Geo-Economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. We searched E-databases for all randomised controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. Fluid strategies (higher versus lower volumes) effect on mortality was analysed per income group, i.e. low-and middle-income countries (LMICs) or high-income countries (HICs) Measurements and Main Results: 29 studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in LMICs studies as compared to HICs (37%[26-41] versus 29%[17-38], p= 0.06). Income group significantly interacted with the effect of fluid volume on mortality: higher fluid volume was associated with higher mortality in LMICs but not in HICs (OR 1.47[95% CI 1.14-1.90] vs. 1.00[95% CI 0.87-1.16], p=0.01 for subgroup differences). Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR 1.24[95% CI 1.08-1.43]) but not in HICs (OR 1.02[95% CI 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45[1.09-1.93]vs. 1.09[0.93-1.28], p=0.02 for subgroup differences). In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher-volume fluid resuscitation associated with increased mortality in LMICs, and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear, and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.