Balanced crystalloids versus normal saline in pediatric sepsis and septic shock: an updated systematic review and meta-analysis

Balanced crystalloids have a more physiologic electrolyte composition than 0.9% normal saline and may reduce chloride-related acid-base disturbances during fluid resuscitation. Several pediatric syntheses predate the large PRoMPT BOLUS trial, and uncertainty remains regarding patient-centered outcomes. We therefore performed an updated, source-audited systematic review and meta-analysis that separates randomized from observational evidence and distinguishes conventional acute kidney injury (AKI) from composite kidney outcomes. PubMed/MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were searched from inception to 30 April 2026. Randomized trials formed the primary efficacy synthesis; observational studies were analyzed separately as supportive evidence. Conventional AKI, major adverse kidney events within 30 days (MAKE30), renal replacement therapy (RRT), and persistent kidney dysfunction were treated as distinct outcomes. Random-effects risk ratios (RRs) used inverse-variance weighting with Paule-Mandel estimation of between-study variance. Because the principal renal meta-analyses contained fewer than five trials, Hartung-Knapp and modified Hartung-Knapp sensitivity analyses were performed. Shared controls and repeated time points were not counted more than once. Eleven primary studies were included. For conventional AKI, the primary random-effects estimate favored balanced crystalloids (RR 0.64, 95% CI 0.50–0.82; 3 RCTs, 819 participants), but the Hartung-Knapp sensitivity interval crossed the null (95% CI 0.40–1.04). PRoMPT BOLUS reported MAKE30 in 137/4073 versus 124/4068 patients (RR 1.10, 95% CI 0.88–1.40). RRT similarly favored balanced crystalloids in the primary model (RR 0.67, 95% CI 0.48–0.92), but not with Hartung-Knapp sensitivity (95% CI 0.37–1.20). Hospital/ICU mortality did not differ (RR 0.99, 95% CI 0.83–1.18). Hyperchloremia was consistently lower with balanced crystalloids (RR 0.66, 95% CI 0.60–0.73). In Sankar et al., metabolic acidosis was lower at 24 and 48 h but not at 6–72 h. Balanced crystalloids consistently reduce hyperchloremia and may improve short-term acid-base outcomes in children treated for sepsis or septic shock. Point estimates for conventional AKI and RRT favor balanced crystalloids, but statistical significance is not robust to Hartung-Knapp small-sample sensitivity analysis. PRoMPT BOLUS showed no benefit for MAKE30, and no mortality advantage was demonstrated. Superiority for major patient-centered outcomes therefore remains unproven. Not applicable.