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BJA Advance Access published online on December 23, 2005
British Journal of Anaesthesia, doi:10.1093/bja/aei306
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted October 12, 2005

Laboratory Investigation

Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys{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, 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. At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block reversal. The present study evaluates the capacity of nine synthetic cyclodextrin derivatives (Org 25288, Org 25289, Org 25467, Org 25168, Org 25169, Org 25555, Org 25166, Org 26142, and Org 25969) to reverse constant neuromuscular block of ~90%, induced by rocuronium infusion in the Rhesus monkey, using single twitch stimulation. The ability of these cyclodextrin derivatives to reverse neuromuscular block was compared with the reversal of the same neuromuscular block by the commonly used combination of neostigmine and atropine.

Methods. After a bolus injection of rocuronium, continuous infusion was started to reduce twitch contractions to ~10% of baseline values. 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 one of the nine cyclodextrin derivatives or a combination of neostigmine and atropine was given.

Results. Recovery with cyclodextrin derivatives Org 26142 and Org 25969 was faster than after a combination of neostigmine and atropine (P<0.05). Injection of these cyclodextrin derivatives did not affect blood pressure or heart rate. Signs of residual block or recurarization were not observed in any of these experiments. In the experiments in which a combination of neostigmine and atropine was given, two animals showed signs of abdominal discomfort as frequently seen after the administration of neostigmine and significant changes in circulatory variables.

Conclusions. Chemical encapsulation or chelation of rocuronium is a new concept in reversing neuromuscular block induced by rocuronium.

Keywords: chemical encapsulation; neuromuscular block, rocuronium; reversal agent, cyclodextrins.
{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.
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