BACKGROUNDIntravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODSIn this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTSWe enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, −1.7 percentage points; 99% CI, −7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONSAmong adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.

Background Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post‐operative phase. Diuretics, including furosemide, are commonly used in post‐operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post‐operatively in adult surgical patients. Methods We conducted a systematic review with meta‐analysis according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post‐operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta‐analysis and trial sequential analysis (TSA). Results Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide‐ vs no furosemide‐treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43‐2.65), all‐cause mortality (RR 1.73, 95% CI 0.62‐4.80, use of vasopressors post‐operatively (RR 1.04, 95% CI 0.74‐1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44‐33.99). TSA highlighted sparse data, and the overall quality of evidence was very low. Conclusion In this systematic review, we found that the quantity and quality of evidence for using furosemide post‐operatively in adult surgical patients were very low with no firm evidence for benefit or harm.