A Randomized Open-Label Phase I Pilot Study of the Safety and Efficacy of Total Intravenous Anesthesia With Fospropofol for Coronary Artery Bypass Graft Surgery

Abstract

To determine safety and efficacy of the water-soluble prodrug fospropofol for anesthesia in cardiac surgery and to compare the pharmacodynamic profiles of fospropofol and propofol. Pilot study and a prospective, phase I, open-label, single-center, randomized clinical trial. University hospital; single institution. Sixteen patients undergoing elective first-time coronary artery bypass surgery. Patients were randomized to receive total intravenous anesthesia with fospropofol (n = 8) or propofol (n = 8) combined with alfentanil as total intravenous anesthesia. Bispectral index, arterial blood pressure, and heart rate were recorded continuously, and pulmonary artery catheter measurements were obtained. Plasma concentrations of formate, phosphate, and Ca(2+) were monitored closely. Safety and tolerability were assessed by adverse events, neurologic examinations, clinical laboratory tests, and vital signs. The total doses of fospropofol and propofol during anesthesia were 11.3±2.5 and 4.4±1.0 mg/kg/h, respectively. According to the achieved bispectral index (BIS) values, fospropofol was as effective as propofol in providing general anesthesia and sedation. There were no clinical signs of formate toxicity in the fospropofol group. The only treatment-related adverse event after administration of fospropofol was a transient burning sensation in the perineal and perianal region during induction of sedation or anesthesia. Fospropofol could be used to provide general anesthesia in patients undergoing coronary artery bypass graft surgery. Further larger studies are needed to prove the safety of fospropofol when given to provide general anesthesia for major cardiac surgical procedures.