Beyond OIRD: The Multiple Negative Effects of Systemic Fentanyl in Adult Goats

Abstract

Opioids are effective analgesics but are addictive and negatively impact multiple physiologic functions. Opioid abuse has reached epidemic levels and led to an exponential increase in deaths and societal costs, with a disproportionate impact on women. A majority of studies have focused on the depressant effect of opioids on breathing frequency. However, there are data suggesting that opioids cause multiple life‐threatening physiologic effects, but there is a paucity of data assessing the multiple deleterious effects simultaneously in freely behaving mammals. Here we tested the dose‐dependent effects of systemic fentanyl (a major cause of the current opioid crisis) in adult female goats. Systemic fentanyl acutely and dose‐dependently depressed breathing frequency through prolongation of expiratory time while increasing tidal volume similar to effects of fentanyl in humans (J Clin Monit Comput 18: 2004; Eur J. Anest 20: 2003; Br J. Anest 96: 2006). Fentanyl also increased the difference between alveolar and arterial PO2 (A‐a oxygen gradient,) and at high doses increased tonic activity of intercostal and abdominal muscles (consistent with “wooden chest”) while also prolonging post‐inspiratory muscle activation and in rare instances caused obstructive apnea. Beyond these acute (<15 min) effects were prolonged increases in body temperature, metabolic rate, and arterial blood pressure and decreases in heart rate. Furthermore, high dose opioids had long‐lasting effects, including induction of acute withdrawal symptoms, and led to decreased fecal output for >24 h. We conclude that a triad of deleterious effects on cardiorespiratory responses (respiratory frequency depression, A‐a oxygen gradient, and sustained contraction of respiratory muscles) conceivably contribute to hypoxemia induced opioids fatalities. Furthermore, opioids have profound, deleterious effects (withdrawal and constipation) beyond cardiorespiratory control.Support or Funding InformationDepartment of PhysiologyZablocki VA Medical Center