Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial

Study Questions:

What is the impact of out-of-hospital emergency medical service (EMS) administration of glucose-insulin-potassium (GIK) in the first hours of suspected acute coronary syndromes (ACS)?


IMMEDIATE was a randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiogram (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) was administered by paramedics in the out-of-hospital setting and continued for 12 hours. The prespecified primary endpoint was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary endpoints included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation.


There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) versus those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.13; p = 0.28). Thirty-day mortality was 4.4% with GIK versus 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; p = 0.27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK versus 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; p = 0.01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK versus 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; p = 0.34); 30-day mortality was 4.9% with GIK versus 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; p = 0.29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK versus 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; p = 0.01). Serious adverse events occurred in 6.8% (n = 28) with GIK versus 8.9% (n = 41) with placebo (p = 0.26).


The authors concluded that among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI.


In this placebo-controlled, double-blind, randomized, clinical effectiveness trial of EMS administration of GIK among patients with suspected ACS, out-of-hospital administration of intravenous GIK by paramedics, compared with administration of glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was also not associated with improvement in 30-day survival, but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality. While additional studies with longer follow-up are needed to assess the out-of-hospital use of GIK as therapy for patients with ACS, the clinical utility remains uncertain.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, ACS and Cardiac Biomarkers, Implantable Devices, SCD/Ventricular Arrhythmias

Keywords: Odds Ratio, Insulin, Acute Coronary Syndrome, Myocardial Infarction, Hospital Mortality, Emergency Medical Services, Heart Arrest, Electrocardiography, Glucose, Potassium, Biological Markers, Hospital Administration, Confidence Intervals

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