Abstract & Commentary
Source: vanderHorst ICC, et al. The Zwolle Infarct Study Group. Glucose-insulin-potassium infusion in patients treated with primary angioplasty for acute myocardial infarction: The glucose-insulin-potassium study: A randomized trial. J Am Coll Cardiol 2003;42:784.
High-dose glucose-insulin-potassium (GIK) infusion for patients presenting with acute myocardial infarction (AMI) has been advocated since the 1960s. Suggested benefits from GIK include improving cardiac energy metabolism by increased glucose utilization and decreased free fatty acid uptake by myocytes, as well as stabilization of cell membranes in ischemic myocardial tissue.
In this controlled trial from Europe, investigators randomized 940 AMI patients (symptom duration greater than 30 minutes, onset within 24 hours of presentation, and electrocardiographic findings of AMI including ST segment elevation or new left bundle-branch block) to either GIK (476 patients) or no infusion (464 patients) prior to undergoing reperfusion via percutaneous transluminal coronary angioplasty. All patients received standard therapy including nitroglycerin, heparin, and aspirin. The GIK group received a continuous infusion of 80 mmol of potassium chloride in 500 mL of 20% glucose solution at a rate of 3 mL/kg/hr, as well as 50 U of insulin over 8-12 hours (to maintain serum glucose level of 70-110 mEq/dL), initiated as soon as possible after presentation.
Overall, the investigators report that there was no difference between the GIK and no infusion groups in terms of 30-day mortality (4.8% vs 5.8% respectively, p = 0.50), as well as no difference in composite 30-day endpoint (death, reinfarction, or revascularization) (8.0% vs 9.9%). However, when patients were stratified by evidence of heart failure on presentation, patients with no signs of heart failure (90.1%, or 856 patients who were Killip Class I) had significantly improved 30-day mortality with GIK (1.2% vs. 4.2%, respectively, p = 0.01), as well as an improved composite endpoint (4.2% vs 8.4%, respectively). In patients who presented with signs of heart failure (8.9% or 84 patients who had Killip Class of at least 2), more patients died from heart failure in the GIK group compared to no infusion (30.4% vs 20.6%, respectively).
The authors conclude that while their study found no overall mortality benefit to GIK infusion in AMI, there was a significant mortality benefit in the large subgroup of AMI patients who did not have evidence of heart failure on presentation. These findings may indicate that GIK does have beneficial effects on cellular metabolism in ischemic cardiac cells, but this benefit may be outweighed by the large GIK volume infusion in patients already presenting with evidence ofvolume overload, cardiac decompensation, and heartfailure.
Commentary by Theodore C. Chan, MD, FACEP
This is the largest prospective, randomized trial studying the utility of GIK infusion in the setting of AMI, as well one of the first studies to investigate the role of GIK in combination with emergent angioplasty. The absolute 3% improvement in mortality in patients without evidence of heart failure on presentation is quite remarkable given how little this therapy would cost. Most AMI patients present without heart failure (90%), and this mortality benefit would translate to 30,000 lives saved per year in this country (based on an annual rate of AMI of 1 million).
A few points are of note regarding this study. First, the overall mortality rate (5.3%) for both the GIK and no infusion groups is remarkably low, likely a result of improvements in emergent care and reperfusion for AMI patients in general. Second, this study was performed at a single site which demonstrated excellent door-to-balloon times (fewer than 50 minutes) which undoubtedly led to improved outcomes in both groups.
Moreover, it suggests the benefit of the 8-12 hour GIK may occur in preventing reperfusion injury after patency is established, as well as improved cellular metabolism during the ischemic period. Third, a relative large volume of fluid was infused with this particular protocol (2 liters over 8 hours for an 80 kg patient). Similar benefit may be seen with smaller infusions with higher concentrations of GIK that pose less risk for patients with volume overload. Finally, while the results of this study are promising, a larger, multi-center study is needed to determine if GIK truly has particular benefit for subgroups of AMI patients.
Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the Editorial Board of Emergency Medicine Alert.