Pharyngeal function, airway protection and anesthetic agents

Anesthesia related complications occur most frequently in the immediate postoperative period. The three most common conditions associated with such events are ventilatory failure, airway obstruction and aspiration. The pharynx is essential for respiration and protection of the upper airway. We hypothesized that residual concentrations of anesthetic agents (neuromuscular blocking agents (NMBA), propofol and inhaled anesthetics) impair pharyngeal function and airway protection.

Using simultaneous solid-state videomanometry we studied the effects of anesthetic agents on pharyngeal function and airway protection in awake human volunteers. Partial neuromuscular block was induced by a continuous infusion of vecuronium or atracurium to train-of-four (TOF) ratios of 0.60 - 0.80, followed by spontaneous recovery. A four- to five-fold increase in the incidence of pharyngeal dysfunction with impaired airway protection and bolus penetrating to the laryngeal inlet was revealed during partial neuromuscular block. The mechanisms behind the pharyngeal dysfunction were delayed initiation of swallowing, impaired pharyngeal muscle function and impaired coordination. The upper esophageal sphincter (UES) was sensitive to partial neuromuscular block with a reduced resting tone even after recovery to a TOF ratio of > 0.90 while the inferior pharyngeal constrictor muscle was more resistant.

Pharyngeal function was also evaluated in volunteers randomized to receive propofol, isoflurane or sevoflurane in subhypnotic concentrations corresponding to 0.50 an 0.25 Cp50asleep (predicted blood propofol concentration for the transition between sleep and consciousness) or 0.50 and 0.25 MACawake (alveolar concentration for the transition between sleep and consciousness). The volunteers estimated their degree of sedation on a visual analogue scale (VAS). The three agents caused a six- to nine-fold increase in the incidence of pharyngeal dysfunction, the majority of dysfunctional swallows leading to penetration of bolus to the larynx. There was a correlation between pharyngeal dysfunction and VAS degree of sedation. The effect on the pharyngeal contraction pattern was most prominent in the propofol group.

Hypothesizing that a difference in nicotinic acetylcholine receptor (nAChR) density would explain the different responses to NMBA in the pharynx, the nAChR density was determined bybungarotoxin binding in muscle samples from the human cricopharyngeal muscle, the main component of the UES, and the pharyngeal constrictor muscle. We were, however, unable to detect a difference in nAChR density between the cricopharyngeal and pharyngeal constrictor muscle.

The muscle fiber size and fiber type composition in the human cricopharyngeal muscle were compared with that of the pharyngeal constrictor muscle. The muscle fiber cross sectional area was generally smaller in the cricopharyngeal than the pharyngeal constrictor muscle while the muscle fiber type composition did not differ between the two muscles.

In conclusion, anesthetic agents cause pharyngeal dysfunction and impaired airway protection in concentrations present during recovery. Residual neuromuscular block with TOF ratios < 0.90 should be considered incomplete neuromuscular recovery. Morphological differences between pharyngeal muscles have been demonstrated but it is unlikely that these findings alone explain the different responses to neuromuscular blocking agents.

List of scientific papers

I. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R (1997). Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology. 87(5): 1035-43.
https://pubmed.ncbi.nlm.nih.gov/9366453

II. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI (2000). The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 92(4): 977-84.
https://pubmed.ncbi.nlm.nih.gov/10754616

III. Sundman E, Witt H, Sandin R, Kuylenstierna R, Boden K, Ekberg O, Eriksson LI (2001). Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology. 95(5): 1125-32.
https://pubmed.ncbi.nlm.nih.gov/11684981

IV. Sundman E, Yost SC, Margolin G, Kuylenstierna R, Ekberg O, Eriksson LI (2002). Acetylcholine receptor density in cricopharyngeal muscle and pharyngeal constrictor muscle. Acta Anaesthesiologica Scandinavica.

V. Sundman E, Ansved T, Margolin G, Kuylenstierna R, Eriksson LI (2002). Fiber type composition and fiber size of the human cricopharyngeal muscle and the pharyngeal constrictor muscle. [Manuscript]