Anesthesia-Related Pharmacology and Toxicology
Neostigmine/Glycopyrrolate Administered after Recovery from Neuromuscular Block Increases Upper Airway Collapsibility by Decreasing Genioglossus Muscle Activity in Response to Negative Pharyngeal Pressure
Herbstreit F, Zigrahn D, Ochterbeck C, et al (Universitätsklinikum Essen, Germany; Universität Duisburg-Essen, Germany) Anesthesiology 113:1280-1288, 2010§
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.
Whether to administer an anticholinesterase to anyone who has received a neuromuscular blocking agent is a decision the clinician frequently makes. Neostigmine and glycopyrrolate have several dose-related adverse effects that include arrhythmias, nausea and vomiting, bronchospasm, and tension on intestinal anastomoses. However, not infrequently patients are admitted to the pediatric acute care unit with postoperative residual paralysis even when they received only a single intubating dose of vecuronium, rocuronium, or atracurium.1 Subtle degrees of residual neuromuscular block may be difficult to detect, yet they are associated with adverse consequences.2–4 Although not administering an anticholinesterase to everyone increases the likelihood of inadequate recovery of neuromuscular function,5 not all patients require it, and administering it to patients who have spontaneously recovery from neuromuscular block may cause weakness.6,7 The increase in weakness may be due to the excessive amount of acetylcholine at the neuromuscular junction.8
These authors have previously reported that unnecessary administration of anticholinesterases can impair genioglossus and diaphragm function.7 The genioglossus is a dilator of the upper airway, and weakness of this muscle can lead to upper airway collapse. In the current volunteer trial, healthy men receiving rocuronium to establish a train-of-4 ratio (TOFR) of 0.5 were allowed to recover spontaneously to a TOFR of 1 and then received neostigmine and glycopyrrolate. Importantly, the dose of neostigmine that was administered was small (30 mcg/kg). Even following administration of this small dose of neostigmine, the upper airway critical closing pressure increased after administration of neostigmine, and the genioglossus activity generated with negative pharyngeal pressure, rather than increasing as it does in the absence of neuromuscular blockade, decreased to values observed during partial paralysis (TOFR = 0.5).
The results of this study speak to the inadequacy of our monitors of neuromuscular blockade. If a clinician can document that a patient has complete recovery of muscle strength, no anticholinesterase will be administered. Our monitors of neuromuscular blockade, however, do not allow us to do this,9 and the decision as to whether to administer anticholinesterase is based on clinical judgment. Previously, administration of small doses (10, 20, or 30 mcg/kg) of neostigmine was recommended when no fade was palpable in the train-of-410 so as to not cause weakness. However, on the basis of the results of the current study, 30 mcg/kg may be too much to administer when muscle strength has recovered to a TOFR = 1.