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(BQ) Part 1 book Critical care update 2017 has contents: Aerosolized antibiotic, biomarkers in invasive fungal infections, optimum dose of colistin in intensive care unit, perioperative dysnatremia, hypophosphatemia in intensive care unit,... and other contents.
CHAPTER tI ~ d ir a: Ii IE Acid Suppression in Critically III: Is It 'Really Necessary? SamirSahu Sl al rE is fc fe g~ a( Vf minimal This is the rationale for the useofacid-suppressive drugs suchasPPI orH2RA for pharmacological prophylaxis.' Gastric mucosa is sensitive to changes in hemodynamics Recent studies report a very low incidence of stress such as hypotension resulting in reduced perfusion and ulcer-related bleeding due to effective pharmacological and cytokine-mediated inflammation This results in stress nonpharmacological prophylactic measures, therefore riskof related mucosal disease (SRMD), which endoscopically mortality appears to be low may range from superficial erosions to multiple ulcers Main riskfactors forbleeding aremechanical ventilation and can lead to clinically important bleeding episodes for more than 48 hours, coagulopathy [international requiring blood transfusion I Prophylaxis of such lesions is normalized ratio (INR) >1.5 orplatelet count(PLT) 2 x Upper Limit ofNormal (ULN)] and histamine-2 receptor antagonists (H2RA) Both ofthese (GrAevidence), cardiogenic shock, burnpatients, thosewith agents are well tolerated and are ableto decrease incidence cramocerebral injury, acute renal failure (Gr B evidence) of bleeding episode." In spite of these pharmacological and history of an upper gastrointestinal bleeding within agents, stress ulcer prophylaxis (SUP) measures and the past 12 months, severe sepsis or septic shock, known decrease in bleeding episode has not been translated into peptic ulcerdisease, post-kidney orliver transplantation and mortality benefit in prospective studies Thus, recently, some those patients taking nonsteroidal anti-inflammatory drugs intensivists have expressed concerns aboutthe safety ofSUP, (NSAIDs) or high-dose glucocorticoids (Gr C evidence) especiallywithrespect to infectious complications Based upon currentevidence, these patients shouldreceive pharmacological ulcer prophylaxis," Almost universal use of stress ulcer prophylaxis in _. ~ _ . I.,~PIDEMIOLOGY intensive careunit (ICU) is due to the above mentioned risk Stress-related mucosal disease is presentin mostcritically ill factors, which arepresentinmanyofthecritically ill patients patients, but only a few patients experience overt bleeding Many observational studies have reported useofSUP inmore complications Only around 1% of them develop SMRD than 80% ofcritically ill patients.' related gastrointestinal (GI) bleeding.P Due to the fact that acid-suppressive medications can effectively lower the SRMD-related bleeding, which are clinicallyimportant asshown inmanymeta-analyses, though based on low-quality studies, national and international Both systemic hypotension due to absolute or relative guidelines have endorsedthis practice in patients with risk hypovolemia, cardiogenic or obstructive shock, use of factors for bleeding." There are several trials and meta vasopressors and local splanchnic hypoperfusion due to analyses comparing PPI to H2RA Most of them favor PPI positive end expiratory pressure in patients on mechanical withrespect to reduction ofbleeding rates PPI arethe agents ventilation, may lead to decrease in gastric mucosal blood ofchoice in SUP flow Hypoperfusion leadsto a reducedproduction ofseveral protective mechanisms that exist in a healthy stomach 'Ihese mechanisms can cause mucosal damage, but need the presence of gastric acid to causemajor ulcerations and We ingest pathogens duringroutine feed and gastric acidacts gastric bleeding Without acid, mucosal damage is only as a natural barrier against these pathogens Suppression of st fo re or is tri of 0\ of pr in is PF pa of as tlu uk Sl ne tri, ph pa of pa m( , T I -.J [ I I I l l s If , , CHAPTER 33:Acid Suppression in Critically III: IsIt Really Necessary? this acid barrier by pharmacological means takes away this defense mechanism This leads to overgrowth of bacteria in upper GI tract This phenomenon is more evident with agents with stronger and longer acid-suppressing effect like pPJ Moreover, acid-suppressing agents can also alter leukocyte function This results in both intestinal infections such as Clostridium difficile-associated diarrhea (CDAD) and also to extraintestinal infections like pneumonia (via retrograde microaspiration)." Ofthese infections, C difficile is the most problematic one C difficile spores or vegetative form are transferred through lackofcontactprecautions and fecal oralroute.Thevegetative form is normally inhibited by gastric acid and spores are resistantto it Suppression of this acid milieu (gastric pH >5) leads to increasedsurvival of the vegetative forms, which are the main culpritin CDAD as the stool ofinfected individuals containstenfoldmorevegetative forms than spores Due to the same reason, frequent CDAD relapses and recurrentdiseasesaremorecommoninpatients onPPI therapy.v' The roleofacidsuppression asa riskfactor forpneumonia isunclear but remainslikely Larger randomizedprospective trials are warrantedto resolve this Issue.' Patients with liver cirrhosis are prone to adverse effects of SUP Use of PPI was an independent risk factor for overall mortality This might be due to an increased risk of spontaneous bacterial peritonitis and higher rates of pneumonia and CDAD.6 Due to polypharmacy, there are important drug-drug interactions with PPI, one of the most important clinically, is between the antiplatelet agent clopidogrel and various PPJ A study reported increased cardiovascular events in patients taking both clopidogrel and ppe Moreover, use of PPI has been associated with liver toxicity manifesting as transaminitis, bone marrow suppression manifesting as thrombocytopenia and hypomagnesemia." Enteral nutrition seems to be protective against stress ulcer-related bleeding and addition of a pharmacological SUP may not result in additional substantial benefit This needs to be further explored in randomized prospective trials as enteral nutrition could be a viable alternative to pharmacological SUp.B,9 It wasobservedthat in enterally fed patients, who have additional SUP therapy, the incidence of pneumonia was increased compared to patients on parenteral nutrition In this subgroup, an increase in mortality wasalso observed.to CONCLUSION The triad of stress-related increased gastric acid formation, reduced perfusion of GImucosa due to sepsis or shockand reductionofprotective mucosal barrier makethe critically ill patients more vulnerable to GI bleed due to SRMD or ulcer This leadstoalmostuniversal application ofpharmacological prophylaxis in the majority of ICU patients at present, with PPI or H2RA effectively preventing GI bleeding Though this common practice has not resulted in decreases mortality and its universal use is questioned as this practice may be associated with some risk Nosocomial pneumonia and C difficile are among the two most serious association of this practice Thus risk benefit needs to be balanced carefully before selecting SUP Other less risky strategies like early enteral-feeding or restricting SUP to very high-risk patients during earlyICU stay, needs to be evaluated in prospective randomizedtrials ?; REFER~NCES Stollman N, Mell DC Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients JCrit Care 2005;20:35-45 Alhazzani W, Alenezi F, Jaeschke RZ, et al Proton pump inhibitors versus histamine receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis Crit Care Moo 2013;41: 693-705 Buendgens l, Koch A, Tacke FPrevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis World J Crit Care Med 2016;5:57-64 Maclaren R, Jarvis Cl, Fish ON Use of enteral nutrition for stress ulcer prophylaxis Ann Pharmacother 2001 ;35:1614-23 Lin PC, Chang CH, Hsu PI, et al The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis Crit Care Moo 2010;38:1197-205 Krag M, Pemer A, Wetterslev J, etal Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients A systematic review of randomised 'clinical trials with meta-analysis and trial sequential analysis Intensive Care Med.2014;40:11-22 Buendgens l, Bruensing J, Matthes M, et al Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium diffici/trassociated diarrhea J Crit Care 2014;29:696 e11-696.e15 Deshpande A, Pasupuleti V, Thota P, et al.Acid-suppressive therapy isassociated with spontaneous bacterial peritonitis in cirrhotic patients: ameta-analysis J Gastroenterol Hepatol 2013;28:235-42 Ho PM, Maddox TM, Wang L, et al Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibilors follOWing acute coronary syndrome JAMA 2009;301 :937-44 10 Marik PE, Vasu T, Hirani A, et al Stress ulcer prophylaxis in the new millennium: asystematic review and meta-analysis Crit Care Med 2010;38:2222-8 197 '" , '" , e ec Ion Infectious Diseases SECTION EDITOR: RAHUL A PANDIT '" , , , , CHAPTER, Sepsis 3: What's New? Manoj KSingh, Mehul KSolanki ! INTRODUCTION 1,2 I The Greeks first described sepsis in 700 BC as an infection leading to organ decomposition and death Sepsis, an inflammatory response to infection, is a leading cause of admission to hospital Worldwide, every minute a patient presents to an emergency department with severe sepsis or septic shock; the mortality for this condition ranges from 25 to 50% While mortality in hospital is probably decreasing in the developed countries, long-term mortality after sepsis has remained high-as many-patients die in the subsequent months Sepsis and septic shock kill one in four (and often more) and is increasing in incidence Similar to other acute events like polytrauma, acute myocardial infarction, or stroke, the rapidity withwhich thetherapy is administered in theinitial hoursofsepsis islikely to influence outcome %DEFINITION 3-14 !t'~,_,_""_" ,,,_,,_,~,,y,>_, _ _ , _ w_ _, _ , _ , • ~_, _ •• ,~ • • • _."._._ •• ~~ •••• ,_~ ••• _ _ '0', _ •• , " In a 1992 consensus conference, the American College of Chest Physicians and the Society of Critical Care Medicine ina jointstatementdefined sepsis as a continuum syndrome and introduced the term systemic inflammatory response syndrome (SIRS), which does not require the presence of infection Sepsis was defined as suspected or proven infection plus a SIRS (e.g., fever, tachycardia, tachypnea, and leukocytosis) Severe sepsis wasdefined as sepsis withorgan dysfunction (hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia, or obtundation) Septic shock was defined as severe sepsis with hypotension, despite adequate fluid resuscitation Septic shock and multiorgan dysfunction arethe mostcommon causes ofdeathinpatients with sepsis The 2001 International Sepsis Definition Conference attempted to improve onthe specificity ofthesedefinitions by elaborating common clinical and laboratory manifestations ofthe disorder One ofthe goals of creating these definitions was to help physicians recognize patients at risk for severe sepsis and initiate therapy promptly In order to reflect the manyprognostic factors in sepsis and provide a hypothesis generating modelfor future research, thePIRO (Predisposing factors, nature of Insult, intensity of Response, number of Organ dysfunction) grading system was also proposed The septic response is an extremely complex cascade of events, including proinflammatory, anti-inflammatory, humoral, cellular, and circulatory involvement There are inherent challenges in defining sepsis and septic shock First and foremost, sepsis is a broad term-applied to-an incompletely understood process There are,asyet, no simple and unambiguous clinical criteria or biological, imaging or laboratory features that uniquely identify a septic patient As such the definitions of sepsis have been largely unchanged formorethan twodecades There was an urgentneed of revised definition of sepsis due to the following reasons: • Emphasizing in the definition that sepsis is a severe entitywith a much poor prognosis than uncomplicated infection, that is to say the term sepsis itself should denoteseverity • Recognizing that at present there is not a validated standard diagnostic test, leading to major variations in reportedincidence and mortality ratesofsepsis • Identify simple, inexpensive, bedside criteria for identifying all elements of sepsis like presence of an infection, typeofhostresponse, and organdysfunction • Provide a more consistent epidemiological definition of sepsis The European Society of Intensive Care Medicine and The Society of Critical Care Medicine convened a taskforce of 19 critical care, infectious disease, and surgical and pulmonary specialists in January 2014 and published the "Third International Consensus Definitions for Sepsis and Septic Shock" (Sepsis-S), The recommendation of the task force was circulated to the major international societies for , , , I I ; SECTION 4: Infectious Diseases endorsement The task force recommended that the new definition be designated as Sepsis-3 Sepsis-l and Sepsis-2 were the terminology given to 1991 and 2001 statements, respectively, to emphasize the need forfuture iterations of in in SCREENING PATIENTS LIKELY TO HAVE SEPSIS Three simple bedside criteria were validated to identify patients with suspected infection who are at increased risk of deterioration These are altered mental status, systolic blood pressure $100 mmHg and/or respiratory rate ~22/min (presence of any two) this is called quickSOFA Or qSOFA Though this is less robust in identifying this patient population in leU than SOFA, but can be used in the emergency departmentand wardsrepeatedly The term septic shock refers to patient with sepsis and persisting hypotension requiring vasopressors to maintain mean arterial pressure~65 mmHgand having a serumlactate level more than mrnol/L (18 mg/dL) despite adequate volume resuscitation In this cohort, the hospital mortality is morethan 40% CHALLENGES The absence of a gold standard diagnostic test for sepsis resulting in a limited definition of constellation of clinical signs and symptoms in a patient with suspected infection is one of the biggest challenge in sepsis research Theconcept ofSIRS may be present in the absence of infection in many critically ill patient The use of two or more SIRS criteria to identify sepsis has been decided arbitrarily in the previous definition and was found to be unhelpful One in eight critically illpatients with infection will not have a minimum of two SIRS criteria Sequential Organ Failure Assessment (SOFA) score" (Table 1) is the current standard to assess severity of organ dysfunction and indicates poor prognosis withincreasing score Simply put, the higherthe SOFA score, the increased probability of mortality One ofthe limitations of this test is requirement of multiple laboratory test thus routineapplication maybedifficult universally OC pa in; an po thl pa thi pe on in m! to Va ou un • CONTROVERSIES/LIMITATIONS The current recommendations of the task force can be seen as pragmatic compromises and general abilities of this poorly understood complex process In all sepsis definitions, the diagnosis of sepsis depends on whether the patient has "suspected infection': Unfortunately, there is little discussion about exactly how to determine whether infection is "suspected" Indeed, formostpatientspresenting with an unclear problem, infection is the differential diagnosis Quick SOFA and SOFA are mortality predictors and not tests for identifying infection or sepsis Although qSOFA is validated in retrospective studiesto identify early sepsis it still needs to be validated prospectively and in various clinical settingwith variableinfrastructure Absence The present task force recommends sepsis to be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection An increase in SOFA score by two points from baseline(or zero, if baseline not known) is identified as new organ dysfunction as this reflects a chord with poor prognosis and an overall mortality of>10% in this population for Sel in qu go; for an: del Thl the pat to nOl TABLE Sequential Organ Failure Assessment score* - SOFA Score Respiratory (PaOiFi02 mmHg) - - - -, >400 ~:e~:~"109IL) €.~ 70 mmHg or I CNS (Glasgow Coma ~re) Renal (creatinin-;mmollLor UOP) t all( - -