Association Between Neuromuscular Blockade and Its Reversal With Postoperative Delirium in Older Patients: A Hospital Registry Study

Abstract

Background: Nondepolarizing neuromuscular blocking agents (ND-NMBAs) are dose-dependently associated with residual paralysis, delayed recovery, and prolonged hospitalization, factors that can predispose patients to postoperative delirium. We hypothesized that neuromuscular blockade is associated with a higher risk of delirium after surgery, and that this can be mitigated by administration of reversal agents.

Methods: In total, 53,772 adult hospitalized patients aged ≥60 years who underwent general anesthesia for noncardiac, nonneurosurgical, nontransplant procedures between 2008 and 2024 at a tertiary health care network in Massachusetts, were included. The exposure was the intraoperative administration of ND-NMBAs. The primary outcome was 7-day delirium, identified from nursing and physician charts using a keyword-based search strategy paired with manual chart review, Confusion Assessment Method assessments, and International Classification of Diseases (9th/10th Revision, Clinical Modification) diagnostic codes.

Results: In total, 43,723 (81.3%) patients received neuromuscular blockade. Approximately 2259 (4.2%) patients developed delirium, 1884 (4.3%) with, and 375 (3.7%) without ND-NMBA administration. In adjusted analyses, administration of ND-NMBAs was dose-dependently associated with a higher risk of postoperative delirium (adjusted odds ratio [OR adj ] 1.15; 95% confidence interval [CI], 1.01-1.31; P = .038 and 1.09; 95% CI, 1.06-1.12; P < .001 per each unit increase in the effective dose required to achieve a 95% twitch reduction). 38,143 (87.2%) patients who received ND-NMBAs also received a reversal agent, which was associated with a lower risk of impaired neuromuscular recovery (preextubation train-of-four ratio <95; OR adj 0.60; 95% CI, 0.49-0.74; P < .001) and delirium (OR adj 0.73; 95% CI, 0.64-0.83; P < .001), compared to no reversal. The adverse effect of ND-NMBAs on delirium risk was eliminated by reversal agent administration (OR adj 1.07; 95% CI, 0.94-1.23; P = .30 with and OR adj 1.52; 95% CI, 1.28-1.79; P < .001 without reversal agent administration). There was no association between administration of neostigmine, compared to sugammadex, with postoperative delirium (OR adj 0.91; 95% CI, 0.73-1.12; P = .36).

Conclusions: Neuromuscular blockade during general anesthesia is dose-dependently associated with a higher risk of postoperative delirium. The administration of reversal agents mitigates this risk and might help reduce the occurrence of delirium after surgery.