Q&A column

Editor: Frederick L. Kiechle, MD, PhD

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Q. After naloxone is administered, are opiates still detectable in the body? If so, for how long and in what quantities?

A.Naloxone has no effect on the concentration of opioids in the body. Opioids, such as fentanyl and morphine, act by triggering the opioid receptors in the brain (primarily the mu-opioid receptors), causing analgesia and, in sufficient dosage, anesthesia. Respiratory depression is a potentially fatal dose-related side effect, especially after illicit opioid use. Naloxone has been widely used in emergency departments for decades as a reversing agent to treat opioid overdoses and, more recently, as a take-home treatment in the form of a nasal spray.

Naloxone works by binding to the same opioid receptors but without triggering the receptors and, therefore, does not cause analgesia or respiratory depression. It competitively blocks the access of opioids to the mu-opioid receptors in the brain and displaces the opioids already bound, but it does not destroy them or change their overall concentration in the body.

A disadvantage of naloxone is that its half-life is shorter than that of most opioids. It has a half-life of about 0.3 to 1.3 hours, whereas fentanyl has a half-life of two to six hours and methadone of 15 to 36 hours. Therefore, opioid-intoxicated patients need to be closely observed after naloxone administration, even if they are awake and alert. They may need to receive additional doses, depending on the severity of the opioid intoxication and type of opioid. An opioid that is still in the body after naloxone administration could cause a relapse into a coma once the naloxone has metabolized and its blood concentration decreased.

The potential need for repeat or continued administration of naloxone is illustrated in a case report from 2019 in which a 22-month-old girl ingested methadone syrup and developed marked somnolence. Her mother administered naloxone nasal spray, which initially reversed the somnolence, and the child was transported to the local emergency department. Her vital signs were very good initially, but four hours after the first dose of naloxone she developed somnolence, respiratory depression, and pinpoint pupils. She was administered one intravenous dose of naloxone without significant improvement, followed by a second dose that reversed the somnolence. The girl was started on a continuous intravenous infusion of naloxone, which was tapered off after about 36 hours. She recovered completely and was discharged about 48 hours after admission.

This case report demonstrates that multiple doses of naloxone may be required to treat an opioid intoxication, especially one involving an opioid with a long half-life, such as methadone. Naloxone may need to be administered until a sufficient amount of opioid is naturally metabolized and excreted from the body.

Lebin JA, Chen BC, Valento MJ. Reversal of pediatric opioid toxicity with take-home naloxone: a case report. J Med Toxicol. 2019;15(2):134–135.