Clarke, William R.

Background Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33 degrees C) versus normothermia (temperature = 36.5 degrees C) in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Anesthesia was dictated by a limited-options protocol with the use of nitrous oxide determined by individual anesthesiologists. All patients were assessed daily for 14 days after surgery or until hospital discharge. Neurologic and neuropsychological testing were conducted at 3 months after surgery. Outcome data were analyzed via both univariate tests and multivariate logistic regression analysis correcting for factors thought to influence outcome. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. Results Outcome data were available for 1,000 patients, of which 373 received nitrous oxide. There was no difference between groups in the development of delayed ischemic neurologic deficit. At 3 months after surgery, there were no significant differences between groups in any outcome variable: Glasgow Outcome Score (OR, 0.84; 95% confidence interval [CI], 0.63-1.14; P = 0.268), National Institutes of Health Stroke Scale (OR, 1.29; 95% CI, 0.96-1.73; P = 0.087), Rankin Disability Score (OR, 0.84; 95% CI, 0.61-1.15; P = 0.284), Barthel Activities of Daily Living Index (OR, 1.01; 95% CI, 0.68-1.51; P = 0.961), or neuropsychological testing (OR, 1.26; 95% CI, 0.85-1.87; P = 0.252). Conclusions In a population of patients at risk for ischemic brain injury, nitrous oxide use had no overall beneficial or detrimental impact on neurologic or neuropsychological outcomes.

Background The authors explored the relationship between nitrous oxide use and neurologic and neuropsychological outcome in a population of patients likely to experience intraoperative cerebral ischemia: those who had temporary cerebral arterial occlusion during aneurysm clipping surgery. Methods A post hoc analysis of a subset of the data from the Intraoperative Hypothermia for Aneurysm Surgery Trial was conducted. Only subjects who had temporary arterial occlusion during surgery were included in the analysis. Metrics of short-term and long-term (i.e., 3 months after surgery) outcome were evaluated via both univariate and multivariate logistic regression analysis. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. Results The authors evaluated 441 patients, of which 199 received nitrous oxide. Patients receiving nitrous oxide had a greater risk of delayed ischemic neurologic deficits (i.e., the clinical manifestation of vasospasm) (OR, 1.78, 95% confidence interval [CI], 1.08-2.95; P = 0.025). However, at 3 months after surgery, there was no difference in any metric of gross neurologic outcome: Glasgow Outcome Score (OR, 0.67; CI, 0.44-1.03; P = 0.065), Rankin Score (OR, 0.74; CI, 0.47-1.16; P = 0.192), National Institutes of Health Stroke Scale (OR, 1.02; CI, 0.66-1.56; P = 0.937), or Barthel Index (OR, 0.69; CI, 0.38-1.25; P = 0.22). The risk of impairment on at least one test of neuropsychological function was reduced in those who received nitrous oxide (OR, 0.56; CI, 0.36-0.89; P = 0.013). Conclusion In this patient population, use of nitrous oxide was associated with an increased risk for the development of delayed ischemic neurologic deficits; however, there was no evidence of detriment to long-term gross neurologic or neuropsychological outcome.