EFFECTS OF INTRAOPERATIVE NITROUS OXIDE ON POSTOPERATIVE HOMOCYSTEINE AND MYOCARDIAL ISCHEMIA IN PATIENTS UNDERGOING NONCARDIAC SURGERY

Abstract

Introduction. We have recently shown that nitrous oxide anesthesia leads to increased postoperative homocysteine serum levels. [1] Homocysteinemia is known to be an independent risk factor for coronary artery and cerebrovascular disease. [2] Elevated homocysteine in the perioperative period may therefore increase cardiovascular risk. The present study was designed to evaluate the effect of nitrous oxide anesthesia and postoperative homocysteine serum levels on myocardial ischemia in patients undergoing carotid endarterectomy. Methods. Following IRB approval and written informed consent, 50 ASA Class I-III patients, age > 18, presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Anesthesia was induced with propofol, opioid and nondepolarizing neuromuscular blocker. In the nitrous oxide group, anesthesia was maintained with opioid, isoflurane, and nitrous oxide/oxygen (inspired nitrous oxide > 50%). In the non-nitrous group, anesthesia was maintained with opioid, isoflurane, and oxygen/air. All patients were monitored with standard clinical monitors. Following emergence and extubation, patients were monitored in standard fashion in the post-anesthesia care unit (PACU) and transferred to the ward. Prior to induction, upon arrival in the PACU, and after 48 hrs, blood samples were obtained for homocysteine analysis, using HPLC by individuals blinded to treatment group. Currently, samples for the first 35 patients have been analyzed. Three hours prior to induction and for 48 hours postoperatively patients were monitored by a three channel, seven lead Holter monitor. Myocardial ischemia was determined by a blinded reader using Mortara MK5 software which averaged patients' heart rate for each hour. ST segments were analyzed after all normal QRS complexes 60 ms after the J point. Ischemic episodes were defined as a 1 mm shift from baseline with a slope of less than 0 lasting for more than 1 min. The ST segment had to return to baseline levels for more than 5 min. for a second episode to be counted. For each ischemic episode absolute ST depression in mm, change from baseline in mm, and duration of the episode in min were determined. Statistical analysis consisted of unpaired t-tests for parametric data and chi-squared analysis for nonparametric data where p < 0.05 was considered significant. Results. There were no significant differences in demographic variables, intraoperative management or preoperative ischemia between the two groups other than inspired isoflurane concentration 0.60 +/- 0.23 vs 0.85 +/- 0.33, p = 0.004 (nitrous vs non nitrous). At 48 hours the nitrous group had an increase in postoperative homocysteine concentrations of 4.3 +/- 3.5 vs a decrease in the non nitrous group of 0.6 +/- 2.3 [micro sign]mol/L, p < 0.0001. Though the incidence of ischemia was the same, the nitrous group had significantly longer ischemic events than the non nitrous group 51 +/- 59 vs 27 +/- 37 min, p = 0.04, and had more patients with events lasting 30 min (8 vs 2, p = 0.044). Discussion. This study reconfirmed that intraoperative nitrous oxide leads to postoperative elevations in homocysteine concentration. This homocysteine elevation correlated with an increase in postoperative myocardial ischemia which could lead to increased morbidity and mortality.