Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics.
BACKGROUND
Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated.


METHODS
Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied.


RESULTS
The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively.


CONCLUSIONS
In male subjects, sugammadex safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium in a dose-dependent manner. Sugammadex enhanced the renal excretion of rocuronium, and its clearance is approximately one third that of rocuronium.
Sparr
Harald J
HJ
Department of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, Innsbruck, Austria. harald.sparr@dornbirn.at
Vermeyen
Karel M
KM
Beaufort
Anton M
AM
Rietbergen
Henk
H
Proost
Johannes H
JH
Saldien
Vera
V
Velik-Salchner
Corinna
C
Wierda
J Mark K H
JM
D000328:Adult; D000732:Androstanols / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D000077123:Rocuronium; D012449:Safety; 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