Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery

A Retrospective Cohort Analysis of Postoperative Side Effects

Kurt Ruetzler, MD, FAHA; Kai Li, MD; Surendrasingh Chhabada, MD; Kamal Maheshwari, MD, MPH; Praveen Chahar, MD, FCARCSI; Sandeep Khanna, MD; Marc T. Schmidt; Dongsheng Yang, MS; Alparslan Turan, MD; Daniel I. Sessler, MD


Anesth Analg. 2022;134(5):1043-1053. 

In This Article


We identified 89,753 surgeries on 70,690 patients who met inclusion and exclusion criteria, including 16,480 (18%) surgeries during which sugammadex was given at the end of surgery and 73,273 (82%) during which neostigmine was given (Figure 1). Table 1 lists the patients who met screening criteria for adjudication of clinically important adverse effects of reversal agents.

Figure 1.

Flow diagram. ASA indicates American Society of Anesthesiologists; ICD, International Classification of Diseases.

Patients were given a mean (SD) of 3.9 (2.5) mg kg–1 sugammadex and a mean of 279 (100) μg kg–1 neostigmine. The average age was 55 (19) years, and 51% were women. Baseline characteristics and surgical factors, after weighting, were well balanced except type of surgery (ASD = 0.23; Table 2; Figure 2). Consequently, the type of surgery was adjusted for in all of the analyses comparing patients who received sugammadex and neostigmine. The histograms of estimated propensity scores showed a good overlap and similar distribution across 2 groups (Supplemental Digital Content 1, Figure 1, Supplemental Digital Content 2, Table 1,, summarized postoperative events by types of surgeries. Supplemental Digital Content 3, Table 2,, reported the balance of baseline characteristics and surgical factors after excluding pediatric and cardiac surgeries, and the type of surgery was also imbalanced (ASD = 0.112).

Figure 2.

Plot of ASD between sugammadex group (N = 16,480) and neostigmine group (N = 73,273) on covariables before and after the inverse propensity score weighting. First, we estimated the probability of receiving sugammadex (ie, the propensity score) for each patient using logistic regression with receiving sugammadex as the outcome using the following prespecified potential confounding variables (listed in Table 1). Then, we calculated the stabilized weights as follows: for the sugammadex group, weight was the proportion of sugammadex patients divided by the propensity score; for the neostigmine group, weight was the proportion of neostigmine patients divided by (1 – propensity score). To be conservative, we also truncated the stabilized weights at 1st and 99th percentiles. ASD is absolute difference in means or proportions divided by the pooled standard deviation. Any covariable with an ASD >0.10 was considered to be imbalanced. ASA indicates American Society of Anesthesiologists; ASD, absolute standardized difference; IPTW, inverse probability of treatment weighting.

During the screening process, a total of 2238 potential episodes of clinically meaningful bradycardia, 180 cases of cardiac arrests, 391 cases with anaphylaxis, and 849 cases with bronchospasm were identified. The adjudicators individually assessed all patients who were given supplemental IV atropine, along with patients who were given epinephrine, methylprednisolone, or diphenhydramine via any route. Patients with documented chest compression, defibrillation, or cardioversion were also evaluated, as were patients in whom a diagnosis of anaphylactic reaction was documented.

A total of 459 cases were individually reviewed by the adjudicators. Assessments of the 3 initial adjudicators were consistent in 416 cases. There were also 41 cases that were reviewed by the chief adjudicator who agreed with the diagnosis of the 2 matching assessments. Just 2 cases required discussion by the adjudication committee, with consensus diagnoses being unanimously assigned. Ultimately, we identified 2004 cases of bradycardia, 14 cases of cardiac arrests, 6 cases of anaphylaxis, and 731 cases of bronchospasm.

The observed incidences of the composite outcome and individual side effects are summarized in Table 3. The incidence of the composite outcome was 3.4% in the sugammadex group and 3.0% in the neostigmine group. The most common individual postoperative side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with the estimated OR of 1.21 (sugammadex versus neostigmine; 95% CI, 1.09–1.34), noninferiority P = .57; (Table 3; Figure 3). However, we found that neostigmine was superior to sugammadex with an estimated OR of 0.83 (0.74–0.92), 1-side superiority P < .001. The results of the sensitivity analysis are consistent with these findings.

Figure 3.

Forest plot for noninferiority testing. There were significantly more side effects with sugammadex than with neostigmine. CI indicates confidence interval.