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Glucose-Insulin-Potassium Infusion May Cause Early Harm After STEMI

New analyses reveal a mortality risk in the first 3 days and confirm a lack of longer-term benefit.

Although several small clinical trials have suggested the utility of glucose-insulin-potassium (GIK) infusion following ST-segment-elevation MI (STEMI), in the largest assessment to date, the CREATE-ECLA study (Journal Watch Cardiology Mar 18 2005), GIK infusion had a neutral effect on 30-day mortality. In an industry-funded follow-up trial, investigators for the Organization for the Assessment of Strategies for Ischemic Syndromes-6 (OASIS-6) evaluated the effect of GIK infusion versus no infusion on 30-day and 6-month mortality and heart failure in 2748 patients with STEMI. They performed prespecified analyses of the combined trial data on 22,943 patients enrolled in the OASIS-6 and CREATE-ECLA studies.

Subjects randomized to intervention were infused with a GIK solution of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of potassium at 1.5 ml/kg/hour for 24 hours. The mean serum glucose level at randomization was 162 mg/dL and was higher in the GIK-infusion group at 6 and 24 hours, as was the mean potassium concentration (see Table 1). Median net fluid balance in the first 24 hours was 550 mL greater in the GIK-infusion group than in the control group.

In the OASIS-6 trial, no statistically significant between-group differences in death, heart failure, or a composite of the two outcomes were observed at either 30 days or 6 months. However, analyses of combined data from both studies revealed a statistically significant increase in death in the GIK group (6.2%) versus the control group (5.5%) in days 0 to 3 (hazard ratio, 1.13; P=0.03). Post-hoc analysis suggested that much of the early harm associated with GIK was directly associated with increased levels of glucose and potassium and net fluid gain.

Comment: This large study confirms a key finding of the CREATE-ECLA assessment — namely, that GIK infusion confers no long-term benefit to MI patients. More importantly, an assessment of the combined studies identified an early hazard of GIK, which appears to be directly related to infusion-associated hyperglycemia, hyperkalemia, and fluid gain. Further studies assessing aggressive hyperglycemia management (including the ongoing SWEET ACS trial) will explore the role of insulin infusion alone in patients with STEMI.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology December 5, 2007

Citation(s):

Díaz R et al. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA 2007 Nov 28; 298:2399.

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