Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

BACKGROUND: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we 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: We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. RESULTS: Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). CONCLUSIONS: Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Innovative designs for trials informing the care of cardiac surgical patients: Part II.

PURPOSE OF REVIEW: This review examines advances in clinical trial methodologies relevant to cardiac anesthesia. It focuses on innovative approaches, including factorial randomization, composite outcomes, and cluster randomized trials, which enhance the efficiency, practical relevance, and generalizability of trial outcomes. RECENT FINDINGS: Factorial randomization is becoming popular because the approach allows investigators to simultaneously evaluate two or more interventions. Furthermore, factorial designs can evaluate interactions among treatments which is highly relevant information that cannot be obtained from separate trials. Composite outcomes are also increasingly utilized, combining multiple individual outcomes into a single measure, which increases statistical power and can better represent relevant physiology. Designing valid composites requires careful consideration of component outcome severity and incidence. Cluster randomized trials, including stepped wedge and multiple crossover designs, address the challenges of group-level effects and shared environments. SUMMARY: The evolution of clinical trial designs is marked by a shift towards methodologies that enhance efficiency and provide more nuanced insights into treatment effects. These include factorial designs for simultaneous intervention assessment, composite outcomes for comprehensive physiological representation, and cluster trials for group-level effect analysis. Such advancements are shaping the future of clinical research, making it more relevant, efficient, and broadly applicable.

Innovative designs for trials informing the care of cardiac surgical patients: part I.

PURPOSE OF REVIEW: Randomized clinical trials, now commonplace and regarded as top-tier evidence, are actually a recent development. The first randomized trial took place in 1948, just six decades ago. As anticipated from a relatively young field, rapid progress continues in response to an ever-increasing number of medical questions that demand answers. We examine evolving methodologies in cardiac anesthesia clinical trials, focusing on the transition towards larger sample sizes, increasing use of pragmatic trial designs, and the innovative adoption of real-time automated enrollment and randomization. We highlight how these changes enhance the reliability and feasibility of clinical trials. RECENT FINDINGS: Recent understanding in clinical trial methodology acknowledges the importance of large sample sizes, which increase the reliability of findings. As illustrated by P value fragility, small trials can mislead despite statistical significance. Pragmatic trials have gained prominence, offering real-world insights into the effectiveness of various treatments. Additionally, the use of real-time automated enrollment and randomization, particularly in situations where obtaining prior consent is impractical, is an important methodological advance. SUMMARY: The landscape of cardiac anesthesia clinical trials is rapidly evolving, with a clear trend towards large sample sizes and innovative approaches to enrollment. Recent developments enhance the quality and applicability of research findings, thus providing robust guidance to clinicians.