Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis

University of California (UC) Davis

Status and phase: Completed; Phase 3

Conditions: Cerebral Edema; Diabetic Ketoacidosis

Treatments: Drug: 0.9% saline Intravenous fluid; Drug: 0.9% saline replacement fluid; Drug: 0.45% saline intravenous fluid; Drug: 0.45% saline replacement fluid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01365793

230233

U01HD062417 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

These data will be compared to observational data from children with type 1 diabetes without DKA.

Enrollment: 1,389 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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1,389 participants in 4 patient groups

Rapid rehydration using 0.45% saline replacement fluid

Experimental group

Description:

This arm will involve more rapid intravenous fluid treatment which will include a second 10cc/Kg bolus of 0.9% saline and assume a 10% fluid deficit. 0.45% saline will be used as the replacement fluid for this arm.

Treatment:

Drug: 0.45% saline replacement fluid

Rapid rehydration using 0.9% saline replacement fluid

Experimental group

Description:

This arm will involve more rapid intravenous fluid treatment which will include a second 10cc/Kg bolus of 0.9% saline and assume a 10% fluid deficit. 0.9% saline will be used as the replacement fluid.

Treatment:

Drug: 0.9% saline replacement fluid

Slower rehydration using 0.45% saline intravenous fluid

Experimental group

Description:

This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fluid bolus) with 0.45% saline used as the replacement fluid.

Treatment:

Drug: 0.45% saline intravenous fluid

Slower rehydration using 0.9% saline intravenous fluid

Experimental group

Description:

This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fuid bolus) with 0.9% saline used as the replacement fluid.

Treatment:

Drug: 0.9% saline Intravenous fluid