Two Bag System for Diabetic Ketoacidosis (2BagDKA)

The "Two Bag" System for Treatment of Adults With Diabetic Ketoacidosis: a Prospective Randomized Study

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Ketoacidosis
• Intervention / Treatment: Other: Two 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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chloe Castro, MD; Phone Number: 2167785935; Email: ccastro@metrohealth.org
• Study Contact Backup: Name: Vidya Krishnan, MD; Phone Number: 2167785864; Email: vkrishnan@metrohealth.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care; Usual care with a one bag system of IV fluids, as recommended in the American Diabetes Association consensus statement guidelines from 2009.
Experimental: Two bag system; A two bag system of IV fluids will be used during insulin infusion administration.	Other: Two bag system; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	During hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemic episodes	Symptomatic episodes of hypoglycemia	During hospitalization
Hypoxic events	Desaturations less than 89% requiring supplemental oxygen	During hospitalization
Pulmonary edema	Pulmonary edema seen on either chest X-ray or with the change in the lung exam	During hospitalization
Chest pain with EKG changes	Onset of new chest pain with new EKG changes concerning for ischemia	During hospitalization
Hyponatremia events	Sodium values less than 135 mmol/L (corrected for glucose)	During hospitalization
Hypokalemia events	Potassium values less than 3.3 mmol/L	During hospitalization
ICU length of stay	Total time the patient was admitted in the stepdown unit and/or medical ICU	During hospitalization
Changes in mental status	Worsening in either CAM-ICU score or Glasgow Coma Scale	During hospitalization
Total volume of intravenous fluids administered	Total volume of intravenous fluids administered	During hospitalization

Collaborators and Investigators

• Sponsor: MetroHealth Medical Center
• Investigators: Principal Investigator: Vidya Krishnan, MD, MetroHealth Medical Center

Publications and helpful links

General Publications

• Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48. doi: 10.2337/dc06-9916. No abstract available.
• Grimberg A, Cerri RW, Satin-Smith M, Cohen P. The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management. J Pediatr. 1999 Mar;134(3):376-8. doi: 10.1016/s0022-3476(99)70469-5.
• So TY, Grunewalder E. Evaluation of the two-bag system for fluid management in pediatric patients with diabetic ketoacidosis. J Pediatr Pharmacol Ther. 2009 Apr;14(2):100-5. doi: 10.5863/1551-6776-14.2.100.
• Munir I, Fargo R, Garrison R, Yang A, Cheng A, Kang I, Motabar A, Xu K, Loo LK, Kim DI. Comparison of a 'two-bag system' versus conventional treatment protocol ('one-bag system') in the management of diabetic ketoacidosis. BMJ Open Diabetes Res Care. 2017 Aug 11;5(1):e000395. doi: 10.1136/bmjdrc-2017-000395. eCollection 2017.
• Poirier MP, Greer D, Satin-Smith M. A prospective study of the "two-bag system'' in diabetic ketoacidosis management. Clin Pediatr (Phila). 2004 Nov-Dec;43(9):809-13. doi: 10.1177/000992280404300904.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): June 15, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: adults; intravenous fluids; two bag system
• Additional Relevant MeSH Terms: Metabolic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Acid-Base Imbalance; Acidosis; Ketosis; Diabetic Ketoacidosis
• Other Study ID Numbers: IRB18-00025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current plan to share individual participant data at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No