Medicine › Epidemiology

Sepsis Diagnosis and Treatment

Works Count: 58416

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Description

This cluster of papers focuses on the epidemiology, diagnosis, management, and prognosis of sepsis and septic shock. It covers topics such as the definition of sepsis, assessment of clinical criteria, evaluation of prediction models, use of biomarkers, antimicrobial therapy, and the impact of various factors on patient outcomes in critical care settings.

Keywords

Sepsis; Septic Shock; Epidemiology; Management; Prognostic Models; Infection; Critical Care; Biomarkers; Antimicrobial Therapy; Microcirculation

The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure

1996-07-01

Jean‐Louis Vincent , Rui P. Moreno , Jukka Takala +6 more

Serial Evaluation of the SOFA Score to Predict Outcome in Critically Ill Patients

2001-10-10

Flávio Lopes Ferreira

Evaluation of trends in organ dysfunction in critically ill patients may help predict outcome.To determine the usefulness of repeated measurement the Sequential Organ Failure Assessment (SOFA) score for prediction of … Evaluation of trends in organ dysfunction in critically ill patients may help predict outcome.To determine the usefulness of repeated measurement the Sequential Organ Failure Assessment (SOFA) score for prediction of mortality in intensive care unit (ICU) patients.Prospective, observational cohort study conducted from April 1 to July 31, 1999.A 31-bed medicosurgical ICU at a university hospital in Belgium.Three hundred fifty-two consecutive patients (mean age, 59 years) admitted to the ICU for more than 24 hours for whom the SOFA score was calculated on admission and every 48 hours until discharge.Initial SOFA score (0-24), Delta-SOFA scores (differences between subsequent scores), and the highest and mean SOFA scores obtained during the ICU stay and their correlations with mortality.The initial, highest, and mean SOFA scores correlated well with mortality. Initial and highest scores of more than 11 or mean scores of more than 5 corresponded to mortality of more than 80%. The predictive value of the mean score was independent of the length of ICU stay. In univariate analysis, mean and highest SOFA scores had the strongest correlation with mortality, followed by Delta-SOFA and initial SOFA scores. The area under the receiver operating characteristic curve was largest for highest scores (0.90; SE, 0.02; P<.001 vs initial score). When analyzing trends in the SOFA score during the first 96 hours, regardless of the initial score, the mortality rate was at least 50% when the score increased, 27% to 35% when it remained unchanged, and less than 27% when it decreased. Differences in mortality were better predicted in the first 48 hours than in the subsequent 48 hours. There was no significant difference in the length of stay among these groups. Except for initial scores of more than 11 (mortality rate >90%), a decreasing score during the first 48 hours was associated with a mortality rate of less than 6%, while an unchanged or increasing score was associated with a mortality rate of 37% when the initial score was 2 to 7 and 60% when the initial score was 8 to 11.Sequential assessment of organ dysfunction during the first few days of ICU admission is a good indicator of prognosis. Both the mean and highest SOFA scores are particularly useful predictors of outcome. Independent of the initial score, an increase in SOFA score during the first 48 hours in the ICU predicts a mortality rate of at least 50%.

The Pathophysiology and Treatment of Sepsis

2003-01-08

Richard S. Hotchkiss , Irene E. Karl

Sepsis is the leading cause of death in critically ill patients in the United States. Yet the individual host response to septicemia is variable, depending on the patient's immune response, … Sepsis is the leading cause of death in critically ill patients in the United States. Yet the individual host response to septicemia is variable, depending on the patient's immune response, age, nutritional status, and coexisting conditions, as well as on the virulence of the organism and the size of the inoculum. This review examines evolving concepts of sepsis and discusses new and potential therapies. Recent clinical advances include therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit. Future therapies may be focused on modulating the immune response in the light of the characteristics of the specific pathogen, the genetic profile of the patient, and the duration of the disease.

Receiver Operating Characteristic Curve in Diagnostic Test Assessment

2010-08-26

Jayawant N. Mandrekar

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Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units

1998-11-01

Jean‐Louis Vincent , Arnaldo de Mendonça , F. Cantraine +6 more

Objective To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients. Design Prospective, multicenter study. … Objective To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients. Design Prospective, multicenter study. Setting Forty intensive care units (ICUs) in 16 countries. Patients Patients admitted to the ICU in May 1995 (n = 1,449), excluding patients who underwent uncomplicated elective surgery with an ICU length of stay <48 hrs. Interventions None. Measurements and Main Results The main outcome measures included incidence of dysfunction/failure of different organs and the relationship of this dysfunction with outcome. In this cohort of patients, the median length of ICU stay was 5 days, and the ICU mortality rate was 22%. Multiple organ dysfunction and high SOFA scores for any individual organ were associated with increased mortality. The presence of infection on admission (28.7% of patients) was associated with higher SOFA scores for each organ. The evaluation of a subgroup of 544 patients who stayed in the ICU for at least 1 wk showed that survivors and nonsurvivors followed a different course. This subgroup had greater respiratory, cardiovascular, and neurologic scores than the other patients. In this subgroup, the total SOFA score increased in 44% of the nonsurvivors but in only 20% of the survivors (p < .001). Conversely, the total SOFA score decreased in 33% of the survivors compared with 21% of the nonsurvivors (p < .001). Conclusions The SOFA score is a simple, but effective method to describe organ dysfunction/failure in critically ill patients. Regular, repeated scoring enables patient condition and disease development to be monitored and better understood. The SOFA score may enable comparison between patients that would benefit clinical trials. (Crit Care Med 1998; 26:1793-1800)

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*

2006-04-19

Anand Kumar , Daniel Roberts , Kenneth E. Wood +7 more

Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design: A retrospective cohort … Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design: A retrospective cohort study performed between July 1989 and June 2004. Setting: Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States. Patients: Medical records of 2,731 adult patients with septic shock. Interventions: None. Measurements and Main Results: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103–1.136, p < .0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12–2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25–75th percentile, 2.0–15.0 hrs). Conclusions: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.

Acute Physiology and Chronic Health Evaluation (APACHE) IV: Hospital mortality assessment for today’s critically ill patients*

2006-03-15

Jack E. Zimmerman , Andrew A. Kramer , Douglas McNair +1 more

To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) method for predicting hospital mortality among critically ill adults and to evaluate changes in the accuracy of … To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) method for predicting hospital mortality among critically ill adults and to evaluate changes in the accuracy of earlier APACHE models.: Observational cohort study.A total of 104 intensive care units (ICUs) in 45 U.S. hospitals.A total of 131,618 consecutive ICU admissions during 2002 and 2003, of which 110,558 met inclusion criteria and had complete data.None.We developed APACHE IV using ICU day 1 information and a multivariate logistic regression procedure to estimate the probability of hospital death for randomly selected patients who comprised 60% of the database. Predictor variables were similar to those in APACHE III, but new variables were added and different statistical modeling used. We assessed the accuracy of APACHE IV predictions by comparing observed and predicted hospital mortality for the excluded patients (validation set). We tested discrimination and used multiple tests of calibration in aggregate and for patient subgroups. APACHE IV had good discrimination (area under the receiver operating characteristic curve = 0.88) and calibration (Hosmer-Lemeshow C statistic = 16.9, p = .08). For 90% of 116 ICU admission diagnoses, the ratio of observed to predicted mortality was not significantly different from 1.0. We also used the validation data set to compare the accuracy of APACHE IV predictions to those using APACHE III versions developed 7 and 14 yrs previously. There was little change in discrimination, but aggregate mortality was systematically overestimated as model age increased. When examined across disease, predictive accuracy was maintained for some diagnoses but for others seemed to reflect changes in practice or therapy.APACHE IV predictions of hospital mortality have good discrimination and calibration and should be useful for benchmarking performance in U.S. ICUs. The accuracy of predictive models is dynamic and should be periodically retested. When accuracy deteriorates they should be revised and updated.

Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care

2001-07-01

Derek C. Angus , Walter T. Linde‐Zwirble , Jeffrey Lidicker +3 more

Objective To determine the incidence, cost, and outcome of severe sepsis in the United States. Design Observational cohort study. Setting All nonfederal hospitals (n = 847) in seven U.S. states. … Objective To determine the incidence, cost, and outcome of severe sepsis in the United States. Design Observational cohort study. Setting All nonfederal hospitals (n = 847) in seven U.S. states. Patients All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. Interventions None. Measurements and Main Results We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. Conclusions Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Sepsis in European intensive care units: Results of the SOAP study*

2006-01-17

Jean‐Louis Vincent , Yasser Sakr , Charles L. Sprung +7 more

To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units.Cohort, multiple-center, observational study.One hundred and ninety-eight intensive care units in 24 … To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units.Cohort, multiple-center, observational study.One hundred and ninety-eight intensive care units in 24 European countries.All new adult admissions to a participating intensive care unit between May 1 and 15, 2002.None.Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries.This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics*

2005-01-01

Brahm Goldstein , Brett P. Giroir , Adrienne G. Randolph

Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the … Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children.Consensus conference.This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting.Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations.We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

APACHE—acute physiology and chronic health evaluation: a physiologically based classification system

1981-08-01

William A. Knaus , Jack E. Zimmerman , Douglas P. Wagner +2 more

Investigations describing the utilization pattern and documenting the value of intensive care are limited by the lack of a reliable and valid classification system. In this paper, the authors describe … Investigations describing the utilization pattern and documenting the value of intensive care are limited by the lack of a reliable and valid classification system. In this paper, the authors describe the development and initial validation of acute physiology and chronic health evaluation (APACHE), a physiologically based classification system for measuring severity of illness in groups of critically ill patients. APACHE uses information available in the medical record. In studies on 582 admissions to a university hospital ICU and 223 admissions to a community hospital ICU, APACHE was reliable in classifying ICU admissions. In validation studies involving these 805 admissions, the acute physiology score of APACHE demonstrated consistent agreement with subsequent therapeutic effort and mortality. This was true for a broad range of patient groups using a variety of sensitivity analyses. After successful completion of multi-institutional validation studies, the APACHE classification system could be used to control for case mix, compare outcomes, evaluate new therapies, and study the utilization of ICUs.

PRISM III

1996-05-01

Murray M. Pollack , Kantilal M. Patel , Urs E. Ruttimann

Objectives The relationship between physiologic status and mortality risk should be reevaluated as new treatment protocols, therapeutic interventions, and monitoring strategies are introduced, and as patient populations change. We developed … Objectives The relationship between physiologic status and mortality risk should be reevaluated as new treatment protocols, therapeutic interventions, and monitoring strategies are introduced, and as patient populations change. We developed and validated a third-generation pediatric physiology-based score for mortality risk, Pediatric Risk of Mortality III (PRISM III). Design Prospective cohort. Setting There were 32 pediatric intensive care units (ICUs): 16 pediatric ICUs were randomly chosen and 16 volunteered. Patients Consecutive admissions at each site were included until at least 11 deaths per site occurred. Measurements and Main Results Physiologic data included the most abnormal values from the first 12 and the second 12 hrs of ICU stay. Outcomes and descriptive data were also collected. Physiologic variables where normal values change with age were stratified by age (neonate, infant, child, adolescent). The database was randomly split into development (90%) and validation (10%) sets. Variables and their ranges were chosen by computing the risk of death (odds ratios) relative to the midrange of survivors for each physiologic variable. Univariate and multivariate statistical procedures, including multiple logistic regression analysis, were used to develop the PRISM III score and mortality risk predictors. Data were collected on 11,165 admissions (543 deaths). The PRISM III score has 17 physiologic variables subdivided into 26 ranges. The variables most predictive of mortality were minimum systolic blood pressure, abnormal pupillary reflexes, and stupor/coma. Other risk factors, including two acute and two chronic diagnoses, and four additional risk factors, were used in the final predictors. The PRISM III score and the additional risk factors were applied to the first 12 hrs of stay (PRISM III-12) and the first 24 hrs of stay (PRISM III-24). The Hosmer-Lemeshow chi-square goodness-of-fit evaluations demonstrated absence of significant calibration errors (p values: PRISM III-12 development equals .2496; PRISM III-24 development equals .1374; PRISM III-12 validation equals .4168; PRISM III-24 validation equals .5504). The area under the receiver operating curve and Flora's z-statistic indicated excellent discrimination and accuracy (area under the receiver operating curve--PRISM III-12 development 947 plus minus 0.007; PRISM III-24 development 0.958 plus minus 0.006; PRISM III-12 validation 0.941 plus minus 0.021; PRISM III-24 validation 0.944 plus minus 0.021; Flora's z-statistic--PRISM III-12 validation equals .7479; PRISM III-24 validation equals .9225), although generally, the PRISM III-24 performed better than the PRISM III-12 models. Excellent goodness-of-fit was also found for patient groups stratified by age (significance levels: PRISM III-12 equals .1622; PRISM III-24 equals .4137), and by diagnosis (significance levels: PRISM III-12 equals .5992; PRISM III-24 equals .7939). Conclusions PRISM III resulted in several improvements over the original PRISM. Reassessment of physiologic variables and their ranges, better age adjustment for selected variables, and additional risk factors resulted in a mortality risk model that is more accurate and discriminates better. The large number of diverse ICUs in the database indicates PRISM III is more likely to be representative of United States units. (Crit Care Med 1996; 24:743-752)

Multiple Organ Dysfunction Score

1995-10-01

John C. Marshall , Deborah J. Cook , Nicolas V. Christou +3 more

To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness.Systematic literature review; prospective cohort study.Surgical intensive care unit (ICU) … To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness.Systematic literature review; prospective cohort study.Surgical intensive care unit (ICU) of a tertiary-level teaching hospital.All patients (n = 692) admitted for > 24 hrs between May 1988 and March 1990.None.Computerized database review of MEDLINE identified clinical studies of multiple organ failure that were published between 1969 and 1993. Variables from these studies were evaluated for construct and content validity to identify optimal descriptors of organ dysfunction. Clinical and laboratory data were collected daily to evaluate the performance of these variables individually and in aggregate as an organ dysfunction score. Seven systems defined the multiple organ dysfunction syndrome in more than half of the 30 published reports reviewed. Descriptors meeting criteria for construct and content validity could be identified for five of these seven systems: a) the respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine concentration); c) the hepatic system (serum bilirubin concentration); d) the hematologic system (platelet count); and e) the central nervous system (Glasgow Coma Scale). In the absence of an adequate descriptor of cardiovascular dysfunction, we developed a new variable, the pressure-adjusted heart rate, which is calculated as the product of the heart rate and the ratio of central venous pressure to mean arterial pressure. These candidate descriptors of organ dysfunction were then evaluated for criterion validity (ICU mortality rate) using the clinical database. From the first half of the database (the development set), intervals for the most abnormal value of each variable were constructed on a scale from 0 to 4 so that a value of 0 represented essentially normal function and was associated with an ICU mortality rate of < 5%, whereas a value of 4 represented marked functional derangement and an ICU mortality rate of > or = 50%. These intervals were then tested on the second half of the data set (the validation set). Maximal scores for each variable were summed to yield a Multiple Organ Dysfunction Score (maximum of 24). This score correlated in a graded fashion with the ICU mortality rate, both when applied on the first day of ICU admission as a prognostic indicator and when calculated over the ICU stay as an outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12 points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of > 20 points. The score showed excellent discrimination, as reflected in areas under the receiver operating characteristic curve of 0.936 in the development set and 0.928 in the validation set. The incremental increase in scores over the course of the ICU stay (calculated as the difference between maximal scores and those scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction Score]) also demonstrated a strong correlation with the ICU mortality rate. In a logistic regression model, this incremental increase in scores accounted for more of the explanatory power than admission severity indices.This multiple organ dysfunction score, constructed using simple physiologic measures of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist sees it and correlates strongly with the ultimate risk of ICU mortality and hospital mortality. The variable, delta Multiple Organ Dysfunction Score, reflects organ dysfunction developing during the ICU stay, which therefore is potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

2003-04-01

Mitchell M. Levy , Mitchell P. Fink , John C. Marshall +7 more

Objective In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a … Objective In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. Design Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the SCCM, The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). Methods The conference was attended by 29 participants from Europe and North America. In advance of the conference, five subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The subgroups corresponded electronically before the conference and met in person during the conference. A spokesperson for each group presented the deliberation of each group to all conference participants during a plenary session. A writing committee was formed at the conference and developed the current article based on executive summary documents generated by each group and the plenary group presentations. The present article serves as the final report of the 2001 International Sepsis Definitions Conference. Conclusion This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence exists to support a change to the definitions. This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research.

The immunopathogenesis of sepsis

2002-12-01

Jonathan B. Cohen

A Randomized Trial of Protocol-Based Care for Early Septic Shock

2014-03-18

Donald M. Yealy , John A. Kellum , David T. Huang +7 more

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who … In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.

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Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine

1993-04-01

M H Zweig , Gregory Campbell

The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to … The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.

Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

2008-02-27

James A. Russell , Keith R. Walley , Joel Singer +7 more

Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as … Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors.In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions.A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10).Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).

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Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

2007-12-03

R. Phillip Dellinger , Mitchell M. Levy , Jean Carlet +7 more

To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Modified Delphi … To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

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The Natural History of the Systemic Inflammatory Response Syndrome (SIRS)

1995-01-11

M. Sigfrido Rangel‐Frausto , Didier Pittet , Michele Costigan +3 more

Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock.Prospective cohort study with a … Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock.Prospective cohort study with a follow-up of 28 days or until discharge if earlier.Three intensive care units and three general wards in a tertiary health care institution.Patients were included if they met at least two of the criteria for SIRS: fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count.Development of any stage of the biologic response to infection: sepsis, severe sepsis, septic shock, end-organ dysfunction, and death.During the study period 3708 patients were admitted to the survey units, and 2527 (68%) met the criteria for SIRS. The incidence density rates for SIRS in the surgical, medical, and cardiovascular intensive care units were 857, 804, and 542 episodes per 1000 patient-days, respectively, and 671, 495, and 320 per 1000 patient-days for the medical, cardiothoracic, and general surgery wards, respectively. Among patients with SIRS, 649 (26%) developed sepsis, 467 (18%) developed severe sepsis, and 110 (4%) developed septic shock. The median interval from SIRS to sepsis was inversely correlated with the number of SIRS criteria (two, three, or all four) that the patients met. As the population of patients progressed from SIRS to septic shock, increasing proportions had adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and shock. Positive blood cultures were found in 17% of patients with sepsis, in 25% with severe sepsis, and in 69% with septic shock. There were also stepwise increases in mortality rates in the hierarchy from SIRS, sepsis, severe sepsis, and septic shock: 7%, 16%, 20%, and 46%, respectively. Of interest, we also observed equal numbers of patients who appeared to have sepsis, severe sepsis, and septic shock but who had negative cultures. They had been prescribed empirical antibiotics for a median of 3 days. The cause of the systemic inflammatory response in these culture-negative populations is unknown, but they had similar morbidity and mortality rates as the respective culture-positive populations.This prospective epidemiologic study of SIRS and related conditions provides, to our knowledge, the first evidence of a clinical progression from SIRS to sepsis to severe sepsis and septic shock.

A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study

1993-12-22

J. R. Le Gall

<h3>Objective.</h3> —To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert … <h3>Objective.</h3> —To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. <h3>Design and Setting.</h3> —The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. <h3>Patients.</h3> —The 13 152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. <h3>Outcome Measure.</h3> —Vital status at hospital discharge. <h3>Results.</h3> —The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (<i>P</i>=.883 and<i>P</i>=.104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. <h3>Conclusion.</h3> —The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units. (<i>JAMA</i>. 1993;270:2957-2963)

Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

2004-07-09

Lauren M. Simon , F. Gauvin , Devendra Amre +2 more

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that … A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations

2015-09-28

Carolin Fleischmann-Struzek , André Scherag , Neill K. J. Adhikari +5 more

Rationale: Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.Objectives: To estimate the worldwide incidence and … Rationale: Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.Objectives: To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies.Methods: We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.Measurements and Main Results: The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215–386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98–226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334–571; τ = 0.38) for sepsis and 270 (95% CI, 176–412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually.Conclusions: Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

The Epidemiology of Sepsis in the United States from 1979 through 2000

2003-04-16

Greg S. Martin , David M. Mannino , Stephanie Eaton +1 more

Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated … Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome.

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2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

2003-03-28

Mitchell M. Levy , Mitchell P. Fink , John C. Marshall +7 more

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

2001-11-08

Emanuel P. Rivers , Bryant Nguyen , Suzanne Havstad +5 more

Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery … Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit.

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Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

2004-03-03

R. Phillip Dellinger , Jean Carlet , Henry Masur +7 more

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Severe Sepsis and Septic Shock

2013-08-28

Derek C. Angus , Tom van der Poll

epsis is one of the oldest and most elusive syndromes in medicine.Hippocrates claimed that sepsis (σ ήψις) was the process by which flesh rots, swamps generate foul airs, and wounds … epsis is one of the oldest and most elusive syndromes in medicine.Hippocrates claimed that sepsis (σ ήψις) was the process by which flesh rots, swamps generate foul airs, and wounds fester. 1 Galen later considered sepsis a laudable event, necessary for wound healing. 2 With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was recast as a systemic infection, often described as "blood poisoning," and assumed to be the result of the host's invasion by pathogenic organisms that then spread in the bloodstream.However, with the advent of modern antibiotics, germ theory did not fully explain the pathogenesis of sepsis: many patients with sepsis died despite successful eradication of the inciting pathogen.Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis. 3n 1992, an international consensus panel defined sepsis as a systemic inflammatory response to infection, noting that sepsis could arise in response to multiple infectious causes and that septicemia was neither a necessary condition nor a helpful term. 4Instead, the panel proposed the term "severe sepsis" to describe instances in which sepsis is complicated by acute organ dysfunction, and they codified "septic shock" as sepsis complicated by either hypotension that is refractory to fluid resuscitation or by hyperlactatemia.In 2003, a second consensus panel endorsed most of these concepts, with the caveat that signs of a systemic inflammatory response, such as tachycardia or an elevated white-cell count, occur in many infectious and noninfectious conditions and therefore are not helpful in distinguishing sepsis from other conditions. 5Thus, "severe sepsis" and "sepsis" are sometimes used interchangeably to describe the syndrome of infection complicated by acute organ dysfunction. Incidence a nd C ause sThe incidence of severe sepsis depends on how acute organ dysfunction is defined and on whether that dysfunction is attributed to an underlying infection.Organ dysfunction is often defined by the provision of supportive therapy (e.g., mechanical ventilation), and epidemiologic studies thus count the "treated incidence" rather than the actual incidence.In the United States, severe sepsis is recorded in 2% of patients admitted to the hospital.Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions. 6,7The number of cases in the United States exceeds 750,000 per year 7 and was recently reported to be rising. 8However, several factors -new International Classification of Diseases, 9th Revision (ICD-9) coding rules, confusion over the distinction between septicemia and severe sepsis, the increasing capacity to provide intensive care, and increased awareness and surveillance -confound the interpretation of temporal trends.Studies from other high-income countries show similar rates of sepsis in the ICU. 9 The incidence of severe sepsis outside modern ICUs, especially in parts of

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Goal-Directed Resuscitation for Patients with Early Septic Shock

2014-10-01

Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with … Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).

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Developing a New Definition and Assessing New Clinical Criteria for Septic Shock

2016-02-22

Manu Shankar‐Hari , Gary Phillips , Mitchell L. Levy +6 more

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. To develop … 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. To develop a new definition and clinical criteria for identifying septic shock in adults. 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. Evidence for and agreement on septic shock definitions and criteria. 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. 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.

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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

2016-02-23

Mervyn Singer , Clifford S. Deutschman , Christopher W. Seymour +7 more

<h3>Importance</h3> 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, … <h3>Importance</h3> 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. <h3>Objective</h3> To evaluate and, as needed, update definitions for sepsis and septic shock. <h3>Process</h3> 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). <h3>Key Findings From Evidence Synthesis</h3> 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<i>severe sepsis</i>was redundant. <h3>Recommendations</h3> 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. <h3>Conclusions and Relevance</h3> 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.

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Assessment of Clinical Criteria for Sepsis

2016-02-22

Christopher W. Seymour , Jean‐Louis Vincent , Theodore J. Iwashyna +7 more

<h3>Importance</h3> The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis … <h3>Importance</h3> The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown. <h3>Objective</h3> To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. <h3>Design, Settings, and Population</h3> Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. <h3>Exposures</h3> Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). <h3>Main Outcomes and Measures</h3> For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). <h3>Results</h3> In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76;<i>P</i> < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76;<i>P</i> < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80;<i>P</i> < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77;<i>P</i> < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. <h3>Conclusions and Relevance</h3> Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.

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Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

2001-03-08

Gordon R. Bernard , Jean‐Louis Vincent , Pierre‐François Laterre +7 more

Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers … Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis.

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Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

2013-01-29

R.P. Dellinger , Mitchell M. Levy , Andrew Rhodes +7 more

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Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

2017-05-21

Christopher W. Seymour , Foster Gesten , Hallie C. Prescott +7 more

In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves … In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients.

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Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis

1992-06-01

Roger C. Bone , R.A. Balk , Frank B. Cerra +5 more

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Sepsis and septic shock

2018-06-21

Maurizio Cecconi , Laura Evans , Mitchell M. Levy +1 more

Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study

2020-01-01

Kristina E. Rudd , Sarah Charlotte Johnson , Kareha M Agesa +7 more

BackgroundSepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis … BackgroundSepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.MethodsWe used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.FindingsIn 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.InterpretationDespite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.FundingThe Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

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ISTH interim guidance on recognition and management of coagulopathy in COVID‐19

2020-03-26

Jecko Thachil , Ning Tang , Satoshi Gando +5 more

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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

2017-01-18

Andrew Rhodes , Laura Evans , Waleed Alhazzani +7 more

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Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

2008-01-01

R. Phillip Dellinger , Mitchell M. Levy , Jean Carlet +7 more

Objective: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. Design: … Objective: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. Design: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose <150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). Conclusions: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

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Surviving Sepsis Campaign

2013-01-26

R. Phillip Dellinger , Mitchell M. Levy , Andrew Rhodes +7 more

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing … To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

2017-01-18

Andrew Rhodes , Laura Evans , Waleed Alhazzani +7 more

Objective: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.” Design: A consensus committee of 55 international experts representing 25 international organizations … Objective: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.” Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

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Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

2021-10-02

Laura Evans , Andrew Rhodes , Waleed Alhazzani +7 more

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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021

2021-10-04

Laura Evans , Andrew Rhodes , Waleed Alhazzani +7 more

INTRODUCTION Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (1). Sepsis and septic shock are major healthcare problems, impacting millions of people around the world … INTRODUCTION Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (1). Sepsis and septic shock are major healthcare problems, impacting millions of people around the world each year and killing between one in three and one in six of those it affects (2–4). Early identification and appropriate management in the initial hours after the development of sepsis improve outcomes. The recommendations in this document are intended to provide guidance for the clinician caring for adult patients with sepsis or septic shock in the hospital setting. Recommendations from these guidelines cannot replace the clinician's decision-making capability when presented with a unique patient's clinical variables. These guidelines are intended to reflect best practice (Table 1). TABLE 1. - Table of Current Recommendations and Changes From Previous 2016 Recommendations Recommendations 2021 Recommendation Strength and Quality of Evidence Changes From 2016 Recommendations 1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. Strong , moderate-quality evidence (for screening) Changed from Best practice statement "We recommend that hospitals and hospital systems have a performance improvement program for sepsis including sepsis screening for acutely ill, high-risk patients." Strong , very low-quality evidence (for standard operating procedures) 2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single-screening tool for sepsis or septic shock. Strong , moderate-quality evidence NEW 3. For adults suspected of having sepsis, we suggest measuring blood lactate. Weak , low quality of evidence INITIAL RESUSCITATION 4. Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately. Best practice statement 5. For patients with sepsis induced hypoperfusion or septic shock we suggest that at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hr of resuscitation. Weak, low quality of evidence DOWNGRADE from Strong , low quality of evidence "We recommend that in the initial resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hr" 6. For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation, over physical examination, or static parameters alone. Weak , very low quality of evidence 7. For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. Weak , low quality of evidence 8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. Weak , low quality of evidence NEW MEAN ARTERIAL PRESSURE 9. For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets. Strong , moderate-quality evidence ADMISSION TO INTENSIVE CARE 10. For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 hr. Weak , low quality of evidence INFECTION 11. For adults with suspected sepsis or septic shock but unconfirmed infection, we recommend continuously re-evaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials if an alternative cause of illness is demonstrated or strongly suspected. Best practice statement 12. For adults with possible septic shock or a high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 hr of recognition. Strong , low quality of evidence (Septic shock) CHANGED from previous: "We recommend that administration of intravenous antimicrobials should be initiated as soon as possible after recognition and within one hour for both a) septic shock and b) sepsis without shock" Strong , very low quality of evidence (Sepsis without shock) strong recommendation , moderate quality of evidence 13. For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus noninfectious causes of acute illness. Best practice statement 14. For adults with possible sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for infection persists, the administration of antimicrobials within 3 hr from the time when sepsis was first recognized. Weak , very low quality of evidence NEW from previous: "We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock" strong recommendation , moderate quality of evidence 15. For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobials while continuing to closely monitor the patient. Weak , very low quality of evidence NEW from previous: "We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock" strong recommendation , moderate quality of evidence 16. For adults with suspected sepsis or septic shock, we suggest against using procalcitonin plus clinical evaluation to decide when to start antimicrobials, as compared to clinical evaluation alone. Weak , very low quality of evidence 17. For adults with sepsis or septic shock at high risk of MRSA, we recommend using empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage. Best practice statement NEW from previous: "We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage." Strong recommendation , moderate quality of evidence 18. For adults with sepsis or septic shock at low risk of MRSA, we suggest against using empiric antimicrobials with MRSA coverage, as compared with using antimicrobials without MRSA coverage. Weak , low quality of evidence NEW from previous: "We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage." Strong recommendation , moderate quality of evidence 19. For adults with sepsis or septic shock and high risk for multidrug resistant (MDR) organisms, we suggest using two antimicrobials with gram-negative coverage for empiric treatment over one gram-negative agent. Weak , very low quality of evidence 20. For adults with sepsis or septic shock and low risk for multidrug resistant (MDR) organisms, we suggest against using two gram-negative agents for empiric treatment, as compared to one gram-negative agent. Weak , very low quality of evidence 21. For adults with sepsis or septic shock, we suggest against using double gram-negative coverage once the causative pathogen and the susceptibilities are known. Weak , very low quality of evidence 22. For adults with sepsis or septic shock at high risk of fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy. Weak , low quality of evidence NEW from previous: "We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage." Strong recommendation , moderate quality of evidence 23. For adults with sepsis or septic shock at low risk of fungal infection, we suggest against empiric use of antifungal therapy Weak , low quality of evidence NEW from previous: "We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage. " Strong recommendation , moderate quality of evidence 24. We make no recommendation on the use of antiviral agents. No recommendation 25. For adults with sepsis or septic shock, we suggest using prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion. Weak , moderate-quality evidence 26. For adults with sepsis or septic shock, we recommend optimising dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic (PK/PD) principles and specific drug properties. Best practice statement 27. For adults with sepsis or septic shock, we recommend rapidly identifying or excluding a specific anatomical diagnosis of infection that requires emergent source control and implementing any required source control intervention as soon as medically and logistically practical. Best practice statement 28. For adults with sepsis or septic shock, we recommend prompt removal of intravascular access devices that are a possible source of sepsis or septic shock after other vascular access has been established. Best practice statement 29. For adults with sepsis or septic shock, we suggest daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment for de-escalation. Weak , very low quality of evidence 30. For adults with an initial diagnosis of sepsis or septic shock and adequate source control, we suggest using shorter over longer duration of antimicrobial therapy. Weak , very low quality of evidence 31. For adults with an initial diagnosis of sepsis or septic shock and adequate source control where optimal duration of therapy is unclear, we suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobials over clinical evaluation alone. Weak , low quality of evidence HEMODYNAMIC MANAGEMENT 32. For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation. Strong , moderate-quality evidence 33. For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation. Weak , low quality of evidence CHANGED from weak recommendation , low quality of evidence. "We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock" 34. For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids. Weak , moderate-quality evidence 35. For adults with sepsis or septic shock, we recommend against using starches for resuscitation. Strong , high-quality evidence 36. For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation. Weak , moderate-quality evidence UPGRADE from weak recommendation , low quality of evidence "We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock." 37. For adults with septic shock, we recommend using norepinephrine as the first-line agent over other vasopressors. Strong Dopamine. High-quality evidence Vasopressin. Moderate-quality evidence Epinephrine. Low quality of evidence Selepressin. Low quality of evidence Angiotensin II. Very low-quality evidence 38. For adults with septic shock on norepinephrine with inadequate mean arterial pressure levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine. Weak , moderate quality evidence 39. For adults with septic shock and inadequate mean arterial pressure levels despite norepinephrine and vasopressin, we suggest adding epinephrine. Weak , low quality of evidence 40. For adults with septic shock, we suggest against using terlipressin. Weak , low quality of evidence 41. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest either adding dobutamine to norepinephrine or using epinephrine alone. Weak , low quality of evidence 42. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest against using levosimendan. Weak , low quality of evidence NEW 43. For adults with septic shock, we suggest invasive monitoring of arterial blood pressure over noninvasive monitoring, as soon as practical and if resources are available. Weak , very low quality of evidence 44. For adults with septic shock, we suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying initiation until a central venous access is secured. Weak , very low quality of evidence NEW 45. There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hr of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after the initial resuscitation. No recommendation NEW "We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock" Weak recommendation , low quality of evidence "We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock." Weak recommendation , low quality of evidence VENTILATION 46.There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure. No recommendation 47. For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over noninvasive ventilation. Weak , low quality of evidence NEW 48. There is insufficient evidence to make a recommendation on the use of noninvasive ventilation in comparison to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure. No recommendation 49. For adults with sepsis-induced ARDS, we recommend using a low tidal volume ventilation strategy (6 mL/kg), over a high tidal volume strategy (> 10 mL/kg). Strong , high-quality evidence 50. For adults with sepsis-induced severe ARDS, we recommend using an upper limit goal for plateau pressures of 30 cm H2O, over higher plateau pressures. Strong , moderate-quality evidence 51. For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP. Weak , moderate-quality evidence 52. For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared with high tidal volume ventilation. Weak , low quality of evidence 53. For adults with sepsis-induced moderate-severe ARDS, we suggest using traditional recruitment maneuvers. Weak , moderate-quality evidence 54. When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy. Strong , moderate-quality evidence 55. For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for greater than 12 hr daily. Strong , moderate-quality evidence 56. For adults with sepsis induced moderate-severe ARDS, we suggest using intermittent NMBA boluses, over NMBA continuous infusion. Weak , moderate-quality evidence 57. For adults with sepsis-induced severe ARDS, we suggest using Veno-venous (VV) ECMO when conventional mechanical ventilation fails in experienced centers with the infrastructure in place to support its use. Weak , low quality of evidence NEW ADDITIONAL THERAPIES 58. For adults with septic shock and an ongoing requirement for vasopressor therapy we suggest using IV corticosteroids. Weak , moderate-quality evidence UPGRADE from Weak recommendation , low quality of evidence "We suggest against using IV hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). If this is not achievable, we suggest IV hydrocortisone at a dose of 200 mg/day." 59. For adults with sepsis or septic shock we suggest against using polymyxin B hemoperfusion. Weak , low quality of evidence NEW from previous: "We make no recommendation regarding the use of blood purification techniques" 60. There is insufficient evidence to make a recommendation on the use of other blood purification techniques. No recommendation 61. For adults with sepsis or septic shock we recommend using a restrictive (over liberal) transfusion strategy. Strong , moderate-quality evidence 62. For adults with sepsis or septic shock we suggest against using IV immunoglobulins. Weak , low quality of evidence 63. For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding, we suggest using stress ulcer prophylaxis. Weak , moderate-quality evidence 64. For adults with sepsis or septic shock, we recommend using pharmacologic venous thromboembolism (VTE) prophylaxis unless a contraindication to such therapy exists. Strong , moderate-quality evidence 65. For adults with sepsis or septic shock, we recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis Strong , moderate-quality evidence 66. For adults with sepsis or septic shock, we suggest against using mechanical VTE prophylaxis, in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone. Weak , low quality of evidence 67. In adults with sepsis or septic shock and AKI, we suggest using either continuous or intermittent renal replacement therapy. Weak , low quality of evidence 68. In adults with sepsis or septic shock and AKI, with no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy. Weak , moderate-quality evidence 69. For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180mg/dL (10 mmol/L). Strong , moderate-quality evidence 70. For adults with sepsis or septic shock we suggest against using IV vitamin C. Weak , low quality of evidence NEW 71. For adults with septic shock and hypoperfusion-induced lactic acidemia, we suggest against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements. Weak , low quality of evidence 72. For adults with septic shock and severe metabolic acidemia (pH ≤ 7.2) and acute kidney injury (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy Weak , low quality of evidence 73. For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 hr) initiation of enteral nutrition. Weak , very low quality of evidence LONG-TERM OUTCOMES AND GOALS OF CARE 74. For adults with sepsis or septic shock, we recommend discussing goals of care and prognosis with patients and families over no such discussion. Best practice statement 75. For adults with sepsis or septic shock, we suggest addressing goals of care early (within 72 hr) over late (72 hr or later). Weak , low quality of evidence 76. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on any specific standardized criterion to trigger goals of care discussion. No recommendation 77. For adults with sepsis or septic shock, we recommend that the principles of palliative care (which may include palliative care consultation based on clinician judgement) be integrated into the treatment plan, when appropriate, to address patient and family symptoms and suffering. Best practice statement 78. For adults with sepsis or septic shock, we suggest against routine formal palliative care consultation for all patients over palliative care consultation based on clinician judgement. Weak , low quality of evidence 79. For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral. Weak , very low quality of evidence 80. For adults with sepsis or septic shock, we suggest using a handoff process of critically important information at transitions of care over no such handoff process. Weak , very low quality of evidence 81. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on the use of any specific structured handoff tool over usual handoff processes. No recommendation 82. For adults with sepsis or septic shock and their families, we recommend screening for economic and social support (including housing, nutritional, financial, and spiritual support), and make referrals where available to meet these needs. Best practice statement 83. For adults with sepsis or septic shock and their families, we suggest offering written and verbal sepsis education (diagnosis, treatment, and post-ICU/post-sepsis syndrome) prior to hospital discharge and in the follow-up setting. Weak , very low quality of evidence 84. For adults with sepsis or septic shock and their families, we recommend the clinical team provide the opportunity to participate in shared decision making in post-ICU and hospital discharge planning to ensure discharge plans are acceptable and feasible. Best practice statement 85. For adults with sepsis and septic shock and their families, we suggest using a critical care transition program, compared with usual care, upon transfer to the floor. Weak , very low quality of evidence 86. For adults with sepsis and septic shock, we recommend reconciling medications at both ICU and hospital discharge. Best practice statement 87. For adult survivors of sepsis and septic shock and their families, we recommend including information about the ICU stay, sepsis and related diagnoses, treatments, and common impairments after sepsis in the written and verbal hospital discharge summary. Best practice statement 88. For adults with sepsis or septic shock who developed new impairments, we recommend hospital discharge plans include follow-up with clinicians able to support and manage new and long-term sequelae. Best practice statement 89. For adults with sepsis or septic shock and their families, there is insufficient evidence to make a recommendation on early post-hospital discharge follow-up compared with routine post-hospital discharge follow-up. No recommendation 90. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation for or against early cognitive therapy. No recommendation 91. For adult survivors of sepsis or septic shock, we recommend assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge. Best practice statement 92. For adult survivors of sepsis or septic shock, we suggest referral to a post-critical illness follow-up program if available. Weak , very low quality of evidence 93. For adult survivors of sepsis or septic shock receiving mechanical ventilation for > 48hr or an ICU stay of > 72 hr, we suggest referral to a post-hospital rehabilitation program. Weak , very low quality of evidence (References 5–24 are referred to in the Methodology section which can be accessed at Supplemental Digital Content: Methodology.) SCREENING AND EARLY TREATMENT Screening for Patients With Sepsis and Septic Shock - Recommendation 1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. Strong recommendation, moderate quality of evidence for screening. Strong recommendation, very low-quality evidence for standard operating procedures. Rationale Sepsis performance improvement programs generally consist of sepsis screening, education, measurement of sepsis bundle performance, patient outcomes, and actions for identified opportunities (25,26). Despite some inconsistency, a meta-analysis of 50 observational studies on the effect of performance improvement programs showed that these programs were associated with better adherence to sepsis bundles along with a reduction in mortality (OR, 0.66; 95% CI, 0.61–0.72) in patients with sepsis and septic shock (27). The specific components of performance improvement did not appear to be as important as the presence of a program that included sepsis screening and metrics. Sepsis screening tools are designed to promote early identification of sepsis and consist of manual methods or automated use of the electronic health record (EHR). There is wide variation in diagnostic accuracy of these tools with most having poor predictive values, although the use of some was associated with improvements in care processes (28–31). A variety of clinical variables and tools are used for sepsis screening, such as systemic inflammatory response syndrome (SIRS) criteria, vital signs, signs of infection, quick Sequential Organ Failure Score (qSOFA) or Sequential Organ Failure Assessment (SOFA) criteria, National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS) (26,32). Machine learning may improve performance of screening tools, and in a meta-analysis of 42,623 patients from seven studies for predicting hospital acquired sepsis the pooled area under the receiving operating curve (SAUROC) (0.89; 95% CI, 0.86−0.92); sensitivity (81%; 95% CI, 80−81), and specificity (72%; 95% CI, 72−72) was higher for machine learning than the SAUROC for traditional screening tools such as SIRS (0.70), MEWS (0.50), and SOFA (0.78) (32). Screening tools may target patients in various locations, such as in-patient wards, emergency departments, or ICUs (28–30,32). A pooled analysis of three RCTs did not demonstrate a mortality benefit of active screening (RR, 0.90; 95% CI, 0.51−1.58) (33–35). However, while there is wide variation in sensitivity and specificity of sepsis screening tools, they are an important component of identifying sepsis early for timely intervention. Standard operating procedures are a set of practices that specify a preferred response to specific clinical circumstances (36). Sepsis standard operating procedures, initially specified as Early Goal Directed Therapy have evolved to "usual care" which includes a standard approach with components of the sepsis bundle, early identification, lactate, cultures, antibiotics, and fluids (37). A large study examined the association between implementation of state-mandated sepsis protocols, compliance, and mortality. A retrospective cohort study of 1,012,410 sepsis admissions to 509 hospitals in the United States in a retrospective cohort examined mortality before (27 months) and after (30 months) implementation of New York state sepsis regulations, with a concurrent control population from four other states (38). In this comparative interrupted time series, mortality was lower in hospitals with higher compliance with achieving the sepsis bundles successfully. Lower resource countries may experience a different effect. A meta-analysis of two RCTs in Sub-Saharan Africa found higher mortality (RR, 1.26; 95% CI, 1.00−1.58) with standard operating procedures compared with usual care, while it was decreased in one observational study (adjusted hazard ratio [HR]; 95% CI, 0.55−0.98) (39). - Recommendation 2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock. Strong recommendation, moderate-quality evidence. Rationale The qSOFA uses three variables to predict death and prolonged ICU stay in patients with known or suspected sepsis: a Glasgow Coma Score < 15, a respiratory rate ≥ 22 breaths/min and a systolic blood pressure ≤ 100 mm Hg. When any two of these variables are present simultaneously, the patient is considered qSOFA positive. Data analysis used to support the recommendations of the Third International Consensus Conference on the Definitions of Sepsis identified qSOFA as a predictor of poor outcome in patients with known or suspected infection, but no analysis was performed to support its use as a screening tool (5). Since that time numerous studies have investigated the potential use of the qSOFA as a screening tool for sepsis (40–42). The results have been contradictory as to its usefulness. Studies have shown that qSOFA is more specific but less sensitive than having two of four SIRS criteria for early identification of infection induced organ dysfunction (40–43). Neither SIRS nor qSOFA are ideal screening tools for sepsis and the bedside clinician needs to understand the limitations of each. In the original derivation study, authors found that only 24% of infected patients had a qSOFA score 2 or 3, but these patients accounted for 70% of poor outcomes (5). Similar findings have also been found when comparing against the National Early warning Score (NEWS) and the Modified Early warning Score (MEWS) (44). Although the presence of a positive qSOFA should alert the clinician to the possibility of sepsis in all resource settings; given the poor sensitivity of the qSOFA, the panel issued a strong recommendation against its use as a single screening tool. -

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Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

2004-01-01

R. Philip Dellinger

Towards Definition, Clinical and Laboratory Criteria, and a Scoring System for Disseminated Intravascular Coagulation

2001-01-01

Fletcher B. Taylor , Cheng‐Hock Toh , Keith Hoots +2 more

* A detailed version of this article including 17 references, three tables and a long list of acknowledgements is available at http//www.isth.org * A detailed version of this article including 17 references, three tables and a long list of acknowledgements is available at http//www.isth.org

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

2004-03-01

R. Phillip Dellinger , Jean Carlet , Henry Masur +7 more

Objective In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the … Objective In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. Design The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. Methods We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. Results Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7–10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7–9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH ≥7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40–60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. Conclusion Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes available.

A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study

1993-12-22

Jean‐Roger Le Gall

APACHE II

1985-10-01

William A. Knaus , Elizabeth A. Draper , Douglas P. Wagner +1 more

This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine … This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.

Troponin I/albumin (TBI) Index: a new tool for the prediction of mortality in hospitalized patients with traumatic brain injury

2025-06-25

Lei Wang , Huamin Ge , Ziyi Wang +2 more | International Journal of Surgery

Comprehensive analysis and experimental validation of BST1 as a novel diagnostic biomarker for pediatric sepsis using multiple machine learning algorithms

2025-06-25

Yang Yang , Genhao Zhang | European Journal of Pediatrics

Hyperprocalcitonemia and Endothelial and Microcirculatory Dysfunction in Children With Sepsis and Septic Shock: Single-Center Observational Cohort Study in Colombia, 2021–2024

2025-06-25

Briam Beltrán Hernandez , Jaime Fernández‐Sarmiento , Hernando Mulett +7 more | Pediatric Critical Care Medicine

Objectives: To evaluate the association between hyperprocalcitonemia and endothelial and microcirculatory dysfunction in children with sepsis and septic shock and clinical outcomes. Design: A prospective observational cohort study, 2021–2024. Setting: … Objectives: To evaluate the association between hyperprocalcitonemia and endothelial and microcirculatory dysfunction in children with sepsis and septic shock and clinical outcomes. Design: A prospective observational cohort study, 2021–2024. Setting: A tertiary PICU with 15 medical-surgical beds in a university hospital. Patients: We included children with sepsis and/or septic shock who had serum procalcitonin measured at admission, 24 hours, and 48 hours, simultaneously with microcirculatory assessment using sublingual videomicroscopy and biomarkers of endothelial injury (syndecan-1, angiopoietin-2, and endocan). Hyperprocalcitonemia was defined as procalcitonin greater than 2 ng/mL. Interventions: None. Measurements and Main Results: In 230 patients, 43.9% (101/230) had hyperprocalcitonemia at PICU admission. After adjusting for confounders, children with hyperprocalcitonemia, compared with those with normal procalcitonin, had higher adjusted odds ratio (aOR [95% CI]) of reduced capillary blood flow at 24 hours (aOR, 1.35 [95% CI, 1.08–1.72]) and 48 hours (aOR, 1.14 [95% CI, 1.04–1.24]) after admission. At 24 hours, children with hyperprocalcitonemia compared with those without hyperprocalcitonemia had higher median (interquartile range [IQR]) syndecan-1 levels (125.87 ng/mL [IQR, 49.56–224.30 ng/mL] vs. 107.71 ng/mL [IQR, 62.82–156.55 ng/mL], respectively; p < 0.01) and greater odds of angiopoietin-2 elevation (aOR, 2.28 [95% CI, 1.08–5.17]; p = 0.042). Hyperprocalcitonemia with severe endothelial/microcirculatory dysfunction was associated with fluid overload greater than 10% (aOR, 2.01 [95% CI, 1.06–3.80]; p = 0.033), multiple organ dysfunction (aOR, 1.87 [95% CI, 1.01–3.57]; p = 0.041), and mortality (aOR, 1.66 [95% CI, 1.06–2.61]; p = 0.022). We failed to identify differences in capillary density (4–6 µm), angiopoietin-2, or Endocan between children with and without hyperprocalcitonemia at PICU admission. Conclusions: Children with sepsis and septic shock with hyperprocalcitonemia represent a phenotype characterized by endothelial and microvascular dysfunction, which is associated with worse clinical outcomes. Our study suggests that preserving microvascular integrity may be a therapeutic target to reduce microcirculatory damage and improve outcomes.

Sepsis und septischer Schock: bessere Ergebnisse durch kontinuierliche Antibiotikagabe

2025-06-25

| Intensivmedizin up2date

Evaluation of urine and blood culture discordance in urosepsis and septic shock in the emergency department

2025-06-24

Stefan Hatzl , Alexander S. Hauser , Dirk von Lewinski +2 more | European Journal of Emergency Medicine

Complete blood count (CBC)-derived indices at admission and short-term outcomes in ICU patients: a retrospective study

2025-06-24

R. R. Shukla , Vinutha Silvanus , Sagar Dahal +4 more | Annals of Medicine

CBC parameters relay comprehensive information about the cellular components of the blood (erythrocytes, leucocytes, and platelets) and get affected by acute and chronic physiological and pathological stresses, as evidenced by … CBC parameters relay comprehensive information about the cellular components of the blood (erythrocytes, leucocytes, and platelets) and get affected by acute and chronic physiological and pathological stresses, as evidenced by the derangements in their parameters. Clinicians have advocated for indices derived by combining the parameters of the CBC and suggested that these parameters can predict outcomes in various inflammatory situations. We aimed to investigate the possible correlation of these indices with short-term outcomes (mortality, duration of ICU, and hospital stay) in ICU-admitted cases in our study. We conducted a retrospective analytical study among patients admitted to the general ICU of Nepal Medical College, Kathmandu. Data collection was performed using records in the ICU register and electronic database. Records of at-admission CBC reports and other information pertaining to the eligible participants were retrieved. Various indices were calculated from the CBC parameters and analyzed for their associations with short-term outcomes. Among 486 ICU patients, 56% were male, and the mean age was 52.95 ± 18.85 years. The average length of the ICU stay was 2 days (1-4), and the total hospital stay was 6 days (3-10), with a 19.7% ICU death rate. Older age (≥68 years), low hemoglobin level (<8 g/dl), and the presence of sepsis with septic shock at admission were the strongest predictors of in-ICU mortality. NLR had some predictive power for in-ICU mortality with an AUC value of 0.55. While TLC alone did not differ significantly between survivors and non-survivors. Among CBC-derived parameters, the neutrophil-to-lymphocyte ratio had some predictive value for all-cause in-ICU mortality. Further research among etiology or diagnosis-specific cohorts of ICU patients that demonstrate dynamic changes in CBC-derived parameters may be needed to elucidate their role in patient outcomes.

Enfermería en la prevención de caídas en pacientes hospitalizados

2025-06-24

Ericka Lizbeth Marca Fajardo , Christel Alexandra Orellana Peláez | LATAM Revista Latinoamericana de Ciencias Sociales y Humanidades

La prevención de caídas constituye una intervención esencial dentro de los programas de seguridad del paciente para mejorar la atención de salud. El siguiente estudio tiene como objetivo determinar el … La prevención de caídas constituye una intervención esencial dentro de los programas de seguridad del paciente para mejorar la atención de salud. El siguiente estudio tiene como objetivo determinar el conocimiento que poseen los profesionales de enfermería en relación con la prevención de caídas en pacientes hospitalizados, para proponer estrategias que fortalezcan conocimientos y competencias. Se realizó un estudio cuantitativo descriptivo de corte transversal, realizado con 110 profesionales de enfermería que laboran en un hospital de segundo nivel de la cuidad de Machala. Los datos fueron recolectados por medio de un cuestionario validado y analizados mediante el coeficiente alfa de Cronbach, obteniendo un valor de 0,788 con un nivel de confianza de 95%. Los resultados señalan que el personal de enfermería posee un buen conocimiento respecto a la prevención de caídas en pacientes hospitalizados, además, existe un alto índice de la aplicación de estrategias preventivas a nivel general de los tres dominios evaluados, el 68,91% lo aplica siempre, el 29,90% a veces y el 1,19% nunca. En conclusión, el conocimiento sólido de enfermería para prevenir caídas es fundamental para garantizar cuidado de calidad en el paciente, asimismo, resulta fundamental fortalecer en la adherencia de protocolos y manuales existentes para que se brinde cuidado integral al usuario.

We Have New Sepsis Criteria for Children…Now What?

2025-06-23

Sarah B. Walker , Justin M. Lockwood , Halden F. Scott +2 more | Hospital Pediatrics

Unsupervised Machine Learning in Identification of Septic Shock Phenotypes and Their In-Hospital Outcomes: A Multicenter Cohort Study

2025-06-23

Song Peng Ang , Jia Ee Chia , Eunseuk Lee +3 more | Journal of Clinical Medicine

Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate … Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in host responses. Aim: To identify discrete subphenotypes of septic shock using admission demographics and laboratory parameters, and to evaluate their relationship with in-hospital outcomes. Methods: We conducted a retrospective multicenter cohort study of 10,462 adult patients with ICD-10-defined septic shock admitted to intensive care units between 2014 and 2015. We used Two-Step Cluster Analysis using log-likelihood distance and the Bayesian Information Criterion to identify two distinct phenotypes. We compared clusters on baseline characteristics, in-hospital outcomes including mortality, days on mechanical ventilation, vasopressor use, acute kidney injury (AKI), AKI requiring renal replacement therapy (RRT), and ICU and hospital lengths of stay. Results: We identified two clusters (Cluster 1, n = 5355 and Cluster 2, n = 5107) in our study. Cluster 1 showed greater biochemical severity at presentation, including higher median lactate (2.40 vs. 2.20 mmol L−1; p < 0.001), serum creatinine (1.39 vs. 1.20 mg dL−1; p < 0.001), blood urea nitrogen (28 vs. 25 mg dL−1; p < 0.001), and neutrophil-to-lymphocyte ratio (11.12 vs. 10.38; p < 0.001), and a higher mean SOFA score (7.05 ± 3.85 vs. 6.76 ± 3.87; p < 0.001). Despite this, Cluster 1 required mechanical ventilation more frequently (46.1% vs. 42.2%; p < 0.001) and had a higher incidence of AKI (58.1% vs. 55.6%; p = 0.009), including more stage 3 AKI (17.2% vs. 15.2%; p < 0.001) and dialysis (6.6% vs. 5.2%; p = 0.005), yet experienced similar in-hospital mortality (15.4% vs. 15.8%; p = 0.615) and comparable ICU (2.18 vs. 2.26 days; p = 0.254) and hospital lengths of stay (6.63 vs. 6.80 days; p = 0.251). Conclusions: Two septic shock phenotypes were identified, one with marked early organ dysfunction (Cluster 1) and another with milder initial derangements (Cluster 2), yet both showed convergent short-term mortality and lengths of stay despite divergent support needs. These results challenge reliance on single-parameter severity markers and underscore the need for phenotype-guided risk stratification and personalized management strategies in septic shock.

Unveiling the research advances of sepsis: pathogenesis, precise intervention and clinical perspective

2025-06-23

Lingxia Cheng , Yu Cao , Shihao Liu +5 more | International Journal of Surgery

Sepsis is a life-threatening multi-organ dysfunction caused by the dysregulated systemic inflammatory and immune responses in the host to an infection. Despite continuous advances in the treatment of sepsis, its … Sepsis is a life-threatening multi-organ dysfunction caused by the dysregulated systemic inflammatory and immune responses in the host to an infection. Despite continuous advances in the treatment of sepsis, its high morbidity and mortality seriously challenge global public health. Symptomatic treatments are currently applied to sepsis patients, while precise treatments acting on the individualized etiological and pathogenic factors are scant. To address the issue, the present review aims to illustrate the pathogenic mechanisms of Gram-negative bacteria, the immune imbalance of co-existing continuous inflammation and immunosuppression, and the increased susceptibility resulting from the imbalanced gut microbiota. Moreover, we summarized the therapeutic strategies for sepsis and the development of precise treatment acting on sepsis patients' individualized subphenotypes and immune statuses. From the perspectives of etiological factors, pathogenesis, and precision treatment, we provide new insights into the future treatment of sepsis.

LIÊN QUAN GIỮA QUÁ TẢI DỊCH TỚI KẾT QUẢ ĐIỀU TRỊ TRẺ DƯỚI 36 THÁNG TUỔI CẦN THỞ MÁY TẠI BỆNH VIỆN NHI TRUNG ƯƠNG

2025-06-23

Phúc Phan Hữu , Hường Bùi Thị Thu | Tạp chí Y học Việt Nam

Đặt vấn đề: Quá tải dịch (Fluid Overload-FO) là tình trạng hay gặp ở bệnh nhân nặng tại các đơn vị hồi sức cấp cứu. Nghiên cứu này nhằm xác … Đặt vấn đề: Quá tải dịch (Fluid Overload-FO) là tình trạng hay gặp ở bệnh nhân nặng tại các đơn vị hồi sức cấp cứu. Nghiên cứu này nhằm xác định mối liên quan quá tải dịch với kết quả điều trị ở trẻ dưới 36 tháng thở máy tại đơn vị hồi sức cấp cứu nhi khoa. Phương pháp: Nghiên cứu mô tả 245 bệnh nhân từ 1 tháng tới 36 tháng tuổi cần hỗ trợ thở máy xâm nhập >24 giờ tại Khoa Điều trị tích cực nội khoa, Bệnh viện Nhi Trung ương. Các dữ liệu về lâm sàng được thu thập tại thời điểm nhập viện và theo dõi hàng ngày. Quá tải dịch (FO) được xác định dựa vào lượng dịch vào ra hàng ngày và lượng dịch tích lũy trong 7 ngày đầu tại khoa. Tất cả bệnh nhân được theo dõi tới khi ra khỏi khoa ĐTTC hoặc tới ngày thứ 28 tại khoa. Áp dụng phân tích hồi quy logistic để xác định giá trị tiên lượng kết quả điều trị của các biến độc lập. Kết quả: Trong vòng 7 ngày nhập khoa hồi sức, 44,0% bệnh nhân có tình trạng quá tải dịch (FO ≥ 5%). Trong đó, 20,0% bệnh nhân có FO ≥ 10%; 9,0% có FO ≥ 15%. 71 (29,0%) bệnh nhân tử vong. Nguy cơ tử vong tăng dần theo mức độ quá tải dịch, (p<0,008). FO ≥ 10% tăng nguy tử vong 3 lần, (OR, 3,1, 95%CI 1,5 – 6,5), tăng nguy cơ cần lọc máu liên tục (OR, 3,2, 95%CI, 1,1 – 9,2), thời gian thở máy dài hơn (p=0.001). Kết luận: Quá tải dịch là tình trạng hay gặp và có tác động xấu tới kết quả điều trị ở trẻ dưới 36 tháng tuổi cần thở máy tại đơn vị hồi sức nhi khoa.

Statins could improve short-term prognosis in patients with traumatic brain injury: a propensity-matched cohort study

2025-06-23

Ping Li , Qiang Liu , Zhuo Zhang +1 more | Inflammopharmacology

Prevalence of Sepsis as Defined by Phoenix Sepsis Definition Among Children With COVID-19

2025-06-23

Sandeep Tripathi , Jeremy McGarvey , Vicki Montgomery +7 more | Hospital Pediatrics

INTRODUCTION A retrospective cohort study on patients aged &lt; 18 years included in the Society of Critical Care Medicine: Viral Infection and Respiratory Illness Universal Study registry from March 2020 … INTRODUCTION A retrospective cohort study on patients aged &lt; 18 years included in the Society of Critical Care Medicine: Viral Infection and Respiratory Illness Universal Study registry from March 2020 to April 2024 with an objective of calculating the prevalence of sepsis as defined by the Phoenix Sepsis Score (PSS) and to validate the PSS with respect to outcomes in children with COVID-19. METHODS Linear mixed-effects regression was used to examine the relationship between the PSS and hospital length of stay after controlling for confounding factors. The performance of the PSS was assessed using the receiver operating characteristic (ROC) and the precision-recall curve (PRC). Cross-validation was performed using leave-one-out cross-validation. RESULTS Out of 1731 patients (58 hospitals), 326 (18.8%) met criteria for sepsis and 167 (9.7%) for septic shock. The overall mortality was 1.4% (25/1731), with significant differences between nonseptic (10/1405, 0.7%) and both sepsis (15/326, 4.6%) and septic shock (9/167, 5.4%) groups. After adjusting for confounders, the septic group was associated with a longer hospital length of stay than the nonseptic group. One unit increase in the numeric PSS led to a 70% increase in risk of mortality (odds ratio 1.70; P &lt; .001). The area under the ROC curve was 0.80 and the area under the PRC curve was 0.13. The threshold of ≥ 2 for detection of mortality had a sensitivity of 0.63, specificity of 0.82, and positive predictive value of 0.05. CONCLUSION Phoenix Sepsis Criteria retain its validity in identifying sepsis in children with COVID-19 and can be used in further epidemiological studies in this population

Dynamic serum amyloid A for the prediction of the trajectory of ventilator-associated pneumonia in elderly patients with acute ischemic stroke undergoing endovascular therapy and general anesthesia

2025-06-22

Pi-xiong Su , Yong Ji | Archives of Medical Science

Introduction In patients with acute ischemic stroke (AIS), current models for predicting ventilator-associated pneumonia (VAP) predominantly rely on multi-parameter approaches, which significantly increase data collection complexity and hinder clinical implementation. … Introduction In patients with acute ischemic stroke (AIS), current models for predicting ventilator-associated pneumonia (VAP) predominantly rely on multi-parameter approaches, which significantly increase data collection complexity and hinder clinical implementation. Here, we further investigate VAP-related risk factors while dynamically analyzing the predictive value of serum amyloid A (SAA) levels for VAP, aiming to bridge the gap between biomarker-driven simplicity and clinical practicality. Material and methods 387 patients were ultimately enrolled and divided into two groups: non-VAP (n = 278) and VAP (n = 109). The least absolute shrinkage and selection operator (LASSO), univariate and multivariate logistic regression analyses were utilized to examine the independent risk factors associated with VAP. Calibration and decision curve analysis (DCA) curves were employed to assess the model's goodness of fit. Results A VAP prediction model incorporating seven multimodal clinical parameters, age, mechanical ventilation duration, DBP, admission NIHSS score, hs-CRP, TC, and SAA-T2, was developed, achieving exceptional predictive performance with an AUC (95% CI) of 0.961 (0.942-0.980). Based on single-parameter AUC values and DCA, SAA-T2 demonstrated the highest diagnostic efficacy and net clinical benefit. The diagnostic performance of Model1 and SAA-T2 yielded AUCs (95% CI) of 0.889 (0.853-0.924) and 0.885 (0.842-0.928), respectively, with no statistically significant difference between them. Notably, the addition of SAA-T2 to Model1 significantly enhanced its diagnostic accuracy for VAP. Conclusions We developed an excellent nomogram model incorporating seven clinical parameters to predict VAP. SAA-T2 may serve as a rapid and practical clinical indicator for predicting VAP in AIS patients, balancing accuracy with clinical feasibility.

Serum Lactate Levels and Their Correlation With Hospital Outcomes in ICU Patients With Shock: A Cross-Sectional Study at a Tertiary Care Center

2025-06-22

Murat Başer , R.R. Ganta , Charan Neeradi +1 more | Cureus

The effect of Colchicine IN Sepsis (COLINS): a study protocol for a randomized, double-blind, placebo-controlled trial

2025-06-21

Fariba Pourkarim , Ata Mahmoodpoor , Hassan Soleimanpour +4 more | Trials

Sepsis is a life-threatening condition with high mortality rates of up to 40% due to multiple organ dysfunction. Systemic inflammatory response plays a key role in the pathophysiology and progression … Sepsis is a life-threatening condition with high mortality rates of up to 40% due to multiple organ dysfunction. Systemic inflammatory response plays a key role in the pathophysiology and progression of this disease. Therefore, anti-inflammatory drugs can be considered as augmentation therapy for the management of the early phase of inflammation in septic patients, along with appropriate antimicrobial therapy and source control. Experimental studies suggest the beneficial effects of colchicine in animal septic models. However, the clinical effects of colchicine in the setting of sepsis have not been investigated yet. This prospective, double-blinded, placebo-controlled, randomized trial will be conducted at Imam Reza Hospital, the largest northwest referral hospital, in Tabriz, Iran. A total of 44 patients aged 18 to 80 years with sepsis diagnosis will be randomized 1:1 to receive colchicine 1 mg daily or placebo for 10 days. The primary outcome is interleukin-6 (IL-6) changes from the baseline through day 4. Sequential organ failure assessment (SOFA) and qSOFA scores will be evaluated at baseline, day 4, and day 10. Patients will be assessed regarding the need for supplemental oxygen, mechanical ventilation, and vasopressor from the randomization through day 4 and day 10. The Colchicine IN Sepsis (COLINS) trial will be the first to investigate colchicine's efficacy versus placebo in sepsis patients. The results of this trial will be a step forward in treating patients with sepsis. Clinical trial ID: IRCTID: IRCT20231017059748N1. Registration date: 21 October 2023. https://irct.behdasht.gov.ir/trial/73232 .

Characterization of limitations of life-sustaining therapy decisions and their impact on outcomes in adults with septic shock – Insights from a retrospective cohort

2025-06-21

Jolan Malherbe , Julien Charpentier , Clément Devautour +7 more | Journal of Critical Care

In-ICU and in-hospital deaths in critically ill patients are often subsequent to decisions of limitations of life-sustaining therapies (LLST). While septic shock remains associated with high mortality and reduced quality … In-ICU and in-hospital deaths in critically ill patients are often subsequent to decisions of limitations of life-sustaining therapies (LLST). While septic shock remains associated with high mortality and reduced quality of life in survivors, we addressed the frequency, the decision-making process, the determinants and the attributable mortality of LLST decisions in this setting. A retrospective (2008-2021) single-center study including consecutive adult patients with septic shock. LLST were distributed into early and delayed when taken within and after the first three days in the ICU, respectively. Determinants of LLST were assessed by multivariate logistic regression and LLST-attributable mortality was assessed after propensity score matching. The cohort comprised 907 patients with septic shock. On admission, median SOFA score was 10 [IQR 7-13] points. LLST were decided for 257 (28.3 %) patients after a median of 5 [IQR 2-10] days in the ICU. The first LLST decisions were taken within and after the first three days following ICU admission in 106 and 151 patients, respectively. Independent determinants associated with early LLST decisions were age, disease severity on admission and increasing year of admission. Delayed LLST decisions were significantly associated with comorbidities, duration of organ-support, in-ICU complications and platelet transfusion. The overall in-ICU mortality rate was 37.6 % and reached 75.9 % among patients with LLST. Among septic shock patients, LLST are frequent, increasingly decided soon after ICU admission, vary during the ICU stay and carry a negative impact on ICU survival.

Enhancing early mortality prediction for sepsis-associated acute respiratory distress syndrome patients via optimized machine learning algorithm: development and multiple databases’ validation of the SAFE-Mo

2025-06-20

Luofeng Jiang , Chuting Yu , Chuan Xie +2 more | International Journal of Surgery

Background Acute respiratory distress syndrome (ARDS) is associated with high mortality, with sepsis accounts for 31–34% of cases. Given the global burden of sepsis (508 cases per 100,000 person-years) and … Background Acute respiratory distress syndrome (ARDS) is associated with high mortality, with sepsis accounts for 31–34% of cases. Given the global burden of sepsis (508 cases per 100,000 person-years) and its association with 20% of all global deaths, early mortality prediction in patients with sepsis-associated ARDS is critical. This study developed and validated the Sepsis-associated ARDS Fatality Evaluation Model (SAFE-Mo), a machine learning model designed to predict early mortality in sepsis-associated ARDS patients, enabling earlier identification of high-risk individuals. Methods Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v3.0), eICU Collaborative Research Database (eICU CRD, v2.0), and Northwest ICU (NWICU, v0.1.0) using Structured Query Language. SAFE-Mo was constructed using machine learning algorithm (svmRadialSigma) focusing on median survival days among deceased patients as the primary outcome. The model’s performance was validated externally using the MIMIC-IV and eICU CRD database and compared against four commonly used clinical risk assessment models (acute physiology score III (APSIII), simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA), charlson comorbidity index (CCI)). Additionally, NWICU was used to further validate SAFE-Mo’s generalization. Discrimination, calibration, and clinical utility were evaluated using area under the curve (AUC), Decision Curve Analysis (DCA), and calibration curves. Results SAFE-Mo demonstrated superior predictive capability of early mortality compared to traditional models. It showed the largest reasonable risk threshold probability range and highest net benefit. Calibration curves indicated a slight overestimation of mortality risk overall. With our simple SAFE-Mo web page, SAFE-Mo can assist clinicians in identifying high-risk patients early, like patients with unusually high levels of lactate in sepsis-associated ARDS, assessing prognosis, and facilitating risk-adjusted comparisons of center-specific outcomes. Practical advantages include guiding personalized treatment strategies, determining the need for aggressive interventions, and optimizing resource utilization. Conclusion This study utilized the MIMIC-IV, eICU CRD, and NWICU databases to construct and validate a machine learning model, SAFE-Mo, which predicts early mortality in patients with sepsis-associated ARDS and outperforms traditional prediction models across all metrics. SAFE-Mo can guide clinicians to focus on critical indicators such as lactate, urine output, anion gap, and others, enabling appropriate measures to improve clinical outcomes for high-risk patients.

Prophylactic proton pump inhibitor use and all-cause mortality in adult sepsis patients: a retrospective analysis based on the MIMIC-IV database

2025-06-19

Chenchen Ma , Lixin Zhang , Min Wang +2 more | Frontiers in Pharmacology

Background Sepsis poses a significant threat to human health, and extensive research has examined the relationship between proton pump inhibitors (PPI) and adverse outcomes in patients with sepsis. However, a … Background Sepsis poses a significant threat to human health, and extensive research has examined the relationship between proton pump inhibitors (PPI) and adverse outcomes in patients with sepsis. However, a consensus on this issue remains elusive. Therefore, this study aims to develop a prognostic model to assess the effectiveness of prophylactic PPI administration in patients with sepsis. Methods A retrospective cohort study was conducted using the open-access Medical Information Mart for Intensive Care (MIMIC-IV) database. Patients diagnosed with sepsis according to the Sepsis-3.0 criteria were selected for inclusion. The primary outcome of interest was all-cause mortality occurring between 28 and 90 days following prophylactic PPI use. Secondary outcomes included in-hospital and intensive care unit (ICU) mortality, duration of hospital and ICU stays, and the incidence of adverse events. Stepwise Cox proportional hazards regression analysis was performed, and multivariate Cox regression models were developed and evaluated using receiver operating characteristic (ROC) curves. Additionally, Kaplan–Meier curves were utilized to compare patient survival at 28 and 90 days. Results This study included 18,198 sepsis patients. The results demonstrated that prophylactic PPI use was significantly associated with increased 90-day all-cause mortality following ICU admission ( P &lt; 0.001). Prediction models incorporating 28-day (training AUC 0.74; 95% CI 0.73–0.75) and 90-day (training AUC 0.73; 95% CI 0.72–0.74) outcomes exhibited superior accuracy compared to conventional CCI and SOFA scores. Notably, prophylactic PPI use reduced ICU stay by approximately 1 day in sepsis patients but did not reduce overall hospitalization. Additionally, PPI administration was linked to adverse events including hypoalbuminemia and opportunistic infections. Conclusion Prophylactic PPI use failed to improve 28-day or 90-day survival rates in adult sepsis patients. Although PPI use was associated with reduced ICU length of stay, it did not shorten total hospital stay duration. Additionally, PPI administration was linked to clinically significant adverse reactions.

Machine learning model for daily prediction of pediatric sepsis using Phoenix criteria

2025-06-19

Daniela Chanci , Jocelyn R. Grunwell , Alireza Rafiei +6 more | Pediatric Research

Neutrophil Lymphocyte Ratio and Clinical Outcome in Children Admitted to PICU: A Prospective Observational Study

2025-06-19

Prasanna Samynathan , Karthi Nallasamy , Prateek Bhatia +3 more | The Indian Journal of Pediatrics

Integration of genomics and transcriptomics predicts septic-associated acute lung injury genes

2025-06-19

Qiong Wu , Yingyuan Tang , Fenghua Zhang +3 more | Journal of Bio-X Research

Open data and Artificial Intelligence: A window of opportunity for septic patients in emergency departments

2025-06-19

Ángel Estella , Miguel Ángel Armengol de la Hoz , Juan González del Castillo | Emergencias

La sepsis sigue siendo una de las principales causas de mortalidad en los servicios de urgencias (SU). A pesar de los avances en definiciones y protocolos de manejo, la identificación … La sepsis sigue siendo una de las principales causas de mortalidad en los servicios de urgencias (SU). A pesar de los avances en definiciones y protocolos de manejo, la identificación temprana sigue siendo un desafío crítico debido a la presentación inespecífica de la enfermedad. El manejo inicial incluye tres pilares fundamentales: control del foco, antibióticos y reanimación hemodinámica, los cuales requieren intervención temprana. Herramientas como la escala SOFA, biomarcadores (proteína C reactiva, procalcitonina, lactato) y protocolos como el código sepsis han mejorado la detección y manejo. Sin embargo, la heterogeneidad clínica de la sepsis y las limitaciones de los modelos actuales dificultan su implementación universal. La inteligencia artificial (IA) se perfila como una herramienta clave para mejorar la detección temprana de sepsis mediante el análisis de grandes volúmenes de datos clínicos. Los datos abiertos, siguiendo principios FAIR (Findable, Accessible, Interoperable, Reusable), facilitan el desarrollo de algoritmos robustos y personalizados, minimizan sesgos y mejoran la colaboración científica. España genera enormes volúmenes de datos clínicos en sus SU, pero carece de una base de datos unificada. La creación de un sistema abierto con acuerdos de uso de datos permitiría el desarrollo de modelos predictivos específicos para su población. El uso de IA en combinación con bases de datos específicas promete mejorar la personalización del tratamiento, reducir la mortalidad y optimizar recursos en la atención de la sepsis, y así cambiar el paradigma actual del manejo clínico.

A novel, rapid, and practical prognostic model for sepsis patients based on dysregulated immune cell lactylation

2025-06-19

Chang Li , Mei He , PeiChi Shi +7 more | Frontiers in Immunology

Background Sepsis is a global health burden characterized by high heterogeneity and uncontrolled immune response, with a notable lack of reliable methods for early prognosis and risk stratification. Epigenetic modifications, … Background Sepsis is a global health burden characterized by high heterogeneity and uncontrolled immune response, with a notable lack of reliable methods for early prognosis and risk stratification. Epigenetic modifications, particularly lactylation, have recently emerged as key regulators in the early pathophysiology of sepsis. However, their potential for immune-related mortality risk stratification remains largely unexplored. This study aimed to investigate dynamic changes in lactylation during sepsis progression and to develop a rapid, lactylation-based prognostic signature. Methods Blood transcriptional profiles and single-cell RNA sequencing data from septic patients were analyzed to assess glycolytic activity and lactylation in relation to patient mortality. Patients were stratified into subgroups using k-means clustering based on lactylation levels. Machine learning algorithms, integrated with pseudotime trajectory reconstruction, were employed to map the temporal dynamics of lactylation. A prognostic model was then constructed using lactylation-associated hub genes and validated in external transcriptomic datasets, a prospective single-center clinical cohort. The underlying mechanism was further explored in vitro using human monocytes. Results The study systematically characterized the dynamic alterations in lactylation patterns and immune microenvironment across distinct patient clusters. A lactylation-based prognostic model was developed, comprising eight key genes (CD160, HELB, ING4, PIP5K1C, SRPRA, CDCA7, FAM3A, PPP1R15A), and demonstrated strong predictive performance for sepsis outcomes (AUC = 0.78 in the training cohort; AUC = 0.73 in the validation cohort). Temporal expression patterns of lactylation-related hub genes revealed dynamic immune responses throughout disease progression. In the prospective cohort of septic patients (N = 51), the model showed high predictive accuracy for survival, with AUCs of 0.82 (7-day), 0.80 (14-day), and 0.86 (28-day). Additionally, global lactylation levels were significantly elevated in THP-1 cells following treatment with Sephin1, a selective PPP1R15A inhibitor, suggesting a mechanistic link. Conclusions Lactylation is significantly associated with increased mortality risk in sepsis. The proposed individualized prognostic model, based on dysregulated immune cell metabolism, accurately predicts early mortality and may inform optimized clinical management of septic patients.

Sepsis et choc septique de l’adulte

2025-06-18

Charles de Roquetaillade , A. Bousta , J. Muchardt +1 more | EMC-Anesthésie réanimation/Encyclopédie médico-chirurgicale. Anesthésie, réanimation

Nonlinear relationship between fibrinogen-to-albumin ratio and mortality in critically ill patients with sepsis: a retrospective cohort study

2025-06-18

Daishan Jiang , Xiaoyu Yuan , Yanbo Shen +1 more | Frontiers in Nutrition

Background The fibrinogen-albumin ratio (FAR) is recognized as a prognostic biomarker in several diseases, but its role in sepsis remains controversial. To elucidate the relationship between FAR and mortality risk … Background The fibrinogen-albumin ratio (FAR) is recognized as a prognostic biomarker in several diseases, but its role in sepsis remains controversial. To elucidate the relationship between FAR and mortality risk in a large cohort of patients with sepsis. Methods In this retrospective cohort study, we analyzed clinical data from the Medical Information Mart for Intensive Care IV Database (version 2.2) to investigate the mortality of sepsis patients. We employed restricted cubic spline curves and Cox regression models to evaluate the effect of FAR on mortality and conducted subgroup analyses to verify the consistency of our primary findings. Results In our analysis of 4,615 sepsis patients, we observed that mortality risk initially decreased with increasing FAR values, reaching a minimum at approximately 94.5*10 −3 , before rising again. Cox regression analysis revealed differing hazard ratios (HRs) for FAR quartiles relative to the second quartile (Q2). At 28 days, adjusted HRs were 1.23 (95% CI: 1.03–1.46) for Q1, 1.14 (0.96–1.36) for Q3, and 1.11 (0.93–1.33) for Q4. By 90 days, these HRs adjusted to 1.25 (1.07–1.46) for Q1, 1.21 (1.04–1.41) for Q3, and 1.21 (1.03–1.42) for Q4. This pattern persisted at 1-year mortality, with HRs of 1.16 (1.00–1.33) for Q1, 1.22 (1.06–1.39) for Q3, and 1.24 (1.07–1.43) for Q4. Conclusion FAR exhibited a nonlinear, U-shaped association with mortality risk at 28 days, 90 days, and 1 year in patients with sepsis. These findings suggest that FAR may serve as a practical prognostic biomarker to support early risk stratification and clinical decision-making in sepsis care.

Plasma procalcitonin and C-reactive protein concentrations in dogs with bacterial sepsis and non-infectious systemic inflammatory response syndrome

2025-06-18

Johanna Rompf , Bérénice Lutz , Katja‐Nicole Adamik +7 more | Frontiers in Veterinary Science

Procalcitonin is a well-established biomarker of bacterial infections in human medicine, used to guide initiation and duration of antimicrobial treatment. C-reactive protein (CRP) is a frequently used marker of inflammation … Procalcitonin is a well-established biomarker of bacterial infections in human medicine, used to guide initiation and duration of antimicrobial treatment. C-reactive protein (CRP) is a frequently used marker of inflammation in dogs, but is not specific for bacterial infection. The main objective of this study was to determine kinetics of plasma PCT (pPCT) and CRP in dogs with sepsis, non-infectious systemic inflammatory response syndrome (nSIRS) and healthy dogs. This prospective, observational study included 17 dogs with sepsis, 16 with nSIRS and 15 healthy dogs. Hematologic parameters, pPCT and CRP were assessed on days 1, 2 and 3 in healthy dogs and on days 1, 2, 3 and 4 in dogs with nSIRS or sepsis. The shortened Acute Patient Physiologic and Laboratory Evaluation (APPLE fast ) score was calculated for dogs with sepsis and nSIRS. Plasma PCT was measured using a validated canine PCT ELISA. There was no significant difference in median pPCT between healthy dogs (110.3 pg/mL; IQR 74.7–138) and dogs with sepsis (81.6 pg/mL; IQR 50.1–157.1) or nSIRS (105.3 pg/mL; IQR 87.6–164.7). Prior antimicrobial treatment was not associated with a decrease in pPCT concentration in septic dogs. In the sepsis group, day 1 pPCT concentrations were significantly higher in non-survivors than in survivors ( p &lt; 0.05). In contrast, median CRP was above the reference range (&lt;10.5 mg/L) in dogs with nSIRS (100.7 mg/L; IQR 67–141.9) or sepsis (131.9 mg/L; IQR 75.7–194.8) and significantly decreased within the first 4 days of successful antimicrobial treatment of sepsis. In conclusion, while plasma PCT showed some prognostic value, it was not a useful biomarker for assessing the efficacy of the chosen antimicrobial treatment in dogs with sepsis.

Development and validation of a predictive model for invasive ventilation risk within 48 hours of admission in patients with early sepsis-associated acute kidney injury

2025-06-18

Hong Li , Bin Wang | Frontiers in Medicine

Objective To identify patients with early sepsis-associated acute kidney injury (SA-AKI) at high risk of requiring invasive ventilation within 48 h of admission, facilitating timely interventions to improve prognosis. Methods … Objective To identify patients with early sepsis-associated acute kidney injury (SA-AKI) at high risk of requiring invasive ventilation within 48 h of admission, facilitating timely interventions to improve prognosis. Methods This retrospective study included patients with early SA-AKI admitted to Dongyang People’s Hospital between January 2011 and October 2024 and Yiwu Tianxiang Dongfang Hospital between January 2016 and December 2024. Variables included age, blood parameters, and vital signs at admission. Patients were divided into training and validation cohorts. Independent risk factors were identified in the training cohort, and a nomogram was developed. The discriminatory ability was assessed using the area under the receiver operating characteristic curves (AUC). Calibration was assessed using GiViTI calibration plots, while clinical utility was evaluated via decision curve analysis (DCA). Validation was performed in the internal and external validation groups. Additional models based on Sequential Organ Failure Assessment (SOFA) and National Early Warning Score (NEWS) scores, machine learning models including Support Vector Machine (SVM), C5.0, Extreme Gradient Boosting (XGBoost), and an ensemble model were compared with the nomogram on the discrimination power using DeLong’s test. Results The key independent risk factors for invasive ventilation in patients with early SA-AKI included lactate, pro-BNP, albumin, peripheral oxygen saturation, and pulmonary infection. The nomogram demonstrated an AUC of 0.857 in the training cohort (Hosmer-Lemeshow P = 0.533), 0.850 in the inner-validation cohort (Hosmer-Lemeshow P = 0.826) and 0.791 in the external validation cohort (Hosmer-Lemeshow P = 0.901). DCA curves indicated robust clinical utility. The SOFA score model exhibited weaker discrimination powers (training AUC: 0.621; validation AUC: 0.676; P &lt; 0.05), as did the NEWS score model (training AUC: 0.676; validation AUC: 0.614; P &lt; 0.05). Machine learning models (SVM, C5.0, XGBoost, and ensemble methods) did not significantly outperform the nomogram in the validation cohort ( P &gt; 0.05), with respective AUCs of 0.741, 0.792, 0.842, and 0.820. Conclusion The nomogram developed in this study is capable of accurately predicting the risk of invasive ventilation in SA-AKI patients within 48 h of admission, offering a valuable tool for early clinical decision-making.

Association between Hemoglobin Dynamic Trajectories and 28-Day Mortality in Elderly Patients with Sepsis: A retrospective cohort study

2025-06-18

Yan Zeng , Jun Wang , Caoyi Liu +1 more | medRxiv (Cold Spring Harbor Laboratory)

Abstract Background Anemia is a common complication in sepsis and is associated with poor prognosis. However, there are few studies on the dynamic changes in hemoglobin (Hb) levels and their … Abstract Background Anemia is a common complication in sepsis and is associated with poor prognosis. However, there are few studies on the dynamic changes in hemoglobin (Hb) levels and their relationship with prognosis in elderly patients with sepsis. This study aims to retrospectively investigate the relationship between Hb trajectories and 28-day mortality in this population. Methods This retrospective observational study used data from 4,961 elderly patients with sepsis from the MIMIC-IV database. A joint latent class model (JLCM) was employed to analyze Hb trajectories. Time-dependent piecewise Cox regression models and Kaplan-Meier survival curves were used to assess the relationship between trajectories and 28-day mortality. Sensitivity analyses included the Schoenfeld residual test, subgroup analysis, and E-value assessment. Results Hb trajectories were classified into three patterns: Class 1 with persistently low levels, Class 2 with medium levels and a gradual decline, and Class 3 with a rapid decline from higher levels. Using Class 2 as the reference, multivariable Cox regression showed that Class 1 (HR = 1.38, 95% CI = 1.18–1.62, p < 0.001) and Class 3 (HR = 1.21, 95% CI = 1.03–1.42, p = 0.020) were associated with higher 28-day mortality. Kaplan-Meier curves indicated the lowest survival probability in Class 1 and the highest in Class 2. Gender-specific analysis revealed consistent trajectory patterns between males and females, but higher Hb values in males. The predictive power of the rapid decline pattern for early mortality was stronger in males. Conclusion The Hb trajectories in elderly sepsis patients are significantly associated with early mortality. Persistently low levels and rapid declines in Hb are indicators of poor prognosis.

Association between Triglyceride-Glucose Index and Risk of Sepsis-Associated Liver Injury and Mortality in Critically Ill Patients: A Retrospective Cohort Study

2025-06-18

Xiaona Yi , Xiao-Ya Yang , Xingkai Shen +5 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background</bold> The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in metabolic dysregulation and adverse clinical outcomes. However, its association with sepsis-associated liver injury (SALI) … <title>Abstract</title> <bold>Background</bold> The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in metabolic dysregulation and adverse clinical outcomes. However, its association with sepsis-associated liver injury (SALI) and mortality in critically ill patients remains unclear. This study aimed to investigate the association between the TyG index and SALI risk, as well as all-cause mortality in intensive care unit (ICU) patients. <bold>Methods</bold> A retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Critically ill patients with complete TyG index measurements were included. The primary outcome was SALI incidence, and secondary outcomes included in-hospital, ICU, 28-day, 90-day, and 365-day mortality. Logistic and cox multivariate regression analyses and restricted cubic spline were applied to evaluate associations. <bold>Results</bold> Among 4343 patients 10.7% developed SALI. In-hospital, ICU, 28-day, 90-day, and 365-day mortality rates were 15.6%, 11.1%, 18.4%, 23.2%, and 28.8%, respectively. A linear positive association was observed between the TyG index and SALI risk [adjusted OR (95% CI) 1.52 (1.12~2.08), <italic>P</italic>-value 0.008]. For mortality, a nonlinear association was identified with TyG index and in-hospital mortality (P for nonlinearity=0.014), with an inflection point at TyG index=9.888. Below this threshold, each TyG index unit increase was associated with higher in-hospital mortality [HR 1.86 (1.49–2.34)，<italic>P</italic><0.001], whereas no significant association was observed above it [HR 1.22 (0.76–1.97)]. The subgroup analysis suggests that our results are robust. <bold>Conclusions</bold> Elevated TyG index was an independent risk factor for SALI in critically ill patients and demonstrated a nonlinear association with in-hospital mortality. These findings highlight TyG as a practical biomarker for risk stratification and targeted management in the ICU setting.

Phenotype-specific dynamics of serum albumin and their impact on sepsis mortality

2025-06-18

Gianni Turcato , Arian Zaboli , Lucia Filippi +7 more | Biomarkers in Medicine

To assess the prognostic value of serial serum albumin measurements in septic patients, with a focus on different clinical phenotypes. We conducted a prospective observational study involving 254 patients with … To assess the prognostic value of serial serum albumin measurements in septic patients, with a focus on different clinical phenotypes. We conducted a prospective observational study involving 254 patients with sepsis admitted to an Intermediate Care Unit in Italy (September 2022-June 2024). Patients were classified into four sepsis phenotypes (α, β, γ, δ), and serum albumin levels were measured daily over five days. The primary outcome was 30-day mortality. Logistic regression, Cox models, and AUROC analysis were used to evaluate associations between albumin dynamics, phenotypes, and outcomes. The δ phenotype showed the lowest mean albumin levels (2.2 g/dL) and the highest mortality (45.4%), while phenotype α had the highest albumin and lowest mortality (3.6%). Each 1 g/dL increase in albumin was associated with a 63% mortality risk reduction (HR 0.37; 95% CI: 0.24-0.56). Albumin's predictive performance was strongest in the δ phenotype (AUROC up to 0.95). Serial albumin monitoring may provide prognostic insights in sepsis, especially in phenotypes associated with endothelial dysfunction. These results are hypothesis-generating and may support more personalized treatment strategies.

Evaluating the Diagnostic Performance of Adult Sepsis Event Criteria in the Emergency Department: Impact of Including Isolated Serum Lactate Elevations

2025-06-17

Hyojun Park , Ryoung‐Eun Ko , Ha Young Oh +3 more | Research Square (Research Square)

<title>Abstract</title> Background The Adult The Adult Sepsis Event (ASE) criteria, developed by the U.S. Centers for Disease Control and Prevention (CDC), utilize electronic Sequential Organ Failure Assessment (eSOFA) scores derived … <title>Abstract</title> Background The Adult The Adult Sepsis Event (ASE) criteria, developed by the U.S. Centers for Disease Control and Prevention (CDC), utilize electronic Sequential Organ Failure Assessment (eSOFA) scores derived from structured electronic health records to retrospectively detect organ dysfunction in patients with suspected sepsis. While validated primarily in inpatient cohorts, their applicability in emergency department (ED) populations remains uncertain. Moreover, the impact of including isolated serum lactate elevation as a marker of organ dysfunction in eSOFA has not been systematically evaluated. Methods We retrospectively reviewed data from 698 patients (aged ≥ 19 years) with suspected infections presenting to the EDs of three institutions from September 1 to 30, 2023. Blood cultures were obtained from all patients. Patients were classified according to Sepsis-3 (≥ 2-point SOFA score increase from baseline) and ASE-defined eSOFA (organ dysfunction occurring within ± 2 days of blood culture collection). Extended eSOFA additionally included isolated lactate elevation (≥ 2.0 mmol/L). Diagnostic accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve (AUROC). Results Among 698 patients, 456 (65.3%) met Sepsis-3 criteria, 251 (35.9%) met ASE-defined eSOFA, and 340 (48.7%) met extended eSOFA criteria. Mortality was highest (19.8%) among patients classified by both SOFA and eSOFA. ASE-defined eSOFA demonstrated moderate sensitivity (52.0%) and high specificity (94.2%), with a PPV of 94.4% and AUROC of 0.730. Extended eSOFA improved sensitivity (64.3%) but lowered specificity (80.6%), with an AUROC of 0.720. Mortality increased with the number of dysfunctional organ caterories. Notably, the inclusion of isolated lactate elevations identified additional high-risk patients not captured by eSOFA. Conclusion ASE-defined eSOFA moderately aligns with Sepsis-3 criteria, effectively identifying high-risk ED sepsis cases. Extended eSOFA criteria with lactate enhance sensitivity but reduce specificity, suggesting tailored application based on clinical settings and available resources.

Predicción de riesgo en sepsis: revisión sistemática sobre la utilidad diagnóstica de escalas clínicas y signos validados

2025-06-17

Daniel Sánchez Knupflemacher , A. Morales , Montserrat Salinas de los Santos +3 more | Revista Científica de Salud y Desarrollo Humano

Introducción: La sepsis es una de las principales causas de mortalidad hospitalaria a nivel mundial. La identificación temprana de pacientes con alto riesgo es esencial para mejorar los desenlaces clínicos. … Introducción: La sepsis es una de las principales causas de mortalidad hospitalaria a nivel mundial. La identificación temprana de pacientes con alto riesgo es esencial para mejorar los desenlaces clínicos. Para ello, se han desarrollado herramientas clínicas como qSOFA, NEWS, MEWS, SOFA y APACHE II, así como signos clínicos validados como taquipnea, hipotensión y alteración del estado mental. Sin embargo, su rendimiento diagnóstico varía según el entorno clínico y el perfil del paciente. Objetivo: Evaluar sistemáticamente la utilidad diagnóstica de escalas clínicas y signos validados para predecir riesgo en pacientes con sepsis, considerando sensibilidad, especificidad y valor pronóstico en diversos contextos asistenciales. Métodos: Se llevó a cabo una revisión sistemática de literatura publicada entre 2018 y 2024 en PubMed, Scopus y Web of Science. Se incluyeron estudios prospectivos, retrospectivos y metaanálisis que evaluaran el desempeño diagnóstico de las escalas qSOFA, NEWS, MEWS, SOFA y APACHE II, junto con signos clínicos validados. La selección se realizó conforme a los lineamientos PRISMA 2020. Se priorizaron estudios que reportaran área bajo la curva (AUC), sensibilidad y especificidad.Resultados: Se incluyeron 27 estudios, de los cuales 10 fueron analizados en profundidad por su alta calidad metodológica. El qSOFA mostró alta especificidad pero baja sensibilidad en servicios de urgencias. NEWS y MEWS evidenciaron un mejor equilibrio entre sensibilidad y especificidad en ámbitos prehospitalarios y hospitalarios. SOFA y APACHE II fueron consistentes en predecir mortalidad a 28 días, especialmente en pacientes en unidades de cuidados intensivos. Además, la presencia de signos clínicos como taquipnea (>22 rpm), presión arterial sistólica <100 mmHg y alteración del estado mental se asoció con mayor riesgo de desenlaces adversos.Conclusión: Las escalas clínicas validadas y ciertos signos clínicos específicos ofrecen un valor diagnóstico significativo para la estratificación del riesgo en sepsis. Dado que su rendimiento varía según el entorno clínico, se recomienda su uso combinado con el juicio clínico y, en algunos casos, herramientas basadas en inteligencia artificial para optimizar la toma de decisiones.

Norepinephrine Dose Threshold at Vasopressin Initiation and Its Association With ICU Mortality in Septic Shock

2025-06-17

Jamil Cedeño , Pablo García-Olivares , Galo Francisco Castañeda +3 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background:</bold> The optimal norepinephrine (NE) dose at which vasopressin should be initiated in septic shock remains unclear. Current recommendations rely largely on expert consensus rather than robust clinical data. … <title>Abstract</title> <bold>Background:</bold> The optimal norepinephrine (NE) dose at which vasopressin should be initiated in septic shock remains unclear. Current recommendations rely largely on expert consensus rather than robust clinical data. <bold>Methods:</bold> We conducted a retrospective observational cohort study in a tertiary ICU from 2022–2025 to determine whether initiating vasopressin at lower NE doses is associated with improved ICU outcomes in patients with septic shock. Patients who received both NE and vasopressin were included. A random derivation subset (n = 93) was used to identify the optimal NE dose cutoff for ICU mortality by means ROC curve and Youden index. This threshold was applied to the remaining validation cohort (n = 127). Multivariable logistic regression models were used to assess ICU mortality and renal failure. <bold>Results:</bold> Of 250 eligible patients, 220 were included. The optimal NE cutoff was 0.40 μg/kg/min (AUC: 0.82; sensitivity: 62.8%, specificity: 87.3%). In the validation cohort, patients receiving vasopressin at NE doses >0.40 μg/kg/min had higher ICU mortality (80% vs. 21%, p < 0.001) and increased renal replacement therapy use (58% vs. 27%, p < 0.001). After adjustment, vasopressin initiation at NE ≤0.40 μg/kg/min was independently associated with reduced ICU mortality (OR, 0.25; 95% CI, 0.07–0.90) and lower risk of renal failure (OR, 0.37; 95% CI, 0.15–0.89), suggesting a protective effect of earlier vasopressin use. <bold>Conclusions:</bold> Initiating vasopressin at NE doses ≤0.40 μg/kg/min may be associated with improved ICU survival and reduced renal dysfunction. These findings support the use of practical NE thresholds in vasopressor management and complement recent data-driven and meta-analytic evidence.

Integrated multi-omics analysis and predictive modeling of heart failure using sepsis-related gene signature

2025-06-17

Yan‐Hong Lang , Tianyu Liang , Fei Li | PLoS ONE

Background Heart failure (HF) is characterized by complex molecular alterations, and recent studies suggest a potential role for sepsis-related genes in cardiovascular dysfunction. This study aimed to develop a predictive … Background Heart failure (HF) is characterized by complex molecular alterations, and recent studies suggest a potential role for sepsis-related genes in cardiovascular dysfunction. This study aimed to develop a predictive model for HF based on sepsis-related gene signatures. Methods Three sepsis-related datasets (GSE65682, GSE54514, and GSE95233) were analyzed to identify differentially expressed genes (DEGs) following batch effect correction using the ComBat algorithm. With the use of elastic net regularization and the glmnet package in R, Lasso Cox regression was employed to screen out gene signatures. A predictive model was developed based on the expression of each gene signature and the co-efficient values. In addition, the predictive model was validated on independent HF datasets (GSE57345, GSE141910, and GSE5406). Model performance was assessed through receiver operating characteristic (ROC) analysis and AUC values of each gene signature, and immune infiltration was evaluated using CIBERSORT, IPS, and xCell. Sepsis models of C57BL/6 mice were established by cecal ligation and puncture (CLP). Results We identified 340 up-regulated and 333 down-regulated sepsis-related genes. The predictive model, incorporating six key genes, demonstrated superior performance compared to individual genes across both training and validation datasets with the AUC value of the risk score above 0.9, significantly higher than that of a single gene. Immune infiltration profiles differed significantly between HF patients and controls, with more pronounced alterations observed at higher risk score levels. Finally, the expression of six key genes in sepsis models was confirmed to be consistent with our prediction. Conclusion The model constructed through sepsis-related characteristic genes provides a highly advantageous method for predicting HF, and the characteristic genes we have screened may be potential biomarkers for predicting HF. This model has potential application value in early diagnosis and risk stratification, which can help improve the clinical management of heart failure and provide new ideas for preventing HF.

Platelet Function in Patients with Disseminated Intravascular Coagulation: Potential Markers for Improving DIC Diagnosis?

2025-06-17

J. Petersen , Christine Lodberg Hvas , Julie Brogaard Larsen | Seminars in Thrombosis and Hemostasis

Abstract Disseminated intravascular coagulation (DIC) is a severe complication often associated with critical illness. DIC is characterized by an uncontrolled systemic activation of the hemostatic system, leading to substantial consumption … Abstract Disseminated intravascular coagulation (DIC) is a severe complication often associated with critical illness. DIC is characterized by an uncontrolled systemic activation of the hemostatic system, leading to substantial consumption of platelets and coagulation factors. The diagnosis of DIC relies on a combination of clinical findings and laboratory results, yet DIC remains challenging to confirm, especially in early stages. This systematic review investigates the reported associations between platelet function and DIC and evaluates the potential of using platelet function markers as a supplement for DIC diagnosis. PubMed and Embase were searched for relevant literature. Human studies, which included patients with DIC and assessed platelet function using dynamic platelet function assays or soluble markers, were included. In total, 24 studies met the inclusion criteria. We found that DIC patients generally exhibit increased platelet activation in vivo, indicated by elevated plasma levels of soluble markers, while ex vivo platelet aggregation was consistently reduced compared to non-DIC patients and healthy controls; however, not all studies adjusted their results for platelet count. Soluble P-selectin was the most frequently studied plasma marker and was consistently increased in DIC patients; this was most pronounced when adjusted for platelet count. However, there was considerable heterogeneity between studies regarding both study design, patient populations, platelet function assessment, and DIC diagnosis, which complicates the comparison of findings across studies. Future studies accounting for low platelet counts in dynamic function tests are necessary to assess the role of platelet aggregation in relation to DIC.

Analytical evaluation of the performances of point-of-care and benchtop procalcitonin assays in comparison with the B⋅R⋅A⋅H⋅M⋅S PCT sensitive KRYPTOR assay

2025-06-17

Ruiqing He , Xiaobing Sun , Lei Su +3 more | Frontiers in Medicine

Background Procalcitonin (PCT) is increasingly utilized in clinical laboratories, leading to the proliferation of commercial PCT assays. However, not all of these assays are traceable to the B⋅R⋅A⋅H⋅M⋅S PCT standard, … Background Procalcitonin (PCT) is increasingly utilized in clinical laboratories, leading to the proliferation of commercial PCT assays. However, not all of these assays are traceable to the B⋅R⋅A⋅H⋅M⋅S PCT standard, which is integral to established PCT clinical algorithms. This study evaluates the suitability of three non-B⋅R⋅A⋅H⋅M⋅S PCT assays for the application of these algorithms. Methods The study assessed PCT assays from Wondfo (PCT-W), Getein (PCT-G), and Snibe (PCT-S), comparing them to the B⋅R⋅A⋅H⋅M⋅S PCT sensitive KRYPTOR assay (PCT-KR). Analytical performance, including linearity, imprecision, and recovery, was evaluated. Additionally, a method comparison study involving 350 routine serum samples was conducted to assess agreement, bias, and correlation with the KRYPTOR assay. Results The KRYPTOR assay exhibited a maximum imprecision of 4.65%, while Wondfo, Getein, and Snibe showed higher imprecision at 8.38, 10.25, and 15.67%, respectively. Wondfo and Getein assays exceeded the maximum allowable deviation from linearity, and the Snibe assay failed the recovery assessment. Passing-Bablok regressions for low-range samples indicated significant bias for Wondfo (PCT-W = 0.663 PCT-KR + 0.076) and Getein (PCT-G = 0.838 PCT-KR−0.06). Agreement with the KRYPTOR assay was Kc = 0.83 and Kc = 0.87 for Wondfo and Getein, respectively, with substantial agreement in lower respiratory tract infections (LRTI) at Kc = 0.78 and Kc = 0.65. The Snibe assay showed better overall agreement (PCT-S = 1.002 PCT-KR−0.069), with Kc = 0.92 for sepsis and Kc = 0.76 for LRTI. Conclusion Despite high overall agreement with the KRYPTOR assay, the evaluated assays (Wondfo, Getein, and Snibe) exhibit insufficient analytical performance at low PCT concentrations, which may limit their reliability in the diagnosis and management of sepsis and LRTI.

Fluid resuscitation in adults with severe infection and sepsis: a systematic review and network meta-analysis

2025-06-17

Binglin Song , Kangrui Fu , Xiangde Zheng +1 more | Frontiers in Medicine

Introduction The choice of optimal resuscitation fluid for patients with septic shock remains a controversial topic. The 2021 Sepsis Surviving Campaign Guidelines strongly recommend using crystalloids as the first-line resuscitation … Introduction The choice of optimal resuscitation fluid for patients with septic shock remains a controversial topic. The 2021 Sepsis Surviving Campaign Guidelines strongly recommend using crystalloids as the first-line resuscitation fluid for adults with sepsis or septic shock, with balanced crystalloids as a weak recommendation. However, two large-scale network meta-analyses in 2020 concluded that balanced crystalloids are most advantageous. This study reevaluates the efficacy and safety of different resuscitation fluids in septic shock through a network meta-analysis (NMA). Methods Databases including PubMed, EMBASE, and WOS were searched, and reference lists of relevant literature up to September 2024 were reviewed. Studies involving adult patients with sepsis requiring fluid resuscitation were selected. The fluids covered include balanced crystalloid (BC), saline, iso-oncotic albumin (Iso-Alb), hyper-oncotic albumin (Hyper-Alb), low molecular weight hydroxyethyl starch (L-HES), high molecular weight hydroxyethyl starch (HES), and gelatin. A network meta-analysis was conducted to assess the effects of different fluid types. Results A total of 32 RCTs were included in the analysis. The NMA probability ranking results show that balanced crystalloid (BC) had the lowest all-cause mortality rate, with the highest SUCRA value (83.1%). Gelatin was shown to confer the greatest advantage in terms of kidney injury, with the highest SUCRA value (80.7%). Hyper-oncotic albumin had the lowest occurrence of renal replacement therapy events, showing the highest SUCRA value (94.1%). Patients treated with balanced crystalloids had the shortest ICU stays and hospital lengths of stay. Conclusion Balanced solutions (BS) are the preferred resuscitation fluids for septic shock. High molecular weight hydroxyethyl starch (H-HES) is associated with increased risks of mortality, acute kidney injury (AKI), and renal replacement therapy (RRT), as well as prolonged hospital stays, and its use is advised against. Gelatin is associated with poorer outcomes in terms of mortality, continuous renal replacement therapy (CRRT), and length of hospital stay. Systematic review registration Registration ID: INPLASY2024100049 https://doi.org/10.37766/inplasy2024.10.0049 .

Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods

2025-06-17

Wei Guo , Hao Chen , Feng Wang +5 more | Frontiers in Immunology

Background Septic shock in children is an infectious disease caused by low immunity, and its mortality is very high. Early prediction of the risk of death in children with septic … Background Septic shock in children is an infectious disease caused by low immunity, and its mortality is very high. Early prediction of the risk of death in children with septic shock is helpful for clinicians to judge the severity of the disease, take active treatment measures, and improve the adverse outcomes of patients. However, the mechanism of death from sepsis in children remains unclear. This study aims to use bioinformatics and machine learning algorithms to identify key genes and pathways associated with fatal sepsis in children, and provide theoretical basis for rational drug use in follow-up TCM treatment. Methods Gene expression profiles were obtained from the GEO database (GSE4607) for 15 blank patients and 14 children with sepsis death. Differentially expressed genes (DEGs) were enriched by GO and KEGG pathways. Construct and visualize protein-protein interaction (PPI) networks to identify candidate genes responsible for fatal sepsis in children. Three kinds of machine learning models were established, and the candidate genes were screened by intersection to obtain the core genes with diagnostic value. ROC curve was drawn for core genes to clarify the diagnostic value of genetic markers. Results Analysis of differences in the preprocessed dataset identified 83 genes, including 78 up-regulated genes and 5 down-regulated genes. 17 candidate genes were screened by protein interaction network analysis. Three machine learning algorithms LASSO, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE) were used to finally screen out three core genes: CD163, MCEMP1 and RETN. CD163, MCEMP1 and RETN may jointly regulate complement and coagulation cascades, toll like receptor signaling pathway, graft versus host disease, type I diabetes mellitus. Conclusion In this study, three core genes (CD163, MCEMP1 and RETN) that lead to sepsis death in children were screened out, providing a new understanding of the lethal mechanism of sepsis in children and a promising new therapeutic approach.

Distribution of Infections in Patients with Renal Failure Followed in the Intensive Care Unit and the Role of Procalcitonin in Infection Follow-Up

2025-06-17

Ferhan Kerget , Edip Erkuş , Buğra Kerget +1 more | Eurasian Journal of Medicine

Background: In this study, the aim was to assess the association between procalcitonin levels and culture positivity in patients with acute renal failure (ARF) admitted to the intensive care unit … Background: In this study, the aim was to assess the association between procalcitonin levels and culture positivity in patients with acute renal failure (ARF) admitted to the intensive care unit due to Type 1 and Type 2 respiratory failure. Methods: About 128 patients with ARF were restrospectively included between January 2022 and December 2023. Based on admission culture results, patients were grouped as infection-positive (n=40) or infection negative (n=88). Laboratory parameters, particularly procalcitonin levels, were compared. Results: Platelet levels were significantly higher in patients with positive culture results (P=.03), while procalcitonin levels did not differ between groups (P=.33). Escherichia coli was the most frequently isolated microorganism (25%), with the urinary tract being the most common site of growth. In culture- positive patients, procalcitonin levels exhibited a stronger negative correlation with glomerular filtration rate (GFR) (R=-0.355, P= .02) and a positive correlation with creatinine (R=0.385, P= .01), highlighting the impact of renal function. Additionally, procalcitonin levels were positively correlated with C-reactive protein (CRP) (R=0.586, P < .001) and negatively correlated with serum sodium (R=-0.39, P=.01) in patients with culture growth. As a secondary observation, platelet levels were elevated in patients with positive cultures. Conclusion: Although procalcitonin is a recognized marker for infection and sepsis, its diagnostic reliability appears limited in critically ill patients with ARF due to its association with renal dysfunction. Additionally, defining infection based solely on culture positivity has inherent limitations, and further research including comprehensive clinical and laboratory parameters is warranted.

Hemodynamic response by polymyxin B hemoperfusion and its clinical outcomes in patients with refractory septic shock: A post-hoc sub-analysis of prospective cohort study

2025-06-17

Kyohei Miyamoto , Yu Kawazoe , Noriko Miyagawa +7 more | Shock

Polymyxin B hemoperfusion (PMX-HP) reportedly improves hemodynamic status in some but not all patients with septic shock. We examined the association between hemodynamic response and clinical outcomes and explored factors … Polymyxin B hemoperfusion (PMX-HP) reportedly improves hemodynamic status in some but not all patients with septic shock. We examined the association between hemodynamic response and clinical outcomes and explored factors that may identify patients with hemodynamic response. BEAT-SHOCK registry is a prospective cohort study of 309 consecutive adult patients with septic shock requiring high-dose norepinephrine. This predefined sub-analysis included 82 patients treated with PMX-HP. We defined hemodynamic response as a ≥ 20% improvement within 6 h of starting PMX-HP in the modified vasopressor dependency index, representing vasopressor dosage divided by mean arterial pressure. The median modified vasopressor dependency index at the start of PMX-HP was 0.56 mmHg-1, and 0.34 mmHg-1 6 h after starting PMX-HP (median relative change -32%). Hemodynamic response was obtained in 53 patients (65%; responder group). The 28-day mortality rate was 8% (4/53) in the responder group and 31% (9/29) in the non-responder group (P = 0.0042). Three potential factors were: lower SOFA score (≤10, adjusted odds ratio [aOR] 3.36), abdominal or urinary tract infection (aOR 2.49), and higher modified vasopressor dependency index at the start of PMX-HP (≥0.5 mmHg-1, aOR 2.14). Patients with two or three factors were likely to respond to PMX-HP. Among patients with refractory septic shock, 65% had hemodynamic response after PMX-HP, and it was associated with better clinical outcomes, as shown by the higher survival rate. The number of the following factors was associated with the likelihood of hemodynamic response: less organ dysfunction, more vasopressors, and abdominal/urinary tract infection. UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).

Letter to the editor: “Performance evaluation of four scoring systems for mortality prediction in a contemporary cardiac intensive care unit”

2025-06-17

Biao Wang , Yanming Wu | International Journal of Cardiology

Presepsin como biomarcador en sepsis y shock séptico

2025-06-16

Engelbert Peña Merlano , Alina Pascual Barrera , Roberto Navarro Quiroz +1 more | Salud Uninorte

Objetivo: Evaluar la utilización de los niveles séricos del biomarcador inmunológico presepsin, en pacientes diagnosticados con sepsis bacteriana, que pudieron o no progresar a shock séptico. Materiales y métodos: Se … Objetivo: Evaluar la utilización de los niveles séricos del biomarcador inmunológico presepsin, en pacientes diagnosticados con sepsis bacteriana, que pudieron o no progresar a shock séptico. Materiales y métodos: Se realizó un estudio analítico, de corte transversal, con una muestra de 125 individuos con sepsis bacteriana, 74 mujeres y 51 hombres entre los 22 a 90 años de edad, determinándoseles las concentraciones séricas del presepsin, mediante inmuno ensayo, utilizando el método de inmunoanálisis ligado por enzima. Para la recolección de los datos, se emplearon las historias clínicas y formularios para recolectar la información. Resultados: Del total de los pacientes sépticos, el 64% (n=32) de las mujeres y el 36% (n=18) de los hombres, progresaron a shock; mientras que, por estratos socioeconómicos, se evidenció que, en el estrato bajo, fue en el que hubo el mayor progreso. La sensibilidad y especificidad del presepsin en progreso a shock fue del 97,9 y 64,4%, respectivamente. Las concentraciones séricas del presepsin que se hallaron, resultaron significativamente mayores, en los pacientes con shock séptico (n = 50), comparados con los pacientes sépticos sin shock (n = 75), media ± DE: 32,7 ± 19,9 ng/mL vs 12,9 ± 7,4 ng/mL, respectivamente (p < 0,0001). Conclusión: Los niveles séricos del presepsin demostraron alta sensibilidad y elevada asociación estadística, tanto en la sepsis, como en el progreso del shock séptico, por lo cual, puede ser factible su uso en los pacientes sépticos.

Lactate trajectories and outcomes in patients with sepsis in the intensive care unit: group-based trajectory modeling

2025-06-16

Wei Yu , Jinqiang Zhuang , Jiaqi Li +4 more | Frontiers in Public Health

Background Sepsis is highly heterogeneous. Therefore, identifying biomarkers that can stratify patients with sepsis into more homogeneous cohorts to develop individualized treatment and care measures for patients and carry out … Background Sepsis is highly heterogeneous. Therefore, identifying biomarkers that can stratify patients with sepsis into more homogeneous cohorts to develop individualized treatment and care measures for patients and carry out early intervention to reduce the risk of death and improve the prognosis of patients has become a current research hotspot. Methods Using the MIMIC-IV database, we analyzed data from 1,575 adult patients with sepsis. Serum lactate levels were measured once daily for 5 consecutive days after admission. The GBTM model was used to stratify the risk of sepsis and explore the relationships between different lactate trajectories and 28-day mortality in septic patients. Results We report a new method for identifying subphenotypes of sepsis patients based on lactate trajectories. Through group-based trajectory modeling, we identified and validated five groups of sepsis patients with different lactate trajectories, namely, “Low-stable group,” “low-slowly declining group,” “high-rapidly decline group,” “Moderate-slow declining group,” and “high-slow decline group.” The relationships between sepsis patients with different lactate trajectories and 28-day mortality were explored. Among them, patients with a “Low-stable group” had the lowest in-hospital 28-day mortality. Patients with a “high-slow decline group” had the highest 28-day mortality. Conclusion In this study, different subtypes of sepsis were successfully identified by analyzing lactate trajectories. Combined with the dynamic changes in lactate levels, the GBTM model was used to stratify patients according to their risk of sepsis. This model provides a theoretical basis for clinicians to evaluate the prognosis of patients using the lactate change trajectory.

Combination of Cv-aCO2/Ca-vO2 and Pv-aCO2 as markers of resuscitation or microcirculation in patients with septic shock: a pilot study

2025-06-16

Luping Cheng , Xin Lou , Xia Hu +1 more | Journal of Intensive Care

Abstract Background The ratio of central venous-to-arterial carbon dioxide content difference to arterial-to-venous oxygen content difference (C v-a CO 2 /C a-v O 2 ) and central venous-to-arterial carbon dioxide … Abstract Background The ratio of central venous-to-arterial carbon dioxide content difference to arterial-to-venous oxygen content difference (C v-a CO 2 /C a-v O 2 ) and central venous-to-arterial carbon dioxide tension difference (P v-a CO 2 ) are indicators for monitoring anaerobic metabolism and tissue perfusion in shock. We hypothesized that significant differences in patient outcomes exist across different C v-a CO 2 /C a-v O 2 and P v-a CO 2 groups during the early stages of shock resuscitation and that these two indicators reflect microcirculatory perfusion in septic shock patients. Methods This single-center, prospective, observational, cohort, exploratory, pilot study involved newly diagnosed patients with septic shock admitted to intensive care unit (ICU) between May 2023 and August 2024. We classified patients into four groups based on their C v-a CO 2 /C a-v O 2 and P v-a CO 2 levels at 6 h post-ICU admission (T6), monitored sublingual microcirculation, and followed them for 28 days. The grouping is as follows: Group A is C v-a CO 2 /C a-v O 2 ≤ 1 and P v-a CO 2 < 6 mmHg; Group B is C v-a CO 2 /C a-v O 2 ≤ 1 and P v-a CO 2 ≥ 6 mmHg; Group C is C v-a CO 2 /C a-v O 2 > 1 and P v-a CO 2 < 6 mmHg; and Group D is C v-a CO 2 /C a-v O 2 > 1 and P v-a CO 2 ≥ 6 mmHg. Results 105 patients were included in the study. The 28-day mortality differed significantly among the four groups of patients (A:8.3%, B:19%, C:30%, and D:46.7%, p < 0.05). The Kaplan–Meier curves for the four groups revealed significant differences in the 28-day survival probabilities. ( p = 0.014). Multivariate Cox regression revealed that the independent risk factors for 28-day mortality were age [hazard ratio (HR) = 1.05, 95% confidence interval (95% CI) = 1.02–1.09, p = 0.001], C v-a CO 2 /C a-v O 2 (HR = 1.67, 95% CI = 1.03–2.69, p = 0.036), and P v-a CO 2 (HR = 1.13, 95% CI = 1.00–1.27, p = 0.043). There were significant differences among the four groups in terms of the proportion of perfused vessels for all (PPV), proportion of perfused vessels for d < 20 μm (sPPV), microvascular flow index (MFI), and heterogeneity index (HI) values ( p < 0.001); correlations were observed for C v-a CO 2 /C a-v O 2 , P v-a CO 2 , and sPPV ( r = −0.49, p < 0.001, R 2 = 0.19; r = −0.22, p = 0.028, R 2 = 0.08). Conclusions The combined assessment of C v-a CO 2 /C a-v O 2 and P v-a CO 2 during the early stages of resuscitation demonstrates a significant association with mortality in septic shock patients. This combination could potentially serve as a resuscitation target and reflect microcirculatory perfusion in septic shock patients.