The treatment of diabetic ketoacidosis (DKA) is, in many ways, unchanged: intravenous  fluids, electrolyte repletion, insulin, and treatment of any precipitating factors. However, as with many treatments, there has been substantial de-escalation in intensity of therapy over time. Historically, patients were given a bolus of intravenous insulin followed by an insulin infusion. In 2009, a consensus statement from the American Diabetes Association (ADA) discussed using a low-dose infusion (0.1 to 0.14 units/kg/hour) rather than a bolus.¹ Additionally, the consensus statement discussed the emerging use of subcutaneous insulin to treat DKA. More recently, evidence has mounted demonstrating that DKA can be managed with subcutaneous insulin in many patients, which is endorsed in the most recent iteration of the Standards of Care in Diabetes from the ADA.^2,3 In fact, traditional insulin infusions do not result in quicker closure of the anion gap or lowering of the serum glucose below 250 mg/dL.^3,4

Logistics of Subcutaneous Insulin Pathways

The eligibility criteria for entry into a subcutaneous insulin pathway for DKA varies. All pathways exclude those who are obtunded (Glasgow Coma Scale below 8) or have another critical illness necessitating intensive care. In some studies, individuals with mild to moderate DKA are eligible (pH at least 7.0, bicarbonate at least 10 mEq/L) whereas some studies have included any non-critically ill patient otherwise eligible, regardless of DKA severity.^4,5 Notably, patients weighing 166 kg or more may have altered absorption of insulin and were eventually excluded from one hospital system’s protocol.

In subcutaneous insulin protocols, patients receive the same supportive care as in infusion pathways—a couple of liters of intravenous fluids (depending on comorbidities) and electrolyte repletion. In addition, patients receive a hefty dose of a short-acting insulin every four hours, as long as the glucose is above 250 mg/dL (e.g., lispro 0.3 units/kg subcutaneously). In a recent protocol that included noncritically ill patients across the spectrum of DKA severity (that is, inclusive of severe DKA), patients also received a dose of long-acting insulin (e.g., glargine 0.3 units/kg subcutaneously or the patient’s usual home dosage) alongside the short-acting insulin. Point-of-care glucose monitoring can be conducted less frequently than in infusion pathways, every two hours until four hours after the last “big” dose of short-acting insulin.

What’s the Advantage?

Intravenous insulin infusions typically require treatment in highly monitored settings, such as an intensive care unit (ICU) or step-down unit for safety and due to the frequency and intensity of monitoring. ICU and step-down beds are a limited resource and generate higher hospital charges. One study found a 57 percent reduction in ICU admissions among patients with DKA at a site that implemented a subcutaneous insulin protocol compared with 21 control sites. However, this profound reduction has not been seen in all studies, possibly due to differences in protocols or, more likely, local comfort and adjusting to a different process of care. Additionally, in the current era of ubiquitous emergency department (ED) boarding, ED length of stay is of critical importance. A single-institution study found an approximately three-hour reduction in ED length of stay after implementation of a subcutaneous protocol.

Management of DKA using insulin exclusively through the subcutaneous route is safe, acceptable, and can have system-level benefits. As protocolized care has improved the quality of care of patients with DKA, it is critical to adapt institutional protocols to ensure safe implementation of subcutaneous pathways.

Dr. Westafer (@Lwestafer) is an attending physician and research fellow at Baystate Medical Center, clinical instructor at the University of Massachusetts Medical School in Worcester, and co-host of FOAMcast.

References

1. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343.
2. ElSayed NA, Aleppo G, Aroda VR, et al. Diabetes care in the hospital: standards of care in diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S267-S278.
3. Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, et al. Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. Cochrane Libr. 2016;2016(1).
4. Rao P, Jiang SF, Kipnis P, et al. Evaluation of outcomes following hospital-wide implementation of a subcutaneous insulin protocol for diabetic ketoacidosis. JAMA Netw Open. 2022;5(4):e226417.
5. Griffey RT, Schneider RM, Girardi M, et al. The SQuID protocol (subcutaneous insulin in diabetic ketoacidosis): Impacts on ED operational metrics. Acad Emerg Med. 2023;30(8):800-808.