Effects of high, sub-lethal doses of fentanyl on respiratory functions in adult female goats

Abstract

Since 1999, the opioid epidemic in the United States has claimed more than 300,000 lives, and data from more recent years indicate annual increases exceeding 80,000 fatalities. Synthetic opioids like fentanyl contribute to these opioid-related deaths through multiple physiologic effects including Opioid-induced respiratory depression (OIRD), impairment of the alveolar to arterial oxygen gradient (A-a), and rigidity of upper airway and pump muscles causing airway dysfunction, or Wooden Chest Syndrome (WCS). We have previously shown (PMID: 37885800) that sub-lethal doses of fentanyl (25-125 μg/kg; IV) cause in healthy adult goats a transient time and dose dependent effect on breathing frequency and tidal volume, WCS and A-a which varied greatly between goats. We hypothesize that high dose fentanyl will exacerbate the effects seen in sub-lethal doses in both a time and dose-dependent manner. Adult female goats (n=3) were surgically instrumented with electromyographic (EMG) wires in both the airway (genioglossus and thyropharyngeal) and respiratory pump muscles (diaphragm, transverse abdominus and diaphragm) and the carotid arteries were relocated to a subcutaneous location. Goats were allowed 2 weeks for recovery before the onset of studies. Arterial blood samples were obtained through carotid catheters and fentanyl injections were made through acute placement of jugular venous catheters. Following a 30-minute control period, we injected saline (vehicle) or high-dose fentanyl (250-500μg/kg). In a time dependent manner, high doses of IV fentanyl injections decreased breathing frequency (FB), increased expiratory time (TE) and increased tidal volume (VT). Arterial oxygen (PaO2) decreased substantially (~35 mmHg; and arterial CO2 (PaCO2) increased to as high as 70mmHg. From about 15 to 90 minutes after fentanyl injections, the overall effect on breathing and respiratory muscle activity was consistent with a stimulatory effect of fentanyl. These data suggest high dose fentanyl increases OIRD and exacerbate life-threatening effects that cause ventilatory suppression, hypoxemia, and hypercapnia. Funded by NIH DA050571. This is the full abstract presented at the American Physiology Summit 2024 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.