Intraoperative Nitrous Oxide Leads to Post-Operative Elevations in Plasma Homocysteine

S426 Introduction: Homocysteinemia is an independent risk factor for coronary artery and cerebrovascular disease, [1] however its significance in the perioperative period is unknown at this time. Nitrous oxide (N2O) has been shown to inhibit methionine synthase which mediates the breakdown of homocysteine both in vitro and in human liver cells. To our knowledge no study has determined the effect of intraoperative N2O exposure on postoperative plasma homocysteine concentrations in a prospective, controlled, randomized fashion. Methods: After IRB approval and written informed consent 20 ASA Class I-III patients, age > 18, presenting for elective craniotomy were randomized to receive general anaesthesia with or without N2O. Patients were excluded for any of the following: anesthetic within 30 days prior to surgery, known vitamin deficient state, family history or past history of homocysteinuria, medications known to inhibit methionine synthase. Anesthesia induction included IV propofol, narcotic, and a non-depolarizing muscle relaxant. In the nitrous oxide group, anesthesia was maintained with narcotic, isoflurane, and N2O/O2 (inspired N2O > 50%). In the non-nitrous group, anesthesia was maintained with narcotic, isoflurane, and oxygen/air. Prior to emergence, neuromuscular blockade was reversed. Following emergence and extubation, the patient was monitored in standard fashion in the post-anesthesia care unit (PACU). Blood samples were obtained for analysis upon arrival in the PACU, and 24 hours following induction. Plasma homocysteine levels were determined using high performance liquid chromatography. Statistical analysis consisted of unpaired t-tests for parametric data and chi-square analysis for nonparametric data. A p value < 0.05 was considered significant. Results: There were no significant differences between the nitrous and non-nitrous groups in terms of demographic (age, weight, gender) or intraoperative (time, procedure) data. There was a clinically and statistically significant elevation of approximately 10 [micro sign]mol/L (p = 0.0023, preinduction vs postoperative) in plasma homocysteine concentration in the nitrous group by the time of arrival in PACU that was maintained at 24 hours. This elevation was significantly different from the non-nitrous group (*p = 0.0031, see Figure 1).Figure 1Discussion: The use of intraoperative nitrous oxide leads to significant elevations in perioperative plasma homocysteine concentrations. The clinical significance, if any, of this rise needs to be determined.