Daily Anesthesiology Research Analysis

IMPORTANCE: The optimal strategy for hemodynamic resuscitation in early septic shock remains uncertain. OBJECTIVE: To determine the effect of a personalized hemodynamic resuscitation protocol targeting capillary refill time (CRT-PHR) on a hierarchical composite outcome of mortality, duration of vital support, and length of hospital stay. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in 86 centers in 19 countries. Patients within the first 4 hours of septic shock were included between March 2022 and April 2025, with last follow-up in July 2025. INTERVENTIONS: Patients were randomized to undergo CRT-PHR (n = 720), including assessment of pulse pressure, diastolic arterial pressure, fluid responsiveness, and bedside echocardiography, to tailor fluids, vasopressors, and inotropes, vs usual care (n = 747). MAIN OUTCOMES AND MEASURES: The primary outcome was a hierarchical composite of mortality, duration of vital support (vasoactives, mechanical ventilation, and kidney replacement therapy), and length of hospital stay assessed at 28 days. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy and stratified by median APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission. Secondary outcomes were mortality, vital support-free days, and length of hospital stay at 28 days. RESULTS: From 1501 randomized patients, 1467 were included in the primary analysis (mean age, 66 [17] years; 43.3% female). There were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04). Individual wins for death were 19.1% vs 17.8%; duration of vital support, 26.4% vs 21.1%; and length of hospital stay, 3.4% vs 3.2% in the intervention vs usual care groups, respectively. CONCLUSIONS AND RELEVANCE: Among patients with early septic shock, a personalized hemodynamic resuscitation protocol targeting capillary refill time was superior to usual care for the primary composite outcome, primarily due to a lower duration of vital support. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05057611.

BACKGROUND: Whether selective decontamination of the digestive tract (SDD) reduces mortality among patients undergoing mechanical ventilation and whether it adversely affects microbial ecology in the intensive care unit (ICU) remain unclear. In an earlier analysis of data from Australia, SDD did not result in a lower incidence of in-hospital death than standard care, but data from the full international trial are needed. METHODS: We randomly assigned ICUs in Australia and Canada to use SDD or to continue standard care for two 12-month periods in patients undergoing mechanical ventilation. Patients in the SDD group received specific oral and gastric antimicrobial interventions for the duration of ventilation and an intravenous antibiotic agent for the first 4 days after enrollment. All other patients in the ICU were included in an observational ecologic assessment. Previously reported data from Australia are now combined with data from Canada. The primary outcome was in-hospital death from any cause at 90 days. The secondary clinical outcomes, assessed at 90 days, were death in the ICU and the number of days alive and free of mechanical ventilation, ICU admission, and hospitalization. Microbiologic secondary outcomes included new positive cultures for bloodstream infections and antibiotic-resistant organisms. For the ecologic assessment, the microbiologic outcomes were tested for noninferiority (noninferiority margin, 2 percentage points). RESULTS: In this trial involving 20,000 patients in 26 ICUs, 9289 patients were enrolled in the randomized trial and 10,711 were included in the ecologic assessment. At 90 days, 1175 of 4215 patients (27.9%) in the SDD group and 1494 of 5065 (29.5%) in the standard-care group had died before hospital discharge (odds ratio, 0.93; 95% confidence interval [CI], 0.84 to 1.05; P = 0.27). New bloodstream infections occurred in 4.9% of the patients in the SDD group and in 6.8% of those in the standard-care group (adjusted mean difference, -1.30 percentage points; 95% CI, -2.55 to -0.05); antibiotic-resistant organisms were cultured in 16.8% and 26.8%, respectively (adjusted mean difference, -9.60 percentage points; 95% CI, -12.40 to -6.80). In the ecologic assessment, noninferiority of SDD was not confirmed for the development of new antibiotic-resistant organisms. Adverse events considered to be related to SDD or standard care were reported in 12 patients (0.3%) in the SDD group and in no patients in the standard-care group. Serious adverse events occurred in 47 patients (1.1%) and 59 patients (1.2%), respectively. CONCLUSIONS: Among critically ill patients undergoing mechanical ventilation, SDD did not result in a lower incidence of in-hospital death than standard care. (Funded by the National Health and Medical Research Council of Australia and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02389036.).

IMPORTANCE: Acute dysfunction of vital organs is the hallmark of critical illness. The Sequential Organ Failure Assessment (SOFA) score, the most widely adopted approach to describe organ dysfunction, has not been updated in 30 years and therefore may not appropriately capture current clinical practice and outcomes. OBJECTIVES: To inform the data-driven component of an updated score (SOFA-2) in varied geographical and resource settings (stages 6-8) after expert input via a modified Delphi process (stages 1-5). DESIGN, SETTING, AND PARTICIPANTS: A federated analysis was performed on data collected from adult patients admitted to 1319 intensive care units (ICUs) in 9 countries (Australia, Austria, Brazil, France, Italy, Japan, Nepal, New Zealand, United States) between 2014 and 2023. Four representative multicenter cohorts containing data from 2 098 356 patients were used for data-driven score development and internal validation. External validation was performed on 6 cohorts containing data from 1 241 114 patients. MAIN OUTCOMES AND MEASURES: Content validity for organ dysfunction identified through the modified Delphi process should be reflected by predictive validity using the area under the receiver operating characteristic (AUROC) curve of the score measured on the first ICU day (higher scores indicate worse organ dysfunction). RESULTS: Of 3.34 million patient encounters, 270 108 (8.1%) died in the ICU (range, 4.5% to 20.5% across the 10 cohorts). SOFA-2 modified the 6 organ systems of the original SOFA score (brain, respiratory, cardiovascular, liver, kidney, hemostasis), including new variables and revised thresholds that better describe the organ dysfunction distribution from 0 to 4 points and their associated mortality (SOFA-2 AUROC, 0.79; 95% CI, 0.76-0.81; SOFA-1 AUROC, 0.77; 95% CI, 0.74-0.81). Evaluation of sequential SOFA-2 data from ICU day 1 to day 7 maintained its predictive validity. Insufficient data and lack of content validity precluded incorporation of gastrointestinal and immune dysfunction scores into SOFA-2. CONCLUSIONS AND RELEVANCE: The SOFA-2 score, updated to include contemporary organ support treatments and new score thresholds, describes organ dysfunction in a large, geographically and socioeconomically diverse population of critically ill adults.