Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function.

Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
Anesthesiology (Impact Factor: 6.17). 10/2008; 109(4):657-63. DOI: 10.1097/ALN.0b013e31818629db
Source: PubMed

ABSTRACT Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide.
The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations.
The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates.
Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Maintenance of homeostasis during anaesthesia in the patient with two major metabolic disorders whose systemic effects either compliment or contradict each other is a challenge to the anaesthesiologist. A 25-year-old male patient with Cushing's syndrome and known hyperhomocysteinemia was scheduled for open adrenalectomy. Both these disorders compound the hypercoagulable state and differ in glucose metabolism. In addition, obesity, difficult airway, electrolyte and metabolic derangements that accompany Cushing's syndrome warrant special attention. He was on anticoagulant therapy and inferior vena cava filter following an episode of pulmonary thromboembolism with deep vein thrombosis. Perioperative hydrocortisone was administered. Thoracic epidural catheter was placed at T10-T11 interspace, standard general anaesthesia was administered without nitrous oxide. Patient was extubated following an uneventful procedure and discharged home on 10(th) post-operative day. Understanding the anaesthetic implications and the pathophysiological interactions of multiple metabolic disorders with a potential for multisystem involvement is key to the successful management of these patients.
    Indian journal of anaesthesia 03/2015; 59(3):182-5. DOI:10.4103/0019-5049.153041
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. Methods We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at, number NCT00430989. Findings Of 10 102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). Interpretation Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. Funding Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.
    The Lancet 10/2014; 384(9952). DOI:10.1016/S0140-6736(14)60893-X · 39.21 Impact Factor