Fentanyl induced disruption of the coordinated reciprocal activity of inspiratory and expiratory respiratory muscles

Opioid induced respiratory depression (OIRD) occurs when respiratory pump and/or airway muscle activity are reduced ostensibly due to reduced output from the brainstem respiratory control system, resulting in central (CA) and/or obstructive apnea (OA) and reduced breathing frequency. Although less commonly reported in the literature, ORID may also result from an inappropriate activation of accessory muscles leading to the “Wooden Chest Syndrome” (WCS) -when airflow is limited due to simultaneous activation of inspiratory and expiratory pump and/or airway respiratory muscles to decrease chest wall compliance and inappropriately increase airway resistance. This phenomenon is difficult to directly study in humans, but here we present data from our large animal model (adult female goats). We tested the hypothesis that IV fentanyl would lead to transient dysfunction in respiratory accessory muscles indicative of WCS. We surgically instrumented goats (n=7) with electromyographic (EMG) wires in inspiratory (diaphragm; DIA) and expiratory (Transversus Abdominus; TA) pump muscles, as well as airway dilator (Thyropharyngeus; Thy) and constrictor (Genioglossus; GG) muscles. After >2 weeks of surgical recovery, responses to saline or various doses of fentanyl citrate (25-125 mcg/kg; IV) were tested for 30 min before and up to 90 min after injection. As described in an adjacent poster, particularly over the first several minutes after fentanyl injection, CA and OA were observed in some goats. However, disruption of airflow was primarily associated with increased simultaneous activation of pump and airway inspiratory and expiratory muscles resembling WCS. For most muscles, the rate of rise in muscle activity (an index of firing intensity) increased within 2 minutes following fentanyl injection and remained significantly (P<0.05) elevated up to 90 minutes. During WCS periods, airflow was oscillatory or interrupted suggesting transient closure of the airway. In addition, there were time- and dose-dependent effects on frequency, duration, and total activity of the pump and airway muscles. By 60 minutes post-injection, there were periods of transient return of muscle activity and airflow to at or below baseline values. There was no significant effect of saline on muscle activity. Overall, these data suggest that following fentanyl injection in awake goats, there was an increase in firing of pump and airway muscles which ultimately disrupts the coordinated reciprocal activity of inspiratory and expiratory muscles and contributes to OIRD. Supported by NIH DA050571 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.