Safety and feasibility of hyperkalemic cardioplegia with diazoxide in cardiac surgery: The Cardioplegia with Diazoxide in Cardiac Surgery Trial

Background: ) channel opener diazoxide in multiple animal models in an effort to reduce myocardial stunning following cardiac surgery. These translational findings supported this first-in-human Phase I safety and feasibility trial evaluating diazoxide as an additive to hypothermic, hyperkalemic cardioplegia. Methods: In this Food and Drug Administration-approved safety and feasibility trial, 30 patients undergoing nonemergent cardiac surgery (coronary artery bypass, aortic, or valve) received intracoronary diazoxide in the first dose of hypothermic, hyperkalemic cardioplegia at the time of cross-clamp placement. Safety and clinical endpoints, including a novel definition of myocardial stunning (need for inotropic support for >24 and <72 hours), myocardial enzymes, change in ejection fraction, and hemodynamic parameters, were collected. Results: Thirty patients received intracoronary diazoxide. The Society of Thoracic Surgeons Predicted Risk of Mortality ranged from 0.3% to 8.0%. An increase in mean arterial pressure was noted with diazoxide administration (mean, 59.8 mm Hg before vs 62.0 mm Hg after). The mean time to arrest was 80 ± 43 seconds. Two patients (6.7%) had myocardial stunning. Mean peak lactate was 5.6 ± 5.1, peak creatine kinase was 939 ± 588 U/L, and peak troponin was 12,531 ± 18,615 ng/L. An increase in left ventricular ejection fraction of 2.1 ± 4.9% (prebypass to postbypass by transesophageal echocardiography) was noted. Conclusions: Intracoronary diazoxide is safe and feasible in patients undergoing nonemergent cardiac surgery.