Daily Respiratory Research Analysis

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.

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.).

BACKGROUND: The ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO METHODS: We used the database of the intensive care unit of Kuopio University Hospital, Finland, for cutoff derivation and the eICU database, a multicenter U.S. intensive care registry, for external validation. We identified cutoffs most discriminative for hospital mortality using the log-rank statistic test with the Contal and O'Quigley method. In external validation, these cutoffs were compared with those in the current respiratory SOFA score. RESULTS: Optimal cutoffs were identified as follows: P/F ratio > 40 kPa (normal), 30-40 kPa (mild impairment), 20-30 kPa (moderate impairment), 10-20 kPa (severe impairment), and ≤ 10 kPa (critical impairment). These cutoffs resulted in clear separation of the severity categories (chi-square for log-rank statistic 356.9). They outperformed the current respiratory SOFA score cutoffs in the validation cohort (AUROC 0.615, 95% CI 0.607-0.622 vs. AUROC 0.610, 95% CI 0.603-0.618, p < 0.001). Advanced respiratory support was associated with higher mortality, but its inclusion as a prerequisite improved discrimination only in the moderately impaired respiratory function category, not in the severely or critically impaired categories. CONCLUSION: P/F ratio cutoffs using 10 kPa (75 mmHg) intervals were identified to be optimal for distinguishing stages of respiratory failure severity. The impact of respiratory support on P/F ratio-mortality associations suggests the need to calibrate any P/F ratio-based score by support level, but optimal calibration methods require further study. EDITORIAL COMMENT: In this study, the cut-off values for the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) were investigated in a large Finnish intensive care database and validated externally with the US intensive care registry. The aim was to support a revision of the cut-off values for the P/F ratio in the Sequential Organ Failure Assessment (SOFA) score. The results showed that incremental changes in the P/F ratio of 10 kPa are better than 13 kPa and emphasize the need for critical assessment of the current SOFA score.