Skip to main content

Advertisement

SpringerLink
Log in

The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty

  • Original Article
  • Published:
Journal of Medical Toxicology Aims and scope Submit manuscript

Abstract

Introduction

Opioid abuse and opioid overdose deaths have increased significantly over the past decade. Naloxone is a potentially life-saving medication that can reverse opioid-induced respiratory depression, though precipitated opioid withdrawal can pose acute risks to the patient and medical personnel. The optimal naloxone dose is unclear and few studies address this question.

Methods

A convenience sample of commonly available references were queried for the recommended IV naloxone dose. When dosing recommendations were different for opioid-tolerant patients these were also recorded.

Results

Twenty-five references were located. 48% recommended a starting dose ≤ 0.05 mg while 36% recommend a dose ten-fold higher. More than half of medical toxicology and general medical sources recommended a low-dose strategy with a starting dose lower than 0.05 mg IV.

Conclusion

There are variations in the recommended doses for naloxone with ranges spanning an order of magnitude. Further exploration is needed to determine the dose that balances reversal of respiratory depression with mitigation of withdrawal.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Volkow N. America’s addiction to opioids: heroin and prescription drug abuse. National Institute on Drug Abuse. 2014. http://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2014/americas-addiction-to-opioids-heroin-prescription-drug-abuse-_ftn4. Accessed 27 January 2015

  2. Warner M, Hedegaard H, Chen L. Trends in drug-poisoning deaths involving opioid analgesics and heroin: United States, 1999–2012. In: Health E-Stat. Centers for Disease Control and Prevention’s National Vital Statistics System. 2014. http://www.cdc.gov/nchs/data/hestat/drug_poisoning/drug_poisoning.htm. Accessed 27 January 2015

  3. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in drug and opioid overdose deaths—United States, 2000–2014. MMWR morbidity and mortality weekly report. 2016;64(50–51):1378–82. doi:10.15585/mmwr.mm6450a3

  4. Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, et al. Increases in heroin overdose deaths—28 States, 2010 to 2012. MMWR Morb Mortal Wkly Rep. 2014;63(39):849–54.

    PubMed  Google Scholar 

  5. Hedegaard H, Chen LH, Warner M. Drug-poisoning deaths involving heroin: United States, 2000–2013. NCHS data brief. 2015(190):1–8

  6. 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):246–52.

    Article  CAS  PubMed  Google Scholar 

  7. Mills CA, Flacke JW, Miller JD, Davis LJ, Bloor BC, Flacke WE. Cardiovascular effects of fentanyl reversal by naloxone at varying arterial carbon dioxide tensions in dogs. Anesth Analg. 1988;67(8):730–6.

    Article  CAS  PubMed  Google Scholar 

  8. Kienbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification. Anesthesiology. 1998;88(5):1154–61.

    Article  CAS  PubMed  Google Scholar 

  9. Johnson C, Mayer P, Grosz D. Pulmonary edema following naloxone administration in a healthy orthopedic patient. J Clin Anesth. 1995;7(4):356–7.

    Article  CAS  PubMed  Google Scholar 

  10. Belz D, Lieb J, Rea T, Eisenberg MS. Naloxone use in a tiered-response emergency medical services system. Prehospital Emergency Care: Official Journal of the National Association of EMS Physicians and the National Association of State EMS Directors. 2006;10(4):468–71. doi:10.1080/10903120600885134

  11. Buajordet I, Naess AC, Jacobsen D, Brors O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emer Med: Off J Eur Soc Emerg Med. 2004;11(1):19–23.

    Article  Google Scholar 

  12. Yip L, Megarbane B, Borron S. Opioids. In: Shannon M, Borron S, Burns M, editors. Haddad and Winchester’s clinical management of poisoning and drug overdose. Philadelphia: Saunders/Elsevier; 2007. p. 635–58.

    Chapter  Google Scholar 

  13. Wong J. Naloxone and nalmefen. In: Olson K, editor. Poisoning & drug overdose. New York: McGraw-Hill; 2012.

    Google Scholar 

  14. Lewin N, Howland M. Antidotes in depth: opioid antagonists. In: Nelson L, Howland M, Hoffman R, Goldfrank L, Flomenbaum N, editors. Goldfrank’s toxicologic emergencies. New York: McGraw-Hill; 2011.

    Google Scholar 

  15. Stolbach A, Hoffman R. Opioid intoxication in adults. In: UpToDate, Traub S (Ed), UpToDate, Waltham, MA. Accessed 13 January 2016; 2013

  16. Naloxone. In: Lexicomp online database [database on the Internet]. Lexicomp Inc., Hudson (OH). Accessed 30 November 2015

  17. Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S829–61. doi:10.1161/circulationaha.110.971069.

    Article  PubMed  Google Scholar 

  18. Doyon S. Opioids. In: Tinitinalli J, Stapczynski J, Ma O, Cline D, Cydulka R, Meckler G, editors. Tintinalli’s emergency medicine: a comprehensive study guide. New York: McGraw-Hill; 2011.

    Google Scholar 

  19. Bardsley C. Opioids. In: Marx J, Hockberger R, Walls R, al. e, editors. Rosen’s emergency medicine: concepts and clinical practice. Philadelphia: Mosby Elsevier; 2014. p. 2055.

  20. Naloxone. In: Butterworth JF, Mackey DC, Wasnick JD, Morgan GE, Mikhail MS, Morgan GE, editors. Morgan & Mikhail’s clinical anesthesiology. New York: McGraw-Hill; 2013.

  21. Hoffmann C, Tourtier J. Antidotes. In: Atchabahian A, Gupta R, editors. The anesthesia guide. New York: McGraw-Hill; 2013.

    Google Scholar 

  22. Opioids. In: Wiki Tox open source clinical toxicology curriculum 2006. Accessed 30 November 2015

  23. Lee C, Tschudy M, Arcara K. Drug doses. In: Tschudy M, Arcara K, editors. The Harriet lane handbook. Philadelphia: Mosby; 2011.

    Google Scholar 

  24. Stephens E. Emedicine: opioid toxicity, treatment and management. 2011.

    Google Scholar 

  25. O’Donnell K, Ewald M. Poisonings. In: Kleigman R, Stanton B, III JG, Schor N, Behrman R, editors. Nelson textbook of pediatrics. Philadelphia: Saunders; 2011.

    Google Scholar 

  26. Kosten TR. Chapter 393. Opioid drug abuse and dependence. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison’s principles of internal medicine, 18e. New York, NY: The McGraw-Hill Companies; 2012

  27. Ford M. Acute poisoning. In: Goldman L, Schager A, editors. Goldman’s Cecil medicine. Philadelphia: Elsevier/Saunders; 2012. p. 670–84.

    Chapter  Google Scholar 

  28. Common medical emergencies. In: Gomella L, Haist S, editors. Clinicians pocket reference. New York: McGraw-Hill; 2007.

  29. Yaksh T, Wallace M. Opioids, analgesia, and pain management. In: Brunton L, Blumenthal B, Murri N, Hilal-Dandan R, Knollmann B, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill; 2011.

    Google Scholar 

  30. Poisoning. In: Stone C, Humphries R, editors. Current diagnosis & treatment: emergency medicine. New York: McGraw-Hill; 2012.

  31. Lank P, Kusin S. Ethanol and opioid intoxication and withdrawal. In: Adams J, Barton E, Collings J, DeBlieux P, Gisondi M, Nadel E, editors. Emergency medicine: clinical essentials. Philadelphia: Elsevier; 2013.

    Google Scholar 

  32. Fukuda K. Opioids. In: Miller R, Eriksson L, Fleisher L, Weiner-Kronish J, Young W, editors. Miller’s anesthesia. Philadelphia: Churchill Livingstone; 2009. p. 769–823.

    Google Scholar 

  33. Rosow C, Dershwitz M. Pharmacology of opioid analgesics. In: Longnecker D, Brown D, Newman M, Zapol W, editors. Anesthesiology. New York: McGraw-Hill; 2012.

    Google Scholar 

  34. Cortazzo MH, Copenhaver, D, Fishman, Scott M. Major opioids and chronic opioid therapy. In: Benzon HT, Rathmell, James P, Wu, Christopher L, Turk, Dennis C, Argoff, Charles E, Hurley, Robert W., editor. Practical Management of Pain. Mosby; 2014. p. 495–507.

  35. Hayes BD. Academic life in emergency medicine: trick of the trade: naloxone dilution for opioid overdose. http://www.aliem.com/2014/trick-trade-naloxone-dilution/. Accessed 30 March 2016

  36. Cadogan M. Life in the fast lane antidotes: naloxone. http://lifeinthefastlane.com/tox-library/antidote/naloxone/. Accessed 30 March 2016

  37. NIH. Monitoring the future 2015 survey results. https://www.drugabuse.gov/related-topics/trends-statistics/infographics/monitoring-future-2015-survey-results. Accessed 30 March 2016

  38. Kim HK, Nelson LS. Reversal of opioid-induced ventilatory depression using low-dose naloxone (0.04 mg): a case series. Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology. 2015. doi:10.1007/s13181-015-0499-3.

Download references

Author information

Authors and Affiliations

  1. Division of Emergency Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

    Nicholas J. Connors

  2. Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA

    Lewis S. Nelson

Authors
  1. Nicholas J. Connors
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lewis S. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicholas J. Connors.

Ethics declarations

Conflicts of Interest

None

Sources of Funding

None

Additional information

Previously Presented as:

Connors NJ, Nelson LS. Wide Variation in Naloxone Dosing Recommendations for Acute Opioid Toxicity. Poster presentation: American College of Medical Toxicology (ACMT) Scientific Meeting. Phoenix, AZ, 2014.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Connors, N.J., Nelson, L.S. The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty. J. Med. Toxicol. 12, 276–281 (2016). https://doi.org/10.1007/s13181-016-0559-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13181-016-0559-3

Keywords

Search

Navigation