Opioid withdrawal

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) 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
  • 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

• Heroin: onset 6-12 hours, peak 24-72 hours, duration 7-10 days
• 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

• Heroin: onset within 24hrs
• Methadone: onset within 2-3 days due to large volume of distribution
• 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

• 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

• Abdominal cramping
• Diarrhea
• Dilated pupils
• Goose bumps
• Nausea
• Vomiting

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

• Sepsis
• Influenza
• Clonidine withdrawal
• Sympathomimetic use

Sedative/hypnotic withdrawal

• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Methanol
  • Isopropyl alcohol
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Gamma hydroxybutyrate (GHB)
• Baclofen
• Barbiturates
• Opioids
• Chloral hydrate

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.

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 and app .

• 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 and hospitalized patients.

NIH National Institute on Drug Abuse ED Buprenorphine algorithm

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

Benzodiazepines

• Can be added along with with clonidine for adequate sedation

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

See Also

• Neonatal abstinence syndrome
• Opioid toxicity
• Harbor:Opiate Withdrawal/MAT/BUP