleft ACh receptor Ca2+ ACh Sarcolemma Na+ ACh Sarcoplasm Postsynaptic potential Action potential Muscle contraction Fig 21-3 Neuromuscular junction (1) The motor nerve action potential arrives at and depolarizes a nerve terminal (2) Depolarization causes voltage-gated calcium channels to open, and calcium diffuses down a concentration gradient into the nerve terminal (3) Inside the nerve terminal, calcium causes vesicles to fuse with the nerve cell membrane and open to the exterior, resulting in exocytosis of Ach into the synaptic cleft (4) Ach binds to the nicotinic receptors of the motor end plate (5) When both α-subunits of the nicotinic receptor channel are occupied by Ach, the channel snaps open, and sodium, calcium, and potassium ions diffuse through the channel Note: Sodium and calcium ions diffuse into the cell, and potassium ions diffuse out to the extracellular space (6) The diffusion of these three type of ions through the channel causes the motor end plate to depolarize (7) At a critical level of depolarization (threshold), an action potential is initiated (8) The action potential sweeps across the skeletal muscle cell and triggers contraction Scleroderma Pathophysiology and diagnosis Scleroderma (systemic sclerosis) is characterized by inflammation, vascular sclerosis, and fibrosis of the skin and viscera (Table 21-1) Microvascular changes produce tissue fibrosis and organ sclerosis Injury to vascular endothelial cells results in vascular obliteration and leakage of serum proteins into the interstitial space These proteins produce tissuea edema, lymphatic obstruction, and, ultimately, fibrosis In some patients, the disease evolves into CREST syndrome (calcinoses, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, telangiectasia) The prognosis is poor and is related to the extent of visceral involvement No drugs or treatments have proven to be safe and effective in altering the underlying disease process.2 307 www.ajlobby.com Mizukawa_Chap_21.indd 307 6/20/17 10:47 AM 21 • The Musculoskeletal System Table 21-1 Summary of scleroderma Condition Scleroderma General comments/ pathophysiology Meaning literally “hard skin,” this group of conditions affects the skin and connective tissues, can manifest as stiff joints and Raynaud phenomenon, a symptom of scleroderma a. Systemic sclerosis b. Limited sclerosis Sometimes associated with CREST syndrome Organ systems involved Skin (especially fingers, hands, face); detection of calcinosis (skin deposits); pulmonary, cardiac, renal, and gastrointestinal involvement Anesthetic considerations Management Work-up Blood pressure management, management for abnormal kidney and lung function, chronic management for gastrointestinal issues, surgery for calcinosis, glucocorticoids, cyclophosphamide Pulmonary function tests to determine interstitial lung disease; for pulmonary vascular disease/pulmonary hypertension, consider preoperative arterial blood gases Endotracheal intubation is a challenge because of decreased mouth aperture; consider avoiding respiratory depressants in office-based surgery Renal work-up for hypertension, albuminuria Hypertension, renal crisis (10% to 15% of patients, usually those with earlystage diffuse scleroderma) Cardiac work-up Heart failure, conduction block, dysrhythmias (from fibrosis) Gastrointestinal work-up for chronic gastroesophageal reflux, chronic esophagitis, stricture formation, Barrett esophagus, abnormal motility Lessened coughing mechanism, higher retention of secretions, increased risk of aspiration (secondary to esophageal dysmotility and gastroesophageal sphincter incompetence) Skin, heart, lungs, kidneys, digestive system; vascular injury and subsequent chronic damage underlie serious complications Difficult IV access (skin scleroderma) Skin Difficult IV access (skin scleroderma) IV, intravenous The etiology of scleroderma is unknown, but the disease process has the characteristics of both a collagen vascular disease and an autoimmune disease The typical age at onset is 20 to 40 years, and women are most often affected Pregnancy accelerates the progression of scleroderma in approximately half of patients The incidence of spontaneous abortion, premature labor, and perinatal mortality is high Manifestations of scleroderma occur in the skin and musculoskeletal system, nervous system, cardiovascular system, lungs, kidneys, and gastrointestinal tract Skin exhibits mild thickening and diffuse nonpitting edema As scleroderma progresses, the skin becomes taut, which results in limited mobility and flexion contractures, especially of the fingers Skeletal muscles may develop myopathy, manifested as weakness, particularly of proximal skeletal muscle groups The plasma creatine kinase concentration is typically increased Mild inflammatory arthritis can occur, but most limitation to joint movement is due to the thickened, taut skin Avascular necrosis of the femoral head may occur.2 308 www.ajlobby.com Mizukawa_Chap_21.indd 308 6/20/17 10:47 AM Scleroderma Peripheral or cranial nerve neuropathy has been attributed to nerve compression by thickened connective tissue surrounding the nerve sheath Facial pain suggestive of trigeminal neuralgia may occur as a result of this thickening Keratoconjunctivitis sicca (dry eyes) exists in some patients and may predispose to corneal abrasions Changes in the myocardium reflect sclerosis of small coronary arteries and the conduction system, replacement of cardiac muscle with fibrous tissue, and the indirect effects of systemic and pulmonary hypertension These changes result in cardiac dysrhythmias, cardiac conduction abnormalities, and congestive heart failure Intimal fibrosis of pulmonary arteries is associated with a high incidence of pulmonary hypertension, which may progress to cor pulmonale Pulmonary hypertension is often present, even in asymptomatic patients Pericarditis and pericardial effusion with or without cardiac tamponade are not infrequent Changes in the peripheral portion of the vascular tree are common and typically involve intermittent vasospasm in the small arteries of the digits Raynaud phenomenon occurs in most cases and may be the initial manifestation of scleroderma Oral or nasal telangiectasias may be present.2 The effects of scleroderma on the lungs are a major cause of morbidity and mortality Diffuse interstitial pulmonary fibrosis may occur independent of the vascular changes that lead to pulmonary hypertension Arterial hypoxemia resulting from decreased diffusion capacity is not unusual in these patients, even at rest Although dermal sclerosis does not decrease chest wall compliance, pulmonary compliance is diminished by fibrosis.2 Renal artery stenosis as a result of arteriolar intimal proliferation leads to decreased renal blood flow and systemic hypertension Development of malignant hypertension and irreversible renal failure used to be the most common cause of death in patients with scleroderma, but now scleroderma renal crisis is relatively rare Angiotensinconverting enzyme inhibitors are effective in controlling hypertension and in improving the impaired renal function that accompanies the hypertension Corticosteroids can precipitate a renal crisis in patients with scleroderma Involvement of the gastrointestinal tract by scleroderma may manifest as dryness of the oral mucosa (xerostomia) Progressive fibrosis of the gastrointestinal tract causes hypomotility of the lower esophagus and small intestine Dysphagia is a common complaint Lower esophageal sphincter tone is decreased, and reflux of gastric fluid into the esophagus is common Symptoms resulting from this esophagitis can be managed with antacids Bacterial overgrowth resulting from intestinal hypomotility can produce a malabsorption syndrome Coagulation disorders reflecting malabsorption of vitamin K may be present Broad-spectrum antibiotics are effective in the management of this type of malabsorption syndrome Intestinal hypomotility can also manifest as intestinal pseudo-obstruction Somatostatin analogs such as octreotide may improve intestinal motility Prokinetic drugs such as metoclopramide are not effective.2 Management Management for scleroderma is tailored to the individual patient, taking into account the disease subset and extent of organ involvement.2 Steroids have been extensively used with varying results and are typically used for patients with diffuse skin involvement and/or severe inflammatory organ involvement.2,3 Anesthesia considerations • Preoperative evaluation of patients with scleroderma must focus attention on the organ systems likely to be involved by this disease Decreased mandibular motion and narrowing of the oral aperture resulting from taut skin must be appreciated before induction of anesthesia • Fiberoptic laryngoscopy may be necessary to facilitate endotracheal intubation through a small oral aperture Oral or nasal telangiectasias may bleed profusely if traumatized during tracheal intubation • Intravenous access may be impeded by dermal thickening Intra-arterial catheterization for blood pressure monitoring introduces the same concerns as in patients with Raynaud phenomenon • Cardiac evaluation may provide evidence of pulmonary hypertension Because of chronic systemic hypertension and vasomotor instability, patients with scleroderma may have a contracted intravascular volume, which may produce hypotension during induction of anesthesia when anesthetic drugs with vasodilating properties exert their effects 309 www.ajlobby.com Mizukawa_Chap_21.indd 309 6/20/17 10:47 AM 21 • The Musculoskeletal System • Hypotonia of the lower esophageal sphincter puts patients at risk of regurgitation and pulmonary aspiration Efforts to increase gastric fluid pH with antacids or histamine receptor antagonists before induction of anesthesia are recommended • Intraoperatively, decreased pulmonary compliance may require higher airway pressures to ensure adequate ventilation Supplemental oxygen is indicated in view of the impaired diffusion capacity and vulnerability to the development of arterial hypoxemia Events known to increase pulmonary vascular resistance, such as respiratory acidosis and arterial hypoxemia, must be prevented • These patients may be particularly sensitive to the respiratory depressant effects of opioids, and a period of postoperative ventilatory support may be required in patients with severe pulmonary disease • The degree of renal dysfunction must be considered when selecting anesthetic drugs dependent on renal elimination Regional anesthesia may be technically difficult because of the skin and joint changes that accompany scleroderma Attractive features of regional anesthesia include peripheral vasodilation and postoperative analgesia Measures to minimize peripheral vasoconstriction include maintenance of the operatory temperature above 21°C and administration of warmed intravenous fluids The eyes should be protected to prevent corneal abrasions Muscular Dystrophy Pathophysiology and diagnosis Muscular dystrophy is a group of hereditary diseases characterized by painless degeneration and atrophy of skeletal muscles (Table 21-2) Progressive, symmetric skeletal muscle weakness and wasting but no evidence of skeletal muscle denervation is present Sensation and reflexes are intact Increased permeability of skeletal muscle membranes precedes clinical evidence of muscular dystrophy Table 21-2 Summary of muscular dystrophy Condition Muscular dystrophy General comments/ pathophysiology Hereditary disease with atrophy of skeletal muscles, depending on variant, also smooth muscle; generally, muscular dystrophy causes muscle weakness beginning in childhood and can start in adulthood Organ systems involved Brain, heart, pulmonary, musculoskeletal muscles Management Glucocorticoid treatment, orthopedic intervention, physical therapy Work-up Anesthetic considerations Pulmonary function Decreased ability to cough, loss of pulmonary reserve, risk of upperairway obstruction, hypoventilation, atelectasis, respiratory failure, reactions to inhaled anesthetics and certain muscle relaxants, difficulty weaning from mechanical ventilation, malignant hyperthermia risk, postoperative pneumonia Cardiac work-up (ECG, cardiac MRI)4 Congestive heart failure risk, degeneration of cardiac muscles leading to failure Baseline Consider shorter-acting agents and muscle function avoidance of respiratory depressants based on pulmonary function, and use caution with depolarizing and nondepolarizing agents ECG, electrocardiography; MRI, magnetic resonance imaging 310 www.ajlobby.com Mizukawa_Chap_21.indd 310 6/20/17 10:47 AM Muscular Dystrophy Patients with neuromuscular disorders are at risk of complications due to poor airway tone, poor secretion clearance, and chronic lower airway disease from chronic aspiration The risk of aspiration is compounded by abdominal muscle weakness with ineffective cough.5 Pseudohypertrophic muscular dystrophy, also known as Duchenne muscular dystrophy (DMD), is the most common and most severe form of childhood progressive muscular dystrophy The disease is caused by an X-linked recessive gene and becomes apparent in boys aged to years Initial symptoms include a waddling gait, frequent falling, and difficulty climbing stairs These findings reflect involvement of the proximal skeletal muscle groups of the pelvic girdle It is believed that DMD is the result of mutations in the dystrophin gene, a 2.5-Mb gene located on chromosome Xp21.1.6 Affected muscles become larger as a result of fatty infiltration, which accounts for the designation of this disorder as pseudohypertrophic Progressive deterioration occurs in skeletal muscle strength, and, typically, these boys are confined to a wheelchair by age to 10 years Kyphoscoliosis can develop Skeletal muscle atrophy can predispose to long bone fractures Mental retardation is often present Death usually occurs at 15 to 25 years of age as a result of congestive heart failure and/or pneumonia By age 30 years, 90% of DMD patients have cardiac involvement.7 The DMD patient develops a cardiomyopathy characterized by a progressive decline in ejection fraction This condition can lead to myocyte hypertrophy, atrophy, and fibrosis.6 Degeneration of cardiac muscle invariably accompanies this muscular dystrophy Characteristically, the electrocardiogram reveals tall R waves in lead V, deep Q waves in the limb leads, a short PR interval, and sinus tachycardia Mitral regurgitation may occur as a result of papillary muscle dysfunction or decreased myocardial contractility Chronic weakness of the respiratory muscles and a weakened cough result in loss of pulmonary reserve and accumulation of secretions These abnormalities predispose to recurrent pneumonia Respiratory insufficiency often remains covert because overall activity is so limited As the disease progresses, kyphoscoliosis contributes to further restrictive lung disease Sleep apnea may occur and may contribute to development of pulmonary hypertension Approximately 30% of deaths in individuals with pseudohypertrophic muscular dystrophy are due to respiratory causes.8 Children with DMD have increased chest wall compliance early in life; however, compliance gradually decreases with age, resulting in an interference with chest wall dynamics and contributing to relative hypoventilation Tongue hypertrophy can contribute to upper airway obstruction or intubation complexity.5 Management No treatment currently exists for individuals with DMD.3 Corticosteroids are used commonly to improve or preserve function.4 As of March 2017, deflazacort (Emflaza, Marathon Pharmaceuticals) has received FDA clearance for use to mitigate muscle weakness and cut inflammation with fewer side effects than prednisone.9 Unfortunately, gene therapy and cardiorespiratory support have been met with only mixed success.10 Anesthesia considerations • If pulse oximetry reveals saturation of peripheral capillary oxygen < 95%, measurement of carbon dioxide in the blood or end-tidal/transcutaneous CO2 should be obtained.5 • Pulmonary function testing, specifically a forced vital capacity (FVC) has predictive value DMD patients with FVC < 50% of predicted value are at increased risk for respiratory complications; patients with FVC < 30% are at high risk.5 • Preparation for anesthesia must take into consideration the implications of increased skeletal muscle membrane permeability and decreased cardiopulmonary reserve • Because of the association of DMD with dilated cardiomyopathy and dysrhythmias, the incidence of abnormal systolic function increases with age (> 80% of men older than 18 years old).5 311 www.ajlobby.com Mizukawa_Chap_21.indd 311 6/20/17 10:47 AM 21 • The Musculoskeletal System • The recommendation from the American Academy of Pediatrics is to have all DMD patients evaluated for a preoperative cardiac work-up.5 • Fluid shifts associated with surgery can increase the likelihood of heart failure.5 • Hypomotility of the gastrointestinal tract may delay gastric emptying and, in the presence of weak laryngeal reflexes, can increase the risk of pulmonary aspiration • Use of succinylcholine is contraindicated because of the risk of rhabdomyolysis, hyperkalemia, and/or cardiac arrest.7 • Cardiac arrest may be due to hyperkalemia or to ventricular fibrillation Indeed, ventricular fibrillation during induction of anesthesia that included succinylcholine administration has been observed in patients later discovered to have this form of muscular dystrophy The response to nondepolarizing muscle relaxants is normal • Rhabdomyolysis, with or without cardiac arrest, has been observed in association with administration of volatile anesthetics to these patients, even in the absence of succinylcholine administration • Dantrolene should be available in light of the increased incidence of malignant hyperthermia in these patients Malignant hyperthermia has been observed after even brief periods of halothane administration, although most cases have been triggered by succinylcholine or prolonged inhalation of halothane Regional anesthesia avoids the unique risks of general anesthesia in these patients • Monitoring is directed at early detection of malignant hyperthermia and cardiac depression • No anesthetic agent is risk free because rhabdomyolysis has been reported with nontriggering anesthetics and the use of barbiturates, benzodiazepines, propofol, and ketamine.7 • Patients are also at risk for thromboembolic events • Postoperative pulmonary dysfunction should be anticipated and attempts made to facilitate clearance of secretions Delayed pulmonary insufficiency may occur up to 36 hours postoperatively even though skeletal muscle strength has apparently returned to its preoperative levels (see Table 21-2) Myasthenia Gravis Pathophysiology and diagnosis Myasthenia gravis (MG) is an autoimmune disease targeting the postsynaptic nicotinic AChR of the neuromuscular junction (Table 21-3) Accordingly, the disease is characterized by weakness and easy fatigability of skeletal muscle Weakness can be asymmetric, regional, or generalized Ocular muscles and other muscles innervated by cranial nerves are most commonly involved, resulting in ptosis, diplopia, dysphagia, dysarthria, and difficulty controlling secretions (Table 21-4).8,11 Strength improves with rest but fades quickly with exertion and repetitive muscle use 312 www.ajlobby.com Mizukawa_Chap_21.indd 312 6/20/17 10:47 AM Myasthenia Gravis Table 21-3 Summary of myasthenia gravis Condition General comments/ pathophysiology Myasthenia gravis Most common disorder of neuromuscular transmission, usually caused by a decrease in functional AChRs at the neuromuscular junction (usually noted in the 20s to 30s for females; 60s to 80s for males), autoimmune disease (antibodies affect the junction of the nerves and muscle) a Ocular 50% of cases are ocular b Generalized Organ systems involved Management Work-up Anesthetic considerations Treatment with AChE Documentation Management of appropriate of current corticosteroid and cyclosporine agents, chronic medications surgical dosing, obtain levels of immunotherapies preoperative calcium if the patient (glucocorticoids, is undergoing plasmapheresis; immuno if possible, consider amide local suppressants), anesthetics, not esters—the AChE thymectomy may impair the hydrolysis of ester (for patients local anesthetics; several classes of aged younger antibiotics can affect neuromuscular than 60 years), transmission, (ampicillin, erythromycin, plasmapheresis, azithromycin, tetracycline, medicines to manage ciprofloxacin) causing weakness; muscle weakness glucocorticoids can cause weakness (pyridostigmine) Eyelids, extraocular muscles Ptosis and diplopia documentation before the procedure Can affect ocular muscles, bulbar, limb, jaw, arm or leg muscles, and respiratory muscles (leads to respiratory insufficiency and failure); facial and neck muscles are commonly affected Note weakness Note aspiration risk; use of propofol of pharyngeal is acceptable without use of and laryngeal neuromuscular blocking agents muscles, degree of ptosis and diplopia, and skeletal muscle weakness Pulmonary work-up if involvement Aspiration risk; use caution with any neuromuscular blocking agents (if one must be used, monitoring with a train-of-four is recommended) Table 21-4 Classification of MG* Class Muscles involved I Extraocular muscle weakness only II Mild nonocular muscle weakness +/- extraocular muscle weakness of any severity III Moderate nonocular muscle weakness +/- extraocular muscle weakness of any severity IV Severe nonocular muscle weakness +/- extraocular muscle weakness of any severity V Intubation or tracheostomy to protect airway, with or without mechanical ventilation *Data modified from Morgan.11 313 www.ajlobby.com Mizukawa_Chap_21.indd 313 6/20/17 10:47 AM 21 • The Musculoskeletal System Management AChE inhibitors are the mainstay of MG management Pyridostigmine is the most common agent employed Monotherapy with AChE inhibitors is often the only treatment needed in patients with mild disease As severity progresses, corticosteroids, immunomodulators, and thymectomy are available treatment options.5 Plasmapheresis and immunoglobulin are reserved for patients with myasthenic crisis and/or respiratory failure.8,11 Some patients with MG not respond to conventional treatment and have severe or life-threatening symptoms Alternate and emerging therapies have not yet proved consistently or durably effective Autologous hematopoietic stem cell transplant has been effective in managing other severe autoimmune neurologic conditions and may have similar application in MG.8,11 Anesthesia considerations • AChE inhibitors should be continued in the perioperative period If necessary, these can be given parenterally at 1/30 the oral dose with the same frequency.11–13 • In addition to AChE inhibition at the neuromuscular junction, AChE inhibitors also inhibit plasma cholinesterase Metabolism of ester-based local anesthetics is therefore prolonged • Patients with respiratory or laryngeal/pharyngeal muscle weakness are at increased risk for aspiration Premedication with metoclopramide or an H2 blocker may help reduce this risk.11 • Opioids and barbiturates should be used with caution as these may cause marked respiratory depression in the MG population • Exercise caution in patients with high-stress physiologic states (eg, infection, recent operation, recent trauma, pregnancy) as these conditions may trigger MG exacerbations.11 • Many antibiotics can aggravate MG weakness and should be used with caution (Box 21-1) Aminoglycosides are an absolute contraindication in the MG patient • MG patients show resistance to succinylcholine; the 95% effective dose (ie, ED95) is approximately 2.6 times higher than normal In contrast, these patients are approximately twice as sensitive to nondepolarizing muscle relaxants.8 BOX 21-1 Common antibiotics that may exacerbate MG Aminoglycosides • Amikacin • Gentamycin • Tobramycin • Neomycin • Streptomycin Fluoroquinolones • Ciprofloxacin • Moxifloxacin • Levofloxacin • Ofloxacin • Norfloxacin • Gemifloxacin Others • Ampicillin • Azithromycin • Clarithromycin • Clindamycin • Erythromycin • Tetracycline Data adapted from Kveraga and Pawlowski.14 At the conclusion of the surgical procedure, it is important to postpone extubation until clear evidence of good respiratory function is present, if an endotracheal tube is used Skeletal muscle strength often seems adequate during the early postoperative period but may deteriorate a few hours later The need for mechanical ventilation during the postoperative period should be anticipated in those patients meeting the criteria known to correlate with inadequate ventilation after surgery 314 www.ajlobby.com Mizukawa_Chap_21.indd 314 6/20/17 10:47 AM Marfan Syndrome Marfan Syndrome Pathophysiology and diagnosis Marfan syndrome (MFS), a connective tissue disorder, is inherited as an autosomal dominant trait (Table 21-5) The incidence is to per 100,000 live births.15 The mutation in the FBN1 gene on chromosome 15 encodes the protein fibrillin.16 Additional skeletal abnormalities include a high-arched palate, pectus excavatum, kyphoscoliosis, and hyperextensibility of the joints Because kyphoscoliosis can contribute to restrictive lung disease, patients are prone to early pulmonary emphysema.15 Furthermore, it is associated with a high incidence of spontaneous pneumothorax Ocular changes such as lens dislocation, myopia, and retinal detachment occur in more than half of patients with MFS.15 MFS patients have a reduction in connective tissue elasticity and strength.17 Table 21-5 Summary of marfan syndrome Condition General comments/pathophysiology Marfan syndrome • One of the most common inherited genetic disorders of connective tissue (primarily affects the support of the skin, bones, blood vessels, and other organs), autosomal dominant, ranges from isolated features to rapidly progressive disease with multisystem involvement; note the commonly high-arched palate, spontaneous pneumothorax, and skin striae (stretch marks) Organ systems involved Management Central nervous system, lung, skin, cardiovascular system, ocular system, musculo skeletal system (joints) Work-up Cardiac Aortic monitoring (aneuwork-up rysm, dissection), drug therapy (β-blockers, drugs targeting renin angiotensin system), restriction of strenuous activity, aortic root replacement, ophthalmologic issue management, scoliosis management • Unknown biochemical defect, which produces a reduction in connective tissue elasticity and strength Anesthetic considerations Consider full work-up; echo, ejection fraction, determining involvement of aortic root dilatation, dissection, mitral valve prolapse, consideration of β-blocker use Pulmonary • Consider pulmonary work-up function tests • Pain control is critical; maintenance of heart rate between 80 and 100 beats per minute is ideal Because cardiovascular manifestations of MFS remain among the central issues in diagnosis and management, the main points are highlighted below.18 Cardiovascular system Cardiovascular abnormalities are responsible for nearly all premature deaths in patients with MFS Defective connective tissue in the aorta and heart valves can lead to aortic dilation, dissection, or rupture, and to prolapse of cardiac valves, especially the mitral valve Mitral regurgitation resulting from mitral valve prolapse is a common abnormality The risk of bacterial endocarditis is increased in the presence of this valvular heart disease Cardiac conduction abnormalities, especially bundle branch block, are common Prophylactic β-blocker therapy is recommended for patients with a dilated thoracic aorta Surgical replacement of the aortic valve and ascending aorta is indicated when the diameter of the ascending aorta exceeds cm and substantial aortic regurgitation is present Pregnancy poses a unique risk of rupture or dissection of the aorta in women with MFS Management β-blocker therapy, specifically atenolol because of its longer half-life, currently remains the standard of care It is recommended that all MFS patients who can tolerate β-blockade should be treated, regardless of the presence 315 www.ajlobby.com Mizukawa_Chap_21.indd 315 6/20/17 10:47 AM 21 • The Musculoskeletal System or absence of aortic dilatation.18 Verapamil (calcium channel blocker) can be considered second-line therapy in individuals unable to tolerate β-blockade Note that other medications may be added to control blood pressure.18 Management of type A (acute dissection of the ascending aorta) is a surgical emergency Type B (initial dissection in the proximal descending thoracic aorta) accounts for 10% of acute dissection and can be medically managed until the aortic diameter exceeds cm.18 Anesthesia considerations • Preoperative evaluation of patients with MFS should focus on cardiopulmonary abnormalities • In most patients, skeletal abnormalities have little impact on the airway Care should be exercised, however, to avoid temporomandibular joint dislocation, to which these patients are susceptible • In view of the risk of aortic dissection, it is prudent to avoid any sustained increase in systemic blood pressure, as can occur during direct laryngoscopy or in response to painful surgical stimulation Invasive monitoring including transesophageal echocardiography may be a consideration in selected patients A high index of suspicion must be maintained for the development of pneumothorax Conclusion Musculoskeletal diseases and their evolving treatment modalities provide a challenge for the practicing clinician Because of the varying degrees of local, regional, and systemic involvement, each patient should be evaluated on an individual basis with customized treatment plans designed for a safe anesthetic exposure and subsequent procedure References Karlet MC, Fort DN Musculokeletal system: Anatomy, physiology, pathophysiology, and anesthesia management In: Nagelhout JJ, Plaus KL (eds) Nurse Anesthesia, ed Philadelphia: Saunders, 2013:817–839 10 Lerman J Perioperative management of the paediatric patient with coexisting neuromuscular disease Brit J Anaesth 2011;107(suppl 1):79I–89I Varga J Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults http://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-sclerosis-scleroderma-in-adults Accessed June 2016 11 Morgan GE, Mikhail MS, Murray MJ Anesthesia for patients with neurologic & psychiatric diseases In: Morgan GE, Mikhail MS, Murray MJ Clinical Anesthesiology, ed New York: McGraw-Hill, 2006:613–630 Smoak LR Anesthesia considerations for the patient with progressive systemic sclerosis (scleroderma) AANA J 1982;50:548–554 12 Berrouschot J, Baumann I, Kalischewski P, Sterker M, Schneider D Therapy of myasthenic crisis Crit Care Med 1997;25:1228–1235 Romero A, Joshi GP Neuromuscular disease and anesthesia Muscle Nerve 2013;48:451– 460 13 Dillon FX Anesthesia issues in the perioperative management of myasthenia gravis Semin Neurol 2004;24;83–94 Blatter JA, Finder JD Perioperative respiratory management of pediatric patients with neuromuscular disease Paediatric Anaesth 2013;23:770–776 14 Kveraga R, Pawlowski J Anesthesia for the patient with myasthenia gravis http://www.uptodate.com/contents/anesthesia-for-the-patient-with-myasthenia-gravis Accessed June 2016 Cripe LH, Tobias JD Cardiac considerations in the operative management of the patient with Duchenne or Becker muscular dystrophy Paediatric Anaesth 2013;23:777–784 15 Kamat S, Travasso B, Borkar D, Dias M Anaesthethic considerations in a patient with Marfan’s syndrome for maxillary corrective osteotomy Indian J Anaesth 2006;50:51–54 Segura LG, Lorenz JD, Weingarten TN, et al Anesthesia and Duchenne or Becker muscular dystrophy: Review of 117 anesthetic exposures Paediatric Anaesth 2013;23:855–864 16 Araújo MR, Marques C, Freitas S, Santa-Bárbara R, Alves J, Xavier C Marfan syndrome: New diagnostic criteria, same anesthesia care? Case report and review [in Portuguese] Rev Bras Anestesiol 2016;66:408–413 Ramani R Skin & musculoskeletal diseases In: Hines RL, Marschall KE (eds) Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Saunders, 2012:437–465 U.S Food & Drug Administration FDA News Release: FDA approves drug to treat Duchenne muscular dystrophy http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm540945.htm Accessed 17 March 2017 17 Wells DG, Podolakin W Anaesthesia and Marfan’s syndrome: Case report Can J Anaesth 1987;34:311–314 18 Keane MG, Pyeritz RE Medical management of Marfan syndrome Circulation 2008;117:2802–2813 316 www.ajlobby.com Mizukawa_Chap_21.indd 316 6/20/17 10:47 AM CHAPTER 22 The Immune System Steven Zambrano, dds Leslie R Halpern, md, dds, phd, mph Immune www.ajlobby.com Mizukawa_Chapter_Openers.indd 317 7/11/17 12:20 PM CHAPTER 22 The Immune System Normal Anatomy and Physiology 319 Human Immunodeficiency Virus .320 Organ Transplantation 323 Diabetes Mellitus 324 Immune Anaphylactic/Anaphylactoid Reactions 325 www.ajlobby.com Mizukawa_Chapter_Openers.indd 318 6/21/17 3:24 PM Normal Anatomy and Physiology Normal Anatomy and Physiology The normal immune response is predicated on the immunologic components within the bone marrow Marrow stem cells receive information that will precipitate a differentiation into either lymphoid or myeloid cell lines Cells of the lymphoid line will differentiate into T lymphocytes, B lymphocytes, and/or non–B cell/non–T cell lineages These “stem” precursors undergo a final differentiation in the thymus, spleen, and/or lymph nodes Other components of the immune system provide the first line of defense; examples of these cellular elements are phagocytic cells, natural killer cells, the complement system, and secreted proteins The adaptive system is highly specific and delayed in response after exposure to an antigen Examples are lymphocytes, humoral mediators and cytokines, T cells, and B cells T lymphocytes can activate B lymphocytes and macrophages, as well as produce cytokines Their ability to mature in the thymus provides them with receptors that provide major histocompatibility complexes and surface membrane receptors (CD-4/CD-8) that recognize antigens B lymphocytes are responsible for antibody production and interact with antigen via immunoglobulins B lymphocytes reach final differentiation within the spleen and lymph nodes and secrete antibodies as plasma cells Five immunoglobulin (Ig) classes exist: IgA, IgE, IgM, IgG, and IgD IgE participates in immediate hypersensitivity reactions The complement system plays a role in natural immunity by protecting against infection either alone or with other humoral agents Complement activation results in release of other inflammatory mediators and increases in neutrophils and vascular permeability Cytokines are proteins that play a role in the regulation of immune reactions, as well as stimulation of immune cell proliferation The myeloid stem cell line differentiates into monocytes that mature in soft tissue and granulocytes that mature in the bloodstream as neutrophils, eosinophils, basophils, and mast cells Neutrophils are the most numerous and play a major role in acute inflammatory responses Eosinophils release granules against specific target cells in late phase reactions Basophils secrete inflammatory granules at areas of local inflammation and mast cells exist in tissue and release histamines that work with other inflammatory mediators affecting the inflammatory cascade of allergic reactions Some surgical patients exhibit an immunosuppression that has arisen during development, whereas other insults to the immune system arise from an acquired exposure.1,2 The majority of immune deficiencies seen in both the pediatric and adult population are acquired1,2 (Table 22-1) Although there is not a single measure of the stage of immunosuppression, the surgeon should maintain a high degree of suspicion when treating all immunocompromised patients Exacerbations of immunosuppression can occur unpredictably, and the surgeon and staff should be familiar with the patient’s history and take necessary precautions Disorders that occur at birth or during development can affect both the innate and adaptive mechanisms of immune function These congenital deficiencies can initiate/exacerbate opportunistic infections with catastrophic sequelae.3,4 As such, infection prevention is a well-established priority Perioperative management with respect to anesthesia, however, may be less routine with the selection of anesthetic drugs based on their modulation of the immune response that is already altered.1–4 Table 22-1 Acquired immunodeficiency disorders* Category Disorder Endocrine Diabetes mellitus Gastrointestinal Hepatic insufficiency, hepatitis, intestinal lymphangiectasia, protein-losing enteropathy Hematologic Aplastic anemia, cancer, graft versus host disease, sickle cell disease Iatrogenic Anticonvulsants: IgA deficiency, general anesthesia; immunosuppressants: radiation therapy, splenectomy Infectious Cytomegalovirus, Epstein-Barr virus, HIV, measles, varicella Nutritional Alcoholism, malnutrition Physiologic Physiologic immunodeficiency in infants, pregnancy Renal Nephrotic syndrome, renal insufficiency, uremia Rheumatologic Rheumatoid arthritis, systemic lupus erythematosus Other Burns, Down Syndrome, congenital asplenia, chronic illness, histiocytosis, sarcoidosis HIV, human immunodeficiency virus *Data adapted from Littlewood.1 319 www.ajlobby.com Mizukawa_Chap_22.indd 319 6/20/17 10:48 AM 22 • The Immune System Human Immunodeficiency Virus Pathophysiology and diagnosis Human immunodeficiency virus (HIV) belongs to the Lentivirus group of retroviruses; two variants are HIV1 and HIV2 Retroviruses contain the enzyme reverse transcriptase that transcribes RNA into DNA and invades the host genome The virus infects T-helper cells (CD4+ T cells) and destroys them It is associated with the acute retroviral syndrome, which is characterized by fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and headache.5–8 The diagnosis and classification of HIV according to the World Health Organization depend on the presence of antibodies to HIV, whereas HIV infection is classified based on associated clinical symptoms1,8 (Table 22-2) In addition, the severity of the immunocompromised state is reflected by the CD4+ T cell count After the flu-like symptoms of early infection, seroconversion occurs with the development of anti-HIV antibodies By months postexposure plasma viremia reaches a steady state and is followed by the period of chronic infection, usually asymptomatic, and associated with a progressive decline in the CD4 count over the next to 10 years AIDS is the outcome of chronic HIV infection, with depletion of the patient’s CD4 cell count to < 200 cells/µL or the presence of a number of AIDS-defining conditions (eg, opportunistic infections).1–8 Important clinical features of AIDS include multi-organ system involvement, which can be a direct consequence of HIV, opportunistic infections, or adverse effects of medications (see Table 22-2) Table 22-2 Clinical staging of HIV infection* Stage Stage (asymptomatic) Symptoms No symptoms, persistent lymphadenopathy Stage (mild symptoms) Moderate weight loss (< 10% body weight), recurrent URI, oral/skin lesions Stage (advanced symptoms) Severe weight loss (> 10% body weight), chronic diarrhea, fever, oral lesions/candida, pulmonary TB, severe bacterial infections, anemia, thrombocytopenia, neutropenia Stage (severe symptoms) Wasting syndrome (> 10% body weight and BMI < 18.5), chronic diarrhea, recurrent bacterial infections, fever, opportunistic infections, encephalopathy, nephropathy, cardiomyopathy, malignancy BMI, body mass index; TB, tuberculosis; URI, upper respiratory infections *Adapted with permission from Nesković.2 Management More than 40 million HIV patients to date have presented to medical and surgical practices for perioperative treatment globally.5 More HIV-positive patients will require surgical procedures because of their increased survival rate Morbidity and mortality from HIV have been reduced with the introduction of highly active antiretroviral therapy (HAART).1–8 The HAART regimen consists of four classes: nucleoside/nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors.1,2,5 Antiretroviral therapy can have important adverse effects that may further impair the immune system (Table 22-3) This “catch 22” is of special concern because adverse effects of active HAART can potentiate the immunomodulatory potential of anesthetic agents.1–8 320 www.ajlobby.com Mizukawa_Chap_22.indd 320 6/20/17 10:48 AM Human Immunodeficiency Virus Table 22-3 Adverse effects at the cellular level of HAART drug therapy for HIV patients* Cellular change Adverse effects Mitochondrial dysfunction Lactic acidosis, hepatic toxicity, pancreatitis, peripheral neuropathy Metabolic abnormalities Fat misdistribution, body habitus changes, dyslipidemia, hypercalcemia, insulin resistance, osteopenia, osteoporosis, osteonecrosis Bone marrow suppression Anemia, neutropenia, thrombocytopenia Hypersensitivity reactions Skin rashes, hypersensitivity reactions *Data adapted from Littlewood.1 Little specific information is available on overall risk of anesthesia and surgery in HIV-infected patients, and no surgery should be deferred on the basis of HIV infection alone.9 American Society of Anesthesiologists risk classification is probably more important than HIV status in establishing risk for perioperative complications.10 Overall health, particularly the presence or absence of organ failure, and nutritional state (albumin level < 2.5 g/dL) have been found to be more reliable predictors of surgical outcome than CD4 cell count or viral load in HIV-infected patients.5,11 Some studies have shown poorer surgical outcomes for individuals with low CD4 cell counts, although this finding has not been consistent.9,10–12 The preoperative surgical assessment must include consideration for impaired wound healing, increased risk of postoperative infection, and poor hemostasis.1–8 A detailed history of the disease, a physical examination, and a variety of laboratory tests for the evaluation of the status of the HIV infection, organ involvement, and HAART drug adverse effects are warranted (see Table 22-3) It is important to review a patient’s history of antiretroviral therapy because of significant drug-to-drug interactions associated with use of the protease and nonnucleoside reverse transcriptase inhibitors Studies have suggested that blood transfusions may increase HIV viral load in those with stage and infection.1,2 Determination of complete blood cell count, platelet count, serum glucose, electrolytes, renal, and liver function tests should be evaluated, as HIV infection and/or medications may cause metabolic, renal, or liver dysfunction Observational data suggest an increased risk of coronary artery disease in HIV-infected patients.13 Further, insulin resistance and diabetes mellitus (DM) are more prevalent in HIVinfected patients.14 Undiagnosed hypoadrenalism may be unmasked by the stress of anesthesia and surgery in the patient with advanced HIV infection Chest radiography is indicated in every patient to screen for tuberculosis or other opportunistic pulmonary infections Cardiac evaluation, such as electrocardiography and echocardiography, are important to identify cardiomyopathy Complete work-up recommendations are listed in Box 22-1 BOX 22-1 Preoperative evaluation for HIV-infected patients The preoperative evaluation of HIV-infected patients should be the same as that for non– HIV-infected patients; however, clinicians should carefully assess for the following conditions: Hepatic and renal dysfunction. Coronary artery disease and cardiac risk. Coagulopathy, thrombocytopenia, and neutropenia. Active alcohol or substance use, including both prescription/nonprescription drug use. History of infection/colonization with MRSA, particularly in men who have sex with men Drug hypersensitivities Clinicians should obtain urine toxicology, with patient consent, if the substance use history is unreliable and concerns about substance use exist Elective surgery should be deferred until active substance use has been addressed Individuals with a history of MRSA colonization/infection should receive vancomycin instead of cefazolin for prophylaxis when indicated Preoperative evaluation of the HIV-infected patient is similar to that of the general population; however, comorbidities, active substance use, and MRSA may be more prevalent in the HIVinfected population MRSA, methicillin-resistant Staphylococcus aureus 321 www.ajlobby.com Mizukawa_Chap_22.indd 321 6/20/17 10:48 AM 22 • The Immune System Anesthetic considerations Intravenous (IV) sedation and general anesthesia may be safely applied in HIV-infected patients, but drug interactions and multisystem disease caused by HIV should be considered preoperatively (see Box 22-1and Table 22-5).1–5 Anesthesia and surgery decrease cell-mediated immunity, and the effects are more pronounced after general anesthesia than after local anesthesia.2,10,11 The dose-related toxicities associated with HAART therapies pose a dilemma for anesthetic drug use in the outpatient setting Many of these adverse events need to be considered because anesthetic drugs are metabolized and redistributed via these cellular/physiologic pathways Specifically, anesthetic agents can induce pharmacodynamic changes in antiretrovirals that then affect both the efficacy of antivirals and the anesthetic drugs.1–12 No substantial evidence-based outcomes suggest one specific approach Studies have supported avoiding anesthetic agents that potentiate renal and hepatic dysfunction The use of benzodiazepines in the presence of protease inhibitors must be carefully considered since an inhibition of hepatic metabolism can increase circulating levels of sedatives.1,2,11,12 Etomidate, atracurium, remifentanil, and desflurane are independent of cytochrome P450 and are preferred because antiretroviral drugs affect cytochrome P450.12 The metabolism of midazolam and fentanyl are affected by cytochrome P450 and should be avoided.2,15 Succinylcholine should be used with caution in patients with renal dysfunction and in the presence of a cardiomyopathy Opportunistic infections such as cytomegalovirus adrenalitis may affect intraoperative hemodynamics, requiring some patients to receive steroid supplementation Careful dosing of opiate analgesics are similarly important since antiretrovirals increase opiate concentrations by way of impairment of hepatic metabolism Wolf and colleagues suggest avoiding propofol infusions in patients receiving nucleoside/nucleotide reverse transcriptase inhibitors due to enhanced mitochondrial toxicity and lactic acidosis.16 Local anesthetics are well tolerated in patients with HIV infection Table 22-5 HAART-related drug interactions with anesthetic agents/pain agents Interaction Potential interaction PI • Alfentanil • Fentanyl • Morphine • Tramadol • Buprenorphine • Propofol No clinically significant • Volatile anesthesia • Ketamine interaction • Paracetamol • NSAIDs NNRTI NRTI • Alfentanil • Fentanyl • Buprenorphine • Tramadol • Codeine • Ketamine • Propofol • Buprenorphine • Codeine • Propofol • Volatile anesthesia • Diamorphine • Morphine • Paracetamol • NSAIDs • Diamorphine • Paracetamol • NSAIDs PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NSAID, nonsteroidal anti-inflammatory drug Antibiotic prophylaxis Surgery itself often causes a disturbance in the native microbial habitat and can lead to complications in the postoperative period.2,5,7 Patients infected with HIV are at increased risk for opportunistic infections and a complicated recovery when their CD4 cell count is below 200 cells/µL Viral loads > 30,000 to 50,000 HIV-RNA copies/mL are associated with increased risk of postoperative complications.5–8 Certainly, in these situations, prophylactic antibiotics effective against oral pathogens should be considered 322 www.ajlobby.com Mizukawa_Chap_22.indd 322 6/20/17 10:48 AM Organ Transplantation Organ Transplantation With advances in the treatment and survival of the transplant patient, the oral and maxillofacial surgeon is likely to provide services for patients who have successfully undergone solid organ or bone marrow transplantation General considerations include the physiologic and pharmacologic problems of allograft denervation, immunosuppression, tissue rejection, and the significant risk for infection The risk of donor organ rejection, specifically, should be considered preoperatively, along with the risk of infection, which causes the greatest degree of morbidity/mortality in transplant patients.1,2,17–20 Management Perioperative assessment should focus on: (1) graft function since rejection and infection can be catastrophic and (2) review drug regimens used in enhancing transplant survival Three types of rejection exist: hyper-acute, acute, and chronic.17–20 The signs/symptoms of rejection are fever, chills, and leukocytosis The definitive diagnosis of organ rejection is by tissue biopsy.2,17–20 The major classes of immunosuppressive agents used in transplant organ survival include: antimetabolites, glucocorticoids, calcineurin inhibitors (ie, cyclosporine and tacrolimus), and several antibodies.2,17–20 Although all are effective in tissue survival, they also have adverse effects that substantially impact perioperative and anesthetic management (Table 22-6) Table 22-6 Immunosuppressive drugs may that impact perioperative/ anesthesia management* Adverse effect CyA Tacr Aza Ster MMF ATG OKT3 Anemia – – + – + – – Leucopenia – – + – + + + Thrombocytopenia – – + – + – – ++ + – + – – – Diabetes mellitus + ++ – ++ – – – Neurotoxicity + + – + – – – Renal insufficiency + ++ – – – – – Anaphylaxis – – – – – + + Fever – – – – – + + Hypertension –, no impact; +, minimal impact; ++, marked impact; ATG, antithymic globulin; Aza, azathioprine; CyA, cyclosporine A; MMF, mycophenolate mofetil; OKT3, monoclonal antibodies directed against CD3 antigen T lymphocyte; Ster, steroids; Tacr, tacrolimus (FK506) *Data adapted from Kostopanagiotou et al.18 During the perioperative period, immunosuppressive therapy should be continued and adjusted according to drug type Cyclosporine and tacrolimus must be monitored specifically on a daily basis during the perioperative period and up to to hours before surgical procedures because of risk of concomitant hepatic/renal impairment and effect of stress-induced organ failure.2,17–20 Supplemental “stress coverage” with steroids may be necessary in renal transplant patients who have recently been taken off steroid therapy and who are suspected of having adrenal supression.17–20 Preoperative testing includes a 12-lead electrocardiogram, complete blood cell count with a differential, and assessment of electrolytes, coagulation panels, and standard renal and liver panels Renal function assessment is of paramount importance because of the nephrotoxic effects of cyclosporine or tacrolimus when combined with certain anesthetic agents (see Table 22-6).18 In addition, risk of infection must be scrutinized, as immunosuppression is exacerbated by bacteria, viruses, fungi, and protozoa and breaches in aseptic technique (see “Antibiotic prophylaxis”) This risk again poses a challenge to the oral and maxillofacial surgeon because the immunocompromised transplant patient may not present with the typical signs/symptoms of sepsis (ie, fever, leukocytosis) 323 www.ajlobby.com Mizukawa_Chap_22.indd 323 6/20/17 10:48 AM 22 • The Immune System The development of osteoporosis is common in 45% to 50% of transplant recipients because of the pathologic sequelae of immunosuppressive drugs and the derangement of the parathyroid-calcium-vitamin D3 axis.1,17–20 Anesthetic considerations Anesthetic management does not differ in transplant patients and other surgical patients Techniques of general, regional, and IV sedation anesthesia have been used successfully in most patients If a secure airway is required, oral intubation is preferred over nasal because the latter potentiates inoculation of nasal flora and increased risk for infection The use of laryngeal mask airways is encouraged.18 Postoperative airway obstruction must be considered because of underlying posttransplant lymphoproliferative disease that may cause physical obstruction.18,19 Fluid and electrolyte management is paramount to maintain cardiovascular preload and afterload during surgical procedures Hyperkalemia and hypomagnesemia are observed with cyclosporine and tacrolimus therapy, so electrolyte status must be monitored for replacement therapy Red blood cell volume must also be monitored to maintain hematocrit levels.2,18 Local anesthetic administration with bupivacaine or ropivacaine is safe in clinically relevant doses.17–20 Most induction agents can be used Several studies have suggested propofol to be a safe choice for induction.2,18–20 A study of cyclosporine interaction with anesthetic agents indicates that propofol infusion does not affect cyclosporine levels.21 Surgical patients induced with propofol have less perioperative suppression of T-helper cells than T-helper cells, indicating better preservation of cell-mediated immunity in the postoperative period.1 Opioids such as fentanyl and morphine are reasonable options for intra- and postoperative analgesia.1,2,18 In renal transplant patients, however, the active metabolites of meperidine (normeperidine) can accumulate, as well as the active metabolites of morphine (morphine-6- and morphine-3-glucuronide), which may cause prolonged sedation postoperatively.18 Short-acting opioids with extrahepatic metabolism, such as remifentanil, may be considered for intraoperative analgesia.1,18 Isoflurane, sevoflurane, and desflurane, in clinically administered doses, are appropriate inhalational anesthetics.21–23 Nitrous oxide must be avoided because of bowel distention Nondepolarizing muscle relaxants, which are not metabolized by the liver and which not rely on renal excretion, such as atracurium and cisatracurium, are superior choices Patients treated with cyclosporine A, however, will require smaller doses of these muscle relaxants to avoid prolonged recovery times Succinylcholine can be administered in the absence of hyperkalemia, but rocuronium or mivacurium are alternatives for rapid sequence induction.1,2,21–23 Antibiotic prophylaxis Immunosuppressed transplant patients should receive prophylactic antibiotics before oral surgical procedures Broad spectrum antibiotics for prophylaxis or for management of a suspected or confirmed infection should be continued during the time of the operation.1,2,18,24 Diabetes Mellitus Although not without controversy, an important group of patients who may present with a compromised immune system is the patient with poorly controlled DM DM is a disease of glucose, fat, and protein metabolism resulting from impaired insulin secretion, insulin resistance, or both and is associated with increased risk of infection when poorly controlled Surgical site infection, for example, is more common in the setting of uncontrolled DM and postoperative hyperglycemia.25,26 Neutrophil adherence, chemotaxis, phagocytosis, bactericidal activity, and cell-mediated immunity are compromised in the hyperglycemic diabetic.27 The plasma glucose threshold for such granulocyte dysfunction is in the range of 198 to 270 mg/dL.28 Both granulocyte29 and T cell30 dysfunction are reversed with the administration of insulin Vascular disease is common in diabetic patients and likely also contributes to an increased risk of infection due to local tissue ischemia that may enhance growth of anaerobic organisms, depress bactericidal functions of leukocytes, and impair local inflammatory response and antibiotic absorption The practical implications of diabetes-associated immune dysfunction are that optimal control of plasma glucose levels is important both in 324 www.ajlobby.com Mizukawa_Chap_22.indd 324 6/20/17 10:48 AM Anaphylactic/Anaphylactoid Reactions the prevention of infection and in the management of established infection The glycosylated hemoglobin (HbA1c) level is a useful measure to assess glucose control over the preceding weeks Poorly controlled DM is reflected in a HbA1c level > 8% Antibiotic prophylaxis The well-controlled diabetic patient is probably at no greater risk for infection than the nondiabetic patient Therefore, routine dentoalveolar surgical procedures in patients with well-controlled DM (HbA1c < 8%) not require prophylactic antibiotics However, when surgery is necessary in patients with poorly controlled DM, prophylactic antibiotics should be considered Notwithstanding the importance of preoperative glucose control, surgery and general anesthesia can cause a state of insulin resistance and decreased insulin secretion to the extent that the patient with otherwise well-controlled DM may become hyperglycemic in the postoperative period.31 Antibiotics in these situations should be administered preoperatively and, for procedures longer than hours, intraoperatively Anaphylactic/Anaphylactoid Reactions Anaphylaxis is an acute life-threatening IgE-mediated hypersensitivity reaction IgE-mediated anaphylaxis indicates the presence of IgE directed toward the causative antigen, whereas anaphylactoid is a non–IgE-mediated event Although mimicking an IgE-mediated event, the mechanism differs because the reaction can occur following a single, first-time exposure to certain agents (eg, vancomycin, IV contrast, etc) in nonsensitized patients Anaphylaxis and anaphylactoid reactions are clinical diagnoses with variable involvement of three major components: generalized skin reactions (flushing, itching, urticaria, angioedema), cardiovascular instability (hypotension), and respiratory obstruction (laryngeal edema or bronchoconstriction) Skin or mucosal involvement may or may not be present initially because the inflammatory mediators released not always appear instantly.32 Anesthesia considerations Most in-office drug hypersensitivity reactions can be prevented with a careful medical history that focuses on any previous adverse events Drugs used in the oral and maxillofacial surgery practice that can lead to an adverse hypersensitivity reaction include the following Antibiotics The most common antibiotics associated with a hypersensitivity reaction are the β lactam antibiotics and vancomycin.32,33 IV penicillin exhibits a significantly greater percentage of cases, as well as the most serious and fatal reactions in those who have not been exposed previously.32,33 Only 10% with a history of a reaction to penicillin actually have a penicillin hypersensitivity.34 Cephalosporins, also in the β-lactam family will cause a hypersensitivity reaction in approximately 2% of individuals with skin-test proven sensitivity to penicillin Nevertheless, cephalosporins should be used cautiously with a known penicillin hypersensitivity, especially in those with a history of anaphylaxis Local anesthetics Nonhypersensitivity reactions to local anesthetics are more common than hypersensitivity reactions Local anesthetics can cause delayed swelling, localized dermatitis, or mucosal inflammation, characteristic of a type IV hypersensitivity reaction IgE-mediated anaphylaxis from local anesthetics can occur, but it is uncommon Whereas IV administration of local anesthetics seldom initiates an immunologic cascade, toxic effects occur secondary to inadvertent, high-dose preparations given intravenously Initial signs/symptoms include a vaso-vagal response, anxiety, and complications in both the cardiac and neurologic systems.35 Positive patch testing occurs more com325 www.ajlobby.com Mizukawa_Chap_22.indd 325 6/20/17 10:48 AM 22 • The Immune System monly with the para-aminobenzoic ester class than the amide class of compounds Bisulfite, present in local anesthetics containing a vasopressor, is another source for hypersensitivity reaction to local anesthetic preparations Methyl paraben, a bacteriostatic agent used in multidose vials of local anesthetic, can also trigger a hypersensitivity reaction Benzodiazepines Although rare, anaphylactic reactions with benzodiazepines have been reported No IgE positivity is seen on skin testing; however, histamine release from lung mast cells with diazepam and from basophils and mast cells with midazolam has been described.36,37 Opioids Reports of anaphylaxis/anaphylactoid reactions have been published in both the medical and surgical literature.38,39 Flushing and urticarial reactions are observed during IV administration The rate of titration usually is correlated with clinical presentation The cutaneous flushing and hives seen with morphine are not seen when fentanyl is administered, as the latter does not cause a release of histamine.40 Hypnotic induction agents Most of the adverse reactions seen with this class of drug are associated with barbiturates, especially thiopental Women appear to be at a threefold greater risk of anaphylaxis than men.41 This association is far less important with the nonbarbiturate induction agents (eg, propofol) Neuromuscular blocking agents Neuromuscular blocking agents represent the largest group of agents that can elicit an anaphylactic event Succinylcholine is the most common triggering agent in anaphylaxis.32,41–43 This agent is especially prone to conform molecularly to allow for IgE cross-linking, leading to an immediate type I reaction The nondepolarizing neuromuscular blocking agents share a common quaternary and tertiary ammonium group that is recognized by IgE.41,42 Latex products Latex rubber sensitivity is the second most common cause of perioperative anaphylaxis.32,44 Health care workers in the surgical specialties have seen an increased rate of anaphylaxis, from just over 10% 10 years ago to 15% in this decade.45,46 The prevalence of latex hypersensitivity in the general population is 0.8% to 6.5%.45,46 Hypersensitivity reactions to latex have increased over the past 50 to 60 years due to many factors, including increased use for infection control purposes, coupled with increased use of latex products in general This increase has brought greater attention to its hypersensitivity potential Products containing latex encountered daily include airway masks, tape, blood pressure cuffs, syringes, catheters, elastic bandages, electrode pads, gloves, IV bags, Penrose drains, stethoscope tubing, suction tips, and tourniquets, among others The management of anaphylaxis/anaphylactoid reactions is discussed in chapter 12 Conclusion The perioperative management of immunocompromised patients is challenging and yet not uncommon Surgical and anesthetic procedures that the oral and maxillofacial surgeons commonly use can initiate or exacerbate the imbalances in immune function with which these patients already present The recognition of symptoms is even more 326 www.ajlobby.com Mizukawa_Chap_22.indd 326 6/20/17 10:48 AM References important since anesthetized patients are subjected both to the drug’s adverse effect as well as the physiologic effects of the anesthetic agent A vigilant approach by the surgeon and staff with modifications based on a particular agent or patient will avoid the morbidity and mortality associated with an adverse event References Littlewood KE The immunocompromised adult patient and surgery Best Pract Res Clin Anaesthesiol 2008;22:585–609 Nesković V Preoperative assessment of the immunocompromised patient Acta Chir Iugosl 2009;58:185–192 Kurosawa S, Kato M Anesthetics, immune cells, and immune responses J Anesth 2008;22:263–277 Fleischer TA, Bleesing JJ Immune function Pediatr Clin North Am 2000;47:1197–1209 Hughes SC HIV and anesthesia Anethesiol Clin North Am 2004;22:379–404 Harris HW, Schecter WP Surgical risk assessment and management in patients with HIV disease Gastroenterol Clin North Am 1997;26:377–391 Parthasarathy S, Ravishankar M HIV and anaesthesia Indian J Anaesth 2007;51:91–99 Shrosbee J, Post FA, Keays R, Vizcaychip MP Anaesthesia and intensive care in patients with HIV Trends Anaesth Crit Care 2011;1:153–161 Jones S, Schechter CB, Smith C, Rose DN Is HIV infection a risk factor for complications for surgery? Mt Sinai J Med 2002;69:329–335 10 Leelanukrom R Anaesthetic considerations of the HIV-infected patients Curr Opin Anaesth 2009;22:412–418 11 Eichler A, Eiden U, Kessler P AIDS and anaesthesia [in German] Anaesthetist 2000;49:1006–1017 12 World Health Organization HIV/AIDS Programme.WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children http:/www who.int/hiv/pub/guidelines/HIVstaging150307.pdf Accessed 12 August 2014 13 Fichtenbaum CJ Inflammatory markers associated with coronary heart disease in persons with HIV infection Curr Infect Dis Rep 2011;13:94–101 14 Stanley TL, Grinspoon SK Body composition and metabolic changes in HIV-infected patients J Infect Dis 2012;205(3, suppl):383S–390S 15 Olkkola KT, Palkama VJ, Neuvonen VJ Ritonavir’s role in reducing Fentanyl clearance and prolonging its half-life Anesthesiology 1999;91:681–691 16 Wolf A, Weir P, Segar P, Stone J, Shield J Impaired fatty acid oxidation in propofol infusion syndrome Lancet 2001;357:606–607 17 Desai DM, Kuo PC Perioperative management of special populations: Immunocompromised host (cancer, HIV, transplantation) Surg Clin North Am 2005;85:1267–1282 18 Kostopanagiotou G, Smyrniotis V, Arkadopoulos N, Theodoraki K, Papadimitriou L, Papadimitriou J Anesthetic and perioperative management of adult transplant recipients in nontransplant surgery Anesth Analg 1999;89:613–622 19 Kosopanagiotou G, Sidiropoulou T, Pyrsopoulos N, et al Anesthetic and perioperative management of intestinal and multivisceral allograft recipient in nontransplant surgery Transpl Int 2008;21:415–427 20 Tran SB Anesthetic considerations for patients post-organ transplantation Semin Anesth Perioperative Med Pain 2003;22:119–124 21 Pertek JP, Chaoui K, Junke E, et al Effects of propofol on blood concentration of cyclosporine [in French] Am Fr Anesth Reanim 1996;15:589–591 22 Puig NR, Ferrero P, Bay ML, et al Effects of Sevoflurane general anesthesia: Immunological studies in mice Int Immunopharmacol 2002;2:95–104 23 Inada T, Yamanouchi Y, Jomura S, et al Effect of propofol and isoforane anesthesia on the immune response to surgery Anaesthesia 2004;59:954–959 24 Shaw IH, Kirk AJ, Conacher ID Anaesthesia for patients with transplanted hearts and lungs undergoing non-cardiac surgery Br J Anaesth 1991;67:772–778 25 Ata A, Lee J, Bestle SL, Desemone J, Stain SC Postoperative hyperglycemia and surgical site infection in general surgery patients Arch Surg 2010;145:858–864 26 Latham R, Lancaster AD, Covington JF, Pirolo JS, Thomas CS Jr The association of diabetes and glucose control with surgical-site infections among cardiothoracic surgery patients Infect Control Hosp Epidemiol 2001;22:607–612 27 Delamaire M, Maugendre D, Morento M, Le Goff MC, Allannic H, Genetet B Impaired leukocyte function in diabetic patients Diabet Med 1197;14:29–34 28 McMahon MM, Bistrain BR Host defenses and susceptibility to infection in patients with diabetes mellitus Infect Dis Clin North Am 1995;9:1–9 29 Joshi N, Caputo GM, Weitekamp MR, Karchmer AW Infections in patients with diabetes mellitus N Engl J Med 1999;341:1906–1912 30 Mahmoud AAF, Waren KS, Rodman HM, Mandel MA Effects of diabetes mellitus on cellular immunity Surg Forum 1975;26:548–550 31 Wright PD, Henderson K, Johnston ID Glucose utilization and insulin secretion during surgery in man Br J Surg 1974;61:5–8 32 Chacko TC, Ledford D Peri-anesthetic anaphylaxis Immunol Allergy Clin North Am 2007;27:213–230 33 Gadde J, Spense M, Wheeler B, Adkinson NF Jr Clinical experience with penicillin skin-testing in a large inner-city STD clinic JAMA 1993;24:2456–2463 34 Park M, Markus P, Matesic D, Li JT Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy Ann Allergy Asthma Immunol 2006;97:681–687 35 Yagiela JA Local anesthetics Anesth Prog 1991;38(48):128–141 327 www.ajlobby.com Mizukawa_Chap_22.indd 327 6/20/17 10:48 AM 22 • The Immune System 36 Fujita Y, Ishikawa H, Yokota K Anaphylactoid reaction to midazolam Anesth Analg 1994;79:811–812 37 Yakel DL, Whittaker SE, Elstad MR Midazolam-induced angioedema and bronchoconstriction Crit Care Med 1992;20:307–308 38 Moscicki RA, Sockin SM, Corsello BF, Ostro MG, Bloch KJ Anaphylaxis during induction of general anesthesia: Subsequent evaluation and management J Allergy Clin Immunol 1990;86:325–332 39 Gueant JL, Aimone-Gastin I, Namour F, Laroche D, Bellou A, Laxenaire MC Diagnosis and pathogenesis of the anaphylactic and anaphylactoid reactions of anesthetics Clin Exp Allergy 1998;28:65–70 40 Rosow CE, Moss J, Philbin DM, Savarese JJ Histamine release during morphine and fentanyl anesthesia Anesthesiology 1989;71:489–494 41 Birnbaum J, Porri F, Pradal M, Charpin D, Vervloet D Allergy during anesthesia Clin Exp Allergy 1994;24:915–921 42 Baldo BA, Fisher MM Mechanisms of IgE-dependent anaphylaxis to anesthetic drugs Ann Fr Anesth Reanim 1993;12:131–140 43 Laxenaire MC Epidemiology of anesthetic anaphylactoid reactions Fourth multicenter survey (July 1994–December 1996) [in French] Ann Fr Anesth Reamin 1999;18:796–809 44 Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology The diagnosis and management of anaphylaxis: An updated practice parameter J Allergy Clin Immunol 2005;115(3, suppl 2):483S–523S [erratum 2008;122:68] 45 Chaiear N, Foulds I, Burge PS Prevalence and risk factors for latex allergy [comment] Occup Environ Med 2000;57;501 46 Lieberman P Anaphylactic reactions during surgical and medical procedures J Allergy Clin Immunol 2002;110(2, suppl):64S–69S 47 Kwittken PL, Becker J, Oyefara B, Danziger R, Pawlowski NA, Sweinberg S Latex hypersensitivity despite prophylaxis Allergy Proc 1992;13:123–127 48 Mak TW, Saunders ME, Jett BD Primer to the Immune Response, ed Amsterdam: Elsevier, 2014 328 www.ajlobby.com Mizukawa_Chap_22.indd 328 6/20/17 10:48 AM SECTION III ANESTHESIA IN SPECIAL PATIENT GROUPS SECTION III www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 329 7/17/17 12:25 PM SECTION III www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 330 7/17/17 12:25 PM CHAPTER 23 Hematopathology and Coagulopathy Robbie J Harris III, dds Matthew Mizukawa, dmd John Mizukawa, dds www.ajlobby.com Mizukawa_Chap_23.indd 331 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy Anatomy and Physiology The hematologic system supports virtually every organ system in the body Blood is required for three main functions: transportation of substances throughout the body, regulation of normal physiologic conditions, and protection from hemorrhage and pathogenic invaders These functions are listed in Box 23-1 BOX 23-1 Functions of blood Distribution • Oxygen • Nutrients: glucose, amino acids, fatty acids • Hormones • Waste products: urea, lactate, CO2 Regulation • Temperature • pH • Fluid volume Protection • Hemostasis • Immune response Constituents of blood Blood can be divided and subdivided into many constituents The first division is cells and plasma Plasma makes up 55% of blood, and cells make up 45% of blood Plasma is 92% water and 8% substances, including plasma proteins, electrolytes, vitamins, and other nutrients (ie, glucose, amino acids, and fatty acids) Plasma proteins are subdivided into albumins (60%), α-, β-, and γ-globulins (36%), and fibrinogen (4%).1 These proteins maintain osmotic pressure in the intravascular space, vital for fluid volume and blood pressure, as well as transport nutrients systemically and aid in hemostasis, respectively.1 Other substances in plasma are listed in Box 23-2 BOX 23-2 Constituents of plasma Proteins • Albumin (60%) • Globulins (α, β, γ) (36%) • Fibrinogen (4%) Vitamins Electrolytes • Na, K, Ca, Mg, Cl, PO4, bicarbonate, sulfate Nutrients • Glucose • Amino acids • Fatty acids Hematopoiesis is the formation of the cellular components of blood The genesis of any of the cellular constituents of blood originates from the hematopoietic stem cell, which resides in bone marrow The hematopoietic stem cell can ultimately become any of three types of cells: platelets, red blood cells (RBCs), and white blood cells Both platelets and RBCs are terminal cell types, but the five distinct white blood cell types can be further subclassified, first into granulocytes and agranulocytes Granulocytes are basophils, eosinophils, and neutrophils, and arise from the myelogenous line of differentiation Agranulocytes include monocytes and lymphocytes, which in turn can be subclassified into B cells and T cells Monocytes arise from myelogenous origins, whereas lymphocytes arise from the lymphogenous progenitor (Fig 23-1).1 332 www.ajlobby.com Mizukawa_Chap_23.indd 332 6/21/17 3:25 PM Anatomy and Physiology Multipotential hematopoietic stem cell (hemocytoblast) Common lymphoid progenitor Common myeloid progenitor Myeloblast Mast cell Erythrocyte Megakaryocyte Thrombocytes Natural killer cell (large granular lymphocyte) Small lymphocyte T lymphocyte B lymphocyte Plasma cell Basophil Neutrophil Eosinophil Monocyte Macrophage Fig 23-1 Lineage of blood cells Oxygen delivery Blood is critical for oxygen delivery to vital organs and tissues The adult human will consume 250 mL of oxygen per minute to provide for the basal metabolic rate On average, RBCs can carry approximately 200 mL of oxygen per liter of blood with an average adult cardiac output of L of blood per minute This rate equates to approximately L/ minute of oxygen delivered to the body, well exceeding the basal demand of 250 mL/minute.2 However, in times of exercise and stress, oxygen demand increases dramatically Three mechanisms can supply the increased oxygen needed to meet this high demand: (1) increased oxygen absorbed from the lungs to the pulmonary vasculature, (2) increased cardiac output, and (3) increased unloading of oxygen to areas of increased demand Increased concentrations of oxygen inspired will increase the volume of oxygen that reaches the pulmonary vessels Therefore, supplemental oxygen is important when administering anesthesia A higher cardiac output translates to an increased volume of oxygen-carrying RBCs delivered to areas of increased demand Increased unloading of oxygen at areas of increased demand is a manifestation of the physiology of hemoglobin RBCs serve a critical role of oxygen delivery from the lungs to the tissue This process is facilitated by hemoglobin, the oxygen-binding protein in RBCs Under normal conditions, three variants of hemoglobin molecules exist, depending on the composition of α, β, or γ subunits: hemoglobin A (α2β2), hemoglobin A2 (α2δ2), or hemoglobin F (α2γ2).2 Each subunit can reversibly bind a molecule of oxygen, so one molecule of hemoglobin can carry four molecules of oxygen The affinity of hemoglobin to oxygen differs in circulation, depending on three factors: temperature, pH, and concentration of 2,3-bisphosphoglycerate (2,3-BPG) These factors facilitate the loading of oxygen onto hemoglobin in the lungs and the unloading in areas of higher oxygen demand Table 23-1 describes these mechanisms 333 www.ajlobby.com Mizukawa_Chap_23.indd 333 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy Table 23-1 Factors influencing the affinity of hemoglobin to oxygen Factor Lungs Tissue Temperature Decreased tissue temperature, including in the pulmonary vasculature, increases oxygen affinity, tending toward binding Increased temperatures from metabolism and increased oxygen demand decreases oxygen affinity, tending toward unloading pH Normal or increased pH will tend toward increase oxygen affinity and oxygen binding Hypoxia from increased oxygen metabolism results in lactic acid production, which will decrease pH and oxygen affinity, tending toward unloading 2,3-BPG Conditions of normal oxygen tension will decrease RBC production of 2,3-BPG, which will promote oxygen affinity and binding Conditions of low oxygen tension will increase RBC production of 2,3-BPG, which binds deoxyhemoglobin and releases oxygen from hemoglobin The oxyhemoglobin dissociation curve illustrates how these factors will promote oxygen delivery to areas of higher oxygen demand For example, Fig 8-1 llustrates that an arterial partial pressure of oxygen (Pao2) of 25 mm Hg elicits a higher oxyhemoglobin saturation under conditions of alkalosis, hypothermia, and lower levels of 2,3-BPG, compared with the lower saturation under conditions of acidosis, hyperthermia, and increased 2,3-BPG, despite the same oxygen tension Hemostasis Of importance to the surgeon, regardless of specialty, is the ability for a physical insult to predictably heal The healing process involves a complex array of events that must occur in both sequential and simultaneous fashion without interruption for tissue integrity to be re-established This cascade of events begins by stopping the hemorrhage (hemostasis), minimizing blood loss, and stabilizing the wound, which enables the harmonious continuation of normal healing The hemostatic process can be broken down into four component phases: (1) vascular, (2) platelet, (3) coagulation, and (4) fibrinolytic Dysfunction of any element involved can alter the procession of the system as a whole to achieve success Vascular phase The intact intimal layer of the vessel wall promotes unimpeded laminar blood flow and inhibition of platelet adhesion via the production of prostacyclin (PGI2) and nitric oxide Derived from cyclooxygenase (COX)-2, PGI2 is secreted by the endothelium through positive feedback in times of steady shear stress on the intimal wall Nitric oxide acts via a second messenger system, guanylate cyclase, and not only curtails platelet adhesion to the vessel wall and cohesion to other platelets but also promotes vasodilation.3,4 However, when the endothelium is compromised, a reflex constriction of the smooth muscle of the vessel wall occurs, decreasing flow of blood to the area of injury and minimizing blood loss Platelet phase The vascular phase serves to decrease flow of blood to the site of injury This phase is needed to facilitate the migration of platelets The platelet phase follows three steps: adhesion, activation, and aggregation Adhesion of platelets to the exposed matrix in the subendothelium is enabled by von Willebrand factor (vWF), which serves as a bridge between the subendothelium and platelets The platelets have a lifespan of to 12 days and possess multiple structural elements and surface receptors that make it ideal for its positioning in the hemostatic process.5 The binding of platelets to collagen activates the platelet, resulting in platelet degranulation and release of chemicals into the site of injury Degranulation releases both α and dense granules, each releasing different substances intricately involved in the platelet phase Some examples can be found in Box 23-3 Adenosine diphosphate (ADP) is 334 www.ajlobby.com Mizukawa_Chap_23.indd 334 6/21/17 3:25 PM Hemostasis one of the chemicals released from platelets and acts not only to enhance platelet aggregation but also to promote continued degranulation ADP also stimulates thromboxane A2 (TXA2), synthesized by COX-1, which facilitates vasoconstriction and platelet aggregation (see Fig 6-1) Nonsteroidal anti-inflammatory drugs inhibit TXA2 as well as PGI2 The aggregation of the platelets continues until a platelet plug is formed.7 Another such receptor, glycoprotein IIb/IIIa, binds fibrinogen The link closely relating the platelet phase to the clotting cascade involves procoagulant phospholipids BOX 23-3 Platelet granules* 𝛂 granules • von Willebrand factor • Fibrinogen • Platelet-derived growth factor • Platelet factor Dense granules • ADP/ATP • Ionized calcium • Serotonin • Histamine ATP, adenosine triphosphate *Data adapted from Turgeon.6 Coagulation phase The model for coagulation that occurs in vivo, in essence, is a synergistic continuum, rather than a separate cascade of events that involves activation of precursor proteins (zymogens) to active enzymes For description purposes and ease of understanding of all involved, the classic model (Fig 23-2) is often used This model, though, does not account for the interrelationship between the intrinsic and extrinsic pathways Figure 23-3 is more consistent with what occurs in vivo Extrinsic pathway Intrinsic pathway aPTT PT Factor XII Factor XI Tissue damage Factor XIa Factor IX Common pathway { Tissue factor Factor IXa Factor X Factor VIIa Factor Xa Factor Xa Factor Va Prothrombin Thrombin Fibrinogen Fibrin Factor XIIIa Factor XIII Stabilized fibrin Fig 23-2 Classic model of coagulation aPTT, activiated partial thromboplastin time; PT, prothrombin time 335 www.ajlobby.com Mizukawa_Chap_23.indd 335 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy TF-bearing cell Platelet Activated platelet Fig 23-3 Cell-based model of coagulation (Adapted with permission from Chacon and Ugalde.5) TF, tissue factor Basically two pathways, the extrinsic and intrinsic pathways, are involved and then converge to a common pathway, at factor X, resulting in the conversion of prothrombin to thrombin and the activation of fibrin.10 The liver is the major organ involved in the synthesis of the majority of proteins involved in this portion of hemostasis Synthesized proteins include factors II, VII, IX, X, XI, XII, and XIII, as well as two precursors, fibrinogen and prothrombin The presence of vitamin K is also required for proper function of factors II, VII, IX, and X Warfarin (Coumadin, Bristol Myers Squibb) inhibits these vitamin K–dependent factors With exposure of the subendothelial tissue as a consequence of vascular insult, a factoar extrinsic to the system, tissue factor (thromboplastin) is then expressed and in turn activates the extrinsic pathway Subsequent activation of factor VII to VIIa, when coupled with ionized calcium, activates factors X to Xa The prothrombin time (PT) is used to measure this extrinsic pathway and is a very sensitive test with much weaker specificity The PT essentially evaluates thrombin and fibrin formation Thromboplastin is added to the sample of blood for activation A range of 11 to 15 seconds is considered normal PT.8 Compromise of factor function, whether by medication, diet, or decreased quantity of factors, can cause extrinsic pathway disruption It should also be noted that the international normalized ratio (INR) is used to normalize the differences in thromboplastin reagent sensitivity, as measured by the international sensitivity index (ISI) and, thus, the INR is derived as follows: INR = (patient PT / mean normal PT)ISI The intrinsic pathway initiates via the contact of negatively charged surfaces with collagen, elastin, factor XII (Hageman factor), prekallikrein (Fletcher factor), platelets, high–molecular-weight kininogens (Fitzgerald factor) or plasmin Factor XII, after activation, then helps to activate factor XI to factor XIa, which in turn activates factors IX to IXa Factor IXa, along with VIIIa, aids in the formation of factor Xa from factor X The activated partial thromboplastin time (aPTT) tests the function of the intrinsic pathway The common pathway then proceeds as follows: Factor Xa, in combination with factor V, activates prothrombin to thrombin (factor II to IIa) Factor Xa, in conjunction with thrombin, activates factor VIII, which also progressively accumulates in the presence of continued activation of factor Xa and thrombin Thrombin activates fibrinogen, converting it to fibrin, which polymerizes and is stabilized by activated factor XIII (XIIIa), as it is intricately involved in the cross-linking of fibrin and thus overall clot stability 336 www.ajlobby.com Mizukawa_Chap_23.indd 336 6/21/17 3:25 PM von Willebrand Disease Fibrinolytic phase A critical portion of the hemostatic process is the regulation of the overall clot formation and limitation of its propagation systemically The hemostatic system involves numerous positive and negative feedback mechanisms that incorporate checks and balances If this regulation fails to occur, thrombosis and eventual tissue damage is likely to occur In addition to those platelet and vascular modifiers mentioned previously, antithrombin and activated proteins C and S are important here Antithrombin binds and inactivates factors IXa through XIIa and thrombin When bound by heparin, be it exogenous or endogenous, the inactivation is increased by 1,000 to 4,000 times.9,10 Activated protein C and protein S are also closely involved with inactivation of factors Va and VIIIa Eventually, the clot must be reorganized to allow for re-establishment of the vessel wall and eventual tissue remodeling Plasminogen, activated by tissue-type plasminogen activator, becomes plasmin, which then cleaves fibrinogen, primarily, but also acts on other coagulation factors and proteins used in the platelet and coagulation phases.6,11 von Willebrand Disease Pathophysiology and diagnosis von Willebrand Disease (vWD) is the most prevalent hereditary coagulopathy As noted earlier, upon sustaining vascular injury, the body launches a series of events to minimize blood loss Among the initial events is platelet activity at the site of injury vWF is expressed on the cell surfaces of platelets, megakaryocytes, and endothelial cells, and serves to bind platelets circulating in the blood to either collagen of the subendothelium, the endothelium, or another platelet, resulting in a “platelet plug” and primary hemostasis Either a genetic aberrance of vWF expression or a decreased amount of vWF will result in vWD and prolonged bleeding Three main subtypes of vWD exist12: Type includes the majority of vWD (70% to 80%) and is a quantitative deficiency in the amount of vWF present Type has four subtypes (ie, 2A, 2B, 2M, and 2N) and represents a qualitative deficiency of vWF, resulting in various dysfunction of platelet adhesion to collagen and endothelium and platelet aggregation Type is a complete deficiency of vWF This subtype, fortunately, is very rare However, these patients can see abnormal bleeding from even minimal tissue insult and extensive bleeding from significant injury Diagnosis • Symptoms: Mucocutaneous bleeding, epistaxis, easy bruising, menorrhagia, and gastrointestinal bleeding.2 • Laboratory test findings: vWF markers are detected in the blood and found to be low or absent: vWF antigen, vWF ristocetin cofactor, and vWF collagen binding activity.12 Factor VIII may also be decreased • One should note that other laboratory tests that measure clotting times usually yield normal values in vWD, including PT and PTT Depending on the type of vWD, platelet count may also be normal.12 Management In general, no intervention is required on a day-to-day basis Bleeding episodes are managed as they are encountered (See the next section.) Anesthesia considerations When uncontrolled bleeding is encountered or anticipated, as in surgery, 1-desamino-8-D-arginine vasopressin (DDAVP, Ferring) can be used as first-line treatment or as prophylaxis, respectively DDAVP is a synthetic form of 337 www.ajlobby.com Mizukawa_Chap_23.indd 337 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy the endogenous hormone, antidiuretic hormone, or vasopressin It stimulates the release of vWF from endothelial cells, resulting in a two- to five-fold increase of vWF and factor VIII in the plasma A total dose of 0.3 µg/kg, diluted in 30 to 50 mL of saline and given slowly over 10 to 20 minutes, will give a duration of action of approximately to 12 hours DDAVP also comes in a nasal spray (Stimate, CSL Behring, 1.5 mg/mL) Each spray delivers 0.1 mL, or 150 µg A 300-µg dose to each nostril will increase the plasma vWF three to fivefold and can help control intraoperative and postoperative bleeding from minor surgical procedures and dental procedures.13 Adverse effects include tachycardia, hypotension, headaches, lightheadedness, nausea, flushing, and water intoxication, which can often be avoided if given slowly Other agents, such as Amicar (Xanodyne; aminocaproic acid) and tranexamic acid, can also be given in conjunction with DDAVP to enhance its efficacy When these measures fail to stop the bleeding, cryoprecipitate can be transfused Cryoprecipitate is a human blood product obtained when fresh frozen plasma is centrifuged, isolating the precipitate, which provides fibrinogen, factor VIII, vWF, and factor XIII There is a commercially available product called Humate-P (CSL Behring), which is also a human product comprised of factor VIII and vWF Both cryoprecipitate and Humate-P are derived from human tissue, so they carry the risk of disease transmission Hemophilia A Pathophysiology and diagnosis Hemophilia A is a sex-linked recessive disease and affects males almost entirely It represents the quantitative or qualitative defect of factor VIII, resulting in dysfunctional coagulation Factor VIII activity levels can be altered either by decreased amounts of normally functioning factor VIII, normal amounts of dysfunctional factor VIII, or a combination of both.13 As noted previously, factor VIII serves as a cofactor with factor IX The factor VIII/IX complex activates factor X, which subsequently, along with its cofactor V, activates thrombin Thrombin, in turn, converts fibrinogen to fibrin, the main constituent of the initial clot Hemophilia A patients are classified into three groups: Mild: Retain 6% to 30% of factor VIII activity level These patients often go undiagnosed, as their clotting ability is largely unaffected or minimally affected.13 Moderate: Retain 1% to 5% of factor VIII activity level These patients have increased risk for clinically significant bleeding from trauma or surgical insult, but they not generally have spontaneous bleeding or hemarthrosis.13 Severe: Retain < 1% of factor VIII activity level These patients are at risk of spontaneous bleeding and spontaneous hemarthrosis Any degree of trauma or surgical insult will result in severe bleeding if untreated, including life-threatening intracranial hemorrhage.13 Hemophilia A is diagnosed by a series of laboratory tests to detect factor VIII deficiency and rule out other diseases Genetic testing can reveal the sex-linked transmission of the disease from a known or unknown carrier Factor VIII levels are decreased, while normal levels of vWF, factor IX, and factor XI are present Because factor VIII is involved in the intrinsic pathway, the PTT is elevated, whereas bleeding time and PT are normal Management Management is dictated by the severity of the disease Spontaneous bleeding is generally seen when < 1% of factor is present, whereas > 5% of factor is sufficient to prevent bleeding unless traumatic or surgical insult is seen Severe disease may require regular factor repletion to maintain adequate factor levels Mild to moderate disease is generally managed when uncontrolled bleeding is encountered.2 338 www.ajlobby.com Mizukawa_Chap_23.indd 338 6/21/17 3:25 PM Hemophilia B Anesthesia considerations When major insult is anticipated and significant bleeding is imminent, factor VIII activity levels should be normalized to as close to 100% as possible A number of methods are available for increasing factor VIII activity levels: • Plasma-derived factor VIII concentrate Early on, devastating numbers of hemophilia A patients receiving transfusion of factor VIII concentrate contracted HIV and hepatitis C So, the development of viral inactivation of these concentrates emerged, and the number of HIV or hepatitis C transmissions from these products has virtually dropped to zero.14 Preoperative goals are to get the patient’s factor VIII activity level as close to 100% as possible for surgical procedures that carry a risk of severe bleeding For most minor procedures, 20% to 40% activity levels are sufficient When an initial dose of 50 to 60 units/kg is infused, nearly 100% activity level is seen Smaller doses of 20 to 30 units/kg will generally elicit 30% to 50% activity level, sufficient for minor procedures Additional dosing of 25 to 30 units/kg every to 12 hours may be required based on the level of bleeding, as the half-life of factor VIII is approximately 12 hours for adults and hours for children Accordingly, children may require more frequent dosing It is advocated to maintain this therapy for up to to weeks after a major surgical procedure, especially one involving bone and joints.13 It should also be noted that vWF levels should be checked and maintained vWF serves as a carrier protein for factor VIII in circulation, without which factor VIII would be degraded soon after infusion by plasma proteases.14 A factor VIII inhibitor phenomenon has been reported as soon as 10 to 12 days after a first exposure to a plasma-derived product or a recombinant product that will functionally negate factor VIII activity levels even after infusion of factor concentrates.13 • DDAVP will increase factor VIII activity level as well as protect factor VIII by increasing circulating concentration of vWF, the carrier protein for factor VIII These increases are modest and generally reserved for mild hemophilia cases.12 • Recombinant factor VIII can be infused in a similar manner as plasma-derived concentrates to raise the circulating factor VIII activity levels Although recombinant products avoid the risk of disease transmission, it is still susceptible to factor VIII inhibitors • Cryoprecipitate can also be infused, which will increase the levels of factor VIII, vWF, fibrinogen, and factor XIII Hemophilia B Pathophysiology and diagnosis Hemophilia B is the quantitative or qualitative deficiency of factor IX and is clinically indistinguishable from hemophilia A Stratification of the disease is similar as well, with < 1% factor IX activity level being severe, 1% to 5% being moderate, and 5% to 40% being mild.13 See “Hemophilia A” section for more information on this stratification Diagnosis of hemophilia B is the same as hemophilia A, in that the laboratory test results will indicate a deficiency of factor IX in the plasma, with normal factor VII, XI, and vWF levels As mentioned previously, because factor IX is involved in the intrinsic pathway, an elevated PTT is seen in the presence of normal PT and bleeding time Management Management of hemophilia B is the same as with hemophilia A, except patients are treated with factor IX 339 www.ajlobby.com Mizukawa_Chap_23.indd 339 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy Anesthesia considerations Replacement of factor IX to suitable levels is the main objective in the management of hemophilia B, similar to that of hemophilia A However, a few exceptions exist When replacing factor IX, dosing and frequency are different As with factor VIII replacement, factor IX can be infused as a plasma-derived product or a recombinant product Factor IX will tend to be chelated by collagen within the vasculature, so dosing of factor IX concentrates are generally doubled Thus, an initial infusion of 100 units/kg should achieve near 100% factor activity levels Smaller doses of 30 to 50 units/kg will provide 20% to 40% factor activity levels, sufficient for minor procedures The half-life of factor IX is approximately double that of factor VIII at 18 to 24 hours, so dosing is spaced out to 12- to 24-hour frequencies between doses.13 Sickle Cell Disease Pathophysiology and diagnosis Sickle cell disease (SCD) is an autosomal recessive disease of hemoglobin, affecting up to 100,000 individuals in the United States.15 It has an ethnic predilection, affecting African Americans at a rate of 1:500 births, a higher rate than other ethnic groups A normal hemoglobin molecule, hemoglobin A, has four subunits, including two α subunits and two β subunits When glutamic acid is replaced by valine in the β subunit, hemoglobin S (HbS) is formed.13 Heterozygous transmission of HbS results in sickle cell trait, which is thought to be clinically insignificant, whereas homozygous inheritance results in SCD SCD is characterized by: • Decreased RBC lifespan, from 120 days to 10 to 12 days.15 Patients can have a profound hemolytic anemia • Occlusion of vessels When oxygen tension is decreased (< 40 mm Hg) for a prolonged period (2 to minutes) the geometry of erythrocytes with HbS changes from its normal circular, biconcave shape to a sicklelike shape.15 This acute condition is termed sickle cell crisis These cells cannot pass through the small diameters of capillaries, and occlusion results • Organ damage Over time, organ damage will ensue, including the heart, spleen, kidneys, lungs, and brain • Occlusion of coronary vessels, causing symptoms of acute coronary syndrome • Acute chest syndrome is an acute occlusive condition of the pulmonary vasculature It can happen anytime the patient has a sickling crisis but is often associated with a pulmonary infection that causes the sickle cell crisis It manifests as chest pain, tachypnea, fever, and wheezing.15 Chest radiographs can help diagnose the condition and will show a pulmonary infiltrate in one or more lobes Broad-spectrum antibiotics should be given to manage the infection • Stroke The risk of stroke in children with SCD is 200 to 400 times higher than that in children without SCD.16 Interestingly, most strokes associated with SCD are not occlusive in nature, but are secondary to vessel damage, causing bleeding and hemorrhagic stroke.15 • Chronic pain Vasoocclusion will cause pain of the abdomen, bone, and joints • Osteomyelitis When infection and trauma affect bones, local vascular stasis and hypoxia result, which triggers sickling in the area The sickling in turn promotes further hypoxia and tissue damage, leading to infection of the bone • Splenic sequestration and hypersplenism • Retinopathy Occlusion of retinal vessels can result in vision changes and, ultimately, blindness 340 www.ajlobby.com Mizukawa_Chap_23.indd 340 6/21/17 3:25 PM Sickle Cell Disease Diagnosis of SCD is accomplished using a variety of blood tests The patient will have a low hematocrit and hemoglobin level accompanied by an elevated number of RBCs, which are likely to be the body’s attempts to compensate for the low hemoglobin levels Reticulocyte levels can be as high as 15% above normal A peripheral blood smear will show sickle cells among normal reticulocytes Howell-Jolly bodies are indicative of hyposplenia.16 Ultimately, diagnosis is most definitively accomplished with hemoglobin electrophoresis, which distinguishes the different hemoglobin species from each other Management Management strategies of patients with SCD have prolonged life expectancy, which has increased from 14 years in 1973 to 42 years in 1994.16 • Because the spleen plays a vital role in isolating and destroying encapsulated bacteria, SCD patients, who tend to have compromised splenic function, are given prophylactic penicillin to protect against Streptococcus pneumoniae • Hydroxyurea elevates fetal hemoglobin levels Fetal hemoglobin has been shown to inhibit HbS polymerization and sickling Hydroxyurea is converted to nitric oxide, which promotes vasodilation and inhibits platelet aggregation.15 • For those patients who fail hydroxyurea therapy, or in severe cases of SCD, stem cell transplant is an option It is accomplished from a human leukocyte antigen–matched sibling Not only can it be therapeutic, but it has the potential to resolve SCD.16 • Because of the hemolytic nature of SCD, many patients require transfusions Frequency will range widely, depending on the severity of the disease • Because external factors such as cold, dehydration, stress, infection, menses, and alcohol consumption can exacerbate a crisis, these conditions should be avoided.16 Anesthesia considerations Perioperative management of SCD patients must be focused on (1) preventing a crisis and (2) promptly recognizing and managing a crisis, if encountered Preoperative consultation should focus on assessing the severity of the disease Stanley and Christian15 have proposed a number of questions that will give the practitioner a better assessment of severity: When was the patient’s last crisis? Is the patient currently in crisis? If the patient has an acute odontogenic infection or has sustained maxillofacial trauma, he or she may be in the middle of a crisis How often does the patient experience a crisis? Does the patient require transfusions? If so, how often? Do specific triggers seem to predispose a crisis for that patient? After consultation with the patient, the practitioner should also consult with the patient’s hematologist regarding perioperative management Box 23-4 shows the common precipitants of crisis and perioperative efforts to avoid crisis 341 www.ajlobby.com Mizukawa_Chap_23.indd 341 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy BOX 23-4 Risk factors and perioperative management of sickle cell crisis* Cold temperatures • Keep the patient warm with blankets • Administer warm IV fluid Hypovolemia • Administer liberal IV fluids, balanced with awareness of baseline anemia and the tendency toward further dilutional anemia with IV fluids Hypoxia • Supplemental oxygen should be administered • If a high risk of hypoxia due to airway complications is present, airway adjuncts such as nasopharyngeal airway, LMA, or endotracheal tube should be used • A baseline hematocrit level should be obtained • In general, a hemoglobin level of 10 g/dL is desired, but the decision to transfuse should be made in conjunction with the hematologist Stress • Anxiolysis can be accomplished with an oral premedication of diazepam or Versed (Roche) • An IV anesthetic is ideal in minimizing stress Profound local anesthesia can help minimize stress if IV anesthesia is contraindicated Infection • Antibiotic prophylaxis should be given before oral surgery procedures • If the patient is acutely infected, the practitioner may consider the urgency of the procedure If oral antibiotics can be given for a period to resolve the acute infection, then the procedure can be postponed until the risk of crisis has decreased • Emergency situations addressed in perioperative management should be done in the operating room Vasoconstriction and stasis • Cardiac output should be maintained to minimize vascular stasis IV, intravenous; LMA, laryngeal mask airway *Data adapted from Stanley and Christian.15 Methemoglobinemia Pathophysiology and diagnosis Methemoglobinemia is a disease state characterized by iron (Fe) atoms within the hemoglobin molecule, where the ferric (3+) state predominates over the ferrous (2+) state It occurs with an imbalance of normal physiologic oxidation and reduction of methemoglobin, which results from a multitude of etiologies, the cytochrome B5 reductase pathway being of primary physiologic importance (Fig 23-4) Assuming this oxidation-reduction reaction mechanism is intact, accepted values for steady-state levels of methemoglobin under normal physiologic conditions are < 1% of the total hemoglobin concentration When reduction of methemoglobin fails, the methemoglobin begins to accumulate with systemic effects manifesting rather rapidly The oxidized hemoglobin molecules in the ferric state being rendered useless in binding oxygen, coupled with ferrous hemoglobin molecules’ increased affinity for the oxygen already bound, result in a leftward shift of the oxyhemoglobin dissociation curve (see Fig 8-1) Physiologically, this equates to impaired tissue oxygenation as a result of the decreased propensity for oxygen to dissociate from the ferrous hemes and into the cells where demand is greatest The ultimate consequence of this condition is system-wide cellular hypoxia that, if not recognized and properly treated in an expeditious manner, can then quickly result in the mortality of the patient.17 342 www.ajlobby.com Mizukawa_Chap_23.indd 342 6/21/17 3:25 PM Methemoglobinemia NADH+ NADH Cytochrome b5 reductase Fe+++–hemoglobin (methemoglobin) NADPH Fe++–hemoglobin NADPH methemoglobin reductase plus exogenous methylene blue NADP+ Fig 23-4 Biochemistry of methemoglobinemia formation (Adapted from Prchal.17) NAD, nicotinamide adenine dinucleotide; NADH, NAD + hydrogen; NADP, NAD phosphate; NADPH, NADP + hydrogen Both congenital and acquired forms have been reported Patients who present with congenital causes typically appear cyanotic and, though some may complain of nonspecific symptoms such as headache and fatigue, are largely asymptomatic, despite methemoglobin levels of up to 40% Cyanosis can initially be noticed with methemoglobin concentrations of 1.5 g/dL, or 10% to 20% of overall hemoglobin, in contrast to hypoxia-induced cyanosis, which does not present itself until g/dL concentrations are seen Patients who have the acquired form have a potentially life-threatening condition that is most often a result of contact with medication or other exogenous agents or contaminants These substances increase the production of methemoglobin directly or through the production of oxidative free radicals subsequent to their metabolism (Box 23-5) An important fact to remember is that even standard doses of these medications can trigger the onset of methemoglobinemia, especially in the population of patients with a cytochrome B5 reductase deficiency.17–19 BOX 23-5 Drugs associated with methemoglobinemia* Local anesthetics Benzocaine, prilocaine, procaine Antineoplastic agents Cyclophosphamide, flutamide Antibiotics Dapsone, sulfamethoxazole Nitrites and nitrates Nitroglycerin, nitroprusside, nitrous oxide Antimalarials Chloroquine, primaquine *Data from Prchal.18 Signs of methemoglobinemia include the following20,21: • Acute onset of cyanosis, especially after a known triggering agent has been administered (hypoxia may not accompany) • Clinical signs of decreased cellular oxygen delivery (eg, tachycardia, anxiety, dizziness) • Hypoxia in spite of increased fraction of inspired oxygen (Fio2) • Increasing disparity between Pao2 and pulse oximetry readings • Chocolate-colored appearance of blood on arterial sampling 343 www.ajlobby.com Mizukawa_Chap_23.indd 343 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy Management The first and most important step in the management of methemoglobinemia is the expedient and accurate diagnosis from the multitude of possible differential diagnoses Box 23-6 can provide some key indicators that would suggest a diagnosis of methemoglobinemia as the systemic effects may closely resemble other pathologic processes Formal diagnosis is confirmed in the laboratory through analysis of the absorption spectrum of methemoglobin with its peak of absorption being 631 nm.17 Once diagnosis is confirmed, the offending agent needs to be halted immediately and supportive measures given This is critical, especially in patients who have medical comorbidities where the oxygen delivery to tissues at baseline is already diminished, such as those with pre-existing cardiovascular or pulmonary disease as well as anemic patients.22 Younger and healthier patients may better tolerate increased methemoglobin levels and may need no other treatment than removal of the triggering agent If the patient becomes symptomatic and methemoglobin levels are > 20%, methlyene blue (MB) administration would be indicated; methemoglobin levels approaching 30% become life threatening.17,18 The MB should be given over minutes at a dose of to mg/kg intravenously In conjunction with nicotinamide adenine dinucleotide phosphate, MB acts as an electron acceptor to make way for the methemoglobin to be returned from its oxidized, ferric state (Fe3+) to its ferrous state (Fe2+) (see Fig 23-4) A response to the MB administration is usually observed quickly Should it be necessary for MB to be re-dosed after hour, it should be done carefully Cumulative levels of MB > mg/kg can be toxic and actually worsen methemoglobinemia In such a case, the MB will start to reverse the intended reduction reaction and compound the methemoglobinemic state BOX 23-6 Clinical findings in acute methemoglobinemia • Sudden onset cyanosis with symptoms of hypoxia and/or symptoms of reduced oxygen availability after administration/ingestion of triggering agent • Hypoxia unresponsive to increased Fio2 • Abnormal blood color (ie, dark brownish/bluish) • Cyanosis with normal arterial Pao2 Anesthetic considerations Pathologic states that affect end-organ oxygen delivery can be quite concerning, especially given an increasing number of patients who are more labile to changes in tissue oxygenation Therefore, careful attention must be given to a detailed medical history and initial physical exam prior to any anesthetic being administered, be it intravenous, local, or topical Dose dependence is a factor in the acquired form However, standard dosing can induce methemoglobinemia as well Prudence should be exercised regarding dosage when known triggers for methemoglobinemia are being administered.22 Although the specific principles of pulse oximetry are outside the scope of this chapter (see chapter 8), the anesthesia provider must remember that while monitoring peripheral oxyhemoglobin saturation (Spo2), methemoglobin will interfere with the accuracy of the values and can be misleading With increasing concentrations of methemoglobin, the pulse oximeter reading converges on 85% So, in the presence of high concentrations of methemoglobin, even an arterial oxyhemoglobin saturation of 20% will show an Spo2 of approximately 85% Thus, CO-oximetry, which utilizes several light-emitting diode wavelengths to detect the various species of hemoglobin, can be used to more accurately monitor oxyhemoglobin saturation.17 344 www.ajlobby.com Mizukawa_Chap_23.indd 344 6/21/17 3:25 PM Oral Anticoagulation Therapy Oral Anticoagulation Therapy Perioperative management of patients taking oral anticoagulant medications is another important consideration for any clinician performing invasive procedures that can cause significant hemorrhage Both the number of patients receiving anticoagulation therapy and the variety of anticoagulant medications are increasing Several management strategies have been employed, including preoperative discontinuation of therapy with or without bridging, alteration of the dosage/regimen, and continuation of the regimen without interruption in therapy The decision of which strategy to use should be made on a case-by-case basis and in conjunction with the clinician who is primarily managing the anticoagulation therapy Clinicians must base this decision on the risk of a thromboembolic event resulting from subtherapeutic levels of anticoagulation relative to the risk of major bleeding A unilateral decision by the oral surgeon to discontinue anticoagulation therapy is not recommended Drugs Oral anticoagulant and antiplatelet medications all act on one or more of the steps of hemostasis As mentioned previously, hemostasis is achieved is three main phases: the vascular phase, which entails vasoconstriction that facilitates the ensuing platelet phase; the platelet phase, which describes platelet aggregation and activation; and the coagulation phase, which results in maturation of the platelet plug to a fibrin-reinforced clot Antiplatelet agents affect the ability of platelets to aggregate Anticoagulants modulate the activation of thrombin and formation of fibrin, inhibiting the development of a thrombus Antiplatelet drugs Many antiplatelet medications are commonly prescribed to patients with a history of coronary artery disease, myocardial infarction, stroke, angina, nonvalvular atrial fibrillation, and peripheral vascular disease They are also given subsequent coronary artery stent placement and valve replacement surgery It is generally agreed that antiplatelet therapy does not need to be interrupted before minor surgical procedures Aspirin, or acetylsalicylic acid (ASA), is a member of the nonsteroidal anti-inflammatory drug family It irreversibly inhibits platelet function by inhibiting the function of the COX enzyme COX is responsible for the conversion of arachidonic acid to prostaglandins, which are further converted to TXA2 TXA2 facilitates platelet aggregation Because binding is irreversible, the effects of ASA last the lifetime of the platelet, or approximately 10 days A low dose of ASA, 75 mg daily, has been shown to nearly completely inhibit TXA2 and platelet function.23 Thus, a “baby aspirin,” 81 mg, is given for long-term, maintenance antiplatelet therapy However, in the acute setting of acute coronary syndrome and after having a percutaneous coronary intervention placed, a full dose, 325 mg, is given Plavix (Bristol Myers Squibb Sanofi), or clopidogrel, is a thienopyridine that also irreversibly inhibits platelet function by blocking ADP binding to the P2Y12 receptor on platelets, resulting in the inhibition of platelet aggregation.23 Plavix exerts its effects as a prodrug; its active metabolite is responsible for the physiologic effects A 75 mg/d dose is generally administered for antiplatelet effects, but it should be noted that this dose can have varying effects based on the function of the cytochrome P450 (CYP) 2C19 hepatic enzyme and the amount of Plavix that is broken down by the enzyme to the active metabolite.23 Anticoagulant drugs Coumadin, or warfarin, exerts its anticoagulant effect by blocking the activation of the vitamin K–dependent coagulation factors (II, VII, IX, X) and proteins C and S.23 It directly inhibits vitamin K epoxide reductase, the enzyme required to convert vitamin K to vitamin K hydroquinone, which is required to carboxylate, and consequently activate, those coagulation factors and proteins Thus, in the absence of carboxylation, the factors are rendered inactive Warfarin reaches peak plasma levels within hours, has a half-life of 40 hours, and has a duration of up to days, as warfarin must be cleared and new factors produced before normal coagulant function is seen.24 345 www.ajlobby.com Mizukawa_Chap_23.indd 345 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy Therefore, when cessation of warfarin therapy is indicated because of a high bleeding risk, it should be stopped at least days before a surgical procedure and bridged appropriately with the shorter-acting heparin options It should generally be resumed within 12 to 24 hours of a surgical procedure, and heparin should be continued until INR is once again therapeutic The effects of warfarin can be highly variable because of variability of the function of the P450 hepatic enzymes, age, body mass index, sex, dietary intake of vitamin K, alcohol consumption, and other comorbid diseases.23 Warfarin undergoes 90% to 100% renal elimination, and dosing should be adjusted appropriately for patients with underlying kidney disease or an acute kidney injury Warfarin undergoes metabolism in the liver via CYP enzymes Therefore, it is sensitive to concomitant administration of drugs that either induce or inhibit CYP enzymes, specifically CYP2C9 Drugs that induce production of P450 enzymes or increase their activity can increase the warfarin dose required to maintain therapeutic levels These include, but are not limited to, barbituates, carbamazepine, cholestyramine, rifampin, thiazide diuretics, and vitamin K In addition, leafy greens are high sources of dietary vitamin K and should be avoided when taking warfarin Drugs that inhibit CYP enzymes reduce warfarin metabolism and can lead to excessive anticoagulation from the patient’s normally therapeutic dose These include, but are not limited to, fluconazole, miconazole, fluexetine, simvastatin, atorvastatin Another source of excessive anticoagulation is antibiotic therapy that alters intestinal flora with a resulting decrease in vitamin K synthesis Examples of such antibiotics are metronidazole, macrolide antibiotics (eg, erythromycin, clarithromycin, azithromycin), and fluroquinolone antibiotics (eg, ciprofloxacin, levofloxacin).25 Warfarin monitoring via INR is a useful tool in determining risk of intraoperative and postoperative bleeding Evidence suggests that most ambulatory oral surgery procedures can be performed without risk of serious bleeding as long as the INR is < 4.0.24 If severe bleeding is encountered, the effects of warfarin can be reversed by intravenous (IV) or oral vitamin K Warfarin is a teratogen and is contraindicated in pregnant women.23 Target-specific anticoagulant drugs A narrow therapeutic index, relatively long half-life, the need for continuous monitoring, and multiple drug/dietary interactions have limited warfarin use and patient compliance A new class of direct oral anticoagulants have emerged with characteristics more favorable than warfarin The main advantages of this class of drugs are the rapid onset of action, relative short duration of action compared with warfarin, predictable therapeutic efficacy, and vastly reduced medication interactions These drugs also not need to be monitored via different laboratory tests like PT and INR; hence, they have a much greater safety profile than warfarin Dabigatran etexilate is a target-specific anticoagulant that binds to thrombin (factor IIa), blocking the conversion of fibrinogen to fibrin It has been shown to be superior to warfarin in preventing stroke in patients with atrial fibrillation, and as effective as warfarin in preventing and managing pulmonary embolism (PE) and recurrent venous thromboembolism Similar to Plavix, dabigatran etexilate is a prodrug that is broken down to dabigatran.26 It reaches a peak plasma level in to hours and has a half-life of 12 to 17 hours If serious bleeding is encountered, discontinuation of the drug should be sufficient to eventually control the bleeding However, idarucizumab has recently emerged as a reversal agent for dabigatran In an emergent situation, hemodialysis and/or administration of IV factor VII can also be used Although the thrombin time and aPTT have been shown to assess the anticoagulant effects of dabigatran, it has been recommended to use the aPTT to monitor the anticoagulant effects of dabigatran.26 Another advantage of dabigatran over warfarin is its ability to bind to both free and clot-bound thrombin Rivaroxaban (Xarelto, Janssen) and apixaban (Eliquis, Bristol-Myers Squibb) are factor Xa–specific inhibitors that inhibit the conversion of prothrombin (factor II) to thrombin Without thrombin, fibrinogen is not cleaved to fibrin Rivaroxaban and apixaban have been approved to prevent stroke with nonvalvular atrial fibrillation, to manage and prevent deep venous thrombosis (DVT) and PE, and reduce the risk of recurrent DVT and PE following initial treatment In addition, rivaroxaban has been approved for DVT and PE prophylaxis after knee and hip replacement surgery Like dabigatran, factor Xa inhibitors have a rapid onset of 2.5 to hours, with a half-life of to hours.26 It is hopeful that in the near future, andexanet alfa will be approved by the US Food and Drug Administration to reverse factor Xa inhibitors; however, no reversal agents are currently available.27 If severe bleeding is encountered with factor Xa inhibitors, factor VII can be administered intravenously, and hemodialysis can be considered Although the 346 www.ajlobby.com Mizukawa_Chap_23.indd 346 6/21/17 3:25 PM Oral Anticoagulation Therapy anti–factor Xa assay can be used to monitor the anticoagulant effect of factor Xa inhibitors, it is not readily available and often unnecessary in light of the rapid half-life Risk assessment Risk associated with discontinuing anticoagulant and/or antiplatelet therapy must be balanced by the risk of perioperative bleeding Knowledge of the various disease states that require anticoagulation therapy is key in treating these patients During a review of the patient’s medical history, mention of a history of mechanical heart valves, coronary artery stent placement, atrial fibrillation, DVT, PE, peripheral vascular disease, myocardial infarction, ischemic strokes, hemodialysis, and hypercoagulable states (eg, congenital vs acquired thrombophilias, cancer, nephrotic syndrome), recent hip or knee replacement surgery should lead to an investigation of potential anticoagulation therapy Questions regarding the timing, severity, and frequency of these events/procedures can give insight to the relative risk of a thromboembolic event if therapy is put on hold The types of medications prescribed, their doses, and their regimens are also useful for risk stratification It is recommended to contact the patient’s primary care physician and/or appropriate medical specialist to obtain more information concerning the patient’s indications for anticoagulation, which will shed light on the risk of discontinuation; discuss the bleeding risk stratification based on the planned procedure; and formulate a plan for managing the patient’s anticoagulation therapy Not all conditions carry the same risk of thromboembolic events Thromboembolic risk can be stratified based on the indication for anticoagulation24 (Box 23-7) BOX 23-7 Thromboembolic risk based on indication for anticoagulation High risk • Mechanical mitral valve • DVT within months • Hypercoagulable state • Atrial fibrillation with a history of stroke • Acute myocardial infarction within months • Recent stroke or transient ischemic attack within month Moderate risk • Mechanical aortic valve with > stroke risk factors • Chronic atrial fibrillation with > stroke risk factors • DVT within months Low risk • Atrial fibrillation without stroke • Cardiomyopathy without atrial fibrillation • DVT > months • Mechanical aortic valve and < stroke risk factors Regarding perioperative bleeding, risk assessment is well documented for antiplatelet agents and for warfarin Aspirin and Plavix can be safely continued in the perioperative period for ambulatory oral surgical procedures, whether alone or combined Warfarin has also been shown to be safely continued in the perioperative period without risk of severe bleeding, as long as the INR is < 4.0.26 Local measures to aid in hemostasis are encouraged28 (Table 23-8) However, due to the novelty of target-specific agents, no current consensus exists on the risk of bleeding associated with continuation of these agents It has been reported that continuation of dabigatran and rivaroxaban during the perioperative period for routine ambulatory oral surgical procedures is not associated with severe bleeding.26 347 www.ajlobby.com Mizukawa_Chap_23.indd 347 6/21/17 3:25 PM 23 • Hematopathology and Coagulopathy BOX 23-8 Local measures for hemostasis Direct pressure and sutures • Gelfoam • Oxidized cellulose (Surgicel, Ethicon) • Bone wax • Tranexamic acid Topical thrombin • Microfibrillar collagen (Avitene, C.R Bard) • Chitosan (HemCon, Tricol Biomedical) • Fibrin glue (Tisseel, Baxter) • Vasoconstrictor (epinephrine) To continue or discontinue anticoagulants Historically, treatment of patients on oral anticoagulant therapy consisted of discontinuing the medication for a number of days before a surgical procedure and checking the INR If it was close to the normal range, then the surgical procedure was performed In situations where the medications could not be put on hold, the patient was hospitalized and bridged with either IV unfractionated heparin or subcutaneous low–molecular weight heparin (Lovenox, Sanofi-Aventis) injections, which have shorter durations of action than warfarin The surgical procedure was performed after briefly stopping the heparin, which generally happened the morning of surgery Heparin was restarted after hemostasis had been achieved, and the regimen was again transitioned to the oral anticoagulant Heparin therapy would be discontinued when INR monitoring indicated that the warfarin returned to its targeted therapeutic range This approach can be logistically cumbersome, costly, and inconvenient to the patient, particularly for those requiring multiple procedures over time Although this approach still presents a viable management option, growing evidence indicates that oral anticoagulation therapy does not need to be held or bridged for simple, low-risk procedures The risk of intraoperative or prolonged postoperative bleeding is determined not only by anticoagulation therapy, but also by the nature of the surgery itself Several authors have attempted to stratify the risk of bleeding associated with dental procedures In a 2013 systematic review, simple dental procedures were defined as dental extractions of up to three teeth, placement of up to three dental implants, scaling and root planing, probing, flap surgery, apex resection, and alveoloplasty For simple dental procedures, the authors recommended no perioperative alteration in single or dual antiplatelet therapy, target specific anticoagulant therapy, or warfarin if it is within a therapeutic INR range of 2.5 to 3.5.29 A 2015 review proposed a four-category perioperative bleeding risk stratification for oral surgery procedures, including low, intermediate, moderate, and high-risk categories Low-risk procedures included < five simple extractions or soft tissue biopsies < cm in size Intermediate risk procedures included to 10 simple extractions, soft tissue biopsies 1.0 to 2.5 cm in size, and simple implant placement Moderate-risk procedures included impacted tooth extraction, > 10 simple extractions, full-mouth extractions, removal of tori, multiple implant placement, osseous biopsy, alveolectomy/alveolplasty High-risk procedures included repair of facial fractures, facial osteotomies, and bone grafts.30 Although numerous stratification strategies exist, a single scheme or management algorithm has not been universally accepted In patients that require full anticoagulation therapy (eg, mechanical heart valves, atrial fibrillation, PE, recent DVT or stroke), and in cases where the possibility of life-threatening complications precludes cessation of therapy, application of local hemostatic agents should be considered for minor surgical procedures If the bleeding risk is high and anticoagulation cannot be stopped, bridging therapy should be considered, and these procedures may be best suited for a hospital setting Summary The hematologic system is critical in all physiologic functions of the body Because disorders of this system can result in surgical and anesthetic morbidity and mortality, the oral and maxillofacial surgeon must appreciate the 348 www.ajlobby.com Mizukawa_Chap_23.indd 348 6/21/17 3:25 PM References pathophysiology associated with these disorders and understand how to manage these patients prior to, during, and after surgical and anesthetic exposures This chapter presents general principles, but individualized care should be directed by consultation with the patient’s hematologist and primary care provider as well References 16 Saunthararajah Y, Vichinsky EP Sickle cell disease—Clinical features and management In: Hoffman R, Benz EJ Jr, Shattil SJ, et al (eds) Hematology: Basic Principles and Practice, ed Philadelphia: Churchill Livingstone, 2013:577–602 Jahangir M Blood In: Jahangir M Anatomy and Physiology for Health Professionals, ed Burlington, MA: Jones & Bartlett Learning, 2016:349–370 Hudnall SD Erythropoiesis and oxygen transport In: Hudnall SD Hematology: A Pathophysiologic Approach St Louis: Mosby, 2012:15–16 17 Prchal JT Clinical Features, Diagnosis, and Treatment of Methemoglobinemia Waltham, MA: UpToDate, 2015 18 Prchal JT Genetics and Pathogenesis of Methemoglobinemia Waltham, MA: UpToDate, 2015 Topper JN, Cai J, Falb D, Gimbrone MA Jr Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: Cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress Proc Natl Acad Sci U S A 1996;93:10417–10422 19 Daly JS, Hultquist DE, Rucknagel DL Phenazopyridine induced methaemoglobinaemia associated with decreased activity of erythrocyte cytochrome b5 reductase J Med Genet 1983;20:307–309 20 Brown C, Bowling M Methemoglobinemia in cronchoscopy: A case series and a review of the literature J Bronchol Intervent Pulmonol 2013;20:241–246 Grosser T, Fries S, FitzGerald GA Biological basis for the cardiovascular consequences of COX-2 inhibition: Therapeutic challenges and opportunities J Clin Invest 2006;116:4–15 21 Cortazzo J, Lichtman A Methemoglobinemia: A review and recommendations for management J Cardiothorac Vasc Anesth 2014;28:1055–1059 Chacon GE, Ugalde CM Perioperative management of patients with hematologic disorders Oral Maxillofac Surg Clin North Am 2006;18:161–171 22 Wright RO, William JL, Woolf AD Methemoglobinemia: Etiology, pharmacology, and clinical management Ann Emerg Med 1999;34:646–656 Turgeon ML Principles of hemostasis and thrombosis In: Turgeon ML Clinical Hematology: Theory and Procedures, ed Philadelphia: Lippincott Williams & Wilkins, 2005:339–368 Clemetson KJ Platelet GPIb-V-IX complex Thromb Haemost 1997;78:266–270 23 Heptinstall S Antiplatelet agents: Current and novel In: Ferro A, Garcia DA (eds) Antiplatelet and Anticoagulation Therapy New York: Springer, 2013 Leung LLK Overview of hemostasis http://www.uptodate.com/contents/overview-of-hemostasis Accessed 21 April 2016 24 Beirne OR Evidence to continue oral anticoagulant therapy for ambulatory oral surgery J Oral Maxillofac Surg 2005;63:540–545 Perry DJ Antithrombin and its inherited deficiencies Blood Rev 1994;8:37–55 25 Hull RD, Garcia DA Biology of warfarin and modulators of INR control UpToDate https://www.uptodate.com/contents/warfarin-and-othervkas-dosing-and-adverse-effects Accessed on April 2017 10 Marcum JA, McKenney JB, Rosenberg RD Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium J Clin Invest 1984;74:341–350 26 Firriolo FJ, Hupp WS Beyond warfarin: The new generation of oral anticoagulants and their implications for the management of dental patients Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:431–441 11 Salem MR Normal hemostasis In: Salem MR Blood Conservation in the Surgical Patient Baltimore: Williams & Wilkins, 1996:3–16 27 Hu TY, Vaidya VR, Asirvatham SJ Reversing anticoagulant effects of novel oral anticoagulants: Role of ciraparantag, andexanet alfa, and idarucizumab Vasc Health Risk Manag 2016:12:35–44 12 Drummond JC, Petrovitch CT, Lane TA Hemostasis and transfusion medicine In: Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC Clinical Anesthesia, ed Philadelphia: Lippincott Williams & Wilkins, 2009:369–412 28 Doonquah L, Mitchell AD Oral surgery for patients on anticoagulant therapy: Current thoughts on patient management Dent Clin North Am 2012;56:25–41 13 Rinder CS Hematologic disorders In: Stoelting RK, Dierdorf SF (eds) Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Churchill Livingstone, 2009:407–435 29 Napeñas JJ, Oost FC, DeGroot A, et al Review of postoperative bleeding risk in dental patients on antiplatelet therapy Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:491–499 14 Powell JS Recombinant factor VIII in the management of hemophilia A: Current use and future promise Ther Clin Risk Manag 2009;5:391–402 30 Weltman NJ, Al-Attar Y, Cheung J, et al Management of dental extractions in patients taking warfarin as anticoagulant treatment: A systematic review J Can Dent Assoc 2015;81:f20 15 Stanley AC, Christian JM Sickle cell disease and perioperative considerations: Review and retrospective report J Oral Maxillofac Surg 2013;71:1027–1033 349 www.ajlobby.com Mizukawa_Chap_23.indd 349 6/21/17 3:25 PM www.ajlobby.com Mizukawa_Chap_23.indd 350 6/21/17 3:25 PM CHAPTER 24 Malignancy Matthew Myers, dmd Gregory Romney, dmd Sudheer J Surpure, md, dds www.ajlobby.com Mizukawa_Chap_24.indd 351 6/20/17 10:49 AM 24 • Malignancy Cancers of various types, specifically malignancies, are a major contributor to morbidity and mortality worldwide.1 Cancer is one of the most prevalent diseases found in patients of all ages, and it is the second leading cause of death in the United States.2,3 Because of advances in the management of cancer and other comorbidities, the number of patients living longer and reaching an older age is increasing in developed countries.4 Thus, the likelihood of treating patients currently suffering from malignancy or having previously been treated for a malignancy has increased This increase has sparked much attention from the anesthesia community, as the disease and its management can complicate patient care in a variety of ways5 and pose an anesthetic risk Chemotherapy, radiation therapy, and surgical resection have all been implicated in contributing to these anesthesia risks.4 Chemotherapy Pathophysiology Chemotherapy is used in various ways to manage cancer Whether it is used for neoadjuvant therapy before resection of a tumor, adjuvant therapy after tumor resection, or as palliative therapy, the agents used have a substantial impact on anesthetic technique.6 Traditional chemotherapeutic drugs are cytotoxic agents that act by interfering with normal function of rapidly dividing cells during various phases of the cell cycle.3 Although chemotherapeutics are effective at damaging rapidly dividing cancer cells, they also damage normal cells Chemotherapeutic agents therefore have the potential to cause substantial toxicities affecting multiple organ systems directly impacting anesthetic delivery.3 Multiple chemotherapeutic agents are available, classified by their mechanism of action and impact on the cell cycle (Table 24-1).3,6,7 More recently, targeted chemotherapy, using agents such as monoclonal antibodies directed towards specific tumor cell processes, has been used in the management of many cancers The typical chemotherapeutic regimen is given every to weeks for to months This regimen allows for short recovery phases between doses to allow a patient’s native tissues to repair and decreases overall toxic effects.6 Chemotherapeutics most commonly cause toxicities affecting the cardiac, pulmonary, hematologic, bone marrow, and gastrointestinal systems (Table 24-2) 3,6,8–10 Table 24-1 Common chemotherapeutic agents Chemotherapeutic class Mechanism of action Examples from class Alkylating agents Promote DNA cross-linking and abnormal base pairing, causing inhibition of enzymes involved in cellular replication, halting reproduction and promoting cell death Mechlorethamine, chlorambucil, cyclophosphamide, melphalan, busulfan, estramustine, carmustine, lomustine, procarbazine, dacarbazine, cisplatin, carboplatin, oxaliplatin, ifosfamide, thiotepa, semustine Metabolites Structural analogs to many vitamins, nucleotides, or amino acids, which compete for active sites on the enzymes or receptors, thus inhibiting their DNA or RNA synthesis and repair • Folic acid antagonists: methotrexate, pemetrexed • Pyrimidine analogues: 5-fluorouracil, cytarabine, gemcitabine • Purine analogues: 6-mercaptopurine, thioguanine Antitumor antibiotics Most are produced from the bacterial and fungal cultures These work by several different mechanisms, but ultimately disrupt cellular function and synthesis of nucleic acids • Anthracyclines: doxorubicin, daunorubicin, epirubicin • Actinomycin D • Bleomycin • Mitomycin C Antimicrotubule agents Effect formation or breakdown of microtubules, which causes inability to enter or complete metaphase and thus a pause in mitosis • Vinca alkaloids: vincristine, vinblastine • Taxoids: paclitaxel, docetaxel Topoisomerase inhibitors Interact with topoisomerase to decrease its function, inhibiting DNA replication, chromatid segregation, and transcription and leading to the inability to enter mitosis • Topoisomerase I inhibitors: camptothecin, irinotecan, topotecan • Topoisomerase II inhibitors: etoposide 352 www.ajlobby.com Mizukawa_Chap_24.indd 352 6/20/17 10:49 AM Chemotherapy Table 24-2 Systems-based effects of chemotherapy System Effect Contributing chemotherapeutics Respiratory • Infection from leukopenia • Interstitial pneumonitis • Chronic fibrosis Methotrexate, bleomycin, busulfan, cyclophosphamide, cytarabine, carmustine, mitomycin, cytosine, arabinoside, lomustine, doxorubicin Cardiac • Arrhythmias • Myocardial infarction • Congestive heart failure • Cardiomyopathies • Pericarditis • Myocarditis • Pericardial effusion • Cardiac tamponade Busulfan, carmustine, cisplatin, cyclophosphamide, ifosfamide, cladribine, cytarabine, fluorouracil, mitomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, etoposide, paclitaxel, trastuzumab Renal • Nephrotoxicity • Hypomagnesemia • Hypokalemia • Hypertension Nitrosoureas, bleomycin, cisplatin, cyclophosphamide, ifosfamide, methotrexate, mitomycin C, vincristine Hepatic • Cirrhosis • Coagulopathies • Elevated liver enzymes • Cholestasis Clofarabine, fludarabine, methotrexate, plicamycin, azacytidine Nervous • Peripheral neuropathies • Encephalopathy • Loss of proprioception Vincristine, cisplatin, cytarabine, ifosfamide, 5-fuorouracil, methotrexate, paclitaxel, procarbazine Gastrointestinal • Nausea • Vomiting • Diarrhea • Anorexia • Mucositis Any chemotherapeutic agent during an active treatment Hematopoietic • Myelosuppression: anemia, thrombocytopenia, leukopenia • Immunosuppression Any chemotherapeutic agent during an active treatment Anesthetic considerations Nonemergency surgical procedures may often be delayed if the patient is actively receiving chemotherapy Regardless of whether the patient is currently undergoing or has previously undergone chemotherapy, obtaining a thorough history and physical examination is important Specifically, information regarding the type of chemotherapeutic agent used, including the total dose, duration, and time since the last dose administration, and information on any adverse effects and/or toxicities that the patient has experienced is necessary A record of any pre-existing conditions can help identify a patient’s risk of further damage from chemotherapy Laboratory studies, including a complete blood cell count, serum electrolytes, and serum creatinine, can be adversely impacted by the malignancy and/or chemotherapy Additional risk may be revealed from pulmonary and cardiac toxicities with pulmonary function tests, electrocardiography, and echocardiography Delaying treatment for further work-up or correction of abnormal findings such as severe anemia, thrombocytopenia, or leukopenia may be necessary.11 Consultation with a patient’s cardiologist, pulmonologist, and/or oncologist is often beneficial preoperatively to identify and discuss potential problems that could be unmasked by the administration of anesthetics, such as cardiac dysrhythmias or reduced pulmonary function Consideration should be given to treating patients in an operating room setting if they have risk factors that could lead to anesthetic complications, especially underlying cardiopulmonary dysfunction.8 Each organ system impacted by chemotherapy should be considered when developing an anesthetic plan for the cancer patient (Box 24-1).3,6,8,12,13 353 www.ajlobby.com Mizukawa_Chap_24.indd 353 6/20/17 10:49 AM 24 • Malignancy BOX 24-1 Anesthetic considerations for chemotherapy Cardiac system • High-risk patients are those with previous cardiac morbidities, age greater than 70 years, female sex, and current or previous radiation therapy to the mediastinum • Previous anthracycline (doxorubicin) use should increase suspicion for cardiotoxicity, including impairment of myocardial contractility • Myocardial ischemia is associated with 5-fluorouracil and capecitabine • Monoclonal antibodies are associated with hypertension • Consultation with cardiology, along with electrocardiography and echocardiography, is recommended • A low threshold should be set for treatment in a hospital setting Gastrointestinal system • Oral mucositis is frequently encountered with anthracyclines, taxanes, antimetabolites, and platinum-based agents • Nausea, vomiting, diarrhea are common −−Continual nausea raises concerns about airway compromise during anesthesia −−Fluid losses may contribute to dehydration and electrolyte imbalances • Patients should be placed on a strict NPO diet before surgical procedures Hematopoietic system • Most common but transient adverse effect of chemotherapy is myelosuppression (leukopenia, thrombocytopenia, anemia) • Tumor factors and chemotherapy can cause a hypercoagulable state, especially thalidomide, cisplatin, tamoxifen • Complete blood cell count should be used to evaluate oxygen-carrying capacity, thrombocytopenia, and leukopenia • Patients are immunocompromised, thus strict aseptic technique and use of broad spectrum antibiotics should be used • Consultation with a hematologist is recommended Hepatic system • Antimetabolites are associated with acute liver dysfunction • CMP should be used to identify elevated liver enzymes • Depletion of vitamin K–dependent clotting factors is possible • PT/INR should be used to assess coagulopathy • Limit drugs with hepatic metabolism such as morphine and amide anesthetics Renal system • Many chemotherapeutics are nephrotoxic; frequently implicated agents include cisplatin, methotrexate, and ifosfamide • Routine CMP should be used to evaluate serum creatinine, GFR, and electrolytes • Judicious fluid management should be used, with avoidance of dehydration or fluid overload • NSAIDs or other nephrotoxic agents should be avoided • Renally excreted anesthetic agents should be properly dosed • Due to the potential buildup of compound A, the use of sevoflurane should be avoided Respiratory system • Dysphonia, dyspnea on exertion, or dyspnea at rest requires further investigation • Chest radiograph and pulmonary function tests recommended • Many agents cause pulmonary toxicity • Patients previously exposed to bleomycin should not receive high concentrations of inspired oxygen, high amounts of intravenous fluids, or nitrous oxide to avoid pulmonary edema and possible progression of pulmonary fibrosis CMP, comprehensive metabolic panel; GFR, glomerular filtration rate; NPO, nil per os (nothing by mouth); NSAIDs, nonsteroidal anti-inflammatory drugs; PT/INR, prothrombin time/international normalized ratio 354 www.ajlobby.com Mizukawa_Chap_24.indd 354 6/20/17 10:49 AM Chemotherapy Numerous chemotherapeutic agents have been documented to damage both the hepatic and renal systems In the face of nephrotoxicity and decreased renal function, a patient’s ability to maintain adequate blood pressure, regulate acid-base balance, and excrete renally metabolized drugs can be altered Obtaining a comprehensive metabolic panel with a focus on creatinine clearance and glomerular filtration rate is recommended Strict fluid management and avoidance of nephrotoxic substances such as nonsteroidal anti-inflammatories is important.8,10 Hepatic impairment may manifest as a coagulopathy, which should be evaluated with a prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time, platelet count, and fibrinogen level.14 Care must be taken to avoid or adjust the doses of anesthetic agents that are metabolized in the liver.10 Depending on the chemotherapeutic agent, the hematopoietic system may be adversely affected with pancytopenia This effect, of course, can have important implications when surgery is required from the standpoint of clotting The coagulopathic patient who must undergo surgery, for example, may be better served in an operating room environment where meticulous local measures can be used to assure adequate hemostasis at the surgical site(s) From an anesthetic standpoint, if tracheal intubation is required, nasal endotracheal intubation should be avoided in the thrombocytopenic patient Conversely, tumor factors and chemotherapy can lead to a hypercoagulable state Thalidomide, cisplatin, and tamoxifen, in particular, are associated with hypercoagulable states Between 2% and 10% of all patients with malignancy will develop a thrombosis, especially patients with adenocarcinoma This symptom will occasionally be the first to indicate an occult malignancy and can present in the postoperative period.13 Tumor lysis syndrome should be considered in the patient who has recently started chemotherapy, especially for a hematologic neoplasm This syndrome is associated with the release of large amounts of potassium, phosphate, and uric acid Renal failure can occur, worsening the hyperkalemia, and cardiac dysrhythmias may result Clearly, patients who are undergoing induction chemotherapy should be carefully evaluated before any surgical procedure requiring anesthesia Paraneoplastic syndromes are conditions that may accompany a variety of cancers and can present with life-threatening pathophysiologic disturbances These disturbances cover a broad range of abnormalities, including fever, cachexia, tumor antibodies causing neurologic disturbances, tumor elaboration of a wide variety of peptides with hormonal activity, and renal damage from the deposition of immunoglobulins and immune complexes A well-known example of paraneoplastic syndrome is the secretion of antidiuretic hormone (ADH) by small cell lung carcinoma, resulting in the syndrome of inappropriate ADH (SIADH) secretion and resulting water intoxication and hyponatremia.13,15 Symptoms of hyponatremia include nausea and headache, which later develop into ataxia, confusion, lethargy, and seizures.10 Other hormonelike peptides elaborated by a number of tumors include adrenocortical hormone (Cushing syndrome), insulinlike peptide (hypoglycemia), and others Drug interactions can occur between chemotherapeutic agents and drugs used in the delivery of an anesthetic (Table 24-3).16 One such example of a drug interaction is that between nitrous oxide and methotrexate When combined, the cytotoxic effect and toxicity of methotrexate is increased dramatically Therefore, before delivery of an anesthetic, the nature of a patient’s chemotherapeutic regimen and potential drug interactions should be carefully investigated Table 24-3 Anesthetic drug interactions with chemotherapeutic agents Anesthetic agent Chemotherapeutic agent Effect Succinylcholine Cyclophosphamide, thiotepa Increases effect of succinylcholine Nondepolarizing neuromuscular blockers Azathioprine Reduces neuromuscular blocking effect CNS depressants Procarbazine, vincristine, vinblastine • Increases sympathomimetic effect • Leads to synergistic CNS depression CNS, central nervous system 355 www.ajlobby.com Mizukawa_Chap_24.indd 355 6/20/17 10:49 AM 24 • Malignancy In summary, attention must be given to a patient’s clinical presentation, laboratory values, and any potential side effects of chemotherapy when considering ambulatory anesthesia Understanding the common effects of chemotherapy on each organ system is critical in making a proper assessment of surgical risk and potential optimization for surgery Radiation Therapy Pathophysiology Radiation therapy has been used effectively for a variety of malignant and nonmalignant lesions and has been proven to be both safe and effective in curative and palliative applications Nearly two-thirds of patients with cancer will be treated with radiation therapy.17 Radiation therapy works by damaging tumor cell DNA, causing an inability of tumor cells to reproduce.17 The dose, type of radiation, and location are usually determined by the size, surrounding tissue, and type of cancer Although no one standardized radiation regimen exists, the typical sequence involves delivery of a predetermined dose over to weeks.18 Radiation therapy can be administered using various methods, including use of an externally located beam or placement of implanted radioactive beads into the target tissues The advantage of the latter is limiting the radiation exposure of surrounding tissue.10 Radiation administration can have acute and chronic effects on native tissues In the acute setting, skin changes in the port of radiation, gastrointestinal problems, and bone marrow suppression leading to pancytopenia can occur.19 Alopecia, erythema, and possible scaling of the skin overlying the radiation site provide clues not only to the location of the radiation but also to the potential effects that it may have on the underlying tissues Chronic changes include possible myocardial fibrosis, radiation-induced coronary artery disease, pericardial effusions, pneumonitis, pulmonary and tracheal fibrosis if the mediastinum is irradiated, and profound peripheral and central nervous system alterations.9 In the head and neck region, radiation therapy is associated acutely with mucositis and chronically with remarkable soft tissue fibrosis, restricted oral opening, and xerostomia Notwithstanding the importance of limited oral opening and the obvious general anesthetic implications, spontaneous oral mucosa breakdown and delayed healing with any violation of oral mucosa can result in osteoradionecrosis Anesthetic considerations During the initial patient consultation, the history of radiation therapy should be carefully investigated, including location, timing, total dose, and any noted complications Many radiation-induced changes, such as xerostomia or restricted oral opening, will be obvious to the patient and clinician A thorough investigation into any known or possible adverse effects of radiation must be completed before surgery to avoid complications Radiation-induced myelosuppression can place a patient at risk for infection, reduction in blood oxygen carrying capacity, and thrombocytopenia.19 Attention to complete blood cell count, INR, and baseline oxygen saturation is warranted Stringent adherence to aseptic technique is crucial to avoid infections in this patient population The use of a broad-spectrum prophylactic antibiotic should be considered, and targeted antibiotic therapy should be employed for known infection Radiation to the head and neck region can cause numerous challenges with anesthetic management, most having to with chronic sequelae of soft tissue fibrosis, airway narrowing, and restricted oral opening Although most patients are not intubated during office oral surgical procedures, the ability to intubate is a critical consideration should the surgeon need to assume control of a patient’s airway and breathing Fibrosis and edema of the 356 www.ajlobby.com Mizukawa_Chap_24.indd 356 6/20/17 10:49 AM Systemic Effects of Metastatic Disease suprahyoid and infrahyoid regions, limited range of motion of the neck and mandible, and mucositis can make tracheal intubation difficult, if not impossible, especially in an office setting.20 Surgery for such patients will probably be safer in a hospital operating room environment Regardless of the location of the anesthesia, the team caring for such a patient should have an algorithm in place for management of the difficult airway and airway rescue Systemic Effects of Metastatic Disease Pain is a common sequela of cancer due to tumor invasion, including metastasis, cancer treatments, and pathologic fracture Metastatic spread to bone is a particularly important cause of cancer pain Pain is often accompanied by depression and anxiety.10,13 Management of cancer pain often requires chronic opioid administration Adjustments in standard perioperative opioid doses may be required because of the development of opioid tolerance.10 Cancer patients frequently suffer from cachexia due to competition between cancer cells and native tissues for nutrients, anorexia, and difficulty swallowing, among others Cachexia leads to weakness and muscle wasting, which can contribute to heart failure In addition to albumin and prealbumin, the levels of hemoglobin, lymphocytes, and triglycerides all typically will be reduced.21 Anemia of chronic disease is common in cancer; it progresses with worsening of the malignancy and is associated with a reduced oxygen carrying capacity Hypercalcemia of malignancy is seen in up to 10% of cancers and can be a manifestation of paraneoplastic syndrome or from osteolysis from bony metastases Local effects of metastatic disease can manifest through compression or obstruction of vital structures Superior vena cava syndrome occurs when a neoplasm obstructs venous return to the heart from the head and neck region through involvement of the mediastinum or from direct involvement of the vena cava by tumor This syndrome presents as edema of the face and upper extremities, and venous distention of the chest wall and neck veins may be seen Increased intracranial pressure presents with headache, altered mental status, visual disturbance, and seizures Spinal cord compression can lead to back pain and neurologic abnormalities from tumor involvement of the epidural space.13 Also, tumors of the upper and lower airway can cause significant changes in the size of the airway and can contribute to obstructive events during anesthesia.22 Anesthesia considerations The patient’s overall status should be assessed before the decision for anesthesia is made This evaluation should take place in the preoperative period with a thorough history and physical examination Consideration must be given to nutritional status, comorbidities, pain management, and risk of disease progression or worsening the patient’s general status secondary to the planned procedure Physiologic status in terms of cardiopulmonary reserve and other major organ function should be assessed and optimized Although consultation is at the discretion of the treating surgeon/anesthetist, a low threshold should be set for consultation and/or hospital-based treatment for those in poor health from malignancy The patient’s oncologist and primary care provider can often be a valuable asset in the preoperative evaluation of the patient, as they have followed the patient throughout their clinical course and have an understanding of comorbidities and problems related to the tumor and/or treatments (Box 24-2).10,13,15 357 www.ajlobby.com Mizukawa_Chap_24.indd 357 6/20/17 10:49 AM 24 • Malignancy BOX 24-2 Anesthesia considerations for metastatic disease • History and physical examination should include: cough, dyspnea-pulmonary fibrosis, signs of heart failure, and careful airway assessment • Confer with oncologist • Cachectic patients should have their nutritional status assessed and nutritional deficiencies corrected before a surgical procedure/anesthesia • Pre-anesthetic laboratory assessment should include: complete blood cell count, absolute neutrophils, platelets, serum electrolytes, creatinine, and PT/INR • Depending on the patient’s treatment history and the magnitude of surgery, additional pulmonary and cardiac evaluation may suggest pulmonary functions tests, 12-lead electrocardiography, echocardiography, etc • Stress doses of corticosteroids should be used if steroids have been used for malignancy • Prophylactic antibiotics should be used if the patient is neutropenic • Venous embolism prophylaxis should be provided, given the possibility for a procoagulative state It is generally accepted that a patient’s current opioid regimen should be continued perioperatively and that any acute intraoperative pain should be managed with short-acting opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and local anesthesia.23 Some advocate continuing the patient’s baseline opiate use postoperatively, with additional narcotic for acute pain up to 30% above the patient’s baseline dose.13 Recent literature has suggested an immunomodulatory effect of opiates, leading to decreased cytotoxic cell activity Suppression of cytotoxic cells, such as natural killer cells, may increase the possibility for metastasis and tumorigenesis Although the importance of this suppression is controversial, some anesthesiologists have recommended restriction of opioids, avoidance of volatile anesthetics, limitation in perioperative stress, and the use of NSAIDs and propofol anesthesia to avoid unnecessary immunosuppression.4 A thorough understanding of the cancer patient preoperatively is critical to providing safe and effective care Intraoperative management changes should be based on the preoperative findings, and a sound anesthetic plan should be considered before a planned procedure Airway considerations The airway can be compromised in patients suffering from malignancy because of premorbid unfavorable anatomy, head and neck radiation, or, secondary to the tumor, invasion of structures adjacent to the airway.24 Radiation therapy can lead to fibrosis of the head and neck soft tissues with decreased neck flexibility, decreased oral opening, and both epiglottic and glottic edema.20 In addition, patients may suffer pulmonary fibrosis, pneumonitis, and tracheal stenosis, all leading to possible restrictive and/or obstructive lung disease.10 Tumors of the mediastinum, pharynx, hypopharynx, or glottis may mechanically obstruct the airway, leading to occlusion of the airway when the patient is sedated in a supine position Further, they can obstruct the airway during mask ventilation or intubation, causing great risk when sedating these patients In fact, many of these patients are most safely managed with awake fiberoptic intubation in an operating room setting.20 If a patient presents with voice changes, dyspnea, dysphagia, exercise intolerance, head and neck radiation, previous head and neck surgeries, or previous tracheostomy, one should suspect possible airway complications (Box 24-3).24 358 www.ajlobby.com Mizukawa_Chap_24.indd 358 6/20/17 10:49 AM Conclusion BOX 24-3 Airway considerations for metastatic disease A careful history should include: • Suspicion for complications in patients with dyspnea, dysphagia, voice changes, previous radiation therapy • Previous airway problems with anesthesia A thorough preoperative airway assessment should include: • Mobility/size of tongue • Neck flexibility • Submandibular space soft tissue compliance • Maximum oral opening • Previous tracheostomy A low threshold should be set for management in the operating room setting with advanced airway capability Proper preoperative airway assessment is critical in these patients Clinical examination of neck mobility, including flexion and extension, maximum mouth opening, Mallampati classification, ability to protrude jaw, thyromental distance, body weight, tongue size and mobility, previous tracheostomy, or history of difficult intubation should all be thoroughly assessed during the initial consultation.25,26 Computed tomography or magnetic resonance imaging studies can help provide a visual assessment of the airway However, given the potential for difficult airway maintenance during anesthesia, a low threshold should be set for taking such a patient to the hospital for treatment under general endotracheal anesthesia to lessen the possibility of an intraoperative airway complication.22 Conclusion The foundation of proper patient assessment includes a thorough history and physical examination and includes specific questions pertaining to previous or active malignancies A history of chemotherapy, whether recent or distant, should prompt investigation into which drug or drugs were used and dosage timing of treatments Treatment complications and comorbidities should be identified and assessed individually through routine laboratory studies or other specific clinical tests to assess function of organs impacted by treatment One should anticipate possible organ dysfunction based on the nature of chemotherapeutic agent used, such as that seen with doxorubicin and cardiac toxicity Tumors and/or radiation to the head, neck, or the mediastinum should be managed as a possible airway risk, and these patients should undergo a thorough clinical airway assessment Notable systemic changes from either the malignancy or chemotherapy should be identified and corrected before ambulatory anesthesia is pursued Consultation with a patient’s oncology team and primary care physician should be routinely considered if important questions regarding comorbidities and cancer therapy remain after the history provided by the patients is reviewed Cancer stands as the second most common cause of death in developed countries, second only to cardiovascular disease Improvements in cancer treatment, the management of co-existing disease, and increased life expectancy have all contributed to a higher likelihood of the oral surgeon encountering patients who have previously or are currently undergoing therapy for a malignancy It is the duty of the clinician providing ambulatory anesthesia services to properly assess and make thoughtful selections of appropriate candidates for ambulatory anesthesia 359 www.ajlobby.com Mizukawa_Chap_24.indd 359 6/20/17 10:49 AM 24 • Malignancy References 15 Castillo JJ, Vincent M, Justice E Diagnosis and management of hyponatremia in cancer patients Oncologist 2012;17:756–765 Ash SA, Buggy DJ Does regional anesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence Best Pract Res Clin Anaesthesiol 2013;27:441–456 16 Lacerda MA Chemotherapy and anesthesia Rev Bras Anestesiol 2001;51:250–270 Bovill JG Surgery for cancer: Does anesthesia matter? Anesth Analg 2010;110:1524–1526 17 Berkey F Managing the adverse effects of radiation therapy Am Fam Physician 2010;82:381–388 Maracic L, Van Nostrand J, Beach D Update for nurse anesthetists Anesthetic implications for cancer chemotherapy AANA J 2007;75:219–226 18 American Cancer Society External beam radiation https://www cancer.org/treatment/treatments-and-side-effects/treatment-types/ radiation/science-behind-radiation-therapy/how-is-radiationgiven-external-beam-radiation.html Accessed 22 March 2017 Kurosawa S Anesthesia in patients with cancer disorders Curr Opin Anaesthesiol 2012;25:376–384 Sessler DI Long-term consequences of anesthetic management Anesthesiology 2009;111:1–4 Allan N, Siller C, Breen A Anaesthetic implications of chemotherapy Contin Educ Anaesth Crit Care Pain 2012;12:52–56 Gleeson MJ (ed) Scott-Brown’s Otorhinolaryngology, Head and Neck Surgery, ed Boca Raton: CRC Press, 2008 Gehdoo RP Anticancer chemotherapy and its anaesthetic implications (current concepts) Indian J Anaesth 2009;53:18–29 van der Pal HJ, van Dalen EC, Hauptmann M, et al Cardiac function in 5-year survivors of childhood cancer: A long-term follow-up study Arch Intern Med 2010;170:1247–1255 19 Mac Manus M, Lamborn K, Khan W, Varghese A, Graef L, Knox S Radiotherapy-associated neutropenia and thrombocytopenia: Analysis of risk factors and development of a predictive model Blood 1997;89:2303–2310 20 Balakrishnan M, Kuriakose R, Koshy RC Radiation induced changes in the airway—Anesthetic implications S Afr J Anaesth Analg 2004;10:1921 21 Araỳjo JP, Lourenỗo P, Rocha-Gonỗalves F, Ferriera A, Bettencourt P Nutritional markers and prognosis in cardiac cachexia Int J Cardiol 2011;146:359–363 22 Flory S, Appadurai IR Special considerations in anesthesia for laryngeal cancer surgery Otorhinolaryngol Clin 2010;2:185–190 10 Hines RL, Marschall KE Stoelting’s Anesthesia and Co-Existing Disease, ed Philadelphia: Saunders, 2012 23 Mehta V, Langford R Acute pain management in opioid dependent patients Rev Pain 2009;3:10–13 11 Twersky RS, Philip BK (eds) Handbook of Ambulatory Anesthesia, ed New York: Springer, 2008 24 Garg R, Darlong V, Pandey R, Punj J Anesthesia for oncological ENT surgeries: Review Internet J Anesthesiol 2008;20:1–8 12 Vaja R, McNicol L, Sisley I Anaesthesia for patients with liver disease Contin Educ Anaesth Crit Care Pain 2010;10:15–19 25 el-Ganzouri AR, McCarthy RJ, Tuman KJ, Tanck EN, Ivankovich AD Preoperative airway assessment: Predictive value of a multivariate risk index Anesth Analg 1996:82:1197–1204 13 Arain MR, Buggy DJ Anesthesia for cancer patients Curr Opin Anesthesiol 2007;20:247–253 14 Kujovich JL Hemostatic defects in end stage liver disease Crit Care Clin 2005;21:563–587 26 Miller RD, Pardo MC Jr (eds) Basics of Anesthesia, ed Philadelphia: Saunders, 2012 360 www.ajlobby.com Mizukawa_Chap_24.indd 360 6/20/17 10:49 AM CHAPTER 25 Geriatrics Wayne H Dudley, dds Ryan M Dudley, md www.ajlobby.com Mizukawa_Chap_25.indd 361 6/20/17 10:49 AM 25 • Geriatrics In 2013, the United States Census Bureau concluded that 14.1% (> 44 million) of the United States population was aged 65 years or older.1 It is estimated that by the year 2030, the percentage of individuals in this group will reach 20% of the US population, or > 70 million people With a growing geriatric population, more patients requiring oral and maxillofacial surgical services will be aged older than 65 years It is therefore important for the clinician to have an understanding of the many physiologic changes that occur in elderly individuals.2 This chapter discusses common organ systems that undergo physiologic change with aging and the practical implications of these changes in the administration of anesthesia to the geriatric patient (Box 25-1) It also provides key points in the pre-anesthetic assessment of the geriatric patient BOX 25-1 • • • • • • Age-related concomitant disease in elderly patients* Systemic hypertension Coronary artery disease Congestive heart failure Peripheral vascular disease (stroke, claudication) Chronic obstructive pulmonary disease Anemia • • • • • • Renal disease Liver disease Diabetes mellitus Subclinical hypothyroidism Arthritis Dementia *Data from Leung.2 Cardiovascular Function A large percentage (80%) of individuals older than 80 years have cardiovascular disease, making it the most common comorbid condition in the geriatric patient.3,4 As individuals age, cardiac reserve is diminished, and an increase in heart failure is seen Ventricular stiffness is found in the aging heart, which results in reduced left ventricular end diastolic volume and a subsequent reduction in cardiac output Conduction abnormalities are also more common with aging A decrease in autonomic function that is seen with aging affects the heart’s ability to increase heart rate when hypotension is present These changes illustrate the necessity to monitor the cardiovascular system, maintaining a normal sinus rhythm and blood pressure throughout the surgical procedure.4 The elderly patient’s vasculature also undergoes physiologic changes With age, the human vasculature loses elastin and collagen, resulting in increased vascular stiffness.5 The increase in vascular stiffness leads to an elevated systolic blood pressure, mean arterial pressure, pulse pressure, and resistance to ventricular emptying.4,5 To compensate for the vascular stiffness and resistance to ventricular emptying, the heart will undergo left ventricular hypertrophy.5 Respiratory Function Changes in respiratory function with aging are extremely variable As patients age, changes in respiratory function can be extremely variable, with the loss of intrinsic recoil and alveolar surface area accounting for the major alterations; rendering the geriatric patient more susceptible to respiratory problems.6 Respiratory function declines with aging as a result of changes in chest wall and lung compliance.7,8 Large airways increase in diameter, resulting in increased dead space, whereas smaller airways tend to decrease in diameter The lung parenchyma loses elastic tissue and gains collagen.2 With aging, alterations in ventilatory drive are also noted By 70 years of age, ventilatory response to hypoxemia and hypercapnia is decreased by approximately 50%, and alveolar surface area available for gas exchange is reduced by 15%.2,6,9 The prevalence of co-existing factors, including smoking, obesity, and chronic obstructive pulmonary disease, predispose the elderly surgical patient to pulmonary complications.6 362 www.ajlobby.com Mizukawa_Chap_25.indd 362 6/20/17 10:50 AM Cognitive Function Elderly patients are more susceptible to respiratory depression and apnea with the use of opioids and benzodiazepines, and these drugs need to be used with caution and in reduced doses A decrease in pharyngeal muscular support predisposes the elderly patient to airway obstruction, necessitating a heightened awareness for airway support.6 Owing to impaired laryngeal reflexes and cough reflex, elderly individuals are also at risk for aspiration.6 Therefore, the airway should be assiduously protected with use of an oral pharyngeal screen and meticulous suctioning of blood, secretions, and irrigating fluids Central Nervous System With aging, 30% of total brain mass is lost by the age of 80, and there is a gradual loss of neural function, cerebral blood flow, and cerebral oxygen consumption.2 An age-related decline in nerve conduction velocity accompanies this loss, along with a loss of afferent nerve fibers and a decrease in neurotransmitters.10 Elderly patients also exhibit a decrease in pain perception, and/or their interpretation of pain may be altered, which can affect both the preoperative work-up of the patient as well as pain management Elderly patients are also at greater risk of postoperative cognitive difficulties and even delirium Renal Function Renal function decreases with advancing age Approximately 25% of renal mass is lost between the ages of 20 to 85, functional glomeruli and renal blood flow decreases 50% by 80 years of age, and glomerular filtration rate decreases 50% to 63% in patients between 30 to 80 years old.2,11–13 Therefore, nephrotoxic drugs should be avoided Because of their adverse effect on renal blood flow, nonsteroidal anti-inflammatory drugs should be used with caution, especially in cases of dehydration Maintaining normal intravascular volume and preventing dehydration in the elderly surgical patient is imperative.13 Cognitive Function Postoperative cognitive dysfunction and even delirium is a common problem in elderly surgical patients Apart from increased age, risk factors associated with postoperative delirium include chronic impaired cognitive functioning, physical debilitation, and dementia (Box 25-2).4 Reducing the risk of postoperative cognitive changes and delirium involves minimizing, if not avoiding altogether, medications such as benzodiazepines, opioids, antihistamines and other drugs with central nervous system depressant properties Additional methods to minimize the risk of significant cognitive problems include avoiding hypoxemia and hypercapnia/hypocapnia and providing adequate postoperative pain control.2 BOX 25-2 Factors associated with postoperative delirium in the elderly patient* • • • • • Hypoxia • Pain • Drugs (eg, benzodiazepines, opioids, antihistamines) Impaired vision and hearing Anxiety, depression Pre-existing dementia Endocrine and metabolic compromise *Data from Stone and Doherty.13 363 www.ajlobby.com Mizukawa_Chap_25.indd 363 6/20/17 10:50 AM 25 • Geriatrics Pharmacokinetics/Pharmacodynamics With aging, drug pharmacokinetics (ie, drug absorption, distribution, metabolism, and excretion) are influenced by a number of factors that generally result in increased concentrations and increased elimination times Lean muscle mass decreases with aging, whereas total body fat generally increases with some difference between sexes Circulating blood volume tends to decrease as a result of decreased total water A quantitative and qualitative reduction in protein binding sites is also noted with aging.2 The increase in total body fat increases lipid storage availability, thus increasing elimination times and prolonging the effect of drugs.2 The decrease in blood volume will result in elevated initial blood concentration of the drug, thus resulting in an increased drug potency Decreasing protein binding sites allows for increased levels of circulating unbound drug, which results in more profound pharmacologic effects.2 Age-related changes in pharmacodynamics (the physiologic effect of a drug) also must be considered in the elderly population As many elderly patients will be taking a number of daily medications, they are at risk for drug-drug interactions Therefore, great care must be exercised in administering and prescribing medications in the elderly population (Table 25-1) Table 25-1 Recommendations for dosage adjustment in the elderly population Drug class Dosage adjustment Etomidate Reduction of up to 50% in bolus dose Propofol Reduction of 30% to 50% in bolus dose and infusion rates Benzodiazepines Reduction of up to 75% in bolus dose and infusion rates Opioid Reduction of up to 50% in bolus dose and infusion rates *Modified from Sadean and Glass.14 Propofol Propofol has an increased clinical effect in elderly patients To achieve a 50% peak electroencephalogram effect, the concentration of propofol is reduced by 30% in a 90-year-old patient compared with the amount needed in a 30-year-old patient.14,15 A 75-year-old patient requires an approximately 30% to 75% smaller propofol drug dose than a 25-year-old patient to achieve the same effect.15 Decreased renal clearance associated with aging will also affect propofol blood levels Therefore, whether it is administered as an infusion or a bolus, a reduction in dosage amounts is appropriate Benzodiazepines Aging patients have an increased susceptibility to benzodiazepines given their pharmacodynamic and pharmacokinetic properties Midazolam demonstrates an increased potency and decreased clearance with an increased half-life Pharmacokinetic studies show an approximate 30% reduction in clearance at age 80 years compared with age 20 years Therefore, dose reduction by as much as 25% to 55% and a longer duration of action should be anticipated when administering benzodiazepines to the geriatric patient.14,16 Diazepam, although no longer commonly used in conscious sedation, is metabolized via hydroxylation and produces desmethyldiazepam, an active metabolite with a significant clinical effect on the central nervous system.14 Accumulation of this metabolite will increase the duration of action with the use of diazepam 364 www.ajlobby.com Mizukawa_Chap_25.indd 364 6/20/17 10:50 AM Pre-anesthetic Assessment Ketamine Pharmacokinetic and pharmacodynamic changes with ketamine use in the elderly population result in a decrease in clearance and an increase in duration of action.14 In addition, ketamine should be used cautiously in patients with ischemic heart disease, in whom an increase in blood pressure and myocardial oxygen demand may be poorly tolerated Opioids An increased response to fentanyl, alfentanil, and remifentanil is seen in elderly patients Therefore, opioid doses should be decreased.14 An 85-year-old patient requires an approximate 50% smaller dosage than a 20-year-old patient.17 Prolonged duration of action of opioids is also noted in the elderly patient, owing to decreased hepatic clearance, especially with high dosages.2 The elimination half-life of fentanyl is greater in elderly patients than in younger patients because of the larger volume of distribution As a result, respiratory depression and prolonged analgesia may result in the elderly patient who receives a dose that would not be associated with any ill effects in a younger patient.2 Pre-anesthetic Assessment As a result of the progressive decline in organ function and diminished physiologic reserves with aging, comorbid conditions will have a greater effect on morbidity and mortality than age.18 The pre-anesthetic assessment of elderly patients should be focused on identifying co-existing diseases and physiologic deficits that place the patient at risk during anesthesia and in the early recovery period A comprehensive evaluation of all organ system decline is not practical or necessary in most situations However, the assessment of the physical manifestations of impaired organ systems can generally provide sufficient information to plan operative and postoperative care for the patient.3 The functional status of a patient is one of the most valuable tools for predicting postoperative outcome The American Society of Anesthesiologist Physical Status Classification continues to be a reliable indicator of mortality in surgical patients Studies have shown that the American Society of Anesthesiologist classification is a reliable predictor of postoperative mortality in patients 80 years of age.3,19 The functional status of the patient as determined by their ability to perform activities of daily living (eg, bathing, dressing) correlates with postoperative outcomes Exercise tolerance as a demonstration of functional capacity has been shown to be a very important predictor of cardiac and pulmonary complications following noncardiac surgery.3 Exercise tolerance can be assessed using metabolic equivalents (METs) (Table 25-2) When using METs, it is important to note that the inability to perform METs is associated with increased perioperative cardiac events.3,20 A patient who can perform activities of daily living, such as light housework, washing dishes, and walking two blocks or more, would score METs A patient who can perform moderate activity, such as climbing a flight of stairs, scrubbing floors, or running short distances would score greater than METs The evaluation and documentation of a patient’s functional status using the American Society of Anesthesiologists and/or METs classification systems remains an important and reliable measure of an elderly patient’s ability to undergo anesthesia and surgical care 365 www.ajlobby.com Mizukawa_Chap_25.indd 365 6/20/17 10:50 AM 25 • Geriatrics Table 25-2 Metabolic equivalents Activity level Examples MET Eating, dressing Walking, 1.7 mph, level ground; strolling 6 7.0 8.0 10.0 Light Moderate Vigorous mph, miles per hour Conclusion With an increasing elderly population, there is a necessity to understand and implement clinical practices related to the elderly Physiologic changes of the heart, lungs, and liver, when combined with the pharmokinetic and pharmodynamic properties of an anesthestic agent will alter the elderly patient’s response to anesthesia Prior to surgery and administering anesthesia, an assessment of the patient’s medical history and exercise tolerance should be performed In summary, it is the anesthesia provider’s responsibility to review, understand, and be prepared to adapt their anesthetic plan to the physiologic changes found in the elderly population References United States Census Bureau QuickFacts http://quickfacts.census gov/qfd/states/00000.html Accessed 18 September 2014 12 Lindeman RD, Tobin J, Shock NW Longitudinal studies on the rate of decline in renal function with age J Am Geriatr Soc 1985; 33:278–285 Leung JM Elderly patients In: Stoelting RK, Miller RD (eds) Basics of Anesthesia, ed Philadelphia: Churchill Livingstone Elsevier, 2007:518–529 13 Stone P, Doherty P Anaesthesia for elderly patients Anaesth Intensive Care Med 2007;8(9):361–364 Rosenthal RA, Kavick SM Assessment and management of the geriatric patient Crit Care Med 2004;32(4, suppl):92S–105S 14 Sadean MR, Glass PS Pharmacokinetics in the elderly Best Pract Res Clin Anaesthesiol 2003;17:191–205 Loran DB, Hyde BR, Zwischenberger JB Perioperative management of special populations: The geriatric patient Surg Clin North Am 2005;85:1259–1266 15 Schnider TW, Minto CF, Shafer SL, et al The influence of age on propofol pharmacodynamics Anesthesiology 1999;90:1502–1516 Sieber F, Pauldine R Geriatric anesthesia In: Miller RD (ed) Miller: Miller’s Anesthesia, ed Philadelphia: Churchill Livingstone, 2009:2261–2276 16 Maitre PO, Bührer M, Thomson D, Stanski D A three-step approach combining Bayesian regression and NONMEM population analysis: Application to midazolam J Pharmacokinet Biopharm 1991;19:377–384 Zaugg M, Lucchinetti E Respiratory function in the elderly Anesthesiol Clin North Am 2000;18:47–58 17 Shafer SL The pharmacology of anesthetic drugs in the elderly patients Anesthesiol Clin North Am 2000;18:1–29 DeLorey D, Babb T Progressive mechanical ventilatory constraints with aging Am J Respir Crit Care Med 1999;160:169–177 18 Schneider JR, Droste JS, Schindler N, Golan JF Carotid endarterectomy in octogenarians: Comparison with patient characteristic and outcomes in younger patients J Vasc Surg 2000;31:927–935 Zeleznik J Normative aging of the respiratory system Clin Geriatr Med 2003;19:1–18 Kronenberg RS, Drage CW Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men J Clin Invest 1973;52:1812–1819 10 Severn A Anaesthesia and the preparation and management of elderly patients undergoing surgery Euro J Cancer 2007;43:2231–2234 19 Djokovic J, Hedley-Whyte J Prediction of outcome of surgery and anesthesia in patients over 80 JAMA 1979;242:2301–2306 20 Fleisher LA, Fleischmann KE, Auerbach AD, et al 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing non cardiac surgery: Executive summary Circulation 2014;130:e278–e333 11 Beck LH The aging kidney Defending a delicate balance of fluid and electrolytes Geriatrics 2000;55:26–28, 31–32 366 www.ajlobby.com Mizukawa_Chap_25.indd 366 6/20/17 10:50 AM CHAPTER 26 Special Needs Populations Pamela J Hughes, dds Mae Hyre, dmd, md www.ajlobby.com Mizukawa_Chap_26.indd 367 6/20/17 10:50 AM 26 • Special Needs Populations Autism Spectrum Disorder Background Autism, a noun derived from Latin references to the self, which describes unusual behavior with an inward preoccupation, was first used in its modern sense by Hans Asperger, a German psychologist, in 1938.1 The term was applied by Leo Kanner to 11 children who exhibited a unique set of characteristics at Johns Hopkins in 1943.2 Since then, and after much evolution and controversy, the group of diagnoses including autistic disorder, Asperger disorder, Rett syndrome, childhood disintegrative disorder, and pervasive developmental delay have emerged as the autistic spectrum disorders (ASDs) Etiology Multiple genetic changes have been identified as contributors to what is clearly a multifactoral etiology.3–5 Strong hereditary factors have been demonstrated by twin and family studies, and advanced paternal age has been shown to be a risk factor.6,7 ASDs have a clear male predilection, with reported ratios of affected male vs female individuals as high as 5:1.8 Some theorize that females have been underdiagnosed as a result of different expression of ASD traits.9 Independent correlation of ASD with social, ethnic, or socioeconomic factors has not been demonstrated.4 Controversial reports suggesting that childhood vaccinations (particularly measles, mumps, and rubella) are to blame have been contradicted by overwhelming evidence and have been subsequently formally retracted.10 Although ASD research is “in its infancy,” a growing body of evidence suggests that the origin of these disorders is neuropathologic.11 Comorbidities Several comorbidities that accompany ASD with variable frequency should be kept in mind The most clinically significant may be seizure activity As many as 30% of patients with ASD have had at least two epileptic seizures.12 Seizures are seen with increased prevalence in individuals with trisomy 21 (Down syndrome) and 5p deletion syndrome (cri du chat).11 Fragile X syndrome and tuberous sclerosis have a high rate of ASD correlation.13 Abdominal pain, chronic diarrhea or constipation, and gastroesophageal reflux disease are commonly seen and should be taken seriously, as patients in this population have difficulty expressing themselves Disordered eating patterns are common, and adults with ASD have a tendency for obesity.11,14 Sleep patterns and circadian rhythms are often deranged, with demonstrable exacerbation of challenging clinical behavior.15,16 Other psychiatric diagnoses are not currently considered intrinsic to the ASD process, but they are seen so frequently in this population that all patients with ASD should be screened Higher functioning patients with ASD may engage in substance abuse at higher rates than the general population.17–19 Treatment Changes to The Diagnostic and Statistical Manual of Mental Disorders (DSM) emphasize early detection and intervention, which are critical in the management of ASD.8 Applied and functional behavioral analysis techniques have been particularly successful in helping very young patients with ASD learn to function in the world around them, cope with stressful experiences like dental treatment, and mature into adults with as much independence as possible.20 Regional and homeopathic alternative treatments, vitamin supplements, and special diets have been advocated, but evidence-based conclusions have not been drawn about their effectiveness.21 Patients may be on a ketogenic diet for seizure control, which is an established treatment approach with abundant supporting evidence.21 Current pharmacotherapy is generally targeted at managing specific behavioral manifestations in addition to any comorbidities Medications frequently taken for these conditions (such as antiepileptics, selective serotonin reuptake inhibitors and antidepressants, antipsychotics, and stimulants) and relevant adverse effects should be reviewed.3 368 www.ajlobby.com Mizukawa_Chap_26.indd 368 6/20/17 10:50 AM Autism Spectrum Disorder Anesthesia considerations Safe and effective treatment for patients with moderate and severe ASD, whether performed with the patient’s cooperation or under some level of anesthesia, requires the coordination of the entire care team Efficient admission and preoperative processes should minimize wait time, be minimally invasive, and involve as few strangers as possible Teams report success with quiet, darkened rooms and minimal interruptions.22,23 Interactions between staff and the patient should consist of calm, clear, brief, direct messages with positive reinforcement, preferably from one provider at a time.24–27 ASD patients are often easily startled and benefit especially from “tell-show-do” techniques and visual pedagogy Important information can be gathered from the patient’s family or caregivers who know the patient best Questions about previous medical experiences, including specific anesthetic drugs and techniques that were successfully employed in the past, should be among the first asked during a preoperative phone call or office visit Family or caregivers may know of particular triggers to be avoided or be able to point out signs that the patient is stressed to the limits of their coping ability and on the verge of a “meltdown.” They should be encouraged to bring small, comforting security objects that can be incorporated into the perioperative management to put the patient more at ease Perioperative behavioral management techniques for patients with ASD are much more common in the literature than specific anesthetic recommendations Most data available come from the reported experience of several teams, either as a case series or as prospective trials Current recommendations22,23,28–31 are summarized as follows: Premedication is almost universally recommended to ease transitions, intravenous (IV) line placement, and anxiety associated with induction Oral midazolam and ketamine, dosed at 0.5 mg/kg and to mg/kg, respectively, can be used either individually or together in patients with mild or more severe disorder When used together, the individual doses should be reduced One team reported great success after allowing the patient to have the oral medication of choice dissolved in a few milliliters of a favorite clear liquid 30 to 60 minutes before induction A familiar caregiver can encourage the patient by sharing a nonmedicated sip of the same.23 If the patient will tolerate a nasal hood, nitrous oxide can contribute to the sedation and help gain IV access Pulse oximetry and supplemental oxygen are applied once the patient is sedated sufficiently to accept them As the sedation deepens, IV access is generally tolerated well For those patients who cannot tolerate oral premedication, preventing IV access, intramuscular (IM) administration has been the most reliable Midazolam is dosed at 0.1 to 0.2 mg/kg (maximum, 7.5 mg), and ketamine is dosed at to mg/kg Again, a combination of midazolam and ketamine can be used, which would warrant a reduction of each individual dose Once the patient is compliant, pulse oximetry is monitored, and supplemental oxygen is administered Sedation sufficient to achieve IV access is typically seen within minutes, depending on the dose given Because of the pain and fear associated with needles, the provider should remember the dangers of IM administration in a combative adult patient All team members and family members in the vicinity of the patient should be warned to remain clear of the patient, unless they are specifically assigned to restrain the patient during administration In general, oral and IM premedication is aimed at IV access Once achieved, IV agents are immediately administered to deepen the anesthetic plane ASD patients who are able to tolerate peripheral IV access, or those who have existing lines or ports, generally well with a peaceful IV induction that minimizes noxious stimuli EMLA (Actavis), LET (ie, lidocaine, epinephrine, tetracaine), or other topical lidocaine preparations are recommended if tolerated and may ease IV placement In settings where inhalational induction is available, sevoflurane with or without nitrous oxide is generally used Patients might be allowed to habituate to the mask slowly with the aid of familiar caretakers Gas can be slowly titrated to effect Patients may even be given a mask, nasal cannula, or other inexpensive devices to take home and use for practice if it is appropriate/safe for the patient and relevant to the care plan.22,23,28 Dexmedetomidine has been used with success for procedural sedation in ASD patients, particularly when undergoing electroencephalography, as it mimics natural sleep and is associated with minimal changes in 369 www.ajlobby.com Mizukawa_Chap_26.indd 369 6/20/17 10:50 AM 26 • Special Needs Populations central nervous system activity Known drug adverse effects of hypotension and bradycardia have been observed but are easily managed Conflicting evidence makes it unclear whether dexmedetomidine raises or lowers the seizure threshold, an important consideration in this population, although no intraoperative seizures have been noted.29,32 It is critical to be aggressive in prophylactic administration of an antiemetic either pre- or intraoperatively, as postoperative nausea and vomiting can trigger a rocky recovery and prolong discharge.23 Familiar people can be especially comforting to patients with ASD as they awaken from anesthesia in a strange environment They should be invited to be with the patient as early as appropriate after completion of the procedure Postoperative pain management for these patients should be comparable to that for traditional patient populations and is best approached with intraoperative IV narcotics and oral analgesics as needed and tolerated All lines, monitors, and even peripheral IV access should be discontinued as soon as it safe to so to avoid unnecessary discomfort and annoyances The patient should be discharged to home and returned to familiar surroundings as soon as possible 22–28 Conclusion The ability of an entire clinic or hospital treatment team is put to the test when they are caring for this distinct group of patients ASD is best understood as an impairment of social interaction, with manifestations ranging from subtle traits in high-functioning people to profound disability requiring 24-hour hands-on care Anesthetic considerations for the provider include the following: (1) reducing sensory input; (2) providing clear, succinct, and direct communication; (3) minimizing changes to the patient’s comfortable routine; (4) involving direct caregivers familiar with the patient as much as is appropriate; (5) administering oral or IM premedication; (6) aggressively treating postoperative pain, nausea, and vomiting; and (7) planning for discharge to familiar surroundings as soon as it is safe to so Trisomy 21 (Down Syndrome) Patients with trisomy 21, or Down syndrome, present a unique set of considerations to anesthesia providers Down syndrome is one of the most prevalent genetic disorders worldwide and affects in 800 to in 1,400 live births.33 Patients with Down syndrome are afflicted with multiple congenital anomalies that affect almost all of their organ systems Skillful management during the perioperative period is essential for a good outcome in these patients Background Down syndrome is a genetic disorder first described by John Langdon Down in 1866 French researchers identified the genetic cause of the syndrome, the presence of all or part of a third copy of chromosome 21, in 1959.34 The syndrome typically is associated with physical growth impairment, variable cognitive impairment, and congenital and acquired organ system diseases.35 Because of advances in medicine, the median life expectancy of an individual with Down syndrome has increased drastically, from 12 years of age in the 1950s to 60 years of age in the early 2000s.36 Comorbidities associated with the aging Down syndrome patient present challenges in addition to the typical physical and cognitive issues that traditionally have been noted with respect to anesthesia management Physical characteristics Down syndrome individuals typically have physical and cognitive disabilities These disabilities have mental and physiologic manifestations The cognitive development of an adult with Down syndrome is typically at a preado370 www.ajlobby.com Mizukawa_Chap_26.indd 370 6/20/17 10:50 AM Attention Deficit Hyperactivity Disorder (ADHD) lescent level Their intellect generally approaches that of a 7- to 10-year-old child.37 The musculoskeletal features typically affect facial structures, the cervical spine, and extremities Other potential organ system problems are implicated as well Anesthesia considerations Preoperative evaluation of a patient with Down syndrome should focus on the physical, cognitive, and systemic anomalies that are frequently associated with the disease Once the provider has recognized the need for sedation due to cognitive/behavioral or procedural factors, first and foremost, a very thorough airway examination should be conducted These individuals typically exhibit large tongues; short, thick necks; and mandibular retrognathia The presence of obstructive sleep apnea is also very common in these individuals, further complicating airway management.38,39 These variables place the patient at risk for difficult ventilation or intubation, especially in an emergency situation The anesthesia provider should give careful consideration for providing anesthesia with a protected airway (intubation) in cases where a deeper plane of anesthesia is the desired goal When intubation is considered, a thorough neurologic examination should be performed preoperatively due to the possibility of alanto-axial instability; a radiographic evaluation may also be considered.40 The incidence of tracheal narrowing is substantial in patients with Down syndrome and also should be considered when intubating the patient Initial intubation of a child with Down syndrome should be performed with an endotracheal tube at least two sizes smaller than that normally used in a child of the same age without Down syndrome.36 Along with reduced immunologic function, predisposition to acute lymphocytic leukemia, and premature aging, individuals with Down syndrome may present with visual impairment, hearing loss, thyroid disorders, obesity, dental disease, and dementia as they age These disabilities can become severe and progress quickly after age 40.41 The remainder of the preoperative assessment and plan should focus on the systemic diseases noted previously The frequency of congenital cardiac anomalies in this population is high, reaching 40% to 50%.36 As such, a thorough cardiopulmonary examination should be carried out and may include electrocardiography and ultrasonography to evaluate for the presence of right-sided heart failure and congenital heart disease Those individuals with sleep apnea will often also exhibit pulmonary hypertension Fixed and irreversible pulmonary hypertension has been known to develop in Down syndrome patients with obstructive sleep apnea.36 Screening for upper respiratory tract infections is also prudent given that they are common in the Down syndrome population It is postulated that this prevalence is due to immunologic dysfunction as well as primary cilia ultrastructure abnormalities Conclusion Down syndrome is a multifaceted, complex disease that demands attention to almost every organ system and several anatomical issues when considering anesthesia options in this patient population The preoperative assessment should focus on the common disease processes and anatomical malformations that accompany Down syndrome Ultimately, the anesthesia plan should reflect the unique needs of the Down syndrome patient Attention Deficit Hyperactivity Disorder Background Attention deficit hyperactivity disorder (ADHD) is a disorder of inattention, impulsivity, and hyperactivity that affects 8% to 12% of children worldwide.42 Although the rate of ADHD falls with age, at least half of children with the disorder will have impairing symptoms in adulthood.42 Traditionally, the disorder has been managed with the stimulant drugs methylphenidate and amphetamine The mechanism of action suggests enhancement of neurotransmission of dopamine and norepinephrine Studies during the past decade have shown the safety and effectiveness of new nonstimulant drugs and long-acting formulations of methylphenidate and amphetamine.42 371 www.ajlobby.com Mizukawa_Chap_26.indd 371 6/20/17 10:50 AM 26 • Special Needs Populations Anesthesia considerations At the given rate of the prevalence of ADHD, it is likely that the oral and maxillofacial surgery anesthesia team will encounter such patients presenting for treatment and may require outpatient office anesthesia It is thus important that the anesthesia clinician and team recognize and understand the potential issues with treating patients with ADHD Unfortunately, the literature is lacking regarding ADHD and anesthesia However, research of this disorder and the perioperative issues that may accompany the diagnosis is evolving Potential issues may include difficulty in managing behavioral symptoms perioperatively, emergence issues, and stimulant drug interactions with anesthetic agents.43 In recent history, these drugs were implicated in anesthesia complications, and a debate about management of these drugs perioperatively has ensued Anesthesia concerns mainly focus on the potential interaction of the anesthetics and ADHD, including potential cardiovascular disturbances, alterations in the minimum alveolar concentration of anesthetic, postoperative nausea and vomiting, and a reduction in seizure threshold.43,44 Tait et al45 prospectively studied anesthesia induction, emergence, and postoperative behaviors in 134 children with ADHD compared to 134 controls In this study, it was found that children with ADHD were less cooperative at induction of anesthesia; exhibited an increase in maladaptive behaviors postoperatively; had greater difficulties in concentration and decision making; were more disobedient, impulsive, and fidgety; were more likely to have a poor appetite; were difficult to talk to; and exhibited an increase in temper tantrums after surgery.45 It has been theorized that children taking stimulant medications for the management of ADHD may require a change in the amount of anesthetic delivery or require routine monitoring of depth of anesthesia In a case control study46 comparing 17 children taking stimulants for ADHD with 17 control patients, no difference in depth of anesthesia at minimum alveolar concentration of sevoflurane was observed The authors concluded that the results did not support a change in anesthetic practice for children having ingested stimulants up to the day of surgery in terms of the amount of anesthetic agent delivered or monitoring of the depth of anesthesia Similar findings were reported by Schmerler et al when performing procedural sedation for fracture reduction using midazolam and fentanyl.47 Because chronic use of stimulant medications may downregulate endogenous catecholamines, it has been suggested that patients undergoing an anesthetic may become hypotensive However, several case reports and small cohort studies suggest that discontinuing the stimulant medication may not be necessary.44 Conclusion Clinicians involved in the anesthesia care of patient with ADHD will likely be faced with patient cooperation issues; however, the actual anesthesia plan and amount of agent needed for sedation should not necessarily differ from a patient without a diagnosis of ADHD The theory that chronic stimulants may potentate hypotension and that stimulants may put the patient at risk of cardiac disturbance does warrant appropriate monitoring of the cardiovascular system as in any anesthetic delivery, but does not seem to be significant enough to recommend discontinuing the stimulant perioperatively References Wolff S The history of autism Eur Child Adolesc Psychiatry 2004; 13:201–208 Kanner L Autistic disturbances of affective contact Nerv Child 1943; 2:217–250 Friedlander AH, Yagiela JA, Paterno VI, Mahler ME The neuropathology, medical management and dental implications of autism J Am Dent Assoc 2006;137:1517–1527 Udhya J, Varadharaja MM, Parthiban J, Srinivasan I Autism disorder (AD): An updated review for paediatric dentists J Clin Diagn Res 2014;8:275–279 Spence SJ The genetics of autism Semin Pediatr Neurol 2004;11: 196–204 Piven J, Palmer P, Landa R, Santangelo S, Jacobi D, Childress D Personality and language characteristics in parents from multipleincidence autism families Am J Med Genet 1997;74:398–411 372 www.ajlobby.com Mizukawa_Chap_26.indd 372 6/20/17 10:50 AM References Reichenberg A, Gross R, Weiser M, et al Advancing paternal age and autism Arch Gen Psychiatry 2006;63:1026–1032 Wing L, Gould J, Gilberg C Autism spectrum disorders in the DSM-V: Better or worse than the DSM-IV? Res Dev Disabil 2011; 32:768–773 Elliot GR Autistic disorder and other pervasive developmental disorders In: Rudolph AM (ed) Rudolph’s Pediatrics, ed 20 Stamford, CT: Appleton & Lange, 1996:168–170 10 Halsey NA, Hyman SL; Conference Writing Panel Measles-mumpsrubella vaccine and autistic spectrum disorder: Report from the New Challenges in Childhood Immunizations Conference Convened in Oak Brook, Illinois, June 12–13, 2000 Pediatrics 2001;107:84E 11 DiCicco-Bloom E, Lord C, Zwaigenbaum L, et al The developmental neurobiology of autism spectrum disorder J Neurosci 2006;26: 6897–6906 26 Scarpinato N, Bradley J, Kurbjun K, Bateman X, Holtzer B, Ely B Caring for the child with an autism spectrum disorder in the acute care setting J Spec Pediatr Nurs 2010;15:244–254 27 Delli K, Reichart PA, Bornstein MM, Livas C Management of children with autism spectrum disorder in the dental setting: Concerns, behavioural approaches and recommendations Med Oral Patol Oral Cir Bucal 2013;18:e862–e868 28 Rainey L, van der Walt JH The anaesthetic management of autistic children Anaesth Intensive Care 1998;26:682–686 29 Ray T, Tobias JD Dexmedetomidine for sedation during electroencephalographic analysis in children with autism, pervasive developmental disorders, and seizure disorders J Clin Anesth 2008;20: 364–368 30 Lubisch N, Roskis R, Berkenbosch JW Dexmedetomidine for procedural sedation in children with autism and other behavioral disorders Pediatr Neurol 2009;41:88–94 12 Spence SJ, Sharifi P, Wiznitzer M Autism spectrum disorders: Screening, diagnosis, and medical evaluation Semin Peiatr Neurol 2004;11:186–195 31 Bachenberg KL Oral ketamine for the management of combative autistic adult Anesthesiology 1998;89:549–550 13 Smalley SL Autism and tuberous sclerosis J Autism Dev Discord 1992;22:339–355 32 American Psychiatric Association Autism Spectrum Disorder Fact Sheet Arlington, VA: American Psychiatric Publishing, 2013 14 Buie T, Fuchs GJ 3rd, Furuta GT, et al Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs Pediatrics 2010;125(1, suppl):19S–29S 33 Pikora T, Bourke J, Bathgate K, Foley K, Lenox N, Leonard H Health conditions and their impact among adolescents and young adults with Down syndrome PLoS One 2014;9:96868E 15 Cortesi F, Giannotti F, Ivanenko A, Johnson K Sleep in children with autism spectrum disorder Sleep Med 2010;11:659–664 34 Hickey F, Hickey E, Summar KL Medical update for children with Down syndrome for the pediatrician and family practitioner Adv Pediatr 2012;59:137–157 16 Rzepecka H, McKenzie K, McClure I, Murphy S Sleep anxiety and challenging behavior in children with intellectual disability and/or autism spectrum disorder Res Dev Disabil 2011;32:2758–2766 17 Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity and associated factors in a population-derived sample J Am Acad Child Adolesc Psychiatry 2008;47:921–929 18 Matson JL, Nebel-Schwalm MS Comorbid psychopathology with autism spectrum disorder in children: An overview Res Dev Disabil 2007;28:341–352 19 Hofvander B, Delorme R, Chaste P, et al Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders BMC Psychiatry 2009;9:35 20 Hernandez P, Ikkanda Z Applied behavior analysis: Behavior management of children with autism spectrum disorders in dental environments J Am Dent Assoc 2011;142:281–287 21 Levy SE, Hyman SL Use of complementary and alternative treatments for children with autistic spectrum disorders is increasing Pediatr Ann 2003;32:685–691 22 Seid M, Sherman M, Seid AB Perioperative psychosocial interventions for autistic children undergoing ENT surgery Int J Pediatr Otorhinolarynogol 1997;40:107–113 23 van der Walt JH, Moran C An audit of perioperative management of autistic children Pediatric Anesth 2001;11:401–408 24 Rada RE Treatment needs and adverse events related to dental treatment under general anesthesia for individuals with autism Intellect Dev Disabil 2013;5:246–252 35 Roizen NJ, Patterson D Down’s syndrome Lancet 2003; 361:1281–1289 36 Glasson EJ, Dye DE, Bittles AH The triple challenges associated with age-related comorbidities in Down syndrome J Intellect Disabil Res 2014;58:393–398 37 Capone G, Aidikoff JM, Taylor K, Rykiel N Adolescents and young adults with Down syndrome presenting to a medical clinic with depression: Co-morbid obstructive sleep apnea Am J Med Genet A 2013;161A:2188–2196 38 Hoffmire CA, Magyar CI, Connolly HV, Fernandez ID, van Wijngaarden E High prevalence of sleep disorders and associated comorbidities in a community sample of children with Down syndrome J Clin Sleep Med 2014;10:411–419 39 Morton R, Ali Kahn M, Murray-Leslie C, Elliott S Atlantoaxial instability in Down’s syndrome: A five-year follow up study Arch Dis Child 1995;72:115–119 40 Santamaria L, DiPaola C, Mafrica F, Fodale V Preanesthetic evaluation and assessment of children with Down’s syndrome Sci World J 2007;7:242–251 41 Stores RJ, Stores G The significance of aspects of screening for obstructive sleep apnoea in children with Down syndrome J Intellect Disabil Res 2014;58:381–392 42 Biederman J, Faraone S Attention-deficit hyperactivity disorder Lancet 2005;366:237–248 43 Forsyth I, Bergesio R, Chambers NA Attention-deficit hyperactivity disorder and anesthesia Paediatr Anaesth 2006;16:371–373 25 Nelson D, Amplo K Care of the autistic patient in the perioperative area AORN J 2009;89:391–397 373 www.ajlobby.com Mizukawa_Chap_26.indd 373 6/20/17 10:50 AM 26 • Special Needs Populations 44 Chang CH, Yang CF, Huang YC, Tang GJ, Chan KH, Ting CK General anesthesia in a juvenile with attention deficit hyperactivity disorder accompanied by long-term use of methylphenidate (Concerta) Acta Anaesthesiol Taiwan 2009;47:208–211 46 Chambers NA, Pascoe E, Kaplanian S, Forsyth I Ingestion of stimulant medications does not alter bispectral index or clinical depth of anesthesia at MAC sevoflurane in children Paediatr Anaesth 2012; 22:341–344 45 Tait AR, Voepel-Lewis T, Burke C, Doherty T Anesthesia induction, emergence, and postoperative behaviors in children with attention-deficit/hyperactivity disorders Paediatr Anaesth 2010; 20: 323–329 47 Schmerler BL, Cohen DM, Leder MS, Bonsu BK Procedural sedation for fracture reduction in children with hyperactivity Am J Emerg Med 2008;26:661–664 374 www.ajlobby.com Mizukawa_Chap_26.indd 374 6/20/17 10:50 AM CHAPTER 27 Pediatric Considerations Brent DeLong, dds Adam S Pitts, dds, md Matthew Mizukawa, dmd www.ajlobby.com Mizukawa_Chap_27.indd 375 6/20/17 10:50 AM 27 • Pediatric Considerations The anesthetic management of the pediatric population in oral and maxillofacial surgery presents a unique set of challenges compared with that of the adult population Although operating with an unsecured airway is a challenge unto itself, the pediatric patient has an elevated baseline risk for airway complications owing to anatomical and physiologic differences from the adult patient As a result, clinicians must clearly understand these differences and their effect on pharmacodynamics/kinetics, as well as the different stages of psychologic development of children, to safely administer anesthesia to this population Anatomical and Physiologic Considerations Cardiovascular system Cardiac output (CO) is dependent on heart rate (HR) and stroke volume (SV), such that CO = HR × SV Because the pediatric heart is less compliant than the adult heart and SV remains constant, CO is largely dependent on HR Furthermore, the pediatric patient’s peripheral vascular system has not matured to the point of being able to significantly modify peripheral vascular resistance (PVR), making HR the largest contributing factor to a pediatric patient’s blood pressure (BP), where BP = CO × PVR This issue is significant because children have an underdeveloped sympathetic nervous system and are more prone to bradycardia under anesthesia than adults.1 Table 27-1 lists reference ranges for these key functions Normal systolic BP = 90 + (age in y) Normal diastolic BP = / (systolic BP) Table 27-1 Vital sign reference ranges* Age (y) Function 2–6 7–13 14–18 Heart rate (mean BPM and range) 100 (60–140) 90 (60–110) 80 (55–95) Systemic arterial pressure (mm Hg) 75–115/50–75 95–125/60–80 105–140/65–85 150–170 100–140 90–115 Cardiac output (mL/kg/min) *Data from Bennett et al, Parworth et al, and American College of Surgeons Committee on Trauma BPM, beats per minute Respiratory system The respiratory systems of children have anatomical features that differ from the respiratory systems of adults, which can predispose children to increased risk for airway complications Differences between the adult and pediatric respiratory system can be broken down into the upper and lower airway The upper airway contains the nasal cavity; the naso-, oro-, and hypopharynx; and the larynx, whereas the lower airway comprises the tracheobronchial tree and alveoli In the upper airway, the tongue is large relative to the oral cavity, and it is positioned more superiorly against the soft palate than the rostrally positioned larynx Moreover, in children, the larynx is funnel shaped, and the narrowest point of the airway is the cricoid cartilage, as opposed to the glottis in adults Additionally, lymphoid hypertrophy, present from ages to 10 years, can pose an increased risk for obstruction in the upper airway.1 The differences between pediatric and adult upper airways gradually equalize until they become comparable around ages 10 to 12 years (Table 27-2).1 376 www.ajlobby.com Mizukawa_Chap_27.indd 376 6/20/17 10:50 AM Anatomical and Physiologic Considerations Table 27-2 Summary of differences between pediatric and adult airway anatomy* Anatomy Pediatric Adult Tongue Large Normal Epiglottis shape Floppy, omega shaped Firm, flatter Epiglottis level Level of C3–C4 Level of C5–C6 Trachea Smaller, shorter Wider, longer Larynx shape Funnel shaped Column shaped Larynx position Angles posteriorly away from glottis Straight up and down Narrowest point Cricoid cartilage Glottic opening 250 mL at birth 6,000 mL as adult Lung volume *Data from Kache The pediatric patient’s lower airway has increased airway resistance due to decreased airway diameter and fewer numbers of alveoli leading to a lower surface area for gas exchange.1 The trachea has increased compliance, which can lead to collapse during inspiration and negative thoracic pressure Pediatric patients’ ribs are angled more horizontally than adult ribs, and their intercostal muscles are less developed, leading to less effective thoracic expansion and greater dependence on diaphragmatic breathing As a result, children are at higher risk for ventilatory fatigue Children also have an increased closing volume (CV), defined as the volume above residual volume at which the small airways close Ideally, the closing capacity (residual volume + CV) would be below the functional residual capacity (FRC), which would mean that the alveoli remain open for gas exchange after a normal expiration If the CV increases and the closing capacity creeps above the FRC, then the alveoli will begin to close before a normal tidal volume has been exhaled, and a ventilation/perfusion mismatch will occur In other words, those alveoli that are closed will be perfused, but no gas exchange will occur This process can be particularly problematic during anesthesia, when the FRC is already decreased (Fig 27-1) Inspiratory capacity Normal tidal volume Total lung capacity Airway closure occurs prematurely Airway closure begins Functional residual capacity Closing volume Increased closing volume Closing capacity Residual volume Zero lung volume Fig 27-1 Lung volumes and capacities The vertical red arrow indicates an increased closing volume, meaning the terminal alveoli begin to collapse at a higher volume The horizontal red arrow indicates that, in the pediatric population, there can be a tendency for the alveoli to collapse even before a normal tidal volume is exhaled With collapsed alveoli, there is a ventilation:perfusion mismatch where the alveoli are perfused but no gas exchange is observed 377 www.ajlobby.com Mizukawa_Chap_27.indd 377 6/20/17 10:50 AM 27 • Pediatric Considerations Summary Given the previously discussed differences in anatomy and physiology in the pediatric population, clinicians must establish a generalized age limit and appropriate facility setting in which they are comfortable performing these anesthetics, based on their knowledge of anatomical and physiologic differences and their comfort level in treating this age group Psychologic Assessment The oral and maxillofacial surgery office is an unfamiliar environment with unfamiliar people for pediatric patients Moreover, threats of impending pain and needles, as well as separation from parents, can lead to behavioral manifestations such as hyperventilation, trembling, crying, agitation, or physical resistance It is estimated that 50% to 75% of children develop significant anxiety during the perioperative period.5 Children aged younger than years cannot comprehend the need or benefits of surgery, whereas older children are generally capable of understanding and expressing concerns or fear and may participate in the anesthetic plan Allowing the parents to be present during induction may reduce the child’s stress and improve cooperation, although parents can also complicate matters through expression of their own anxiety and fear.1 Moreover, parental presence can be a major distraction if management of an adverse event needs to be initiated.5 Lastly, the surgeon must be aware of the possibility of illicit drug use in the older children/adolescent group Recent studies have estimated 10.8% of 12- to 17-year-olds have used illicit drugs at one time.1 Monitoring During Anesthesia In addition to the pharmacologic advances that have occurred in outpatient anesthesia, huge technologic advances have occurred over the past 50 years Many of these technologies have trickled down from operating room environments to now being the standard of care in outpatient anesthesia Most recently, the clinically relevant and cost-effective end-tidal carbon dioxide (etCO2) monitoring has become an invaluable tool when used in conjunction with other “standard” monitors in the outpatient environment Following the lead of organizations such as the American Society of Anesthesiologists, the Commission on Accreditation of Healthcare Organizations, the American Heart Association and the American Academy of Pediatrics, the American Association of Oral and Maxillofacial Surgeons board of trustees aligned its monitoring requirements by mandating the use of etCO2 monitoring in oral and maxillofacial surgery offices starting in 2014.6 Current standards for respiratory monitoring, including respiratory rate and pulse oximetry, not always indicate, in real time, the adequacy of alveolar ventilation during spontaneous breathing.7 In fact, airway obstruction caused by secretions or by the tongue and epiglottis falling back against the posterior wall of the pharynx does not necessarily reduce the respiratory rate when measured via impedence.7 Inspection of the chest is a subjective measure and a weak indicator of adequate ventilation.7 Moreover, arterial desaturation due to hypoventilation or obstruction is a late finding, especially in the presence of oxygen administration While etCO2 ranges between 35 and 45 mm Hg in exhaled air under normal ventilation, this quantitative analysis is only pertinent in a “closed” system with a secured airway In the absence of a closed system, such as when monitoring a patient without a secured airway, it is the qualitative analysis of etCO2 waveform that gives the practitioner a real-time objective evaluation of alveolar gas exchange Considering that children are more prone to airway obstruction, the addition of etCO2 monitoring provides an invaluable adjunct to monitoring ventilation during administration of anesthetics In addition, while monitoring a pediatric patient under anesthesia, clinicians must ensure that appropriately sized equipment is present, including a blood pressure cuff, nasal cannula, pulse oximeter probe, endotracheal tubes, and nasal and oral airways 378 www.ajlobby.com Mizukawa_Chap_27.indd 378 6/20/17 10:50 AM Common Comorbidities Affecting Anesthesia Management Common Comorbidities Affecting Anesthesia Management Upper respiratory infections Upper respiratory infections are common among the pediatric population and can have a significant impact on respiratory function and lead to serious complications during anesthesia Studies have shown that upwards of 22.5% of children report for surgery with signs of an upper respiratory infection and that 45.8% present with a recent history of symptoms.8 Physiologic changes in the pulmonary system include increased nasal and lower airway secretions, airway edema/inflammation, and increased airway tachykinins.1 These physiologic changes have been shown to have a positive correlation with perioperative bronchospasm, laryngospasm, and resulting hypoxia.9 Moreover, these changes have been shown to persist for at least weeks and potentially for to weeks after an upper respiratory infection In the presence of clinical symptoms of upper respiratory infection (eg, productive cough, fever, mucopurulent discharge), elective surgical procedures should be postponed at least weeks and preferably to weeks However, it is generally agreed that chronic nasal discharge does not pose significant anesthesia risk.9 Postponing surgical procedures for weeks is probably sufficient for short office-based procedures with an unsecured airway However, for elective cases, the author of this chapter recommends postponing procedures for to weeks Children with active or recent upper respiratory infections require approximately 30% less apneic time to desaturate than healthy children.10 Asthma Asthma is the most prevalent systemic disease in children, occurring in approximately 10% of the pediatric population.11 Current reports show this number is increasing, especially in urban pediatric populations.11 The astute clinician must be able to evaluate for severity of disease and determine whether to proceed with treatment Because airway resistance is inversely proportional to the diameter of the airway lumen, pediatric patients are predisposed to rapid decompensation during an acute bronchospasm.11 Patients should be asked about their medication regimens, frequency of acute attacks, precipitating factors, history of hospitalizations, and history of intubation and mechanical ventilation Elective surgery is contraindicated in poorly controlled patients.11 Intraoperative management should focus on oxygenation, avoiding airway stimulation, and appropriate treatment, if necessary In the event of an intraoperative bronchospasm, treatment should focus on early detection, evaluation of vital signs, oxygenation, inhaled β-agonists, sympathomimetics, corticosteroids, and ventilatory support, if needed.11 For more information on the management of bronchospasms, please refer to chapter 16 Attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is defined as a persistent severe pattern of inattention or hyperactivity-impulsivity symptoms compared with other children at a comparable developmental level.12 Approximately 5% of children are diagnosed with ADHD and are commonly treated with psychostimulants such as methylphenidate, dextroamphetamine, or pemoline.13 Additionally, 1% to 2% of high school students are reported to have abused these drugs.14 Psychostimulants tend to increase blood pressure and heart rate and, when taken appropriately, are well tolerated However, careful consideration of these medications and their physiologic effects should be included in the anesthetic treatment of this patient population No contraindications currently exist for any commonly used anesthetic medications in this population, including ketamine, assuming medication abuse has not taken place.13 Preoperative fasting guidelines The American Society of Anesthesiologists’ recommendations for patient fasting before elective surgery have been modified and relaxed from the previously strict prohibition of solids and liquids for several hours before induction of 379 www.ajlobby.com Mizukawa_Chap_27.indd 379 6/20/17 10:50 AM 27 • Pediatric Considerations anesthesia (Table 27-3).15 Many hospitals have adopted guidelines that apply to all patients regardless of age Pediatric patients are more prone to dehydration than adults, and, therefore, extended fasting periods for these patients lead to increased irritability.2 As a result, pediatric fasting periods are generally shorter and less strict, although the risk for aspiration is three times higher in pediatric patients, indicating the need for careful attention to the matter Table 27-3 Summary of fasting recommendations* Ingested material Minimal fasting period (all ages) Clear liquids (water, pulp-free juices, carbonated beverages, clear tea, black coffee) hours Breast milk hours Infant formula, nonhuman milk hours Light meal (excludes fried or fatty meals, which may prolong gastric emptying) hours *Data from Stoehlting and Miller.15 Routes of Anesthesia Administration The primary goals in the treatment of the pediatric patient are to reduce anxiety, establish cooperation, ensure comfort, establish amnesia and analgesia, and ensure hemodynamic stability Medications can be administered via oral, intranasal, transmucosal, rectal, intramuscular (IM), inhalational, and intravenous (IV) routes The IV route is preferred given that it offers the most rapid onset, rapid offset, and predictable effect, as well as provides a route of rapid administration of rescue drugs in the event of an emergency However, an intense fear of needles may preclude IV placement without additional means of sedation The other routes of drug administration can be used alone or to facilitate venous access, depending on the patient and the anesthetic needs Many children report the needle puncture from either IV placement or IM injection as the worst part/memory of their care.13 Inhalation The inhalational induction of anesthesia with a potent anesthetic agent also provides rapid onset, rapid offset, and a predictable effect similar to that of the IV route The advantage of this approach is the option to use short-acting agents, enabling the anesthetic state to be rapidly terminated upon conclusion of the procedure, without the use of venipuncture.1 The approach begins with administering oxygen or oxygen plus an inhalational anesthetic, maintaining ≥ 30% oxygen concentration Two techniques are commonly employed The first involves gradually increasing the concentration of the anesthetic agent until induction is achieved, whereas the second involves beginning with a high concentration of the agent A modification of the second technique is the single-breath technique, where the patient takes a deep breath of a high concentration of the agent and holds his or her breath until induction is complete.1 General anesthesia can be maintained with the inhalational agent via a nasal hood for short procedures or with an laryngeal mask airway or endotracheal tube for longer procedures Alternatively, IV access can be obtained and anesthesia maintained via the IV route One disadvantages of the inhalational route is the objectionable scent of certain potent anesthetic agents, although this disadvantage can be overcome by applying a scent to the face mask.1 Additionally, the child may not accept the face mask, in which case distraction or restraining techniques can be used The use of inhalation anesthesia alone does not provide a route of rapid administration of rescue drugs in the event of an emergency Moreover, its use requires the presence of dantrolene in the facility to manage malignant hyperthermia Refer to chapter for more information on specific agents Whereas a thorough discussion of the common inhalational agents are discussed in chapter 3, the present discussion will concentrate on the most commonly administered outpatient inhalational anesthetic, nitrous oxide (N2O) 380 www.ajlobby.com Mizukawa_Chap_27.indd 380 6/20/17 10:50 AM Routes of Anesthesia Administration Nitrous oxide N2O can be an effective and safe anesthetic option in the pediatric population Although it is not a potent anesthetic agent when used alone, it may be used in conjunction with other techniques to provide a more profound level of anesthesia The primary use of N2O is to provide anxiolysis, amnesia, and mild sedation Pharmacodynamic advantages of N2O include rapid induction and emergence, minimal cardiovascular effects, and no significant decrease in respiratory drive when used in an appropriate manner Contraindications to N2O include severe pulmonary obstructive disease.16 Nausea and vomiting are the most common adverse effects, occurring in 0.5% of patients.16 Fasting is not required before induction with N2O alone; however, if any additional sedation is planned, a period of fasting is required Administration of N2O is preceded by 100% oxygen for to minutes and for minutes following termination of N2O.16 Oral The oral route of drug administration can be the least threatening and easiest mode of delivery for children Although some practitioners use the oral route as the sole method of sedation, this route can also be used as an adjunct premedication before venipuncture, inhalation, or IM induction Oral administration is widely accepted by a majority of pediatric patients, but it does result in a slow onset, variable response, and prolonged recovery.2,13 Midazolam Midazolam is available in a syrup formulation; however, the parenteral formulation can be added to a flavored beverage for oral administration Oral midazolam is delivered at a dose between 0.5 and 1.0 mg/kg, with a maximum of 15 to 20 mg It is usually effective within 15 to 30 minutes of administration, with peak plasma level occurring at 20 to 50 minutes The bioavailability is 35% to 44% due to the gastric acidity of the stomach Disadvantages include the inability to titrate, unreliable absorption as a result of a high degree of hepatic first-pass metabolism, and moderate failure rates Ketamine No oral form of ketamine is available, and, therefore, the parenteral formulation is mixed with a liquid carrier for administration.2 When used alone, oral ketamine is delivered between to 10 mg/kg, although most studies show mg/kg as the ideal dose Extensive hepatic first-pass metabolism is present, with reports of bioavailability between 17% and 60%.17 Onset of action ranges from 17 to 25 minutes, with a mean duration of 36 minutes Oral ketamine can be used as the solo agent for sedation, but most current studies combine ketamine with midazolam to decrease the risk of emergence delirium.2,17 One study found that oral ketamine in combination with midazolam was superior to midazolam alone and that it provided sufficient anesthesia for complete dental procedures.17 Clonidine Clonidine has also been reported for oral use; however, no liquid oral form is available, and, therefore, the pill is crushed and dissolved in a fixed volume for administration Oral availability is 75% to 95%, and peak plasma levels are seen between 60 and 90 minutes One study showed an onset of action of 90 minutes, with no episodes of hypotension, bradycardia, or saturation of peripheral capillary oxygen < 95%.18 In the same study, 33% of children were sedated for venipuncture, and 26% were sedated for mask induction.18 381 www.ajlobby.com Mizukawa_Chap_27.indd 381 6/20/17 10:50 AM 27 • Pediatric Considerations Intranasal The intranasal route was initially proposed for pediatric sedation because it was believed to avoid first-pass metabolism, be rapid in onset, and be less traumatic than other routes of administration The intranasal route results in rapid increases in plasma concentration through the rich vascular and neuronal networks found beneath the thin nasal mucosa In addition, drugs can enter the central nervous system directly through the cribriform plate.2 However, although it was initially thought to be less traumatic, intranasal administration is often not well accepted by children.1,19,20 Medications are irritating to the nasal mucosa, and the large volume of medication required results in a portion of it passing into the pharynx and being swallowed.1 Therefore, the unpleasant taste is not avoided, and the drug is subjected to first-pass metabolism through gastric mucosa.1 Midazolam The parenteral formulation of midazolam can be used intranasally, although it can result in a higher volume administered, which may account for the salivation, lacrimation, burning, and overall discomfort associated with intranasal midazolam.21 Alternatively, a metered-dose atomizer can be used, which, unlike intranasal liquid, is not partly swallowed, and absorption from the nasal mucosa is virtually complete.21 Dosages range from 0.2 to 0.6 mg/kg, with 0.2 and 0.3 mg/kg being more common The bioavailability has been shown to range from 55% to 83%,22 far surpassing that of oral midazolam, which ranges from 15% to 27%.21 In a study comparing oral versus nasal midazolam, onset of action, sedation score, and recovery time were more satisfactory in the group who received nasal midazolam (0.2 mg/kg).23 Dexmedetomidine Dexmedetomidine (Precedex [Hospira]) is a potent, highly selective, and specific α2-adrenergic agonist that has both sedative and analgesic effects In one prospective, randomized, double-blinded study comparing intranasal midazolam versus dexmedetomidine, the parenteral formulation of dexmedetomidine was used by adding a dose of μg/kg to 0.9% saline for a total volume of mL Intranasal administration resulted in superior sedation, less nasal irritation, and reduced postoperative pain and agitation than intranasal midazolam.24 Ketamine In one study in which intranasal ketamine was used alone for the repair of lacerations in the pediatric emergency room, mg/kg was required to achieve adequate sedation.25 For most office-based oral and maxillofacial surgeons, this approach would most likely be used to allow for venipuncture, where additional medications would be administered intravenously or alone for very brief dentoalveolar procedures.25 Fentanyl Fentanyl can be administered intranasally between 0.75 and 1.5 μg/kg for children older than year in moderate to severe pain.26 It can be used in conjunction with Versed (Roche) and ketamine; however, as more anesthetics are added, more volume is needed to inject, which greatly reduces the acceptance by the child Contraindications to intranasal administration of medications include known allergies to the medications, altered consciousness, occluded nasal passages, or epistaxis 382 www.ajlobby.com Mizukawa_Chap_27.indd 382 6/20/17 10:50 AM Routes of Anesthesia Administration Intramuscular The IM administration of anesthetics is advantageous owing to its ease of administration, rapid onset of action, better absorption than oral and rectal routes, and greater predictability of the duration of action However, this route does not overcome the fear of needles or injections that some children present with Ketamine Ketamine (initial dose, to mg/kg) is the most common agent administered through the intramuscular route because of its onset within to minutes and a working time of 15 to 30 minutes.13 A disadvantage of IM ketamine is the unpredictable recovery time One study showed a mean recovery of 82 minutes; however, recovery from injection to discharge took upwards of hours.27 Midazolam In a study comparing IM versus intranasal midazolam, the IM route (0.1 to 0.2 mg/kg) produced a significantly better level of sedation for either local anesthesia or venipuncture.28 Less movement was also noted with the IM route.28 Intravenous sedation technique A variety of premedication/sedation combinations are available; however, variable responses are seen between patients and practitioners If the patient has significant anxiety regarding the IV, eutectic mixture of local anesthesia (EMLA, Actavis) cream can be used in conjunction with N2O to accomplish venipuncture The EMLA cream can be prescribed and applied by a parent before arrival at the office considering the length of time for onset (1 to hours) Alternatively, the oral and maxillofacial surgeon can combine oral premedication with N2O to allow for venipuncture As stated previously, oral clonidine, ketamine, or midazolam—alone or in combination—are effective to accomplish venipuncture and may provide sufficient anesthesia alone depending on the planned procedure Ideally, allotting appropriate time and resources for the specific needs of this population will result in a pleasant perioperative experience On the basis of this author’s experience, the vast majority of children aged > 10 years will undergo venipuncture without significant morbidity For the small percentage that require additional presedation, this author’s preferred method begins with oral midazolam (0.5 mg/kg) or a combination of oral midazolam and ketamine (1 to mg/kg) approximately 30 minutes before initiation of the procedure This approach generally provides sufficient sedation to allow for venipuncture and sometimes to accomplish very short, nonstimulating procedures Once IV access is established, anesthesia can be titrated and maintained using the recommended weight-based dosing of midazolam (0.05 to 0.1 mg/kg), fentanyl (1 μg/kg), ketamine (1 mg/kg), and propofol (1 mg/kg) Note that the dose per kilogram of midazolam and/or ketamine should be decreased in the presence of premedication The addition of fentanyl and propofol can be very beneficial in the balanced technique Medications such as glycopyrrolate (0.01 mg/kg) may be used for their anticholinergic effects on salivation when working in/around the oral cavity Although it is outside of the scope of this chapter to discuss pediatric advanced life support, it would be remiss to not mention the appropriate “rescue” medications that should be immediately available when administering anesthetics to this population 383 www.ajlobby.com Mizukawa_Chap_27.indd 383 6/20/17 10:50 AM 27 • Pediatric Considerations Succinylcholine In the event of a suspected laryngospasm refractory to head-lift, jaw-thrust maneuvers, suctioning, and positivepressure ventilation, succinylcholine (1 to mg/kg) should be administered to paralyze the laryngeal muscles In children in which significant bradycardia is common after administration of succinylcholine, premedication with atropine (0.02 mg/kg) can decrease the likelihood of this cardiac response.29 In situations where IV access is not available or has been lost, succinylcholine can be administered IM at a dose of to mg/kg into the lateral thigh, deltoid, or submental region Following administration, the provider must be prepared to assist/control ventilations until the patient regains adequate respiratory mechanics Succinylcholine is only used in children for emergency airway control, as children are more susceptible to malignant hyperthermia from undiagnosed myopathies, hyperkalemic cardiac arrest, and masseter muscle spasm than adults.29 Atropine Atropine is a tertiary amine anticholinergic medication that prevents the muscarinic effects of acetylcholine by competing for the same receptors that are normally occupied by the neurotransmitter.15 Cardiac dysrhythmias, such as sinus bradycardia, are frequent after succinylcholine administration, especially after a second IV dose less than minutes from the initial dose.15 Prior administration of IV atropine (0.02 mg/kg) can reduce the incidence of cardiac dysrhythmias and should be given to all children and teenagers unless a contraindication to tachycardia is present.30 Dosages are listed in Table 27-4 Table 27-4 Pediatric drug doses* Drug Comment Dose Onset Premed (PO) Maximum dose (PO) Premed (IN) Premed/sedation (IM) Maximum dose (IM) Sedation/GA (IV) 0.5 mg/kg 20 mg 0.2–0.6 mg/kg 0.1–0.2 mg/kg 7.5 mg 0.05 mg/kg Fentanyl Pain relief (IV) Premed/pain relief (IN) Anesthetic adjunct (IV) 1–2 μg/kg 0.75–2.0 μg/kg 1–5 μg/kg Dexmedetomidine Premed (IN) 0.5–1 μg/kg 20–40 Ketamine Premed (PO) Premed/sedation (IN) Initial dose (IM) Supplemental dose (IM) Sedation (IV) 1–10 mg/kg 3–9 mg/kg 4–5 mg/kg 1–2 mg/kg 0.5–1.0 mg/kg 17–25 30–60 Propofol Induction (IV) Maintenance infusion (IV) 2–3 mg/kg 60-250 μg/kg/min Clonidine Premed (PO) μg/kg (maximum, 200 μg) Atropine Bradycardia (IV) 0.02 mg/kg (minimum, 0.1 mg; maximum, 0.5 mg) Succinylcholine Laryngospasm (IV) Laryngospasm (IM) 1–2 mg/kg mg/kg Midazolam 15–30 10–25 30–120 30 sec Slightly longer than IV Premed, premedication; IN, intranasal; PO, by mouth; GA, general anesthesia *Data from Bennett et al,1 Butterfield et al,13 Sequeira,18 Sheta et al,24 Tsze et al,25 Lam et al,28 and the American Association of Oral and Maxillofacial Surgeons.31 384 www.ajlobby.com Mizukawa_Chap_27.indd 384 6/20/17 10:50 AM References References Bennett J, Dembo J, Butterfield K Pediatric Sedation In: Miloro M, Ghali GE, Larsen PE, Waite PD (eds) Peterson’s Principles of Oral and Maxillofacial Surgery, ed Hamilton: BC Decker, 2004:103–128 17 Alfonzo-Echeverri E, Berg JH, Wild TW, Glass NL Oral ketamine for pediatric outpatient dental surgery sedation Pediatr Dent 1993;15:182–185 Parworth L, Listello T, Bell G Pediatric Pharmacosedation and General Anesthesia In: Fonseca RJ, Marciani RD, Turvey TA Oral and Maxillofacial Surgery, ed St Louis: Saunders, 2008:93–111 18 Sequeira T A comparison of midazolam and clonidine as an oral premedication in pediatric patients Saudi J Anesth 2012;6:8–11 American College of Surgeons Committee on Trauma Pediatric trauma In: Advanced Trauma Life Support for Doctors, ed Chicago: American College of Surgeons, 2012:246–270 Kache S Pediatric airway & respiratory physiology Stanford Medicine, Department of Pediatrics http://peds.stanford.edu/Rotations/ picu/pdfs/10_Peds_Airway.pdf Last modified August 2016, accessed 10 February 2017 Kain ZN, Caldwell-Andrews AA Preoperative psychological preparation of the child for surgery: An update Anesthesiol Clin North Am 2005;23:591–614 American Association of Oral & Maxillofacial Surgeons Parameters of Care: Clinical Practice Guidelines for Oral and Maxillofacial Surgery (AAOMS ParCare 2012)—Anesthesia in Outpatient Facilities http://www.aaoms.org/docs/govt_affairs/advocacy_white_papers/ parcare_anesthesia.pdf Accessed 22 March 2017 Sammartino M, Volpe B, Sbaraglia F, Garra R, D’Addessi A Capnography and the bispectral index—Their role in pediatric sedation: A brief review Int J Pediatr 2010;2010:828347 Parnis S, Barker D, Van Der Walt J Clinical predictors of anaesthetic complications in children with respiratory tract infections Paediatr Anaesth 2001;11:29–40 Maestrello C, Abubaker AO Intravenous Sedation In: Abubaker AO, Benson KJ (eds) Oral and Maxillofacial Surgery Secrets, ed St Louis: Mosby, 2007 10 Kinouchi K, Tanigami H, Tashiro C, Nishimura M, Fukumitsu K, Takauchi Y Duration of apnea in anesthetized infants and children required for desaturation of hemoglobin to 95%: The influence of upper respiratory infection Anesthesiology 1992;77:1105 11 Lee JT, Bagheri SC Acute asthma attack In: Bagheri SC, Jo C (eds) Clinical Review of Oral and Maxillofacial Surgery Missouri: Mosby, 2008 12 American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, ed Washington, DC: American Psychiatric, 2013 13 Butterfield KJ, Bennett JD, Dembo JB Outpatient anesthesia In: Miloro M, Ghali GE, Larsen P, Waite P (eds) Peterson’s Principles of Oral and Maxillofacial Surgery, ed Beijing: People’s Medical Publishing House–USA, 2012:63–93 14 SAMHSA National Survey on Drug Use and Health (NSDUH) Data Review https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR22015/NSDUH-FFR2-2015.htm Accessed on 22 March 2017 15 Stoehlting RK, Miller RD Basics of Anesthesia, ed Philadelphia: Churchill Livingstone, 2007 16 American Academy of Pediatric Dentistry Council on Clinical Affairs Guideline on Use of Nitrous Oxide in Pediatric Dental Patients http:// www.aapd.org/media/Policies_Guidelines/G_Nitrous.pdf Accessed 25 January 2017 19 Fishbein M, Lugo RA, Woodland J, Lininger B, Linscheid T Evaluation of intranasal midazolam in children undergoing esophagogastroduodenoscopy J Pediatr Gastroenterol Nutr 1997;25:261–266 20 Lejus C, Renaudin M, Testa S, Malinovsky JM, Vigier T, Souron R Midazolam for premedication in children: Nasal vs rectal administration Eur J Anaesthesiol 1997;14:244–249 21 Baldwa NM, Padvi AV, Dave NM, Garasia MB Atomised intranasal midazolam spray as premedication in pediatric patients: Comparison between two doses of 0.2 and 0.3 mg/kg J Anesth 2012;26:346–350 22 Knoester PD, Jonker DM, Van Der Hoeven RT, et al Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray A study in healthy volunteers Br J Clin Pharmacol 2002;53:501–507 23 Verma RK, Paswan A, De A, Gupta S Premedication with midazolam nasal spray: An alternative to oral midazolam in children Anesth Pain Med 2012;1:248–251 24 Sheta SA, Al-Sarheed MA, Abdelhalim AA Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: A double-blinded randomized controlled trial Paediatr Anaesth 2014;24:181–189 25 Tsze DS, Steele DW, Machan JT, Akhlaghi F, Linakis JG Intranasal ketamine for procedural sedation in pediatric laceration repair: A preliminary report Pediatr Emerg Care 2012;28:767–770 26 The Royal Children’s Hospital Melbourne Clinical practice guidelines: Intranasal fentanyl http://www.rch.org.au/clinicalguide/guideline_index/Intranasal_fentanyl/ Accessed 25 January 2017 27 Green SM, Nakamura R, Johnson NE Ketamine sedation for pediatric procedures: Part I, A prospective series Ann Emerg Med 1990;19:1024–1032 28 Lam C, Udin RD, Malamed SF, Good DL, Forrest JL Midazolam premedication in children: A pilot study comparing intramuscular and intranasal administration Anesth Prog 2005;52:56–61 29 Butterworth JF, Mackey DC, Wasnick JD Pediatric anesthesia In: Butterworth JF, Mackey DC, Wasnick JD (eds) Morgan & Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill Education/Medical, 2013: 877–905 30 Cote C, Lerman J, Anderson B Pharmacokinetics and pharmacology of drugs used in children In: Coté CJ, Lerman J, Todres DI (eds) Coté and Lerman’s A Practice of Anesthesia for Infants and Children, ed Philadelphia: Saunders, 2013:77–149 31 American Association of Oral and Maxillofacial Surgeons Pediatric anesthesia In: Office Anesthesia Evaluation Manual Rosemont, IL: American Association of Oral and Maxillofacial Surgeons, 2006: 75–81 385 www.ajlobby.com Mizukawa_Chap_27.indd 385 6/20/17 10:50 AM www.ajlobby.com Mizukawa_Chap_27.indd 386 6/20/17 10:50 AM CHAPTER 28 Pregnancy Steven I Kaltman, dmd, md Trevor Johnson, dmd www.ajlobby.com Mizukawa_Chap_28.indd 387 6/20/17 10:51 AM 28 • Pregnancy Ambulatory surgical treatment and anesthetic management of the pregnant patient must be considered carefully and require a thorough understanding of the risks and benefits of treatment options versus no treatment Elective surgical treatment is contraindicated in the pregnant patient However, pregnancy should not preclude emergency treatment Oral and maxillofacial surgical procedures with anesthesia during pregnancy are justified when it is clear that failure to perform the procedure could expose the mother, the fetus, or both to harm Ambulatory emergency oral and maxillofacial surgery procedures in the pregnant patient can safely be performed with local anesthesia, procedural sedation, and general anesthesia Procedural sedation for anxiolysis with local anesthesia is the anesthetic technique of choice for office-based oral and maxillofacial surgery procedures involving a pregnant patient with anxiety, pain, fear, and distress The authors of this chapter acknowledge the controversial nature of sedating pregnant patients, but cases have occurred—and will continue to occur—in which procedural sedation is in the best interests of both the mother and developing fetus Understanding the potential risks and benefits is paramount in treatment planning for these patients Anesthetic considerations in the pregnant patient include concern for two patients: the mother and the fetus The basic objectives in the anesthetic management of pregnant patients requiring surgery are maternal safety, avoidance of teratogenic drugs, avoidance of intrauterine fetal asphyxia, and prevention of preterm labor.1 Consultation with the patient’s obstetrician or primary care physician is essential before proceeding with the planned procedure Several physiologic changes need to be considered when sedating a pregnant patient for an office-based procedure Toward the beginning of pregnancy these changes are regulated by hormones; as the pregnancy continues to progress the mechanical effects of the growing uterus and metabolic demands of the fetus take over.2 Physiologic Changes of Pregnancy Respiratory changes During pregnancy, the mother’s airway mucosal tissues become edematous, and their fragility increases.3 These changes can make an already difficult intubation even more so.4 Epistaxis is also more likely in the placement of the nasal airway or nasogastric tube.5 Airway resistance is decreased because of progesterone-mediated relaxation of the bronchial muscles, and even relatively short periods of apnea or hypopnea will lead to a rapid decrease in partial pressure of arterial oxygen (Pao2) Several factors contribute to this rapid reduction in Pao2 First, maternal oxygen consumption increases by an estimated 20% to 50%; second, functional residual capacity decreases, reaching 20% by the third trimester owing to the physical obstruction of the expanding uterus.6 Other mitigating factors contributing to a decrease in functional residual capacity can include preeclampsia and maternal obesity Additionally, as the uterus enlarges, the respiratory pattern shifts from mainly diaphragmatic to mostly thoracic In the third trimester, the diaphragm rises, and the anterior posterior diameter of the chest increases to help in this transition.7 The natural response to increase oxygen supply with increased demand in pregnancy is progesterone-mediated maternal hyperventilation (increased minute ventilation by 50%).8 This mechanism includes increased brainstem sensitivity to partial pressure of arterial carbon dioxide (Paco2) (as Paco2 is decreased by 15% and Pao2 is increased by 10%), leading to a tidal volume increase of 40% and respiratory rate rise of 15%.8 This increase in minute ventilation is counteracted during procedural sedation, and general anesthesia can contribute to an unanticipated precipitated desaturation.9,10 Because hypoxia and hypercapnia develop more rapidly in a pregnant patient with hypoventilation or apnea, caution should be exercised in administering any level of sedation One has to be able to rescue a pregnant patient from an inadvertent deeper plane of anesthesia, as difficulty in intubation of a pregnant patient is a major cause of anesthesia-related maternal mortality 388 www.ajlobby.com Mizukawa_Chap_28.indd 388 6/20/17 10:51 AM Physiologic Changes of Pregnancy Cardiac changes As the fetus grows and develops, total blood volume increases 35% (1 to 1.5 L) with an associated 55% increase in plasma volume, creating a dilutional anemia that persists until to weeks postpartum.11 Cardiac output begins to increase at week five; the greatest increase occurs during the first and second trimesters, accelerating to a total increase of 30% to 50% at term.12,13 This elevation in cardiac output is due to a stroke volume increase of 30% coupled with a heart rate increase of 20% Concomitantly, systemic blood pressure decreases (systolic blood pressure, −5%; diastolic blood pressure, −15%).14 If the need to manage hypotension during a procedural sedation in the office setting occurs, it is important to note that the response to adrenergic agents and vasoconstrictors is blunted as peripheral vascular resistance decreases by 15% and pulmonary vascular resistance decreases by 30% in the pregnant patient compared with the nonpregnant patient.15 As the fetus grows in size and weight, the risk of aortocaval compression increases Aortocaval compression is the physical compression of the uterus on the abdominal aorta and vena cava.16 This compression causes a decrease in blood return, which leads to profound hypotension and a subsequent decrease in cardiac output This effect is clinically significant during the second half of gestation Approximately 5% of women at term develop supine hypotension syndrome, which involves hypotension, pallor, sweating, and nausea/vomiting when in a supine position Cardiac output is reduced by up to 25% in these cases and can cause near to complete occlusion of inferior vena cava by the gravid uterus.17 When combined with hypotensive effects of anesthesia, aortocaval compression can readily produce fetal asphyxia Secondary to procedural sedation techniques, physiologic compensation for aortocaval compression can be compromised, especially when combined with a pharmacologic loss of sympathetic tone leading to profound hypotension Therefore, proper positioning of the pregnant patient during procedural sedation is very important Left uterine displacement is achieved by turning the patient on her left side This positioning will prevent the uterus from compressing the aorta and vena cava It is recommended that a 15-degree wedge or a small pillow be placed under the right hip during procedures to maintain the appropriate position Alternatively, the patient can lean on her left side.18,19 Hematologic changes Pregnancy is considered a hypercoaguable state as the body prepares for delivery and the prevention of excessive blood loss.11 To so, clotting factors are increased 30% to 250%, depending on the factor Factors VII, VIII, IX, X, and XII all increase, whereas only factor XI levels may decrease Of note is the paradoxical decrease of platelets by 10% Other hematologic effects include decreased oncotic pressure leading to lower extremity edema, decreased maternal hemoglobin/hematocrit (20%), and leukocytosis, with a white blood cell count of up to 21,000/µL.15 A decrease in hemoglobin/hematocrit levels starts in the first trimester, progresses through the mid-second trimester, and then is mitigated in the third trimester by increased red blood cell production if iron stores are adequate This increase in red blood cell production will correspondingly create an increase in red blood cell volume (25% to 30%).20 A reduction in hematocrit and an increase in red blood cell volume is offset by an increase in cardiac output and a shift to the right of the oxyhemoglobin dissociation curve Because of fetal utilization, iron and folate levels may decrease in the pregnant patient if not supplemented.21 Chronic partial obstruction of the abdominal large vessels in the third trimester predisposes to venous stasis, phlebitis, and edema in the lower extremities and can also increase the risk of deep vein thrombosis.12 389 www.ajlobby.com Mizukawa_Chap_28.indd 389 6/20/17 10:51 AM 28 • Pregnancy Renal changes Progesterone-induced dilation of the renal tree is the mechanism for a few changes in the renal system Glomerular filtration rate is increased by 50%; laboratory results will also show a decrease in serum creatinine and blood urea nitrogen.15 Another function of pregnancy is urinary stasis, which leads to a greater risk of and more frequent urinary tract infections The growing uterus will also apply pressure to the bladder, resulting in a more frequent need to urinate Minimizing the length of the procedure, maintaining adequate hydration, and allowing for preoperative restroom breaks can help to minimize the risk of urinary tract infections in pregnant patients.22 Gastrointestinal changes The incidence of gastroesophageal reflux disease is increased in the pregnant patient secondary to reduced tone in the lower esophageal sphincter and superior-anterior displacement of the stomach from the growing uterus.23 This risk is even higher in pregnant patients with pain and/or obesity.23 For many years, delayed gastric emptying was thought to occur in all pregnant patients undergoing general anesthesia, and therefore, even after receiving nothing by mouth for or more hours, pregnant patients were induced using rapid sequence intubation with cricoid pressure More recent studies have established that delayed emptying is only a factor during active labor and the postpartum period and not likely to be clinically relevant during general pregnancy.21 An increased risk of gastric acid aspiration is thought to be associated with sedation after the 16th week of gestation24; although one study by Dean et al25 demonstrated no cases of pulmonary aspiration with deep sedation in 62,125 first- and second-trimester abortions Proper positioning of these patients, therefore, should also include keeping the head elevated during the sedation Avoiding excessive use of narcotics during the sedation is also important to avoid blunting the cough and gag reflexes These steps will help minimize the risk of aspiration of gastric contents.26 Anesthetic Considerations The risks associated with anesthetizing the pregnant patient are divided into three major categories: maintenance of fetal oxygenation, avoidance of teratogenic agents, and prevention of preterm labor The most concerning risk associated with current commonly used anesthetics is related to maintenance of fetal oxygenation Maternal hypoxemia causes uteroplacental vasoconstriction and decreased perfusion, causing fetal hypoxia, acidosis, and, ultimately, death.26 The vasculature of the uterus in the pregnant female is normally in a state of wide dilation and is not autoregulated Perfusion of the uterus is dependent on the maintenance of adequate maternal cardiac output, blood pressure, and dilation of uterine vasculature A severe constriction of uteroplacental vasculature can be caused by maternal hypoxia, extreme hyper- and hypocarbia, and hypotension.8 These factors will trigger direct vasoconstriction that will further reduce uteroplacental intervillous blood flow and therefore must be avoided.27 It is less of a concern with sedation cases than with cases requiring general anesthesia with intubation Maternal hypotension is probably the greatest intraoperative concern Deep levels of sedation will 390 www.ajlobby.com Mizukawa_Chap_28.indd 390 6/20/17 10:51 AM Anesthetic Considerations cause rapid maternal hypotension, which can result in fetal hypoxia Therefore, sufficient levels of anesthetic agents should be used to alleviate surgical stress while maintaining maternal blood pressure If maternal hypotension does occur, treatment should be administered immediately Hypotension caused by anesthetic medications or aortocaval compression needs to be managed aggressively by positional left lateral tilt, intravenous fluids, and vasopressors if needed Ephedrine has considerable β-adrenergic activity and has traditionally been considered the vasopressor of choice for hypotension during pregnancy However, clinical studies suggest that α-adrenergic agonists such as phenylephrine and metaraminol are just as effective in managing hypotension and are associated with less fetal acidosis than ephedrine.22 Although anesthetic agents are less of a risk to the fetus when compared with maternal hypoxia or hypotension, one needs to be concerned with the potential for these agents to cause spontaneous abortion or exert teratogenic effects.28 Teratogenicity is defined as dysgenesis of fetal organs and the observation of any significant change in the function of physical form of a child secondary to prenatal treatment.29 The teratogenicity of a drug depends upon dose, route of administration, timing of fetal exposure, and the species receiving the medication.26 In humans, the timing of most concern is the third to eighth week of development, when the fetus is undergoing organogenesis and drugs can exert their most serious teratogenic effects Subsequent to the eighth week of gestation, organ development is thought to no longer be at risk, but growth retardation may occur Although concerns for teratogenicity exist during the first trimester, commonly used anesthetics have never been proven to be teratogenic in humans The US Food and Drug Administration (FDA) has classified the safety profile of medications for use in pregnancy into a pregnancy section with three subheadings: risk summary, clinical considerations, and data This information includes potential risks to the fetus, known dosing alterations during pregnancy, effects of time and exposure during pregnancy, adverse maternal reactions, and any effect on labor and delivery There is also data available in the pregnancy exposure registry for the specific drug if available (Tables 28-1 and 28-2) It is important that all medications used for the pregnant patient be administered at the lowest effective dose and for the shortest duration possible Table 28-1 FDA pharmaceutical pregnancy classifications* Pregnancy category Assessment of risk A Safety established using human studies B Presumed safety based on animal studies C Uncertain safety No adverse effect demonstrated in human and animal studies D Unsafe Evidence of risk that may in certain clinical circumstances be justifiable X Highly unsafe Risk of use outweighs any possible benefit *Data from the FDA.30 391 www.ajlobby.com Mizukawa_Chap_28.indd 391 6/20/17 10:51 AM 28 • Pregnancy Table 28-2 Safety profiles of medications for use during pregnancy Class Analgesics FDA risk factor Drug Possible use in pregnant patients Acetaminophen Acetaminophen with codeine B C Codeine C Oxycodone Hydrocodone Meperidine Morphine Fentanyl Ibuprofen (first and second trimesters) Naproxen (first and second trimesters) Ibuprofen (third trimester) Naproxen (third trimester) Aspirin B C B B C B B D D D Local anesthetics Lidocaine Prilocaine Procaine Articaine Mepivicaine Bupivicaine B B C C C C Yes Yes Considered safe at dosages normally used in OMS offices Considered safe at dosages normally used in OMS offices Considered safe at dosages normally used in OMS offices Considered safe at dosages normally used in OMS offices, may cause hypotension at high doses Adrenergic agent Epinephrine C Ephedrine Metaraminol Phenylephrine C C C Use with local anesthetic only and take care not to give intravascularly Associated with fetal acidosis Yes Yes Antihypertensive Esmolol Labetalol Hydralazine C C C Yes, not for chronic use Yes More for chronic control of preeclampsia Inhalational agent Nitrous oxide Desflurane Sevoflurane Isoflurane Diazepam Midazolam Not assigned B B C D D Lorazepam Methohexital D B Controversial teratogenicity in first two trimesters Yes Yes Inadequate studies Associated with malformations in chronic use Associated with malformations in chronic use, no contraindication for single dose Associated with malformations in chronic use Yes Ketamine Propofol Etomidate B B C Yes Yes No Muscle relaxants Succinylcholine Rocuronium Vecuronium C C C Emergency situations only Emergency situations only Emergency situations only Antimicrobials Chlorhexidine B Yes Anticholinergic Glycopyrrolate, injected Glycopyrrolate, oral B C Yes Sedatives General anesthetics Yes Associated with first-trimester malformations; may use in second and third trimesters Associated with first-trimester malformations, may use in second and third trimesters Yes Yes Yes Yes Yes First and second trimesters and for 24 to 17 h only First and second trimesters and for 24 to 17 h only Contraindicated in third trimester, may close PDA Contraindicated in third trimester, may close PDA Not used OMS, oral and maxillofacial surgery; PDA, patent ductus arteriosus 392 www.ajlobby.com Mizukawa_Chap_28.indd 392 6/20/17 10:51 AM Anesthetic Considerations Nitrous oxide The safe use of nitrous oxide inhalation in the pregnant patient is highly controversial In multiple animal studies, nitrous oxide was found in a dose-dependent manner to increase rates of embryonic death and severe malformations.31–35 Nitrous oxide inactivates methionine synthetase, and methionine synthetase is responsible for the conversion of homocystiene and methyltetrahydrofolate to methionine and tetrahydrofolate Methionine is an essential amino acid, and tetrahydrofolate is needed for the synthesis of DNA.36 Therefore, nitrous oxide has the potential to impact fetal growth, especially during the first weeks of gestation during organogenesis, when the fetus undergoes rapid growth and development requiring DNA synthesis Infertility, spontaneous abortion, and congenital abnormalities have been reported following prolonged occupational exposure.37–39 The effect has not proven to be clinically significant in humans undergoing a single procedure, and the concern is greater with long-term exposure It is acceptable for nitrous oxide to be used when needed for surgical procedures that cannot be postponed during pregnancy and may be employed for labor analgesia.37,39 No human studies have shown adverse fetal outcomes after brief maternal exposures to nitrous oxide, although, for many health care providers, the medicolegal issue is sufficient to preclude its use in the treatment of the pregnant patient Benzodiazepines Chronic in utero exposure to benzodiazepines has been associated with increased incidences of cleft palate, central nervous system dysfunction, and dysmorphism.40 Neurotransmitters regulate palate-shelf reorientation γ-aminobutyric acid (GABA) inhibits reorientation It is thought that chronic benzodiazepines, diazepam specifically, may mimic GABA, thus causing incomplete palatal closure Early case studies of benzodiazepine use in pregnancy suggested an association with cleft palate and cardiac abnormalities40–43; however, more recent and better controlled studies have refuted this association.44 The risk for congenital malformations with the use of benzodiazepines during the first trimester of pregnancy was addressed by Motherisk in a 1998 meta-analysis that included 23 case-controlled studies.45 Evaluation of the pooled data demonstrated a substantial risk of oral clefts, with an odds ratio of 1.79 and a 95% confidence interval of 1.13 to 2.82 The fact that these case studies were heterogenous greatly decreased the validity of these marginally significant results On the other hand, the same meta-analysis relying on pooled data from cohort studies demonstrated no association between fetal exposure to benzodiazepines and the risk of oral clefts, with an odds ratio of 1.19 and a 95% clinical incidence of 0.344.15 At present, insufficient evidence proves that benzodiazepines are human teratogens.46 Single doses as used for a procedure appear to be safe for both the mother and the developing fetus.47 Flumazenil Teratogenic effects of flumazenil were not seen in animal reproduction studies.48 Embryocidal effects were seen at large doses Use during labor and delivery is not recommended In general, when using medications used as reversal agents, clinicians should take into consideration the health and prognosis of the mother Reversal agents should be administered to pregnant women in cases with a clear indication for use and should not be withheld because of fears of teratogenicity.49 Propofol Propofol crosses the placenta and may be associated with neonatal central nervous system and respiratory depression Reproduction studies on rats and rabbits receiving a dose equivalent to a normal human propofol induction dose demonstrated no evidence of harm to the fetus or impaired fertility.50 Although propofol has been implicated in maternal hypotension as an adverse effect, a study by Soares et al demonstrated that propofol has a dilating effect on fetal placental vessels and adequately maintains appropriate umbilical blood flow.51 When indicated, propofol can be used safely in low doses (2 mg/kg) without concerns regarding the mother or any neonatal depression 393 www.ajlobby.com Mizukawa_Chap_28.indd 393 6/20/17 10:51 AM 28 • Pregnancy Ketamine Ketamine is characterized as a rapid and short-acting general anesthetic that produces a profound analgesia while maintaining normal laryngeal and pharyngeal reflexes with slightly enhanced cardiovascular and respiratory stimulation In pregnancy, ketamine is known to increase maternal blood pressure and heart rate as much as 30% to 40% and is therefore not recommended for use in pregnant patients with pre-existing history of hypertension.52 Adverse events have not been observed in animal reproduction studies Ketamine crosses the placenta and can be detected in fetal tissue Ketamine produces dose-dependent increases in uterine contractions; effects may vary by trimester.53 The plasma clearance of ketamine is reduced during pregnancy Dose-related neonatal depression and decreased Apgar scores have been reported with large doses administered at delivery.52,54,55 Ketamine may be used in low doses during pregnancy, but other anesthetic agents may be more desirable Barbiturates Evidence suggests that barbiturates cause congenital anomalies in animals, but teratogenic human effects have not been reported Their use in procedural sedation has declined in recent years in lieu of safer techniques with a wider spectrum of safety Opioids Much evidence suggests that opioids are not teratogenic when used in limited doses in the perioperative period Fentanyl is a pregnancy category “C” drug Fentanyl has been shown to impair fertility and to have an embryocidal effect in rats when given in doses 0.3 times greater than the upper human dose for a period of 12 days, but no evidence of teratogenic effects have been observed when administered to rats.56 When used for pain relief during labor, opioids may temporarily affect the heart rate of the fetus Fentanyl injection may be used for the management of pain during labor.57 Meperidine and morphine both appear to be safe when administered for anesthesia and analgesia for short periods, although chronic use has been shown to cause fetal growth retardation and neonatal withdrawal.50 Naloxone Naloxone is a rapid-acting opiate antagonist that crosses the blood-brain barrier within to minutes after intravenous administration.50 It does not appear clinically to exhibit teratogenic effects Naloxone should only be used as a reversal drug for respiratory depression, hypotension, or unresponsiveness in the monitored setting When administering general medications used as reversal agents, clinicians should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if their use is clearly indicated and should not be withheld because of fears of teratogenicity.49 Local anesthetics Pregnancy increases sensitivity to local anesthetics Onset time has been shown to be faster and duration longer in pregnant patients compared with nonpregnant patients, with differences found to be highly significant.58 Local anesthetics also freely cross the placental barrier, so the issue of fetal toxicity must be considered Most amide-type anesthetics bind to α1-acid glycoprotein; this protein is reduced in pregnancy, which results in an increased amount of free plasma concentration and, therefore, an increased risk of toxic reactions (especially bupivacaine) Few seismically significant effects have been reported in the neonate as a result local anesthetics, and generally speaking, effects are minimal even at higher doses Lidocaine, the most commonly used local anesthetic, and its metabolites cross the placenta and can be detected in the fetal circulation after injection.59,60 The Collaborative Perinatal Project showed that the administration of benzocaine, procaine, tetracaine, and lidocaine during pregnancy did not result in an increased rate of fetal malformations.61 394 www.ajlobby.com Mizukawa_Chap_28.indd 394 6/20/17 10:51 AM Summary Some are hesitant to use epinephrine on pregnant patients because of concern of an intravascular injection causing uterine vasoconstriction and decreasing uterine blood flow.62 In oral and maxillofacial surgery (OMS) setting, epinephrine is commonly dispensed in a 1:100,000 epinephrine concentration, or 10 μg/mL This dose is not associated with any fetal abnormality and is considered safe for use in pregnant patients.63 Additionally, as discussed previously, the use of α-adrenergic agonist agents for hypotension has more recently been shown to be effective, with less fetal acidosis Analgesics In oral and maxillofacial surgical practice, the need for either surgical or nonsurgical pain control for the pregnant patient is necessary The two main categories for pain relief consist of nonopioid and opioid medications When choosing the proper analgesic, it is important to consider the potential harm to the mother and fetus (Table 28-3) Table 28-3 Analgesic considerations for pregnant patients Analgesic Medication class Common dosage (mg) Dosage schedule* Maximum dosage Precautions Ibuprofen NSAID 400–800 Every 4–6 h 3,200 mg in 24 h Avoid in third trimester of pregnancy; use caution if the patient has a history of GI bleeding or in cases of renal disease, coagulation disorders, or asthma Naproxen NSAID 250–500 Every 12 h 1,500 mg in 24 h Ketoprofen NSAID 50–100 Every h 300 mg in 24 h Ketorolac NSAID 10 Every 4–6 h 40 mg in 24 h Acetaminophen Other 325–1,000 Every 4–6 h 1,000 mg in h or Use caution in patients with hepatic disease or those 4,000 mg in 24 h at risk for methemoglobinemia Codeine Opioid 15–60 Every 4–6 h 360 mg in 24 h Hydrocodone Opioid 2.5–10 Every 4–6 h 40 mg in 24 h Use caution in pediatric and elderly patients or in cases of urethral stricture or biliary disease Oxycodone Opioid 5–15 Every 4–6 h 60 mg in 24 h Hydromorphone Opioid 2–8 Every 3–4 h 48 mg in 24 h Meperidine Opioid 50–150 Every 3–4 h 600 mg in 24 h Tramadol Other 50–100 Every 4–6 h 400 mg in 24 h or Use caution in elderly patients, in those with a history 300 mg in patients of seizures, and in those with psychiatric disorder, risk aged > 75 y for serotonin syndrome, or risk for Stevens-Johnson syndrome Use caution if the patient has a hypersensitivity to sulfites, urethral stricture, biliary disease, or seizure disorder Use caution with use of MAO inhibitors and in patients with sickle cell disease GI, gastrointestinal; MAO, monoamine oxidase; NSAID, nonsteroidal anti-inflammatory drug *All dosages are for medications taken by mouth Summary In conclusion, when emergency OMS is deemed necessary during pregnancy, it is important to consider the physiologic changes of pregnancy before determining the choice of anesthesia For those office procedures requiring anxiolysis and treatment of the difficult patient, conscious procedural sedation is the anesthesia of choice It is critical to avoid hypoxia, hypotension, hyperventilation, hypercarbia, and acidosis A high concentration of oxygen is recommended during maintenance of anesthesia, and avoidance of fetal hypoxia, teratogenic drugs, and inducing preterm labor is essential As with any other decision, the risks, benefits, and alternatives, as well as the legal liabilities, of performing emergency or urgent procedures with an office-based anesthetic versus the surgical center setting must be weighed carefully Although studies have shown high levels of safety of many commonly used drugs in the pregnant patient, the reality is that if any adverse event were to happen, or if teratogenicity were to occur, 395 www.ajlobby.com Mizukawa_Chap_28.indd 395 6/20/17 10:51 AM 28 • Pregnancy it would trigger a very emotionally charged reaction from the parents, and liability could be attributed to the OMS clinican Every practitioner must establish his or her boundaries regarding the anesthetic care of pregnant patients, based on sound evidence and his or her own comfort levels References Rosen MA, Hughes S Obstetrics In: Stoelting RK, Miller RD (eds) Basics of Anesthesia, ed Edinburgh: Churchill Livingstone, 2006:498–499 19 Gianopoulos JG Establishing the criteria for anesthesia and other precautions for surgery during pregnancy Surg Clin N Am 1995;75: 33–45 Chapman AB, Abraham WT, Zamudio S, et al Temporal relationships between hormonal and hemodynamic changes in early human pregnancy Kidney Int 1998;54:2056–2063 20 Suresh L, Radfar L Pregnancy and lactation Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:672–682 Toppozada H, Michaels L, Toppozada M, El-Ghazzari I, Talaat M, Elwany S The human respiratory nasal mucosa in pregnancy: An electron microscopic and histochemical study J Laryngol Otol 1982;96: 613–626 Rocke DA, Murray WB, Rout CC, Gouws E Relative risk analysis of factors associated with difficult intubation in obstetric anesthesia Anesthesiology 1992;77:67–73 Ellegård EK Pregnancy rhinitis Immunol Allergy Clin North Am 2006; 26:119–135 Graves CR Acute pulmonary complications in pregnancy In: Fink MP, Abraham E, Vincent J, Kochanek PM (eds) Textbook of Critical Care Philadelphia: Saunders, 2005:1551–1556 Turner AF The chest radiograph in pregnancy Clin Obstet Gynecol 1975;18:65–74 21 Loughlin KR Management of urologic problems during pregnancy Urology 1994;44:159–169 22 Frolich MA Maternal and fetal physiology and anesthesia In: Butterworth JF, Mackey DC, Wasnick JD Morgan and Mikhail’s Clinical Anesthesiology, ed New York: McGraw-Hill, 2013:825–841 23 Turner M, Azis SR Management of the pregnant oral and maxillofacial surgery patient J Oral Maxillofac Surg 2002;60:1479–1488 24 Goodman S Anesthesia for nonobstetric surgery in the pregnant patient Semin Perinatol 2002;26:136–145 25 Dean G, Jacobs AR, Goldstein RC, Gevirtz CM, Paul ME The safety of deep sedation without intubation for abortion in the outpatient setting J Clin Anesth 2011;23:437–442 26 Van De Velde M, De Buck F Anesthesia for non-obstetric surgery in the pregnant patient Minerva Anestesiol 2007;7:235–240 Wolfe LA, Weissgerber TL Clinical physiology of exercise in pregnancy: A literature review J Obstet Gynaecol Can 2003;25:473–483 27 Ralston DH, Schnider SM, DeLorimier AA Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe Anesthesiology 1974;40:354–370 Reitman E, Flood P Anaesthetic considerations for non-obstetric surgery during pregnancy Br J Anaesth 2011;107(suppl 1):i72–i78 28 Rosen M Management of anesthesia for the pregnant surgical patient Anesthesiology 1999;91:1159–1563 10 Hegewald MJ, Crapo RO Respiratory physiology in pregnancy Clin Chest Med 2011;32:1–13, vii 29 Koren G, Pastuszak A, Ito S Drugs in pregnancy N Engl J Med 1998; 338:1128–1237 11 Pritchard JA Changes in the blood volume during pregnancy and delivery Anesthesiology 1965;26:393–399 30 The US Food and Drug Administration Pregnancy and Lactation Labeling (Drugs) Final Rule www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/labeling/ucm093307.htm Last updated 18 November 2016, accessed 10 February 2017 12 Katz R, Karliner JS, Resnik R Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects Circulation 1978;58(3 pt 1):434–441 13 Robson SC, Hunter S, Boys RJ, Dunlop W Serial study of factors influencing changes in cardiac output during human pregnancy Am J Physiol 1989;256(4 pt 2):H1060–H1065 14 Camann WR, Ostheimer GW Physiological adaptations during pregnancy Intern Anesth Clin 1990;28:2–10 15 Almeida FA, Pavan MV, Rodrigues CI The haemodynamic, renal excretory and hormonal changes induced by resting in the left lateral position in normal pregnant women during late gestation BJOG 2009;116:1749–1754 16 Marx GF, Bassell GM Hazards of the supine position in pregnancy Clin Obstet Gynecol 1982;9:255–271 17 Kerr MG The mechanical effects of the gravid uterus in late pregnancy J Obstet Gynaecol Br Commonw 1965;72:513–529 18 Triolo PK Nonobstetric surgery during pregnancy J Obstet Gynecol Neonatal Nurs 1985;14:179–183 31 Fink BR, Shepard TH, Blandau RJ "Teratogenic activity of nitrous oxide" Nature 1967 Apr 8;214(5084):146-148 32 Corbett TH, Cornell RG, Endres JL, Millard RI Effects of low concentrations of nitrous oxide on rat pregnancy Anesthesiology 1973; 39:299–301 33 Pope WD, Halsey MJ, Lansdown AB, Simmonds A, Bateman PE Fetotoxicity in rats following chronic exposure to halothane, nitrous oxide, or methoxyflurane Anesthesiology 1978;48:11–16 34 Ramazzotto LJ, Carlin RD, Warchalowski GA Effects of nitrous oxide during organogenesis in the rat J Dent Res 1979;58:1940–1943 35 Vieira E, Cleaton-Jones P, Austin JC, Moyes DG, Shaw R Effects of low concentrations of nitrous oxide on rat fetuses Anesth Analg 1980;59:175–177 36 Shessel BA, Portnof JE, Kaltman SI, Nitsch R Dental treatment of the pregnant patient: Literature review and guidelines for the practicing clinician Today’s FDA 2013;25:26–33 396 www.ajlobby.com Mizukawa_Chap_28.indd 396 6/20/17 10:51 AM References 51 Soares de Moura R, Silva GAM, Tano T, Resende AC Effect of propofol on human fetal placental circulation Int J Obstet Anesth 2010;19: 71–76 37 Becker DE, Rosenberg M Nitrous oxide and the inhalation anesthetics Anesth Prog 2008;55:124–130 38 Brodsky JB, Cohen EN Adverse effects of nitrous oxide Med Toxicol 1986;1:362–374 39 Rooks JP Safety and risks of nitrous oxide labor analgesia: A review J Midwifery Womens Health 2011;56:557–565 40 Zimmerman EF, Venkatasubramanian K, Wee EL Role of neurotransmitters and teratogens on palate development Progr Clin Biol Res 1985;163C:405–408 52 Little B, Chang T, Chucot L, et al Study of ketamine as an obstetric anesthetic agent Am J Obstet Gynecol 1972;113:247–260 53 Oats JN, Vasey DP, Waldron BA Effects of ketamine on the pregnant uterus Br J Anaesth 1979;51:1163–1166 54 Ghoneim MM, Korttila K Pharmacokinetics of intravenous anaesthetics: Implications for clinical use Clin Pharmacokinet 1977; 2: 344–372 41 Laegreid L, Olegård R, Wahlström J, Conradi N Abnormalities in children exposed to benzodiazepines in utero Lancet 1987; 1:108–109 55 White PF, Way WL, Trevor AJ Ketamine—Its pharmacology and therapeutic uses Anesthesiology 1982;56:119–136 42 Saxen I, Saxen L Letter: Association between maternal intake of diazepam and oral clefts Lancet 1975;2:498 43 Saxen I, Lahti A Cleft lip and palate in Finland: Incidence, secular, seasonal, and geographical variations Teratology 1974;9:217–224 56 Society of Gastroenterology Nurses and Associates Medications: Medication considerations during sedation https://www.sgna.org/ GI-Nurse-Sedation/Medications Accessed 23 March 2017 57 Goetzl LM; American Congress of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics ACOG practice bulletin Clinical management guidelines for obstetrician-gynecologists number 36, July 2002 Obstetric analgesia and anesthesia Obstet Gynecol 2002;100:177–191 44 Einarson A The safety of psychotropic drug use during pregnancy: A review MedGenMed 2005;7:3 45 Dolovich LR, Addis A, Regis Vaillancourt JM, Barry Power JD, Koren G, Einarson TR Benzodiazepine use in pregnancy and major malformations or oral cleft: Meta-analysis of cohort and case-controlled studies BMJ 1998;317:839–843 58 Yurth DA Placental transfer of local anesthetics Clin Perinatol 1982;9:13–28 46 Addis A, Dolovich LR, Einarson TR, Koren G Can we use anxiolytics during pregnancy without anxiety? Can Fam Physician 2000;46: 549–551 59 Cavalli Rde C, Lanchote VL, Duarte G, et al Pharmacokinetics and transplacental transfer of lidocaine and its metabolite for perineal analgesic assistance to pregnant women Eur J Clin Pharmacol 2004; 60:569–574 47 Wikner BN, Stiller CO, Bergman U, Asker C, Källén B Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: Neonatal outcome and congenital malformations Pharmacoepidemiol Drug Saf 2007;16:1203–1210 60 Mitani GM, Steinberg I, Lien EJ, Harrison EC, Elkayam U The pharmacokinetics of antiarrhythmic agents in pregnancy and lactation Clin Pharmacokinet 1987;12:253–291 48 Genetech Romazicon (Flumaxenil) Injection Drug Information https:// www.gene.com/download/pdf/romazicon_prescribing.pdf Accessed 23 March 2017 61 Yellich GM Perioperative considerations in the pregnant patient Oral Maxillofac Surg Clin North Am 1992;4:651–657 62 Ralston DH, Schnider SM The fetal and neonatal effects of regional anesthesia and obstetrics Anesthesiology 1968;48:34–64 49 Bailey B Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women? Birth Defects Res A Clin Mol Teratol 2003;67:133–140 50 American Society for Gastrointestinal Endoscopy Standard of Practice Committee; Shergill AK, Ben-Menachem T, Chandrasekhara V, et al Guidelines for endoscopy in pregnant and lactating women Gastrointest Endosc 2012;76:18–24 63 Martin C, Varner MW Physiologic changes in pregnancy: Surgical implications Clin Obstet Gynecol 1994;37:241–255 397 www.ajlobby.com Mizukawa_Chap_28.indd 397 6/20/17 10:51 AM www.ajlobby.com Mizukawa_Chap_28.indd 398 6/20/17 10:51 AM CHAPTER 29 Obesity and Obstructive Sleep Apnea Salam O Salman, md, dds Jeffrey Dembo, dds, ms www.ajlobby.com Mizukawa_Chap_29.indd 399 6/21/17 3:28 PM 29 • Obesity and Obstructive Sleep Apnea Obesity Obesity is a substantial health problem in the United States and beyond, reaching epidemic proportions Body mass index (BMI) is used to classify obesity, with obesity defined as BMI > 30 kg/m2 and morbid (or severe) obesity as BMI > 40 kg/m2 (Fig 29-1).1 300 280 40 260 35 240 30 27 Weight (lbs) 120 200 25 Obese 22 BMI 30 & above 180 160 140 120 100 18.5 Overweight BMI 25–30 Normal BMI 18.5–25 Underweight BMI < 18.5 80 4'8" 4'10" 5'0" 5'2" 5'4" 5'6" 5'8" 5'10" 6'0" 6'2" 6'4" 6'6" 6'8" 6'10" 7'0" Height (no shoes) Fig 29-1 BMI chart for adults (Data from the National Institutes of Health.1) The National Health and Nutrition Examination Survey, conducted in the United States from 2011 to 2014, found that more than half of the adults were overweight, 33.2% of adults aged > 20 years were obese, and 4.8% were morbidly obese.2 Patients with obesity are at greater risk of developing diabetes mellitus and of having cardiovascular disease, restrictive lung disease, obstructive lung disease, and obstructive sleep apnea (OSA), along with several other comorbid conditions The obese patient is at greatly increased risk for pre-, intra-, and postoperative desaturation because of3: • Increased metabolic demand for oxygen due to increased tissue mass • Reduced respiratory system compliance due to abdominal and chest wall fat • Decreased functional residual capacity (particularly when supine) because the mass of the abdomen leads to persistent elevation of the diaphragm • Diminished size of oro- and hypopharyngeal airway secondary to large tongue and buccal fat pads • Decreased ability to extend the neck because of cervical fat • Increased chance for unrecognized emesis and aspiration of gastric contents These factors have many implications when planning or performing outpatient in-office anesthesia, most importantly with regard to respiratory status 400 www.ajlobby.com Mizukawa_Chap_29.indd 400 6/21/17 3:28 PM Risk Assessment Obstructive Sleep Apnea Upper airway patency is essential for normal respiratory function, and maintenance of patency is primarily dependent on pharyngeal structures OSA is a common disorder caused by repetitive partial or complete obstruction of the upper airway, characterized by episodes of hypopnea and apnea.4 Prevalence of OSA is estimated to be in for men and in 10 for women, with a significantly higher prevalence of in 10 for obese individuals.4 OSA is diagnosed using overnight polysomnography, and the apnea hypopnea index (AHI) is calculated based on the number of abnormal respiratory events per hour of sleep The American Academy of Sleep Medicine Task Force defines OSA as an AHI > plus symptoms of excessive daytime sleepiness or an AHI > 15 with or without these symptoms (Table 29-1).5 Patients with OSA may be at higher risk for adverse perioperative outcomes, including death.6 Table 29-1 American Academy of Sleep Medicine’s definitions of OSA AHI OSA rating 30 Severe Obesity and OSA share many of the same comorbidities and risk factors for anesthesia (Box 29-1).Because of their similarities and frequent coexistence, OSA’s and obesity’s impact on outpatient in-office sedation/anesthesia will be discussed together However, the treating clinician needs to remain aware that the presence of obesity does not always signify that OSA exists and that the absence of obesity (a thin patient) does not signify that OSA is absent BOX 29-1 • • • • • • • Common comorbidities associated with obesity and OSA • • • • • • Gastroesophageal reflux disease Hypertension Ischemic heart disease Obesity-hypoventilation syndrome Hyperdynamic cardiovascular state Cardiac arrhythmias Congestive heart failure Left ventricular hypertrophy Asthma Pulmonary hypertension Diabetes mellitus Psychiatric disorders Electrolyte imbalances Risk Assessment Many studies that suggest that obesity and OSA increase the risk of perioperative respiratory complications, difficulty in airway management, and diminished perioperative cardiac function; therefore, these patients should undergo a thorough preoperative assessment before they are considered for outpatient in-office sedation and anesthesia.5 As many patients who have OSA have never received a formal diagnosis, the clinician should have a high index of suspicion and perform preoperative screening in all patients suspected of suffering from OSA The “gold standard” for diagnosis of OSA remains overnight polysomnography, but it is unrealistic to expect this test to be performed immediately before ambulatory anesthesia Therefore, a preoperative screening tool such as the STOP-BANG 401 www.ajlobby.com Mizukawa_Chap_29.indd 401 6/21/17 3:28 PM 29 • Obesity and Obstructive Sleep Apnea screening questionnaire (see Box 10-1) should be used whenever the diagnosis of OSA is suspected.5,7,8 The questionnaire has a low specificity but a high sensitivity and can immediately indicate the need for further testing Ankichetty and Chung9 provided a useful algorithm for the treatment of patients with OSA who are scheduled to undergo ambulatory surgery and anesthesia (Fig 29-2) Perioperative care of a patient with OSA for ambulatory surgery Preoperative evaluation Postoperative management Suspected OSA Known OSA Monitor > 60 in PACU after meeting modified Aldrete criteria Screening using STOP or STOP-Bang questionnaire Assess severity by PSG, history, and clinical examination Recurrent respiratory adverse event‡ Low risk of OSA: High risk of OSA: Moderate-to-severe OSA: Mild OSA: < on STOP < on STOP-BANG ≥ on STOP ≥ on STOP-BANG AHI > 15 Spo2 < 94% on room air AHI < Spo2 > 94% on room air Comorbid conditions*: Optimized Mild-to-moderate-risk surgery Comorbid conditions*: Not optimized Postoperative opioids required Comorbid conditions*: Optimized Mild-to-moderate-risk surgery Ambulatory surgery: Safe with perioperative OSA precautions† Ambulatory surgery: May be unsafe Ambulatory surgery: Safe with perioperative OSA precautions† No Yes Plan discharge if uneventful perioperative period Plan hospitalization *Comorbid conditions: Obesity (BMI > 35 kg/m2), metabolic syndrome, cerebrovascular disease, uncontrolled hypertension, arrhythmias, heart failure † Perioperative OSA precautions: Anticipate possible difficult airway, short-acting anesthetic medications, ensure adequate reversal of neuromuscular blockade, extubate in head-up position ‡ Recurrent respiratory adverse event: Any event occurring more than once in each 30-minute evaluation period It includes one of the following events: oxygen saturation less than 90% on nasal cannula (three episodes), hypopnea less than 8/minute (three episodes), apnea more than 10 seconds (one episode), pain sedation mismatches (high pain and sedation scores concurrently) Fig 29-2 Perioperative management of obstructive sleep apnea patients undergoing ambulatory surgery (Reprinted with permission from Ankichetty and Chung.9) AHI, apnea hypopnea index; PACU, postanesthetic care unit; PSG, polysomnography; Spo2, saturation of peripheral capillary oxygen 402 www.ajlobby.com Mizukawa_Chap_29.indd 402 6/21/17 3:28 PM Risk Assessment Airway examination Obesity has been associated with difficult airway management, with the incidence of difficult intubation reported to be as high as 15% in morbidly obese patients.10 A nearly threefold increase in difficult direct laryngoscopy has been documented in obese patients, compared with those with a normal BMI Neck circumference and high Mallampati score were more reliable predictors of difficult direct laryngoscopy and face-mask ventilation than BMI alone.10 Therefore, in addition to the usual notation of Mallampati score, maximum interincisal opening, thyromental distance, neck range of motion, and upper lip bite test, a thorough airway examination of these patients should include measurement of neck circumference Assessment of pre-existing respiratory function Because of the obstructive and restrictive effects of obesity on respiration in combination with other factors described previously, acute postoperative pulmonary events are twice as likely to occur in obese patients compared with their nonobese counterparts.11 An excellent screening tool is measuring room air pulse oximetry before administration of any medications (with levels less than 96% warranting further investigation).9 Important preoperative questions to ask include those assessing exercise tolerance (such as ability to walk up a flight of stairs without becoming dyspneic or tachypneic) Patients known to have OSA should be questioned about their use of continuous positive airway pressure devices at home Assessment of cardiovascular system Obese patients carry an increased risk of cardiovascular comorbidities, including hypertension, coronary artery disease, venous stasis, cerebral vascular accidents, cardiomyopathies, and arrhythmia Insuring that these patients are medically optimized (ie, controlled hypertension, no current angina, etc) is essential before scheduling ambulatory surgery Patients with OSA are at a significantly increased risk of developing cardiovascular derangements (ie, arrhythmias) due to increased sympathetic tone; therefore, careful monitoring of electrocardiography recordings should be performed perioperatively Other considerations • Gastroesophageal reflux disease is one of the most common comorbidities associated with obesity All obese patients need to be questioned directly regarding the presence of reflux symptoms and should be advised to continue all antireflux medications (H2 blockers, proton pump inhibitors) preoperatively to decrease the risk of aspiration.12 • Obesity may make intravenous (IV) access difficult, thus preoperative assessment of IV access should be performed Patients can provide important clues, such as claiming to have “no veins” or that “doctors need to stick me many times” to successfully obtain IV access Although patients are required to have nothing by mouth before sedation, patients should be instructed to hydrate as much as possible the day before the surgical procedure to aid in IV access.12 It is reasonable for the clinician to forewarn a patient that failure to obtain reliable IV access could result in the surgical procedure being canceled and/or performed without use of parenteral agents • It is sometimes overlooked that manufacturers of operatory equipment (eg, surgical chairs, gurneys, etc) have determined the maximum weight limit for their equipment, which is published in the user’s manual Obese patients should be weighed during the pre-anesthetic visit to ensure that they can be safely placed on or transported with these pieces of equipment 403 www.ajlobby.com Mizukawa_Chap_29.indd 403 6/21/17 3:28 PM 29 • Obesity and Obstructive Sleep Apnea A pre-anesthetic checklist for the evaluation of obese patients and those with OSA is included in Table 29-2, summarizing all the components mentioned previously All aspects of the screening checklist should be taken into consideration when evaluating a patient for anesthesia For example, an “acceptable” BMI alone does not indicate that it is safe to provide ambulatory anesthesia, as it is possible that a patient with a BMI of 35 may fail a majority of the other screening guidelines Table 29-2 Screening checklist for anesthesia Factor Parameters BMI < 40 Mallampati score Class 1–2 Thyromental distance > cm Maximum interincisal opening > 40 mm Upper lip bite test Class I or II Neck circumference < 35 cm (F) or < 39 (M) Room Air Pulse Oximetry > 96% STOP-BANG Questionnaire < positive responses Actual weight of patient < Equipment max capacity Potential IV catheter sites Y/N F, female; M, male Anesthetic Considerations The following basic principles of practicing safe outpatient in-office sedation/anesthesia must be followed: (1) secure the IV catheter to ensure continuous patency and stability throughout the anesthetic, (2) test all monitors for placement and accuracy before induction, (3) place all reversal drugs in an easily accessible location, (4) have the emergency airway kit ready in the operatory room, including an appropriately sized laryngeal mask airway (LMA) placed on the instrument tray or back table, (5) inform all personnel how the patient should be monitored after the completion of the surgical procedure and anesthesia, and (6) define discharge criteria that will minimize any chance for adverse events during transport or at home Understanding the pharmacokinetics of commonly used agents in ambulatory surgery is important when treating obese patients Most common anesthetic agents are highly lipid soluble to rapidly cross the blood-brain barrier Drug doses should usually be based on ideal body weight (IBW); adipose tissue has low blood flow, and early transfer of drugs from the vascular compartment to the fat compartment is minimal, so calculating drug dosages using total body weight (TBW) may lead to overdosing As further redistribution into non–vessel-rich tissues occurs, the most lipid-soluble drugs will be redistributed into fat and may be stored for a longer time This process can lead to prolonged elimination of the drug due to the slow return of the drug into the plasma.13 For example, opioids like fentanyl should be dosed based on IBW in the obese patient population because of an increased plasma concentration when compared with patients with a BMI < 30 who are dosed based on TBW.14 On the other hand, administering propofol on the basis of TBW, not IBW, has an unchanged volume of distribution and clearance and, therefore, can be dosed based on TBW The American Society of Anesthesiologists’ guidelines state that opioid use should be limited in patients with OSA because of their increased propensity to exacerbate OSA Opioids may also profoundly impair respiration in the postoperative period, leading to obstructive and apneic episodes with commensurate and sometimes drastic oxygen desaturation during recovery Use of local anesthesia should be maximized to decrease anticipated postoperative pain and use of opioids Use of postoperative opioids should be avoided, with pain being primarily managed by nonsteroidal anti-inflammatory drugs and/or acetaminophen Another alternative, dexamethasone, has been shown to have significant analgesic and opioid-sparing efficacy.7 404 www.ajlobby.com Mizukawa_Chap_29.indd 404 6/21/17 3:28 PM Management of Potential Complications The primary concern with providing sedation for patients with OSA and obese patients is loss of airway due to the upper respiratory muscle relaxant and central respiratory depressant properties of most agents Moderate sedation with reversible agents (ie, benzodiazepines and low-dose, short-acting opioids) is preferred, but deep sedation techniques can be considered with caution for very carefully selected patients Propofol is associated with increased collapsibility of the upper airway due to inhibition of genioglossus muscle activity, depression of central respiratory regulation, and upper airway reflexes Therefore, even though its very short half-life would appear to be an advantage, propofol use should be limited—if it is used at all—in obese patients and those with OSA.8 For a short-term deeper level of sedation, propofol is preferred because of its improved awakening time when compared with longer-acting agents like barbiturates Despite this advantage, the use of propofol is not highly recommended Midazolam, when administered at sedative doses, can increase supraglottic airway resistance, leading to obstructive episodes; therefore, caution should be used with obese patients and those with OSA.15 Another option may include adding low-dose ketamine to the drug regimen because it preserves airway muscle tone better than most anesthetic agents However, this respiratory benefit of ketamine must be weighed against the cardiovascular risk caused by the drug’s sympathomimetic cardiovascular effects These adverse effects, while typically well-tolerated by younger and nonobese patients, can be dangerous to obese patients and those with OSA because of their greater risk of having pre-existing cardiovascular derangements.13 Dexmedetomidine, a selective α2-adrenergic receptor agonist, has gained some popularity because of its sedative/hypnotic, analgesic, and sympatholytic properties Its use reduces opioid-induced respiratory depression in morbidly obese patients and in those with OSA.16 Once the decision is made to provide parenteral and/or inhalation anesthesia, the clinician should decide how the airway will be maintained intraoperatively, with choices as follows: spontaneous ventilation with head positioning as needed, spontaneous ventilation with insertion of an airway adjunct (oral or nasal airway or LMA) after induction of anesthesia, or elective placement of an endotracheal tube after induction with either spontaneous or controlled ventilation Management of Potential Complications Several factors influence perioperative outcomes of these patients undergoing ambulatory surgery, including invasiveness of surgery, length of surgery, surgeon experience, and anesthetic technique; therefore, BMI alone should not be used to determine appropriateness for ambulatory surgery However, because it has been shown that a patient with a BMI > 50 is at higher risk for perioperative complications, strong consideration should be given to treating the patient in a facility where additional trained personnel are available to help treat the patient during the perioperative period Assuming comorbid conditions are well controlled, ambulatory anesthesia appears to be safe for those with a BMI < 40 For patients with a BMI between 40 and 50, careful preoperative assessment should be performed to evaluate commonly occurring comorbidities before a planned sedation and procedure.17 The most common, and life-threatening, perioperative complications with obese patients and those with OSA concern airway management and oxygenation A recent study demonstrated that primary airway management with an LMA was equally as efficient in morbidly obese patient as in lean patients,18 further emphasizing the need to have an LMA readily available when administering sedative agents to such patients Several studies reported that patients with OSA undergoing upper airway surgery (uvulopalatopharyngoplasty) had a higher rate of unanticipated hospital admission due to oxygen desaturation.9 In this patient population, postoperative oxygenation should be watched closely The use of supplemental oxygen via nasal cannula should be used with caution, as it may reduce hypoxic respiratory drive Positive airway pressure devices, especially if used at home, were found to provide improved oxygenation immediately after surgical procedures when compared with nasal cannula oxygen delivery.19 Obesity is an independent risk factor for venous thromboembolism, and many with this condition exhibit venous stasis at baseline If a lengthy surgical procedure is anticipated, consideration should be given to performing the procedure in a hospital setting so that appropriate mechanical and/or pharmacologic anti-embolic prophylaxis can be provided.12 405 www.ajlobby.com Mizukawa_Chap_29.indd 405 6/21/17 3:28 PM 29 • Obesity and Obstructive Sleep Apnea Finally, ambulatory surgical facilities providing care to obese patients and those with OSA should be well equipped to handle any complications such as difficult airway (see Fig 11-9) or respiratory depression and have clearly identified transfer arrangements to an inpatient facility should the need arise.20 Conclusion Medical and anesthetic management of the obese patient population, and those suffering with OSA, present unique and complex challenges to the practitioner As the prevalence of both of these conditions continues to rise, it is imperative to have a thorough understanding of the pathophysiology and management of these comorbidities Clinicians should have a high level of suspicion for these conditions and have a standardized preoperative assessment Anesthetic techniques and management, specifically regarding airway management and safe administration of sedative medications, should also be well understood by the clinician prior to providing outpatient anesthesia for this patient population References National Institutes of Health: National Heart, Lung, and Blood Institute Calculate your body mass index http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm Accessed 22 March 2017 12 Cullen A, Ferguson A Perioperative management of the severely obese patient: A selective pathophysiological review Can J Anaesth 2012;59:974–996 Polk SL Definitions and demographics of obesity: Diagnosis and risk factors Anesthesiol Clin North Am 2005;23:397–403 13 Chacon GE, Viehweg TL, Ganzberg SI Management of the obese patient undergoing office-based oral and maxillofacial surgery procedures J Oral Maxillofac Surg 2004;62:88–93 Kuchta KF Pathophysiologic changes of obesity Anesthesiol Clin North Am 2005;23:421–429 Stierer T, Punjabi NM Demographics and diagnosis of obstructive sleep apnea Anesthesiol Clin North Am 2005;23:405–420 14 Passannante AN, Rock P Anesthetic management of patients with obesity and sleep apnea Anesthesiol Clin North Am 2005;23: 479–491 Seet E, Chung F Obstructive sleep apnea: Preoperative assessment Anesthesiol Clin 2010;28:199–215 15 Montravers P, Dureuil B, Desmonts JM Effects of I.V midazolam on upper airway resistance Br J Anaesth 1992;68:27–31 Pashayan AG, Passannante AN, Rock P Pathophysiology of obstructive sleep apnea Anesthesiol Clin North Am 2005;23:431–443 16 Candiotti, K, Sharma, S, Shankar, R Obesity, obstructive sleep apnea, and diabetes mellitus: Anesthetic implications Br J Anaesth 2009; 103(suppl 1):23I–30I Joshi GP, Ankichetty SP, Gan TJ, Chung F Society for Ambulatory Anesthesia consensus statement on preoperative selection of adult patients with obstructive sleep apnea scheduled for ambulatory surgery Anesth Analg 2012;115:1060–1068 17 Joshi GP, Ahmad S, Riad W, Eckert S, Chung F Selection of obese patients undergoing ambulatory surgery: A systematic review of the literature Anesth Analg 2013;117:1082–1091 Chung F, Yegneswaran B, Liao P, et al STOP questionnaire: A tool to screen patients for obstructive sleep apnea Anesthesiology 2008; 108:812–821 18 Yildiz T, Ozdamar D, Arslan I, Solak M, Tokar K The LMA CTrach™ in morbidly obese and lean patients undergoing gynecological procedures: A comparative study J Anesth 2010;24:849–853 Ankichetty S, Chung F Considerations for patients with obstructive sleep apnea undergoing ambulatory surgery Curr Opin Anesthesiol 2011;24:605–611 19 Ogunnaike B The morbidly obese patient undergoing outpatient surgery Int Anesthesiol Clin 2013;51:113–135 10 Cartagena R Preoperative evaluation of patients with obesity and obstructive sleep apnea Anesthesiol Clin North Am 2005; 23: 463–478 11 Rose DK, Cohen MM, Wigglesworth DF, DeBoer DP Critical respiratory events in the postanesthesia care unit Patient, surgical, and anesthetic factors Anesthesiology 1994;81:410–418 20 American Society of Anesthesiology Task Force on Management of the Difficult Airway Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway Anesthesiology 2013;118:251–270 406 www.ajlobby.com Mizukawa_Chap_29.indd 406 6/21/17 3:28 PM CHAPTER 30 Considerations for the Substance Abuse Patient Julie Ann Smith, dds, md, mcr www.ajlobby.com Mizukawa_Chap_30.indd 407 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient Marijuana use is increasingly becoming more commonplace as more states are decriminalizing its use As a result, oral surgeons must be familiar with the physiologic effects of marijuana and its impact on anesthesia Additionally, the illicit or prescription drug–abusing or –dependent patient is also commonly seen by oral and maxillofacial surgeons.1 The use of illicit drugs or chronic opioids can affect both surgery and anesthesia It is therefore imperative for the surgeon to (1) know the physiologic effects of these drugs and be able to recognize signs and symptoms of use, (2) understand the potential interaction of these drugs with a planned anesthetic, and (3) be prepared to manage emergencies related to drug abuse The 2013 data from the National Institute on Drug Abuse indicate that 24.6 million US adults aged older than 12 years (9.4% of the population) have used an illicit drug during the previous month.2 Among those 24.6 million users, marijuana is the most commonly used drug, used by 19.8 million Approximately 6.5 million have illicitly used prescription drugs, another 1.5 million have used cocaine, and over 500,000 methamphetamine.2 Marijuana and methamphetamine use had increased in 2013 compared with the previous 10 years.2 Most first-time users of illicit drugs are in their teens (54.1% are aged younger than 18 years) Males have been reported to be more likely than females to use illicit drugs (10.8% versus 6.6%).3 Morbidity and mortality statistics from the American Association for Accreditation of Ambulatory Surgery Facilities indicate that of deaths that occurred in US ambulatory surgery facilities from 2001 to 2006 out of 1,141,418 outpatient procedures, three were related to postoperative opioid overdose; two of those three patients had a drug abuse history.4 Drug abusers also experience more postoperative complications Serena-Gómez and Passeri found in their review of mandibular fracture complications that 37.5% were in patients who abused intravenous drugs.5 Marijuana Marijuana is by far the most commonly used illicit substance, and it can be smoked or ingested, resulting in relaxation, pleasure, and euphoria It also impacts memory, sensory and time perception, and physical coordination Chronic use can result in dependence with the potential for withdrawal to occur, during which users can exhibit irritability, anxiety, sleep disturbance, poor appetite, and drug craving.6 The main psychoactive ingredient of cannabinoids is Δ-9-tetrahydrocannabinol, or THC, which causes agonism of the cannabinoid receptor type in the brain, which in turn results in marijuana’s psychologic effects THC is highly lipid soluble, easily crossing the blood-brain barrier Its distribution half-life is approximately 30 minutes, with a terminal half-life of up to 56 hours in occasional users, and 28 hours in chronic users.7,8 Signs of acute marijuana use include conjunctival congestion, tachycardia, dull reflexes, confusion, anxiety, inability to problem solve, and distorted time perception The tongue may be tinged with a green color due to inhaled chlorophyll or green dye A urine drug screen may reveal evidence of marijuana use in a first-time user for up to days and in a chronic user for to weeks after use Pulmonary effects The pulmonary effects of marijuana smoking are due to the inhaled carcinogens and irritants as well as the actual physical act of smoking Primarily, marijuana smoking causes inflammation, with increased coughing, phlegm production, bronchospasm, and bronchitis The amount of bronchial inflammation caused by smoking three to four marijuana cigarettes daily has been compared to that caused by smoking 20 regular cigarettes daily.7 Marijuana smoking usually involves deep inspiration with prolonged breath holding, which may predispose patients to developing bullous emphysema and put them at risk of spontaneous pneumothorax, especially during the delivery of positive pressure ventilation.9 It has been hypothesized that the deep inspiration during marijuana smoking results in a higher forced vital capacity and total lung capacity and perhaps helps preserve lung function This hypothesis is supported by a study in which Pletcher et al found that in patients with up to joint-years of exposure, low or occasional marijuana use did not adversely affect the forced expiratory volume or forced vital capacity.10 408 www.ajlobby.com Mizukawa_Chap_30.indd 408 6/21/17 3:34 PM Marijuana Cardiac effects Marijuana causes a dose-dependent increase in heart rate of 20% to 100%, with a peak occurring approximately 10 to 30 minutes after smoking Further, it may cause elevated blood pressure while supine but also may cause postural hypotension.11 Larger doses may cause bradycardia and hypotension.12 If a patient is suspected of having recently used marijuana, it would be prudent to avoid subjecting the patient to rapid positional changes to reduce the risk of significant postural hypotension Reports have been published of an elevated risk of myocardial infarction (MI) associated with marijuana use, the mechanism of which is poorly understood.11–13 Marijuana may be accompanied by other concomitant activities such as cocaine use that also can place the patient at an elevated cardiac risk Increased MI risk has been reported in patients who were otherwise believed to be of low cardiac risk.11,12 Mittleman et al performed a case-crossover study of 3,882 acute MI patients to evaluate potential MI triggers.11 They found a 4.8-fold increased risk of MI within the first hour after marijuana smoking, which declined rapidly to 1.7 during the second hour However, three of the patients who had an MI within that first hour after marijuana use had also engaged in other potential MI triggering behaviors during the same hour Exclusion of these three patients resulted in a relative increased risk of 3.2 fold for MI occurring within the first hour after marijuana use.11 MI related to marijuana use is rare, but the surgeon should remember that a chronic marijuana user may have an unexpectedly elevated cardiac risk Generally, life-threatening arrhythmias are not reported in these patients, but occasional electrocardiogram changes such as reversible ST-segment and T-wave abnormalities and supraventricular and ventricular ectopy may be observed Neurologic/psychiatric complications Evidence has been reported of an association between the use of cannabis and an increased risk of ischemic stroke Possible etiologies of this risk include orthostatic hypotension, labile blood pressure, cerebral vasomotor function alterations, vasospasm, or multifactoral causes of intracranial stenosis.14 Westover et al found an adjusted odds ratio of 1.76 for an association of ischemic stroke with cannabis use in a population-based study of stroke patients.15 After adjusting for all other risk factors, 1% of the 998 ischemic strokes studied were attributed to the use of cannabis Wolff et al describe 59 case reports of cannabis-related stroke, most of which were ischemic (49).14 These patients were more likely to be males with a history of chronic tobacco and alcohol use Marijuana is well known to cause euphoria, relaxation, and enhanced sensorium; however, it can cause problems with memory, judgment, balance, and concept of time Some users may experience extreme anxiety, disorientation, paranoia, and psychosis Cannabis use has been linked to psychotic symptoms, but a link to the development of schizophrenia is controversial.16 Anesthetic and surgical concerns Because of the mucosal inflammation caused by marijuana, chronic users should be expected to have a reactive airway and be at an increased risk of developing bronchospasm, laryngospasm, and upper airway edema Intravenous dexamethasone may be useful if airway edema occurs It should also be remembered that by performing deep inspiration and breath holding while smoking marijuana, these patients are at risk of having pulmonary blebs, which could result in a pneumothorax from excessive airway pressure during bag-mask ventilation Tachycardia and blood pressure instability can be associated with acute marijuana use Epinephrine, ketamine, or atropine may potentiate the tachycardia and should be avoided or minimized in these cases Acute marijuana intoxication can reduce the anesthetic requirement owing to the sedation it causes The marijuana user may also be using other illicit drugs, which may have even more concerning effects As far as drug interactions are concerned, it is important to remember that marijuana is a central nervous system depressant Sedation caused by benzodiazepines, opioids, barbiturates, and antihistamines may be potentiated by the use of marijuana 409 www.ajlobby.com Mizukawa_Chap_30.indd 409 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient Cannabis metabolism is poorly understood, but the cytochrome P450 enzymes CYP2C9 and CYP3A4 are believed to be involved.17 The involvement of the cytochrome P450 system may result in less efficient metabolism of other drugs, causing an increased risk of sedation from the concomitant use of cannabis with barbiturates, sedative-hypnotics, anticholinergics, and alcohol.17 It has been suggested that cannabis may interact with tricyclic antidepressants, causing tachycardia or delirium; with selective serotonin reuptake inhibitors, resulting in mania; and with disulfiram, resulting in hypomania.17 A number of other potential drug interactions exist with marijuana, which are nicely summarized by Lindsey et al.17 Yamreudeewong et al have published a case report describing a marijuana smoker who was also taking warfarin and experienced international normalized ratios as high as 11.5, which were attributed to the effect of marijuana on the metabolism of warfarin.18 Cocaine Cocaine, an ester local anesthetic with vasoconstrictive and other sympathomimetic properties, is the second most commonly abused illicit drug As a local anesthetic, it reversibly inactivates sodium channels, causing anesthesia Additionally, it directly inhibits the re-uptake of dopamine, norepinephrine, and serotonin, resulting in euphoria and sympathomimetic effects including vasoconstriction and tachycardia It is used in various forms The water-soluble salt, cocaine hydrochloride, is taken through nasal insufflation (ie, “snorted”), the most common method of use Cocaine hydrochloride may also be injected, ingested, applied topically to oral mucous membranes, or inserted vaginally or anally The insoluble base form is smoked Crack cocaine is a type of freebase cocaine; however, freebase and crack (the more commonly used form) are manufactured differently from each other.19 The manufacture of freebase cocaine involves dissolving the water soluble salt cocaine hydrochloride in water and adding ether as a solvent and ammonia as a base The ether is presumed to have evaporated, and freebase cocaine is then smoked However, the ether may not completely evaporate, and the smoker may sustain facial or tracheal burns Crack cocaine manufacture is simpler, performed by dissolving cocaine hydrochloride in water, mixing in baking soda, and then heating it, which produces a hard mass (“rock”) when dry.19 Crack is known to be highly addictive due to the quick and intense euphoria that ensues upon smoking it When smoked, crack is rapidly absorbed, but the euphoria does not last as long as it does as when cocaine is nasally insufflated Dependence upon crack develops quickly, and a dramatic withdrawal may present, manifested by symptoms of fatigue, depression, and drug craving Metabolism is via plasma and liver esterases, and cocaine has a plasma half-life of 30 to 90 minutes, with crack having a slightly shorter half-life Metabolites are detectable in the urine for up to 15 days after use The health provider must be able to recognize clinical manifestations of cocaine use The intense vasoconstriction and ischemia caused by cocaine use may result in septal, nasal, or palatal defects in chronic users Nasal collapse may be evident in patients with significant septal perforations Additionally, those who nasally insufflatecocaine may have an absence of nasal hair on their dominant side Cocaine is often topically applied along the maxillary alveolar gingiva posterior to the canine, which may result in well-localized gingivitis in this location One long fingernail—usually on the pinky—may be maintained to serve as a scoop for the salt form of cocaine Those who smoke crack often sustain pipe burns or develop calluses on the tips of their fingers It is very important to remember that it is common for adulterants to be combined with cocaine, which may have negative effects as well For example, levamisole, which is no longer on the market in the United States but was originally an immunomodulatory drug used to manage colorectal cancer and autoimmune/rheumatologic disorders, has been added to cocaine to dilute it (increasing volume and profit), to enhance sympathetic stimulation, or to monitor supply and distribution.20,21 Rat studies have demonstrated that levimasole may cause an elevation in endogenous opioids and may modulate norepinephrine, dopamine, and serotonin metabolism.22 Levimasole’s adverse effects include agranulocytosis, leukoencephalopathy, neutropenia, coagulopathy, vasculitis, arthralgias, purpura, and skin necrosis.20,21 As of 2009, it has been found in 70% of the cocaine and in 3% of the heroin seized in the United States.20,23 The use of levimasole as an adulterant was discovered in 2008 because cases of unexplainable agranulocytosis in cocaine users were reported, and levamisole was found in seized lots of cocaine.23 Local an410 www.ajlobby.com Mizukawa_Chap_30.indd 410 6/21/17 3:34 PM Cocaine esthetics are also added to cocaine to dilute it or enhance its nasal mucosal anesthetic effect The seizure threshold is lowered by cocaine, and the presence of local anesthetics may lower that threshold further In 2014, Saraghi and Hersch reported on two cases of methemoglobinemia and seizures in cocaine users.24 Toxicology testing in both patients were positive for lidocaine and benzocaine Other reported adulterants include, but are not limited to, procaine, caffeine, aminophenazone (may cause agranulocytosis), diphenhydramine, ephedrine, and phenobarbital.25 However, levamisole and local anesthetics seem to be the most commonly used adulterants It is important to be aware that cocaine may be contaminated by unknown adulterants, each with their own worrisome adverse effects Cardiac effects The increased levels of norepinephrine, dopamine, and serotonin caused by cocaine use may result in hypertension, tachycardia, dysrhythmias, cardiomyopathy, myocardial ischemia, and MI Dysrhythmias are believed to be due to contraction band necrosis from myocardial scarring, which results from overstimulation of cardiac muscle fibers as well as from a direct cardiotoxic effect of cocaine.26 Cardiovascular effects are not dose dependent, and even small amounts of cocaine can be fatal An increased risk of MI is present in cocaine users independent of underlying coronary artery disease Several theories exist for this increased risk.27 It may be secondary to increased myocardial oxygen demand caused by the tachycardia, hypertension, and increased contractility resulting from sympathetic stimulation Coronary vasoconstriction also occurs, further reducing myocardial blood flow Acute arterial hypertension may cause disruption of atherosclerotic plaques, which, combined with the increased platelet aggregation potentially induced by cocaine, may cause coronary thrombus formation.26,27 Mittleman et al evaluated the potential link between cocaine use and MI in a population of acute MI (AMI) patients.27 It was determined that the relative risk of AMI was 23.7 times higher during the first hour after cocaine use The AMI risk decreased significantly during the hours after use, but was still elevated and hours after use However, this elevated risk during hours and after use was not found to be significant compared with that of AMI patients who did not use cocaine in the hours before AMI However, the authors did indicate that the confidence interval for the relative risk for AMI during the second and third hours after cocaine use were large enough that it may be wise to still consider the second and third hours after cocaine use to be a period of increased risk for AMI.27 The authors extrapolated from this data that the annual excess risk for a daily cocaine user to have a coronary event is approximately 1.5% to 3% Hollander et al studied 246 patients with chest pain after use of cocaine (cocaineassociated chest pain [COCHPA] study) and found that the median onset of chest pain occurred within 60 minutes of cocaine use, corroborating that the first hour after use is the riskiest time for a coronary event to occur in a cocaine user.28 Additionally, they found that of patients who presented to the emergency department with chest pain after cocaine use, 6% were having an MI Other studies have reported an incidence of MI associated with cocaine use ranging from 0.7% to 6%.29 Cocaine users also have an increased risk of aortic dissection; 9.8% to 37% of acute aortic dissections have been reported as being temporally related to cocaine use.30–32 Hsue et al and Daniel et al report that the mean time from cocaine use to presentation with aortic dissection was 12.0 to 12.8 hours, and their studies also found that patients with aortic dissection associated with cocaine use were younger than aortic dissection patients who did not use cocaine.30,31 Pulmonary effects The pulmonary impact of smoking crack cocaine is related not just to the direct effects of crack, but also to the high comorbidity with tobacco smoking Crack itself is toxic, and the crack smoker exposes his lungs to many other unknown chemicals that may be present as adulterants Deep inspiration and breath holding leads to an increased risk of developing bullae and subsequent pneumothorax.9 “Crack lung” may present to 48 hours after smoking crack and is typically associated with pruritus, fever, chest pain, and bronchospasm Further evaluation may reveal diffuse alveolar infiltrates without effusion and eosinophilia.33 Cocaine users also have more frequent pneumonias 411 www.ajlobby.com Mizukawa_Chap_30.indd 411 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient Acute crack smoking should be expected to cause cough, bronchospasm, exacerbation of asthma, and black sputum production Central nervous system effects Cocaine lowers the seizure threshold, and adulterants such as lidocaine may reduce it even further Other neurologic adverse effects of cocaine use include pupillary dilation, emotional instability, hyperreflexia, and cerebrovascular accident.33 A link between cocaine use and stroke has been established.15 In a study of stroke patients aged 18 to 44 years old, Westover et al found that cocaine abuse increased the risk of hemorrhagic as well as ischemic stroke.15 The adjusted odds ratio for hemorrhagic stroke in cocaine abusers was 2.33, and for ischemic stroke, it was 2.03.15 This finding was lower, however, than the adjusted odds ratio for the association of ischemic stroke with hypertension, which was 5.69, and for the association of hemorrhagic stroke with hypertension, which was 7.68 The increased risk of stroke related to cocaine abuse is believed to be due to associated hypertension, vasospasm, vasculitis, and cerebrovascular autoregulation disruption Hematologic effects Cocaine has been reported to cause increased platelet activation and aggregation.34 Further, it may increase plasminogen activator-inhibitor, thereby increasing the risk of thrombogenesis.34 Interestingly, case reports of thrombocytopenia related to cocaine abuse have been published.35,36 The etiology is unknown, but theories include bone marrow suppression, excess platelet activation, autoimmune destruction, hypersplenism, or chronic hepatitis The true risk of thrombocytopenia, however, is unclear Gershon et al found no substantial increase in thrombocytopenia in their study of 671 cocaine-using obstetric patients, compared with obstetric patients who did not use cocaine.37 Anesthetic and surgical concerns The anesthetic concerns of the cocaine user primarily involve the effects of cocaine on the cardiovascular system The first hour after cocaine use appears to be the most dangerous period Although it is generally recommended to allow hours to pass between cocaine use and anesthetic use, it would be prudent to allow 24 hours to pass.7 Because of the risk of cocaine-induced arrhythmias, cardiomyopathy, and ischemia, one should obtain an electrocardiogram before administering an anesthetic, and one should consider performing electrocardiograph monitoring during procedures Intravascular injection of epinephrine should be avoided because it could lead to myocardial ischemia.7 Additionally, the author of this chapter recommends the avoidance of ketamine because of its cardiac and central nervous system stimulation The emergency management of tachycardia, hypertension, and chest pain in a cocaine-using patient differs somewhat from the non–cocaine-using patient It is recommended that β-blockers be avoided as monotherapy in cocaine-abusing patients because unopposed α-adrenergic stimulation may occur, resulting in hypertension and coronary vasoconstriction.7,33 Propranolol worsens coronary vasoconstriction and is contraindicated.38 Intravenous hydralazine has been used in these patients to manage hypertension, but it is limited by its effect of causing reflex tachycardia A combined nonselective β-blocker and α-adrenergic blocker, labetalol, is considered safe to use in hypertensive cocaine users However, its β-blocking effect is greater than its α-blocking effect, so its use can still result in unopposed α activity, exacerbating hypertension or causing coronary vasoconstriction If a cocaine-using patient develops chest pain, nitroglycerin and verapamil are safe to use.33 Benzodiazepines are recommended for the treatment of a cocaine user with chest pain because they decrease both blood pressure and heart rate The American Heart Association recommends benzodiazepines and nitroglycerin as first-line therapy for cocaine-associated acute coronary syndrome, and the α-blocker phentolamine is recommended as second-line therapy.38 Hypotension may be managed with low doses of phenylephrine, which has minimal chronotropic and inotropic activity Acute use of cocaine may increase anesthetic requirements because of its sympathetic stimulation 412 www.ajlobby.com Mizukawa_Chap_30.indd 412 6/21/17 3:34 PM Methamphetamine Methamphetamine Synthetic drugs such as tryptamines, phenethylamines, cathinones, and synthetic cannabinoids are made in clandestine laboratories from readily available toxic components such as paint thinner, shoe polish, lye, drain cleaner, and lithium Additionally, the purity of the manufactured drug is unpredictable because suppliers add various adulterants The unpredictability of drug content makes it difficult to predict adverse effects in a patient who uses synthetic drugs Methamphetamine and 3, 4-methylenedioxy-N-methylamphetamine (ie, MDMA) are the most common synthetic drugs, but other novel psychoactive substances are constantly being manufactured Some are labeled “bath salts” and are sold on the Internet Legislation is quickly put into place to illegalize these drugs as they become available, but once a chemical is made illegal, drug developers simply modify the chemical slightly Many of these novel psychoactive substances are not part of routine drug screening, and individual novel psychoactive substances would need to be specifically tested for on the basis of suspicion The mechanism of action of synthetic drugs is complex, but in general, phenethylamines and tryptamines exert their effect via norepinephrine, serotonin, and dopamine The monoamine oxidase system decreases these effects by inactivating these monoamine neurotransmitters Therefore, ingestion of monoamine oxidase inhibitors concurrently with one of these synthetic drugs may augment the synthetic drug’s effects, leading to a drug overdose and potentially serotonin syndrome.39 Amphetamine, a phenethylamine stimulant, is often legally prescribed in the management of attention deficit disorder, depression, and narcolepsy, as well as to promote weight loss Methamphetamine, an N-methyl analogue of amphetamine, is the most commonly used synthetic recreational drug In an effort to reduce the ability to manufacture methamphetamine, the United States has restricted the sale of ephedrine and pseudoephedrine, which are used in the manufacture of methamphetamine As a consequence, 80% of methamphetamine in the United States comes from Mexico, which is extremely potent at a purity of 90%.40 Methamphetamine made in Mexico predominates in US urban and suburban areas, whereas methamphetamine made in the United States in clandestine laboratories predominates in US rural areas.40 It is estimated that the prevalence of methamphetamine use in the United States is 10.4 million.41 Used for its stimulant properties, the drug is highly addictive and is either smoked, nasally insufflated, ingested, or injected intravenously Most frequently, it is smoked, which results in a rapid high Methamphetamine causes release of dopamine, norepinephrine, and serotonin and also blocks their reuptake The half-life of methamphetamine ranges from to 30 hours, which is longer than the half-life of cocaine.41 Rapid dependence occurs, especially when it is injected intravenously Significant tolerance develops, and the user requires higher doses more frequently to achieve the desired high Chronic use causes depletion of dopamine from the brain, potentially resulting in significant dysphoria, hypersomnia, suicidal or homicidal ideation, or severe depression upon withdrawal.41 It is metabolized by the liver and excreted by the kidney, although chronic use does not result in liver enzyme elevation The oral manifestations of methamphetamine abuse (xerostomia, rampant caries, and bruxism) are well known Xerostomia is believed to be the result of methamphetamine’s stimulation of inhibitory α2-adrenergic receptors in the salivatory nuclei.41 The elevated caries rate is probably due to a combination of xerostomia, poor oral hygiene, methamphetamine-induced oral acidity, a high carbohydrate diet, and increased vomiting frequency The pattern of decay typically involves the buccal smooth surfaces of the teeth, as well as interproximal areas of the anterior teeth Use of methamphetamine increases muscle activity that can manifest as severe bruxism, trismus, and even facial and masticatory muscle choreiform motor activity.41 Other signs of methamphetamine use include an ammonia odor, formication resulting in open skin wounds, extreme mood swings, cachexia, and hallucinations Amphetamine use can be detected via routine urine toxicology.7 413 www.ajlobby.com Mizukawa_Chap_30.indd 413 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient Cardiac effects Methamphetamine is a strong sympathomimetic and can cause tachycardia, hypertension, heart failure, arrhythmias, and MI MI is not as closely associated with methamphetamine use as it is with cocaine use, but it does pose increased cardiac risk Westover et al studied a Texan population of 11,011 AMI patients aged 18 to 44 years between 2000 and 2003.42 The adjusted odds ratio for risk of AMI in methamphetamine users was 1.61 In comparison, the adjusted odds ratio for AMI was 2.14 in cocaine users, 6.32 in tobacco users, and 11.61 in hyperlipidemia patients In the studied population, 0.2% of AMIs were associated with amphetamine abuse, and 1.9% of AMIs were associated with cocaine abuse The mechanism by which methamphetamine is believed to increase the risk of MI is thought to be similar to that of cocaine, by increasing myocardial oxygen demand, increasing platelet aggregation, stimulating atherosclerotic plaque rupture, and inducing coronary artery spasm Autopsy studies have shown that methamphetamine users are to times more likely to have coronary artery disease than nonusers and that users are also at risk of developing cardiomyopathy.42 Methamphetamine use has also been associated with aortic dissection Westover and Nakonezny reviewed 3,116 aortic dissection patients aged 18 to 49 years between 1995 and 200743 and found a significant association between amphetamine abuse and aortic dissection, which was stronger than the association between cocaine abuse and aortic dissection The adjusted odds ratio of aortic dissection occurring in methamphetamine abusers was 3.33; in cocaine abusers, it was 1.6 In comparison, the odds ratio of aortic dissection in hypertensive patients was 7.68 The average age of patients with aortic dissection related to methamphetamine use was 41 years, younger than the average age in nonusers (52 years) The reason methamphetamine use is believed to increase the risk of aortic dissection is its hypertensive effect, vasculitis, or both.43 Pulmonary effects Methamphetamine itself has few significant pulmonary effects However, smoking methamphetamine may cause barotrauma and may increase the risk of pneumothorax/pneumomediastinum Acute noncardiogenic pulmonary edema and idiopathic pulmonary hypertension have been reported Bronchoconstriction typically does not occur, as methamphetamine actually causes bronchodilation Central nervous system effects Use of or withdrawal from methamphetamine can result in neuropsychiatric emergencies such as hallucinations, psychosis, depression, or anxiety Cloutier et al, in their retrospective review of emergency department visits related to methamphetamine use, found that 18% of visits were for psychiatric complaints.44 Methamphetamine use was responsible for 7.6% of psychiatric visits to the emergency department Other neurologic complaints of methamphetamine users visiting the emergency department included altered mental status (6.2%), headache (1%), and seizure (0.83%).44 Chronic use depletes dopamine transporters in the brain, potentially causing decreased motor performance and diminished verbal learning.7 In Westover et al’s study of stroke in amphetamine or cocaine abusers, methamphetamine was associated with a greater risk of hemorrhagic stroke than cocaine.15 The adjusted odds ratio of hemorrhagic stroke associated with methamphetamine use was 4.95 (2.33 for cocaine users), and the odds ratio of death after hemorrhagic stroke related to methamphetamine use was 2.63 No significant association linking amphetamine use with ischemic stroke was found.15 Anesthetic concerns and management One should expect the methamphetamine-abusing patient to be at risk of hyperthermia, hypertension, arrhythmias, and—potentially—hemorrhagic stroke The anesthetic concerns in such a patient are similar to the anesthetic con414 www.ajlobby.com Mizukawa_Chap_30.indd 414 6/21/17 3:34 PM Opioids cerns in a cocaine-abusing patient It is essential to remember methamphetamine’s half-life is longer than cocaine’s Methamphetamine’s duration of action is approximately to 12 hours, but it can be as long as 24 hours Therefore, a minimum waiting period of 24 hours is recommended before anesthesia If a patient has potentially used methamphetamine within the prior 24 hours, medications that could potentiate sympathetic cardiovascular effects should be avoided, such as epinephrine and ketamine.41 Acute methamphetamine intoxication may increase anesthetic requirements.7 It can decrease thiopental duration and can decrease the effectiveness and duration of action of succinylcholine.7 Ketamine should be avoided not only because of its sympathetic effects, but also because it is associated with an additive increase in hallucinations when given while systemic methamphetamine is present.17 Chronic use of methamphetamine may reduce catecholamine levels, which may blunt a sympathetic response to hypotension induced by anesthesia Therefore, phenylephrine may be necessary to support the blood pressure during use of a general anesthetic Drugs that cause cardiovascular depression, such as propofol, should be carefully titrated.7 As in the cocaine-abusing patient, β-blocker monotherapy should be avoided in the management of hypertension or chest pain of a methamphetamine abuser so as to avoid the unopposed α effects Additionally, one should consider benzodiazepines, nitroglycerin, or phentolamine in the management of hypertension or chest pain Prescribed amphetamines not impact adult hemodynamics, so they not need to be withheld before an anesthetic Opioids Opioid abuse has been steadily increasing, especially that of prescription opioids From 2000 to 2005, lifetime heroin use increased from 1.2% to 1.5%, whereas the lifetime use of prescription opioids for nonmedicinal purposes increased from 8.6% to 13.4%.45 Deaths due to opioid analgesic overdose currently exceed the number of deaths from suicide, motor vehicle crashes, and cocaine and heroin overdose combined.46 Between 1999 and 2014, more than 165,000 opioid pain prescription–related deaths occurred in the United States.47 A particularly dangerous combination of prescription drugs is that of benzodiazepines and opioids Various studies of fatal overdoses have revealed concurrent use of benzodiazepines and opioids in 31% to 61% of cases.47 The risk is substantial enough that the US Centers for Disease Control and Prevention (CDC) recommends that providers avoid prescribing opioids concurrent with benzodiazepines.47 In its 2016 opioid prescribing guideline, the CDC also recommends avoiding prescribing opioids for patients with moderate or severe sleep disordered breathing/sleep apnea to avoid oversedation.47 Providers are also encouraged to take advantage of their state’s prescription drug monitoring program, or PDMP, website The PDMP may provide the prescriber with essential information such as whether the patient in question is already receiving controlled substances from other providers or if the patient has been prescribed other controlled substances that may prove dangerous when combined with a prescribed opioid Opioids act at the µ receptor, providing pain relief as well as sedation and euphoria Opioids may be nasally insufflated, ingested, smoked, or injected Track marks or skin necrosis may be noted on the skin of a patient who injects opioids A chronic opioid user may develop withdrawal after 12 to 14 hours without an opioid Withdrawal symptoms include yawning, lacrimation, diaphoresis, rhinorrhea, and restless sleep However, symptoms may progress, and diarrhea and vomiting with resultant electrolyte imbalances may occur, potentially resulting in acidosis and cardiovascular collapse.26 Respiratory effects Opioids reduce respiratory rate and tidal volume and also decrease chemoreceptor sensitivity to hypoxia and hypercarbia, resulting in the well-known adverse effect of respiratory depression Large doses of certain opioids, such as fentanyl and heroin, can cause chest wall rigidity People who inject heroin have an increased risk of pneumonia 415 www.ajlobby.com Mizukawa_Chap_30.indd 415 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient Cardiovascular effects Certain opioids have had specific cardiovascular effects Propoxyphene, removed from the market in 2010, was associated with fatal arrhythmias Methadone may cause QT interval prolongation, leading to Torsade de pointes Some opioid abusers may experience hypotension during anesthesia induction and may require the administration of a pressor Some heroin addicts also take clonidine (a centrally acting α agonist), to enhance the heroin high Abrupt withdrawal of clonidine may result in a life-threatening hypertensive crisis.7 Anesthesia, pain control, and addiction management Anesthesia requirements are reduced in the face of acute opioid use However, significant opioid tolerance develops in chronic users, so these patients tend to have increased anesthesia requirements Long-term users may develop opioid hyperalgesia and allodynia, which are believed to be a result of opioid activation of N-methyl-D-aspartate receptors Therefore, ketamine is proposed in its management in addition to the gradual cessation of opioid use Postoperative pain control may be complicated in the chronic opioid user Opioid needs may be two to four times higher than in the opioid-naive patient The patient’s opioid maintenance dose will need to be continued, and additional opioids will need to be provided to cover acute pain On the day of the surgical procedure, the patient should be instructed to take his or her usual daily opioid dose Because of incomplete tolerance of various opioids, opioid rotation may be useful in long-term pain relief Adjunctive pain medications, including intravenous acetaminophen, nonsteroidal anti-inflammatory drugs, tramadol, gabapentin, or clonidine may also be considered Pain management of these patients can be complex, so it is important to involve the patient’s chronic pain physician in developing a plan for pain management Methadone or buprenorphine is used to manage opioid addiction, and methadone is also used to manage chronic pain Methadone has a very long half-life, with effects lasting for 24 hours, and it can potentially be systemically present for 59 hours Methadone has been associated with a prolonged QT interval, potentially leading to Torsade de pointes Overdose of methadone is associated with clinically significant respiratory depression In fact, methadone is responsible for approximately 30% of overdose deaths related to prescription pain medications.48 Therefore, methadone should only be prescribed by an addiction or pain specialist Again, owing to the danger of oversedation with concomitant use of opioids with benzodiazepines, one should avoid prescribing benzodiazepines to patients who are already taking methadone Buprenorphine, a semisynthetic opioid analgesic, is primarily prescribed to manage narcotic addiction It may be prescribed alone or in combination with naloxone (Suboxone [Indivior]) It also has a long duration of action (elimination half-life of 20 to 73 hours), but it has a better margin of safety than methadone because its use results in less respiratory depression Planning anesthetic administration and postoperative pain management in patients taking methadone, buprenorphine, or especially buprenorphine/naloxone can be very complicated Some addiction specialists recommend holding the buprenorphine/naloxone before the surgical procedure and replacing it with an opioid equivalent until recovery from surgery has occurred Other specialists recommend continuing buprenorphine/naloxone through the surgical procedure and the postoperative period and providing an opioid-like hydromorphone as well as adjunctive pain medication through the postoperative period It is highly recommended that one seek the assistance and recommendations of a pain/addiction specialist when planning surgery in patients taking one of these long-acting opioids because of the complexity of the situation Conclusion Drug abuse is more common than most practitioners realize It does not just involve illicit drugs, but it also includes prescription drugs This chapter only touched on the most commonly abused drugs—novel psychoactive substances are constantly being adapted to change drug composition Drug abuse affects people of all socioeconomic and educational levels Drug abusers often are not forthcoming about their use, but a prudent practitioner will recognize clinical signs of drug use and develop a way to encourage open communication with patients so as 416 www.ajlobby.com Mizukawa_Chap_30.indd 416 6/21/17 3:34 PM References to provide care safely It may be necessary to prepare for patient care based on clinical suspicion Polysubstance abuse is common Recognizing signs of drug abuse and knowing how to safely manage these patients is essential in mitigating surgical and anesthetic risk References Hupp JR Emergency department bane—Dental pain used to obtain narcotics J Oral Maxillofac Sur 2013; 71:2009–2010 [erratum 2014;72:647–648] 17 Lindsey WT, Stewart D, Childress D Drug interactions between common illicit drugs and prescription therapies Am J Drug Alcohol Abuse 2012;38:334–343 The Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health (NSDUH) National Institute on Drug Abuse https://www.drugabuse.gov/publications/ drugfacts/nationwide-trends Accessed May 2016 18 Yamreudeewong W, Wong HK, Brausch LM, Pulley KR Probable interaction between warfarin and marijuana smoking Ann Pharmacother 2009;43:1347–1353 19 Boghdadi MS, Henning RJ Cocaine: Pathophysiology and clinical toxicology Heart Lung 1997;26:466–483 Lohmeyer S Survey reveals most popular illicit drugs, most likely users The State of the USA http://www.stateoftheusa.org/content/ most-popular-illicit-drugs.php Accessed May 2016 20 Vagi SJ, Sheikh S, Brackney M, et al Passive multistate surveillance for neutropenia after use of cocaine or heroin possibly contaminated with levamisole Ann Emerg Med 2013;61:468–474 Keyes GR, Singer R, Iverson RE, et al Mortality in outpatient surgery Plast Reconstr Surg 2008;122:245–250 21 Magliocca KR, Coker NA, Parker SR The head, neck, and systemic manifestations of levimasole-adulterated cocaine use J Oral Maxillofac Sur 2013;71:487–492 Serena-Gómez E, Passeri LA Complications of mandible fractures related to substance abuse J Oral Maxillofac Surg 2008;66: 2028–2034 22 Spector S, Munjal I, Schmidt DE Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain Neuropsychopharmacology 1998;19:417–427 Fratta W, Fattore L Molecular mechanisms of cannabinoid addiction Curr Opin Neurobiol 2013;23:487–492 Cone JD Jr, Harrington MA, Kelley SS, Prince MD, Payne WG, Smith DJ Jr Drug abuse in plastic surgery patients: Optimizing detection and minimizing complications Plast Reconstr Surg 2011;127: 445–455 23 Centers for Disease Control and Prevention Agranulocytosis associated with cocaine use—Four states, March 2008–November 2009 MMWR Recomm Rep 2009;58:1381–1385 Borgelt LM, Franson KL, Nussbaum AM, Wang GS The pharmacologic and clinical effects of medical cannabis Pharmacotherapy 2013; 33:195–209 24 Saraghi M, Hersch EV Potential diversion of local anesthetics from dental offices for use as cocaine adulterants J Am Dent Assoc 2014; 145:256–259 Jay AL Reduced lung function and bullae resulting from illicit drug use JAAPA 2011;24:26–33 25 Fucci N, De Giovanni N Adulterants encountered in the illicit cocaine market Forensic Sci Int 1998;95:247–252 10 Pletcher MJ, Vittinghoff E, Kalhan R, et al Association between marijuana exposure and pulmonary function over 20 years JAMA 2012; 307:173–181 26 Sandler NA Patients who abuse drugs Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:12–14 27 Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE Triggering of myocardial infarction by cocaine Circulation 1999; 99:2737–2741 11 Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE Triggering myocardial infarction by marijuana Circulation 2001;103: 2805–2809 28 Hollander JE, Hoffman RS, Gennis P, et al Prospective multicenter evaluation of cocaine-associated chest pain Acad Emerg Med 1994; 1:330–339 12 Lindsay AC, Foale RA, Warren O, Henry JA Cannabis as a precipitant of cardiovascular emergencies Int J Cardiol 2005;104:230–232 13 Thomas G, Kloner RA, Rezkalla S Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: What cardiologists need to know Am J Cardiol 2014;113:187–190 29 McCord J, Jneid H, Hollander JE, et al; American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology Management of cocaine-associated chest pain and myocardial infarction A scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology Circulation 2008;117:1897–1907 14 Wolff V, Armspach JP, Lauer V, et al Cannabis-related stroke: Myth or reality? Stroke 2013;44:558–563 15 Westover AN, McBride S, Haley RW Stroke in young adults who abuse amphetamines or cocaine: A population-based study of hospitalized patients Arch Gen Psychiatry 2007;64:495–502 30 Hsue PY, Salinas CL, Bolger AF, Benowitz NL, Waters DD Acute aortic dissection related to crack cocaine Circulation 2002; 105: 1592–1595 16 Minozzi S, Davoli M, Bargagli AM, Amato L, Vecchi S, Perucci CA An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflicting results Drug Alcohol Rev 2010; 29: 304–317 31 Daniel JC, Huynh TT, Zhou W, et al Acute aortic dissection associated with use of cocaine J Vasc Surg 2007;46:427–433 [erratum 2007; 46:1090] 417 www.ajlobby.com Mizukawa_Chap_30.indd 417 6/21/17 3:34 PM 30 • Considerations for the Substance Abuse Patient 32 Singh S, Trivedi A, Adhikari T, Molnar J, Arora R, Khosla S Cocaine-related acute aortic dissection: Patient demographics and clinical outcomes Can J Cardiol 2007;23:1131–1134 41 Hammamoto DT, Rhodus NL Methamphetamine abuse and dentistry Oral Dis 2009;15:27–37 33 Kuczkowski KM The cocaine-abusing parturient: A review of anesthetic considerations Can J Anesth 2004;51:145–154 42 Westover AN, Nakonezny PA, Haley RW Acute myocardial infarction in young adults who abuse amphetamines Drug Alcohol Depend 2008;96:49–56 34 Lange RA, Hillis LD Cardiovascular complications of cocaine use New Engl J Med 2001;345:351–358 43 Westover AN, Nakonezny PA Aortic dissection in young adults who abuse amphetamines Am Heart J 2010;160:315–321 35 Orser B Thrombocytopenia and cocaine abuse Anesthesiology 1991;74:195–196 44 Cloutier RL, Hendrickson RG, Fu RR, Blake B Methamphetamine-related psychiatric visits to an urban academic emergency department: An observational study J Emerg Med 2013;45:136–142 36 Burday MJ, Martin E Cocaine-associated thrombocytopenia Am J Med 1991;91:656–660 37 Gershon RY, Fisher AJ, Graves WL The cocaine-abusing parturient is not at an increased risk for thrombocytopenia Anesth Analg 1996; 82:865–866 38 Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Part 8: Advanced challenges in resuscitation: Section 2: Toxicology in ECC The American Heart Association in collaboration with the International Liaison Committee on Resuscitation Circulation 2000;102(suppl 8):223I–228I 39 Brush DE, Bird SB, Boyer EW Monoamine oxidase inhibitor poisoning resulting from internet misinformation on illicit substances J Toxicol Clin Toxicol 2004;42:191–195 45 Bryson EO The anesthetic implications of illicit opioid abuse Int Anesth Clin 2011;49:67–78 46 Manchikanti L, Helm S 2nd, Fellows B, et al: Opioid epidemic in the United States Pain Physician 2012;15(3, suppl):9ES–38ES 47 Dowell D, Haegerich TM, Chou R CDC guideline for prescribing opioids for chronic pain—United States, 2016 MMWR Recomm Rep 2016;65:1–49 48 Centers for Disease Control and Prevention Morbidity and mortality weekly report Vital signs: Risk for overdose from methadone used for pain relief—United States, 1999–2010 https://www.cdc.gov/ mmwr/preview/mmwrhtml/mm6126a5.htm?s_cid=mm6126a5_w Accessed 23 March 2017 40 Associated Press Mexican cartels flooding U.S with potent meth CBS News http://www.cbsnews.com/news/mexican-cartels-flooding-us-with-potent-meth Accessed 29 June 2016 418 www.ajlobby.com Mizukawa_Chap_30.indd 418 6/21/17 3:34 PM A APPENDICES A Comprehensive Drug Index Commonly Used Drugs B and Doses C Algorithms APPENDICES www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 419 7/17/17 12:25 PM APPENDICES www.ajlobby.com Mizukawa_Section_Openers_Rev3.indd 420 7/17/17 12:25 PM APPENDIX A Comprehensive Drug Index www.ajlobby.com Mizukawa_Appendix A.indd 421 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A1 Addiction Aids Aid type EtOH Mechanism of action • GABA agonist/ glutamate antagonist • Aldehyde dehydrogenase inhibitor • Opioid antagonist • α2 agonist Opioid Opioid agonist Indications for use Effects on anesthesia administration Common drugs • Chronic EtOH abuse • EtOH abuse • Acute/chronic EtOH abuse • Alcohol withdrawal Can have synergistic effect with other opioids; can cause drop in BP • Acamprosate, topiramate, gabapentin • Disulfiram • Naltrexone, nalmefene • Clonidine, guanfacine, methyldopa Opioid abuse Can have synergistic effect with other opioids; can prolong QTc interval, leading to arrhythmias Methadone, buprenorphine Opioid antagonist Opioid abuse; maintenance Will block effect of opioids treatment to prevent relapse Naltrexone α2 agonist Opioid abuse Can have synergistic effect with other opioids; can cause drop in BP Clonidine; guanfacine, methyldopa Partial nicotine agonist Smoking cessation Can have negative neuropsychiatric effects; can increase risk for adverse cardiovascular events Varenicline BP, blood pressure; EtOH, ethanol; GABA, γ-aminobutyric acid Appendix A2 α-Adrenergics* Name Central or peripheral acting α-adrenergic Central (α2)† agonists Indications for use Mechanism of action Stimulates α2 receptors, causing inhibition of norepinephrine release Peripheral (α1) Stimulates α1 receptors, causing activation of phospholipase C, leading to smooth muscle contraction α-adrenergic Central (α2) antagonists Competitively antagonizes α2 receptors Peripheral (α1) Competitively inhibits α1 receptors Effects on anesthesia Common drugs Antihypertensive, sedative, opioid/ alcohol withdrawal Vasoconstriction, eye examinations (mydriasis), nasal decongestants Can have synergistic Dexmedetomidine effect with other sedatives Can cause increase Epinephrine, norepiin HR and BP nephrine, phenylephrine, dobutamine, ephedrine, dopamine Mostly for reversal of sedative characteristics of α2 agonists No significant effects on anesthesia Hypertension Can cause excessive Prazosin, doxazosin, hypotension when alfuzosin combined with other vasodilating drugs Atipamezole, idazoxan, mirtazapine AMP, adenosine monophosphate; BP, blood pressure; HR, heart rate *Some drugs will exhibit both α1 and α2 antagonistic characteristics as well as β-antagonism (eg, labetolol) † Peripheral in high doses Appendix A3 Analgesics Indications for use Effects on anesthesia administration Acetaminophen Not fully understood; selectively inhibits COX-2 centrally Fever and pain Can help raise pain threshold if given preoperatively Acetaminophen NSAIDs Nonselective COX-1 and COX-2 inhibitors Selectively inhibits COX-2 Fever, pain, and inflammation Pain and inflammation Can help raise pain threshold if given preoperatively Can increase risk of vascular events, MI, and CVA Aspirin, ibuprofen, naproxen Binding to µ, κ, and δ opioid receptors Pain Can cause respiratory Morphine, fentanyl, depression, nausea/vomiting, hydromorphone, hydrocodone, drowsiness, itching oxycodone, codeine Name Opioids Mechanism of action Common drugs Celecoxib, rofecoxib COX, cyclooxygenase; CVA, cerebrovascular accident; MI, myocardial infarction; NSAID, nonsteroidal anti-inflammatory drug 422 www.ajlobby.com Mizukawa_Appendix A.indd 422 6/22/17 9:50 AM Appendix A4 • Antihypertensives Appendix A4 Antihypertensives Name Mechanism of action Indications Effects on anesthesia Common drugs α-adrenergic receptor antagonists • Competitively inhibits α1-adrenergic receptors, causing vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure • Competitively inhibits α1-adrenergic receptors in prostate bladder neck tissues • Hypertension Can potentiate the hypotensive effects of sedation medications • BPH and decrease effectiveness of • PTSD phenylephrine in management of hypotension • Terazosin • Doxazosin • Tamsulosin • Prazosin α2-agonists Stimulates α2-adrenergic receptors in the brain stem, resulting in reduced sympathetic outflow and a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure • Hypertension • Can cause hypotension • Anxiolysis • Can cause bradycardia • Nicotine • Abrupt discontinuation withdrawal in clonidine can result in hypertension and agitation • Can potentiate effects of other CNS depressants • Clonidine • Methyldopa • Dexmedetomidine • Hypertension • May result in hypertension if patient does not take morning • CHF dose • Prevention • Disables the RAA mechanism of MI for blood pressure control, • Diabetic making management nephropathy of hypotension difficult intraoperatively • Dilation of the efferent glomerular artery can decrease glomerular perfusion pressure and lead to kidney dysfunction and failure • Lisinopril • Enalapril • Captopril • Ramipril ACE inhibitors • Inhibits conversion of AT-I to AT-II, leading to increased renin release and decreased aldosterone release • Reduces AT-II concentration in vascular walls, causing vasodilation Aldosterone receptor antagonists Antagonizes the effect of aldosterone in distal Systolic heart renal tubules, causing increased sodium and failure water excretion while conserving potassium; may also block the effect of aldosterone on arteriolar smooth muscle Can pose risk for hyperkalemia Spironolactone Selectively blocks aldosterone receptors, reducing blood pressure Hypertension Excessive diuresis can lead to hypotension Eplerenone Inhibits entry of calcium into excitable cells and causes vascular smooth muscle relaxation and vasodilation, decreased myocardial force generation, decreased HR, and decreased artioventricular conduction velocity; most smooth muscle selective • Hypertension Can potentiate hypotensive effects of sedation medication • Angina • Felodipine • Isradipine • Nicardipine • Nifedipine • Nisoldipine • Amlodipine • Lacidipine • Hypertension • Depressive effect on cardiac contractility and conduction • Angina • Less of a vasodilator than the dihydropyridines but can still potentiate hypotension • Amlodipine • Verapamil • Diltiazem* Calcium channel blockers Dihydro pyridines Nondihydro Same as dihyropyridines but greater pyridines myocardial selectivity and less vascular smooth muscle activity *Benzothiazepine class with vasuular and myocardial activity intermediate between dihydropyridine and nondyhydropyridine 423 www.ajlobby.com Mizukawa_Appendix A.indd 423 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A4 (cont) Antihypertensives Name Diuretics Loop diuretics Mechanism of action Indications Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and proximal and distal renal tubule, causing increased excretion of water, sodium, chloride, magnesium, and calcium Effects on anesthesia • Hypertension • Can lead to hypotension due to • Heart failure excessive diuresis • Can lead to hypokalemia, causing cardiac arrhythmias Common drugs • Furosemide • Torsemide • Bumetanide • Ethacrynic acid Thiazide diuretics Inhibits sodium and chloride reabsorption in • Hypertension • Can lead to hypotension the distal tubules causing increased excretion • Heart failure due to excess diuresis and of sodium, chloride, and water dehydration • Can lead to hypokalemia • Chlorothiazide • Hydrochlorothiazide Potassium-sparing diuretics Blocks sodium channels in the late distal convoluted tubule, and collecting duct, which inhibits sodium reabsorption from the lumen • Amiloride • Triamterene • Hypertension • Can lead to hypotension due to • Heart failure excess diuresis • Can lead to hyperkalemia and cardiac arrhythmias Antagonizes the effect of aldosterone in distal Systolic heart renal tubules, causing increased sodium and failure water excretion while conserving potassium; may also block the effect of aldosterone on arteriolar smooth muscle Can pose risk for hyperkalemia Spironolactone Selectively blocks aldosterone receptors, reducing blood pressure Hypertension Excessive diuresis can lead to hypotension Eplerenone Dopamine agonist Selective postsynaptic dopamine agonist that exerts hypotensive effects by decreasing peripheral vasculature resistance, causing increased renal blood flow, diuresis, and natriuresis Hypertension Can pose risk for hypotension Fenoldopam Endothelin receptor antagonist Blocks endothelin receptors on vascular endothelium and smooth muscle, blocking endothelin receptor–mediated vasoconstriction PAH Can lead to hepatic insufficiency and decrease metabolism of sedative medications Bosentan Nonselective α-blocker Competitively blocks α-adrenergic receptors (nonselective) to produce antagonism of the α-effects of circulating catecholamines; also has a positive inotropic and chronotropic effect on the heart Hypertension Can lead to hypotension, causing MI and CVA Phentolamine Prostacyclin inhibitor Pulmonary and systemic arterial vasodilation PAH • Inhibits platelet aggregation • Can produce symptomatic hypotension Treprostinil Renin inhibitor Direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to AT-I Hypertension Can pose risk for hypotension Vasodilator Direct vasodilation of arterioles leading to decreased systemic resistance Hypertension • Can pose risk for hypotension • Can lead to reflex tachycardia • Aliskiren • Ambrisentan • Macitentan • Hydralazine • Minoxidil • Nitroprusside ACE, angiotensin converting enzyme; AT, angiotensin; BPH, benign prostatic hyperplasia; CHF; congestive heart failure, CNS; central nervous system; CVA, cerebrovascular accident; HR, heart rate; MI, myocardial infarction; PAH, pulmonary arterial hypertension; PTSD, posttraumatic stress disorder; RAA, renin angiotensin aldosterone 424 www.ajlobby.com Mizukawa_Appendix A.indd 424 6/22/17 9:50 AM Appendix A5 ãAntidiabetics ỗỗ Appendix A5 Antidiabetics Name Mechanism of action Indications Effects on anesthesia Common drugs α-glucosidase inhibitors Inhibits pancreatic α-amylase and intestinal α-glucosidases, resulting in delayed hydrolysis of ingested carbohydrates and delayed absorption of glucose Diabetes mellitus Can lead to hypoglycemia Acarbose Amylin analogs • Prolongation of gastric emptying time • Reduction of glucagon secretion • Reduction of caloric intake by appetite suppression Diabetes mellitus Can lead to hypoglycemia Pramlintide Biguanide Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity • Diabetes mellitus • Polycystic ovarian disease Can lead to lactic acidosis with hypoperfusion or hypoxemia Metformin Insulin Acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats; increases glycogen and fatty acid synthesis Insulin-dependent diabetes mellitus Can lead to hypoglycemia Fast acting • Insulin lispro • Insulin aspart Intermediate acting • Novolin • Humulin Long acting • Insulin glargine • Insulin detemir Meglitinides Blocks ATP-dependent potassium channels, increasing intracellular calcium, which stimulates insulin release from the pancreatic β-cells Diabetes mellitus Can lead to hypoglycemia • Nateglinide • Repaglinide DPP-4 inhibitors Decreases breakdown of incretins, increasing insulin secretion and decreasing glucagon secretion Diabetes mellitus Can lead to hypoglycemia • Sitagliptin • Saxagliptin • Vildagliptin • Linagliptin • Alogliptin • Pioglitazone GLP-1 Glucose-dependent increase in insulin release, slows Diabetes mellitus gastric emptying, suppresses inappropriately elevated glucagon levels, and decreases food intake Can lead to hypoglycemia • Exenatide • Liraglutide Sulfonylureas bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic β-cells, leading to increased insulin release; reduces liver glucose production; increases insulin sensitivity Diabetes mellitus Can cause hypoglycemia in NPO patients • Glipizide • Glyburide • Glimepiride • Gliclazide • Carbutamide • Acetohexamide • Chlorpropamide • Tolbutamide • Glisoxepide • Gliquidone • Glibornuride • Glyclopyramide Diabetes mellitus Can lead to hypoglycemia Rosiglitazone Peptide analogs Sulfonylureas Thiazolidinediones Increases the sensitivity response of target cells to insulin ATP, adenosine triphosphate; DPP, dipeptidyl peptidase; GIP, gastric inhibitory polypeptide; GLP, glucagon-like peptide; NPO, nothing by mouth 425 www.ajlobby.com Mizukawa_Appendix A.indd 425 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A6 Antiasthmatics Name Mechanism of action Indications Effects on anesthesia Common drugs Adrenergic bronchodilators Relaxes bronchial smooth muscle by action on β2 receptors, little effect on heart rate • Asthma • COPD • Can cause irritability • Can lead to tachycardia • Some patients may exhibit relative resistance to β-agonists during attack, requiring increased dosage of β-agonist to overcome bronchoconstriction • Delivery method: inhaled (MDI or nebulized) or SQ > oral; IV β-agonist therapy not recommended, as it is associated with adverse cardiac effects, bronchoconstriction, airway edema, mucus secretion, inflammation • Short-acting albuterol, levalbuterol (use of albuterol inhaler > to times per day from MDI or use exceeding one canister per month are warning signs of inadequately controlled disease) • SABA + ipratropium (anticholinergic) in acute exacerbation • Long-acting salmeterol, formoterol, arformoterol, indacaterol, vilanterol, olodaterol • Epinephhrine (0.01 mg/kg to maximum dose of 0.3 to 0.5 mg SQ or IM in acute exacerbation) Anticholinergics • Blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS; increases HR and cardiac output • Causes bronchodilation by blocking muscarinic receptors in bronchial smooth muscle • Anti sialagogues • Asthma • GI disorders • Vertigo • Can cause increases in HR • Can increase intraocular pressure • Can cause constipation • Can cause urinary retention • Atropine • Glycopyrrolate • Dicyclomine • Oxybutynin • Tiotropium • Scopolamine • Ipratropium • Oxitropium • Dimenhydrinate Inhaled corticosteroids Decrease inflammation and mucus production of the bronchiole tree • Asthma • COPD • Can cause adrenal suppression with prolonged use • Can cause immuno suppression with prolonged use • Can cause bronchospasm immediately following use • Budesonide • Beclomethasone • Ciclesonide • Flunisolide • Fluticasone • Mometasone • Triamcinolone Leukotriene receptor antagonist Inhibits leukotriene receptor that is associated with airway edema, smooth muscle contraction, and the inflammatory process Asthma No alterations in anesthesia indicated • Montelukast • Zafirlukast Mast-cell stabilizers Prevents mast cell release of histamine, leukotrienes, and slowreacting substance of anaphylaxis Asthma Can be associated with PVCs, palpitations, and tachycardia Cromolyn PDE-4 inhibitors Inhibits PDE-4, leading to an accumulation of cAMP within inflammatory and structural cells, suppression of cytokine release, and decreased neutrophil lung infiltration COPD Can be associated with headaches and nausea Roflumilast Theophylline and aminophylline Blocks phosphodiesterase, resulting in increase cAMP levels and relaxation of bronchial smooth muscles; also suppresses airway response to stimuli • Asthma • COPD • Can cause exacerbation of tachyarrhythmias • May diminish the effect of benzodiazepines cAMP, cyclic adenine monophosphate; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal; HR, heart rate; IM, intramuscular; IV, intravenous; MDI, metered-dose inhaler; PDE, phosphodiesterase; PVC, premature ventricular contraction; SABA, short-acting β-agonists; SQ, subcutaneously 426 www.ajlobby.com Mizukawa_Appendix A.indd 426 6/22/17 9:50 AM Appendix A8 • Antiarrhythmics Appendix A7 Anorexigenics Name Mechanism of action Indications Effects on anesthesia Common drugs Appetite suppressant Sympathomimetic amine reducing appetite secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine Obesity • Can cause hypertension, tachycardia, ischemic events, pulmonary hypertension • Fenfluramine/phentermine (ie, “fen-phen”) has been associated with cardiac valvular dysfunction • Phentermine • Diethylpropion • Benzphetamine • Phendimetrazine Lipase inhibitor Inhibits gastric and pancreatic lipases, decreasing absorption of dietary fats by 30% Obesity No alterations in anesthetic Orlistat Serotonin 5-HT2C receptor agonist Stimulates pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus; increases α-melanocortin-stimulating hormone release at melanocortin-4 receptors and resulting in satiety and decreased food intake Obesity Rarely causes valvular disease Lorcaserin CNS, central nervous system Appendix A8 Antiarrhythmics Name Mechanism of action Indications Class I sodium channel blockers Cardiac arrhythmias Effects on anesthesia Common drugs QTc prolongation Moderate block of cardiac sodium channels with lengthened Class Ia antiarrhythmics action potential, decreased conduction velocity in non-nodal cardiac tissue, and increased refractory period • Quinidine • Disopyramide • Procainamide Class Ib Weak block of cardiac sodium channels, with shortened action antiarrhythmics potential, shortened repolarization, and decreased refractory period • Mexiletine • Lidocaine Strong block of sodium channels; no change in action potential Class Ic antiarrhythmics duration; no change in refractory period • Flecainide • Propafenone Class II β-blockers Inhibition of β-adrenergic receptors Tachy arrhythmias • Bradycardia • Hypotension • Metoprolol • Sotalol • Bisoprolol • Atenolol • Carvedilol • Labetalol • Esmolol • Propanolol • Pindolol Class III K+ blocking agents Blocks potassium channels; prolongs action potential duration Cardiac arrhythmias QTc prolongation • Dofetilide • Ibutilide • Dronedarone • Sotalol • Amiodarone Cardiac arrhythmias • Verapamil • Hypotension • Bradyarrhythmias • Diltiazem Class IV calcium Blocks calcium channel, decreases artrioventricular node channel blockers conduction, shortens action potential duration, and reduces contractility; relaxes coronary vascular smooth muscle Class V Other mechanisms that not fit categories class I to class IV • Adenosine • Digoxin • Magnesium sulfate 427 www.ajlobby.com Mizukawa_Appendix A.indd 427 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A9 Anticholinesterase Inhibitors Name Mechanism of action Anticholinesterase inhibitors Indications • Inhibits destruction of acetylcholine by acetylcholinesterase, facilitates transmission of impulses across myoneural junction • Myasthenia gravis • Reversal of nondepolarizing muscle relaxants • Postoperative urinary retention • Glaucoma Effects on anesthesia • Can cause bradycardia, atrioventricular block, hypotension • Can cause bradycardia, hypotension, flushing Common drugs • Neostigmine • Pyridostigmine • Physostigmine • Edrophonium • Echothiophate • Parathion Appendix A10 Muscle Relaxants Name Depolarizing muscle relaxant Mechanism of action Indications Mimics acetylcholine and causes a persistent depolarization of the motor endplate without being hyrolysed by acetylcholine esterase; prevents muscle endplate repolarization Nondepolarizing Blocks acetylcholine from binding to muscle relaxants motor endplate, inhibiting depolarization Dosage Common drugs • To break laryngospasm • For rapid sequence intubation • For short procedures requiring paralysis • Adult: 0.6 mg/kg • RSI: to 1.5 mg/kg • Pediatric: to mg/kg Succinylcholine Procedures requiring prolonged paralysis Inability for nerve monitoring • Vecuronium • Rocuronium • Cis-atracurium RSI, rapid sequence intubation Appendix A11 Herbals Name Indications Effects on anesthesia Clove Unknown Mechanism of action • Pain relief (dental) • Increase gastric peristalsis No adverse anesthetic effects Echinacea Variety of bioactive ingredients that increase chemotactic factors and cytokines No adverse anesthetic effects • Common cold • Increase immune system Garlic Antioxidant that fights free radicals in the body, also inhibits HMG-CoA reductase, decreasing cholesterol • Atherosclerosis • Common cold May pose increased risk of bleeding Ginkgo biloba Increases neurotransmitters, vasodilator, antioxidant • Dementia • Memory loss • PVD • Macular degeneration • May increase risk of bleeding • May interact with antihypertensives Ginseng Has structure similar to steroid hormones • Stimulant • Type II diabetes mellitus • Erectile dysfunction May interact with antihypertensives Glucosamine and chondroitin Stimulates production of hyaluronic acid and proteoglycans and decreases catabolic activity of chondrocytes Osteoarthritis No adverse anesthetic effects Saw palmetto Exact mechanism unknown BPH No adverse anesthetic effects St John’s wort Multiple biologic compounds with therapeutic effects, also decreases uptake of serotonin, neuroepinephrine, and dopamine • Depression • OCD • Can increase sedative effects of benzodiazepines • Can increase risk of serotonin syndrome BPH, benign prostatic hyperplasia; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA; OCD, obsessive-compulsive disorder; PVD, peripheral vascular disease 428 www.ajlobby.com Mizukawa_Appendix A.indd 428 6/22/17 9:50 AM Appendix A13 • GERD Drugs Appendix A12 Parkinson Disease Drugs Name Mechanism of action Indications Effects on anesthesia Common drugs Anticholinergics Inhibits parasympathetic nervous system • Drug-induced • Tachycardia can occur EPS • Do not discontinue abruptly • Parkinson disease • Trihexyphenidyl • Benztropine • Biperiden • Orphenadrine • Procyclidine Amantadine Increases dopamine availability in the CNS by promoting dopamine release and blocking its reuptake; also has been shown to be an NMDA receptor antagonist and displays anticholinergic effects Carbidopalevodopa Increases dopamine availability in the • Parkinson CNS through conversion of levodopa to disease dopamine by striatal enzymes; carbidopa • Restless leg inhibits the metabolism of levodopa syndrome Dopamine precursor • Do not stop before surgical procedures due to concern for neuroleptic malignant syndrome • Can cause orthostatic hypotension • Antihypertensive agents can increase the orthostatic effects of levodopa COMT inhibitors COMT degrades catacholamines, including dopamine; thus, inhibition of this enzyme maintains an increase in plasma dopamine levels Parkinson disease • May pose risk of hepatotoxicity • Increases effects of CNS depressants • Tolcapone • Entacapone Dopamine agonists Directly stimulate the dopamine receptors • Parkinson disease • Restless leg syndrome • Can cause orthostatic hypotension • Previously used agents (pergolide and carbergoline) have been associated with valvular disease • Bromocriptine • Pramipexole • Ropinirole • Rotigotine • Apomorphine • Increases risk for serotonin syndrome of antiemetic agents • Greatly increases the risk of drug interactions Selegiline • Can cause orthostatic hypotension • Parkinson • May potentiate effects of disease glycopyrrolate • Drug-induced EPS • Influenza A prophylaxis MAO-B inhibitors MOA-B degrades dopamine; inhibition of • Parkinson this enzyme increases bioavailability of disease dopamine in the CNS • Depression CNS, central nervous system; COMT, catechol-O-methyltransferase; EPS, extrapyramidal symptoms; MAO, monoamine oxidase; NMDA, N-methyl-D-aspartate Appendix A13 GERD Drugs Name Mechanism of action Indications Effects on anesthesia Class Antacids Elevates the pH of gastric contents by directly neutralizing the GERD acidity; may also improve lower esophageal sphincter tone, minimizing reflux of contents to the esophagus No adverse effects H2 receptor antagonists H2 receptors of gastric parietal cells promote acid production; antagonists of these receptors block the production of gastric acid • Duodenal ulcer • GERD Cimetidine can interfere with • Ranitidine the P450 pathway; increase • Famotidine • Cimetidine serum concentration of sedative agents Surface agents and alginates Binds to the gastric lining and the surface of an active peptic ulcer, forming a protective barrier against acid and pepsin • GERD • Duodenal ulcer No adverse effects PPIs Inhibits the parietal cell proton pump (H+/K+ ATP pump), decreasing gastric acid secretion • GERD No adverse effects • Esophagitis • Duodenal ulcer • Calcium carbonate • Aluminum hydroxide Sucralfate • Omeprazole • Pantoprazole • Esomeprazole ATP, adenosine triphosphate; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor 429 www.ajlobby.com Mizukawa_Appendix A.indd 429 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A14 Thyroid Drugs Name Mechanism of action Indications Levothyroxine Synthetic form of thyroxine (T4 ) T4 is subsequently converted to T3, the more active form of the thyroid hormones These hormones act intracellularly by binding the thyroid hormone receptor in the nucleus, resulting in the increased basal metabolic rate and other metabolic effects controlled by the thyroid gland • Hypothyroidism • Myxedema No significant anesthesia effects Effects on anesthesia Thyroid hormone Class Methimazole Inhibits the production of T3 and T4 by preventing the oxidation of iodine in the thyroid gland Hyperthyroidism Can cause bone marrow suppression Thioamide Propylthiouracil Inhibits the conversion of T4 to T3, leaving the majority of circulating thyroid hormone in the less active (T4) state • Hyperthyroidism Can cause bone • Grave disease marrow suppression Thioamide Appendix A15 CNS Stimulants Name Mechanism of action Indications Effects on anesthesia Common drugs Armodafinil Increases bioavailability of dopamine in the CNS by inhibiting dopamine reuptake • Narcolepsy May cause palpitations and • Shift work tachycardia syndrome Nuvigil Dextroamphetamine and amphetamine • Increases bioavailability of dopamine and norepinephrine by promoting their release from the presynaptic nerve terminal • Blocks catecholamine reuptake • ADHD • Can cause hypertension • Narcolepsy and tachycardia • May increase analgesic effect of opioids Adderall Phentermine Exerts appetite suppression by stimulating norepinephrine release from the hypothalamus Obesity (anorexiant) Can cause hypertension and tachycardia • Adipex-P • Suprenza Lisdexamfetamine Converts to dextroamphetamine and exerts its effects as noted in the dextroamphetamine section above Binge eating disorder Associated with a small chance of hypertension and tachycardia in adults Vyvanse Methamphetamine Another sympathomimetic amine similar to dextroamphetamine that exerts its CNS stimulant effects in a similar manner to dextroamphetamine Of note, it may raise heart rate and blood pressure due to its relation to ephedrine and amphetamine • ADHD • Obesity • May lower the seizure threshold • Increases hypertension and tachycardia Desoxyn Methylphenidate Exerts its CNS stimulant effects by blocking catecholamine reuptake into presynaptic nerve terminals • ADHD • May lower seizure • Narcolepsy threshold • Can increase hypertension Ritalin Modafinil Mechanism unknown; possibly increases CNS stimulation by decreasing GABA-mediated neuroinhibition • Narcolepsy May increase hypertension • ADHD • Shift work disorder Provigil ADHD, attention-deficit/hyperactivity disorder; CNS, central nervous system; GABA, γ-aminobutyric acid Appendix A16 CNS Depressants Name Mechanism of action Indications Effects on anesthesia Common drugs • Seizures • Sedation • Status epilepticus • May potentiate the sedative effects of sedation medications • May potentiate respiratory depression of sedation medications • Pentobarbital • Phenobarbital • Methohexital • Secobarbital • Amobarbital • May potentiate the sedative effects of sedation medications • May potentiate respiratory depression of sedation medications • Midazolam • Lorazepam • Diazepam • Flumazenil (reversal) Barbiturates Binds to GABA receptor, which directly results in chloride ion flow intracellularly and hyperpolarizes the nerve membrane Benzodiazepines Binds to the GABA receptor, which • Sedation increases the affinity of GABA to its • Seizures • Ketamine receptor and increases the flow of emergence chloride ion intracellularly, resulting in a delirium hyperpolarized nerve membrane CNS, central nervous system; GABA, γ-Aminobutyric acid 430 www.ajlobby.com Mizukawa_Appendix A.indd 430 6/22/17 9:50 AM Appendix A17 • Heme-Related Agents Appendix A17 Heme-Related Agents Name Subclasses Mechanism of action Indications Effects on anesthesia Common drugs Anticoagulants* Vitamin K antagonists Antiplatelet agents Glycoprotein Platelet aggregation inhibitor IIb/IIIa inhibitors Status post-PCI No adverse effects • Abciximab • Eptifibatide • Tirofiban Irreversible inhibitors on P2Y12 Platelet aggregation inhibitor Acute coronary syndromes No adverse effects Clopidogrel ADP receptor Important for platelet activation • Unstable angina and eventual cross-linking • NSTEMI undergoing PCI No adverse effects • Prasugrel • Ticlopidine COX inhibitors Inhibits platelet aggregation by blocking production of thromboxane • Status post-PCI • Coronary artery disease • CVA Nonselective COX inhibition can cause broncho constriction as the leukotriene pathway is favored Aspirin Aminocaproic acid Inhibitors of fibrinolysis Inhibits proteolytic enzyme plasmin, responsible for fibrinolysis Bleeding Increased risk of thrombosis Amicar Tranexamic acid Lysine analog Inhibits plasmin activation from Bleeding plasminogen Increased risk of thrombosis • Lysteda • Cyklokapron Antihemophilic agent Factor VIII replacement • Activates factor X in coagulation cascade • Factor X activates prothrombin to thrombin • Thrombin: fibrinogen to fibrin Bleeding in the presence of hemophilia No adverse effects • Advate • Kogenate • Recombinate • Xyntha Novel anticoagulants† Direct thrombin • Prevent thrombin from inhibitors cleaving fibrinogen to fibrin • Bind to thrombin directly • Heparins enhance activity of antithrombin • Venous thromboembolism • Atrial fibrillation • Unstable angina • MI • Coronary stenting No adverse effects • Bivalirudin • Argatroban • Desirudin • Dabigatran Factor Xa inhibitors Heparin-induced thrombocytopenia Inhibit factors II, VII, IX, X • Atrial fibrillation • Atrial flutter • Cardiac valve replacement • MI • CVA, recurrent transient ischemic attack Suspect bleeding if hypotensive Coumadin Antifibrinolytics Bind to factor Xa; prevent cleaving of prothrombin to thrombin • Rivaroxaban • Apixaban • Edoxaban • Fondaparinux ADP, adenosine diphosphate; COX, cyclooxygenase; CVA, cerebrovascular accident; MI, myocardial infarction; NSTEMI, non–ST segment elevation myocardial infarction; PCI, percutaneous coronary intervention *Elderly patients tend to require lower dosages to produce a therapeutic level of anticoagulation † Unable to induce heparin-induced thrombocytopenia, as they not induce or react with antiheparin/PF4 antibodies 431 www.ajlobby.com Mizukawa_Appendix A.indd 431 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A18 Antiepileptics Name Calcium channel blockers GABA activity Barbiturates Benzodiazepines Glutamate receptors Effects on anesthesia Indications Diminish T-type calcium currents in thalamic neurons, which are further reduced as membrane potentials become more hyperpolarized Absence seizures • Bind to GABA receptors, increasing the duration of open chloride channels • Enhance GABA action by specific inhibition of GABA reuptake into presynaptic neurons • Decrease elimination of GABA from the synaptic space, making endogenously produced GABA more available for postsynaptic inhibitory effects • Irreversibly inhibit GABAtransaminase, which raises the concentration of GABA in the CNS • Sedating effects • Generalized and • May limit clinical use potentiate focal seizures for management of the sedative • Status seizures effects of epilepticus • Visual field/vision loss sedation • Adjunct medications treatment for • May focal seizures potentiate • Adjunct for respiratory refractory focal depression seizures of sedation medications Increase the flow of chloride ions through the GABA ion channel, causing postsynaptic hyperpolarization and a decreased ability to initiate an action potential • Sedation • Seizures • Treatment for ketamine emergence delirium • May potentiate the sedative effects of sedation medications • May potentiate respiratory depression of sedation medications When taken with opioids or other CNS depressants including alcohol, may see respiratory depression and/ or apnea, resulting in death • Midazolam • Lorazepam • Diazepam • Flumazenil (reversal) Noncompetitive AMPA-type glutamate receptor antagonist Adjunctive treatment for focal-onset seizures No significant effects Can see aggression, hostility, and violent ideation Perampanel Binds to voltage-dependent sodium channels in the inactivated state and thus inhibit the generation of rapid action potentials • Focal and generalized seizures • Bipolar disorders • Chronic pain (trigeminal neuralgia) No significant effects Can be associated with aplastic anemia Carbamazepine CNS depression Adverse effects Common drugs Mechanism of action No adverse effects Ethosuximide • Pentobarbital • Phenobarbital • Methohexital • Secobarbital • Amobarbital • Tiagabine • Vigabatrin Sodium channel blockers Carbamazepine 432 www.ajlobby.com Mizukawa_Appendix A.indd 432 6/22/17 9:50 AM Appendix A18 • Antiepileptics Appendix A18 (cont) Antiepileptics Name Mechanism of action Indications Effects on anesthesia Adverse Effects Common drugs Phenytoin • Blocks voltage-dependent neuronal sodium channels • Causes diminishing synaptic transmission • Focal and generalized seizures • Mixed seizures Severe hypotension and cardiac arrhythmia possible with rapid injection Phenytoin • May reduce the effectiveness of most forms of hormonal contraception • Gingival hyperplasia (folic acid supplementation reported to help diminish) • Associated with Stevens-Johnson syndrome and toxic epidermal necrolysis (particularly during first weeks of therapy) • Decreased bone density • Neurotoxic adverse effects: confusion, slurred speech, double vision, ataxia Lamotrigine • Blocks the repetitive firing of neurons by inactivating voltagegated sodium channels • May selectively influence neurons that synthesize glutamate and aspartate (both excitatory neurotransmitters) • Focal seizures • Tonic-clonic seizures • Mixed seizure disorders No significant effects • Rash • Nausea • Dizziness • Somnolence • Aseptic meningitis (causal association) Lamotrigine Oxcarbazepine Binds to voltage-dependent sodium channels in the inactivated state and thus inhibit the generation of rapid action potentials Focal and generalized seizures No significant effects • May reduce the effectiveness of most forms of hormonal contraception • Sedation • Headache • Dizziness • Rash • Vertigo • Ataxia • Nausea • Diplopia • Hyponatremia (increased responsiveness of collecting tubules to ADH); one of causes of SIADH Oxcarbazepine Zonisamide Blocks both voltage-gated sodium and calcium channels Add-on therapy for focal and generalized seizures No significant effects • Somnolence • Abnormal thinking (psychosis, aggression, depression) Zonisamide Lacosamide Enhance slow inactivation of Partial onset voltage-dependent sodium channels, seizure stabilizing hyperexcitable neuronal membranes and inhibiting neuronal firing No significant effects May see prolongation of PR Lacosamide interval and atrioventricular block Rufinamide Prolongs inactive state of sodium channels No significant effects • Somnolence • Vomiting • QT shortening Adjunct treatment for seizures Rufinamide 433 www.ajlobby.com Mizukawa_Appendix A.indd 433 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A18 (cont) Antiepileptics Name Mechanism of action Indications Effects on anesthesia Adverse Effects Common drugs Eslicarbazepine Causes preferential blockade of voltage-gated sodium channels in rapidly firing neurons Adjunctive treatment for focal-onset seizures No significant effects • Dizziness • PR interval increase • Abnormal liver function tests • Hyponatremia Eslicarbazepine Valproate • Blocks voltage-gated sodium channels, suppressing high frequency, repetitive neuronal firing • Increases brain GABA concentrations • Inhibits nerve terminal GABA transaminase • Blocks calcium currents Generalized and focal seizures No significant effects • Nausea and vomiting • Tremor • Insulin resistance • Metabolic syndrome • Thrombocytopenia/ coagulation disturbances • Fetal malformations • Hepatotoxicity Valproate Topiramate • Blocks voltage-gated sodium channels • Enhances GABA activity at nonbenzodiazepines site on GABA(A) receptor • Antagonizes an NMDA-glutamate receptor • Weakly inhibits carbonic anhydrase in the CNS Focal and mixed seizures No significant effects • Impaired cognition (common reason for discontinuing therapy) • Paresthesias • Decreased sweating leading to heat intolerance/ hyperthermia • Metabolic acidosis Topiramate Gabapentin Binds voltage-gated calcium channel, inhibiting inward calcium currents and attenuating neurotransmitter release Adjunctive therapy for focal seizures No significant effects No significant drug interactions Gabapentin Levetiracetam Adjunctive therapy • Unknown MOA • Thought to bind synaptic vesicles, for focal seizures resulting in modulated synaptic transmission through alteration of vesicle fusion No significant effects • May see acute kidney injury • Paradoxic worsening of seizures in first few weeks of starting in those who are intellectually disabled and those with baseline behavioral problems Levetiracetam Pregabalin • Inhibits neuronal excitability • Binds to voltage-gated calcium channels and modulates calcium currents • Modulates the release of several neurotransmitters, including glutamate, noradrenalin, and substance P No significant effects • May cause euphoria • Can see thrombocytopenia and prolongation of PR interval Pregabalin Drugs with other MOAs • Adjunctive therapy for focal seizures • Neuropathic pain • Diabetic peripheral neuropathy • Postherpetic neuralgia • Fibromyalgia ADH, antidiuretic hormone secretion; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; CNS, central nervous system; GABA, γ-aminobutyric acid; MOAs, mechanisms of action; NMDA, N-methyl-D-aspartate; SIADH, syndrome of inappropriate antidiuretic hormone secretion 434 www.ajlobby.com Mizukawa_Appendix A.indd 434 6/22/17 9:50 AM Appendix A19 • Antidepressants Appendix A19 Antidepressants Name Effects on anesthesia Mechanism of action Indications • Structurally related to amphetamine • Inhibit presynaptic reuptake of dopamine and norepinephrine • Major depression with inadequate response • Intolerable adverse effects from firstline therapy • ADHD • Tobacco dependence • Obesity Can pose dosedependent risk of seizures May see CNS stimulation Bupropion and hypertension Increases release of serotonin and norepinephrine by blockade of presynaptic α-receptors and postsynaptic serotonin receptors • Major depression • Anxiety disorder • Tension-type headaches Sedative profile from high affinity for histamine H1 receptors • Cardiac arrest has been reported with overdoses • May see anticholinergic effects, QT prolongation; caution for serotonin syndrome Monoamine oxidase inhibitors • Irreversibly block monoamine oxidase, the enzyme responsible for degradation of serotonin, norepinephrine, and dopamine • Block histamine receptor Depression Hypertensive crisis has been reported • Tranylcypromine • Dietary restrictions • Phenelzine • May see postural hypotension, particu- • Selegiline larly when taken with other medications that cause hyptension SNRIs • Block presynaptic serotonin and norepinephrine transporter proteins • Inhibit reuptake of neurotransmitters, leading to increased stimulation of postsynaptic receptors • Depression with poor response to SSRI • Panic disorders • OCD • PTSD Can pose risk of serotonin syndrome • Little to no effect on dopaminergic, cholinergic, histaminergic, or A1 receptors • Stimulate norepinephrine receptors in SNS, leading to pseudoanticholinergic effects (eg, constipation, dry mouth, urinary retention) • May see increased BP over the course of treatment • Desvenlafaxine • Duloxetine • Milnacipran • Venlafaxine SSRIs • Inhibit the serotonin reuptake pump and increase postsynaptic serotonin receptor occupancy • Little to no effect on norepinephrine or dopamine reuptake • First-line antidepressants • Anxiety • Panic disorders • OCD • PTSD • Eating disorders • Can potentiate sedative medications • Can increase risk of serotonin syndrome • Sedation • Doses > 40 mg of citalopram result in dose-dependent QT prolongation • Citalopram • Fluoxetine • Sertraline • Paroxetine • Escitalopram • Fluvoxamine Atypical antidepressants Bupropion Mirtazapine Adverse effects Common drugs Mirtazapine 435 www.ajlobby.com Mizukawa_Appendix A.indd 435 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A19 (cont) Antidepressants Name Tricyclic and tetracyclic antidepressants Mechanism of action Inhibit reuptake of both serotonin and norepinephrine Effects on anesthesia Indications • Depression • Panic attacks • Generalized anxiety • PTSD • Sedative profile (antihistaminic) • All are potentially cardiotoxic and can cause orthostatic hypotension • Can potentially produce arrhythmias • Can cause dose-dependent lowering of seizure threshold Adverse effects Common drugs May see anticholinergic effects • Amitriptyline • Amoxapine • Clomipramine • Desipramine • Doxepin • Imipramine • Maprotiline • Nortriptyline • Protriptyline • Trimipramine ADHD, attention-deficit hyperactivity disorder; BP, blood pressure; OCD, obsessive-compulsive disorder; PTSD, posttraumatic stress disorder; SNRI, serotonin-norepinephrine reuptake inhibitor; SNS, sympathetic nervous system; SSRI, selective serotonin reuptake inhibitors Appendix A20 Antihistamines Common drugs Name Mechanism of action Effects on anesthesia Indications First generation (nonselective, sedating) Second generation (selective, nonsedating) H1 blockers Antagonists of H1 receptor • Hypersensitivity • Pruritus • Urticaria • Angioedema • Adjunct in anaphylaxis • Sedative profile on first generation H1 • Euphoria • Dizziness • Tinnitus • Diphenhydramine • Promethazine H2 blockers • Antagonists of H2 receptor (parietal cells in stomach) • Decreasing acid production • Dyspepsia • GERD • Peptic ulcer disease • Prevention of stress ulcer (ranitidine) No adverse effects NA • Cimetidine (Tagamet [SmithKline Beecham])* • Ranitidine (Zantac [GlaxoSmithKline]) • Famotidine (Pepcid [Johnson and Johnson]) • Loratadine • Cetirizine • Terfenadine Third generation Fexofenadine NA *Multiple drug interactions due to effect on cytochrome P450 system GERD, gastroesophageal reflux disease; NA, not applicable Appendix A21 Vasopressors* Name Dobutamine Mechanism of action Indications Effects on anesthesia Considerations • β1-agonist increasing inotropy and chronotropy • Minimal α and β2 effects with overall result of vasodilation • Severe, medically refractory HF • Cardiogenic shock Patient requiring dobutamine may not be a candidate for office-based anesthesia, depending on the indication for the vasopressor May be used to induce cardiac stress when treadmill is not tolerated in a stress test Mainly dopaminergic to produce renal and mesenteric vasodilation Increases renal blood flow and consequently urine output Patient requiring dopamine may not be a candidate for office-based anesthesia, depending on the indication for the vasopressor More arrhythmias than norepinephrine/ longer hospital stay vs norepinephrine Dopamine† Low doses 436 www.ajlobby.com Mizukawa_Appendix A.indd 436 6/22/17 9:50 AM Appendix A21 • Vasopressors Appendix A21 (cont) Vasopressors* Name Mechanism of action Indications Effects on anesthesia Considerations • Dopaminergic and β1, producing cardiac stimulation and renal vasodilation • Stimulate α-adrenergic receptors Patient requiring dopamine α- and ß-adrenergic may not be a candidate for effects predominate, resulting in increased blood office-based anesthesia, depending on the indication for pressure, chronotropy, the vasopressor inotropy, and an overall increase in cardiac output No evidence to support routine use of low-dose dopamine for renal protective effects Ephedrine Indirect α- and β-agonist as it causes release of norepinephrine Hypotension in setting of bradycardia • Slightly delayed onset • Longer acting and less potent than epinephrine Epinephrine • Anaphylaxis • Septic shock (secondβ1 response predominates as line agent) 1Đ vasoconstriction is offset by ã Hypotension || vasodilation • Bronchospasm • Severe asthma attack α1-receptor effect predominates High doses Low doses High doses Isoproterenol ‡ • β1‡ with increasing inotropy and significant chronotropic effects • β2||: relaxation of bronchial, GI, smooth muscle, vasodilation Effectively used in anesthesia to treat hypotension and/or bradycardia Increased cardiac output • Splanchnic vasoconstriction • Dysrhythmias Increased systemic vascular resistance Hypotension from bradycardia Increased cardiac output Use in ACLS has become outdated; use for bronchospasm and shock are also not recommended Norepinephrine α1- and β-agonist, with α effects dominant over the β effects Hypotension • Increase MAP • May see reflex bradycardia due to vasoconstriction • Preferred vasopressor in septic shock • Less arrhythmias than dopamine/shorter hospital stay vs dopamine Phenylephrine Pure α-agonist Hypotension • Increase MAP • Reflex bradycardia • Effective in treating hypotension with tachycardia May be more useful when tachycardia or dysrhythmias preclude the use of agents with β-adrenergic activity Phospho diesterase inhibitors (milrinone) Selective phosphodiesterase • Impaired cardiac inhibitor in cardiac and vascular function tissues, leads to vasodilation • Medically refractory HF and inotropic effects with few chronotropic effects Patient requiring milrinone Vasodilatory properties may not be a candidate for limit use in hypotensive office-based anesthesia, patients depending on the indication for the vasopressor Vasopressin • ADH action: increases water permeability at renal tubules • Direct vasoconstrictor without ionotropic/ chronotropic effects Patient requiring vasopressin • Rebound hypotension is common and may not be a candidate for requires a slow taper office-based anesthesia, depending on the indication for • Adverse effects: the vasopressor hyponatremia, pulmonary vasoconstriction • Vasodilatory shock • Hypotension • Diabetes insipidus • Esophageal variceal bleeding ADH, antidiuretic hormone secretion; GI, gastrointestinal; HF, heart failure; MAP, mean arterial pressure *Need to correct hypovolemia prior to initiation of vasopressors Also, responsiveness to these drugs decreases over time due to tachyphylaxis † Located in renal, splanchnic (mesenteric), coronary, and cerebral vascular beds, leads to vasodilation, a second type of dopamine receptor leads to norepinephrine release ‡ Increased iontropy and chronotropy of cardiac musculature with minimal vasoconstriction || Vasodilation § Vasoconstriction of peripheral vascular walls, also located in the heart, and increase duration of contraction without increased chronotropy 437 www.ajlobby.com Mizukawa_Appendix A.indd 437 6/22/17 9:50 AM Appendix A: Comprehensive Drug Index Appendix A22 Antiemetics Name Anticholinergics Dopamine receptor antagonists Benzamides −−Low doses −−High doses Mechanism of action M1 receptor antagonist Indications Prophylaxis against nausea and vomiting • Antiemesis • Gastroparesis Central and periph- • GERD eral D2 antagonism D2 antagonism + weak serotonin blockade Effects on anesthesia Apply patch hour prior to surgery Common drugs Scopolamine • Can be given when Metocloprathere is a concern mide for residual gastric contents • PONV prophylaxis • Increases lower esophageal sphincter tone Considerations • As effective as mg Zofran, 1.25 mg droperidol • Adverse effects: visual disturbances, dry mouth, drowsiness • FDA black box warning: risk of irreversible tardive dyskinesia with higher dosing and long-term use • Speeds gastric emptying • EPS can be managed with diphenhydramine • May see arterioventribular block Nausea May see some inhibition of α1-receptors, resulting in hypotension • Droperidol • If given IV: QT prolongation • Haloperidol and torsade de pointes (recommendation: monitor QT for to hours) • EPS can be managed with diphenhydramine • Antagonizing D2 receptors • Antagonizing M1 receptors • Antagonizing H1 receptors • Nausea from GI disorders and chemotherapy • Hiccups • Acute intermittent porphyrisa May see some inhibition of α1-receptors, resulting in hypotension • Prochlor• QT prolongation perazine • EPS can be managed with diphenhydramine • Chlorpromazine Glucocorticoids Unknown mechanism of antiemetic activity Nausea/vomiting Should be given prior to surgical insult Dexamethasone Adverse effects: A dose of mg provides maximum prophylaxis when given with Zofran Histamine (H1) blockers • Antagonists of H1 receptor • Also block muscarinic cholingeric effects • Hypersensitivity • Pruritus • Urticaria • Angioedema • Adjunct in anaphylaxis • Nausea and vomiting May see respiratory depression Promethazine • Euphoria, dizziness, tinnitus • May be associated with severe tissue injury and gangrene, resulting from extravasation into perivascular space, inadvertent arterial injection, and neural damage • IV administration discouraged; oral, intramuscular, and rectal routes preferred • EPS can be managed with diphenhydramine Serotonin receptor antagonists Blocks serotonin receptor PONV prophylaxis No significant effects • Ondanse- • Electrocardiogram changes can be seen with Zofran (most tron prominent hours after a dose), • Granisetron QT prolongation, torsade de • Dolasetron pointes have been reported • Palonosetron (long- • Electrocardiography usually returns to baseline in 24 hours acting new • Improved efficacy if given with agent) dexamethasone • PO as effective as IV Butyrophenones • Antagonist of D2-receptors • α-blocker Phenothiazines D2, dopamine; EPS, extrapyramidal symptoms; FDA, US Food and Drug Administration; GERD, gastroesophogeal reflux disease; GI, gastrointestinal; H1, histamine; IV, intravenously; M1, muscarinic; NK1, neurokinin1 (substance P); PO, by mouth; PONV, postoperative nausea and vomiting 438 www.ajlobby.com Mizukawa_Appendix A.indd 438 6/22/17 9:50 AM APPENDIX B Commonly Used Drugs and Doses www.ajlobby.com Mizukawa_Appendix B.indd 439 6/20/17 12:19 PM Appendix B: Commonly Used Drugs and Doses Appendix B Commonly Used Drugs and Doses Name Class Target receptor Dose for TIVA Time to onset Time of duration 0.5–1 mg/kg bolus, 50–150 µg/kg/min infusion 10–20 s, depending on dose 5–10 A decrease in BP; may see reflex tachycardia, but this reflex is generally attenuated by propofol Cardiovascular effects Propofol Sedative/ hypnotic Midazolam Benzodiazepine GABA 0.05–0.1 mg/kg 20–30 s 20–30 Modest drop in BP; HR and CO maintained Diazepam Benzodiazepine GABA 0.3–0.5 mg/kg 30–60 s 60 Modest drop in BP; HR and CO maintained Fentanyl Opioid µ, δ, k 0.001 µg/kg, titrated to effect 20–30 s 20–30 Stable but modest hypotension and bradycardia may be seen Remifentanyl Opioid µ, δ, k µg/kg induction, 0.050.1 µg/kg/min infusion 20–30 s 5–10 Stable, but modest hypotension and bradycardia may be seen Meperedine Opioid µ, δ, k 0.5–1 mg/kg, titrated to effect 30–45 Stable; tachycardia can be seen Ketamine Phencyclidine NMDA mg/kg IV; 2–4 mg/ kg IM, mg/kg PO for premedication 30–60 s 10–15 Increased HR and BP Methohexital Barbiturate GABA 1–2 mg/kg, less when used with other agents 10–15 s 5–10 Vasodilation, drop in BP, reflex tachycardia, negative inotropy Thiopental Barbiturate GABA 3–4 mg/kg, less when used with other agents 15–30 s 10–15 Vasodilation, drop in BP, reflex tachycardia, negative inotropy Etomidate Sedative/ hypnotic GABA 0.2–0.4 mg/kg 15–20 s 100 s/0.1 Minimal CV changes are seen mg/kg dose α2 receptor 0.25–0.5 ug/kg bolus, or < 0.5–1 µg/kg/h 30 Negative inotropy/chronotropy, lowers SVR 0.2 mg, repeated every 2–5 30–60 s 20–30 None 0.4–0.8 mg 1–2 30–45 Stable 36–54 h Stable 35–50 None Dexmedetomidine α2 agonist GABA Flumazenil Benzodiazepine GABA antagonist Naloxone Opioid antagonist Dexamethasone Steroid Rocuronium Nondepolarizing relaxant Sugammadex NMB antagonist µ, δ, k 4–8 mg IV Acetylcholine 0.6 mg/kg 90–120 s mg/kg 1.9–2.1 None BP, blood pressure; CO, cardiac output; CV, cardiovascular; GABA, γ-aminobutyric acid; HR, heart rate; IM, intramuscular; IV, intravenous; NMB, neuromuscular blockade; NMDA, N-methyl-D-asparate; MH, malignant hyperthermia; PO, by mouth; PONV, postoperative nausea and vomiting; SVR, systemic vascular resistance; TIVA, total intravenous anesthesia 440 www.ajlobby.com Mizukawa_Appendix B.indd 440 6/20/17 12:19 PM Appendix B Pulmonary effects Seizure threshold Metabolism MH Other Profound depression; bronchodilation Raises Liver; excreted in kidneys No Euphoria, antiemetic; once bottle is opened, it must be used within h; propofol infusion syndrome Modest respiratory depression when used alone; opioids synergistically augment depression Raises Liver, active metabolites; hydroxymidazolams have weak effects and are quickly cleared No Muscle relaxation Modest respiratory depression when used alone; opioids synergistically augment depression Raises Liver, active metabolites; oxazepam and desmethyldiazepam can prolong effects No Phlebitis Respiratory depression; may suppress cough reflex None Liver, inactive metabolite; norfentanyl No Rigid chest wall Respiratory depression; may suppress cough reflex None Plasma esterase No Rigid chest wall Respiratory depression; histamine release may cause bronchospasm; may suppress cough reflex Lowers Liver, active metabolite; normeperidine No May have properties similar to those of atropine, such as tachycardia and decreased secretions; histamine release; treatment for shivering; asthma, PONV; active metabolite (normeperidine), a potent convulsant Respiratory drive preserved; modest depression may be seen when used with other drugs; bronchodilation; beware of increased secretions that may stimulate the airway Lowers Liver, active metabolite; norketamine can prolong action No PO, IM, and nasal routes available for premedication; pupils dilate; salivation increases; emergence delirium can occur, which can be avoided with concomitant use of benzodiazepines or propofol; use with caution in patients with a history of substance abuse or some psychiatric disorders Respiratory depression and apnea; may increase airway reactivity and laryngospasms Lowers Liver No Phlebitis; use caution in patients with acute intermittent porphyria and severe respiratory or cardiac disease Respiratory depression and apnea; may increase airway reactivity and laryngospasm; histamine release may lead to bronchospasm None Renal clearance No Phlebitis; use caution in patients with acute intermittent porphyria, severe respiratory or cardiac disease, and asthma Respiratory drive is preserved; modest depression may be seen when used with other drugs Lowers Liver; inactive metabolites No PONV, myoclonus, hiccups, thrombophlebitis; adrenocortical suppression may be seen, especially in critically ill patients Minimal ventilatory depression Lowers Liver No Treats shivering; emergence delirium; reversed by atipamezole Reverses respiratory depression associated with benzodiazepines, but not that associated with opioids Lowers Liver; activity of metabolites unknown No May cause withdrawal symptoms in high doses; may reverse amnesia; use caution for resedation; monitor the patient for 20–30 after dose Reverses respiratory depression seen with opioid use None Liver No Will reverse analgesia Decreases airway edema None Liver No Also provides antiemetic effects None None Liver No Reversed by sugammadex None None Renal clearance No None 441 www.ajlobby.com Mizukawa_Appendix B.indd 441 6/20/17 12:19 PM www.ajlobby.com Mizukawa_Appendix B.indd 442 6/20/17 12:19 PM APPENDIX C Algorithms www.ajlobby.com Mizukawa_Appendix C.indd 443 6/20/17 12:20 PM Appendix C: Algorithms Appendix C1: Algorithm for Adult Cardiac Arrest* CPR Quality Start CPR • Push hard (at least inches [5 cm]) and fast (100-120/min) and allow complete chest recoil • Minimize interruptions in compressions • Avoid excessive ventilation • Rotate compressor every minutes, or sooner if fatigued • If no advanced airway, 30:2 compression-ventilation ratio • Quantitative waveform capnography −− If PETCO2 < 10 mm Hg, attempt to improve CPR quality • Intra-arterial pressure −− If relaxation phase (diastolic) pressure < 20 mm Hg, attempt to improve CPR quality • Give oxygen • Attach monitor/defibrillator Yes VF/pVT No Rhythm shockable? Asystole/PEA Shock CPR Shock Energy for Defibrillation Rhythm shockable? • Biphasic: Manufacturer recommendation (eg, intital dose of 120-200 J); if unknown, use maximum available Second and subsequent doses should be equivalent, and higher doses may be considered • Monophasic: 360 J • IV/IO access No Yes Shock Drug Therapy 10 • IV/IO access • Epinephrine every 3-5 • Consider advanced airway, capnography • Epinephrine every 3-5 • Consider advanced airway, capnography No Rhythm shockable? • Epinephrine IV/IO dose: mg every 3-5 minutes • Amiodarone IV/IO dose: First dose: 300 mg bolus Second dose: 150 mg CPR CPR Rhythm shockable? Yes Shock Advanced Airway Yes No 11 CPR • Amiodarone • Treat reversible causes CPR Return of Spontaneous Circulation (ROSC) Rhythm shockable? • Pulse and blood pressure • Abrupt sustained increase in PETCO2 (typically ≥ 40 mm Hg) • Spontaneous arterial pressure waves with intra-arterial monitoring • Treat reversible causes No • Endotracheal intubation or supraglottic advanced airway • Waveform capnography or capnometry to confirm and monitor ET tube placement • Once advanced airway in place, give breath every seconds (10 breaths/min) with continuous chest compressions Yes 12 Reversible Causes Go to or • If no signs of return of spontaneous circulation (ROSC), go to 10 or 11 • If ROSC, go to Post– Cardiac Arrest Care *Reprinted with permission from the American Heart Association • Hypovolemia • Hypoxia • Hydrogen ion (acidosis) • Hypo-/hyperkalemia • Hypothermia • Tension pneumothorax • Tamponade, cardiac • Toxins • Thrombosis, pulmonary • Thrombosis, coronary 444 www.ajlobby.com Mizukawa_Appendix C.indd 444 6/20/17 12:20 PM Appendices C1/C2: Algorithms for Cardiac Arrest Appendix C2: Algorithm for Pediatric Cardiac Arrest* CPR Quality Start CPR • Push hard (≥ 1/3 of anteroposterior diameter of chest) and fast (100-120/ min) and allow complete chest recoil • Minimize interruptions in compressions • Avoid excessive ventilation • Rotate compressor every minutes, or sooner if fatigued • If no advanced airway, 15:2 compression-ventilation ratio • Give oxygen • Attach monitor/defibrillator Yes No Rhythm shockable? VF/pVT Asystole/PEA Shock Energy for Defibrillation • First shock J/kg, second shock J/kg, subsequent shocks ≥4 J/kg, maximum 10 J/kg or adult dose Shock Drug Therapy CPR • Epinephrine IO/IV dose: 0.01 mg/kg (0.1 mL/kg of 1:10 000 concentration) Repeat every 3-5 minutes • If no IO/IV access, may give endotracheal dose: 0.1 mg/kg (0.1 mL/ kg of 1:1000 concentration) • Amiodarone IO/IV dose: mg/kg bolus during cardiac arrest May repeat up to times for refractory VF/pulseless VT • Lidocaine IO/IV dose: Initial: mg/kg loading dose Maintenance: 20-50 mcg/ kg per minute infusion (repeat bolus dose if infusion initiated >15 minutes after initial bolus therapy) • IV/IO access Rhythm shockable? No Yes Shock 10 CPR CPR • IV/IO access • Epinephrine every 3-5 • Consider advanced airway • Epinephrine every 3-5 • Consider advanced airway No Rhythm shockable? Rhythm shockable? Yes Shock Advanced Airway Yes No 11 CPR Return of Spontaneous Circulation (ROSC) CPR • Amiodarone or lidocaine • Treat reversible causes • Treat reversible causes No Rhythm shockable? Yes ⃗ ⃗ • Pulse and blood pressure • Spontaneous arterial pressure waves with intra-arterial monitoring Reversible Causes 12 Go to or • Asystole/PEA 10 or 11 • Organized rhythm check pulse • Pulse present (ROSC) post-cardiac arrest care • Endotracheal intubation or supraglottic advanced airway • Waveform capnography or capnometry to confirm and monitor ET tube placement • Once advanced airway in place, give breath every seconds (10 breaths/min) with continuous chest compressions ⃗ *Reprinted with permission from the American Heart Association • Hypovolemia • Hypoxia • Hydrogen ion (acidosis) • Hypoglycemia • Hypo-/hyperkalemia • Hypothermia • Tension pneumothorax • Tamponade, cardiac • Toxins • Thrombosis, pulmonary • Thrombosis, coronary 445 www.ajlobby.com Mizukawa_Appendix C.indd 445 6/20/17 12:20 PM Appendix C: Algorithms Appendix C3: Algorithm for Adult Bradycardia with a Pulse* Doses/Details Assess appropriateness for clinical condition Heart rate typically 50%, or maximum dose 17 mg/kg given Maintenance infusion: 1-4 mg/min Avoid if prolonged QT or CHF Amiodarone IV dose: First dose: 150 mg over minutes Repeat as needed if VT recurs Follow by maintenance infusions of mg/ for first hours Sotalol IV dose: 100 mg (1.5 mg/kg) over minutes Avoid if prolonged QT • IV access and 12-lead ECG if available • Vagal maneuvers • Adenosine (if regular) • β-Blocker or calcium channel blocker • Consider expert consulation *Reprinted with permission from the American Heart Association 448 www.ajlobby.com Mizukawa_Appendix C.indd 448 6/20/17 12:20 PM Appendices C5/C6: Algorithms for Tachycardia with a Pulse Appendix C6: Algorithm for Pediatric Tachycardia with a Pulse and Poor Perfusion* Doses/Details Identify and treat underlying cause Synchronized Cardioversion • Maintain patent airway; assist breathing as necessary • Oxygen • Cardiac monitor to identify rhythm; monitor blood pressure and oximetry • IO/IV access • 12-Lead ECG if available; don’t delay therapy Begin with 0.5-1 J/kg; if not effective, increase to J/kg Sedate if needed, but don’t delay cardioversion Drug Therapy Narrow ( ≤ 0.09 sec) Wide ( > 0.09 sec) Evaluate QRS duration Evaluate rhythm with 12-lead ECG or monitor Probable sinus tachycardia • Compatible history consistent with known cause • P waves present/normal • Variable RR; constant PR • Infants: rate usually < 220/min • Children: rate usually < 180/min Probable supraventricular tachycardia Search for and treat cause Possible ventricular tachycardia • Compatible history (vague, nonspecific); history of abrupt rate changes • P waves absent/abnormal • HR not variable • Infants: rate usually ≥ 220/min • Children: rate usually ≥ 180/min 10 Cardiopulmonary compromise? • Hypotension • Acutely altered mental status • Signs of shock Yes 11 Consider vagal maneuvers (No delays) Adenosine IO/IV dose: First dose: 0.1 mg/kg rapid bolus (maximum: 6mg) Second dose: 0.2 mg/kg rapid bolus (maximum second dose: 12 mg) Amiodarone IO/IV dose: mg/kg over 20-60 minutes or Procainamide IO/IV dose: 15mg/kg over 30-60 minutes Do not routinely administer amiodarone and procainamide together 12 No Consider adenosine if rhythm regular and QRS monomorphic Synchronized cardioversion 13 • If IO/IV access present, give adenosine or • If IO/IV access not available, or if adenosine ineffective, synchronized cardioversion Expert consultation advised • Amiodarone • Procainamide *Reprinted with permission from the American Heart Association 449 www.ajlobby.com Mizukawa_Appendix C.indd 449 6/20/17 12:20 PM www.ajlobby.com Mizukawa_Appendix C.indd 450 6/20/17 12:20 PM INDEX Page numbers followed by “f” indicate figures; those followed by “t” indicate tables; those followed by “b” indicate boxes A A fibers, 40 A-a gradient, 223–224 Absorption, 4–5 Acetaminophen characteristics of, 66t, 67, 422 in liver disease patients, 270 liver failure and, 271, 274 in pregnancy, 395t Acetylcholine, 9, 13, 306 Acetylcholine receptors, 12t, 13, 24, 306 Acetylcholinesterase, 306 Acetylcholinesterase inhibitors, 314 Acetylsalicylic acid, 345 Acini, liver, 261 Acquired immunodeficiency disorders, 319, 319t ACS See Acute coronary syndrome ACTH See Adrenocorticotropic hormone Acute adrenal insufficiency, 300, 300b Acute chest syndrome, 340 Acute coronary syndrome, 152–153, 153t, 412 Acute kidney injury, 254–255 Acute liver failure, 271 Acute noncardiogenic pulmonary edema, 414 Acute porphyric crisis, 179–180 Acute respiratory infection, 232–233 Acute tubular necrosis, 254 Acutely decompensated heart failure, 204 Addiction aids, 422 Adenohypophysis, 280t–281t, 281 Adenosine diphosphate, 334–335 ADHD See Attention deficit hyperactivity disorder Adrenal cortex, 280t–281t, 284–285, 285f Adrenal crisis, 159, 160b Adrenal glands, 280t–281t, 284–286, 285f Adrenal insufficiency, 158–159, 159b–160b, 299–300, 299b–300b Adrenal medulla, 280t–281t, 284–285 Adrenergic agents α-, 422 in pregnancy, 392t Adrenergic bronchodilators, 426 Adrenergic receptors, 222 Adrenocorticotropic hormone, 158 Adverse events emotional impact on surgeon and staff, 171 hospital transport for, 167b in-office management of, 168 malpractice lawsuits filed after See Malpractice lawsuits patient’s response to, 166 preparing for, 168, 171 reporting of, to dental and medical licensing boards, 168 responding to, 168–169 Afterload, 201–202 Agonists, See also specific agonist Agranulocytes, 332 AHA See American Heart Association AHI See Apnea hypopnea index Airway anatomy of, 221–222 assessment of, 126, 126b difficult, 117–118, 121, 126, 126b, 144, 144f, 403, 406 emergency See Emergency airway evaluation of, 117–122, 118f–122f laryngeal mask, 119, 119f, 132b, 132t, 132–133, 324 malignancy effects on, 358 Mallampati classification of, 121, 121f, 403 nasopharyngeal, 118f, 131, 131f, 134, 140 in obese patients, 403, 405 oral, 118 in organ transplant patients, 324 oropharyngeal, 118f, 131, 132f, 134, 140 in pediatric patients, 376–377, 377f propofol effects on, 405 upper, 221–222 Airway compromise, 126, 127b Airway management adjuncts for, 130–133, 131f–132f, 132b, 132t–133t in Down syndrome patients, 371 endotracheal intubation, 120–122, 120f–122f, 133, 133t face mask, 118, 118f head tilt/chin lift, 130, 130f, 140 jaw thrust, 130, 130f, 140 maneuvers for, 130, 130f supraglottic devices, 119, 119f, 134 Airway obstruction, 140, 324, 363, 378 Airway rescue tray, 127b, 127f Airway urgencies and emergencies aspiration, 140, 141b bronchospasm, 142, 143b emesis, 140, 141b hyperventilation, 139 hypoventilation, 140 laryngospasm, 141, 142b supraglottic obstruction, 140 AKI See Acute kidney injury Akinosi block, 44 Alanine aminotransferase, 265, 266t, 268 Albumin, 5, 259, 266t Albuterol, 158b, 226, 227t Alcoholic cirrhosis, 270 Aldosterone, 280t–281t, 285 Aldosterone receptor antagonists, 207t, 423 Alfentanil, 8t Alginates, 430 Alkalemia, 161 Alkaline phosphatase, 266t Alkylating agents, 352t α2 antagonists, 24 α2 receptor, 11 α1-acid glycoprotein, α1-hydroxymidazolam, 256 α-blocker, 424 ALT See Alanine aminotransferase Alveolar carbon dioxide, 223 Alveolar oxygen tension, 223 Alveolar partial pressure, Alzheimer disease, 182 Amantadine, 430 American Heart Association algorithms for bradycardia, 446–447 algorithms for cardiac arrest, 444–445 algorithms for tachycardia, 448–449 451 www.ajlobby.com Mizukawa_Index.indd 451 6/22/17 11:17 AM A • Index antibiotic prophylaxis recommendations from, 51, 52t preoperative electrocardiography on, 111 American Society of Anesthesiologists class I and II patients, 114 difficult airway, 117, 126b, 144, 144f fasting guidelines, 379–380, 380t monitoring requirements of, 82 opioid guidelines, 404 Physical Status Classification, 365 Aminocaproic acid, 432 Aminolevulinic acid, 179–180 Aminophylline, 427 Aminosalicylates Crohn disease treated with, 248, 248b ulcerative colitis treated with, 246, 246b Amoxicillin, 52t Amoxicillin/clavulanate, 54 Amphetamine, 371, 413, 431 Ampicillin, 52t Ampicillin-sulbactam, 52t Amylin analogs, 425 Analgesia See also Pain definition of, 64 intraoperative, 65–66 nonsteroidal anti-inflammatory drugs for, 67 opioids for, 65, 68–69 preoperative, 64–65 Analgesics characteristics of, 422 description of, 66t, 66–68 in liver disease patients, 270 in liver failure patients, 274 in pregnancy, 392t, 395t seizures caused by, 190b Anaphylactoid reactions, 115, 325–326 Anaphylaxis, 157, 157t, 158b, 325 Andexanet alfa, 346 Anemia, 248 Anesthesia records, 168 Angina, 153t Angiotensin I, 253 Angiotensin II, 253 Angiotensin-converting enzyme inhibitors, 155b, 204, 423 Anorexigenics, 428 Antacids, 430 Antagonists, See also specific antagonist Anterior pituitary, 280t–281t, 281 Antiarrhythmics, 428 Anti-asthmatics, 426–427 Antibiograms, 53 Antibiotic prophylaxis adverse reactions of, 53–54 American Heart Association recommendations, 51, 52t in bone grafting, 55 cardiac conditions that require, 51, 51b in dental implant placement, 53t, 54 in dentoalveolar surgery, 54 in diabetic patients, 56, 325 dosing for, 52t gastrointestinal disturbances caused by, 54 in head and neck cancer, 56 in head and neck surgery, 53t, 56 in hepatic failure patients, 57 in HIV-positive patients, 57, 322 in infectious endocarditis, 50–51, 51b, 52t in maxillofacial fracture management, 55 in organ transplant patients, 324 in orthognathic surgery, 54 orthopedic implant infection prevention with, 53t in osteonecrosis of the jaw prevention, 56 pain management through, 65 principles of, 52–54 in prosthetic joints, 55–56 purpose of, 50 in renal failure patients, 57 in third molar extractions, 54 Antibiotics See also specific antibiotic hypersensitivity reactions to, 325 in liver disease patients, 270 in liver failure patients, 274 myasthenia gravis exacerbation from, 314, 314b prophylactic uses of See Antibiotic prophylaxis seizures induced by, 190b Anticholinergics antiemetic uses of, 439 asthma treated with, 426 in chronic kidney disease patients, 258 description of, 74t, 74–75, 182 in end-stage renal disease patients, 258 in hyperthyroidism patients, 294 Parkinson disease treated with, 430 Anticholinesterase inhibitors, 429 Anticoagulants, oral andexanet alfa, 346 antiplatelet drugs, 345 apixaban, 346 characteristics of, 432 dabigatran etexilate, 346 description of, 345 idarucizumab, 346 pre-surgical discontinuation of, 347–348 risk assessments with, 347–348, 347b rivaroxaban, 346 warfarin, 345–348 Antidepressants, 190b, 191, 436–437 Antidiabetics, 425–426 Antidiuretic hormone, 253, 282, 355 Antiemetics anticholinergics, 74t, 74–75, 439 antihistamines, 74t, 75 in autism spectrum disorder patients, 370 benzamides, 74t, 77 butyrophenones, 74t, 77 characteristics of, 439–440 in chronic kidney disease patients, 258 description of, 73 dopamine antagonism caused by, 193 in end-stage renal disease patients, 258 phenothiazines, 74t, 76 serotonin receptor antagonists, 74t, 78 transdermal delivery system for, 75 types of, 74t Antiepileptics, 188–189, 189b, 433–435 Antifibrinolytics, 432 Antihemophilic agents, 432 Antihistamines, 74t, 75, 437, 439 Antihypertensives characteristics of, 423–424 goals for, 206 intraoperative hypertension treated with, 155 in pregnancy, 392t types of, 207t Antimicrobial resistance patterns, 53 Antimicrobials, 392t Antimicrotubule agents, 352t Antiparkinsonism drugs, 183 Antiplatelet drugs, 345, 432 Antipsychotics, 190b, 193 Antiretroviral therapy, 320 Antithrombin, 337 Antitumor antibiotics, 352t Aorta, coarctation of, 214–215 Aortic dissection, 414 Aortic regurgitation, 211t, 212, 213t Aortic stenosis, 211t–213t, 212 Aortic valve, 199–201 Aortocaval compression, 389 Apixaban, 346 Apnea definition of, 140 obstructive sleep See Obstructive sleep apnea Apnea hypopnea index, 401, 401t Apneustic center, 223 Appetite suppressants, 428 Aquaporins, 253 Armodafinil, 431 452 www.ajlobby.com Mizukawa_Index.indd 452 6/22/17 11:17 AM Index • C Arrhythmias, 97, 428 Arterial carbon dioxide, 223 Arterial oxygenation, 223 Articaine half-life of, 44 in liver disease, 269 in liver failure patients, 273 properties of, 40t, 42t ASA See Acetylsalicylic acid; American Society of Anesthesiologists Ascites, 272–273 ASD See Autism spectrum disorder Aspartate, 13 Aspartate transaminase, 265, 266t, 268 Asperger, Hans, 368 Aspiration, 140, 141b, 363 Aspirin, 154, 345, 347 AST See Aspartate transaminase Asthma anesthetic considerations in, 228, 228b bronchospasm risks, 228 chronic obstructive pulmonary disease versus, 116 classification of, 226t diagnosis of, 225 management/treatment of, 226, 227t medications for, 426–427 pathophysiology of, 225 peak flow meter for, 228 in pediatric patients, 379 prevalence of, 225 Asystole, 106, 106f Atipamezole, 24 Atopy, 225 Atracurium, Atrial fibrillation, 99, 99f, 211 Atrial flutter, 99, 99f Atrial septal defect, 215 Atrial systole, 200–201 Atropine, 258, 384, 384t Attention deficit hyperactivity disorder, 371–372, 379, 413 Auditory assessment, 83 Autism spectrum disorder anesthesia considerations in, 369–370 comorbidities associated with, 368 etiology of, 368 premedication in, 369 treatment of, 368 Automated blood pressure monitors, 83–84 AV block, first-degree, 101, 101f AV bundle, 92, 200 AV valve, 199 Azithromycin, 52t Azotemia, 254 B B cells, 319, 332 Bacteremia, 50–51 Bag valve mask, 126, 129, 133 Barbiturates characteristics of, 432–433 in chronic kidney disease patients, 257 in congestive heart failure patients, 204 in end-stage renal disease patients, 257 as intravenous anesthetics, 17–18 pK a of, in pregnancy, 394 in seizure patients, 189 seizures treated with, 433 Baseline effect, Basophils, 319 Belladonna alkaloids, 74 Benzamides, 74t, 77, 440 Benzodiazepines anaphylactic reactions to, 326 characteristics of, 432–433 in chronic kidney disease patients, 256–257 in cocaine users, 412 in elderly, 364, 364t in end-stage renal disease patients, 256–257 opioids and, 415–416 in pregnancy, 393 properties of, 16b, 16–17 protease inhibitors and, 322 seizures treated with, 433 β-blockers asthma treated with, 227t characteristics of, 428 chronic obstructive pulmonary disease treated with, 231t congestive heart failure treated with, 204 contraindications for, 412 in coronary artery disease patients, 210 hypertension managed with, 155, 155b Marfan syndrome managed with, 315–316 types of, 207t Betamethasone, 28t Bigeminy, 104, 104f Biguanides, 288t, 425 Bile ductular cells, 261 Bilirubin, 266t Bioavailability, Biologic agents Crohn disease treated with, 248, 248b ulcerative colitis treated with, 246, 246b Biotransformation, hepatic, 2,3-Bisphosphoglycerate, 333–334, 334t Bisulfite, 326 Bleeding risks, perioperative, 347 Blood, 332b, 332–333, 333f Blood glucose, 265 Blood pressure calculation of, 83 classification of, 205t elevated See Hypertension monitoring of, 83–84 pregnancy-related changes in, 389 Blood pressure monitors, 83–84 Blood-brain barrier, 178 BMI See Body mass index Body mass index, 234t, 400, 400f, 404 Body temperature monitoring, 89 Bone grafting, antibiotic prophylaxis in, 55 Botulinum toxin, Bougies, 133, 137 Bowman capsule, 253 Bradycardia, algorithm for, 446–447 Brain, 177 Brainstem, 177 Bridion See Sugammadex Bronchial circulation, 222 Bronchial inhaled administration, Bronchitis, chronic, 229 Bronchodilators asthma treated with, 226, 227t, 426 chronic obstructive pulmonary disease treated with, 230, 231t description of, 151, 152b Bronchospasm, 142, 143b, 150–151, 151b, 152b, 228 Bundle branch block left, 107, 108f right, 106, 107f, 215 Bundle of His, 92, 92f Bupivacaine cardiovascular compromise caused by, 47 in elderly, 44 lidocaine and, 44 in organ transplant patients, 324 properties of, 40t, 42t Buprenorphine, 416 Bupropion, 436 Butyrophenones, 440 C C fibers, 40 Cachexia, 357 CAD See Coronary artery disease Calcitonin, 280t–281t, 283 453 www.ajlobby.com Mizukawa_Index.indd 453 6/22/17 11:17 AM C • Index Calcium channel blockers, 155b, 204, 207t, 423, 428 Cancer See Malignancies Cancer cachexia, 357 Cannabinoids, 408 Capnometry, 87 Captopril, 208 Carbamazepine, 189b Carbidopa, 183 Carbidopa-levodopa, 430 Carbon dioxide, 87, 223 Carboxyhemoglobin, 85, 230 Cardiac arrest, algorithm for, 444–445 Cardiac catheterization, 215 Cardiac consultation, 111 Cardiac cycle, 200–201 Cardiac output calculation of, 83 definition of, in pediatric patients, 376, 376t physiology of, 201–202 pregnancy-related changes in, 389 Cardiac veins, 200 Cardiovascular disorders atrial septal defect, 215 coarctation of the aorta, 214–215 congenital heart disease, 214–216, 371 congestive heart failure, 202b, 202–204, 203b coronary artery disease See Coronary artery disease in Down syndrome patients, 371 hypertension See Hypertension ischemic heart disease, 209–211, 210b patent ductus arteriosus, 215–216 pulmonary stenosis, 214 valvular heart disease, 211–213, 211t–213t ventricular septal defect, 216 Cardiovascular system anatomy of, 199–200 cardiac cycle, 200–201 cardiac output, 201–202 cardiac veins, 200 chemotherapy effects on, 353t, 354b cocaine effects on, 411–412 conduction system, 200 coronary arteries, 199–200 desflurane effects on, 35 disorders of See Cardiovascular disorders echocardiography of, 202 in elderly, 362 great vessels, 199 heart See Heart history-taking about, 115 isoflurane effects on, 34 local anesthesia-related complications of, 46, 47b Marfan syndrome involvement of, 315 methadone effects on, 416 methamphetamine effects on, 414 muscular dystrophy involvement of, 309 nitrous oxide effects on, 33 in obese patients, 403 opioid effects on, 416 in pediatric patients, 376 pericardium, 199 physiology of, 199–200 pregnancy-related changes in, 389 scleroderma involvement of, 309 sevoflurane effects on, 36 Catecholamines, 28, 155, 280t–281t, 284–286, 372, 415 Catechol-O-methyltransferase inhibitors, 183, 430 CD4+ T cells, 320–321 Cefazolin, 52t Ceftriaxone, 52t Cefuroxime, 52t, 54 Central α2 agonists, 207t Central chemoreceptors, 223 Central nervous system anatomy of, 177–179 anesthetic agents’ effect on, 178–179 blood-brain barrier, 178 cerebral blood flow, 34, 177–178 chemotherapy effects on, 353t cholinergic defects of, 13 cocaine effects on, 412 excitatory neurotransmitters, 13 inhibitory neurotransmitters, 10–12 local anesthesia-related complications of, 46–47, 47b methamphetamine effects on, 414 physiology of, 177–179 Central nervous system depressants, 432 Central nervous system disorders Alzheimer disease, 182 cerebrovascular accident, 185–188, 186t, 340 multiple sclerosis, 184f, 184–185 neoplasms, 190b, 190–191 Parkinson disease, 183 porphyria, 179–181, 179b, 180b, 181t primary tumors, 190b, 190–191 psychiatric, 191–193, 192b, 192t seizures, 188–189, 189b, 190b Central nervous system stimulants, 431 Centrally acting drugs, 207t Cephalexin, 52t Cephalosporins, 325 Cerebellum, 177 Cerebral anoxia, 134 Cerebral blood flow, 34, 177–178 Cerebral cortex, 177 Cerebral hypoxia, 134 Cerebral metabolic rate, 177 Cerebral perfusion pressure, 177–178 Cerebrovascular accident, 185–188, 186t, 340 See also Stroke Cervical mobility, 122, 122f Chemoreceptor trigger zone, 72, 75–76 Chemotherapy agents used in, 352t anesthetic considerations for, 353–356, 354b drug interactions with, 355, 355t pathophysiology of, 352 system-based effects of, 353t, 354b, 355 Chest pain, 153t Chief cells, 240 Children See Pediatric patients Child-Turcotte-Pugh classification, 269, 269t, 273 Chondroitin, 429 Chronic bronchitis, 229 Chronic kidney disease anesthetic considerations in, 256–258 diagnosis of, 255 electrolyte disturbances in, 260 fluid disturbances in, 260 management of, 256 pathophysiology of, 255 Chronic obstructive pulmonary disease anesthetic considerations for, 232 characteristics of, 229t cigarette smoking as cause of, 230, 230b description of, 116 diagnosis of, 229–230 management of, 230, 231t oxygen supplementation for, 232 pathophysiology of, 229–230 Chyme, 240 Cigarette smoking, 230, 230b Cirrhosis, 270–272 CKD See Chronic kidney disease Clara cells, 221 Clarithromycin, 52t Clean-contaminated wounds, 56 Clindamycin, 52t Clonidine characteristics of, 66 hypertensive urgencies treated with, 208 in pediatric patients, 381, 384t Clopidogrel, 345, 347 Closing volume, 377, 377f Clostridium difficile, 54 Clotting factors, 389 Clove, 429 CMR See Cerebral metabolic rate CNS See Central nervous system CO See Cardiac output Coagulation, 335–336 454 www.ajlobby.com Mizukawa_Index.indd 454 6/22/17 11:17 AM Index • D Coagulation factors, 336, 338 Coarctation of the aorta, 214–215 Cocaine, 410–412 Cocaine-associated chest pain, 411 Codeine, 66t, 68, 395t Cognitive function, 363, 363b Collecting duct, 253 “Common cold,” 232 Communication, with patient’s family, 169 Comorbidities, in pediatric patients, 379–380 Competitive antagonists, Complement system, 319 Complications cricothyroidotomy, 139, 139b local anesthesia, 45–47 medical malpractice lawsuits for, 167 Congenital heart disease, 214–216, 371 Congestive heart failure, 202b, 202–204, 203b Cooling measures, for malignant hyperthermia, 149, 149b COPD See Chronic obstructive pulmonary disease Cor pulmonale, 235 Coronary arteries, 199–200 Coronary artery disease anesthetic considerations in, 210 deaths caused by, 209 description of, 95, 152, 209 hypertension as risk factor for, 206 ischemic heart disease caused by, 209 risk factors for, 206, 210b Coronary sinus, 200 Corticosteroids in adrenal insufficiency, 159, 159b airway inflammation managed with, 151 asthma treated with, 227t catecholamines and, 28 chronic obstructive pulmonary disease treated with, 231t Crohn disease treated with, 248, 248b pain management using, 65 ulcerative colitis treated with, 246, 246b Corticotropin-releasing hormone, 158 Cortisol, 27, 159, 285 Cortisone, 28t Cosyntropin, 159 Coumadin See Warfarin COX, 345 COX-1, 243 COX-2, 243 CPP See Cerebral perfusion pressure Crack cocaine, 410–411 “Crack lung,” 411 Crackles, 117 Cranial nerve neuropathy, 309 CREST syndrome, 307 CRH See Corticotropin-releasing hormone Cricothyroid artery, 135 Cricothyroid membrane, 135 Cricothyroidotomy complications of, 139, 139b indications for, 134 instruments/supplies for, 136b needle, 138–139, 139b surgical, 134–138, 135f–137f, 136b, 138b Crohn disease, 247f, 247–248, 248b–249b Cromolyn sodium, 227t, 231t Cryoprecipitate, 338 Cushing syndrome See Hypercortisolism CVA See Cerebrovascular accident Cyclic antidepressant overdose, 192t Cyclizine, 74t, 75 Cyclooxygenase enzymes, 67, 67f, 243, 345 Cyclosporine, 323–324 Cytochrome P450, 6, 265, 345–346, 410 Cytokines, 319 D Dabigatran etexilate, 346 Dantrolene, 149, 149b DDAVP, 337–339 Death communicating with patient’s family after, 169 emotional impact on surgeon and staff, 171 legal allegations in, 167b Deep venous thrombosis, 346–348 Defense attorney, 170 Dehydroepiandrosterone sulfate, 285 Delayed gastric emptying, 390 Delirium, 363, 363b δ receptor, 20 Demand valve masks, 129 Dental implant placement, antibiotic prophylaxis during, 53t, 54 Dental licensing boards, 168 Dentoalveolar surgery, 54 Depolarizing neuromuscular blockers, 24–25, 89, 429 Desflurane blood/gas coefficient of, inhalational anesthesia use of, 35–36 properties of, 7t Desmethyldiazepam, 364 Dexamethasone characteristics of, 29 in diabetic patients, 289 dosing of, 442–443 potency of, 28t Dexmedetomidine in autism spectrum disorder patients, 369–370 characteristics of, 23–24, 66 dosing of, 442–443 intranasal administration of, 382 in pediatric patients, 382, 384t in restrictive lung disease patients, 235 sedation uses of, 11, 216, 235 in ventricular septal defect patients, 216 Dextroamphetamine, 431 Dextrose, 156 DHEAS See Dehydroepiandrosterone sulfate Diabetes mellitus anesthetic considerations in, 289 antibiotic prophylaxis in, 56, 325 definition of, 324 diagnosis of, 287 glycemic control in, 287, 289 human immunodeficiency virus and, 321 hyperglycemia in, 287, 289 hypoglycemia in, 156, 289 infection risks associated with, 56 management of, 287, 288t, 290b medications for, 288t, 425–426 pathophysiology of, 287 symptoms of, 287b type 1, 287, 288t type 2, 287, 288t vascular disease in, 324 Diabetic ketoacidosis, 289 Diaphragm, 223 Diastole, 200–201 Diastolic blood pressure, 205 Diazepam in chronic kidney disease patients, 256 dosing of, 442–443 in elderly patients, 364 in porphyria patients, 181 properties of, 17, 17b Difficult airway, 117–118, 121, 126, 126b, 144, 144f, 403, 406 Diffuse interstitial pulmonary fibrosis, 309 Digestive system anatomy of, 239t, 239–241 chemotherapy effects on, 353t, 354b esophagus, 239t, 240 large intestine, 239t, 241 oral cavity, 239, 239t pharynx, 240 455 www.ajlobby.com Mizukawa_Index.indd 455 6/22/17 11:17 AM D • Index physiology of, 239–241 pregnancy-related changes in, 390 salivary glands, 239t, 239–240 small intestine, 239t, 241 stomach, 239t, 240–241 Digestive system disorders Crohn disease, 247f, 247–248, 248b–249b gastroesophageal reflux disease See Gastroesophageal reflux disease peptic ulcer disease, 243–244, 244b ulcerative colitis, 245f, 245–246, 246b Dimenhydrate, 74t, 75 Dipeptidyl peptidase-4 inhibitors, 288t, 425 Diphenhydramine, 158b Direct bilirubin, 266t Direct laryngoscopy, 116, 120, 122 Direct thrombin inhibitors, 433 Distal convoluted tubule, 253 Distribution, Diuretics characteristics of, 424 for congestive heart failure, 204 for hypertension, 207t DKA See Diabetic ketoacidosis Dobutamine, 438 Documentation, 168–169 Dopamine, 192, 413, 438 Dopamine agonists, 430 Dopamine receptor antagonists, 74t, 76–77, 440 Dose-response curves, 8, 8f Down syndrome, 370–371 Droperidol, 74t, 77–78, 258 Drug(s) clearance of, efficacy of, hyperthermic syndromes induced by, 192t pharmacodynamics of See Pharmacodynamics pharmacokinetics of See Pharmacokinetics potency of, 8, 8f safety of, seizures induced by, 190b Drug abuse See Substance abuse Drug allergy, 115 Drug-eluting stents, 209 Duchenne muscular dystrophy, 311 Ductus arteriosus, patent, 215–216 DVT See Deep venous thrombosis Dyspnea, 203 Dysrhythmias cocaine as cause of, 411 medications for, 213 sinus, 97, 99–101 ventricular, 103–108, 103f–108f Dystrophin gene, 311 E Echinacea, 429 Echocardiography congestive heart failure evaluations, 203 description of, 202 E-cylinders, 128 ED50 See Median effective dose EF See Ejection fraction Efficacy, Einthoven triangle, 94, 95f Ejection fraction, 201 Elderly age-related concomitant disease in, 362b airway obstruction in, 363 benzodiazepines in, 364, 364t cardiovascular system in, 362 cognitive function in, 363, 363b delirium in, 363, 363b ketamine in, 365 local anesthetic dosing in, 44 opioids in, 364t, 365 pharmacodynamics in, 364–365 pharmacokinetics in, 364–365 population statistics for, 362 pre-anesthetic assessment in, 365, 366t propofol in, 364, 364t renal function in, 363 respiratory system in, 362–363 vasculature in, 362 Electrical axis, mean, 108–109, 109f Electrocardiogram asystole on, 106, 106f atrial fibrillation on, 99, 99f atrial flutter on, 99, 99f atrial septal defect findings on, 215 bigeminy on, 104, 104f definition of, 92 elements of, 93, 93f first-degree AV block on, 101, 101f heart rate evaluations, 96, 97f heart rhythm evaluations, 97–108, 98f–108f hyperkalemia findings on, 260 left bundle branch block on, 107, 108f normal sinus rhythm on, 98, 98f P wave, 93, 93f P-R interval, 93, 93f premature atrial contraction on, 100, 100f premature ventricular contraction on, 103, 103f QRS interval, 93, 93f QT interval, 93f, 94 right bundle branch block on, 106, 107f R-R interval, 93, 93f second-degree AV block on, 102, 102f sinus block on, 101, 101f sinus dysrhythmias on, 99f–101f, 99–101 ST segment, 93f, 94 supraventricular tachycardia on, 100, 100f T wave, 93f, 94 third-degree AV block on, 103, 103f trigeminy on, 104, 104f ventricular fibrillation, 105, 105f ventricular septal defect findings on, 216 ventricular tachycardia, 105, 105f Electrocardiography cardiac consultation after, 111 hypertrophy on, 110 leads used in, 94, 94f, 96f left ventricular hypertrophy on, 110 mean electrical axis on, 108–109, 109f monitoring uses of, 83, 95, 96f myocardial infarction on, 110f, 110–111 myocardial ischemia on, 111 preoperative, 111 right ventricular hypertrophy on, 110 Electrolyte disturbances, 260 Eliquis See Apixaban Emergence delirium, 19b Emergency airway in children, 134 indications for, 134 needle cricothyroidotomy, 138–139, 139b surgical cricothyroidotomy, 134–138, 135f–137f, 136b, 138b Emesis, 140, 141b EMLA, 40, 383 Emphysema, 229 Enalaprilat, 155b Endocrine disorders diabetes mellitus See Diabetes mellitus hypercortisolism, 297–298, 297b–298b hyperthyroidism, 293–294, 294b–295b hypocortisolism, 299–300, 299b–300b hypoglycemia, 156, 156b, 289, 291–293, 291b–293b hypothyroidism, 295–296, 296b–297b Endocrine system adrenal glands, 280t–281t, 284–286 anterior pituitary, 280t–281t, 281 axes and pathways of, 286, 286f definition of, 279 gonads, 280t–281t, 283 456 www.ajlobby.com Mizukawa_Index.indd 456 6/22/17 11:17 AM Index • G hormones produced by, 279, 280t–281t hypothalamus, 279–280, 280t–281t overview of, 279f pancreas, 280t–281t, 282f, 282–283 parathyroid glands, 280t–281t, 283–284 pineal gland, 280t–281t, 282 pituitary gland, 280t–281t, 281–282 posterior pituitary, 280t–281t, 281 thyroid gland, 280t–281t, 283 Endothelial cells, 261 Endothelin receptor antagonist, 424 Endotracheal intubation, 120–122, 120f–122f, 140 Endotracheal tubes, 133, 133t End-stage renal disease anesthetic considerations in, 256–258 complications of, 255 electrolyte disturbances in, 260 fluid disturbances in, 260 management of, 255 pathophysiology of, 255 End-tidal carbon dioxide in bronchospasm, 150 endotracheal tube placement confirmed with, 133 monitoring uses of, 82, 87–89, 88f–89f in pediatric patients, 378 Entacapone, 183 Eosinophils, 319 Ephedrine, 438 Epileptic seizures, 188–189, 189b, 190b Epinephrine anaphylaxis managed with, 157, 158b bronchospasm managed with, 151 characteristics of, 438 neurotransmitter properties of, 11 physiologic actions of, 285–286 in pregnancy, 395 vasoconstrictor use of, 42, 211 Epstein-Barr virus, 267 Erythropoietin, 253, 255 Esmolol, 155b Esophagus, 239t, 240 ESRD See End-stage renal disease et CO See End-tidal carbon dioxide Ethosuximide, 189b Etomidate in adrenal insufficiency patients, 299 characteristics of, 22–23, 23b dosing of, 442–443 in elderly patients, 364t properties of, 8t Eutectic mixture of the local anesthetics See EMLA Excitatory neurotransmitters, 13 Exercise capacity, 115–116 Exercise tolerance, 210 Exertional dyspnea, 203 Exophthalmos, 294 Extrinsic pathway, of coagulation, 336 F Face masks fitting of, 118, 118f types of, 129 Face-mask ventilation, 117 Factor IX, 340 Factor Xa inhibitors, 346–347, 433 Family, 169 Fasting, 379–380, 380t Fatigue, 203 FDA pharmaceutical pregnancy classifications, 391, 391t Fentanyl characteristics of, 20–21, 21b dosing of, 442–443 in elderly, 365 intranasal administration of, 382 midazolam and, 208 in pediatric patients, 382, 384t pharmacokinetics of, 65, 257, 274 Fetal oxygenation, 390 Fetor hepaticus, 271 FEV1 See Forced expiratory volume in second Fibrin, 336 Fibrinogen, 336, 338, 346 Fick’s law of diffusion, Fight-or-flight response, 285 Fio2 See Fraction of inspired oxygen First heart sound, 200 First-degree AV block, 101, 101f Fluid disturbances, 260 Fluid overload, 260 Flumazenil antagonism effects of, 179 characteristics of, 17, 17b dosing of, 442–443 in pregnancy, 393 Forced expiratory volume in second, 224–225 Forced vital capacity, 224 Fourth heart sound, 200 Fraction of inspired oxygen, 128–129, 223 Fragile X syndrome, 368 FRC See Functional residual capacity Frequency-dependent blockade, 40 Functional residual capacity, 224, 224f, 377, 377f Furosemide, 208 G G protein–coupled receptors, 9–10 G proteins, 9, 13 GABA, 32, 393 GABA receptor description of, 10, 12t, 16 flumazenil antagonism of, 17 GABA A receptor, 10, 16–17 GABAergic receptors, 11 Gabapentin, 189b Garlic, 429 Gas absorption, Gas exchange, 223–224 Gastric acid aspiration, 390 Gastric outlet obstruction, 244 Gastrin, 240 Gastroesophageal reflux disease description of, 241–242, 390, 403 medications for, 430 Gastroesophageal varices, 271–273 Gastrointestinal tract See also Digestive system anatomy of, 239, 239t scleroderma manifestations in, 309 General anesthesia/anesthetics complications of, 148 in pediatric patients, 380 in pregnancy, 392t seizures induced by, 190b Generalized seizures, 188 GERD See Gastroesophageal reflux disease Geriatrics See Elderly Ginkgo biloba, 429 Ginseng, 429 Glenoid fossa, 120 Glomerular filtration rate, 255 Glottic obstruction See Laryngospasm Glucagon, 280t–281t, 282–283 Glucagon-like peptide-1, 425 Glucocorticoid(s) adrenal insufficiency caused by, 297 characteristics of, 440 Crohn disease treated with, 246 description of, 27 dexamethasone, 28t, 29 duration of action, 28t inhaled, 427 in multiple sclerosis, 185 office-based anesthesia use of, 28 physiologic effects of, 28 potency of, 28t ulcerative colitis treated with, 246 Glucocorticoid receptors, 29 Glucosamine, 429 α-Glucosidase inhibitors, 288t, 425 Glucuronidation, Glucuronide metabolites, Glutamate, 13 Glutamate receptors, 434 457 www.ajlobby.com Mizukawa_Index.indd 457 6/22/17 11:17 AM G • Index Glutamate-gated receptors, 10 Glycemic control, 287, 289 Glycine, 11, 12t Glycogenolysis, 283 Glycopyrrolate, 182, 258 Gonads, 280t–281t, 283 Gow-Gates block, 44 GPCR See G protein–coupled receptors Granulocytes, 332 Graves disease, 293 Great vessels, 199 H HAART See Highly active antiretroviral therapy Half-life, Halothane, 7t Haustra coli, 241 H-cylinders, 128 Head and neck cancer, 56 Head and neck surgery, 53t, 56 Head tilt/chin lift, 130, 130f, 140 Heart See also Cardiovascular system anatomy of, 92, 92f, 199 auscultation of, 117, 203, 211t chambers of, 199 conduction system of, 200 echocardiography of, 202 mean electrical axis of, 108–109, 109f physical examination of, 117 valves of, 199 Heart disease ischemic, 209–211, 210b valvular, 211–213, 211t–213t Heart failure, 202b, 202–204, 203b Heart rate in cardiac output, 201 description of, 96 intraoperative management of, 210 marijuana effects on, 409 in pediatric patients, 376, 376t square counting method for estimating, 97f Heart rhythm evaluations, 97–108, 98f–108f Heart sounds, 200 Helicobacter pylori, 243 Hematologic disorders hemophilia A, 338–339 hemophilia B, 339–340 methemoglobinemia, 342–344, 343f, 343t oral anticoagulant therapy See Oral anticoagulants sickle cell disease, 340–341, 342b von Willebrand disease, 337–338 Hematologic system anatomy of, 332–334 blood, 332b, 332–333, 333f chemotherapy effects on, 353t, 354b, 355 cocaine effects on, 412 hemostasis, 334–337, 335f–336f physiology of, 332–334 pregnancy-related changes in, 389 Hematopoiesis, 332 Heme-related agents, 432–4266 Hemodynamics, pulmonary, 222 Hemoglobin, 225, 333 Hemoglobin A1c, 289, 325 Hemoglobin S, 340–341 Hemoglobin saturation, 225 Hemophilia A, 338–339 Hemophilia B, 339–340 Hemorrhagic stroke, 186t, 187, 412 Hemostasis local measures for, 347b physiology of, 334–337, 335f–336f Henderson-Hasselbalch equation, Heparin, 347–348 Hepatic diseases See Liver diseases Hepatic encephalopathy, 272 Hepatic failure See Liver failure Hepatic porphyrias, 179 Hepatitis A, 266, 268 anesthetic considerations in, 268–270 B, 266–268 C, 267–268 D, 267–268 definition of, 266 diagnosis of, 266–268 E, 267–268 management of, 268 pathophysiology of, 266–268 Hepatitis B surface antibody, 267–268 Hepatocytes, 261 Hepatopulmonary syndrome, 272 Hepatorenal syndrome, 259, 272 Herbals, 429 Heroin, 415–416 Hiatal hernia, 241 Highly active antiretroviral therapy, 57, 320–321, 322t Histamine, 240 History-taking, 114–117 Howell-Jolly bodies, 341 HR See Heart rate H1-receptor antagonists, 437 H -receptor antagonists, 242, 242b, 430, 437 Human immunodeficiency virus antibiotic prophylaxis in, 57 description of, 320–322, 320t–322t, 321b Human leukocyte antigen sensitization, 255 Humate-P, 338 Hydralazine, 155b, 412 Hydrochloric acid, 240, 274 Hydrocodone in hepatitis patients, 270 in pregnancy, 395t properties of, 66t, 68 Hydrocortisone, 28t, 158b, 246 Hydromorphone in myocardial ischemia patients, 154 pharmacokinetics of, 257 in pregnancy, 395t properties of, 66t Hydroxyurea, 341 Hydroxyzine, 74t, 75 Hypercalcemia of malignancy, 357 Hypercapnia, 224, 362, 388 Hypercoagulable state, 355, 389 Hypercortisolism, 297–298, 297b–298b Hyperglycemia, 287, 289 Hyperkalemia, 25, 149b, 260, 324 Hypersensitivity reactions, 325–326 Hypersplenism, 271 Hypertension anesthetic considerations in, 208 antihypertensive medications for, 155, 206, 207t blood pressure monitoring in, 82 classification of, 205, 206t definition of, 154 diagnosis of, 154, 205–206 elective procedures in patients with, 208 as emergency, 154–155, 155b intraoperative, 155b lifestyle modifications for, 206–207, 207b management of, 155, 206–208 pathophysiology of, 154, 205–206 portal, 271, 273 prevalence of, 205 primary, 154, 205, 206t secondary, 154, 205, 206t as stroke risk factor, 186 symptoms of, 206 Hypertensive urgency/emergency, 154–155, 155b, 207 Hyperthermia, malignant, 148–149, 149b–150b, 192t Hyperthyroidism, 293–294, 294b–295b Hypertrophy, 110, 212 Hyperventilation, 139, 161–162, 162b, 178 Hypnotic induction agents, 326 Hypocalcemia, 203 Hypocarbia, 139 458 www.ajlobby.com Mizukawa_Index.indd 458 6/22/17 11:17 AM Index • I Hypocortisolism, 299–300, 299b–300b Hypoglycemia, 156, 156b, 289, 291–293, 291b–293b Hypoperfusion, 186t Hypophosphatemia, 203 Hypophyseal-portal circulation, 279 Hyposplenia, 341 Hypotension attention deficit hyperactivity disorder patients, 372 in cocaine users, 412 maternal, 390–391 perioperative, 160, 160b Hypothalamic-pituitary-adrenal axis, 159, 159b, 286, 286f, 297–298 Hypothalamic-pituitary-thyroid axis, 286, 286f Hypothalamus, 177, 279–280, 280t–281t Hypothermia, 178 Hypothyroidism, 295–296, 296b–297b Hypoventilation, 140 Hypoventilatory hypercapnia, 191 Hypovolemia, 342b Hypoxemia description of, 134, 178, 223 in elderly patients, 362 endotracheal intubation for, 151 in hyperventilation management, 162 maternal, 390 Hypoxia, 342b, 388 I Ibuprofen characteristics of, 64, 66t, 67 in pregnancy, 395t ICP See Intracranial pressure Idarucizumab, 346 I-Gel, 119, 119f IgE-mediated hypersensitivity reactions, 115, 157, 325 IHD See Ischemic heart disease Ileocecal valve, 241 Illicit drugs adolescent use of, 378 cocaine, 410–412 marijuana, 408–410 Immune response, 319 Immune system/disorders acquired immunodeficiency disorders, 319, 319t anaphylactic/anaphylactoid reactions, 325–326 anatomy of, 319 diabetes mellitus See Diabetes mellitus human immunodeficiency virus, 320–322, 320t–322t, 321b organ transplantation, 323–324 physiology of, 319 Immunoglobulins, 319 Immunosuppressants anesthesia affected by, 323t Crohn disease treated with, 248, 248b opioids as, 358 ulcerative colitis treated with, 246, 246b Infants See also Pediatric patients coarctation of the aorta in, 214 local anesthetic dosing in, 44 Infections See also specific infection in diabetic patients, 56 opportunistic, 57 orthopedic implant, 53t postoperative, 50b prosthetic joint, 55–56 surgical site, 50, 54, 324 upper respiratory, 232–233, 379 Infectious endocarditis, 50–51, 51b, 52t Inferior alveolar nerve block, 45–46 Inflammatory bowel disease Crohn disease, 247f, 247–248, 248b–249b ulcerative colitis, 245f, 245–246, 246b Infraorbital nerve, 45 Inhalation anesthesia advantages and disadvantages of, 32 in autism spectrum disorder patients, 369 balanced techniques, 37 clinical techniques for, 36–37 disadvantages of, 380 intravenous anesthesia and, 37 one-breath technique, 37 in pediatric patients, 380–381 Inhalation/inhaled anesthetics cerebral blood flow affected by, 178 elimination of, at equilibrium, induction of, isoflurane, 4, 34 mechanism of action, 32 minimum alveolar concentration of, 7, 7t nitrous oxide See Nitrous oxide pharmacokinetics of, 7, 7t potency of, 8, 8f in pregnancy, 392t solubility of, Inhibitory neurotransmitters, 10–12 Inhibitory postsynaptic currents, 11 INR See International normalized ratio Inspiratory capacity, 377f Insulin, 156, 280t–281t, 282–283, 288t, 425 Interincisal distance, 120, 120f International normalized ratio, 266t, 336, 346 International sensitivity index, 336 Interstitial cells, 282 Intracellular signaling, 13 Intracerebral hemorrhage, 186t Intracranial pressure, 177–178, 191 Intramuscular administration absorption efficiency of, in pediatric patients, 383 Intranasal anesthesia, 382 Intraoperative period bronchospasm prevention strategies, 151b hypoglycemia in, 156 hypotension in, 160, 160b myocardial ischemia in, 154b pain management in, 65–66 postoperative nausea and vomiting risk factors in, 73t Intraosseous administration, 4, 45 Intravenous anesthesia anesthetics used in See Intravenous anesthetics description of, 16 inhalational anesthesia and, 37 in obese patients, 403 in pediatric patients, 383–384, 384t receptors involved in, 16 Intravenous anesthetics in Alzheimer disease patients, 182 barbiturates, 17–18 benzodiazepines, 16b, 16–17 dexmedetomidine, 11, 23–24 diazepam, 17, 17b etomidate, 22–23, 23b flumazenil, 17, 17b glucocorticoids See Glucocorticoid(s) ketamine, 19 methohexital, 17–18, 18b midazolam, 16, 16b neuromuscular blockers See Neuromuscular blockers opioids, 20–22 propofol, 18, 19b thiopental, 18 Intrinsic azotemia, 254 Intrinsic factor, 240 Intrinsic pathway, of coagulation, 336 Inverse agonists, Ion channels, 10 Ionophore, 10 IPSCs See Inhibitory postsynaptic currents Ischemic heart disease, 209–211, 210b Ischemic stroke, 186t, 187, 412 ISI See International sensitivity index Isoflurane, 4, 7t, 34 Isoproterenol, 438 459 www.ajlobby.com Mizukawa_Index.indd 459 6/22/17 11:17 AM J • Index J Janeway lesions, 51 Jaundice, 269, 271 Jaw, osteonecrosis of, 56 Jaw thrust, 130, 130f, 140 Jet ventilation, 138 Juxtaglomerular apparatus, 253 K Kainic acid, 13 Kappa receptor, 20 Ketamine analgesic uses of, 66 antipsychotics and, 193 in asthma patients, 228 in autism spectrum disorder patients, 369 blood pressure affected by, 155 central nervous system effects of, 179 in chronic kidney disease patients, 258 in congestive heart failure patients, 204 in coronary artery disease patients, 210 description of, 19, 19b dexmedetomidine and, 216 dosing of, 442–443 in elderly patients, 365 in end-stage renal disease patients, 258 intracranial pressure affected by, 191 intramuscular administration of, 383 intranasal administration of, 382 metabolites of, 258 nicotinic acetylcholine receptor inhibition by, 13 in obese patients, 405 in obstructive sleep apnea patients, 405 in pediatric patients, 381–382, 384t in porphyria patients, 181 in pregnancy, 394 properties of, 8t in seizure patients, 189 in valvular heart disease patients, 213 Ketoprofen, 66t, 395t Ketorolac characteristics of, 64–65, 66t in pregnancy, 395t Kidney/kidney diseases See also Renal system acute kidney injury, 254–255 anatomy and physiology, 253 chronic kidney disease See Chronic kidney disease end-stage renal disease See Endstage renal disease hepatorenal syndrome, 259, 272 summary of, 261 Korotkoff sounds, 83 Kupffer cells, 261 Kyphoscoliosis, 311, 315 L Labetalol, 155b Lactated Ringer solution, 260 Lactation, 44 Lamotrigine, 189b, 192 Large intestine, 239t, 241 Laryngeal mask airway applications of, 119, 132–133 illustration of, 119f in obese patients, 405 in organ transplantation patients, 324 placement of, 132b sizes of, 132t Laryngospasm, 141, 142b Larynx, pediatric, 376 Latex allergy, 326 LD50 See Median lethal dose Left bundle branch block, 107, 108f Left coronary artery, 199–200 Left ventricular hypertrophy, 110, 212, 215 LET, 40 Leukotriene receptor antagonists, 226, 227t, 231t, 427 Levamisole, 410 Levodopa, 183 Levonordefrin, 42 Levothyroxine, 296, 431 Liability insurance, 170 Licensing boards, 168 Lidocaine bupivacaine and, 44 in elderly, 44 half-life of, 44 onset of action, 41 in pregnancy, 394–395 properties of, 40t, 42t Lidocaine, epinephrine, and tetracaine See LET Lifestyle modifications for gastroesophageal reflux disease, 241 for hypertension, 206–207, 207b Ligand-gated ion channels, 10 Ligands, Limited sclerosis, 308t Liotrix, 296 Lipase inhibitor, 428 Lipophilic drugs absorption of, distribution of, half-life of, volume of distribution of, Lipoproteins, 261 Lisdexamfetamine, 431 Lithium, 192 Litigation, 170 Liver anatomy and physiology of, 261 chemotherapy effects on, 353t, 354b, 355 drug biotransformation in, transplantation of, 272 Liver diseases analgesics in, 270 antibiotics in, 270 Child-Turcotte-Pugh classification of, 269, 269t, 273 cirrhosis, 270–272 hepatitis See Hepatitis jaundice associated with, 269 local anesthetics in, 269 sedatives in, 270 Liver failure acute, 271 anesthetic considerations in, 273–274 antibiotic prophylaxis in, 57 coagulation factors affected by, 272 management of, 272–273 pathophysiology of, 270–272 Liver function tests, 265, 266t LMA See Laryngeal mask airway Local anesthesia cardiac complications of, 46, 47b complications of, 45–47 in ischemic heart disease patients, 211 misconceptions related to, 45 nerve damage caused by, 45–46 pain management with, 65 patient monitoring during, 82 in seizure patients, 189 techniques for, 44–45 Local anesthetics amide, 40, 40t, 43 as cocaine adulterant, 411 comorbidities that affect, 43 dosing of, 43–44 in elderly, 44 esters, 40, 43 factors that affect, 41t forms of, 41 in hepatic-compromised patients, 44 hypersensitivity reactions to, 325–326 in infants, 44 in lactation, 44 lipophilicity of, 41t, 41–42 in liver disease, 269 in liver failure, 273–274 mechanism of action, 40–42, 41f 460 www.ajlobby.com Mizukawa_Index.indd 460 6/22/17 11:17 AM Index • M multiple, 44 overdose of, 46–47 pK a of, 41, 41t potency of, 42 in pregnancy, 44, 392t, 394–395 protein binding of, 41, 41t seizures induced by, 190b toxicity of, 46–47, 47b vasoconstrictors used with, 42–44, 43t vasodilation caused by, 42 Local infiltration, 44 Loop diuretics, 424 Loop of Henle, 253 Lorazepam, 256–257 Lower esophageal sphincter, 240–241, 310 Low-molecular weight heparin, 347 LSP Elder demand valve, 129 Lung(s), 221f, 221–222 Lung capacities, 377, 377f Lung volumes, 224, 377, 377f Lymphoid hypertrophy, 376 M MAC See Minimum alveolar concentration MACawake, Magill fo rceps, 133, 140 Magnesium sulfate, 151 Malignancies airway considerations in, 358 chemotherapy for See Chemotherapy metastatic disease, 357–358, 358b, 359b radiation therapy for, 356 summary of, 359 Malignant hyperthermia, 148–149, 149b–150b, 192t Mallampati classification, 121, 121f, 403 Malnutrition, 248 Malpractice lawsuits allegations in, 167b defense to, 168, 170 documentation as defense to, 168 litigation process, 170 Mandibular condyle, 120, 121f MAOIs See Monoamine oxidase inhibitors MAP See Mean arterial pressure Marijuana, 408–410 Mask ventilation, 116 Mast-cell stabilizers, 427 Maternal hypoxemia, 390 Maxillofacial fractures, antibiotic prophylaxis in, 55 Mean arterial pressure, 177–178, 205 Mean electrical axis, 108–109, 109f Median effective dose, Median lethal dose, Medical emergencies adrenal insufficiency, 158–159, 159b–160b anaphylaxis, 157, 157t, 158b bronchospasm, 142, 143b, 150b, 150–151, 151b hypertension, 154–155, 155b hyperventilation, 161–162, 162b hypoglycemia, 156, 156b malignant hyperthermia, 148–149, 149b–150b myocardial infarction, 110f, 110–111, 152–154, 153t, 154b myocardial ischemia, 111, 152–154, 153t, 154b perioperative hypotension, 160, 160b vasovagal syncope, 160–161, 161b Medical licensing boards, 168 Medical records, 168 Medulla adrenal, 280t–281t, 284–285 brain, 177, 223 Meglitinides, 288t, 425 Membrane receptors, 9–10 Mendelson syndrome, 242 Meperidine characteristics of, 21, 22b, 66t contraindications for, 189 dosing of, 442–443 pharmacokinetics of, 258, 274 in pregnancy, 395t in renal transplantation patients, 324 Mepivacaine, 40t, 42t MET units See Metabolic equivalent units Metabolic equivalent units, 115–116, 365, 366t Metabolism, Metabotropic glutamate receptors, 13 Metastatic disease, 357–359, 358b–359b Methadone, 68, 416 Methamphetamine, 413–415, 431 Methemoglobin, 85, 342–343 Methemoglobinemia, 46, 342–344, 343f, 343t Methimazole, 431 Methionine, 393 Methohexital description of, 17–18, 18b dosing of, 442–443 properties of, 8t in seizure patients, 189 Methotrexate, 355 Methyl paraben, 326 Methylene blue, 46, 343f 3,4-Methylenedioxy-Nmethylamphetamine, 413 Methylphenidate, 371, 431 Methylprednisolone, 28t Methylxanthines, 227t, 231t Metoclopramide, 74t, 77–78 Metronidazole, 52t Midazolam in autism spectrum disorder patients, 369 characteristics of, 16, 16b in chronic kidney disease patients, 256 in chronic obstructive pulmonary disease patients, 232 dosing of, 442–443 in elderly patients, 364 fentanyl and, 208 intramuscular administration of, 383 intranasal administration of, 382 in pediatric patients, 381–382, 384t properties of, 8t in restrictive lung disease patients, 235 Minimum alveolar concentration, 7, 32 Minimum inhibitory concentration, 52 Miosis, opioid-related, 20 Mirtazapine, 436 Misoprostol, 243 Mitral regurgitation, 211t, 212, 213t Mitral stenosis, 211, 211t, 213t Mitral valve, 199, 201 Mitral valve prolapse, 211t, 212, 213t Mobitz type I block, 102, 102f Modafinil, 431 Modulation, of pain, 64 Monitoring, of patient auditory assessment in, 83 blood pressure, 83–84 body temperature, 89 electrocardiography, 83, 95, 96f See also Electrocardiography end-tidal carbon dioxide, 82, 87–89, 88f–89f importance of, 82 in local anesthesia, 82 palpation, 83 pediatric patients, 378 principles of, 82 pulse oximetry, 84–87, 85f–86f requirements, 82 twitch, 89–90, 90f visual assessment in, 83 Monoamine oxidase inhibitors, 191, 430, 435–436 Monoclonal antibodies, 352 Monocytes, 332 Monro-Kellie doctrine, 178 Mood-stabilizing agents, 192 Morphine, 257 Motor nerve, 305–306 Motor unit, 305–306, 305f–306f μ receptors, 12, 12t, 20 Multiple sclerosis, 184f, 184–185 Murmurs, 117 461 www.ajlobby.com Mizukawa_Index.indd 461 6/22/17 11:17 AM M • Index Muscarinic acetylcholine receptors, 13 Muscle fibers, 305 Muscle relaxants, 392t, 429 See also Neuromuscular blockers Muscular dystrophy, 310t, 310–312 Musculoskeletal system/diseases anatomy of, 305–306, 305f–307f Marfan syndrome, 315t, 315–316 motor unit, 305–306, 305f–306f muscular dystrophy, 310t, 310–312 myasthenia gravis, 312–314, 313t, 314b neuromuscular junction, 306, 307f scleroderma, 307–310, 308t MVP See Mitral valve prolapse Myasthenia gravis, 312–314, 313t, 314b Myocardial infarction cocaine use and, 411 description of, 152–154, 153t, 154b, 209 electrocardiographic findings, 110f, 110–111 marijuana use and, 409 methamphetamine as cause of, 414 Myocardial ischemia, 111, 152–154, 153t, 154b, 209 Myopathy, 308 N NADPH See Nicotine adenine dinucleotide phosphate Naloxone characteristics of, 19, 22, 22b, 394 dosing of, 442–443 in substance abuse patients, 416 Naproxen, 64, 66t, 395t Nasal cannula, 129 Nasal hood, 129 Nasal trumpets, 131 Nasopharyngeal airway, 118f, 131, 131f, 134, 140 National Health and Nutrition Examination Survey, 400 Needle cricothyroidotomy, 138–139, 139b Neoplasms, 190b, 190–191 Nephrons, 253 Nephrotoxic drugs, 363 Neurodegenerative disorders Alzheimer disease, 182 cerebrovascular accident, 185–188, 186t, 340 multiple sclerosis, 184f, 184–185 Parkinson disease, 183 Neurohypophysis, 280t–281t, 282 Neurokinin receptor antagonists, 440 Neuroleptic malignant syndrome, 192t Neuroleptics, 193 Neurom uscular blockers anaphylactic reactions to, 326 definition of, 24 depolarizing, 24–25, 89 non-depolarizing, 24–25, 89 rocuronium, 25–26, 26b succinylcholine See Succinylcholine Sugammadex, 27, 27b twitch monitoring of, 89–90, 90f Neuromuscular junction, 306, 307f Neurotransmitters See also specific neurotransmitter excitatory, 13 inhibitory, 10–12 Neutrophils, 319 New York Heart Association classification, 203, 203b Nicotine adenine dinucleotide phosphate, 343f Nicotinic acetylcholine receptors, 13, 32, 312 Nitric oxide, 334 Nitric oxide inhibitors, 438 Nitroglycerin, 154, 155b Nitrous oxide analgesic effects of, 12, 65 central nervous system effects of, 178 in chronic kidney disease patients, 258 contraindications for, 33, 381 in end-stage renal disease patients, 258 inhalational anesthesia uses of, 32–33, 37 in liver disease patients, 269 in liver failure patients, 274 methotrexate and, interaction between, 355 in pediatric patients, 381 in pregnancy, 393, 392t properties of, 7t systemic effects of, 33 NMDA receptors, 12t, 13, 32, 179, 216, 416 Nociception, 64 Nonalcoholic fatty liver disease, 271 Noncompetitive antagonists, Non-depolarizing neuromuscular blockers, 24–25, 89, 324, 355t, 429 Non-rebreather mask, 129 Non–ST-elevation myocardial infarction, 152, 209 Nonsteroidal anti-inflammatory drugs analgesic uses of, 67 peptic ulcer disease caused by, 243–244 properties of, 422 Norepinephrine, 11, 285, 438 Norketamine, 258 Normal sinus rhythm, 98, 98f Normeperidine, 21 NSAIDs See Nonsteroidal antiinflammatory drugs O Obesity airway considerations, 403, 405 anesthetic considerations in, 404t, 404–405 body mass index, 234t, 400, 400f comorbidities associated with, 400, 401b, 403 complications in, 405–406 gastroesophageal reflux disease associated with, 403 intravenous access in, 403 nonalcoholic fatty liver disease secondary to, 271 restrictive lung diseases associated with, 233–235, 234b risk assessments in, 401–405 venous thromboembolism risks, 405 Obstructive sleep apnea airway management in, 405 algorithm for, 402f apnea hypopnea index, 401, 401t cardiovascular system assessments in, 403 comorbidities associated with, 401b complications in, 405–406 description of, 116b, 116–117, 235 diagnosis of, 401 opioid considerations in, 404, 415 prevalence of, 401 respiratory function assessments in, 403 risk assessments in, 401–405 STOP-Bang questionnaire for, 401–402, 402b Office-based anesthesia glucocorticoids for, 28 growth of, 148 principles of, 404 safety of, 166 Office-based surgery, 148 OMSNIC See Oral and Maxillofacial Surgery National Insurance Company Ondansetron, 74t, 78, 258 Opioid(s) abuse of, 415–416, 422 acetaminophen with, 67 American Society of Anesthesiologists guidelines for, 404 analgesic uses of, 65, 68 anaphylactic reactions to, 326 benzodiazepines and, 415–416 462 www.ajlobby.com Mizukawa_Index.indd 462 6/22/17 11:17 AM Index • P central nervous system effects of, 179 in chronic kidney disease patients, 257–258 in chronic obstructive pulmonary disease patients, 232 in congestive heart failure patients, 204 constipation caused by, 68 dependence on, 68–69 in elderly, 363, 364t, 365 in end-stage renal disease patients, 257–258 fentanyl, 20–21, 21b, 65 immunosuppressive effects of, 358 as intravenous anesthetics, 20–22 in malignancy patients, 358 meperidine, 21, 22b miosis caused by, 20 naloxone antagonism of, 22, 22b in obstructive sleep apnea patients, 404, 415 overdose of, 415–416 pain management uses of, 65, 68–69, 416 postoperative nausea and vomiting caused by, 20, 68, 72 in pregnancy, 394 properties of, 422 remifentanil, 8t, 21, 21b, 65–66 respiratory depression caused by, 20, 235, 363, 415 routes of administration of, 415 in seizure patients, 189 side effects of, 20, 68, 72 Opioid receptors, 12, 12t, 20, 415 Opportunistic infections, 57 Oral administration advantages of, in pediatric patients, 381 Oral and Maxillofacial Surgery National Insurance Company, 166, 168 Oral anticoagulants andexanet alfa, 346 antiplatelet drugs, 345 apixaban, 346 dabigatran etexilate, 346 description of, 345 idarucizumab, 346 pre-surgical discontinuation of, 347–348 risk assessments with, 347–348, 347b rivaroxaban, 346 warfarin, 345–347 Oral cavity, 239, 239t Orbital floor fractures, 55 Organ transplantation, 323–324 Oropharyngeal airway, 118f, 131, 132f, 134, 140 Oropharyngeal screen, 141 Oropharynx, 240 Orthognathic surgery, 54 Orthopedic implant infection, 53t OSA See Obstructive sleep apnea Osteomyelitis, 340 Osteonecrosis of the jaw, 56 Ovaries, 280t–281t, 283 Oxcarbazepine, 189b Oximetry, pulse, 84–87, 85f–86f Oxycodone acetaminophen and, 270, 274 characteristics of, 66t, 68 in pregnancy, 395t Oxygen blood delivery of, 333–334, 334t bronchospasm treated with, 151 chronic obstructive pulmonary disease treated with, 230 delivery methods for, 129 maternal consumption of, in pregnancy, 388 in obstructive sleep apnea patients, 405 sources of, in office setting, 128 supplemental, 128, 151, 223, 232, 395 Oxygen transport, 225 Oxyhemoglobin, 85 Oxyhemoglobin dissociation curve, 85f, 161, 225, 334, 342 Oxyhemoglobin saturation, 84, 87 Oxytocin, 280, 282 P P wave, 93, 93f Paco2 See Partial pressure of arterial carbon dioxide Pain intraoperative, 65–66 malignancy-related, 357 mechanisms of, 64 opioids for, 65, 68–69, 416 postoperative, 66–68, 155, 370 preoperative management of, 64–65 Pain perception, 64 Palpation, 83 Pancreas, 280t–281t, 282f, 282–283 Pancytopenia, 355 Pao2 See Partial pressure of oxygen Paracetamol, 67 Paraneoplastic syndromes, 355 Parathyroid glands, 280t–281t, 283–284 Parathyroid hormone, 280t–281t, 283, 284f Parenteral anesthetics definition of, pharmacokinetics of, 7–8 properties of, 8t Parietal cells, 240 Parkinson disease, 183, 430 Parkinsonism, 183 Partial pressure, Partial pressure of arterial carbon dioxide, 88, 388 Partial pressure of arterial oxygen, 84, 225 Partial pressure of oxygen, 223 Partial seizures, 188 Patent ductus arteriosus, 215–216 Patient positioning, 128 PDNV See Postdischarge nausea and vomiting PE See Pulmonary embolism Peak flow meter, 228 Pediatric patients See also Infants airway in, 376–377, 377f algorithm for bradycardia in, 447 algorithm for cardiac arrest in, 445 algorithm for tachycardia in, 449 asthma in, 379 attention deficit hyperactivity disorder in, 371–372, 379, 413 cardiac output in, 376, 376t cardiovascular system in, 376 coarctation of the aorta in, 214 comorbidities in, 379–380 emergency airway in, 134 fasting guidelines for, 379–380 illicit drug use by, 378 inhalation anesthesia in, 380–381 intramuscular administration in, 383 intranasal administration in, 382 intravenous sedation in, 383–384, 384t monitoring of, during anesthesia, 378 nitrous oxide in, 381 oral administration in, 381 psychologic assessment in, 378 respiratory system in, 376–377, 377f upper airway in, 376 upper respiratory infections in, 379 Penicillin hypersensitivity, 325 Peptic ulcer disease, 243–244, 244b Peptide analogs, 425 Perception, of pain, 64 Percutaneous balloon valvuloplasty, 214 Pericardium, 199 Periodontal ligament, local anesthetic injections in, 45 Perioperative hypotension, 160, 160b Peripheral chemoreceptors, 223 Peripheral nerve neuropathy, 309 Peripheral oxygen saturation, 225 Peripheral vascular disease, 208, 210 Peripheral vascular resistance, 83 Pharmacodynamics definition of, 4, in elderly, 364–365 ligands, 463 www.ajlobby.com Mizukawa_Index.indd 463 6/22/17 11:17 AM P • Index receptors, 9–10 Pharmacokinetics absorption, 4–5 body mass index effects on, 404 definition of, distribution, in elderly, 364–365 inhaled anesthetics, 7, 7t metabolism, models of, 5, 6f parenteral anesthetics, 7–8 Pharynx, 240 Phase I biotransformation, Phase II biotransformation, Phenothiazines, 74t, 76, 440 Phentermine, 431 Phentolamine, 412 Phenylephrine, 412, 439 Phenytoin, 189b Phosphodiesterase-4 inhibitors, 231t, 427, 439 Phospholipase A2, 285 Phrenic nerve, 223 Physician Litigation Stress Resource Center, 171 Physostigmine, 13 Pineal gland, 280t–281t, 282 Pinealocytes, 282 Pituitary gland, 280t–281t, 281–282 pK a description of, local anesthetics affected by, 41, 41t Plasma, 332, 332b Plasma proteins, 5, 332 Plasminogen, 337 Platelets, 334–335, 335b, 345 Plavix See Clopidogrel Polar metabolites, Pons, 177 PONV See Postoperative nausea and vomiting Porphyria, 179–181, 179b, 180b, 181t Portal hypertension, 271, 273 Portal vein, 261 Postdischarge nausea and vomiting, 72, 78 Posterior pituitary, 280t–281t, 281 Postoperative nausea and vomiting antiemetics for See Antiemetics in autism spectrum disorder patients, 370 glucocorticoids for, 28 incidence of, 72 opioids as cause of, 20, 68, 72 pathophysiology of, 72 prophylactic management of, 78 risk factors for, 72, 73t Postoperative period infections in, 50b pain management in, 66t, 66–68, 155, 370 postoperative nausea and vomiting risk factors, 73t Postrenal azotemia, 254 Potassium, 11 Potassium leak channels, 11, 12t Potassium-sparing diuretics, 207t, 424 Potency of glucocorticoids, 28t of inhalation anesthetics, 8, 8f lipophilicity effects on, 42 of local anesthetics, 42 P-R interval, 93, 93f Pre-anesthetic evaluation airway evaluation, 117–122, 118f–122f chronic obstructive pulmonary disease, 116 in elderly, 365, 366t elements of, 114 exercise capacity assessments, 115–116 history-taking, 114–117 obstructive sleep apnea, 116, 116b physical examination, 117 pulmonary system, 116 Prednisolone, 28t Prednisone, 159, 297 Pregabalin, 189b Pregnancy anesthetic considerations in, 390–395 aortocaval compression in, 389 cardiovascular system in, 389 FDA pharmaceutical classifications in, 391, 391t fetal oxygenation in, 390 gastrointestinal system in, 390 hematologic system in, 389 local anesthetics in, 44 maternal hypotension in, 390–391 maternal hypoxemia in, 390 maternal oxygen consumption in, 388 overview of, 388 oxygen supplementation in, 395 physiologic changes of, 388–390 renal system in, 390 respiratory system in, 388 teratogenicity in, 391, 392t warfarin contraindications in, 346 Preload, 201–202 Premature atrial contraction, 100, 100f Premature ventricular contraction, 103, 103f Preoperative period bronchospasm prevention strategies, 151b in Crohn disease patients, 249b pain management in, 64–65 postoperative nausea and vomiting risk factors, 73t, 78 Prerenal azotemia, 203, 254 Presynaptic α-adrenergic receptors, 12t Prilocaine, 40t, 42t, 46 Primary central nervous system tumors, 190b, 190–191 Primary hypertension, 154, 205, 206t Prinzmetal angina, 209 Prochlorperazine, 74t, 76 Professional licensing boards, 168 Promethazine, 74t, 76, 78, 258 Propofol antidepressants and, 193 in children, 216 in chronic kidney disease patients, 256 in congenital heart disease patients, 216 in congestive heart failure patients, 204 description of, 18, 19b dosing of, 442–443 in elderly, 364, 364t in end-stage renal disease patients, 256 immunosuppressive effects of, 358 intracranial pressure affected by, 191 in liver disease patients, 269 in obese patients, 405 in obstructive sleep apnea patients, 405 in pediatric patients, 384t pK a of, in pregnancy, 393 properties of, 8t in seizure patients, 189 Propofol infusion syndrome, 18 Propylthiouracil, 431 Prostacyclin, 334 Prostacyclin inhibitor, 424 Prosthetic joints antibiotic prophylaxis in patients with, 55–56 infections involving, 55–56 Protease inhibitors, 322 Protein C, 337 Protein S, 337 Protein-bound drugs, Prothrombin time, 336 Proton-pump inhibitors, 241, 242b, 430 Proximal convoluted tubule, 253 Pseudomembranous colitis, 54 Psychiatric disorders, 191–193, 192b, 192t Psychosis, 192 Psychostimulants, 379 PT See Prothrombin time PTH See Parathyroid hormone PUD See Peptic ulcer disease 464 www.ajlobby.com Mizukawa_Index.indd 464 6/22/17 11:17 AM Index • S Pulmonary circulation, 222 Pulmonary disorders acute respiratory infection, 232–233 asthma See Asthma chronic obstructive pulmonary disease See Chronic obstructive pulmonary disease restrictive lung diseases, 233–235, 234b, 273 Pulmonary edema, 414 Pulmonary embolism, 346, 348 Pulmonary function tests, 228 Pulmonary hypertension, 235, 309 Pulmonary stenosis, 214 Pulmonary system See also Respiratory system anatomy of, 221–225 chemotherapy effects on, 353t, 354b evaluations of, 116 functions of, 221 gas exchange in, 223–224 hemodynamics of, 222 lung volumes, 224 lungs, 221f, 221–222 muscular dystrophy involvement of, 309 opioid-induced depression of, 20, 235, 363 oxygen transport in, 225 physiology of, 221–225 ventilation, 221, 223 Pulmonary valve, 199–201 Pulpal anesthesia, 45 Pulse oximetry, 84–87, 85f–86f Purkinje fibers, 92, 92f PVD See Peripheral vascular disease Pyridostigmine, 314 Q QRS complex, 92, 108 QRS interval, 93, 93f, 97 QT interval, 93f, 94 R Radiation therapy, 356 Radionuclide angiography, 203 Rales, 117 Ranitidine, 158b Rapid sequence intubation, 24–25 Raynaud phenomenon, 309 Receptors, 9–10 See also specific receptors Recombinant factor VIII, 339 Rectum, 241 Red blood cells, 332–333 Regional blocks, 44–45 Remifentanil characteristics of, 21, 21b, 65–66 dosing of, 442–443 in liver disease patients, 274 pharmacokinetics of, 257 properties of, 8t Renal artery stenosis, 309 Renal failure, antibiotic prophylaxis in, 57 Renal system age-related decreases in, 363 anatomy of, 253 chemotherapy effects on, 353t, 354b, 355 in elderly, 363 physiology of, 253 pregnancy-related changes in, 390 Renal system disorders acute kidney injury, 254–255 chronic kidney disease See Chronic kidney disease end-stage renal disease See Endstage renal disease hepatorenal syndrome, 259, 272 Renal transplantation, 57 Renin, 253 Renin inhibitor, 424 Residual volume, 377f Respiratory system See also Pulmonary system chemotherapy effects on, 353t, 354b cocaine effects on, 411–412 in elderly, 362–363 methamphetamine effects on, 414 obstructive sleep apnea assessments, 403 opioid-induced depression of, 20, 235, 363, 415 in pediatric patients, 376–377, 377f pregnancy-related changes in, 388 Restrictive lung diseases, 233–235, 234b, 273 Retinopathy, 340 Review of systems, 115 Rhabdomyolysis, 312 RIFLE criteria, 254 Right atrium, 199 Right bundle branch block, 106, 107f, 215 Right coronary artery, 199–200 Right ventricular hypertrophy, 110 Rivaroxaban, 346 RLDs See Restrictive lung diseases Rocuronium, 25–27, 26b, 442–443 Ropivacaine, 40t, 42t, 324 Roth spots, 51 RR interval, 93, 93f Ryanodine receptor gene, 148 S Safety, Saliva, 239–240 Salivary glands, 239t, 239–240 Sao2 See Oxyhemoglobin saturation Saw palmetto, 429 SCD See Sickle cell disease Scleral icterus, 271 Scleroderma, 307–310, 308t Scopolamine, 74t, 75, 78 Second heart sound, 200 Secondary hypertension, 154, 205, 206t Second-degree AV block, 102, 102f Sedatives in liver disease patients, 270 in liver failure patients, 274 in pregnancy, 392t Seizures antiepileptics for, 189b, 433–435 in autism spectrum disorder, 368 description of, 188–189, 189b, 190b Selective serotonin reuptake inhibitors, 191, 192b, 193, 436 Septal defects atrial, 215 ventricular, 216 Serotonin receptor agonists, 428 Serotonin receptor antagonists, 74t, 78, 440 Serotonin syndrome, 191, 192b, 192t, 193 Serotonin-norepinephrine reuptake inhibitor, 436 Sevoflurane dexmedetomidine effects on, 24 inhalational anesthesia use of, 36 one-breath technique with, 37 properties of, 7t SIADH See Syndrome of inappropriate antidiuretic hormone Sickle cell crisis, 340, 342b Sickle cell disease, 340–341, 342b Sinoatrial node, 92, 199–200 Sinus block, 101, 101f Sinus dysrhythmias, 99–101, 99f–101f Small intestine, 239t, 241 Smoking, 230, 230b Sodium channel blockers, 428, 434–435 Sodium polystyrene sulfonate, 260 Somatostatin, 280t–281t, 283 Spinal cord, 177 Spinal cord compression, 357 Spirometry, 224, 224f Splenomegaly, 271 “Square counting” method, 96, 97f SSRIs See Selective serotonin reuptake inhibitors St John’s wort, 429 465 www.ajlobby.com Mizukawa_Index.indd 465 6/22/17 11:17 AM S • Index ST segment, 93f, 94 Stable angina, 153t, 209 Status epilepticus, 189 Stellate cells, 261 STEMI See ST-segment myocardial infarction Stensen ducts, 240 Steroid sex hormones, 280t–281t, 283 Stimulants, 372 Stomach, 239t, 240–241 STOP-BANG questionnaire, 116, 116b, 235, 401–402, 402b Stress reduction, 188 Stroke, 185–188, 186t, 340, 412 Stroke volume, 201 ST-segment myocardial infarction, 110, 110f, 152 Subarachnoid hemorrhage, 186t Subarachnoid space, 177 Sublingual salivary glands, 240 Substance abuse cocaine, 410–412 marijuana, 408–410 methamphetamine, 413–415 opioids, 415–416 overview of, 408 polysubstance, 417 summary of, 416–417 Succinylcholine in Alzheimer disease patients, 182 characteristics of, 24–25, 26b chemotherapeutic agents and, 355t in organ transplantation patients, 324 in pediatric patients, 384, 384t Sufentanil, 8t Sugammadex, 27, 27b, 442–443 Sulfonylureas, 156, 288t, 426 Superagonists, Superior vena cava syndrome, 357 Supine hypotension syndrome, 389 Supplemental oxygen description of, 128–129, 223, 232 in pregnancy, 395 Supraglottic devices, 119, 119f, 134 Supraglottic obstruction, 140 Supraventricular tachycardia, 100, 100f Surgical cricothyroidotomy, 134–138, 135f–137f, 136b, 138b Surgical site infections, 50, 54, 324 SV See Stroke volume Sympathomimetics, 190b Syncope, vasovagal, 160–161, 161b Syndrome of inappropriate antidiuretic hormone, 355 Systemic arterial pressure, 376t Systemic sclerosis, 308t Systemic vascular resistance, 205 Systole, 200–201 Systolic blood pressure, 205 T T3 See Triiodothyronine T4 See Thyroxine T cells, 319, 332 T wave, 93f, 94 Tachycardia algorithms for, 448–449 supraventricular, 100, 100f ventricular, 105, 105f Tacrolimus, 323 TASK potassium leak channels, 11, 12t Temporomandibular joint mobility, 120, 121f Teratogenicity, 391, 392t Terminal bronchioles, 221–222 Testicles, 280t–281t, 283 Tetracyclic antidepressants, 437 Tetrahydrocannabinol, 408 Thalamus, 177 Theophylline, 427 Thiazide diuretics, 204, 207t, 424 Thiazolidinediones, 288t, 426 Thiopental, 8t, 18, 442–443 Third heart sound, 200 Third molar extractions, antibiotic prophylaxis in, 54 Third-degree AV block, 103, 103f Thrombin, 336 Thromboembolism, 186t Thromboplastin, 336 Thrombosis, 186t Thromboxane A 2, 335, 345 Thyroid drugs, 431 Thyroid gland, 280t–281t, 283 Thyroid storm, 294 Thyromental distance, 120 Thyroxine, 280t–281t, 283 Tidal volume, 224, 224f, 377f Tolcapone, 183 Topiramate, 189b Topoisomerase inhibitors, 352t Total bilirubin, 266t Total body weight, 404 Total lung capacity, 224, 224f Toxic megacolon, 246 Trachea anatomy of, 222 mobility of, 122 narrowing of, in Down syndrome patients, 371 in pediatric patients, 377 Trachea hook, 137f Tracheobronchial tree, 221 Tramadol, 66t, 68, 395t Tranexamic acid, 432 Transdermal delivery system, for scopolamine, 75 Transduction, of pain, 64 Transjugular intrahepatic portosystemic shunt, 259, 272 Transmission, of pain, 64 Transtracheal ventilation, 134 TREK potassium leak channels, 11, 12t Triamcinolone, 28t Tricuspid valve, 199 Tricyclic antidepressants, 191, 437 Trigeminy, 104, 104f Triiodothyronine, 280t–281t, 283 Trimethobenzamide, 74t, 77–78 Trismus, 45 Trisomy 21 See Down syndrome Tumor lysis syndrome, 355 Tumor necrosis factor inhibitors, 427 Twitch monitoring, 89–90, 90f Two-pore-domain potassium channels, 11 Type I pneumocytes, 221–222 Type II pneumocytes, 222 U Ulcerative colitis, 245f, 245–246, 246b Unfractionated heparin, 347 Unstable angina, 209 Upper airway, pediatric, 376 Upper respiratory infections description of, 232–233 in pediatric patients, 379 Uremic syndrome, 255 URI See Upper respiratory infection Uteroplacental vasoconstriction, 390 V Valproate, 189b Valvular heart disease, 211–213, 211t–213t Vasoconstrictors β-adrenergic effects of, 76–77 local anesthetics with, 42–44, 43t Vasodilators, 155b, 424 Vasopressin, 280, 282, 439 Vasopressors, 438–439 Vasovagal syncope, 160–161, 161b Vecuronium, 27 Venous partial pressure, Venous thromboembolism, 405 Ventilation, 221, 223 Ventilation-perfusion mismatch, 128 Ventricular dysrhythmias, 103–108, 103f–108f Ventricular fibrillation, 105, 105f Ventricular septal defect, 216 Ventricular systole, 200–201 Ventricular tachycardia, 105, 105f Visual assessment, 83 Vital capacity, 224, 224f Vital signs, 117, 376t Vitamin K, 345–346 466 www.ajlobby.com Mizukawa_Index.indd 466 6/22/17 11:17 AM Index • Z Vitamin K–dependent clotting factors, 269, 336 Voltage-gated calcium channels, 10, 306 Voltage-gated ion channels, 10 Voltage-gated potassium channels, 10 Voltage-gated sodium channels, 10 Volume of distribution, Vomiting postoperative See Postoperative nausea and vomiting in sedated patient, 140, 141b von Willebrand disease, 337–338 von Willebrand factor, 334, 337 W Y Warfarin, 345–348 Wenckebach block, 102, 102f Wharton ducts, 240 Wheezes, 117 Yellow fever virus, 267 X Xarelto See Rivaroxaban Xerostomia, 413 Z Zona fasciculata, 284 Zona glomerulosa, 284–285 Zona reticularis, 284 467 www.ajlobby.com Mizukawa_Index.indd 467 6/22/17 11:17 AM www.ajlobby.com Mizukawa_Index.indd 468 6/22/17 11:17 AM ... inhalation anesthesia The primary disadvantages of inhalation anesthesia are cost and the need for an anesthesia circuit and vaporizers Sevoflurane costs approximately US $130 per bottle (250 mL) The anesthesia. .. Will, and Anna, who have supported my career and the many nights and weekends in the hospital or at my desk Thank you for your unwavering love and support To the many Vanderbilt oral and maxillofacial. . .Anesthesia Considerations for the Oral and Maxillofacial Surgeon www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM www.ajlobby.com Mizukawa_FM.indd 6/22/17 10:15 AM ANESTHESIA CONSIDERATIONS