Restrictive Versus Liberal Fluid Regimen in Refractory Sepsis and Septic Shock: A Systematic Review and Meta-Analysis

The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal fluid regimens on mortality, adverse events, and other clinical outcomes in patients with sepsis. We systematically reviewed 11 randomized controlled trials published between 2008 and 2023, comprising a total of 4,121 participants. The studies assessed 90-day mortality, 30-day mortality, adverse events, hospital length of stay, ICU admission rate, mechanical ventilation, ventilator-free days, ICU-free days, and vasopressor-free days. Quality assessments indicated minimal bias across the studies. The meta-analysis showed no statistically significant difference in 90-day mortality between restrictive and liberal fluid regimens (OR, 0.93; 95% CI, 0.80 to 1.70; P=0.30). Similar results were observed for 30-day mortality (OR, 0.73; 95% CI, 0.30 to 1.80; P=0.50). Adverse events were comparable between the two groups (OR, 0.81; 95% CI, 0.55 to 1.19; P=0.28). Furthermore, there were no significant differences in hospital length of stay (OR, 0.47; 95% CI, -0.85 to 1.80; P=0.48) or ICU admission rate (OR, 1.09; 95% CI, 0.66 to 1.77; P=0.75) between the restrictive and liberal fluid regimens. Regarding mechanical ventilation and ventilator-free days, no significant distinctions were observed (OR, 0.87; 95% CI, 0.65 to 1.17; P=0.48; OR, 0.99; 95% CI, -0.17 to 2.15; P=0.09, respectively). ICU-free days and vasopressor-free days also showed no significant differences between the two groups (OR, 0.97; 95% CI, -0.28 to 2.21; P=0.13; OR, -0.38; 95% CI, -1.14 to 0.37; P=0.32, respectively). This comprehensive meta-analysis of clinical trials suggests that restrictive and liberal fluid management strategies have comparable outcomes in patients with sepsis, including mortality, adverse events, and various clinical parameters. However, most studies favored restrictive fluid regimen over liberal approach regarding the number of vasopressor-free days, need for mechanical ventilation, adverse events, 30-day mortality, and 90-day mortality in sepsis patients.