Abstract
There is a large controversy as to whether nitrous oxide (N2O) added to the anaesthetic gas mixture is harmful or harmless for postoperative cognitive function recovery. We performed a nested study in the ENIGMA-II trial and compared postoperative neurocognitive recovery of patients randomly receiving N2O (70%) or Air (70%) in 30% O2 during anesthesia. We included adults having non cardiac surgery. We compared recovery scores for episodic memory, decision making/processing speed and executive functions measured with the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB). Assessments were performed at baseline, seven and ninety days. At first interim analysis, following recruitment of 140 participants, the trial was suspended. We found that the mean (95%CI) changes of scores for episodic memory were in the Pocock futility boundaries. Decision making/processing speed did not differ either between groups (P > 0.182). But for executive functions at seven days, the mean number (95% CI) of problems successfully solved and the number of correct box choices made was higher in the N2O group, P = 0.029. N2O with the limitations of an interim analysis appears to have no harmful effect on cognitive functions (memory/processing speed). It may improve the early recovery process of executive functions. This preliminary finding warrants further investigations.
Highlights
The number of surgical procedures performed worldwide is estimated at 312 million[1]
For the primary outcome used for sample size calculation the between group difference observed at 7 days was < 0.0244 and within the stopping boundaries for futility at T1
For all outcome measures of the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests used for episodic memory and decision making/processing speed assessment, there were no between group differences at 7 and 90 days following surgery, suggesting harmlessness of N2O
Summary
The number of surgical procedures performed worldwide is estimated at 312 million[1]. Considered for decades as innocuous, there is emerging evidence that N2O carries a number of potential side e ffects[3]. It enlarges natural air spaces (bowels, lungs, tympanic cavity). Whilst some reports (both animal and human studies) attribute postoperative learning difficulties, loss of memory, disorientation[11,12,13] and reduced psychomotor performance to N2O14,15, others including randomized trials, fail to identify any detrimental effect of N 2O on cognitive p erformance[16,17,18,19,20]. Using three computerized neuropsychological tests (thirteen outcome scores) of the Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared postoperative neurocognitive recovery of patients receiving N2O in the anesthetic gas mixture administered during surgery with patients receiving N2O free anesthesia
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