Kuppermann N, Ghetti S, Schunk JE, et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018;378:2275-2287. DOI: 10.1056/NEJMoa1716816.
In treatment of diabetic ketoacidosis (DKA), brain injuries and less severe neurologic symptoms have been observed and attributed to rapid infusion of intravenous fluids. Best clinical practice has not been established. In this randomized, controlled trial at 13 emergency departments (EDs) in the US, 1255 children 0-18 years old were given a bolus of either 0.45% or 0.9% sodium chloride solution, administered either slow or fast (i.e., 4 different treatment groups), followed by insulin. Clinically apparent brain injury occurred in 0.9% of patients and did not differ significantly by treatment regimen.
Written informed consent was obtained from the parents or guardians of all patients enrolled in the trial, and assent was obtained from children who had reached the age of assent according to each institution's review board. Clinicians were aware of the randomized treatment regimen because they needed to know the regimen for purposes of further treatment. The primary outcome was worsening of neurologic status as measured by 2 consecutive Glasgow Coma Scale scores <14 during any hour within the first 24 hours of treatment for DKA. Secondary outcomes were short-term memory (digit-span recall) during treatment for DKA, and then short-term memory, contextual memory, and IQ 2 to 6 months after the DKA episode. Some children who had repeat episodes of DKA were randomized more than once. In subgroup analyses, decline in mental status and brain injury were less common in the fast-infusion groups, but not statistically significantly so. A key challenge to achieving sufficient statistical power in this trial was that the primary outcome occurred less than 1% of the time, making it impractical to design a trial large enough to detect a difference in neurologic changes.