This graph is an easy-to-understand guideline to help determine if a patient’s clinical status is likely to improve with naloxone administration.
How to Use the Graph
Assess patient’s level of consciousness, respiratory rate, pupil size, and oxygen saturation. Plot those four assessments on the graph. Naloxone administration should be strongly considered in patients who fall into the highlighted quadrant.
Notes: Some patients may not show all of the signs of opioid toxicity. Some opioids do not cause pinpoint pupils (eg, meperidine and propoxyphene). Visit ACEPNow.com for a list of resources for further reading about opioid overdose management.
Opioid-naive patients: 0.4 mg IV should reverse or improve respiratory depression. This dose may be repeated and sequentially increased up to a 10 mg dose.
Opioid-dependent patients: 0.04–0.1 mg IV should reverse or improve respiratory depression without inducing severe precipitated opioid withdrawal. This dose may be repeated and sequentially increased up to a 10 mg dose.
If reversal of respiratory depression does not occur at a naloxone dose of 10 mg IV push, the diagnosis of opioid intoxication must be reconsidered.
- Naloxone binds to all three recognized opioid receptors (delta, kappa, and mu), with a particularly high affinity for the mu receptor. This causes a competitive antagonism and displacement of opioids, primarily in the central nervous system.
- Naloxone causes a reversal of the opioid-induced toxic effects, with a primary goal of improving ventilation by reversing respiratory depression and obtundation.
- Although naloxone is synthesized from thebaine (paramorphine), a natural compound obtained from the opium poppy plant, it has no opioid effects.
- Naloxone has no intrinsic toxicity in opioid-naive patients even at high doses. It is safe for use in children and adults.
- Naloxone is well-absorbed by most parenteral routes, most commonly intravenous, intramuscular, subcutaneous, and intranasal.
- Onset of action depends on route of administration and rate of absorption, ranging from one to six minutes.
- Naloxone’s duration of effect is 20 to 90 minutes, depending upon the route of administration.
- Continuous infusion of naloxone, at two-thirds the bolus dose that resulted in arousal, may be required in patients with repeated episodes of respiratory depression or re-sedation.
Resources for Further Reading
- Boyer EW. Management of opioid analgesic overdose. New Eng J Med. 2012;367(2):146-155.
- Dowling J, Isbister GK, Kirkpatrick CM, et al. Population pharmacokinetics of intravenous, intramuscular, and intranasal naloxone in human volunteers. Ther Drug Monit. 2008;30(4):490-496.
- Evans JM, Hogg MI, Lunn JN, et al. Degree and duration of reversal by naloxone of effects of morphine conscious subjects. Br Med J. 1974;2(5919):589-591.
- Hoffman JR, Schriger DL, Luo JS. The empiric use of naloxone in patients with altered mental status: a reappraisal. Ann Emerg Med. 1991;20(3):246-252.
- Kerr D, Dietze P, Kelly AM. Intranasal naloxone for the treatment of suspected heroin overdose. Addiction. 2008;103(3):379-386.
- Naloxone hydrochloride–drug summary. Physicians’ Desk Reference website. Available at: https://www.pdr.net/drug-summary/Naloxone-Hydrochloride-Injection–0-4-mg-mL–naloxone-hydrochloride-777. Accessed May 15, 2019.
- Nelson LS, Howland MA. Opioid antagonists. In: Nelson LS, Howland MA, Lewin NA, et al, eds. Goldfrank’s Toxicological Emergencies. 11th ed. New York: McGraw-Hill; 2019:538-544.
- Wanger K, Brough L, Macmillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed opioid overdose. Acad Emerg Med. 1998;5(4):293-299.