Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship.
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 T₄/T₁ 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 T₄/T₁ 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.
Pühringer
F K
FK
Klinik für Anästhesiologie und Operative Intensivmedizin, Klinikum am Steinenberg, Reutlingen, Germany. puehringer_f@kreiskliniken-reutlingen.de
Gordon
M
M
Demeyer
I
I
Sparr
H J
HJ
Ingimarsson
J
J
Klarin
B
B
van Duijnhoven
W
W
Heeringa
M
M
D000328:Adult; D000732:Androstanols / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade / Q000379:methods; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077123:Rocuronium; D016037:Single-Blind Method; D000077122:Sugammadex; D014673:Vecuronium Bromide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D014673:Vecuronium Bromide; D000077123:Rocuronium