Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.
BACKGROUND
Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced by rocuronium or the non-steroidal neuromuscular blocking drugs, mivacurium or atracurium, in the anaesthetized Rhesus monkey.


METHODS
After a bolus injection of rocuronium, mivacurium or atracurium, a continuous infusion of these drugs was started to maintain the first twitch contraction of the train-of-four at approximately 10% of its baseline value. After a steady state block of at least 10 min the infusion was stopped and the preparation was allowed to recover spontaneously. This process was repeated, but at the time the infusion was stopped, either sugammadex 0.5 or 1.0 mg kg(-1) was given in the rocuronium-induced blockade and sugammadex 1.0 mg kg(-1) was given in the mivacurium- and atracurium-induced blockade.


RESULTS
Sugammadex caused a rapid and complete reversal of rocuronium-induced neuromuscular block. The recovery time to train of four ratio=0.9 after spontaneous recovery was 14.4 min (sd=3.4 min; n=14). This was reduced significantly (P<0.001) to 3.7 min (sd=3.3 min; n=4) with sugammadex 0.5 mg kg(-1) and to 1.9 min (sd=1.0 min; n=4) with sugammadex 1.0 mg kg(-1). Signs of residual blockade or re-curarization were not observed. Reversal of mivacurium- or atracurium-induced neuromuscular block (n=2 in each experiment) by sugammadex (1.0 mg kg(-1)) was not effective. In all experiments, injection of sugammadex had no effects on blood pressure or heart rate.


CONCLUSIONS
Sugammadex is effective in reversing rocuronium, but not mivacurium- or atracurium-induced neuromuscular block.
de Boer
H D
HD
Department of Anaesthesiology, Radboud University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands. HD.de.Boer@mzh.nl
van Egmond
J
J
van de Pol
F
F
Bom
A
A
Booij
L H D J
LH
D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D001279:Atracurium / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007546:Isoquinolines / Q000037:antagonists & inhibitors; D008253:Macaca mulatta; D000077590:Mivacurium; D008958:Models, Molecular; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
D000732:Androstanols; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D001279:Atracurium; D000077122:Sugammadex; D000077590:Mivacurium; D000077123:Rocuronium