Frazure, M. | Search bioRxiv

bioRxiv2023

Dysphagia as a missing link between post-surgical- and opioid-related pneumonia

ObjectivePostoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk. MethodsEight healthy adult cats were evaluated for dysphagia in 2 experiments. 1) In 4 female cats airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015mg/kg, IM, q8-12h; n=5). 2) Using a cross-over design (2 male, 2 female) cats were treated with moderate (0.02mg/kg) or high (0.04mg/kg) dose buprenorphine (IM, q8-12h; n=5) to determine changes in airway protection status or evidence of dysphagia. ResultsAirway protection was significantly affected in both experiments, but most severely post-surgically where 75% of the animals exhibited silent aspiration. ConclusionOropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the post-operative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.

physiology↗

bioRxiv2023

Serotonin therapies for opioid-induced dysphagia and respiratory depression: sex differences in a rat electromyography model

Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We sought to test the effects of the clinically-relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated utility of serotonin 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing outcomes following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing behaviors. We evaluated the hypotheses that swallow varies by stimulus, opioids depress swallow and breathing, and that 5-HT1A agonists improve these depressions. Our results largely confirmed the hypotheses: 1) Swallow-related muscle activity was larger during swallows elicited by oral water infusion plus esophageal distension than by either stimulus alone. 2) Buprenorphine depressed swallow in both sexes, but most significantly in females. 3) Female animals were more susceptible to buprenorphine-induced respiratory arrest. 4) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pre-treatment with the partial 5-HT1A agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. 5) 8- OH-DPAT enhanced swallow-related mylohyoid drive, but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide pre-clinical evidence of a 5HT1A agonist for the treatment of respiratory depression and dysphagia. New & NoteworthyThis is the first manuscript to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females than males, and are the first to produce this effect with the partial mu-opioid-receptor agonist buprenorphine. Our study is the first to demonstrate that activation of 5-HT1A receptors can improve swallow and breathing outcomes following systemic buprenorphine administration.

physiology↗