Wake Them Slowly (How to use Naloxone Safely)

Wake Them Slowly — How to use Naloxone safely. 1,2

Dr Benoit Phelan, PGY3, FMEM, Dalhousie University

Reviewed by Dr Paul Atkinson


Starting at a low dose as opposed to the conventionally recommended doses of 0.4 – 2 mg IV followed by small incremental doses is effective and may decrease risk of OWS.

Opioid Overdose

  • Opioid prescription and use are on the rise.
  • Prescription drug overdose has surpassed MVC as the #1 cause of unintentional injury-related death.
  • Opioid-overdose fatalities are a result of respiratory depression and hypoxia.

Naloxone (Narcan)

  • Introduced in 1967 as the first pure competitive mu opioid-receptor antagonist, naloxone is an effective antagonist for all currently available opioids with the exception of buprenorphine. It is seen as very safe and has minimal adverse effect when given in absence of exogenous opioids
  • Possible routes of administration are IV, IO, IM, SubQ and inhalation. There is low bioavailability with SL and Intranasal administrations. Bioavailability is negligible with oral administration due to substantial first pass hepatic metabolism (>99%).
  • Required dose affected by the specific opioid, opioid dose, genetics, tolerance
  • Onset <2min. Duration of action 20-90min. Elimination half-life longer in patients without dependence. Inactive breakdown product via hepatic metabolism.

Opioid withdrawal syndrome (OWS)

  • Rapid reversal may precipitate acute OWS causing vomiting, agitation, delirium, seizures, as well as catecholamine release, which may cause hypertensive emergencies and ventricular arrhythmias.
  • OWS is different from Opioid abstinence, which is non-life-threatening, and causes yawning, lacrimation, pilo-erection, diaphoresis, vomiting, diarrhea.

Approach for safe use of naloxone

  • Recognition of opioid-induced respiratory depression
    • <8 breaths/min, shallow efforts, hypercapnia.
  • Monitor with Pulse oxymetry and capnography
  • Consider not adding supplemental O2 (if endtidal CO2 not being used) as this can delay recognition of hypoventilation.
  • Use basic airway maneuvers to open the airway
  • Apply noxious stimuli
  • Administer Naloxone in small initial dose
    • 0.04mg IV q 2-3min
      • Alternative regiment using escalating dose q2-3min
        • 0.04mg, 0.5mg, 2mg, 4mg, 10mg, 15mg.
      • If IV access unavailable, alternative routes (SubQ, IM, IO, ET) may be used
    • Reversal of respiratory depression should be the desired end point not reversal of CNS depression.
    • Remember to search for and remove Fentanyl patches
    • Consider GI decontamination



  • 4h observation if short acting opioid.
  • >8h observation if long-acting opioid (Methadone, Fentanyl patch) as these may require repeat doses. Consider ICU admission for Naloxone infusion / ET intubation if recurrence of respiratory depression


  1. Boyer EW. Management of Opioid Analgesic Overdose. N Engl J Med. 2012;367(2):146-155. doi:10.1056/NEJMra1202561.
  2. Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015:1-10. doi:10.1517/14740338.2015.1037274.
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