Carfentanil Depresses Inspiratory Motor Drive

Carfentanil exposure could cause severe ventilatory depression associated with muscle stiffness, hypoxemia/hypercapnia (due to hypoventilation) and hypothermia; however, its effect on inspiratory motor drive alone (without these associated effects) has not been investigated. This, along with the inhibitory impact of opioids on hypoxic and hypercapnic ventilation, allows us to determine the impacts of carfentanil on the phrenic nerve (PN) activities before and during hypoxia and hypercapnia in this study. Two groups of anesthetized and spontaneously breathing rats were initially exposed to aerosolized vehicle (Ctrl) and carfentanil (1.7 mg/m3) for 10 min. After vagotomy, paralysis and artificial ventilation, the peak and frequency of integrative PN activity (ʃPN and fR), minute PN (MPN = ʃPN × fR), arterial blood pressure (ABP) and heart rate (HR) were recorded before and during hypoxia (10% O2 for 1 min) and hypercapnia (10% CO2 for 3 min). Our results showed that: 1) carfentanil significantly reduced MPN and ʃPN by ~50% and led to hypertension without change in fR and HR; 2) hypoxia enhanced MPN, ʃpn and fR and decreased ABP and hypercapnia brought about similar PN responses with HR decreased in the Ctrl rats; and 3) carfentanil strikingly attenuated the MPN, fR and ʃPN during both chemical challenges and exacerbated the hypotension during hypoxia and the bradycardia during hypercapnia. Our results suggest that carfentanil greatly suppresses the inspiratory motor drive, at least partially, via attenuating the chemoreflexes to substantially contribute to carfentanil-induced ventilatory depression and failure.