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).
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Intensivist/Critical Care |  |
As an emergency and critical care physician, I appreciate the work done to synthesise these data based on the available (largely) clinical observational literature, with the inclusion of RCTs. My current clinical practice of individual patient-tailored fluid and vasopressor circulatory support in early sepsis resuscitation is not changed by the results of this systematic review. I await the conclusion of ongoing RCTs to provide a higher-quality evidence base.
More evidence that we should not fluid overload our patients and should focus on early pressors alongside a reasonable bolus.
The data on fluid support remain messy. Give some fluid early, yes. Not too much, though
The methodology was robust and the authors examined the impact of fluid resuscitation in many different time frames. Although the evidence against liberal fluid is building up, there was not a sufficient number of studies or strength of the studies to support any other fluid strategies. Clinicians should provide the fluid according to each patient's clinical status.
