Unwarranted administration of acetylcholinesterase inhibitors can impair genioglossus and diaphragm muscle function

Anesthesiology. 2007 Oct;107(4):621-9. doi: 10.1097/01.anes.0000281928.88997.95.

Abstract

Background: It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume.

Methods: The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9).

Results: Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram (to 70.3 +/- 7.6, 49.2 +/- 3.2, and 39.7 +/- 2.3% of control, respectively), decreases in diaphragm electromyogram (to 103.1 +/- 6.5, 83.1 +/- 4.7, and 68.7 +/- 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 +/- 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 +/- 3% of control, whereas end-expiratory lung volume remained constant.

Conclusions: The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Atropine / pharmacology
  • Cholinesterase Inhibitors / pharmacology*
  • Data Interpretation, Statistical
  • Diaphragm / drug effects
  • Dose-Response Relationship, Drug
  • Electromyography
  • Glycopyrrolate / pharmacology
  • Magnetic Resonance Imaging
  • Male
  • Muscarinic Antagonists / pharmacology
  • Neostigmine / pharmacology*
  • Neuromuscular Nondepolarizing Agents / pharmacology
  • Pilot Projects
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mechanics / drug effects
  • Respiratory Muscles / drug effects*
  • Respiratory System / drug effects
  • Vecuronium Bromide / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Muscarinic Antagonists
  • Neuromuscular Nondepolarizing Agents
  • Neostigmine
  • Atropine
  • Vecuronium Bromide
  • Acetylcholinesterase
  • Glycopyrrolate