Initially, the infusion was made using U-100 insulin; the hospital standardized the concentration of insulin drips (1 U/mL) in order to reduce medication errors. But concern was raised about excessive fluid intake (approximately 12L/d) if 1 U/mL insulin infusion was used. The patient’s own U-500 regular insulin was used instead to prepare the continuous infusion; the insulin was supplied to him by the NIH. Going by the patient’s previous hospitalization requirements, an insulin drip using 2000 U of Humulin R U-500 into a 100mL bag of normal saline was prepared. The infusion rate of 500 U/h was maintained for the first seven hours; at around the 9th hour, blood glucose reached the target range, with no evidence of complications. 

After 23 hours of treatment, the anion gap closed and the drip was subsequently discontinued. The patient was then transitioned to a subcutaneous (SC) regimen (2000 U with breakfast, 1000 U with lunch and dinner). At discharge (after four days in the ICU), the patient’s respiratory symptoms had improved and anion gap was 14. For the 2-week period after discharge, the patient was instructed to check daily urine ketones; he was also given dietary recommendations (1800–2000 calories per day; 75g of carbohydrates/meal). 

Given the rarity of the disorder, there is limited literature pertaining to the care of patients with RMS, with few cases reporting on how best to combat extreme insulin resistance. In RMS, patients often require high doses of insulin and concentrated insulin is often prescribed to reduce the need for multiple injections or continuous infusion insulin pumps. While U-500 insulin (500 U/mL) is considered a short-acting insulin, when given subcutaneously, it works more like an intermediate-acting insulin, with delayed absorption and longer duration of action. The prescribing information for U-500 indicates that it is only approved for SC administration, however as seen in this case, during periods of extreme insulin resistance, when rapid reduction in blood glucose is necessary, it can be used safely and effectively via the IV route. In addition, as reported in this case, many steps were taken in order to minimize potential medication errors including stickers alerting staff that the insulin was for IV continuous infusion and labels that indicated that a nonstandard, concentrated product was being used. 


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In RMS, doses of insulin above 10,000 U/d may be necessary when patients experience complications (DKA) secondary to uncontrolled hyperglycemia. The authors conclude that “this case report has shown the use of IV U-500 insulin to be both effective and safe in treating conditions of extreme insulin resistance if proper precautions are taken.”

Reference:

1.  Moore MM, Bailey AM, Flannery AH, Baum RA. Treatment of Diabetic Ketoacidosis With Intravenous U-500 Insulin in a Patient With Rabson-Mendenhall Syndrome: A Case Report. Journal of Pharmacy Practice. 2016.