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The choice of general anaesthetics may affect postoperative cognitive outcomes. This study was designed to compare the potential impact of propofol-based vs sevoflurane-based general anaesthesia on the development of delayed neurocognitive recovery in older adults early after major cancer surgery.Older adults (aged ≥65 and <90 yr) who were scheduled to undergo major cancer surgery (≥2 h) were randomised to receive either propofol- or sevoflurane-based general anaesthesia. Cognitive function was assessed before and 1 week after surgery with a battery of neuropsychological tests. Age- and education-matched non-surgical controls were recruited, and their cognitive functions were tested at comparable time intervals in order to adjust for learning effects from repeated tests. Delayed neurocognitive recovery was diagnosed according to the International Study of Postoperative Cognitive Dysfunction 1 definition.From April 1, 2015 to October 15, 2016, 392 patients were enrolled and randomised. Of these patients, 387 completed the intervention and 30-day follow-up, and 379 completed 1-week neuropsychological tests. Fifty-nine control subjects were enrolled and completed repeated neuropsychological tests. The incidence of delayed neurocognitive recovery at 1 week was significantly lower in the propofol group [14.8% (28/189)] than in the sevoflurane group [23.2% (44/190); odds ratio=0.577; 95% confidence interval, 0.342–0.975; P=0.038]. Safety outcomes did not differ between the two groups.When compared with sevoflurane-based general anaesthesia, propofol-based general anaesthesia might decrease the incidence of delayed neurocognitive recovery in older adults after major cancer surgery.NCT02662257; Chinese Clinical Trial Registry (identifier: ChiCTR-IPR-15006209).