Risk Factors for Cerebral Edema in Pediatric Diabetic Ketoacidosis: a Systematic Review and Meta-Analysis of Observational Studies.

Abstract

Background: Cerebral edema is a rare but serious complication of pediatric diabetic ketoacidosis, and risk factors remain uncertain.

Objective: To synthesize current evidence on risk factors associated with the development of cerebral edema (CE) in pediatric patients with diabetic ketoacidosis (DKA).

Methods: A systematic search was conducted in MEDLINE, EMBASE, LILACS, and the Cochrane Library through January 2025. Observational studies were included. Risk of bias was assessed with Joanna Briggs Institute tools, and evidence certainty was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results: Eleven studies (n=2,545) were included. Bicarbonate administration may be associated with CE (OR 4.21; 95% CI: 2.37, 7.46; low certainty). The evidence is very uncertain about the associations between CE and younger age (MD -1.60 years; 95% CI: -2.38, -0.82), newly diagnosed type 1 diabetes (OR 1.54; 95% CI: 1.01, 2.35), and a more severe presentation phenotype characterized by greater acidosis and elevated urea (very low certainty). The evidence is also very uncertain about the association between higher early fluid volume and CE (MD 9.86 mL/kg; 95% CI: 5.06, 14.66; very low certainty).

Conclusion: Bicarbonate administration may be associated with CE, which is consistent with current recommendations against its routine use in pediatric DKA. The evidence is very uncertain about the associations of younger age, new-onset diabetes, and a severe metabolic phenotype with CE; these findings may indicate increased risk but should be interpreted with caution. Prospective studies with standardized definitions and confounder adjustment are needed.