To Infuse or Not to Infuse (Insulin)?

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Rachel Rafeq
Rachel Rafeq
Emergency medicine pharmacist and toxicology enthusiast. Trained in medication safety and I apply that to everything. I love photography and world schooling my kids.

The Pre-brief

DKA patients are common in our ED. Diagnosis and treatment are standard with the utilization of a continuous infusion of insulin, but is it worth it for all patients? Should admission to the ICU be dictated by the route of insulin administration?  

How are mild, moderate and severe DKA defined

Why is intravenous administration recommended? 

Regular insulin has a pharmacokinetic profile that is suitable for continuous infusion. Onset is 30-60 minutes and most importantly, the duration is up to 12 hours compared to rapid-acting insulin, which acts quicker within 10-20 minutes but only lasts 3-5 hrs. Its ability to last longer makes it a great agent for intravenous infusions, and in patients with DKA, they will continue to require insulin for several hours before their gap closes and acidosis resolves. 

However, IV is also associated with higher hospitalization costs and resource requirements compared to subcutaneous (subQ). Starting a patient on an infusion of a high alert medication means that patient safety is even more imperative. These patients are usually managed in an ICU where nursing patient ratios are tighter and glucose checks can be completed frequently. In fact, many hospitals restrict the use of insulin infusions to intensive care units only. With this limitation, it drives up cost. One study found that treatment of DKA in an ICU was associated with 39% higher hospitalization costs compared to subQ insulin without ICU utilization ($14,429 +/- $5,243 vs $8,801 +/- $5,549, P < 0.01).  In patients with severe DKA or concomitant severe infections, admitting to an intensive care unit is intuitive; however, in patients that are only there for the insulin infusion, it begs the question of if it’s worth it.  

Is there a role for subQ insulin? 

In patients with mild to moderate DKA, an alternative approach is to use rapid-acting subQ insulin. Insulins in this category include aspart, glulisine, and lispro. SubQ administration does not require intensive care unit level of care or hourly glucose checks. However, the dosing strategy is cumbersome and perhaps a downside to this method since subQ insulin should be dosed every 1-2 hours. Therefore, although hourly glucose checks are not required with subQ as they are with an infusion, administration of subQ insulin is required at least every two hours if not hourly. 

Unfortunately, the literature supporting this method is sparse. There was a review of the evidence completed in 2013, which evaluated four small randomized studies (156 patients total) that directly compared continuous infusion of insulin against subQ insulin. In all the studies, average time to DKA resolution was similar between both groups (lispro 10-14.8 hrs. vs regular insulin 10-13.2 hrs.) In addition, they found no difference in adverse events, total insulin dose requirements, or number of hospitalization days.  Recently in 2018, Razavi and colleagues assessed the safety and efficacy in pediatric patients.6 50 children were included of which 64% had moderate DKA. The subQ group received 0.15 units/kg of insulin aspart every two hours in a regular medical ward and the intravenous group received 0.05-0.1 unit/kg/hr of regular insulin in an intensive care unit. The mean total insulin dose in the subQ group was lower than the IV group (p <0.001). No serious safety events occurred in either group. The authors ultimately concluded that subQ insulin was an appropriate alternative to IV insulin. 

Considerations

Based on the limited literature it appears from a clinical standpoint that subQ insulin and intravenous insulin provide similar outcomes. From a financial standpoint, subQ is associated with less cost, largely due to less level of care requirements and resources. So, is there a downside to subQ? Why hasn’t it been adopted already? My guess is that because it still requires every one hour or every two hours of nursing demand this may or may not be feasible on a general floor where patient to nursing ratios are greater. Additionally, the dosing required is exactly that, every one hour or every two hours. In adult patients, an initial subQ injection of 0.3 units/kg of rapid-acting insulin may be given followed by hourly (0.1 units/kg) or every two hours (0.2 units/kg) administration. In pediatric patients, it is reasonable to administer 0.15 units/kg every two hours without an initial bolus. This is a needle stick to the patient every one to two hours, compared to zero needle sticks with continuous infusion. While I was unable to find any studies that evaluated patient satisfaction with subQ insulin administration in DKA,  it is reasonable to believe that an increased number of injections would result in increased pain and discomfort to the patient. The use of every one to two hours of insulin injections equals more than six injections daily to achieve resolution of DKA. On the contrary, the use of infusion therapy is associated with complications including infection and damage to blood vessels.

So, what say you? Are you pro IV or pro subQ? Let us know in the comments below.  

The Debrief

1) The mainstay therapy for DKA is a continuous insulin infusion for mild, moderate or severe cases.  

2) IV insulin infusions generally require intensive care unit level of care but mild DKA may not. Therefore, there may be an opportunity to utilize SubQ insulin to allow for reduced resource requirements and hospitalization costs without compromising clinical outcomes. 

3) The benefits of subQ insulin for DKA over IV insulin should be weighed against patient satisfaction.  

References

  1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. doi:10.2337/dc09-9032
  2. Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online, Hudson, Ohio: UpToDate, Inc.; 2013; April 15, 2013
  3. Haas RM, Hoffman AR. Treatment of diabetic ketoacidosis: should mode of insulin administration dictate use of intensive care facilities?. Am J Med. 2004;117(5):357-358. doi:10.1016/j.amjmed.2004.06.020
  4. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117(5):291-296. doi:10.1016/j.amjmed.2004.05.010
  5. Vincent M, Nobécourt E. Treatment of diabetic ketoacidosis with subcutaneous insulin lispro: a review of the current evidence from clinical studies. Diabetes Metab. 2013;39(4):299-305. doi:10.1016/j.diabet.2012.12.003
  6. Razavi Z, Maher S, Fredmal J. Comparison of subcutaneous insulin aspart and intravenous regular insulin for the treatment of mild and moderate diabetic ketoacidosis in pediatric patients. Endocrine. 2018;61(2):267-274. doi:10.1007/s12020-018-1635-z 
  7. Cohn BG, Keim SM, Watkins JW, Camargo CA. Does Management of Diabetic Ketoacidosis with Subcutaneous Rapid-acting Insulin Reduce the Need for Intensive Care Unit Admission?. J Emerg Med. 2015;49(4):530-538. doi:10.1016/j.jemermed.2015.05.016 

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