zoniporide and Postoperative-Complications

To compare the effects of a volatile anesthetic to a non-volatile anesthetic regimen on the incidence of postoperative cardiac events, including the postoperative elevation of troponin I values after arterial vascular surgery in high risk patients.. Retrospective analysis of data of a phase II study that compared the Na+/H+ exchanger type II inhibitor, zoniporide to placebo on the occurrence of cardiac events.. Multicenter study conducted in 105 sites throughout the United States, South America, Europe and Asia.. 784 subjects scheduled for urgent or elective major arterial vascular surgery and a history of at least 3 of the following: age > or = 65 years, hypertension, documented stroke or transient ischemic attack, previous myocardial infarction, active angina pectoris diabetes mellitus, congestive heart failure, or symptomatic cardiac arrhythmia.. Type of anesthesia was retrospectively retrieved from the database and patients were subdivided in two groups: inhalational (group A) vs non-inhalational anesthetic regimen (group B). Incidence of postoperative cardiac events was compared between the two groups.. The incidence of postoperative cardiac events was not different between the two groups. Maximum postoperative troponin I levels was not different between the two groups in the total population and in the patients undergoing peripheral arterial surgery. In patients undergoing aortic surgery the incidence of elevated troponin levels higher than 1.5 and 4 ng x mL(-1) tended to be lower in group A than in group B in the aortic surgery (28% vs 18% and 30% vs 20% respectively) but this difference did not reach statistical significance.. The results of this hypothesis-generating study suggest that potential beneficial effects on extent of postoperative myocardial damage in high risk patients undergoing arterial surgery will probably be more apparent in abdominal aortic surgery than in peripheral vascular surgery. Further sufficiently powered studies using a standardized protocol should now be performed to definitively address this question.

Topics: Aged; Anesthetics, Inhalation; Female; Guanidines; Heart Diseases; Humans; Male; Middle Aged; Postoperative Complications; Pyrazoles; Retrospective Studies; Troponin I; Vascular Surgical Procedures

To determine whether a novel Na+/H+ exchange ion inhibitor, zoniporide, is associated with reduced perioperative myocardial ischemic injury in high-risk surgery patients.. Randomized double-blind placebo-controlled multidose trial.. Multicenter worldwide (105 centers) trial.. Patients with known or multiple risk factors for coronary artery disease undergoing noncardiac vascular surgery.. Four parallel groups received 1 of 3 doses of zoniporide or placebo, delivered as a 60-minute loading dose immediately before surgery, and followed by a continuous intravenous infusion for up to 7 days.. A total of 824 subjects were randomized into the study from 105 centers worldwide. Of these, 784 subjects received study drug infusion in the 3-mg/kg/d, 6-mg/kg/d, and 12-mg/kg/d groups and the placebo group, and 769 satisfied the criteria for the primary efficacy analysis population. This is 68% of the planned sample size of 1125 subjects. Anesthetic management and perioperative cardiac medications were at the discretion of the attending anesthesiologists, surgeons, and cardiologists. The proportion of subjects who experienced the composite endpoint event (death, myocardial infarction, congestive heart failure, arrhythmia) by postsurgical day 30 was 18.5% in the 12-mg/kg/d group, compared with 15.7% in the placebo group, resulting in a relative risk (RR) of 1.17% (95% confidence interval [CI], 0.80-1.72; p = NS) favoring placebo. The proportions in the lower 2 zoniporide dose groups were slightly lower than in the placebo group, although the sample size is inadequate to reach any firm conclusions.. The results fail to demonstrate the efficacy of zoniporide in reducing the proportion of patients at high risk undergoing noncardiac vascular surgery who experience a composite cardiovascular endpoint, which led the corporate sponsor to stop enrollment early on the basis of a futility analysis of the chance of demonstrating efficacy with a larger sample size.

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Asia; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Guanidines; Heart Failure; Heart Rate; Humans; Liver; Male; Middle Aged; Myocardial Ischemia; Perioperative Care; Postoperative Complications; Pyrazoles; Risk Factors; Sodium-Hydrogen Exchangers; South America; Treatment Outcome; United States; Vascular Surgical Procedures