Non-opioid MoA in Fentanyl explains failure of Naloxone in opioid crisis (2019)

Traditionally, opioids/opiates kill via mu-opioid receptor agonism, which is why administration of a mu-opioid antagonist (Naloxone, brand name Narcan) is the first line of defense for avoiding mortality. However Fentanyl is unique in that respiratory depression isn't the only major cause of death, but noradrenergic and cholinergic mechanisms down-stream of the mu-opioid agonism can cause Wooden Chest Syndrome which can lead to cardiopulmonary arrest.

This has relevant implications for first-responders since this is generally only known in the anesthesiology community.