GLUTAMICS - A randomized clinical trial on glutamate infusion in 861 patients undergoing surgery for acute coronary syndrome

Abstract

Objective: Glutamate has been claimed to protect the heart from ischemia and to facilitate metabolic and hemodynamic recovery after ischemia. The GLUTAmate for Metabolic Intervention in Coronary Surgery trial investigated whether an intravenous glutamate infusion given in association with surgery for acute coronary syndrome could reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. Methods: In the present prospective, triple-center, double-blind study, 861 patients undergoing surgery for acute coronary syndrome were randomly assigned to an intravenous infusion of glutamate (n = 428) or saline (n = 433) perioperatively. Results: The incidence of the primary endpoint - a composite of 30-day mortality, perioperative myocardial infarction, and left ventricular heart failure at weaning from cardiopulmonary bypass - was 7.3% versus 5.8% (P = .41) in the glutamate and control groups, respectively. Patients with left ventricular failure at weaning from cardiopulmonary bypass had a shorter median intensive care unit stay (25 vs 92 hours; P = .02) if they were treated with glutamate. In patients with unstable angina (Canadian Cardiovascular Society class IV) undergoing isolated coronary artery bypass grafting (n = 458), the incidence of severe circulatory failure according to the prespecified criteria was significantly lower in the glutamate group (1.3% vs 6.9%; P = .004). On multivariate analysis, glutamate infusion was associated with a reduced risk of developing severe circulatory failure (odds ratio, 0.17; 95% confidence interval, 0.04-0.72; P = .02). A relative risk reduction exceeding 50% for developing severe circulatory failure was seen in most risk groups undergoing isolated coronary artery bypass grafting, with those with diabetes a notable exception. Conclusions: The primary endpoint did not differ significantly between the groups. The secondary outcomes and post hoc analyses warrant additional studies with regard to the potential beneficial effect of glutamate on postischemic myocardial recovery.