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Member Research & Reports

Member Research & Reports

Northwestern: Rethinking Longstanding Treatment for Diabetes Complications

Rapid fluid administration to children suffering from complications related to diabetic ketoacidosis does not increase the risk of brain injury, according to a study published in the New England Journal of Medicine.

These findings stand in contrast to the current standard of care, which suggests slow rehydration to avoid brain injury, according to Dr. Jennifer Trainor, associate professor of pediatrics in the division of emergency medicine at the Northwestern University Feinberg School of Medicine and a co-author of the study.

Diabetic ketoacidosis is a serious complication of diabetes, where a lack of insulin causes the body to produce high levels of blood acids called ketones, leading to symptoms such as vomiting, abdominal pain, weakness or loss of consciousness. Treatment protocols often call for slow rehydration, stemming from early theories that rapid rehydration could result in brain swelling.

“After those studies were published in the late 1980s and early 1990s, slow rehydration was universally recommended in pediatric diabetic ketoacidosis, and fluids were always limited in order to prevent cerebral edema,” said Dr. Trainor, who’s also an associate professor of medical education and a member of the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago. “This belief was so strong that even when a well-designed multi-center retrospective case-control study adjusting for these confounders failed to find an association between fluid volume and rate of cerebral edema, the dogma still persisted and practice did not change.“

In the new study, a randomized trial was conducted at 13 emergency departments across the United States, all members of the Pediatric Emergency Care Applied Research Network. Patients under the age of 18 were given one of four rehydration treatments, consisting of two rates of fluid administration and two different intravenous solutions.

In 1,361 episodes of diabetic ketoacidosis, the authors found no significant differences in rates of mental status decline or brain injury, when comparing rehydration treatments.

These findings demonstrate the lack of causal association between rapid fluid administration and diabetic ketoacidosis-related brain injury, according to the authors. In fact, analyses of patients with severe ketoacidosis suggested faster administration improved scores on certain neurological tests, underlining the need to further understand the mechanistic basis of the disease.

Studies in rodent models have found similarities between diabetic ketoacidosis-related injury and injuries that can occur when blood supply is cut off and then later returned to tissue, known as reperfusion. Abnormalities in inflammation are another hypothesis, providing multiple avenues of further study, according to the authors.

“Now that we have hopefully laid this dogma to rest, investigators can focus on better characterizing what actually is occurring and leading to what we now believe is a brain injury, which can subsequently result in cerebral edema,” Dr. Trainor said.

The study was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U01HD062417; the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau; and Health Resources and Services Administration awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684 and U03MC22685.

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