Fluid regimens for diabetic ketoacidosis in children and adolescents: systematic review and meta-analysis

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.