What is the initial intravenous (IV) insulin bolus for diabetic ketoacidosis (DKA)?

From the Guidelines

The initial IV insulin bolus for DKA is not recommended, and instead, a continuous insulin infusion at 0.1 units/kg/hour should be started immediately. This approach is supported by the most recent guidelines, which prioritize avoiding hypoglycemia and achieving specific glycemic goals in the critical care setting 1. For example, a 70 kg patient would receive a continuous infusion of 7 units/hour. This method quickly establishes therapeutic insulin levels to suppress ketogenesis, promote glucose utilization, and correct metabolic acidosis. The insulin infusion should be continued until the anion gap normalizes, serum bicarbonate rises above 18 mEq/L, and the patient is able to eat. Importantly, IV fluids and potassium replacement must be administered concurrently, and glucose should be added to IV fluids once blood glucose falls below 200-250 mg/dL to prevent hypoglycemia while continuing insulin to clear ketones.

Some key points to consider when managing DKA include:

• Using validated written or computerized protocols for insulin infusion adjustments 1
• Avoiding prolonged use of correction or supplemental insulin without basal insulin in the inpatient setting 1
• Monitoring blood glucose and potassium concentrations closely to adjust insulin infusion rates as needed
• Providing adequate fluid and electrolyte replacement to correct dehydration and electrolyte imbalances

It's worth noting that the use of an initial IV insulin bolus has been a topic of debate, with some guidelines suggesting that it may not be necessary and may even increase the risk of hypoglycemia 1. However, the most recent guidelines prioritize a continuous insulin infusion approach, which is supported by the highest quality evidence 1.

From the FDA Drug Label

The intravenous administration of Humulin R U-100 was tested in 21 patients with type 1 diabetes The patients' usual doses of insulin were temporarily held, and blood glucose concentrations were maintained at a range of 200 – 260 mg/dL for one to three hours during a run-in phase of intravenous Humulin R U-100 followed by a 6-hour assessment phase. During the assessment phase patients received intravenous Humulin R at an initial dose of 0. 5 U/h, adjusted to maintain blood glucose concentrations near normoglycemia (100 to 160 mg/dL).

The initial intravenous (IV) insulin dose for the study patients was 0.5 U/h, however, this study does not directly address the treatment of diabetic ketoacidosis (DKA).

• The study involved patients with type 1 diabetes, but it was not specifically focused on DKA.
• The initial dose of 0.5 U/h may not be applicable to DKA treatment. 2

From the Research

Initial Intravenous (IV) Insulin Bolus for Diabetic Ketoacidosis (DKA)

• The initial IV insulin bolus for DKA is a topic of debate, with some studies suggesting its use and others questioning its necessity 3, 4, 5.
• A study published in 2022 compared two protocols of IV insulin therapy in the management of DKA, one with an initial bolus of 0.10 UI/Kg and the other without a bolus, and found no significant differences in outcomes between the two groups 4.
• Another study published in 2010 found that the administration of an initial bolus dose of insulin was not associated with significant benefit to patients with DKA and demonstrated equivalent changes in clinically relevant endpoints when compared to patients not administered the bolus 5.
• A study published in 1974 used a continuous IV infusion of small doses of insulin, with a mean loading dose of 6.5 units, to treat DKA, and found this regimen to be clinically effective and simple to follow 6.
• More recent studies have explored the use of subcutaneous insulin as an alternative to traditional IV insulin infusion for the treatment of mild to moderate DKA, with some finding it to be a safe and effective option with fewer hypoglycemic effects 7.

Key Findings

• The use of an initial IV insulin bolus in the treatment of DKA is not universally recommended, and its necessity is still a topic of debate 3, 4, 5.
• Continuous IV infusion of small doses of insulin can be an effective treatment for DKA, with a mean loading dose of 6.5 units and a sustaining infusion of 6.5 U/hr 6.
• Subcutaneous insulin may be a safe and effective alternative to traditional IV insulin infusion for the treatment of mild to moderate DKA, with fewer hypoglycemic effects 7.