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Septic Shock Advances in Diagnosis and Treatment Clinical Review & Education Review Septic Shock Advances in Diagnosis and Treatment Christopher W. Seymour, MD, MSc; Matthew R. Rosengart, MD, MPH Supplemental content at IMPORTANCE Septic shock is a clinical emergency that occurs in more than 230 000 jama.com US patients each year. CME Quiz at jamanetworkcme.com and OBSERVATIONS AND ADVANCES In the setting of suspected or documented infection, septic CME Questions page 725 shock is typically defined in a clinical setting by low systolic (Յ90 mm Hg) or mean arterial blood pressure (Յ65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. Author Affiliations: Author affiliations are listed at the end of this CONCLUSIONS AND RELEVANCE The prompt diagnosis of septic shock begins with article. obtainment of medical history and performance of a physical examination for signs Corresponding Author: Christopher and symptoms of infection and may require focused ultrasonography to recognize more W. Seymour, MD, MSc, Departments of Critical Care complex physiologic manifestations of shock. Clinicians should understand the Medicine and Emergency Medicine, importance of prompt administration of intravenous fluids and vasoactive medications University of Pittsburgh School of aimed at restoring adequate circulation, and the limitations of protocol-based therapy, Medicine, 3550 Terrace St, Scaife as guided by recent evidence. Hall, Office 639, Pittsburgh, PA 15261 ([email protected]). Section Editors: Edward Livingston, JAMA. 2015;314(7):708-717. doi:10.1001/jama.2015.7885 MD, Deputy Editor, and Mary McGrae McDermott, MD, Senior Editor. hock is life-threatening circulatory failure with inadequate tissue perfusion.1 The typical presentation is hypotension Methods S (low systolic Յ90 mm Hg) or mean arterial blood pressure (Յ65 mm Hg) accompanied by clinical signs of We performed a review of the MEDLINE and the Cochrane Data- hypoperfusion. Historically, shock was attributed to a neurologic base of Systematic Reviews from 2010 to 2015 using specific search response to injury, vasomotor changes to the circulation, or a strategies. Our primary search used the terms shock, septic shock, problem of missing blood.2 By the mid- 20th century, Blalock and diagnosis, and treatment, among others. We provide search strings Weil organized shock into distinct constructs: cardiogenic, and Preferred Reporting Items for Systematic Reviews and Meta- obstructive, hypovolemic, or vasogenic.3,4 Although these cat- Analyses diagram in eAppendix (in the Supplement). We restricted egories are valuable teaching concepts, the diagnosis of articles to adult (age Ն18 years) human data reported in the English shock is far more complex. We focus this review on septic shock, language only. We screened articles published between January 1, which is the most common cause of noncardiogenic shock and 2010, and June 1, 2015, and excluded opinion articles, commentar- has several of the Blalock and Weil physiologic constructs at the ies, case series, and cohort studies—focusing on randomized clini- same time.5 Septic shock occurs in more than 230 000 US cal trials (RCTs), meta-analyses, systematic reviews, and clinical prac- patients each year, with more than 40 000 US deaths annually. A tice guidelines. After screening 8329 titles and abstracts, more recent Burden of Diseases article found that primary risk factors articles were identified for full-text review, after which manual re- for septic shock (ie, infection) is the fifth leading cause of years of view of bibliographies generated additional references. A total of 181 productive life lost due to premature mortality.6 Given the articles were manually reviewed, of which 35 were selected with rel- public health burden, we review advances in diagnosis, treat- evant content (eFigure in the Supplement). We selected only ar- ment, and areas of uncertainty in septic shock from January 2010 ticles deemed to provide major advances in the diagnosis or treat- to June 2015. ment of septic shock. We considered sources of bias in these articles 708 JAMA August 18, 2015 Volume 314, Number 7 (Reprinted) jama.com Copyright 2015 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by a University Of New Mexico User on 08/19/2015 Septic Shock: Advances in Diagnosis and Treatment Review Clinical Review & Education and defined areas of uncertainty as those in which the evidence con- Table 1. Major Advances in the Diagnosis and Treatment of Traumatic flicted. We used the American Heart Association classification of rec- and Septic Shock ommendations to grade the quality of evidence (grade A, data from Action Caveat many large RCTs; grade B, data from fewer, smaller RCTs, careful Diagnostic analyses of nonrandomized studies, or observational registries; and Clinical diagnosis is the criterion Normotensive shock with isolated grade C, expert consensus). standard: hyperlactemia needs clarity; Typically, systolic blood pressure Lactate and systolic blood pressure ≤90 mm Hg or mean arterial thresholds are uncertain; blood pressure ≤65 mm Hg Biologic phenotyping may be promising or >40-mm Hg decrease but not yet feasible in real time or Results from baseline; tested in randomized clinical trials Poor peripheral perfusion, low Major Diagnostic Advances urinary output, altered mentation, elevated lactate A conceptual framework for the diagnosis of shock has multiple do- Pulmonary artery catheterization May have a role in right ventricular mains including an initial evaluation of the etiology and clinical fea- and continuous monitoring of dysfunction, complex cases with tures, assessment of the primary hemodynamic manifestations, and central venous oxygen saturation diagnostic uncertainty not recommended for routine consideration of alterations in cellular biology and the degree of lo- diagnosis caltissueinjury.Majoradvancesandareasofuncertaintywithinthese Focused ultrasonography is Practical, easy to use, and recommended 7 domains (Table 1) will be discussed. suggested if there is concern for by expert consensus overlapping hemodynamic manifestations of shock Initial Evaluation Arterial pulse contour analysis Awaiting randomized clinical trials for patient outcomes; At the bedside, a clinician begins by asking, “Is this patient in Requires controlled mechanical shock?” Consensus guidelines for septic shock agree on core diag- ventilation and sinus rhythm nostic elements including suspected or documented infection Treatment accompanied by arterial hypotension and evidence of tissue Prompt fluid bolus is recommended Fluid therapy with balanced crystalloids (500-1000 mL) with appropriate vs albumin is suggested based on hypoperfusion (eg, oliguria, altered mental status, poor periph- safety limits meta-analyses,8,9 while specific fluid eral perfusion, or hyperlactemia).10,11 Yet the requirement for comparisons undergo additional adequate fluid resuscitation, absence of vasopressors, or thresh- randomized clinical trials Norepinephrine is recommended as Vasopressin may spare norepinephrine olds for blood pressure vary across shock definitions. In fact, a a first-line vasopressor at higher doses recent European Society of Intensive Care Medicine (ESICM) con- Hydroxylethyl starch may cause Increases mortality and worsens renal sensus statement suggests shock may present in the absence of harm outcomes among survivors hypotension.12 There is no reference standard for the bedside Protocolized early goal-directed Tested among patients with prompt therapy is not superior to usual care shock recognition, intravenous fluid diagnosis of shock. Rather, observational studies report how mor- in early septic shock boluses, and early antibiotics tality varies across combinations of shock features from 29% to Low-dose corticosteroids to be Dosing regimen and timing of 46%.13 considered for vasopressor- discontinuation remains controversial dependent shock If shock is present, the clinician must determine the inciting cause by asking, “What just happened?” Such clinical risk factors will guide immediate intervention. And although severe infection may be evident, it is often more difficult to recognize. We found Invasive Hemodynamic Monitoring no changes to the typical clinical approach to the diagnosis of Decades ago, the standard care of shock patients included inva- infection in septic shock during our review. However, many bio- sive devices like the pulmonary artery catheter (PAC) or continu- markers and blood culture–independent, molecular diagnostics ous central venous oxygen saturation (SCVO2) catheterization. are undergoing study to help discriminate sterile inflammation The PAC can estimate cardiac output and measure mixed venous from infection.14 oxygen saturation, among other parameters, to refine the etiol- The primary physiologic manifestations of shock should be as- ogy of shock and potentially affect patient outcomes. A 2013 sessed, although they are unlikely to fit simply into the Blalock and Cochrane
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