Clinical trial NCT00629707: Cerebral Edema in Pediatric Diabetic Ketoacidosis
Official title: Cerebral Edema in Pediatric Diabetic Ketoacidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Ketoacidosis
Keywords: diabetic ketoacidosis
DKA
cerebral edema
brain edema
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2008-03-06
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to compare two different rates of fluid administration during diabetic ketoacidosis (DKA) treatment in children to determine which fluid administration rate is more beneficial for brain metabolism and for preventing or decreasing brain swelling during DKA.

Detailed description: Cerebral edema (swelling of the brain) is the most frequent serious complication of diabetic ketoacidosis (DKA) in children. The cause of cerebral edema during DKA is not well understood. Recent studies suggest that it may result from lack of adequate blood flow to the brain during DKA, before treatment starts. Brain injury, resulting in edema, may occur before treatment because of lack of adequate blood flow to the brain and additional injury may occur when adequate blood flow is re-established during treatment (called reperfusion injury). Because additional injury may occur during treatment, it is important to understand whether the rate of administration of intravenous fluids, and, therefore, the speed of reperfusion of the brain, is related to the degree of brain swelling and injury. Most current treatment protocols indicate that intravenous fluids should be administered slowly, but it may be possible that brain injury and swelling might be lessened if adequate blood flow is established more quickly.

In this study, researchers will use magnetic resonance (MR) imaging to compare two different rates of fluid administration during DKA treatment in children. The investigators will use MR imaging to measure brain swelling and metabolism at three time points-twice during treatment and once after recovery from DKA-and will compare these measurements to determine which fluid administration rate has more beneficial effects on brain metabolism and brain swelling.

The study's researchers hypothesize that more rapid re-establishment of blood flow to the brain (via more rapid administration of intravenous fluids) will result in less brain swelling and injury than slower rehydration with delayed re-establishment of adequate brain blood flow will.

Eligibility criteria: Inclusion Criteria:

* age 8-18 years
* diagnosis of diabetic ketoacidosis
* able to cooperate with MR scanning

Exclusion Criteria:

* pre-existing cerebral injury or brain structural abnormality
* dental hardware or other metal devices which would interfere with MR imaging

Primary outcomes:
measure: Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient)
timeFrame: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
Secondary outcomes:
measure: Brain NAA/Creatine Ratio & Brain Lactate Measured by MR Spectroscopy, Cerebral Blood Flow & Oxygen Saturation Measured by MR Perfusion Weighted Imaging & Near Infrared Spectroscopy, Mental Status Evaluated by Glasgow Coma Scale Scores.
timeFrame: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Medical Center, 2315 Stockton Blvd
state: California
Study officials:
affiliation: University of California, Davis
name: Nicole Glaser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rewers A, Kuppermann N, Stoner MJ, Garro A, Bennett JE, Quayle KS, Schunk JE, Myers SR, McManemy JK, Nigrovic LE, Trainor JL, Tzimenatos L, Kwok MY, Brown KM, Olsen CS, Casper TC, Ghetti S, Glaser NS; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group. Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis. Diabetes Care. 2021 Sep;44(9):2061-2068. doi: 10.2337/dc20-3113. Epub 2021 Jun 29.
citation: Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816.