Opioid overdose

Last updated: October 4, 2023

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Summarytoggle arrow icon

Opioid overdose results from the toxic effects of exogenous opioids. Deaths related to opioid overdose have been steadily increasing in the United States over the past two decades because of a sharp increase in the prescription of opioids for chronic pain and increasing amounts of illegally manufactured fentanyl. Common clinical features of opioid overdose include respiratory depression, CNS depression, and miosis. Treatment of suspected opioid overdose requires airway management and prompt assessment of the need for naloxone to counter opioid-induced respiratory depression, which can be fatal. Inpatient admission is indicated for patients with ongoing respiratory depression, overdose from long-acting opioids, or medical complications from an opioid overdose. All patients with a noniatrogenic opioid overdose should undergo an assessment for substance use disorder (SUD) and be discharged with take-home intranasal naloxone.

Epidemiologytoggle arrow icon

  • Opioid overdose is the most common cause of drug overdose death. [2]
    • From 2015 to 2022, annual opioid overdose deaths nearly tripled. [2]
    • Deaths typically involve high-potency synthetic opioids (e.g., fentanyl).

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Iatrogenic overdose occurs when a prescribed dose exceeds an individual's tolerance for opioids. Noniatrogenic overdose (i.e., in the setting of unhealthy drug use) may be intentional or unintentional (e.g., use of a higher dose than intended).

Risk factors for opioid overdose [3][4]

Opioid-induced CNS depression is intensified when combined with other sedative-hypnotics (e.g., alcohol, benzodiazepines).

Clinical featurestoggle arrow icon

Opioid toxidrome [6]

The classic triad consists of:

The absence of miosis does not rule out opioid intoxication.

Opioid-induced respiratory depression (OIRD) [8][9]

OIRD is the most common cause of death from opioid overdose and is treated with naloxone for opioid overdose.

Other clinical features [6]

Diagnosticstoggle arrow icon

Clinical evaluation

Supportive investigations

Typically performed to evaluate for comorbid conditions, complications, and differential diagnoses.

Do not delay treatment of suspected opioid overdose to await drug test results.

Managementtoggle arrow icon

Acute management [6][7]

See “Approach to the poisoned patient” for a stepwise approach to patients with known or suspected poisoning.

If possible, perform basic airway maneuvers prior to administering naloxone to reduce the risk of pulmonary edema or acute lung injury after the reversal of apnea. [7]

Avoid naloxone in intoxicated patients without OIRD, i.e., with spontaneous respiratory rate > 12 breaths/minute. [12]

Naloxone for opioid overdose [7][12]

Naloxone has a dose-dependent duration of action that is shorter than most opioids. It does not shorten the duration of opioid toxicity. Repeat dosing and monitoring are often required. [7]

Starting dose [6][7][13]

The following dosages are suggested based on expert opinion and FDA guidance. [14]

Lower doses are typically sufficient for opioid-dependent patients. Higher doses are appropriate for opioid-naive patients and are typically required for any patients with synthetic opioid (e.g., fentanyl) overdose. [6][13][15]

In cardiac arrest, do not delay ACLS in order to administer naloxone. [14][15]

Subsequent dosage

Titrate further dosing of naloxone to clinical response: e.g., respiratory rate, tidal volume, EtCO2, and other signs of respiratory distress or respiratory failure.

  • No improvement
    • Repeat the dose every 2–3 minutes as needed.
    • Consider increasing the dose on each repeat administration if there is no response.
    • Repeat doses can range widely; follow local protocols and tailor to the individual clinical response. [7]
    • After ≥ 10 mg of naloxone, reconsider the diagnosis and evaluate for other causes of respiratory depression e.g., xylazine intoxication.
  • Initial improvement with recurrent OIRD: Consider continuous naloxone infusion.
    • Start infusion at ⅔ the naloxone dose that initially reversed OIRD. [16]
    • Titrate the infusion based on clinical response.
  • Precipitated opioid withdrawal: Do not administer additional naloxone.

Naloxone is typically unnecessary in intubated and mechanically ventilated patients. [12]

Mental health disorder management [4]

Disposition [6][7]

  • Observation period: 4–6 hours after the last naloxone dose [17]
  • Admit patients with:
    • Ongoing respiratory depression, e.g., mechanically ventilated patients requiring critical care admission.
    • Toxicity from long-acting or extended-release opioids (e.g., methadone, fentanyl patch)
    • Complications requiring inpatient management (e.g., rhabdomyolysis, suicidal ideation)
  • Discharge criteria
    • All patients: alert with normal vital signs
    • Known or suspected intentional overdose: after safety assessment (e.g., by psychiatry)
    • Consider prescribing or providing home naloxone kits.

Monitor patients for 4–6 hours after administering naloxone for a resumption of opioid effects. [7]

Differential diagnosestoggle arrow icon

Xylazine intoxication [18][19][20]

Sedation caused by xylazine intoxication does not improve with naloxone for opioid overdose and increases the risk of airway compromise. [18]

Toxicity from other substances [22]

Cerebrovascular conditions [22]

The differential diagnoses listed here are not exhaustive.

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Preventiontoggle arrow icon

Provide take-home naloxone kits to all patients with risk factors for opioid overdose. Train patients and close contacts on the use of naloxone for treating opioid overdose. [4]

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Referencestoggle arrow icon

  1. $Contributor Disclosures - Opioid overdose. All of the relevant financial relationships listed for the following individuals have been mitigated: Alexandra Willis (copyeditor, was previously employed by OPEN Health Communications). None of the other individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy.
  2. Provisional drug overdose death counts. Updated: September 14, 2022. Accessed: September 29, 2022.
  3. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  4. Boyer EW. Management of Opioid Analgesic Overdose. N Engl J Med. 2012; 367 (2): p.146-155.doi: 10.1056/nejmra1202561 . | Open in Read by QxMD
  5. Bateman JT, Saunders SE, Levitt ES. Understanding and countering opioid‐induced respiratory depression. Br J Pharmacol. 2021; 180 (7): p.813-828.doi: 10.1111/bph.15580 . | Open in Read by QxMD
  6. Gupta K, Nagappa M, Prasad A, et al. Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses. BMJ Open. 2018; 8 (12): p.e024086.doi: 10.1136/bmjopen-2018-024086 . | Open in Read by QxMD
  7. Miller SC, Fiellin DA, Rosenthal RN, Saitz R. The ASAM Principles of Addiction Medicine. LWW ; 2018
  8. Clarke SFJ. Naloxone in opioid poisoning: walking the tightrope. Emerg Med J. 2005; 22 (9): p.612-616.doi: 10.1136/emj.2003.009613 . | Open in Read by QxMD
  9. Connors NJ, Nelson LS. The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty. J Med Toxicol. 2016; 12 (3): p.276-281.doi: 10.1007/s13181-016-0559-3 . | Open in Read by QxMD
  10. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020; 142 (16_suppl_2).doi: 10.1161/cir.0000000000000916 . | Open in Read by QxMD
  11. Dezfulian C, Orkin AM, Maron BA, et al. Opioid-Associated Out-of-Hospital Cardiac Arrest: Distinctive Clinical Features and Implications for Health Care and Public Responses: A Scientific Statement From the American Heart Association. Circulation. 2021; 143 (16).doi: 10.1161/cir.0000000000000958 . | Open in Read by QxMD
  12. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Goldfrank's Toxicologic Emergencies, 11th edition. McGraw-Hill Education ; 2019
  13. Crotty K, Freedman KI, Kampman KM. Executive Summary of the Focused Update of the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder. J Addict Med. 2020; 14 (2): p.99-112.doi: 10.1097/adm.0000000000000635 . | Open in Read by QxMD
  14. Heaton JD, Bhandari B, Faryar KA, Huecker MR. Retrospective Review of Need for Delayed Naloxone or Oxygen in Emergency Department Patients Receiving Naloxone for Heroin Reversal. J Emerg Med. 2019; 56 (6): p.642-651.doi: 10.1016/j.jemermed.2019.02.015 . | Open in Read by QxMD
  15. Gupta R, Holtgrave DR, Ashburn MA. Xylazine — Medical and Public Health Imperatives. N Engl J Med. 2023.doi: 10.1056/nejmp2303120 . | Open in Read by QxMD
  16. Mbabazi Kariisa, Priyam Patel, Herschel Smith, Jessica Bitting. Notes from the Field: Xylazine Detection and Involvement in Drug Overdose Deaths — United States, 2019. MMWR Morb Mortal Wkly Rep. 2021; 70 (37): p.1300-1302.doi: 10.15585/mmwr.mm7037a4 . | Open in Read by QxMD
  17. Holt AC, Schwope DM, Le K, Schrecker JP, Heltsley R. Widespread Distribution of Xylazine Detected Throughout the United States in Healthcare Patient Samples. J Addict Med. 2023.doi: 10.1097/adm.0000000000001132 . | Open in Read by QxMD
  18. Reed MK, Imperato NS, Bowles JM, Salcedo VJ, Guth A, Rising KL. Perspectives of people in Philadelphia who use fentanyl/heroin adulterated with the animal tranquilizer xylazine; Making a case for xylazine test strips. Drug Alcohol Depend Rep. 2022; 4: p.100074.doi: 10.1016/j.dadr.2022.100074 . | Open in Read by QxMD
  19. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Elsevier Health Sciences ; 2018
  20. Manini AF, Nair AP, Vedanthan R, Vlahov D, Hoffman RS. Validation of the Prognostic Utility of the Electrocardiogram for Acute Drug Overdose. J. Am. Heart Assoc. 2017; 6 (2).doi: 10.1161/jaha.116.004320 . | Open in Read by QxMD
  21. Weiner SG, El Ibrahimi S, Hendricks MA, et al. Factors Associated With Opioid Overdose After an Initial Opioid Prescription. JAMA Netw Open. 2022; 5 (1): p.e2145691.doi: 10.1001/jamanetworkopen.2021.45691 . | Open in Read by QxMD
  22. Park TW, Lin LA, Hosanagar A, Kogowski A, Paige K, Bohnert ASB. Understanding Risk Factors for Opioid Overdose in Clinical Populations to Inform Treatment and Policy. J Addict Med. 2016; 10 (6): p.369-381.doi: 10.1097/adm.0000000000000245 . | Open in Read by QxMD
  23. Winer JM, Yule AM, Hadland SE, Bagley SM. Addressing adolescent substance use with a public health prevention framework: the case for harm reduction. Ann Med. 2022; 54 (1): p.2123-2136.doi: 10.1080/07853890.2022.2104922 . | Open in Read by QxMD
  24. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016; 65 (1): p.1-49.doi: 10.15585/mmwr.rr6501e1 . | Open in Read by QxMD
  25. Theisen-Toupal J, Ronan MV, Moore A, Rosenthal ES. Inpatient Management of Opioid Use Disorder: A Review for Hospitalists. Journal of Hospital Medicine. 2017; 12 (5): p.369-374.doi: 10.12788/jhm.2731 . | Open in Read by QxMD

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