Effect of Nitrous Oxide Use on Long-term Neurologic and Neuropsychological Outcome in Patients Who Received Temporary Proximal Artery Occlusion during Cerebral Aneurysm Clipping Surgery

Abstract

Background We explored the relationship between nitrous oxide use and neurological and neuropsychological outcome in a population of patients likely to experience intraoperative cerebral ischemia: i.e., 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 post-surgery) outcome were evaluated via both univariate and multivariate logistic regression analysis. An odds ratio (OR) of greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. Results We 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’s 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 our 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.

Anesthesia in Experimental Stroke Research

“…In contrast, 70% N 2 O worsened outcome when administered during an intermediate duration of global forebrain ischemia in gerbils (5 min), while no effect was observed in either brief (3 min) or prolonged (7 min) ischemic insults [88]. In a large human trial involving temporary vessel occlusion during cerebral aneurysm clipping, N 2 O increased the frequency of delayed ischemic deficits, but an effect on long-term neurologic or neuropsychiatric outcome was not detected [89]. Altogether these data do not support a substantive neuroprotective effect of N 2 O in cerebral ischemia.…”

Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: a non-randomized subgroup analysis of the General Anaesthesia compared with Local Anaesthesia for carotid surgery (GALA) trial

“…4 Nitrous oxide exposure has also been associated with an increased incidence of delayed ischaemic neurological deficits reported in a non-randomized secondary analysis of the Intraoperative Hypothermia in Aneurysm Surgery Trial. 5 While controversial, these findings suggest that nitrous oxide may increase vulnerability to ischaemic injury. As nitrous oxide inhibits methionine synthase function leading to the generation of homocysteine, 6 potentially leading to endothelial dysfunction and vasospasm, 7 this hypothesis is plausible.…”

Research studies that have influenced practice of neuroanesthesiology in recent years: A literature review

“…[44] However, in subset of patients who underwent temporary clipping and were thus likely to experience intraoperative cerebral ischemia, nitrous oxide use was found to be associated with an increased risk of developing DIND, but again with no evidence of detriment to neurologic outcome. [45]…”