Association Between Neuromuscular Blockade and Its Reversal With Postoperative Delirium in Older Patients: A Hospital Registry Study
Elena Ahrens, Luca J. Wachtendorf, Denys Shay, Theresa Tenge, Béla‐Simon Paschold, Maíra I. Rudolph, Simone Redaelli, Lars Kaiser, Aiman Suleiman, Haobo Ma, Philipp Faßbender, Maximilian S. Schaefer
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.