Diabetic Ketoacidosis
Conditions
Keywords
diabetic ketoacidosis, DKA, cerebral edema, brain edema
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.
Interventions
OTHERintravenous fluid treatment
infusion of intravenous fluids (0.9% saline and 0.45% saline)
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient) | 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 | In both groups, brain Apparent Diffusion Coefficient (ADC) measures at 3-6 hours and 9-12 hours after beginning DKA treatment were averaged to determine overall brain ADC during DKA treatment. The brain ADC indicates the distribution of water in the brain and is an indicator of brain swelling (edema). The overall brain ADC values during DKA treatment were compared with the brain ADC measured after recovery to assess the degree of brain edema formation during DKA treatment. The difference in brain ADC, calculated as the averaged treatment values minus the recovery value, was used as the main outcome measure to indicate the degree of brain edema formation |
Secondary
| Measure | Time frame |
|---|---|
| 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. | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Slow Fluid Infusion Slower infusion rate: Patients in this arm will receive an initial intravenous fluid bolus of 10cc/Kg followed by rehydration calculated to replace a deficit of 7.5% of body weight over 48 hours. | 10 |
| Rapid Fluid Infusion More rapid infusion: Patients in this arm will receive an initial bolus of 20 cc/Kg of intravenous fluids followed by replacement of an estimated deficit of 10% of body weight over 36 hours plus replacement of 1/2 of urine output volume. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Rapid Fluid Infusion | Slow Fluid Infusion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 11.4 years STANDARD_DEVIATION 1.8 | 14.2 years STANDARD_DEVIATION 3.4 | 12.9 years STANDARD_DEVIATION 3.1 |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 |
Outcome results
Primary
Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient)
In both groups, brain Apparent Diffusion Coefficient (ADC) measures at 3-6 hours and 9-12 hours after beginning DKA treatment were averaged to determine overall brain ADC during DKA treatment. The brain ADC indicates the distribution of water in the brain and is an indicator of brain swelling (edema). The overall brain ADC values during DKA treatment were compared with the brain ADC measured after recovery to assess the degree of brain edema formation during DKA treatment. The difference in brain ADC, calculated as the averaged treatment values minus the recovery value, was used as the main outcome measure to indicate the degree of brain edema formation
Time frame: 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
Population: Data from all enrolled participant that completed the study were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Fluid Infusion | Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient) | 36 mm^2/sec | Standard Deviation 30 |
| Rapid Fluid Infusion | Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient) | 48 mm^2/sec | Standard Deviation 41 |
Secondary
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.
Time frame: 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