Reversal of fentanyl-induced apnea: a randomized comparison between intramuscular (Zimhi) and intranasal naloxone (Narcan)

Respiratory depression followed by cardiac arrest is the primary cause of death in opioid overdoses cases. Opioid-induced respiratory depression may be treated with one of several naloxone formulations such as intranasal (IN) or intramuscular (IM) naloxone. It is highly relevant to compare the efficacy of these formulations and determine the best strategy to restore breathing activity following opioid-induced respiratory depression. In this randomized, crossover, open-label trial, we compared the required number of IM (5 mg/0.5 mL) versus IN naloxone (4 mg/0.1 mL) doses following 10 µg/kg intravenous fentanyl-induced apnea in healthy volunteers and chronic opioid users. After 2-min of apnea, both naloxone formulations were given at 2-min intervals until restoration of ventilation to baseline levels. If necessary, rescue intravenous naloxone was administered. In sixteen volunteers, the median number of naloxone doses was 1.5 (IQR 1–2) for IM versus 2 (1–3) for IN naloxone (p = 0.0002). One subject required rescue intravenous naloxone after 2 IN doses. Mean reversal times were 2.2±0.8 min after IM and 3.9±2.0 min after IN naloxone (p = 0.002). Similarly, in six opioid users, IM naloxone was more effective than IN naloxone in reversing opioid-induced apnea, requiring fewer doses without need for rescue naloxone.