Lower versus higher fluid volumes during initial management of sepsis – a systematic review with meta-analysis and trial sequential analysis

Abstract Purpose Intravenous fluids are recommended during the initial management of sepsis, but the quality of evidence is low, and clinical equipoise exists. We aimed to assess patient-important benefits and harms of lower versus higher fluid volumes in adult patients with sepsis. Methods We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials of intravenous fluid volume separation in adult patients with sepsis. We adhered to our published protocol, the Cochrane Handbook, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the Grading of Recommendations Assessment, Development and Evaluation statements. The primary outcomes were all-cause mortality, serious adverse events and quality-of-life. Results We included 9 trials (n=637); all were published after 2015 and had overall high risk of bias. We found no statistically significant difference between lower versus higher fluid volumes on all-cause mortality (relative risk 0.87, 95% confidence interval (CI) 0.69 to 1.10, I2=0%; TSA adjusted Cl 0.34 to 2.22), or serious adverse events (relative risk 0.91 95% CI 0.78 to 1.05, I2=0%; TSA adjusted CI 0.68 to 1.21). No trials reported on quality-of-life. We did not find differences in the secondary or exploratory outcomes. The quality of evidence was very low across all outcomes. Conclusions In this systematic review, we found very low quantity and quality of evidence supporting the decision on the volumes of IV fluid therapy in adults with sepsis.