Neostigmine/Glycopyrrolate Administered after Recovery from Neuromuscular Block Increases Upper Airway Collapsibility by Decreasing Genioglossus Muscle Activity in Response to Negative Pharyngeal Pressure

• Published in: Anesthesiology (Philadelphia) 2010-12, Vol.113 (6), p.1280-1288
• Main Authors: HERBSTREIT, Frank, ZIGRAHN, Daniela, OCHTERBECK, Christof, PETERS, Jürgen, EIKERMANN, Matthias
• Format: Article
• Language: English
• Subjects: Adult; Air Pressure; Androstanols; Anesthesia; Anesthesia Recovery Period; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Cholinesterase Inhibitors - pharmacology; Electric Stimulation; Electromyography; Glycopyrrolate - pharmacology; Humans; Lung Volume Measurements; Male; Medical sciences; Muscarinic Antagonists - pharmacology; Muscle Contraction - physiology; Neostigmine - pharmacology; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Pharyngeal Muscles - drug effects; Pharynx - physiology; Plethysmography; Respiratory System - drug effects; Tidal Volume - physiology; Ulnar Nerve - physiology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e3181f70f3d

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. 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. 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. 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.