Systematic Review and Meta-Analysis of Insulin Dose and Route of Administration Regimens for Diabetic Ketoacidosis in Children and Adolescents

Background: Non-communicable diseases represent a major global health challenge. Among these, diabetic ketoacidosis (DKA), an acute complication of type 1 diabetes mellitus in children and adolescents, significantly contributes to worldwide morbidity and mortality. Effective management of DKA relies on adequate insulin therapy, but variability in dosing, administration, and frequency leads to increased risk of complications and delayed DKA resolution. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the insulin dose and route of administration regimens for managing pediatric DKA. Methods: This review followed the PRISMA guidelines and was registered on PROSPERO (CRD42024568747). A comprehensive search of PubMed, CINAHL, Cochrane Library, and Scopus identified studies examining insulin regimens in pediatric DKA. Eligible studies were assessed for risk of bias using the Cochrane’s Risk of Bias (RoB-2) tool, and data were pooled using Review Manager for meta-analysis. Outcomes included morbidity (cerebral injury, hypoglycemia, hypokalemia), mortality, hospital stay, and adverse events. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. This review was commissioned by the WHO for the development of consolidated guidelines on common childhood illnesses. Results: Twelve RCTs, involving 530 participants, were included. A lower insulin dose (0.05 U/kg/h) was associated with a significantly reduced risk of hypoglycemia (RR = 0.39, 95% CI: 0.18–0.88, p = 0.02) and hypokalemia (RR = 0.54, 95% CI: 0.33,0.89, p = 0.01) compared to 0.1 U/kg/h. There were no significant differences in mortality and length of hospital stay between the dosing regimens. Additionally, no significant differences were observed in the incidence of cerebral injury and other adverse events. Conclusions: Findings suggest that lower insulin doses may reduce the risks of hypoglycemia and hypokalemia in children with mild-to-moderate DKA without increasing the risk of mortality, cerebral injury, or length of hospital stay. Further studies are needed to provide an evidence-based core outcome set and refine insulin dosing strategies across the full spectrum of disease severity.