The Effect of Early Fluid Resuscitation on Mortality in Sepsis: A Systematic Review and Meta-Analysis

OBJECTIVES: While general agreement exists on many sepsis management principles, the details of early fluid resuscitation in sepsis remain contentious. The aim of the current review is to examine the impact of early (≤ 8 hr) fluid dosing, timing, and guideline-based resuscitation on mortality in sepsis. DATA SOURCES: PubMed, Scopus, Cochrane, and Google Scholar from January 1, 2000, to November 8, 2024. STUDY SELECTION: Randomized controlled trials and observational data, adjusting for confounding, for adults (≥ 18 yr) with sepsis. DATA EXTRACTION: From 2,169 citations, 30 studies with 119,583 patients were included. DATA SYNTHESIS: Dosing: three randomized trials suggest no mortality difference between more liberal (~43-72 mL/kg) vs. more restrictive (as low as 30 mL/kg) fluid resuscitative strategies (relative risk, 1.00 [0.81-1.24]). Eleven of 13 studies observed mortality risk when low-fluid volumes were administered (< 20 mL/kg; effect direction/sign test: p < 0.001). Six of 11 studies observed mortality risk when fluid volume dosing exceeded higher limits (> 45 mL/kg; p = 0.55). Timing: four of four studies observed a survival benefit with earlier completion of 30 mL/kg (within 3 hr; p = 0.12). Thirty mL/kg by discrete time: less than or equal to 1 and less than or equal to 2 hours-two studies observed survival benefit; less than or equal to 3 hours-one study observed survival benefit and three studies observed no mortality impact; and less than or equal to 6 hours-two studies observed a survival benefit, four studies observed no impact, and two studies observed increased mortality risk (both > 30 groups received > 50 and > 70 mL/kg). CONCLUSIONS: For fluid resuscitation within 8 hours of sepsis diagnosis: 1) randomized trials suggest no mortality difference between more restrictive and more liberal fluid resuscitative strategies (certainty of evidence: low); 2) dosing less than 20 mL/kg has an effect on increased mortality (low certainty); 3) observational studies trend toward increased mortality with higher volume resuscitation (> 45 mL/kg) but are not supported by randomized trials (very low certainty); and 4) survival benefit is observed when 30 mL/kg is completed within 3 hours (low certainty).