The effects of fentanyl and dexmedetomidine on cardiorespiratory activity: implications for morbidity and mortality associated with adulterated fentanyl products.

INTRODUCTION: A recent driver of opioid-related overdose deaths has been the adulteration of illicitly manufactured fentanyl with alpha-2 (α2)-adrenergic agonists; however, little research has examined their toxicity when combined with fentanyl. The purpose of this study was to examine the effects of fentanyl and the α2-adrenergic agonist, dexmedetomidine, on cardiorespiratory measures that may contribute to the toxicity of these drug combinations (i.e., respiratory rate, heart rate, oxygen (O2) saturation, and pulse distention).

METHODS: Male and female rats were administered fentanyl (0.01-0.1 mg/kg) and dexmedetomidine (0.003-0.01 mg/kg) intravenously, and pulse oximetry was used to measure respiratory and cardiovascular activity.

RESULTS: When administered alone, both drugs decreased respiratory rate and heart rate relative to baseline, albeit with different time courses. Fentanyl, but not dexmedetomidine, decreased O2 saturation. Dexmedetomidine enhanced the suppression of respiratory rate and heart rate produced by fentanyl in a time-dependent manner. The effects of the drug combination on O2 saturation and pulse distention were less consistent. Although not a primary endpoint, mortality occurred in 3 of 16 rats after the high-dose drug combination, suggesting that increases in lethality can be observed in the absence of explicit pharmacological synergy.

DISCUSSION: These data indicate that dexmedetomidine exacerbates the cardiorespiratory effects of fentanyl in a manner that may contribute to the morbidity and mortality associated with α2-adrenergic adulteration of illicitly manufactured fentanyl.