Comparing the efficacy of subcutaneous intermittent soluble insulin versus intravenous continuous soluble insulin infusion in the treatment of diabetic ketoacidosis in an emergency department setting.

Abstract

Background: As the prevalence of diabetes increases in both industrialized and developing countries, the incidence of diabetic ketoacidosis (DKA) is also increasing. DKA is a potentially fatal condition, but is highly treatable and has an excellent prognosis when timely intervention is available. Mainstay treatment for DKA includes intravenous fluids and low-dose fast-acting insulin regardless of the route of administration (IV infusion or intermittent IM/SC). Intravenous infusion of insulin, however, requires extra resources such as infusion pumps, monitored beds, and additional training for personnel, and may be associated with an increased rate of adverse events if not monitored. While many guidelines recommend treatment of DKA with continuous IV infusion, to date there is no definitive study establishing the superiority of either IV infusion or intermittent SC administration of insulin for the treatment of DKA. Current inpatient treatment at Muhimbili National Hospital (MNH) is based on intramuscular administration of insulin, while current Emergency Medical Department (EMD) practice includes both continuous IV infusion and intermittent subcutaneous (SC) administration of insulin, based on equipment availability and provider preference. Aim of the study: To compare the efficacy of SC intermittent soluble insulin over IV continuous soluble insulin infusion in the treatment of DKA in a randomized open-label trial carried out at the MNH EMD. Methodology: This was a randomized controlled open-label clinical trial study that was carried out at the MNH Emergency Department in patients diagnosed with DKA. 30 patients were randomly assigned to one of two groups. One group had 14 patients who were treated with IV continuous regular soluble insulin and other group had 16 patients who were treated with SC intermittent regular soluble insulin. Data collected included vital signs, RBG every 1 hour, and VBG every 2 hours. All data were collected in EMD by the trained doctors and nurses till to the resolution of ketoacidosis using a guided DKA management protocol algorithm (see attached). The data was collected into a guided flow chart and analyzed in response to therapy by duration of treatment to resolution of DKA as a primary outcome. A difference of ≥ 2 hours between two groups of treatment was considered as clinically significant. Secondary outcomes included amount of insulin administered, and rate of glucose drop per hour until resolution of DKA, adverse events (hypoglycemia and/or hyperkalemia/hypokalemia), and precipitating factors for DKA with either group of insulin therapy. All data was expressed as means or proportions with Standard deviation (SD). Results: The demographic, clinical and biochemical parameters on presentation to the EMD were similar and not statistically significantly between the two groups of treatment. There was no statistical difference between patients treated with IV continuous infusion and SC intermittent of regular soluble insulin in mean time to resolution of DKA (14.9 + 7.9 and 16.4 + 5.0 hours); total amount of insulin required for resolution of DKA (66.5 + 45.7 and 50.4 + 27.0 units); rate of glucose drop per hour (1.3 + 1.2 and 1.3 + 1.0 mmol/L), respectively. The hypoglycemic events were higher in IV infusion group than in SC group. The number of hypokalemic events was slightly higher in patients treated with SC intermittent regular soluble insulin than IV infusion. There were no statistical significant differences in either of the treatment group (IV or SC) for both precipitating factors (infection and poor compliance/out of medication) based on time to resolution of DKA, total amount of insulin used till resolution of DKA and rate of glucose drop per hour. Conclusion and Recommendation: This study suggests that even severe DKA can be managed using SC intermittent low dose regular soluble insulin therapy and this regimen is as effective as and possibly safer than IV infusion of regular soluble insulin. SC intermittent regular soluble insulin administration can be managed effectively even where infusion pumps and rapid acting insulin analogues are not available.