Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis
Condition: Cerebral Edema; Diabetic Ketoacidosis
MeSH terms: Brain Edema; Ketosis; Acidosis; Diabetic Ketoacidosis
Intervention: 0.45% saline replacement fluid; 0.9% saline replacement fluid; 0.45% saline intravenous fluid; 0.9% saline Intravenous fluid
Intervention description: 10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid; 10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid.; 0.45% saline fluid; 0.9% saline fluid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 1389.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No
Keywords: cerebral edema; diabetic ketoacidosis; pediatric diabetes; fluid therapy

Summary:

      The investigators will conduct a randomized controlled trial comparing four different
      intravenous (IV) fluid treatment protocols for pediatric diabetic ketoacidosis (DKA). Two
      rates of rehydration will be compared; a more rapid rate and a slower rate. Within each of
      these two basic rehydration protocols, the investigators will vary the type of rehydration
      fluid used (0.9% saline or 0.45% saline). The investigators will compare the different
      treatments by conducting assessments of neurological injury, by measuring the frequency of
      significant cerebral edema, and by measuring long-term neurocognitive function.

      These studies will allow us to determine whether variations in IV fluid treatment protocols
      affect acute neurological outcomes of DKA. Additionally, they will provide important data
      regarding the impact of DKA and DKA treatment on long-term neurocognitive function in
      children. In this way, the investigators hope to identify a more ideal fluid management
      strategy for children with DKA.

      Previous studies have suggested that DKA may cause blood flow to the brain to be reduced and
      that brain injury might result from this reduction in blood flow and/or the effects of
      re-establishment of normal blood flow during DKA treatment with insulin and iv fluids. The
      investigators hypothesize that more rapidly re-establishing normal blood flow to the brain
      during DKA, by giving fluids more rapidly and using fluids with a higher sodium (salt)
      content, will help to minimize brain injury caused by DKA.
    

Eligibility criteria:

        Inclusion Criteria:

          -  must present or be transferred to a participating emergency department

          -  age less than 18 years

          -  diagnosis of DKA

               -  serum glucose or fingerstick glucose concentration >300 mg/dL

               -  venous pH < 7.25 OR serum bicarbonate concentration < 15 mmol/L.

        Exclusion Criteria:

          -  patients with underlying neurological disorders or neurocognitive deficits which would
             affect either mental status testing during treatment or subsequent neurocognitive
             testing after recovery

          -  patients who present with concomitant alcohol or drug use, head trauma, meningitis or
             other conditions which might affect neurological function

          -  patients transferred to one of the participating emergency departments after
             initiation of DKA treatment other than one 10cc/kg intravenous bolus of 0.9% saline

          -  patients who are known to be pregnant at time of ED evaluation

          -  patients who have been enrolled in this study twice previously

          -  patients for whom the treating physician believed a specific fluid and electrolyte
             regimen was warranted

          -  patients for whom informed consent could not be obtained within 1 hour after
             completion of the initial fluid bolus, or within 2 hours from initiation of fluids,
             whichever is longer

          -  Patients who have been receiving IV fluids at a maintenance rate or greater (defined
             by the 4-2-1 rule) for more than two hours; OR

          -  Patients for whom it has been more than four hours since DKA therapy (IV fluids, IV
             bolus, or IV insulin) began; OR

          -  Patients who have been given hyperosmolar therapy (i.e. mannitol or 3% normal saline)
             prior to or since arriving at one of the participating PECARN emergency departments;
             OR

          -  Patients for whom the treating physician intends to immediately administer
             hyperosmolar therapy (i.e. mannitol or 3% normal saline); OR

          -  Patients whose baseline GCS is 11 or less.