Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship

Sugammadex shows a dose-response relationship for reversal of neuromuscular block (NMB) during propofol anaesthesia. Sevoflurane, unlike propofol, can prolong the effect of neuromuscular blocking agents (NMBAs), increasing recovery time. This open-label, randomized, dose-finding trial explored sugammadex dose-response relationships, safety, and pharmacokinetics when administered for reversal of moderate rocuronium- or vecuronium-induced NMB during sevoflurane maintenance anaesthesia. After anaesthesia induction with propofol, adult patients were randomized to receive single-dose rocuronium 0.9 mg kg(-1) or vecuronium 0.1 mg kg(-1), with maintenance doses as needed. Anaesthesia was maintained with sevoflurane. NMB was monitored using acceleromyography. After the last dose of NMBA, at reappearance of T-2, single-dose sugammadex 0.5, 1.0, 2.0, or 4.0 mg kg(-1) or placebo was administered. The primary efficacy variable was time from the start of sugammadex administration to recovery of T-4/T-1 ratio to 0.9. Safety assessments were performed throughout. The per-protocol population comprised 93 patients (rocuronium, n=46; vecuronium, n=47). A statistically significant dose-response relationship was demonstrated for mean recovery times of T-4/T-1 ratio to 0.9 with increasing sugammadex dose with both NMBAs: rocuronium, 96.3 min (placebo) to 1.5 min (sugammadex 4.0 mg kg(-1)); vecuronium, 79.0 min (placebo) to 3.0 min (sugammadex 4.0 mg kg(-1)). Plasma sugammadex concentrations indicated linear pharmacokinetics, independent of NMBA administered. No study drug-related serious adverse events occurred. Evidence of reoccurrence of block was reported in seven patients [sugammadex 0.5 mg kg(-1) (suboptimal dose), n=6; 2.0 mg kg(-1), n=1]. During sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.