Balanced Solutions Versus Normal Saline in Pediatric Septic Shock: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: In pediatric septic shock, early fluid resuscitation is a vital approach to treat this condition. The appropriate isotonic crystalloid to use (balanced salt solution [BSS] vs normal saline [NS]) remains debated. We performed an updated systematic review and meta-analysis to evaluate the safety and efficacy of both isotonic crystalloid solutions in this patient population. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception until May 1, 2026, for randomized controlled trials (RCTs) comparing BSS with NS for fluid resuscitation in children (<18 years) with septic shock or sepsis. The primary outcome was hospital or 30-day mortality. We synthesized data using frequentist inverse-variance random-effects models. The protocol was registered in PROSPERO (CRD420261391864), and the certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for all outcomes. Results: Six RCTs involving 9743 participants were included. For the primary outcome, BSS and NS demonstrated no significant differences in hospital or 30-day mortality rates (3.5% vs 3.7%; RR: 0.97, 95% CI: 0.81-1.16, P = .72). Secondary analyses revealed that BSS significantly reduced the requirement for renal replacement therapy (RRT) (RR: 0.68, 95% CI: 0.47-0.97) and hyperchloremia (RR: 0.65, 95% CI: 0.57-0.75). Conclusion: The use of BSS versus NS showed no significant difference in short-term mortality among children with septic shock; however, BSS provided significant clinical and physiological advantages, including reduced incidences of hyperchloremia and the need for RRT.