UMEM Educational Pearls

Naloxone has been used to reverse opioid-induced respiratory depression for decades. The “standard” dose of opioid intoxication has been 0.4 mg.  However, over the past decade, initial naloxone dose for opioid intoxication has evolved to recommend a lower initial dose (0.04 – 0.05 mg).


A recent article by Connors et al. reviewed 25 medical resources (internet, medical texts and study guides) of different medical specialties (internal medicine, medical toxicology, emergency medicine, pediatrics, anesthesiology, pain medicine and general medicine)



  • 12 medical resources (48%) recommend using 0.05 mg or less IV as an initial dose.
  • 9 medical resources (36%) recommend using 0.4 – 0.5 mg or higher as an initial dose.
  • Maximum dose also ranged widely from 2 to 20 mg.


Recent editions of emergency medicine text (Rosen’s and Tinitinalli) recommend using 0.04 – 0.05 mg IV in ED patients with history of opioid dependence. Higher doses of naloxone are recommended for non-opioid dependent/apneic patients.


However, history of opioid dependence is difficult to obtain in patients with opioid induced CNS/respiratory depression.


Administering 0.4 mg or higher dose may/can acute agitation or opioid withdrawal symptoms that can utilize more ED resources to calm agitated patient/management of withdrawal. Thus it may be prudent to use low-dose strategy (0.04 mg IV with titration) to minimize the risk of precipitating naloxone-induced opioid withdrawal/agitation.


Bottom line:

In opioid-induced respiratory depression/apneic patients:

  1. Ventilate with bag-valve mask for apnea/hypoxia
  2. Administer naloxone: 0.04 mg IV every 2 – 3 min until reversal of respiratory depression/hypoxia is achieved.

To make 0.04 mg naloxone solution:

  • Dilute 1 mL of 0.4 mg naloxone with 9 mL normal saline in 10 mL syringe. 



Connors NJ, Nelson LS. The evolution of recommneded naloxone dosing for opioid overdose by medical specialty. J Med Toxicol 2016;12:276-281.