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Incomplete Reversal of Pancuronium Neuromuscular Blockade by Neostigmine, Pyridostigmine, and Edrophonium

Received from the Department of Anesthesiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Address correspondence to Dr. R. R. Bartkowski, Department of Anesthesiology, Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA 19107.

Abstract

Three clinically used anticholinesterases—neostigmine, pyridostigmine, and edrophonium—were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED₅₀ for 95% block 5.5 ± 4 nM), followed by pyridostigmine (0.27 ± 0.06 µM) and edrophonium (2.1 ± 0.05 µM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.

Key Words: ANTAGONISTS, NEUROMUSCULAR RELAXANTS—neostigmine, pyridostigmine, edrophonium. • NEUROMUSCULAR RELAXANTS—pancuronium.

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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