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

Abstract Background 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. Methods 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. Results 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]. Conclusions During sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.