The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Prevention of Postoperative Events following Reversal with Sugammadex or Neostigmine (the P-PERSoN Trial): Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial.

Background: Residual paralysis following anaesthesia is common and can lead to postoperative morbidity. While sugammadex has been shown to be effective in minimising residual paralysis, uncertainty exists as to whether its use reduces any associated morbidity. We designed this trial to determine if the use of sugammadex for the reversal of intraoperative aminosteroid neuromuscular blockade results in improvements in postoperative pulmonary complications, complications in the recovery unit, postoperative nausea and vomiting, and patient satisfaction, when compared to reversal with neostigmine. Methods: A prospective, double-blind, randomised controlled trial in adult patients admitted for surgical operations at two Australian hospitals between December 2018 and March 2019 was performed comparing the reversal of neuromuscular paralysis using sugammadex 2 mg/kg versus neostigmine 50mcg/kg. Statistical analysis of continuous data was performed using two tailed t-tests, with categorical and ordinal data being assessed by chi-squared analysis. Results: The trial was terminated due to a combination of resource constraints and the 2019 novel coronavirus disease (COVID-19) pandemic. Of 51 patients screened, 33 were eligible for participation and 30 subsequently recruited and randomised. All patients received the intended treatment allocated. Data for the primary outcome was obtained in all patients. There was no difference in the rates of postoperative pulmonary complications between the sugammadex and neostigmine groups (0% (0/19) vs 9% (1/11) RR 5.0 (95% CI 0.22-113) p=0.37. There was no difference in any of the secondary outcomes between the groups. Conclusions: The P-PERSoN trial showed no difference in postoperative pulmonary complications between sugammadex and neostigmine based reversal of aminosteroid neuromuscular block, but was underpowered to show any difference due to early trial termination. The randomisation and data collection was feasible. We support the need for an adequately resourced and funded randomised controlled trial to address this important clinical question.

The use of sugammadex in critical events in anaesthesia: A retrospective review of the webAIRS database.

Sugammadex has been used for more than ten years in Australia and New Zealand and has been implicated as an effective treatment, and in some cases a potential cause, of a critical incident. We aimed to identify and analyse critical incidents involving sugammadex reported to webAIRS, a de-identified voluntary online critical incident reporting system in Australia and New Zealand. We identified 116 incidents where the reporter implicated sugammadex as either a cause (23 cases) or a treatment (93 cases) during anaesthesia. There were 17 incidents suggestive of sugammadex anaphylaxis, although not all were confirmed by skin testing. There were six incidents when bradycardia was temporally related to sugammadex administration, although it was not possible to exclude other causes or contributory factors. There were nine incidents in which sugammadex was used to reverse aminosteroid-related neuromuscular blockade successfully in a 'can't intubate, can't oxygenate' (CICO) situation, and a further 67 incidents in which sugammadex was used to reverse aminosteroid neuromuscular blockade as part of the management of other critical incidents. While sugammadex was used during the management of 16 cases of anaphylaxis, there was no clear indication that this altered the course of the anaphylaxis in any of the cases. These reports indicate that sugammadex can be a potential trigger for anaphylaxis and that its use may be associated with the development of significant bradycardia. However, it is not possible to estimate or even speculate on the incidence of these sugammadex-related incidents on the basis of voluntary reporting to a database such as webAIRS. The reports also indicate that sugammadex has been used successfully to reverse residual or deep aminosteroid neuromuscular blockade in critical incident situations and to help rescue CICO scenarios. These findings provide further support for ensuring the ready availability of sugammadex wherever aminosteroid muscle relaxants are used.

A survey of current management of neuromuscular block and reversal in Australia and New Zealand.

In recent years there has been a significant investment in education on the management of neuromuscular blockade and increased availability of sugammadex in anaesthetic practice. This survey aimed to examine contemporary practice of Australian and New Zealand anaesthetists in managing neuromuscular blockade and its reversal. A web-based, voluntary survey was distributed to a cohort of 1000 Fellows of the Australian and New Zealand College of Anaesthetists. We received 229 completed responses (survey response rate of 23%). Seventy-one percent (95% confidence interval (CI) 64% to 76%) of the survey respondents thought that 5% or fewer of the patients in their hospital display clinically significant postoperative paralysis. Only 35% (95% CI 18% to 29%) thought that quantitative neuromuscular twitch monitors should be used to monitor neuromuscular block, and the dose and time given for reversal agents was often inconsistent with published recommendations. Sugammadex was the preferred reversal agent for 78% (95% CI 72% to 83%) of survey respondents, but they indicated that cost remains a significant barrier to its widespread uptake. Despite the low response rate, this survey identified that some reported practices in Australia and New Zealand deviate from guidelines and current recommendations in the management of neuromuscular blockade. If the respondents are representative of the broader anaesthetic community, there appears be a greater preference for sugammadex over neostigmine for reversal of neuromuscular blockade.

The effect of routine availability of sugammadex on postoperative respiratory complications: a historical cohort study.

BACKGROUND: Postoperative residual curarisationf is a preventable cause of postoperative morbidity. Although sugammadex has been shown to reduce the risk of residual curarisation, it has not yet been shown if this directly translates to a reduction in morbidity. We aimed to demonstrate whether the introduction of unrestricted sugammadex for routine reversal changed the incidence of post-operative respiratory diagnoses and the rate of airway and respiratory complications in the post-operative care unit. METHODS: A historical cohort study of 1257 patients who underwent general surgical or ear, nose and throat (ENT) procedures before and after the introduction of unrestricted availability of sugammadex. Patient records were used to identify the incidence of postoperative in-hospital respiratory diagnoses and of airway complications in PACU, the pattern of muscle relaxant use and the relative costs associated with the routine availability of sugammadex. RESULTS: Unrestricted sugammadex availability was associated with a significant reduction in the rate of a postoperative in-hospital respiratory diagnosis; Odds Ratio (OR) = 0.20 (95%CI 0.05-0.72, p=0.01). Furthermore, the use of sugammadex itself was also associated with a reduction in inhospital respiratory diagnoses; OR = 0.26 (95%CI 0.08-0.94, p=0.04). Unrestricted sugammadex was also associated with a decrease in the need for manual airway support in the recovery room (3.2% vs 1.1%, p=0.02) and a decrease in patients being transferred intubated to ICU (5.5% vs 1.3%, p<0.001). CONCLUSION: Unrestricted sugammadex availability is associated with a reduction in post-operative respiratory complications. A well-designed, prospective randomised trial is needed to provide further validation of the data.