Sepsis and septic shock remain leading causes of morbidity and mortality among children worldwide. Fluid resuscitation is the foundation of initial treatment. Usually, 0.9% saline is commonly used; however, its high chloride content might lead to adverse kidney outcomes. This systematic review compares the efficacy and safety of balanced crystalloids vs normal saline for fluid resuscitation in children with sepsis. This systematic review followed PRISMA guidelines. Databases including PubMed, Google Scholar, and Cochrane were searched until May 2026. Inclusion criteria were pediatric patients diagnosed with sepsis or septic shock in randomized controlled trials and observational studies. Statistical analysis was performed using Review Manager 5.4, utilizing Risk ratios (RR) and 95% confidence intervals (CI). Nine studies involving 20,713 pediatric patients were included. Overall pooled analysis demonstrated no statistically significant difference in AKI (RR 0.93, 95% CI 0.74–1.18; p = 0.57) or hospital mortality (RR 0.92, 95% CI 0.82–1.02; p = 0.11). However, analysis showed a significantly lower requirement for RRT (RR 0.74, 95% CI 0.56–0.96; p = 0.03) and significantly lower incidence of hyperchloremia (RR 0.65, 95% CI 0.61–0.69; p < 0.00001). No significant difference was found in hospital length of stay (MD 1.21 days, 95% CI − 0.06 to 2.49; p = 0.06), PICU length of stay (MD 0.62 days, 95% CI − 0.02 to 1.25 days; p = 0.06), need for mechanical ventilation (RR 0.98, 95% CI 0.90–1.08; p = 0.73), or vasoactive therapy (RR 0.98, 95% CI 0.91–1.04; p = 0.45). The administration of balanced crystalloids has an advantage for renal and biochemical outcomes related to sepsis; however, there was no observed effect on overall survival. Additionally, the use of balanced crystalloids decreased the rate of occurrence of hyperchloremia and the necessity of renal replacement therapy.
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