Remifentanil Hydrochloride for injection was originally administered to 225 subjects undergoing elective CABG surgery in two dose-ranging studies without active comparators. Subsequently, two double-blind, double-dummy clinical studies (N = 426) evaluated Remifentanil Hydrochloride for injection (n = 236) at recommended doses versus active comparators (n = 190).

The first comparator study, a multi-center, randomized, double-blind, double-dummy, parallel-group study (N = 369), compared Remifentanil Hydrochloride for injection (n = 201) with fentanyl (n = 168) in adult patients undergoing elective CABG surgery. Subjects received 1 to 3 mg midazolam and 0.05 mg/kg morphine IV as premedication. Anesthesia was induced with propofol 0.5 mg/kg (higher doses administered with Remifentanil Hydrochloride for injection were associated with excessive hypotension) over one minute plus 10-mg boluses every 10 seconds until loss of consciousness followed by either cisatracurium 0.2 mg/kg or vecuronium 0.15 mg/kg. Patients randomized to Remifentanil Hydrochloride for injection received a 1 mcg/kg/min infusion of Remifentanil Hydrochloride for injection followed by a placebo bolus administered over 3 minutes. In the active control group, a placebo IV infusion was started and a fentanyl bolus 10 mcg/kg was administered over 3 minutes. All subjects received isoflurane titrated initially to end tidal concentration of 0.5%. During maintenance, the group randomized to Remifentanil Hydrochloride for injection received as needed 0.5-1 mcg/kg/min IV rate increases (to a maximum of 4 mcg/kg/min) of Remifentanil Hydrochloride for injection and 1 mcg/kg IV boluses of Remifentanil Hydrochloride for injection. The active control group received 2 mcg/kg IV boluses of fentanyl and increases in placebo IV infusion rate.

The second comparator study, a multi-center, double-blind, randomized, parallel group study (N = 57), compared Remifentanil Hydrochloride for injection (n = 35) to fentanyl (n = 22) in adult patients undergoing elective CABG surgery with poor left ventricular function (ejection fraction < 0.35). Subjects received oral lorazepam 40 mcg/kg as premedication. Anesthesia was induced using etomidate until loss of consciousness, followed by a low-dose propofol infusion (3 mg/kg/hr) and pancuronium 0.15 mg/kg. Subjects in the group administered Remifentanil Hydrochloride for injection received a placebo bolus dose and a continuous infusion of Remifentanil Hydrochloride for injection1 mcg/kg/min and subjects in the fentanyl group received a bolus loading dose of 15 mcg/kg and placebo continuous infusion. During maintenance, supplemental bolus doses of Remifentanil Hydrochloride for injection (0.5 mcg/kg) and infusion rate increases of 0.5 to 1 mcg/kg/min (maximum rate allowed was 4 mcg/kg/min) of Remifentanil Hydrochloride for injection were administered to one group; while the fentanyl group was given intermittent maintenance bolus doses of 2 mcg/kg and increases in the placebo infusion rate.

In these two studies, using a high dose opioid technique with Remifentanil Hydrochloride for injection as a component of a balanced or total intravenous anesthetic regimen, the remifentanil regimen effectively attenuated response to maximal sternal spread generally better than the dose and regimen studied for the active control (fentanyl). While this provides evidence for the efficacy of remifentanil as an analgesic in this setting, caution must be exercised in interpreting these results as evidence of superiority of remifentanil over the active control, since these studies did not make any attempt to evaluate and compare the optimal analgesic doses of either drug in this setting.