Journal: Br J Anaesth 100(3):373 379, 2008. 13 References
Reprint: Dept of Anaesthesiology and Critical Care Medicine, Onze Lieve Vrouw Clinic, Moorselbaan 164, 9300 Aalst, Belgium (G Cammu, MD) SO.05 JU0810/160 ©2008 Financial support was provided by N.V. Organon, Oss, The Netherlands.
Faculty Disclosure: Abstracted by S. Ouellette, who has nothing to disclose.
Sugammadex is a gamma-cyclodextrin that encapsulates steroidal non-depolarizing neuromuscular blocking agents such as rocuronium and vecuronium, thereby reversing their effects. Because of its mode of action, sugammadex does not have cardiovascular effects associated with muscarinic receptor stimulation.
Many drugs used in anesthesia may prolong the QT interval of the ECG. Prolongation may cause development of cardiac arrhythmias including torsade de pointes, which can degenerate into ventricular fibrillation leading to sudden death. A thorough QT study is required for any new drug introduced into clinical practice. The purpose of this study was to establish the safety and tolerability of single IV doses of sugammadex administered simultaneously with rocuronium and vecuronium, first in anesthetized and then in non-anesthetized healthy volunteers. The secondary objective was to investigate the plasma pharmacokinetic profiles of sugammadex, rocuronium, and vecuronium.
Twelve subjects were anesthetized with propofol/remifentanil and received sugammadex 16, 20 and 32 mg/kg combined with 1.2 mg/kg rocuronium or vecuronium 0.1 mg/kg. Four subjects were not anesthetized and received sugammadex 32 mg/kg with rocuronium 1.2 mg/kg or vecuronium 0.1 mg/kg. Neuromuscular function was assessed by TOF-WATCH® SX monitoring in anesthetized subjects and by clinical tests in non-anesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points.
No serious adverse events were reported. Fourteen subjects reported 23 adverse events after study drug administration. Episodes of mild headache, tiredness, cold feeling, dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma¬glutamyl-transferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium and vecuronium plasma concentrations declined faster than those of sugammadex. Single dose sugammadex was well tolerated with no signs of residual neuromuscular block. The combination can safely be administered to non-anesthetized subjects. Since plasma levels of the blocking agent cleared faster than sugammadex, the theoretical risk of neuromuscular block developing again over time is reduced. |
