A 2020 meta-analysis aimed to evaluate the clinical efficacy and safety of sugammadex compared to neostigmine or placebo for the reversal of rocuronium-induced neuromuscular blockade (NMB) in adult patients. A total of 22 studies were evaluated to quantify the mean difference in train-of-four (TOF) recovery time to at least 90% of complete reversal. Sugammadex was found to lead to significantly faster recovery time from two of four twitches (T2) to TOFR > 0.9 recovery of twitch height compared to neostigmine (mean difference 11.7 minutes; 95% confidence interval [CI], -15.6 to -7.8 minutes; p<0.0001). Reversal with sugammadex compared with neostigmine resulted in less anesthesia time (mean difference -18.6 minutes, 95% CI, -37.3 to 0.2 min, p= 0.056) and less post-anesthesia recovery unit (PACU) time (mean difference of -12.0 min; 95% CI, -24.7 to 0.6 minutes, p= 0.063); however, the differences were not statistically significant. Patients receiving sugammadex were significantly less likely to experience bradycardia (odds ratio [OR] 0.22; 95% CI, 0.1 to 0.5; p= 0.0003) and postoperative nausea and vomiting (OR 0.64; 95% CI, 0.46 to 0.87; p= 0.0065) compared to neostigmine patients. Overall, sugammadex leads to a faster recovery time based on the TOFR and appears better tolerated than neostigmine. [1]
A 2010 systematic review including three randomized controlled trials (RCTs) compared sugammadex with neostigmine/glycopyrrolate for the reversal of moderate or profound NMB produced by rocuronium or vecuronium. Methods of stimulation included post-tetanic count (PTC) and TOF stimulation. It was shown that recovery from moderate block had significantly faster recovery times after rocuronium or vecuronium with sugammadex versus neostigmine/glycopyrrolate. Additionally, a significant difference in moderate block recovery times was reported between rocuronium with sugammadex compared with cisatracurium with neostigmine/glycopyrrolate. There were similar trends for recovery from moderate block to a TOFR= 0.8 and 0.7 (p<0.00001). The authors suggested that sugammadex produces a substantially faster and more predictable recovery from rocuronium- or vecuronium-induced moderate NMB than neostigmine/glycopyrrolate. However, since the number of studies was limited, its clinical relevancy in practice and cost-effectiveness remain uncertain. Additionally, the clinical trials of sugammadex were not sufficiently powered to evaluate the rates of significant adverse events (AEs). Overall, the authors concluded that there are potential benefits of sugammadex in increased patient safety and predictability in NMB recovery. [2]
A 2021 meta-analysis (N= 386; 7 trials) evaluated the efficacy and safety of sugammadex versus neostigmine in the reversal of NMB in morbidly obese (MO) patients undergoing bariatric surgery. Sugammadex resulted in a significantly reduced time of reversal of moderate NMB-to-TOF ratio >0.9 compared to neostigmine (mean difference −14.52; 95% CI, −20.08 to −8.96; p<0.00001). Moreover, the number of patients who had composite adverse events was significantly lower with sugammadex compared to neostigmine (21.2% vs. 52.5%; OR 0.15; 95% CI, 0.07 to 0.32; p<0.00001). This meta-analysis may be limited by the quality of included trials and high heterogeneity among studies. [3]
A 2020 single-center, non-blinded controlled trial including 41 patients undergoing liver transplantation evaluated sugammadex versus neostigmine for recovery after rocuronium continuous infusion. NMB was maintained by continuous intravenous (IV) infusion of rocuronium bromide (Esmeron® 50 mg/5 mL) 0.3-0.6 mg/kg/h. At the end of the surgery, either sugammadex 2 mg/kg based on actual body weight (Bridion® 100 mg/mL) or neostigmine 50 mcg/kg based on adjusted body weight plus 10 mcg/kg of atropine (Intrastigmina®, 0.5 mg/mL) were administered. The mean recovery from the NMB was significantly faster after sugammadex administration compared with neostigmine administration (9.4 ± 4.6 min vs. 34.6 ± 24.9 min; p<0.0001). No AEs were reported in either group. The authors concluded that despite considerably faster recovery time in sugammadex than that of neostigmine, further large-scale, prospective RCTs are warranted to examine its efficacy and safety in other surgical populations. [4]
Numerous studies have identified various factors that may delay the clearance of the sugammadex-rocuronium complex. Many of these factors pertain to the clinical disposition of the patient. Rocuronium excreted both biliary (> 75%) and renal excretion (26%) but the sugammadex-rocuronium complex is primarily excreted via urine (65% to 97%). Rocuronium bond to sugammadex increases urine excretion by two- to three-fold within the first 24 hours of healthy adults and surgical patients. Therefore, patients with impaired renal function can lead to prolonged exposure but the effect on the efficacy of sugammadex appears to be unaltered, and unblocking of the complex does not seem to occur. The sugammadex-rocuronium complex is characterized by a low dissociation rate (dissociation constant Kd = 0.1 × 10^-6 M) suggesting that only a minuscule fraction is completely disassociated. [5], [6], [7], [8], [9]
The nondepolarizing neuromuscular blocking agents can be divided into two classes, steroidal and benzylisoquinolinium. Steroidal neuromuscular blocking agents include rocuronium, vecuronium, and pancuronium. The benzylisoquinolinium group consists of atracurium, mivacurium, and cisatracurium. Sugammadex is approved for the reversal of steroidal agents rocuronium, along with vecuronium in non-immediate reversal situations. But sugammadex cannot reverse the benzylisoquinolinium group whereas neostigmine plus an anticholinergic agent (e.g., glycopyrrolate or atropine) may be used to reverse either nondepolarizing neuromuscular blocking classes which have not been categorized based on potency between classes. [10], [11], [12]