Anesthesia With and Without Nitrous Oxide and Long-term Cognitive Trajectories in Older Adults

BACKGROUND: We evaluated the hypothesis that the rate of postoperative decline in global cognition is greater in older adults exposed to general anesthesia with nitrous oxide (N2O) compared to general anesthesia without N2O. METHODS: Longitudinal measures of cognitive function were analyzed in nondemented adults, 70–91 years of age, enrolled in the Mayo Clinic Study of Aging. Linear mixed-effects models with time-varying covariates assessed the relationship between exposure to surgery with general anesthesia (surgery/GA) with or without N2O and the rate of long-term cognitive changes. Global cognition and domain-specific cognitive outcomes were defined using z scores, which measure how far an observation is, in standard deviations, from the unimpaired population mean. RESULTS: The analysis included 1819 participants: 280 exposed to GA without N2O following enrollment and before censoring during follow-up (median [interquartile range {IQR}] follow-up of 5.4 [3.9–7.9] years); 256 exposed to GA with N2O (follow-up 5.6 [4.0–7.9] years); and 1283 not exposed to surgery/GA (follow-up 4.1 [2.5–6.4] years). The slope of the global cognitive z score was significantly more negative following exposure to surgery/GA after enrollment (change in slope of −0.062 [95% confidence interval {CI}, −0.085 to −0.039] for GA without N2O, and −0.058 [95% CI, −0.080 to −0.035] for GA with N2O, both P < .001). The change in slope following exposure to surgery/GA did not differ between those exposed to anesthesia without versus with N2O (estimated difference −0.004 [95% CI, −0.035 to 0.026], P = .783). CONCLUSIONS: Exposure to surgery/GA is associated with a small, but statistically significant decline in cognitive z scores. Cognitive decline did not differ between anesthetics with and without N2O. This finding provides evidence that the use of N2O in older adults does not need to be avoided because of concerns related to decline in cognition.