A randomized, dose-finding, phase II study of the selective relaxant binding drug, Sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular block.
BACKGROUND
The reversal of a deep neuromuscular blockade remains a significant clinical problem. Sugammadex, a modified gamma-cyclodextrin, encapsulates steroidal neuromuscular blocking drugs, promoting their rapid dissociation from nicotinic receptors. Sugammadex is the first drug that acts as a selective relaxant binding agent.


METHODS
We enrolled 50 patients into a Phase II dose-finding study of the efficacy and safety of sugammadex. Subjects, anesthetized with nitrous oxide and propofol, were randomized to one of two doses of rocuronium (0.6 or 1.2 mg/kg) and to one of five doses of sugammadex (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg). Neuromuscular monitoring was performed using the TOF Watch SX acceleromyograph. Recovery was defined as a train-of-four ratio > or =0.9. Sugammadex was administered during profound block when neuromuscular monitoring demonstrated a posttetanic count of one or two.


RESULTS
Reversal of neuromuscular block was obtained after administration of sugammadex in all but the lowest dose groups (0.5-1.0 mg/kg) where several subjects could not be adequately reversed. At the 2 mg/kg dose all patients were reversed with sugammadex, but there was significant variability (1.8-15.2 min). Patient variability decreased and speed of recovery increased in a dose-dependent manner. At the highest dose (8 mg/kg), mean recovery time was 1.2 min (range 0.8-2.1 min). No serious adverse events were reported during this trial.


CONCLUSIONS
Sugammadex was well tolerated and effective in rapidly reversing profound rocuronium-induced neuromuscular block. The mean time to recovery decreased with increasing doses. Profound rocuronium-induced neuromuscular block can be reversed successfully with sugammadex at doses >/=2 mg/kg.
Groudine
Scott B
SB
Department of Anesthesiology, Albany Medical Center, Albany, New York 12208-34798, USA. groudis@mail.amc.edu
Soto
Roy
R
Lien
Cynthia
C
Drover
David
D
Roberts
Kevin
K
D000732:Androstanols / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008956:Models, Chemical; D019148:Neuromuscular Blockade / Q000379:methods*; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage*; D009609:Nitrous Oxide / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D011978:Receptors, Nicotinic / Q000378:metabolism; D000077123:Rocuronium; D016037:Single-Blind Method; D000077122:Sugammadex; D013997:Time Factors; D047408:gamma-Cyclodextrins / Q000008:administration & dosage* / Q000378:metabolism
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D011978:Receptors, Nicotinic; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D009609:Nitrous Oxide; D000077123:Rocuronium; D015742:Propofol