Intranasal naloxone reversal of opioid-induced respiratory depression in opioid-naïve individuals and self-reported daily opioid users

A single Narcan® dose reversed moderate fentanyl- and sufentanil-induced respiratory depression, though effectiveness varied by endpoint and opioid receptor affinity. Rapid V̇E-recovery suggests clinical utility of intranasal naloxone, but delayed and sometimes incomplete recovery of end-tidal pCO2, particularly during exposure to the high-affinity opioid sufentanil, indicating reversal inefficacy and persistence of respiratory instability. Further studies are needed to address optimal naloxone doses and alternative formulations to address high-dose potent opioid threats.