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.

Background: Diabetic ketoacidosis (DKA), a life-threatening complication of type 1 diabetes, requires prompt fluid resuscitation to restore circulatory volume and correct metabolic abnormalities. However, the optimal fluid type, volume, and tonicity remain unclear due to concerns regarding cerebral injury and electrolyte imbalances. Methods: We searched PubMed, CINAHL, Cochrane, Scopus, Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform without date restrictions for randomized controlled trials (RCTs) evaluating fluid regimens in children with DKA. Risk of bias was assessed using the Cochrane RoB-2 tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was conducted using RevMan 5.4. Results: The review included 10 RCTs (n = 2291). Children receiving a 20 mL/kg bolus followed by 0.9% saline exclusively for rehydration may have a higher risk of adverse events (AEs) than those receiving 10 mL/kg (risk ratio [RR] = 1.11, 95% CI = 1.01-1.23, low certainty of evidence). However, in children given 0.9% saline exclusively for rehydration, there was a significantly lower risk of hypoglycemia in the 20 mL/kg bolus group compared to the 10 mL/kg group (RR = 0.78, 95% CI = 0.62-0.99, high certainty). For rehydration fluid, compared to 0.45% saline, 0.9% saline (48-72 hours) was associated with a higher risk of hypoglycemia (RR = 1.35, 95% CI = 1.06-1.72, high certainty) and AEs (RR = 1.18, 95% CI = 1.05-1.31, low certainty). Over 36 hours, 0.9% saline may be associated with more AEs (RR = 1.15, 95% CI = 1.03-1.27, low certainty). Conclusion: Smaller bolus volumes may be safer than larger ones, and prolonged use of 0.9% saline may increase the risk of hypoglycemia and AEs, although the certainty of evidence was low.