The pathogenesis of CE in children with DKA is controversial. There are those who propose that it is caused by excessive administration of IV fluids and cerebral osmotic shifts. Alternatively it might be caused by cerebral hypoperfusion and reperfusion during DKA treatment. Should we be giving more fluid or less fluid… Who knows?
In an ideal world, we would answer this question by conducting a large randomized control trial in the sickest subset of children. These are the kids who develop CE. We would randomize two groups. One gets lots of fluids and the other not so much. The primary outcome would be death as this is usually caused by cerebral oedema. Unfortunately such a study would be near impossible to conduct given the rarity of clinical apparent CE in children with DKA.
The authors of this paper perhaps tried the next best thing. They conducted an RCT using 2 different rehydration protocols (but some would argue were not that different). In the end, one group got 60ml/kg and the other 40ml/kg in the first 8 hours. They used the “apparent diffusion coefficient” on serial MRI’s as a surrogate marker to look for cerebral oedema. All of kids recovered well.
The conclusion of the paper? Cerebral oedema does not appear to be substantially affected by the rate of IV fluid administration.
But hold on a minute… There were only 18 children included in this study. Clearly there would have only been enough statistical power to find very large differences in the study arms. In addition, one might question the validity of the surrogate marker looking for subclinical CE. The conclusion as written in the paper clearly overstates any reasonable interpretation of this study.
In the end, this paper raises more questions than it answers. It certainly would raise the hypothesis (again) calling for a large RCT which will probably never happen.
Before we get too critical, we should remember that the lead author, Dr Nicole Glaser, a professor of pediatric endocrinology at UC Davis has done some fantastic work well over the past decade looking at this subject. (Remember NEJM 2001;344(4):264-269?) This is a very challenging niche of research and we see look forward to see more of her work.
Glaser NS, Wootton-Gorges SL, Buonocore MH et al. Subclinical Cerebral Edema in Children With Diabetic Ketoacidosis Randomized to 2 Different Rehydration Protocols. Pediatrics 2013;131;e73-e80.http://www.ncbi.nlm.nih.gov/pubmed/?term=subclinical+cerebral+edema+in+children+with+diabetic+ketoacidosis+randomized+to+2