Reversal of neuromuscular block by sugammadex is associated with less postoperative respiratory dysfunction in the PACU compared with neostigmine: a retrospective study

Editor—Postoperative respiratory dysfunction, defined by requirements for supplemental oxygen, hypoxaemia, or tracheal reintubation, is a known potential complication of general anaesthesia.^1,2 Respiratory dysfunction can encompass many respiratory complications occurring after emergence from anaesthesia, such as pneumonia, respiratory failure, atelectasis, and acute respiratory distress syndrome (ARDS).^3,4 Risk factors include airway surgery, multiple tracheal intubation attempts, and patient factors such as pre-existing respiratory disease.^5,6 Although multifactorial, one probable contributor is continued weakness as a result of residual neuromuscular block.7, 8, 9 Residual neuromuscular block occurs in 20–60% of patients in the PACU and can result from incomplete reversal prior to emergence from anaesthesia. In the immediate postoperative period, residual neuromuscular block is associated with increased postoperative hypoxaemia, atelectasis, and unplanned reintubations.¹⁰

Prior studies examining the impact of sugammadex vs neostigmine on residual neuromuscular block and postoperative respiratory dysfunction resulted in mixed findings. Some studies reported a risk reduction in total postoperative pulmonary complications for sugammadex compared with neostigmine as high as 30%, whereas some studies found no significant reduction.11, 12, 13, 14 Although several studies have primary endpoints of post-PACU respiratory outcomes, such as pneumonia, ARDS, and prolonged mechanical ventilation, few studies examined the impact of sugammadex vs neostigmine on PACU respiratory outcomes. We hypothesised that more rapid and effective neuromuscular block reversal using sugammadex is associated with decreased PACU respiratory dysfunction compared with reversal with neostigmine.

Surgical cases were extracted from the UCLA Perioperative Data Warehouse from May 2014 to May 2021. Cases were divided into pre-sugammadex and post-sugammadex cohorts relative to the date when sugammadex was first made available at UCLA. The pre-sugammadex cohort ranged from May 2014 to May 2016. The post-sugammadex cohort ranged from May 2017 to May 2021 to allow for 1 yr of sufficient data collection. This study was registered at clinicaltrials.gov (NCT04263363).

A propensity score for the likelihood to receive sugammadex was created using a logistic regression model which was used to estimate individual likelihood of receiving sugammadex based upon the following criteria: age, BMI, history of lung disease (chronic obstructive pulmonary disease [COPD], obstructive sleep apnoea, asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension, and lung transplant), and procedure type. Patients who received sugammadex in the post-sugammadex period were matched with patients who were equally likely to have received sugammadex in the pre-sugammadex period. Using the matched data, the association between sugammadex use and postoperative readiness for PACU discharge and postoperative respiratory dysfunction, defined as time of SpO₂ <90%, <93%, and <95% in the PACU, were calculated using regression models. Subgroup analysis was performed on patients with history of lung disease. Time series analysis was also performed to adjust for underlying trends in institutional practice during the study period.

The study included 116 722 patients in the initial unmatched cohort from May 2014 to May 2021. The pre-sugammadex group included 26 989 patients and the post-sugammadex group included 89 733 patients. In the matched cohort comparing patients who received sugammadex vs neostigmine, the odds ratio (OR) for SpO₂ <90%, <93%, and <95% was 0.991 (confidence interval [CI] 0.989–0.993, P<0.001), 1.02 (CI 1.02–1.03, P<0.001), and 1.13 (CI 1.12–1.14, P<0.001), respectively. For PACU discharge time, the coefficient was –7.13 (CI –8.13 to –6.12, P<0.001). For supplemental oxygen duration, the coefficient was –29.4 (CI –31.2 to –27.6, P<0.001). These results can be seen in Table 1. In patients with lung disease, the OR for SpO₂ <90%, <93%, and <95% was 0.88 (CI 0.82–0.94, P<0.001), 1.10 (CI 1.05–1.15, P<0.001), and 1.16 (CI 1.15–1.17, P<0.001), respectively. The regression coefficients for PACU discharge time and supplemental oxygen duration were –8.72 (CI –10.75 to –6.97, P<0.001) and –27.75 (CI –31.45 to –24.06, P<0.001). Patients who received sugammadex had a mean PACU time to discharge of 116 min compared with 122 min for those receiving neostigmine. Similarly, patients receiving sugammadex had a mean postoperative supplemental oxygen duration of 167 min compared with 197 min with neostigmine.

Table 1.

Outcomes analysis of matched and unmatched cohorts. The odds ratio (OR) for the primary endpoints in the unmatched and propensity score-matched cohorts comparing sugammadex and neostigmine are shown. In both unmatched and matched cohorts, sugammadex reversal was associated with higher incidences of hypoxaemia (SpO₂ <95%) compared with neostigmine, but shorter time to PACU discharge and duration of supplemental oxygen use in PACU. CI, confidence interval.

	Unmatched			Matched
	OR	CI	P-value	OR	CI	P-value
Incidence of SpO2 <90%	0.995	(0.992–0.999)	<0.001	0.991	(0.989–0.993)	<0.001
Incidence of SpO2 <93%	1.02	(1.02–1.03)	<0.001	1.02	(1.01–1.03)	<0.001
Incidence of SpO2 <95%	1.14	(1.14–1.15)	<0.001	1.13	(1.12–1.14)	<0.001
	Beta	CI	P-value	Beta	CI	P-value
Time to PACU discharge	–6.42	(–7.93 to –4.91)	<0.001	–7.13	(–8.13 to –6.12)	<0.001
Duration of supplemental oxygen	–31.39	(–33.72 to –29.08)	<0.001	–29.38	(–31.19 to –27.58)	<0.001

Overall, patients who received sugammadex had a lower PACU length of stay and duration of supplemental oxygen than those receiving neostigmine. The incidence of moderate or severe hypoxaemia (saturation <93% and 90%) was statistically but not clinically significantly lower in the sugammadex cohort. The sugammadex cohort had an increased incidence of mild hypoxaemia (saturation <95%).

Our findings regarding hypoxaemia are consistent with recent studies by Murphy and colleagues¹⁵ and Togioka and colleagues¹⁶ that showed no difference in the number of PACU moderate–severe hypoxaemia events. This is further supported by recent studies by Schmidt and colleagues¹⁷ which suggested that PACU postoperative oxygenation requirement was statistically, but not clinically significantly, lower for sugammadex. Suleiman and colleagues¹⁸ found that there was no significant difference in postoperative respiratory complications between use of sugammadex or neostigmine, although their primary endpoint measured desaturation (SpO₂ <90%) within 10 min of extubation, at which time patients might have not have arrived in the PACU. In contrast, patients with COPD, pulmonary hypertension, and lung transplant showed a significant decrease in severe hypoxaemia in the PACU when reversed with sugammadex compared with neostigmine. Regarding shorter PACU length of stay, our findings are corroborated by those of Azimaraghi and colleagues¹⁹ who also found a similar statistically significant, albeit small, reduction in postoperative length of stay when sugammadex was given.

These results are interesting and potentially contradictory. In the short term, patients receiving sugammadex may have more low-grade respiratory dysfunction, but the duration of dysfunction is decreased. A possible explanation, supported by anecdotal clinical practice, is that the superior reversal with sugammadex leads providers to keep patients paralysed longer and ‘deeper’ than with reversal by neostigmine. We observed an increase in mean total rocuronium dose between the pre-sugammadex and post-sugammadex cohorts. Other possibilities include over-capturing hypoxaemic events. We considered a single reading below threshold to indicate hypoxaemia; however, there is a possibility of artifact in any single reading. After removing single measurements of hypoxaemia below threshold, the OR magnitudes for those desaturation outcomes diminished slightly, though the risk of desaturation with sugammadex remained elevated compared with neostigmine.

This study is limited by its retrospective propensity score-matched design. Although the large sample size and relatively good fit of our propensity score model means that the model performed well from a statistical perspective, it is not possible to know what would have happened if sugammadex was available in the pre-sugammadex cohort. The best way to measure these differences would be with a large prospective randomised trial. A further limitation is that this study did not control for potential intraoperative confounders such as intraoperative haemodynamics and train-of-four count at the time of reversal because of data availability. Future work on this topic would control for these intraoperative factors.

We were able to demonstrate that reversal of neuromuscular block by rocuronium with sugammadex can improve PACU throughput and reduce the duration of supplemental oxygen use despite a risk of mild to moderate desaturation. Patients with respiratory disease could experience a significant reduction in severe hypoxaemia in the PACU, though this outcome is not ubiquitous for the whole sugammadex cohort. Although the ultimate choice of agent to reverse neuromuscular block depends on many factors, our results highlight the benefits of sugammadex use in patients with respiratory disease.

Authors’ contributions

Study design: IH, TG

Data analysis: AL, TG

Manuscript writing: IH, AL, EG

Declarations of interest

IH is co-founder and president, and EG is a co-founder of Extrico Health (Los Angeles, CA, USA), a company that helps hospitals leverage data from their electronic health record for decision-making purposes. The Extrico Platform was used to help obtain data for this study. IH and EG receive research support and serves as a consultant for Merck (Los Angeles, CA, USA).

Funding

Merck (EG); US National Institutes of Health (1K01HL150318).