title: Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure.
abstract: BACKGROUND
  Reversal of residual neuromuscular blockade by acetylcholinesterase inhibitors (e.g., neostigmine) improves respiratory function. However, neostigmine may also impair muscle strength. We hypothesized that neostigmine administered after recovery of the train-of-four (TOF) ratio impairs upper airway integrity and genioglossus muscle function.
  
  
  METHODS
  We measured, in 10 healthy male volunteers, epiglottic and nasal mask pressures, genioglossus electromyogram, air flow, respiratory timing, and changes in lung volume before, during (TOF ratio: 0.5), and after recovery of the TOF ratio to unity, and after administration of neostigmine 0.03 mg/kg IV (with glycopyrrolate 0.0075 mg/kg). Upper airway critical closing pressure (Pcrit) was calculated from flow-limited breaths during random pharyngeal negative pressure challenges.
  
  
  RESULTS
  Pcrit increased significantly after administration of neostigmine/glycopyrrolate compared with both TOF recovery (mean ± SD, by 27 ± 21%; P = 0.02) and baseline (by 38 ± 17%; P = 0.002). In parallel, phasic genioglossus activity evoked by negative pharyngeal pressure decreased (by 37 ± 29%, P = 0.005) compared with recovery, almost to a level observed at a TOF ratio of 0.5. Lung volume, respiratory timing, tidal volume, and minute ventilation remained unchanged after neostigmine/glycopyrrolate injection.
  
  
  CONCLUSIONS
  Neostigmine/glycopyrrolate, when administered after recovery from neuromuscular block, increases upper airway collapsibility and impairs genioglossus muscle activation in response to negative pharyngeal pressure. Reversal with acetylcholinesterase inhibitors may be undesirable in the absence of neuromuscular blockade.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Essen, Germany. frank.herbstreit@uni-due.de
authors.forename: Frank
authors.initials: F
authors.lastname: Herbstreit
authors.forename: Daniela
authors.initials: D
authors.lastname: Zigrahn
authors.forename: Christof
authors.initials: C
authors.lastname: Ochterbeck
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.forename: Matthias
authors.initials: M
authors.lastname: Eikermann
mesh_terms: D000328:Adult; D000399:Air Pressure; D000732:Androstanols; D000762:Anesthesia Recovery Period; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D004576:Electromyography; D006024:Glycopyrrolate / Q000494:pharmacology*; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents; D010609:Pharyngeal Muscles / Q000187:drug effects*; D010614:Pharynx / Q000502:physiology*; D010991:Plethysmography; D012137:Respiratory System / Q000187:drug effects*; D000077123:Rocuronium; D013990:Tidal Volume / Q000502:physiology; D014459:Ulnar Nerve / Q000502:physiology
chemical_list: D000732:Androstanols; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D009388:Neostigmine; D006024:Glycopyrrolate; D000077123:Rocuronium