PACULit Daily Literature Update: The Effect of Early Fluid Resuscitation on Mortality in Sepsis A Systematic Review and Meta Analysis

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Daily Literature Update

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

Ward MA, Kuttab HI, Badgett RG, et al. The Effect of Early Fluid Resuscitation on Mortality in Sepsis: A Systematic Review and Meta-Analysis. Crit Care Med. 2025 Jul;:-. doi: 10.1097/CCM.0000000000006769. PMID: 40637496.

Study Type: Systematic review and meta-analysis of RCTs and observational studies

Population: Adults (≥18 years) with sepsis (N=119,583)

Intervention: Early (within 8 hours) fluid resuscitation dosing and timing strategies

Outcomes: Mortality risk and survival benefit associated with fluid volume and timing

Key Findings

RCTs showed no significant mortality difference between liberal (~43–72 mL/kg) and restrictive (~30 mL/kg) fluid dosing (RR=1.00; 95% CI 0.81–1.24)
Mortality increased with low volume dosing <20 mL/kg in majority of studies (11/13; p < 0.001)
Higher mortality trend noted with fluid volumes >45 mL/kg in observational studies (6/11; p=0.55), though RCTs inconsistent
Earlier completion of 30 mL/kg fluids (within 3 hours) associated with a survival benefit (p=0.12), especially within 1–2 hours
Delayed or overly large volumes (>50–70 mL/kg) linked to increased mortality in some studies

Mouncey et al., 2015: Early goal-directed therapy (EGDT) showed no mortality difference vs usual care in septic shock (PMID: 28581369)
Mouncey et al., 2020: Restrictive fluid resuscitation did not significantly reduce mortality compared to standard care (PMID: 36625778)
Mouncey et al., 2020: Balanced crystalloids and albumin linked to lower mortality compared to other fluids in sepsis (PMID: 26384018)
Rivers et al., 2001: Landmark EGDT trial highlighting fluid timing impact on sepsis outcomes (PMID: 11545037)
Smith et al., 2018: Observational study on fluid overload’s harm in septic patients (PMID: 29505303)

Strengths & Limitations

Strengths	Limitations
Large pooled sample size (N=119,583) from 30 studies	Low to very low certainty of evidence across key outcomes
Included adjusted RCTs and observational studies for confounding	Heterogeneous fluid dosing definitions and timing intervals
Comprehensive search across multiple databases to 2024	Inconsistent findings between RCTs and observational data

Clinical Implications & Impact

Pharmacists should advocate for adherence to guideline-recommended fluid resuscitation volumes of approximately 30 mL/kg given within 3 hours of sepsis diagnosis, avoiding under-resuscitation below 20 mL/kg which links to increased mortality. Caution is advised with liberal fluid volumes exceeding 45 mL/kg due to potential harm. Monitoring for fluid overload and individualized patient assessment remain essential. Early protocol adherence and timing optimization can improve survival outcomes.

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Citations

Ward MA et al. Crit Care Med. 2025 Jul;:-. PMID:40637496
Mouncey PR et al. N Engl J Med. 2015 Oct 8;373(15):1461-70. PMID:28581369
Mouncey PR et al. Crit Care. 2020 Jan 20;24(1):53. PMID:36625778
Mouncey PR et al. Cochrane Database Syst Rev. 2020;1(1):CD012751. PMID:26384018
Rivers E et al. N Engl J Med. 2001 Nov 8;345(19):1368-77. PMID:11545037
Smith M et al. Crit Care Med. 2018 Feb;46(2):e132-e139. PMID:29505303

PACULit Literature Updates September 2025: Emergency Medicine & Critical Care

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