Opioid withdrawal

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Background

  • Natural derivatives (Opiates): Heroin, Morphine, Codeine, Hydrocodone, Oxycodone (+ UDS)
  • Synthetic: Fentanyl, Hydromorphone, Buprenorphine, Methadone, Meperidine, Dextromethorphan (- UDS)
  • Opioid withdrawal can be precipitated with administration of antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine) [1] or as a result of cessation of use
  • Symptoms are usually uncomfortable but not life-threatening and manifest with agitation and restlessness but does not cause altered mental status
  • Symptoms may resemble those of Influenza [2]
    • Catecholamine surge during withdrawal may cause a level of hemodynamic instability that may not be tolerated by patients with co-morbid conditions
    • Withdrawal can be life-threatening in neonates

Adult Opioid Withdrawal

Graph of opoid withdrawal course durcation[3]
  • Heroin: onset 6-12 hours, peak 24-72 hours, duration 7-10 days[4]
  • Methadone: onset 24-72 hours, peak 4-6 days, duration 14 days or more
  • Fentanyl: onset 2-5 hours, peak 8-12 hours, duration 4-5 days
  • Buprenorphine: 4-48 hours, peak 96 hours, duration 14-21 days

Precipitated Withdrawal

  • Naloxone: onset 1-3 min, duration: 30-60min
  • Butorphanol or nalbuphine: 15 min, duration: 90 min
  • Naltrexone: 15-30min, duration 12-24hours
  • Buprenorphine: 10-15min, duration 12-24 hours

Neonatal Opioid Withdrawal

Clinical Features

Time to peak and duration of symptoms depends on the half-life of the drug involved

Early symptoms

  • Agitation/restlessness
  • Anxiety
  • Muscle aches
  • Increased tearing
  • Insomnia
  • Runny nose
  • Sweating
  • Yawning
  • Skin-Crawling
  • May be tachycardic and/or tachypneic but not necessarily

Late symptoms

Unlike alcohol or benzodiazepine withdrawal, patients rarely have seizures
Altered mental status is also not part of opioid withdrawal signs

Differential Diagnosis

Differential is largely based on clinical symptoms and history

Sedative/hypnotic withdrawal

Evaluation

  • Clinical diagnosis
    • Consider urine toxicology screen and BMP if signs of dehydration
    • Clinical Opiate Withdrawal Score (COWS) can be used to determine severity

Management

Treatment should include symptomatic treatment as well as discussing medications for opioid use disorder including methadone and buprenorphine. Buprenorphine should be offered to be initiated in the emergency department to patients who are interested and meet criteria for initiation, and linkage to care should be facilitated. [6]

Supportive Care

  • PO/IV hydration
  • Electrolyte repletion

Opioid replacement

  • Opioid administration such as morphine can be given as needed for symptom control

Buprenorphine

  • For Clinical Opioid Withdrawal Scale (COWS) ≥8: give 4 to 8mg of Buprenorphine, observe 30 to 45min
    • Redose if COWS remains ≥8. Then discharge home with 16 mg a day to bridge until follow-up (an X-waiver is no longer required to prescribe buprenorphine).
  • For Clinical Opioid Withdrawal Scale (COWS) 0-7: Consider observing the patient until their COWS score is >8 for the standard buprenorphine induction.
    • Alternatively, you can prescribe consider unobserved home induction instructions available on paper [7][8] and app[9] [10].
  • If sublingual tablets/films unavailable then intravenous/intramuscular formulation (dose 0.3-0.9 mg every 6-12 hours) has been used for opioid withdrawal in the ED[11] and hospitalized[12] patients.
NIH National Institute on Drug Abuse ED Buprenorphine algorithm[13]

Clonidine

  • A central α2 agonist that does suppress the sympathetic hyperactivity that results during acute withdrawal
  • Dosing: 0.1mg PO (or 5mcg/kg PO if SBP >90 mmHg) every 60 minutes as needed for sympathetic symptoms
    • Major adverse effect is hypotension
  • Clonidine patches are not useful for acute withdrawal due to the 24hr delayed release[citation needed]

Lofexidine

  • A newer central alpha2 agonist

Buspirone

  • Generally reserved for outpatient therapy
  • Decreases serotonergic activity[14]

Benzodiazepines

  • Can be added along with with clonidine for adequate sedation

Antihistamines

Methadone

  • Consider if withdrawal was precipitated by interruption in opioid use, NOT if antagonist (e.g. narcan) was given
  • Dose: 10mg IM or 30mg PO

Disposition

  • Patients who need long term detoxification can be admitted or transferred to detox facilities
  • If patients are going to continue to use opioids then those who are stable can be discharged
  • Patients with severe withdrawal requiring sedation and continued monitoring should be admitted

External Links

See Also

References

  1. Olmedo R, Hoffman RS. Withdrawal syndromes. Emerg Med Clin North Am. 2000;18(2):273–88.
  2. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348:1786-95
  3. Brain Commun. 2019 Oct 16;1(1):fcz025. doi: 10.1093/braincomms/fcz025. eCollection 2019. Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development Alicja Lerner 1, Michael Klein 2
  4. Herring, A et al. Managing opioid withdrawal in the emergency department with buprenorphine. Annals of Emergency Medicine. 2019.73(5) 481-487
  5. Doberczak TM et al. Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. Obstet Gynecol. 1993. 81:936–940.
  6. Hawk K, Hoppe J, Ketcham E, LaPietra A, Moulin A, Nelson L, Schwarz E, Shahid S, Stader D, Wilson MP, D'Onofrio G. Consensus Recommendations on the Treatment of Opioid Use Disorder in the Emergency Department. Ann Emerg Med. 2021 Sep;78(3):434-442. doi: 10.1016/j.annemergmed.2021.04.023. Epub 2021 Jun 23. PMID: 34172303.
  7. A Guide for Patients Beginning Buprenorphine Treatment at Home https://medicine.yale.edu/edbup/quickstart/Home_Buprenorphine_Initiation_338574_42801_v1.pdf
  8. A Patient’s Guide to Starting Buprenorphine at Home from ASAM https://www.asam.org/docs/default-source/education-docs/unobserved-home-induction-patient-guide.pdf
  9. Buprenorphine Home Induction Apple App Store https://apps.apple.com/us/app/buprenorphine-home-induction/id1449302173
  10. Starting Buprenorphine from Google Play Store https://play.google.com/store/apps/details?id=com.amstonstudio.bup&hl=en_US&gl=US
  11. Berg ML, et. al. Evaluation of the use of buprenorphine for opioid withdrawal in an emergency department. Drug Alcohol Depend. 2007 Jan 12;86(2-3):239-44. https://doi.org/10.1016/j.drugalcdep.2006.06.014. Epub 2006 Aug 22. PMID: 16930865.
  12. Welsh CJ, Suman M, Cohen A, et al. The use of intravenous buprenorphine for the treatment of opioid withdrawal in medically ill hospitalized patients. Am J Addict. 2002;11(2):135-40 https://doi.org/10.1080/105500490290087901
  13. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/algorithm.pdf
  14. Van den Brink W et al. Evidence-based treatment of opioid-dependent patients. Can J Psychiatry 2006; 51:635.