Originally published by our sister publication Anesthesiology News

SAN FRANCISCO—The incidence of postoperative delirium after the reversal of neuromuscular blockade is similar with sugammadex or neostigmine plus anticholinergics in adults undergoing noncardiac surgery, according to new research.

Interestingly, the retrospective study also found that sugammadex (Bridion, Merck) use was associated with a statistically significant increased risk for postoperative emergence delirium, although the investigators reported the difference was not clinically relevant.

“While many risk factors for delirium are nonmodifiable, the use of cholinesterase inhibitors plus anticholinergics for neuromuscular block reversal is one risk factor that may precipitate delirium that we can act upon,” said Emily Abramczyk, a medical student at Cleveland Clinic. “This may be avoided by substituting sugammadex as a reversal agent,” she added.

The researchers sought to evaluate the primary hypothesis that postoperative delirium is less common when neuromuscular blockade is reversed with sugammadex relative to neostigmine combined with glycopyrrolate or atropine. To do so, they conducted a retrospective cohort study of 49,468 adult patients undergoing general anesthesia for noncardiac surgery, who received either neostigmine (n=42,587) or sugammadex (n=6,881) between January 2016 and March 2022. The study’s primary outcome was the presence of delirium within the first four days following surgery, which was defined as at least one positive screening on the brief Confusion Assessment Method (bCAM). The secondary outcome was the presence of emergence delirium within 24 hours of surgery.

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In a presentation at the 2023 annual meeting of the American Society of Anesthesiologists (abstract A1104), Abramczyk reported that following propensity weighting, the incidence of delirium was found to be 1.09% in sugammadex patients, compared with 0.82% in the neostigmine group (odds ratio [OR], 1.33; 95% CI, 0.91-1.95; P=0.147).

The researchers also performed a sensitivity analysis of the primary outcome, which was limited to only those cases with at least six bCAM measurements over the first four postoperative days. Although the analysis led to a patient cohort that was generally sicker than that in the primary analysis, the results were comparable. Sugammadex was associated with an estimated OR for postoperative delirium of 1.20 (95% CI, 0.82-1.77; P=0.346).

Conversely, sugammadex was found to be significantly associated with an increased incidence of postoperative emergence delirium, with an estimated OR of 1.71 (95% CI, 1.07-2.72; P=0.025). An exploratory analysis found no treatment-by-age interaction for either postoperative delirium (P=0.637) or postoperative emergence delirium (P=0.904).

As the investigators concluded, the significantly increased risk for postoperative emergence delirium found with sugammadex proved surprising.

“We thought that this likely reflected the presence of confounding factors, as we can’t think of a mechanistic reason why sugammadex will be more likely to induce delirium in the early postoperative period compared to neostigmine,” Abramczyk explained. “Sugammadex is a relatively large molecule, does not cross the blood–brain barrier, and has not been shown in previous studies to be associated with a greater risk for postoperative emergence delirium.

“We conclude that the choice of a neuromuscular block reversal agent does not affect the development of postoperative delirium,” she said. “Therefore, when we’re looking for risk factors to mitigate the development of delirium, this should not be one of our factors that we consider.”

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Session moderator Detlef Obal, MD, PhD, an assistant professor of anesthesiology, perioperative and pain medicine at Stanford University, in California, noted the difficulties inherent in identifying delirium as part of a retrospective analysis. “So how did you identify delirium in your cohort?” he asked.

“Given our low incidence, we were wondering if delirium was accurately detected,” Abramczyk replied. “However, at our institution, every patient on our postoperative ward is screened for delirium at least twice a day with the bCAM, and any patient suspected of delirium would be screened again. This made us think that we were likely not missing many cases.

“However, we recognize the limitations of retrospective research, which is why we are undertaking a prospective study comparing neostigmine to sugammadex in a trial looking at urinary retention,” she continued.

“Will the prospective study be performed in general surgery patients, or will you include other patient populations, such as those where we normally see a higher incidence of postoperative delirium?” Dr. Obal asked.

“That trial is being done in patients undergoing orthopedic surgery,” Abramczyk responded. “However, in the current retrospective study, we also performed a second sensitivity analysis looking at some of our exclusion groups, such as those requiring postoperative ICU admission or those with a previous history of delirium. And we found an incidence of postoperative delirium in that group that was close to 20%, although those patients were a small part of our general surgery population.”

—By Michael Vlessides

Abramczyk and Obal reported no relevant financial disclosures.