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BJA Advance Access published online on February 7, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael013
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted December 5, 2005

Laboratory Investigation

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey{dagger}

H. D. de Boer 1 *, J. van Egmond 1, F. van de Pol 1, A. Bom 2, and L. H. D. J. Booij 1

1 Department of Anaesthesiology, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
2 Department of Pharmacology, Organon Newhouse, ML1 5SH, Scotland, UK

* To whom correspondence should be addressed.
H. D. de Boer, E-mail: HD.de.Boer{at}mzh.nl


  Abstract

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.

Keywords: neuromuscular block, atracurium; neuromuscular block, mivacurium; neuromuscular block, rocuronium; reversal agent, sugammadex (Org 25969).
{dagger}Declaration of interest. This study was supported by a grant from Organon. A. Bom is employed by Organon and L.H.D.J. Booij is a member of their scientific advisory board. H.D. de Boer is currently working at the Department of Anaesthesiology at the Martini Hospital Groningen, Groningen, The Netherlands.
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