Critical Care Sedation Angelo Raffaele De Gaudio Stefano Romagnoli Editors 123 Critical Care Sedation Angelo Raffaele De Gaudio Stefano Romagnoli Editors Critical Care Sedation Editors Angelo Raffaele De Gaudio Department of Anesthesia and Critical Care Azienda Ospedaliero-Universitaria Careggi Firenze Italy Stefano Romagnoli Department of Anesthesia and Critical Care Azienda Ospedaliero-Universitaria Careggi Firenze Italy ISBN 978-3-319-59311-1 ISBN 978-3-319-59312-8 (eBook) https://doi.org/10.1007/978-3-319-59312-8 Library of Congress Control Number: 2017963645 © Springer International Publishing AG 2018 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface In the last 20 years, victims of critical illness have become increasingly elderly and frequently subject to multiple organ dysfunction Critical illness is currently defined by certain syndromes, such as sepsis or acute renal failure, or by physiological alterations, such as shock states or hypoxemia It is hence often necessary to integrate the more traditional subspecialties of medicine into critical care practice For these reasons, critical care demands continuous advances in technology, therapeutics, and monitoring to improve the prognosis of disease states that influence organ physiology, especially in elderly patients Attention to sedation and analgesia in intensive care units (ICUs) has evolved during the last years, and significant evidence of its influence on patient outcomes has emerged In light of this, those privileged to take care of patients in the ICU have witnessed a dramatic evolution from former practices of deep sedation lasting for several days to a gentler approach that treats “light sedation” for cooperative patients as the indisputably preferable option Patients’ brains are vulnerable organs in the context of the multiple organ dysfunction that commonly characterizes critically ill patients Sedation causes both brief and long-lasting injury that may manifest delirium and cognitive impairment This book, with its precious contributions from authors selected from physicians and researchers who handle sedatives and analgesics in their daily clinical practice, provides readers with an overview of current knowledge and the most up-to-date literature The contents are designed to cover a number of issues directly or indirectly related to analgo-sedation in the ICU. Drugs currently in use (e.g., benzodiazepines or propofol) and newer molecules or applications (e.g., dexmedetomidine, halogenates) are discussed in relation to different aspects of patient care, including stress response, pain management, instrumental and clinical monitoring, the immune system, and sleep quality and quantity Issues such as pediatric population, neuromuscular blocking agents, regional anesthesia techniques, and delirium are also addressed Our aim was to design a text that would both revise and update the basic subject matter while directing practitioners toward the confident use of a specific drug or technique As editors, we found the revision of individual manuscripts rewarding, and we believe that the subject matter displays a healthy balance between theoretical understanding and practical clinical implementation We hope that readers will find the chapters both informative and useful for improving patient care in their everyday clinical practice v vi Preface Finally, we wish to thank the editorial team members of Springer International Publishing AG; Mr Andrea Ridolfi, Clinical Medicine Books Editor; and Mr Rakesh Kumar Jotheeswaran, Project Coordinator, for having provided support in editing all chapters of this book Florence, Italy January 2018 A. Raffaele De Gaudio, M.D Stefano Romagnoli, M.D Contents 1 Critical Care Sedation: The Concept ���������������������������������������������������������� Giovanni Zagli and Lorenzo Viola 2 The Stress Response of Critical Illness: Which Is the Role of Sedation? �������������������������������������������������������������������������������� A Raffaele De Gaudio, Matteo Bonifazi, and Stefano Romagnoli 3 Pain Management in Critically Ill Patient������������������������������������������������ 21 Cosimo Chelazzi, Silvia Falsini, and Eleonora Gemmi 4 Common Practice and Guidelines for Sedation in Critically Ill Patients ������������������������������������������������������������������������������ 35 Massimo Girardis, Barbara Rossi, Lorenzo Dall’Ara, and Cosetta Cantaroni 5 The Subjective and Objective Monitoring of Sedation���������������������������� 47 Carla Carozzi and Dario Caldiroli 6 Intravenous Sedatives and Analgesics�������������������������������������������������������� 69 Francesco Barbani, Elena Angeli, and A Raffaele De Gaudio 7 Volatile Anesthetics for Intensive Care Unit Sedation���������������������������� 103 Giovanni Landoni, Omar Saleh, Elena Scarparo, and Alberto Zangrillo 8 Regional Anaesthesia Techniques for Pain Control in Critically Ill Patients ���������������������������������������������������������������������������� 121 Francesco Forfori and Etrusca Brogi 9 Neuromuscular Blocking Agents�������������������������������������������������������������� 139 Elena Bignami and Francesco Saglietti 10 Sedation and Hemodynamics�������������������������������������������������������������������� 155 Federico Franchi, Loredana Mazzetti, and Sabino Scolletta 11 Sedation and the Immune System������������������������������������������������������������ 167 Gianluca Villa, Chiara Mega, and Angelo Senzi vii viii Contents 12 Sleep in the ICU ���������������������������������������������������������������������������������������� 185 Stefano Romagnoli, Rosa Giua, and A Raffaele De Gaudio 13 Delirium in the Critically Ill Patients������������������������������������������������������ 197 Fulvio Pinelli, Elena Morettini, and Elena Cecero 14 Sedation in Pediatric Critically Ill Patients �������������������������������������������� 213 Cristiana Garisto, Alessandra Rizza, and Zaccaria Ricci 15 Sedation in Cardiac Surgery Intensive Care Unit���������������������������������� 245 Sergio Bevilacqua and Ilaria Galeotti Index������������������������������������������������������������������������������������������������������������������ 257 List of Contributors Elena Angeli, M.D. Department of Health Science, University of Florence, Florence, Italy Francesco Barbani, M.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Sergio Bevilacqua, M.D. Cardiac Anaesthesia and Intensive Care Unit, Department of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria Careggi, Florence, Italy Elena Bignami, M.D. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy Matteo Bonifazi, M.D. Department of Health Science, University of Florence, Florence, Italy Etrusca Brogi, M.D. Department of Anaesthesia and Intensive Care, University of Pisa, Pisa, Italy Dario Caldiroli, M.D. Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milan, Italy Cosetta Cantaroni, M.D. Department of Anaesthesiology and Intensive Care, University of Modena and Reggio Emilia, Modena, Italy Carala Carozzi, M.D. Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milan, Italy Elena Cecero, M.D. Department of Health Science, University of Florence, Florence, Italy Cosimo Chelazzi, M.D., Ph.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Lorenzo Dall’Ara, M.D. Cattedra di Anestesia e Rianimazione Struttura Complessa di Anestesia e Rianimazione, Università degli Studi di Modena e Reggio Emilia, Modena, Italy ix x List of Contributors A. Raffaele De Gaudio, M.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Department of Health Science, University of Florence, Florence, Italy Silvia Falsini, M.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Department of Health Science, University of Florence, Florence, Italy Francesco Forfori, M.D. Department of Anaesthesia and Intensive Care, University of Pisa, Pisa, Italy Federico Franchi, M.D. Unit of Intensive and Critical Care Medicine, Department of Medical Biotechnologies, University Hospital “Santa Maria alle Scotte”, University of Siena, Siena, Italy Ilaria Galeotti, M.D. Cardiac Anaesthesia and Intensive Care Unit, Department of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria Careggi, Florence, Italy Cristiana Garisto, M.D. Pediatric Cardiac Intensive Care Unit, Department of Cardiology and Cardiac Surgery, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Eleonora Gemmi, M.D. Department of Health Science, University of Florence, Florence, Italy Massimo Girardis, M.D. Cattedra di Anestesia e Rianimazione Struttura Complessa di Anestesia e Rianimazione, Università degli Studi di Modena e Reggio Emilia, Modena, Italy Rosa Giua, M.D. Department of Health Science, University of Florence, Florence, Italy Giovanni Landoni, M.D. Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy Loredana Mazzetti, M.D. Department of Medical Biotechnologies, University of Siena, Siena, Italy Chiara Mega, M.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Department of Health Science, University of Florence, Florence, Italy Elena Morettini, M.D. Department of Health Science, University of Florence, Florence, Italy Fulvio Pinelli, M.D. Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy 248 S Bevilacqua and I Galeotti Table 15.1 The fast-track cardiac model in use in Azienda Ospedaliera Careggi—Firenze Operating room Premedication Anesthesia induction Muscle relaxation Anesthesia maintenance Surgery Intensive care unit Sedation Hypnotic Analgesia Opioids Diazepam 0.05–0.2 mg/kg on the day of surgery Fentanyl 0.5–3 μg/kg Sufentanil 0.25–1 μg/kg Midazolam 0.05–0.2 mg/kg Propofol 0.5–2 mg/kg Rocuronium 0.6–0.9 mg/kg (single dose at the induction) Remifentanil 0.1–0.3 μg/kg/min Sufentanil 0.3–1 μg/kg/h titrated until the end of CPB Propofol 1–3 mg/kg/h Sevoflurane 0.5–1.5 MAC Desflurane 0.5–1.5 MAC Preservation of normothermia at the end of surgery Maintenance of normothermia or mild hypothermia during CPB Off-pump procedures when possible Minimally invasive procedures when indicated Minimize bleeding (thromboelastography-guided therapy) Propofol Remifentanil Morphine 0.5–1 mg/kg/h (stop at weaning) 0.05–0.1 μg/kg/min (stop at weaning) 1–3 mg before starting weaning and if VAS >3 Acetaminophen 0.5–1 g before starting weaning and then Q8h Ketorolac 30 mg as rescue analgesic if VAS still >3 Active rewarming: until 37 °C core temperature is regained Weaning started as soon as Core temperature > 36.9 °C Stable hemodynamics No significant ECG abnormalities No excessive bleeding (≤100 ml/h) Extubation as soon as Conscious and obeyed commands Spontaneous ventilation with pressure support of 10–12 cmH2O Positive end-expiratory pressure (PEEP) of 5 cmH2O Fraction of inspired oxygen (FiO2) of ≤0.4 during surgery, and of sedation in ICU, although pivotal, is only part of the overall cardiac patient management, leading to the early weaning of patients from the ventilator The main reason of success of the fast-track model of care is merely organizational, due to the increasing demand of cardiac surgery care, unbalanced by limited resources Furthermore, huge factors are also the belief that excessive or prolonged sedation could favor the insurgence of delirium and prolong the patient’s ICU stay and the need for circulatory support, thus increasing the total cost of care and worsening outcomes [10] Although this could be true, several trials and meta-analysis failed to find an ultimate outcome advantage of this model of care in comparison with the standard one [11] A recent Cochrane review concluded that the fast-track 15 Sedation in Cardiac Surgery Intensive Care Unit 249 model has risks of mortality and major postoperative complications similar to those of conventional care but appear to be safe in patients at low or moderate risk [12] Anyway, while the time to extubation, the length of the intensive care treatment, and sometimes also the patient length of stay in ICU are reduced, the total length of stay in the hospital is generally unchanged [13] A method for maximizing the advantage of the fast-track model would be that of developing an institutional structure comprising a dedicated cardiac surgery PACU. When applied on selected patients at lower risk (EuroSCORE less or equivalent to 10, not hemodialysis dependent, and not in cardiogenic shock), patients could be early extubated in the dedicated PACU, and safely discharged in the step- down care unit in the same day of surgery, without passing through the CSICU [14] These authors found a shortened length of stay of the early extubated patients in the intensive care area but failed to prove any differences in the total hospital length of stay in respect to patients submitted to standard care inside a CSICU. Advanced age and left ventricular dysfunction were the main preoperative predictors of failure of a similar sedation protocol [15] However, the ability to perform a goal-directed sedation and analgesia is unquestionable advantage of this model of care, that is, to tailor sedation, anxiolysis, and analgesia to every individual patient’s need, both in those who achieve early readiness to be weaned and in the frailest or hemodynamically instable patients who not Actually, short-acting sedatives are crucial also for those patients who cannot be extubated in a short time or in whom early or repetitive neurological windows are needed, as are patients at higher risk of neurologic complication after complex cardiac or aortic surgery Our institutional cardiac fast-track model is summarized in Table 15.1 15.4 Delirium in CSICU Delirium is a common complication after cardiac surgery Its incidence is highly variable among the various studies that have been set in CSICU, from 3.07% [16] to 52% [17] Reasons for this variability may be the different case mix, the specific tool used to make the diagnosis, and the difficulty to recognize some types of delirium, especially the hypoactive form [18] Although delirium is often a self-limiting occurrence, it is one of the main reasons why cardiac patients may lengthen their stay in ICU slowing down the weaning from mechanical ventilation [19] Moreover, delirium has been associated with persistent cognitive dysfunction, reduced quality of life, and even higher mortality [20] Predisposing factors, frequently associated with cardiac surgery, which put this specialty at higher risk of developing delirium are the advanced age of cardiac patients and the coexisting morbidities as cerebrovascular disease, cognitive impairment, peripheral vascular disease, atrial fibrillation, depression, or previous history of stroke [10] On the other hand, precipitating factors for developing postoperative delirium are prolonged duration of sedation and mechanical ventilation, prolonged duration of surgery or aortic cross-clamping, anemia, and blood transfusion [10] 250 S Bevilacqua and I Galeotti Also hypokalemia and SOFA score has been highly correlated with delirium, as well as sepsis, hyponatremia, cardiogenic shock, low left ventricular ejection fraction (