Diabetic Ketoacidosis
Conditions
Keywords
intravenous fluids, adults, two bag system
Brief summary
This is a study investigating the best way to treat diabetic ketoacidosis (DKA) with intravenous (IV) fluids in the hospital. The purpose of this study is to determine whether the two bag system of administering IV fluids for the treatment of adults with DKA leads to a shorter time requiring intravenous insulin (a shorter time to anion gap closure), when compared to usual care the traditional one bag system of IV fluids. Participants will be assigned randomly to either the usual care group or the two bag system group. Based on studies performed in the past, the investigators predict that patients treated with the two bag system of IV fluids for DKA will have a significantly shorter time requiring treatment with intravenous insulin when compared to the traditional one bag system.
Detailed description
The two bag system has been studied in the pediatric population and is used frequently in pediatric intensive care units. It involves two bags of identical fluids with electrolytes, except one bag has 0% dextrose and the other has 10% dextrose. The two fluid bags run simultaneously into a single IV. The rates of the two fluid bags are adjusted according to the patient's blood sugar. Since the hyperglycemia in DKA typically corrects before the ketosis, this provides a more efficient method of titrating the dextrose concentration based on the patient's needs, while continuing to infuse the insulin at a constant rate to prevent further ketogenesis. The benefits of the two bag system from the pediatric literature include: decreased response time to IV fluid changes, decreased time to correction of bicarbonate and ketones, and decreased total IV fluid volume administered. There was one retrospective study of the two bag system in adults, which showed decreased time to anion gap closure and decreased hypoglycemic events. To this date, there are no prospective randomized trials to evaluate the efficacy of the two bag system in adults. Patients admitted with DKA in the critical care pavilion will be randomized to either the two bag system or usual care group. Patients in both groups will be treated for DKA with IV fluid resuscitation for dehydration and an insulin infusion according to usual care, recommended at 0.1 U/kg/hr. The two bag system of IV fluids will be ordered as delineated below: If blood sugar is \> 300, run D10 solution at 0 ml/hr and saline solution at 200 ml/hr. If blood sugar is 250-299, run D10 solution at 50 ml/hr and saline solution at 150 ml/hr. If blood sugar is 200-249, run D10 solution at 100 ml/hr and saline solution at 100 ml/hr. If blood sugar is 150-199, run D10 solution at 150 ml/hr and saline solution at 50 ml/hr. If blood sugar is \< 150, run D10 solution at 200 ml/hr and saline solution at 0 ml/hr. The control group will be usual care of DKA based on the American Diabetes Association Guidelines using a one bag system. In both groups, blood sugars will be checked every hour while on the insulin drip. A basic metabolic panel will be checked every 4 hours to monitor the anion gap. Once the anion gap is closed on two occasions and the subject is able to tolerate an enteral diet, the patient will be transitioned to subcutaneous insulin and insulin drip will be discontinued.
Interventions
The two IV fluid bags have identical fluids and electrolytes, except one has 10% dextrose and the other has no dextrose. The two fluid bags run simultaneously and their rates are adjusted according to the patient's blood sugar.
Sponsors
Study design
Eligibility
Inclusion criteria
1. Diagnosis of diabetic ketoacidosis defined as: 1. Blood sugar greater than 250 mg/dl 2. Venous pH less than 7.25 3. Bicarbonate less than 18 4. Evidence of ketone formation with either positive urine ketones or elevated beta-hydroxybutyrate \> 3 5. Anion gap greater than 10 +/ - 2 (or higher than expected anion gap corrected for albumin) 2. 18-85 years of age
Exclusion criteria
1. Pregnancy 2. Hyperglycemic hyperosmolar state 3. Ketosis from other etiology such as starvation or alcoholic ketosis 4. Acute exacerbation of congestive heart failure 5. Acute coronary syndrome or non-ST elevation MI 6. Pulmonary edema from other cause such as decompensated liver failure or acute renal failure 7. Renal failure requiring renal replacement therapy (hemodialysis) 8. Septic shock
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Anion Gap Closure in Hours | while in DKA | Anion gap (Na - Cl - HCO3) is within normal range when corrected for the albumin (time to anion gap closure will be defined as the time to the first occurrence of a normal anion gap). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypernatremia | while in DKA | Maximum sodium level \> 153 mmol/L |
| Hyperkalemia | while in DKA | Maximum K level \> 5.3 mmol/L |
| Number of Participants Experiencing Hypoglycemic Episodes | while in DKA | Symptomatic episodes of hypoglycemia |
| Number of Participants Experiencing Hypoxic Episodes | while in DKA | Desaturations less than 89% requiring supplemental oxygen |
| Pulmonary Edema | while in DKA | Pulmonary edema seen on either chest X-ray or with the change in the lung exam |
| Total Volume of Intravenous Fluids Administered | while in DKA | Total volume of intravenous fluids administered |
| Hyponatremia Events | while in DKA | Sodium values less than 135 mmol/L (corrected for glucose) |
| Hypokalemia Events | while in DKA | Potassium values less than 3.3 mmol/L |
| ICU Length of Stay | during hospitalization | Total time the patient was admitted in the stepdown unit and/or medical ICU |
| Changes in Mental Status | while in DKA | Worsening in either CAM-ICU score or Glasgow Coma Scale |
| Chest Pain With EKG Changes | while in DKA | Onset of new chest pain with new EKG changes concerning for ischemia |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Usual care with a one bag system of IV fluids, as recommended in the American Diabetes Association consensus statement guidelines from 2009. | 25 |
| Two Bag System A two bag system of IV fluids will be used during insulin infusion administration.
Two bag system: The two IV fluid bags have identical fluids (normal saline or half normal saline) and electrolytes (optional addition of potassium chloride or potassium phosphate), except one has 10% dextrose and the other has no dextrose. The two fluid bags run simultaneously and their rates are adjusted according to the patient's blood sugar. Total fluid rate (sum of rates of two bags) is 200mL/hour. | 32 |
| Total | 57 |
Baseline characteristics
| Characteristic | Usual Care | Two Bag System | Total |
|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 13.3 | 38.6 years STANDARD_DEVIATION 13.6 | 37.1 years STANDARD_DEVIATION 13.5 |
| pH on VBG (venous blood gas) at time of presentation | 7.11 unitless STANDARD_DEVIATION 0.14 | 7.09 unitless STANDARD_DEVIATION 0.14 | 7.10 unitless STANDARD_DEVIATION 0.14 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 25 participants | 32 participants | 57 participants |
| Sex: Female, Male Female | 15 Participants | 21 Participants | 36 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
| Type of Diabetes (Number of Participants with Type 1 DM) | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 32 |
| other Total, other adverse events | 0 / 25 | 0 / 32 |
| serious Total, serious adverse events | 0 / 25 | 0 / 32 |
Outcome results
Time to Anion Gap Closure in Hours
Anion gap (Na - Cl - HCO3) is within normal range when corrected for the albumin (time to anion gap closure will be defined as the time to the first occurrence of a normal anion gap).
Time frame: while in DKA
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual Care | Time to Anion Gap Closure in Hours | Time to AG closure (from ED admit) | 11.2 hours | Standard Deviation 5.1 |
| Usual Care | Time to Anion Gap Closure in Hours | Time to AG closure (from first BMP) | 12.0 hours | Standard Deviation 6.7 |
| Two Bag System | Time to Anion Gap Closure in Hours | Time to AG closure (from ED admit) | 12.2 hours | Standard Deviation 3.9 |
| Two Bag System | Time to Anion Gap Closure in Hours | Time to AG closure (from first BMP) | 13.5 hours | Standard Deviation 7.7 |
Changes in Mental Status
Worsening in either CAM-ICU score or Glasgow Coma Scale
Time frame: while in DKA
Chest Pain With EKG Changes
Onset of new chest pain with new EKG changes concerning for ischemia
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Chest Pain With EKG Changes | 0 Participants |
| Two Bag System | Chest Pain With EKG Changes | 0 Participants |
Hyperkalemia
Maximum K level \> 5.3 mmol/L
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Hyperkalemia | 3 Participants |
| Two Bag System | Hyperkalemia | 5 Participants |
Hypernatremia
Maximum sodium level \> 153 mmol/L
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Hypernatremia | 1 Participants |
| Two Bag System | Hypernatremia | 2 Participants |
Hypokalemia Events
Potassium values less than 3.3 mmol/L
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Hypokalemia Events | 2 Participants |
| Two Bag System | Hypokalemia Events | 5 Participants |
Hyponatremia Events
Sodium values less than 135 mmol/L (corrected for glucose)
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Hyponatremia Events | 9 Participants |
| Two Bag System | Hyponatremia Events | 12 Participants |
ICU Length of Stay
Total time the patient was admitted in the stepdown unit and/or medical ICU
Time frame: during hospitalization
Number of Participants Experiencing Hypoglycemic Episodes
Symptomatic episodes of hypoglycemia
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Participants Experiencing Hypoglycemic Episodes | 0 Participants |
| Two Bag System | Number of Participants Experiencing Hypoglycemic Episodes | 0 Participants |
Number of Participants Experiencing Hypoxic Episodes
Desaturations less than 89% requiring supplemental oxygen
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Participants Experiencing Hypoxic Episodes | 0 Participants |
| Two Bag System | Number of Participants Experiencing Hypoxic Episodes | 1 Participants |
Pulmonary Edema
Pulmonary edema seen on either chest X-ray or with the change in the lung exam
Time frame: while in DKA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Pulmonary Edema | 0 Participants |
| Two Bag System | Pulmonary Edema | 0 Participants |
Total Volume of Intravenous Fluids Administered
Total volume of intravenous fluids administered
Time frame: while in DKA