Publication:

Cerebral injury in diabetic ketoacidosis: multifactorial pathogenesis beyond sodium and osmolality shifts and implications for clinical management

Background Cerebral injury is the leading cause of mortality in pediatric diabetic ketoacidosis (DKA). Historically attributed to rapid osmotic shifts during fluid resuscitation, emerging evidence suggests that intrinsic disease severity and biochemical derangements play a primary role. The objective of this study was to systematically review and meta-analyze the association between intrinsic non-osmotic markers and cerebral injury in children with DKA.

Methods Following PRISMA 2020 guidelines, we searched PubMed, Embase, and Scopus. We performed a random-effects meta-analysis on human clinical studies evaluating non-osmotic risk factors.

Results Five human studies (n=1,528) met the inclusion criteria. Meta-analysis demonstrated a significant association between intrinsic severity markers- specifically low partial pressure of arterial carbon dioxide (pCO2) and elevated blood urea nitrogen (BUN)-and cerebral injury (Pooled OR=1.55; 95% CI 1.04-2.30; p=0.031).

Conclusions Cerebral injury in DKA is primarily driven by biochemical derangements present at admission. Clinical protocols should prioritize early identification of high-risk metabolic profiles.