Trick of the Trade: Naloxone Dilution for Opioid Overdose

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 Use³

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.

1. Obtain a 1 mL vial or syringe of naloxone 0.4 mg/mL.
2. Grab a 10-mL syringe. Draw up 9 mL of normal saline.
3. Draw up the 1 mL of naloxone. You now have 10 mL of a 0.04 mg/mL naloxone solution.
4. Clearly label the syringe with drug name and concentration. 
5. 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

1. 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.
2. 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

Author information

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules and EM Pharm Pearls Series
Attending Pharmacist, EM and Toxicology, MGH
Associate Professor of EM, Division of Medical Toxicology, Harvard Medical School

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