Opioid withdrawal: Difference between revisions
 
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==Background==
==Background==
*Opioid withdrawal can be precipitated with administration of antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). <ref> Olmedo R, Hoffman RS. Withdrawal syndromes. Emerg Med Clin North Am. 2000;18(2):273–88. </ref> or as a result of cessation of use.
*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]]) <ref> Olmedo R, Hoffman RS. Withdrawal syndromes. Emerg Med Clin North Am. 2000;18(2):273–88. </ref> 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 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]] <ref> Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348:1786-95 </ref>
**Catecholamine surge during withdrawal may cause a level of hemodynamic instability that may not be tolerated by patients with co-morbid conditions
**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
**Withdrawal can be life-threatening in neonates


==Clinical Presentation==
===Adult Opioid Withdrawal===
*Time to peak and duration of symptoms depends on the half-life of the drug involved.  
[[File:OpioidWithdrawalCourse.jpg|thumb|Graph of opoid withdrawal course durcation<ref>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</ref>]]
===Estimated Time to Onset of Withdrawal===
*[[Heroin]]: onset 6-12 hours, peak 24-72 hours, duration 7-10 days<ref>Herring, A et al. Managing opioid withdrawal in the emergency department with buprenorphine. Annals of Emergency Medicine. 2019.73(5) 481-487</ref>
*[[Heroin]]: onset 6-12 hours, peak 36-72 hours, duration 7-10 days
*[[Methadone]]: onset 24-72 hours, peak 4-6 days, duration 14 days or more
*[[Methadone]]: onset 30 hours, peak 72-96 hours, duration 14 days or more
*[[Fentanyl]]: onset 2-5 hours, peak 8-12 hours, duration 4-5 days
*If symptoms are from [[naloxone]]-induced withdrawal, typically the duration of symptoms are generally < 1 hour but can be severe
*[[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===
*[[Heroin]]: onset within 24hrs
*[[Methadone]]: onset within 2-3 days due to large volume of distribution<ref>Doberczak TM et al. Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. Obstet Gynecol. 1993. 81:936–940.</ref>
*[[Buprenorphine]]: onset within 2-3 days
==Clinical Features==
Time to peak and duration of symptoms depends on the half-life of the drug involved
===Early symptoms===
===Early symptoms===
*Agitation/restlessness
*Agitation/restlessness
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*[[Vomiting]]
*[[Vomiting]]


*Unlike alcohol or benzo withdrawal, unlikely to have seizures
;Unlike [[alcohol]] or [[benzodiazepine]] withdrawal, patients rarely have seizures'''
**Typically normal mental status despite agitation
;Altered mental status is also not part of opioid withdrawal signs'''


==Differential Diagnosis==
==Differential Diagnosis==
''Differential is largely based on clinical symptoms and history''
*[[Sepsis]]
*[[Influenza]]
*[[Clonidine]] withdrawal
*[[Sympathomimetic]] use


{{Sedative/hypnotic withdrawal types}}


==Diagnosis==
==Evaluation==
*Clinical diagnosis
*Clinical diagnosis
**Consider a [[Urine toxicology screen|UDS]]
**Consider [[urine toxicology screen]] and BMP if signs of dehydration
**Clinical Opiate Withdrawal Score ([http://www.mdcalc.com/cows-score-for-opiate-withdrawal/ COWS]) can be used to determine severity
**Clinical Opiate Withdrawal Score ([http://www.mdcalc.com/cows-score-for-opiate-withdrawal/ COWS]) can be used to determine severity


==Management==
==Management==
*PO/IV hydration PRN
''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.'' <ref> 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. </ref>
*[[Clonidine]]
 
**Mild opioid withdrawal - 0.1 - 0.3 mg PO
===Supportive Care===
***Monitor heart rate and blood pressure and may titrate to effect
*PO/IV hydration
**5mcg/kg PO (as long as SBP >90)
*Electrolyte repletion
*[[Benzodiazepines]] (e.g. diazepam 10-20mg IV)
===Opioid replacement===
**Can add with clonidine for adequate sedation
*Opioid administration such as [[morphine]] can be given as needed for symptom control
*Antihistamines
 
**[[Diphenhydramine]]  
===[[Clonidine]]===
**[[Hydroxyzine]] 50-100mg PO QID x5d
*A central α<sub>2</sub> agonist that does suppress the sympathetic hyperactivity that results during acute withdrawal
*[[Antiemetics]]
*Dosing:  0.1mg PO (or 5mcg/kg PO if SBP >90 mmHg) every 60 minutes as needed for sympathetic symptoms
*Antidiarrheals
**Major adverse effect is hypotension
**[[Loperamide]] or Octreotide
*Clonidine patches are not useful for acute withdrawal due to the 24hr delayed release{{Citation needed|reason=Reliable source needed|date=March 2016}}
*[[NSAIDS]]
 
===[[Lofexidine]]===
*A newer central alpha<sub>2</sub> agonist
 
===[[Buspirone]]===
*Generally reserved for outpatient therapy
*Decreases serotonergic activity<ref>Van den Brink W et al. Evidence-based treatment of opioid-dependent patients. Can J Psychiatry 2006; 51:635.</ref>
 
===[[Benzodiazepines]]===
*Can be added along with with clonidine for adequate sedation
===[[Antihistamines]]===


For select cases:
===[[Methadone]]===
*Buprenorphine
*Consider if withdrawal was precipitated by interruption in opioid use, NOT if antagonist (e.g. narcan) was given
**Partial agonist, may induce withdrawal in opioid intoxicated patients
*Dose: 10mg IM or 30mg PO
*Methadone 10mg IM or 20mg PO
**Consider if withdrawal precipitated by interruption in opioid use, NOT if antagonist (e.g. narcan) was given


==Disposition==
==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==
==See Also==
*[[Neonatal abstinence syndrome]]
*[[Neonatal abstinence syndrome]]
*[[Opioid toxicity]]
*[[Opioid toxicity]]
*[[Harbor:Opiate Withdrawal/MAT/BUP]]


==References==
==References==
<references/>
<references/>


[[Category:Tox]]
[[Category:Toxicology]]

Latest revision as of 17:10, 18 October 2023

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

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[7]

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. ↑ Van den Brink W et al. Evidence-based treatment of opioid-dependent patients. Can J Psychiatry 2006; 51:635.
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