Friday 21 September 2018

Clinical Trial of Fluid Infusion Rates for Pediatric DKA

Dr Annoying Bowtie, RACP

Emergency physicians often get criticised for overhydrating children with DKA. “Too much fluids will cause their heads to explode,” as spoken from an annoying bow tie.

But there has never been good quality evidence to prove fluid administration causes cerebral edema. In fact, a study by Glaser etal. in 2001 showed no association between fluids and bad outcomes.

But as there is no definitive RCT, the debate still rages!

Hopefully this clinical trial will put matters to rest.

After 17 years, Dr Nicole Glaser is back! Now teamed up with the PECARN mega-group, they randomised 1255 children with 1389 DKA episodes to one of 4 treatment arms (please see original paper for further details)

  • Fast administration of 0.9% normal saline
  • Fast administration of 0.45% normal saline
  • Slow administration of 0.9% normal saline
  • Slow administration of 0.45% normal saline

(Just to give an idea of what is fast vs. slow, a 50 kg child would get an infusion started of 300ml/hour vs. 140ml/hour.)

The primary outcome was a decline in mental status (measured by GCS) during treatment. Secondary outcomes included clinically apparent brain injury during treatment and some measures of memory.


No difference. Neither the rate of administration nor the sodium chloride content of the IV fluids resulted in bad outcomes. 

So the debate is over?

Unfortunately, no.

98% of the children recruited in this study started out at GCS 14-15.  We know it is the sickest cohort of DKA that develop bad complications. This study was never going to show a difference. The clear majority were going to get better with any reasonable management... regardless of fluid protocols.

What about the child with a pH of 6.9 and GCS 6? Does the rate of fluid administration matter?


Unfortunately, an adequately powered RCT of severe DKA will never happen. It is simply not feasible. 

Alas, the annoying bow ties will continue...


Kupperman N, Ghetti S, Schunk J, et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med 2018;378:2275-87. [link to original full text article]

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