Correspondence  |   August 2018
In Reply
Author Notes
  • Mayo Clinic College of Medicine, Jacksonville, Florida (S.J.B.). sjbrull@me.com
  • (Accepted for publication May 8, 2018.)
    (Accepted for publication May 8, 2018.)×
Article Information
Correspondence
Correspondence   |   August 2018
In Reply
Anesthesiology 8 2018, Vol.129, 383-384. doi:10.1097/ALN.0000000000002296
Anesthesiology 8 2018, Vol.129, 383-384. doi:10.1097/ALN.0000000000002296
We thank Drs. Phillips and Stewart for their interest in the work by Murphy et al.1  and our accompanying editorial.2  They “respectfully questioned five areas of the study” by Murphy et al., and we are delighted to respond; we feel this topic has significant implications on clinical care and that a thorough understanding of the effects of neostigmine on neuromuscular transmission is paramount for optimal anesthetic care and patient safety.
Drs. Phillips and Stewart are absolutely correct about the potential for neostigmine to induce a depolarizing block, and thus, neuromuscular weakness. However, neostigmine may cause a depolarizing block (and clinical weakness) if it is not preceded by a nondepolarizing neuromuscular blocking drug. In most clinical settings, neostigmine is administered during periods of neuromuscular recovery, when a significant proportion of postsynaptic acetylcholine receptors are still occupied (blocked) by the neuromuscular blocking drug; in fact, it has been estimated that up to 70 to 75% of the receptors may be blocked by a neuromuscular blocking drug before fade to repetitive stimulation becomes apparent.3  This partial nondepolarizing block appears to be protective of the depolarizing actions of excess acetylcholine produced by neostigmine. Published data confirm Murphy et al.’s observation1  that neostigmine administration at neuromuscular recovery was not associated with evidence of muscle weakness. For instance, Caldwell4  studied the effect of neostigmine 40 µg/kg administered at 1, 2, 3, and 4 h after a single dose of vecuronium (0.10 mg/kg) to groups of 10 patients each during nitrous oxide/oxygen/isoflurane anesthesia. At 1, 2, or 3 h after vecuronium administration, neostigmine was always followed by an increase in the train-of-four ratio. At 4 h, a slight transient decrease in the mean train-of-four ratio (from 0.91 to 0.83) was noted 10 min later, followed by return to a train-of-four ratio value of 0.95 at the end of the surgical procedure. In an additional 10 patients antagonized with only 20 µg/kg at 4 h, no decrease in the train-of-four ratio was observed. It must also be noted that in eight patients in whom the train-of-four ratio decreased after neostigmine, the amplitudes of both the first twitch and the fourth twitch increased after neostigmine administration, but the magnitude of the first twitch increase was proportionately greater than that of fourth twitch, resulting in a lower train-of-four ratio.4 
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