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JAMA Feb 2016Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function,...
IMPORTANCE
Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
OBJECTIVE
To evaluate and, as needed, update definitions for sepsis and septic shock.
PROCESS
A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).
KEY FINDINGS FROM EVIDENCE SYNTHESIS
Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.
RECOMMENDATIONS
Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.
CONCLUSIONS AND RELEVANCE
These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Topics: Advisory Committees; Biomarkers; Blood Pressure; Delphi Technique; Hospital Mortality; Humans; International Classification of Diseases; Lactates; Organ Dysfunction Scores; Peer Review, Research; Respiratory Rate; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Terminology as Topic; Vasoconstrictor Agents
PubMed: 26903338
DOI: 10.1001/jama.2016.0287 -
Acta Clinica Croatica Jun 2022Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood pressure, which decreases tissue perfusion pressure, causing hypoxia that is characteristic of shock. Sepsis is still one of the leading causes of mortality worldwide. Its incidence has increased since the first consensus definitions were established in 1991. Raising sepsis awareness, its significance and the need for better treatment, has led to an improvement in in defining sepsis and the development of guidelines for its treatment. The first guidelines were published in 2004, the second 2008, the third 2013, the fourth 2016, and the last revised guidelines appeared in 2021. This paper will describe the previous and new definitions of sepsis and septic shock, the previous guidelines for the recognition and treatment, and the latest recommendations for treatment. Timely diagnosis is crucial for the outcomes for patients with sepsis and septic shock. The fact is that the sepsis care bundles have been modified to increasingly shorter time determinants, which emphasizes the importance of emergency physicians, who frequently first recognize and begin emergency treatment of septic patients.
Topics: Humans; Shock, Septic; Sepsis; Critical Care; Blood Pressure; Time Factors
PubMed: 36304809
DOI: 10.20471/acc.2022.61.s1.11 -
JAMA Feb 2019Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial.
IMPORTANCE
Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established.
OBJECTIVE
To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018.
INTERVENTIONS
Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay.
RESULTS
Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed.
CONCLUSIONS AND RELEVANCE
Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03078712.
Topics: Aged; Capillaries; Cause of Death; Female; Fluid Therapy; Hemodynamics; Humans; Intensive Care Units; Kaplan-Meier Estimate; Lactic Acid; Male; Middle Aged; Organ Dysfunction Scores; Proportional Hazards Models; Renal Replacement Therapy; Respiration, Artificial; Resuscitation; Shock, Septic; Vasoconstrictor Agents
PubMed: 30772908
DOI: 10.1001/jama.2019.0071 -
Polish Archives of Internal Medicine Aug 2022The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines... (Review)
Review
The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.
Topics: Adult; Humans; Sepsis; Shock, Septic
PubMed: 35791800
DOI: 10.20452/pamw.16290 -
Intensive Care Medicine Dec 2014Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the...
OBJECTIVE
Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.
METHODS
The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? Four types of statements were used: definition, recommendation, best practice and statement of fact.
RESULTS
Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring.
CONCLUSIONS
This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock.
Topics: Blood Pressure; Cardiac Output; Critical Care; Echocardiography; Europe; Guidelines as Topic; Hemodynamics; Humans; Monitoring, Physiologic; Shock, Septic; Societies, Medical; Stroke Volume
PubMed: 25392034
DOI: 10.1007/s00134-014-3525-z -
Biomedical Journal Feb 2022Sepsis remains a major cause of morbidity and mortality among children worldwide. Furthermore, refractory septic shock and multiple organ dysfunction syndrome are the... (Review)
Review
Sepsis remains a major cause of morbidity and mortality among children worldwide. Furthermore, refractory septic shock and multiple organ dysfunction syndrome are the most critical groups which account for a high mortality rate in pediatric sepsis, and their clinical course often deteriorates rapidly. Resuscitation based on hemodynamics can provide objective values for identifying the severity of sepsis and monitoring the treatment response. Hemodynamics in sepsis can be divided into two groups: basic and advanced hemodynamic parameters. Previous therapeutic guidance of early-goal directed therapy (EGDT), which resuscitated based on the basic hemodynamics (central venous pressure and central venous oxygen saturation (ScvO2)) has lost its advantage compared with "usual care". Optimization of advanced hemodynamics, such as cardiac output and systemic vascular resistance, has now been endorsed as better therapeutic guidance for sepsis. Despite this, there are still some important hemodynamics associated with prognosis. In this article, we summarize the common techniques for hemodynamic monitoring, list important hemodynamic parameters related to outcomes, and update evidence-based therapeutic recommendations for optimizing resuscitation in pediatric septic shock.
Topics: Child; Hemodynamic Monitoring; Hemodynamics; Humans; Prognosis; Sepsis; Shock, Septic
PubMed: 34653683
DOI: 10.1016/j.bj.2021.10.004 -
Seminars in Fetal & Neonatal Medicine Oct 2020The current standard approach to manage circulatory insufficiency is inappropriately simple and clear: respond to low blood pressure to achieve higher values. However,... (Review)
Review
The current standard approach to manage circulatory insufficiency is inappropriately simple and clear: respond to low blood pressure to achieve higher values. However, the evidence for this is limited affecting all steps within the process: assessment, decision making, therapeutic options, and treatment effects. We have to overcome the 'one size fits all' approach and respect the dynamic physiologic transition from fetal to neonatal life in the context of complex underlying conditions. Caregivers need to individualize their approaches to individual circumstances. This paper will review various clinical scenarios, including managing transitional low blood pressure, to circulatory impairment involving different pathologies such as hypoxia-ischemia and sepsis. We will highlight the current evidence and set potential goals for future development in these areas. We hope to encourage caregivers to question the current standards and to support urgently needed research in this overlooked but crucial field of neonatal intensive care.
Topics: Hemodynamics; Humans; Hypotension; Infant, Newborn; Intensive Care, Neonatal; Neonatology; Shock, Septic
PubMed: 32473881
DOI: 10.1016/j.siny.2020.101121 -
JAMA Feb 2016Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology... (Meta-Analysis)
Meta-Analysis Review
Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
IMPORTANCE
Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.
OBJECTIVE
To develop a new definition and clinical criteria for identifying septic shock in adults.
DESIGN, SETTING, AND PARTICIPANTS
The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets.
MAIN OUTCOMES AND MEASURES
Evidence for and agreement on septic shock definitions and criteria.
RESULTS
The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets.
CONCLUSIONS AND RELEVANCE
Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.
Topics: Adult; Advisory Committees; Biomarkers; Blood Pressure Determination; Cohort Studies; Consensus; Delphi Technique; Fluid Therapy; Humans; Hypotension; Lactates; Observational Studies as Topic; Resuscitation; Review Literature as Topic; Shock, Septic; Vasoconstrictor Agents
PubMed: 26903336
DOI: 10.1001/jama.2016.0289 -
Jornal de Pediatria 2020Review the main aspects of the definition, diagnosis, and management of pediatric patients with sepsis and septic shock. (Review)
Review
OBJECTIVE
Review the main aspects of the definition, diagnosis, and management of pediatric patients with sepsis and septic shock.
SOURCE OF DATA
A search was carried out in the MEDLINE and Embase databases. The articles were chosen according to the authors' interest, prioritizing those published in the last five years.
SYNTHESIS OF DATA
Sepsis remains a major cause of mortality in pediatric patients. The variability of clinical presentations makes it difficult to attain a precise definition in pediatrics. Airway stabilization with adequate oxygenation and ventilation if necessary, initial volume resuscitation, antibiotic administration, and cardiovascular support are the basis of sepsis treatment. In resource-poor settings, attention should be paid to the risks of fluid overload when administrating fluids. Administration of vasoactive drugs such as epinephrine or norepinephrine is necessary in the absence of volume response within the first hour. Follow-up of shock treatment should adhere to targets such as restoring vital and clinical signs of shock and controlling the focus of infection. A multimodal evaluation with bedside ultrasound for management after the first hours is recommended. In refractory shock, attention should be given to situations such as cardiac tamponade, hypothyroidism, adrenal insufficiency, abdominal catastrophe, and focus of uncontrolled infection.
CONCLUSIONS
The implementation of protocols and advanced technologies have reduced sepsis mortality. In resource-poor settings, good practices such as early sepsis identification, antibiotic administration, and careful fluid infusion are the cornerstones of sepsis management.
Topics: Anti-Bacterial Agents; Child; Fluid Therapy; Humans; Pediatrics; Resuscitation; Shock, Septic
PubMed: 31843507
DOI: 10.1016/j.jped.2019.10.007 -
PloS One 2015International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.
METHODS
Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.
RESULTS
Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.
CONCLUSIONS
Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.
Topics: Epinephrine; Hemodynamics; Humans; Lypressin; Norepinephrine; Phenylephrine; Shock, Septic; Terlipressin; Treatment Outcome; Vasoconstrictor Agents; Vasopressins
PubMed: 26237037
DOI: 10.1371/journal.pone.0129305