Traditional teaching recommends naloxone doses of at least 0.4 mg IV to reverse opioid toxicity. Drs. Lewis Nelson (@LNelsonMD) and Mary Ann Howland (@Howland_Ann) co-authored the opioid antagonist chapter in Goldfrank’s Toxicologic Emergencies.1 They write:

“However, this dose [0.4 mg] in an opioid-dependent patient usually produces withdrawal, which should be avoided if possible. The goal is to produce a spontaneously and adequately ventilating patient without precipitating significant or abrupt opioid withdrawal. Therefore, 0.04 mg is a practical starting dose in most patients, increasing to 0.4 mg, 2 mg, and finally 10 mg.”

In fact, Dr. Nelson published a recent case series demonstrating the reversal of opioid-induced respiratory depression using low-dose naloxone (0.04 mg).2

Trick of the Trade: Naloxone Dilution for IV Use 3

Given that many ED overdose patients are not opioid-naive, lower naloxone doses are generally sufficient. Here is a quick way to prepare and administer naloxone in doses that will reverse opioid toxicity while limiting the chances of severe withdrawal.

Obtain a 1 mL vial or syringe of naloxone 0.4 mg/mL. Grab a 10-mL syringe. Draw up 9 mL of normal saline. Draw up the 1 mL of naloxone. You now have 10 mL of a 0.04 mg/mL naloxone solution. Clearly label the syringe with drug name and concentration. Administer 1-2 mL IV every 60 seconds until the patient is responsive (and breathing) to the desired level.

This trick also provides a more precise ‘wake up dose.’ If a naloxone infusion is needed, you’ll likely have a more accurate starting rate.

A Few Caveats

If a patient is apneic, in respiratory arrest, or close to respiratory arrest from a suspected opioid overdose, this is NOT the technique to use. Administer at least 0.4 mg IV to reverse toxicity immediately. While it would be simple to use a saline flush for this technique, be advised that the Institute for Safe Medication Practices (ISMP) recommends against drawing up meds into a flush due to the concern for using an unlabeled syringe. 4

Original: November 17, 2014; Last updated: August 20, 2015

1. Kim H, Nelson L. Antidotes in Depth (A6): Opioid Antagonists. In: Goldfrank’s Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill; 2010:579-585. 2. J Med Toxicol. 2016;12(1):107-110. PubMed] Kim H, Nelson L. Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series.. 2016;12(1):107-110. 3. Expert Opin Drug Saf. 2015;14(7):1137-1146. PubMed] Kim H, Nelson L. Reducing the harm of opioid overdose with the safe use of naloxone : a pharmacologic review.. 2015;14(7):1137-1146. 4. Is It Really Saline. Institute for Safe Medication Practices. https://www.ismp.org/newsletters/acutecare/articles/20061116_2.asp. Published November 16, 2006.