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

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 microM) and edrophonium (2.1 +/- 0.05 microM). 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.