Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study.
BACKGROUND
Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.


METHODS
Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9.


RESULTS
Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient.


CONCLUSIONS
At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.
Sorgenfrei
Iben F
IF
Department of Anaesthesia and Intensive Care, Copenhagen University Hospital, Rigshospitalet, Denmark.
Norrild
Kathrine
K
Larsen
Per Bo
PB
Stensballe
Jakob
J
Ostergaard
Doris
D
Prins
Martine E
ME
Viby-Mogensen
Jørgen
J
D000293:Adolescent; D000328:Adult; D000732:Androstanols / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium