Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis

N Engl J Med. 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816.

Abstract

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 .).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain Edema / etiology
  • Brain Injuries / diagnosis
  • Brain Injuries / etiology*
  • Brain Injuries / prevention & control
  • Child
  • Child, Preschool
  • Diabetic Ketoacidosis / complications
  • Diabetic Ketoacidosis / psychology
  • Diabetic Ketoacidosis / therapy*
  • Drug Administration Schedule
  • Female
  • Fluid Therapy / methods*
  • Glasgow Coma Scale
  • Humans
  • Infant
  • Infusions, Intravenous
  • Male
  • Prospective Studies
  • Rehydration Solutions / administration & dosage*
  • Rehydration Solutions / chemistry
  • Sodium Chloride / administration & dosage

Substances

  • Rehydration Solutions
  • Sodium Chloride

Associated data

  • ClinicalTrials.gov/NCT00629707