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Reversal of Neuromuscular Blockade

Dose Determination Studies with Atropine and Glycopyrrolate Given before or in a Mixture with Neostigmine

Rajinder K. Mirakhur, MD, PhD, FFARCS^*, John W. Dundee, MD, PhD, FFARCS, MRCP, Christopher J. Jones, BPharm, Dennis L. Coppel, MB, FFARCS, and Richard S. J. Clarke, MD, PhD, FFARCS

*Senior Tutor. Present address: Consultant Anaesthetist, Royal Victoria Hospital, Beliast, BT12 6BA, Northern Ireland. Professor. Manager of Clinical Research. Consultant Anesthetist. Received from the Department of Anaesthetists, Queen's University of Belfast, Belfast, Northern Ireland; and A. H. Robins Co. Ltd., West Sussex, United Kingdom.

Abstract

Glycopyrrolate and atropine were studied in doses of 5, 10, or 15 µg/kg and 10, 20, or 30 µg/kg, respectively, given intravenously either before or in a mixture with neostigmine, 50 µg/kg, at the time of reversal of neuromuscular block. When given first, both anticholinergic drugs produced a dose-related increase in heart rate; following the administration of neostigmine the heart rates decreased. When administered in a mixture with neostigrnine, the 20– and 30-µg/kg doses, but not the 10-µg/kg dose of atropine were associated with an initial increase in heart rate. This was, however, absent with all the doses of glycopyrrolate. The 5-µg/kg dose of glycopyrrolate and 10-µg/kg dose of atropine given either before or in a mixture with neostigmine were associated with unacceptable decreases in heart rate and needed further anticholinergic drug administration. The 10-µg/kg dose of glycopyrrolate, when administered in a mixture with neostigmine, was associated with the most stable heart rates. Increasing the dose to 15 µg/kg was not associated with undue tachycardia and is not hazardous. Atropine, 20 µg/kg, necessitated a further administration of atropine in nearly a third of patients in this group due to bradycardia (heart rate of 50 beats/min or less) and would be considered inadequate. Increasing the dose to 30 µg/kg prevented bradycardia but was accompanied by significant initial tachycardia and a higher incidence of dysrhythmias when administered before neostigmine. The frequency of dysrhythmias was otherwise similar. It is recommended that anticholinergic drugs be administered in a mixture with neostigmine. Glycopyrrolate, administered in this way in a dose of 10 µg/kg, is associated with stable heart rates.

Key Words: PARASYMPATHETIC NERVOUS SYSTEM: atropine, glycopyrrolate • ANTAGONISTS, Neuromuscular Relaxants, neostigmine.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999