Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.
BACKGROUND
Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated.


METHODS
A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography.


RESULTS
Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min.


CONCLUSIONS
Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.
Pühringer
Friedrich K
FK
Department for Anesthesiology and Intensive Care Medicine, Klinikum am Steinenberg, Reutlingen, Germany.
Rex
Christopher
C
Sielenkämper
Andreas W
AW
Claudius
Casper
C
Larsen
Per Bo
PB
Prins
Martine E
ME
Eikermann
Matthias
M
Khuenl-Brady
Karin S
KS
D000732:Androstanols / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015742:Propofol; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D000732:Androstanols; D018686:Anesthetics, Intravenous; D009467:Neuromuscular Depolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium; D015742:Propofol