medwireNews: Neither the rate of administration nor the sodium chloride content of replacement fluids given to children with diabetic ketoacidosis (DKA) influences their neurologic outcomes, show the results of the PECARN DKA FLUID Study.
Lead researcher Nathan Kuppermann (University of California, Davis, Sacramento, USA) and colleagues note that although treated DKA rarely leads to clinically evident brain injury, it “is an important cause of neurologic damage and death among children with diabetes.”
Their findings, which appear in The New England Journal of Medicine, would appear to contradict the theory that this damage is caused by osmotic changes during DKA management. The other prevailing theory is that the neurologic damage is a form of ischemia–reperfusion injury, they note.
The 1255 trial participants, who had a total of 1389 DKA episodes between them, were randomly assigned to one of four groups. They were given either 0.45% or 0.90% sodium chloride, which was either delivered fast, with half the fluid deficit, assumed to be 10% of bodyweight, administered within 12 hours and the remainder plus maintenance fluids within the subsequent 24 hours, or delivered slowly, with an assumed deficit of 5% of bodyweight plus maintenance fluids given evenly over 48 hours.
In an editorial accompanying the study, Mark Sperling (Icahn School of Medicine at Mt Sinai, New York, USA) notes that these approaches are all used in current clinical practice, although current guidelines, which “are based as much on experience as on comparative trials […] recommend that the replacement of crystalloid fluid after initial bolus resuscitation should be gradual over the course of 48 hours.”
Although rapid delivery of intravenous fluids has been linked to an increased risk for brain damage in retrospective studies, the researchers found that their primary outcome of a decline in Glasgow Coma Scale score to below 14 occurred in slightly (albeit not significantly) more patients assigned to receive slow fluid administration, at 3.3% and 4.7% of those given 0.45% and 0.90% sodium chloride, respectively, compared with 3.0% and 3.2% of those in the fast administration group.
The same was true for rates of clinically apparent brain damage during treatment (deterioration that prompted initiation of hyperosmolar therapy or endotracheal intubation, or resulted in death), at a corresponding 1.4% and 0.9% versus 0.6% and 0.6%. Results for the digit-span recall test, forward slope bordered on significantly better for the fast versus slow administration groups.
Sperling says that these PECARN (Pediatric Emergency Care Applied Research Network) findings “are likely to generate discussion and lead to revision of current recommendations.”
He also highlights that just one of the 12 children with clinically apparent brain damage during treatment died, and that none of the survivors had residual neurologic deficits, contrary to previously reported rates of 30–50%.
This attests “to the need to refer children with diabetic ketoacidosis to specialized centers,” he says.
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