The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18-64 yr) versus elderly adult (aged 65 yr or older) patients.This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1-3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated.Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18-64 yr (adult), 62 were aged 65-74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0-2.6) min (adults) to 2.9 (2.7-3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients.Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.
Background: Residual neuromuscular blockade (NMB) is associated with increased risk of post-operative critical respiratory events. We compared incidence of residual NMB at tracheal extubation after reversal of rocuroniuminduced NMB with sugammadex versus neostigmine.
Methods: Adult patients of American Society of Anesthesiologists Class 1-3, scheduled to undergo open abdominal surgery were included. Patients were randomized to receive sugammadex 4.0 mg/kg at ≥1-2 posttetanic counts after last rocuronium dose, or neostigmine 50mg/kg + glycopyrrolate 10mg/kg, according to usual care practices at each institution. Neuromuscular function was assessed using TOF-Watch® SX. Anesthesiologists were blinded to the TOF-Watch recording, except to ask the TOF-Watch operator whether ≥1 PTC had been reached before administering reversal. Use of a peripheral nerve stimulator was permitted. Clinical criteria defined by the institution were used to determine when to perform extubation. Primary efficacy variable was incidence of residual NMB (train-of-four [TOF] ratio <0.9) at extubation. Safety parameters were assessed by a blinded safety assessor.
Results: The intent-to-treat group comprised 97 patients (sugammadex, n=51; neostigmine, n=46). Among patients with valid TOF data, a TOF ratio of ≥0.9 was reached at or before extubation in 48 of 50 (96.0%) sugammadex and 17 of 43 (39.5%) neostigmine patients (P<0.0001). One sugammadex (2.0%) and 15 neostigmine patients (34.9%) were extubated at TOF ratios ≤0.7. Median (95% CI) time from study drug administration to recovery to a TOF ratio ≥0.9 was 2.0 (1.8-2.5) minutes for sugammadex (n=49) versus 8.0 (3.8-16.5) minutes for neostigmine (n=18) (P<0.0001). Safety was comparable between groups, with no clinical evidence of recurrence of NMB.
Conclusions: Significantly more sugammadex-treated patients recovered to a TOF ratio ≥0.9 at extubation and did so significantly faster than neostigmine-treated patients. This study confirms that sugammadex is more effective than neostigmine in reducing potential for residual blockade in the absence of objective NMB monitoring.
Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group. Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).
