Reversal of Neuromuscular Blockade with Sugammadex at the Reappearance of Four Twitches to Train-of-four Stimulation

Background: Doses of sugammadex required to reverse deep, moderate, and shallow rocuronium-induced neuromuscular blockade have been established. However, no adequate doses for the reversal of reappearance of four twitches of train-of-four (TOF) stimulation (threshold TOF-count-four) have been established. Methods: This single-center, randomized, controlled, double-blind, four-groups parallel-arm study included 80 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Once rocuronium-induced neuromuscular blockade recovered spontaneously to threshold TOF-count-four, patients randomly received 0.5, 1.0, 2.0 mg/kg of sugammadex or 0.05 mg/kg of neostigmine. The time between study drug injection and reversal of TOF ratios to 1.0 was measured. Rapid reversal (<= 2.0 min average, upper limit of 5.0 min) was the primary endpoint and slower reversal (<= 5.0 min average, upper limit of 10 min) was the secondary endpoint of the study. Results: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed threshold TOF-count-four to TOF ratios of 1.0 in 2.1 +/- 0.8 min (mean +/- SD) and 1.8 +/- 0.9 min, respectively. Sugammadex, 0.5 mg/kg, induced a similar degree of reversal in 4.1 +/- 1.9 min (P < 0.001 vs. 1.0 and 2.0 mg/kg). Neostigmine, 0.05 mg/kg, reversed TOF ratios to 1.0 in 8.5 +/- 3.5 min (P < 0.001 vs. sugammadex groups). Conclusion: Sugammadex, 1.0 mg/kg, rapidly and effectively reverses rocuronium-induced block that has recovered spontaneously to a threshold TOF-count-four. A dose of 0.5 mg/kg was equally effective, but satisfactory antagonism took as long as 8 min to take place.