Dose-dependent effects of fentanyl on pulmonary ventilation and arterial blood gases in adult awake goats

Abstract

Synthetic opioids, such as fentanyl, typically suppress breathing frequency (f) and tidal volume (VT) in rodents but decrease and increase f and VT in humans, respectively. In this and the three adjoining posters we present data on the physiologic and behavioral dose-dependent effects of intravenous (IV) fentanyl in adult awake female goats. Here we tested the hypothesis that like humans, goats would show dose-dependent decreases in f and increases in VT and corresponding changes in blood gases and pH. Pulmonary ventilation (VI), f, VT and arterial blood gases were measured for 30 minutes (min) before, during and up to 90 min after IV injection (2 min) of 0, 25, 50, 75, 100, and 125 mcg/kg fentanyl. Ventilatory measures were expressed as a percent of control (room air breathing) in 30 sec intervals for 15 min pre- and post-injection and averaged over longer time intervals (5 or 15 min) thereafter. While we observed no changes in breathing measures over 30 min before and 90 min after saline injection, the responses to IV fentanyl were highly variable and individual- and dose-dependent. However, most goats showed transient decreases in f (20-30%) where the duration of f suppression was dose-dependent (2-10 min), whereas VT increased (25-50%) for 60 min or more without an apparent dose-dependence. As a result, VI was only transiently decreased (2-4 min) and instead was above control for up to 90 min post-injection. Arterial blood was drawn (~3 ml; 30 sec) in duplicate at ~15 and 25 min into the 30 min control period, and then individual samples were obtained continuously during and immediately following the injection and in duplicate at 10, 15, 30, 45, 60, 75 and 90 min post-injection. While some goats showed transient hypoventilation (decreased PaO2/O2 saturation) immediately after fentanyl injection, on average blood gas analyses suggested modest hyperventilation (decreased PaCO2/increased pH) 60-90 min post-injection consistent with the overall effects on VI. The calculated difference in the alveolar to arterial oxygen gradient (A-a gradient) was unaffected with saline or 25 mcg/kg fentanyl, but was increased with higher doses of fentanyl peaking 15-30 min after injection in a dose-dependent manner suggesting increased V/Q mismatch. We conclude that in awake goats, fentanyl has opposite effects on f and VT similar to that in humans. However, individual variation in timing and nature of the ventilatory responses to fentanyl over the dose range tested herein suggests that the compensatory f and VT changes allowed for the maintenance of arterial blood gas and pH status. 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.