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Rossler, J., Abramczyk, E., Paredes, S., et al. | Anesth Analg (2025) 140(1):110-118 | Association of intravenous neostigmine and anticholinergics or sugammadex with postoperative delirium: A retrospective cohort study

November 29, 2025

Background: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular block may precipitate delirium through impairment of central cholinergic transmission, which could potentially be avoided by using sugammadex. This study tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine.

Methods: A single-center retrospective cohort study was conducted including all adult patients undergoing noncardiac surgery under general anesthesia who received either neostigmine or sugammadex between January 2016 and March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for confounding factors. The primary outcome was postoperative delirium within the first 4 days after surgery, defined as at least one positive Brief Confusion Assessment Method (bCAM) screening. The secondary outcome was early postoperative delirium within 24 hours after surgery.

Results: Among 49,468 patients, 6,881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of postoperative delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ significantly between the groups (odds ratio 1.33; 95% confidence interval 0.91-1.95; P = 0.147). A sensitivity analysis including only patients with at least six bCAM assessments during postoperative days 1-4 produced similar results (odds ratio 1.20; 95% confidence interval 0.82-1.77; P = 0.346). Sugammadex was associated with a higher incidence of early postoperative delirium (odds ratio 1.71; 95% confidence interval 1.07-2.72; P = 0.025). No treatment-by-age interaction was observed for either postoperative delirium (P = 0.637) or early postoperative delirium (P = 0.904).

Conclusions: Compared with neostigmine, sugammadex was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Although sugammadex was associated with a statistically significant increase in early postoperative delirium, the difference was small, not clinically relevant, and may reflect residual confounding.