Background: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades.
Methods: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis.
Results: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups.
Conclusions: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).
Conflict of interest statement
No potential conflict of interest relevant to this article was reported.
Pediatric Diabetic Ketoacidosis, Fluid Therapy, and Cerebral Injury: The Design of a Factorial Randomized Controlled TrialNS Glaser et al. Pediatr Diabetes 14 (6), 435-46. PMID 23490311. - Randomized Controlled TrialTreatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid ad …
Low Morbidity and Mortality in Children With Diabetic Ketoacidosis Treated With Isotonic FluidsPC White et al. J Pediatr 163 (3), 761-6. PMID 23499379.Compared with data in recent consensus statements, the Dallas protocol is associated with extremely low rates of death and disability (0.08% vs 0.3%) from DKA.
Sodium Concentration in Rehydration Fluids for Children With Ketoacidotic Diabetes: Effect on Serum Sodium ConcentrationJD Toledo et al. J Pediatr 154 (6), 895-900. PMID 19230907.Sodium concentration in the rehydration fluids behaves as an independent factor that influences positively the trend of the serum concentration of sodium during DKA rehyd …
Emergency Medicine Myths: Cerebral Edema in Pediatric Diabetic Ketoacidosis and Intravenous FluidsB Long et al. J Emerg Med 53 (2), 212-221. PMID 28412071. - ReviewPediatric CE in DKA is rare but severe. Multiple mechanisms result in this disease, and many patients experience subclinical CE. Intravenous fluids are likely not associa …
Evidence-based Emergency Medicine/Critically Appraised Topic. Is Fluid Therapy Associated With Cerebral Edema in Children With Diabetic Ketoacidosis?J Hom et al. Ann Emerg Med 52 (1), 69-75.e1. PMID 18387706. - ReviewAccepting the inherent limitations of observational studies, we found a lack of strong or consistent results implicating rate or volume of fluid administration as a preci …
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- Brain Injuries / etiology *
- Diabetic Ketoacidosis / therapy *
- Fluid Therapy / methods *
- Rehydration Solutions / administration & dosage *
- Brain Edema / etiology
- Brain Injuries / diagnosis
- Brain Injuries / prevention & control
- Child, Preschool
- Diabetic Ketoacidosis / complications
- Diabetic Ketoacidosis / psychology
- Drug Administration Schedule
- Glasgow Coma Scale
- Infusions, Intravenous
- Prospective Studies
- Rehydration Solutions / chemistry
- Sodium Chloride / administration & dosage