Three hundred patients, from twenty-three European medical institutions, participated in this placebo-controlled, double-blind, randomized, parallel-group trial. Ninety-eight were given high-dose
mivazerol (1.5 micrograms.kg-1.h-1); 99, low-dose
mivazerol (0.75 microgram.kg-1.h-1); and 103, placebo, continuously intraoperatively and for 72 h postoperatively. Blood pressure and heart rate were monitored for 96 h.
Myocardial ischemia was assessed by Holter electrocardiography for at least 8 h before induction of
anesthesia until 96 h after surgery. Twelve-lead electrocardiograms and
creatine kinase myocardial band
isoenzyme levels were obtained before and serially after surgery.
Adverse cardiac events were assessed for the intraoperative, early postoperative (0-24 h), and late postoperative (24-72 h) periods.
RESULTS: The incidence of
tachycardia was significantly lower with high-dose
mivazerol (vs. placebo) during the intraoperative (30% vs. 51%; P = 0.002), early postoperative (29% vs. 50%; P = 0.002), and late postoperative periods (46% vs. 70%; P = 0.001). Also, the percentage of patients treated for
tachycardia was significantly lower with the high dose (vs. placebo) during the early (10% vs. 20%; P = 0.043) and late (6% vs. 15%; P = 0.024) postoperative periods. The incidence of
hypertension was significantly lower with both high and low doses (vs. placebo) during the
intraoperative period (46% and 43%, respectively, vs. 63%; P = 0.010); treatment was similar at both high and low doses (33% and 34%, respectively, vs. 46%; P = 0.066). The incidence of
bradycardia was significantly higher at both dose levels than with placebo during and after
drug administration (intraoperatively-3%, 7%, and 9%; early postoperative-0%, 5%, and 6%; late postoperative-0%, 4%, and 6%; after
drug-0%, 6%, and 6%; placebo, low-dose, high-dose, respectively), but the need for treatment did not differ for the groups. The incidence of, and treatment for,
hypotension were similar for the three groups. Intraoperative
myocardial ischemia was significantly lower with high-dose
mivazerol than with placebo (20% vs. 34%, respectively, P = 0.026). When intraoperative data were subdivided into emergence vs. nonemergence periods (post boc analysis), the incidence of
myocardial ischemia was significantly lower with high-dose
mivazerol than with placebo during emergence (11% vs. 30%; P = 0.001). Regarding blood pressure, heart rate, and
ischemia, no rebound response occurred in the 12 h after discontinuation of
mivazerol. The high-dose, low-dose, and placebo groups did not differ in the incidence of adverse cardiac outcomes (3%, 2%, and 8%, respectively) or the diagnosis of
myocardial infarction (2%, 1%, and 6%, respectively).
CONCLUSIONS: