This retrospective observational propensity score-matched study showed that the use of rocuronium/sugammadex compared to cisatracurium/neostigmine decreased the incidence of PPCs and pleural effusion in patients undergoing TA-TAVI. However, the incidence of respiratory infection, pneumothorax, atelectasis, respiratory failure, bronchospasm and aspiration pneumonitis did not differ significantly between the two groups. Of the secondary outcomes, the use of rocuronium/sugammadex was associated with shorter extubation time and length of hospital stay when compared to the use of cisatracurium/neostigmine.
TAVI is an efficient treatment for high-risk and intermediate risk surgical candidates with aortic valve disease, as well as those deemed to high risk to undergo open surgery(25, 26). Among current implanted prostheses available, only J-valve system is suitable for both severe aortic valve stenosis and regurgitation patients(27-29). However, the J-valve is still introduced through TA access which needs sufficient NMB to facilitate the surgical procedure. As a result, the use of nondepolarizing muscle relaxants could increase the risk of postoperative residual NMB and PPCs. Previous meta-analyses have shown that sugammadex reversed NMB more rapidly than neostigmine and was associated with fewer residual NMB rate (TOF ratio of less than 0.9)(30, 31). However, prior observational(16, 18, 32) and randomized trials(15, 17, 33) have reported conflicting results on the effect of sugammadex on PPCs.
Our study showed that rocuronium/sugammadex reduced the composite PPCs rate and pleural effusion rate. Unlike other relevant studies including non-cardiac patients(15, 17, 34), the most common pulmonary complication observed in our study was pleural effusion rather than atelectasis. We considered all pleural effusion to be complications regardless the sides. Because unlike open heart surgery, the delivery catheter and implanted prostheses were inserted through the cardiac apex area on fifth intercostal space without opening the pleural cavity. Pleural effusion is a common complication after cardiac surgery as these TAVI patients are often complicated with heart failure, atrial fibrillation, peripheral vascular disease, receiving therapy with an anticoagulant or antiarrhythmic agent(35). From this, we enrolled the preoperative cardiac function parameters (i.e., NYHA functional class, LV ejection fraction, BNP, CK-MB, cTnT, intraoperative cardioversion or electric defibrillation event) in propensity score matching. After matching, the difference of pleural effusion between the two groups remained statistically significant. In addition, the residual NMB could also contribute to pleural effusion from incomplete recovery of respiratory muscular function(36). Sugammadex can quickly and efficiently re-establish normal muscle strength and cause less postoperative pleural effusion rate after TA-TAVI procedure. This finding was reinforced from a retrospective observational study by Han et al(17). They found that the postoperative pleural effusion rate was lower in patients receiving sugammadex when compared to patients receiving neostigmine, although they failed to found a significant difference of the incidence of PPCs between the groups(17). Furthermore, previous study showed that neostigmine can adversely affect neuromuscular function and impair muscle function (genioglossus muscle and diaphragm) which was associated with respiratory complications(37, 38).
There was a higher rate of NIV in our study (29.06%) compared to other studies for non-cardiac surgeries (1.59% to 12.16%) (18-21). The high rate of COPD in our study may contribute to the higher NIV use. Some studies showed sugammadex was associated with less post-extubation desaturation and consequent NIV use(18, 20). However, in our study, the incidences of NIV (26.4% vs. 31.1%) were similar between the two groups.
In our study, the extubation time was 7.2±6.2 min in the R/S group and 10.3±8.2 min in the C/N group. Our study confirmed that rocuronium/sugammadex was superior to cisatracurium/neostigmine in reducing the extubation time. Lower residual NMB rate following the use of sugammadex(15, 30, 31, 33, 39) may explain the faster extubation in the rocuronium/sugammadex group. Alternatively, this difference in extubation time could be explained by the fact that in the rocuronium/sugammadex protocol reversal agents were administered upon skin closure while the cisatracurium/neostigmine protocol required return of spontaneous breathing prior to dosing of reversal agents. Our finding was consistent with reports of two randomized studies including thoracic surgery with single lung ventilation(33, 40).
Another finding of this trial was that the LOS in hospital was 1.1 days shorter in the R/S group than the C/N group. This was consistent with reports of the association between the PPCs and prolonged hospital LOS(41, 42). However, several previous studies have not detected a reduction of hospital LOS with the use of sugammadex(15, 17, 19, 21, 34, 39, 43, 44). It might be explained by different study population between studies. We included patients with aortic valve disease who had poor clinical conditions from older age, more comorbidities and higher European system for cardiac risk evaluation (EuroSCORE) score when compared with other studies which included non-cardiac surgery patients(15, 17, 19, 21, 34, 39, 43, 44). As a result, the postoperative hospital LOS (7.5 days) in our study was longer than other studies (3.5 to 7.5 days)(15, 21, 34, 43-45) except one study including major abdominal surgery patients (12.5 days)(19).
Recapitulating the results of several studies, our study failed to detect a reduction in respiratory infection with the use of rocuronium/sugammadex(15-17, 19, 34, 40, 45). However, the R/S group showed a significantly lower respiratory infection rate before matching (8.7% vs 17.7%, p=0.04). Although there was no statistical significance after matching, the R/S group showed a relative 44% decrease of respiratory infection rate (11.0% vs 19.6%, p=0.092) which was clinically significant. Actually, relevant studies involving non-cardiac surgeries reported an extremely low respiratory infection rate which ranged from 0.4% to 3.33%(15-17, 19, 34, 40, 45). We supposed that the results in the current and relevant studies might be explained by the insufficient power of the relatively low sample size to detect the difference in respiratory infection with lower event rates. Actually, in a large sample-sized observational study which included 45712 patients, a 47% reduced risk for respiratory infection (adjusted odds ratio, 0.53; 95% CI, 0.44 to 0.62) was found in the sugammadex group compare to the neostigmine group(16).
This study has some limitations. First, this was a retrospective single center series of TA-TAVI. However, we used PSM based on almost all possible variables to control confounding factors. The second weakness is the lack of neuromuscular monitoring. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block(46).
In conclusion, this propensity score match-based study showed that rocuronium/sugammadex decreased the incidence of PPCs in patients undergoing TA-TAVI. A sufficiently powered, prospective randomized study is warranted to confirm this effect size.