Although retrospective studies have reported associations between cerebral injury and declines in sodium concentration during treatment for diabetic ketoacidosis (DKA) in children, a new study found no association between declines in glucose-corrected sodium concentrations and mental status changes in the context of pediatric DKA. Findings from this study were published in Pediatrics.
The study included children and adolescents with DKA who were previously enrolled in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial (PECARN DKA FLUID; ClinicalTrials.gov Identifier: NCT00629707). Investigators compared patients who experienced declines in glucose-corrected sodium concentrations with patients who had either rising or stable glucose-corrected sodium concentrations.
Study participants were randomly assigned to 1 of 4 intravenous fluid protocols, with each protocol featuring a different infusion rate and sodium content. The investigators analyzed data from the first 4, 8, and 12 hours of treatment for a total of 1251, 1086, and 877 DKA episodes, respectively.
The slow infusion arms consisted of an initial intravenous fluid bolus of 10 mL/kg of 0.9% sodium chloride (NaCl) solution. The fast infusion arms consisted of initial intravenous fluid boluses of 20 mL/kg of 0.9% NaCl solution.
Following the initial fluid bolus, the researchers calculated infusion rates to replace an estimated fluid deficit of 5% of body weight over a 48-hour period in patients in the slow infusion arms, which included a 0.45% NaCl arm and a 0.9% NaCl arm,. In the fast infusion arms, the researchers calculated infusion rates to replace a fluid deficit of 10% of body weight, with approximately 50% of the deficit replaced over the first 12-hour period and the remaining 50% over the following 24 hours.
After adjusting for the effects of additional covariates, multivariable models identified several factors that were significantly associated with declines in glucose-corrected sodium concentrations at each time point. At the 4-hour period, factors associated with declines in glucose-corrected sodium concentrations included higher baseline sodium and chloride concentrations (adjusted odds ratio [aOR], 1.16; 95% CI, 1.12-1.20) and previously diagnosed diabetes (aOR, 2.64; 95% CI, 1.89-3.68). These variables were also significant at 8 hours and 12 hours.
Treatment with 0.45% NaCl solution (vs 0.9%) was associated with declines in sodium concentration at each time point. Higher fluid infusion rates, however, correlated with declines in sodium concentration only at the 12-hour period.
There was no difference between the groups of patients with DKA who had vs did not have declines in glucose-corrected sodium concentrations in terms of the rate of clinically diagnosed cerebral injury. Additionally, the frequencies of abnormal Glasgow Coma Scale scores were also similar between the 2 groups. In a generalized estimating equation logistic regression model, the researchers found no significant association between decline in glucose-corrected sodium concentrations and Glasgow Coma Scale score during treatment for DKA (P =.29).
Clinical indicators of potential cerebral dysfunction other than the Glasgow Coma Scale score were not used to define neurologic events; therefore, the researchers suggest the study may have missed possible indicators of neurologic dysfunction. Despite this limitation, the researchers concluded “the rate of fluid infusion plays a minimal role” in cerebral injury or mental status changes of children with DKA.
Glaser NS, Stoner MJ, Garro A, et al. Serum sodium concentration and mental status in children with diabetic ketoacidosis. Pediatrics. Published online August 9, 2021. doi:10.1542/peds.2021-050243