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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 -
Critical Care Medicine Jan 2022To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.
DATA SOURCES
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.
STUDY SELECTION
Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.
DATA EXTRACTION
Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.
DATA SYNTHESIS
One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).
CONCLUSIONS
Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.
Topics: Adolescent; Child; Child, Preschool; Clinical Laboratory Techniques; Consciousness; Female; Global Health; Humans; Infant; Infant, Newborn; Male; Organ Dysfunction Scores; Patient Acuity; Respiration, Artificial; Sepsis; Shock, Septic; Sociodemographic Factors
PubMed: 34612847
DOI: 10.1097/CCM.0000000000005294 -
BMJ (Clinical Research Ed.) Jun 2018Secondary peritonitis accounts for 1% of urgent or emergent hospital admissions and is the second leading cause of sepsis in patients in intensive care units globally.... (Review)
Review
Secondary peritonitis accounts for 1% of urgent or emergent hospital admissions and is the second leading cause of sepsis in patients in intensive care units globally. Overall mortality is 6%, but mortality rises to 35% in patients who develop severe sepsis. Despite the dramatic growth in the availability and use of imaging and laboratory tests, the rapid diagnosis and early management of peritonitis remains a challenge for physicians in emergency medicine, surgery, and critical care. In this article, we review the pathophysiology of peritonitis and its potential progression to sepsis, discuss the utility and limitations of the physical examination and laboratory and radiographic tests, and present a paradigm for the management of secondary peritonitis.
Topics: Abdominal Cavity; Disease Management; Disease Progression; Early Medical Intervention; Humans; Peritonitis; Sepsis
PubMed: 29914871
DOI: 10.1136/bmj.k1407 -
Intensive Care Medicine Mar 2020Early clinical recognition of sepsis can be challenging. With the advancement of machine learning, promising real-time models to predict sepsis have emerged. We assessed... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Early clinical recognition of sepsis can be challenging. With the advancement of machine learning, promising real-time models to predict sepsis have emerged. We assessed their performance by carrying out a systematic review and meta-analysis.
METHODS
A systematic search was performed in PubMed, Embase.com and Scopus. Studies targeting sepsis, severe sepsis or septic shock in any hospital setting were eligible for inclusion. The index test was any supervised machine learning model for real-time prediction of these conditions. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, with a tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist to evaluate risk of bias. Models with a reported area under the curve of the receiver operating characteristic (AUROC) metric were meta-analyzed to identify strongest contributors to model performance.
RESULTS
After screening, a total of 28 papers were eligible for synthesis, from which 130 models were extracted. The majority of papers were developed in the intensive care unit (ICU, n = 15; 54%), followed by hospital wards (n = 7; 25%), the emergency department (ED, n = 4; 14%) and all of these settings (n = 2; 7%). For the prediction of sepsis, diagnostic test accuracy assessed by the AUROC ranged from 0.68-0.99 in the ICU, to 0.96-0.98 in-hospital and 0.87 to 0.97 in the ED. Varying sepsis definitions limit pooling of the performance across studies. Only three papers clinically implemented models with mixed results. In the multivariate analysis, temperature, lab values, and model type contributed most to model performance.
CONCLUSION
This systematic review and meta-analysis show that on retrospective data, individual machine learning models can accurately predict sepsis onset ahead of time. Although they present alternatives to traditional scoring systems, between-study heterogeneity limits the assessment of pooled results. Systematic reporting and clinical implementation studies are needed to bridge the gap between bytes and bedside.
Topics: Diagnostic Tests, Routine; Humans; Machine Learning; Retrospective Studies; Sepsis; Shock, Septic
PubMed: 31965266
DOI: 10.1007/s00134-019-05872-y -
Rhode Island Medical Journal (2013) Dec 2019Sepsis remains a field of active research with many unknown and unanswered questions. Over the past few decades, advancements in sepsis management have led to improved... (Review)
Review
Sepsis remains a field of active research with many unknown and unanswered questions. Over the past few decades, advancements in sepsis management have led to improved mortality and morbidity. This article will review the current evidence-based practices of the treatment of sepsis and septic shock. It will also critically appraise some of the current controversies in sepsis management, such as fluids, steroids, early vasopressors, early goal-directed therapy and immunotherapy.
Topics: Disease Management; Drug Therapy, Combination; Early Goal-Directed Therapy; Evidence-Based Practice; Fluid Therapy; Humans; Immunotherapy; Sepsis; Shock, Septic; Steroids; Vasoconstrictor Agents
PubMed: 31795528
DOI: No ID Found -
BMC Infectious Diseases Jun 2022Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China.
METHODS
We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock.
RESULTS
Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%-32.8%, I = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%-46.0%, I = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed.
CONCLUSIONS
Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).
Topics: Humans; China; Sepsis; Shock, Septic
PubMed: 35729526
DOI: 10.1186/s12879-022-07543-8 -
Critical Care Medicine Nov 2019Rapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our...
OBJECTIVES
Rapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination.
DESIGN
Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics.
SETTING
Urban, tertiary care center between January 1, 2014, and May 31, 2017.
PATIENTS
Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock.
INTERVENTIONS
Administration of IV fluids by bolus.
MEASUREMENTS AND MAIN RESULTS
In total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46-0.83), male (odds ratio, 0.66; CI, 0.49-0.87), obese (odds ratio, 0.18; CI, 0.13-0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13-0.40), heart failure (odds ratio, 0.42; CI, 0.29-0.60), or documented volume "overload" (odds ratio, 0.30; CI, 0.20-0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03-2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02-1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5-3.6), without differential effects for "at-risk" groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05).
CONCLUSIONS
Failure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.
Topics: Age Factors; Cohort Studies; Comorbidity; Emergency Service, Hospital; Female; Fluid Therapy; Hospital Mortality; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Middle Aged; Patient Admission; Resuscitation; Retrospective Studies; Sepsis; Sex Factors; Shock, Septic
PubMed: 31393324
DOI: 10.1097/CCM.0000000000003960 -
Clinical and Applied... Dec 2018Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition...
Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage. Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed.
Topics: Anticoagulants; Antithrombins; Clinical Trials, Phase III as Topic; Disseminated Intravascular Coagulation; Heparin; Humans; Lipoproteins; Protein C; Randomized Controlled Trials as Topic; Recombinant Proteins; Sepsis; Thrombomodulin
PubMed: 30296833
DOI: 10.1177/1076029618806424 -
Journal of the American Medical... Jan 2022To determine the effects of using unstructured clinical text in machine learning (ML) for prediction, early detection, and identification of sepsis.
OBJECTIVE
To determine the effects of using unstructured clinical text in machine learning (ML) for prediction, early detection, and identification of sepsis.
MATERIALS AND METHODS
PubMed, Scopus, ACM DL, dblp, and IEEE Xplore databases were searched. Articles utilizing clinical text for ML or natural language processing (NLP) to detect, identify, recognize, diagnose, or predict the onset, development, progress, or prognosis of systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock were included. Sepsis definition, dataset, types of data, ML models, NLP techniques, and evaluation metrics were extracted.
RESULTS
The clinical text used in models include narrative notes written by nurses, physicians, and specialists in varying situations. This is often combined with common structured data such as demographics, vital signs, laboratory data, and medications. Area under the receiver operating characteristic curve (AUC) comparison of ML methods showed that utilizing both text and structured data predicts sepsis earlier and more accurately than structured data alone. No meta-analysis was performed because of incomparable measurements among the 9 included studies.
DISCUSSION
Studies focused on sepsis identification or early detection before onset; no studies used patient histories beyond the current episode of care to predict sepsis. Sepsis definition affects reporting methods, outcomes, and results. Many methods rely on continuous vital sign measurements in intensive care, making them not easily transferable to general ward units.
CONCLUSIONS
Approaches were heterogeneous, but studies showed that utilizing both unstructured text and structured data in ML can improve identification and early detection of sepsis.
Topics: Humans; Machine Learning; Natural Language Processing; Sepsis; Shock, Septic; Vital Signs
PubMed: 34897469
DOI: 10.1093/jamia/ocab236 -
American Journal of Respiratory and... May 2015Limited data exist about the international burden of severe sepsis in critically ill children.
RATIONALE
Limited data exist about the international burden of severe sepsis in critically ill children.
OBJECTIVES
To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials.
METHODS
A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality.
MEASUREMENTS AND MAIN RESULTS
Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group.
CONCLUSIONS
Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.
Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Databases, Factual; Global Health; Hospital Mortality; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Multiple Organ Failure; Outcome and Process Assessment, Health Care; Prevalence; Prospective Studies; Respiration, Artificial; Sepsis
PubMed: 25734408
DOI: 10.1164/rccm.201412-2323OC