Opioid use disorder

Background

• Opioid use disorder (OUD) is a chronic, relapsing medical condition defined as a problematic pattern of opioid use leading to clinically significant impairment or distress
• ~87,000 opioid-related overdose deaths in the US annually (2023-2024 data); fentanyl is now the dominant illicit opioid
• Medications for opioid use disorder (MOUD) — buprenorphine, methadone, and naltrexone — reduce all-cause mortality by 50-80%
• ED-initiated buprenorphine increases 30-day treatment engagement ~5-fold compared to referral alone (D'Onofrio 2015 landmark RCT)
• No X-waiver or special certification is required to prescribe buprenorphine (eliminated January 2023 by the Consolidated Appropriations Act)
• The ED is often the only point of healthcare contact for patients with OUD — every visit is an opportunity to initiate lifesaving treatment

Clinical Features

Opioid Intoxication

• Miosis (pinpoint pupils — most reliable sign)
• Respiratory depression / bradypnea
• Altered mental status / sedation / coma
• Hypotension, bradycardia
• Hypothermia
• Decreased bowel sounds
• Needle marks / track marks (may be absent with intranasal or smoked use)

Opioid Withdrawal

• Onset varies by substance: heroin 6-12 hrs, prescription opioids 8-24 hrs, fentanyl variable (lipophilic depot may delay onset), methadone 24-72 hrs
• Pupils: mydriasis (opposite of intoxication)
• GI: nausea, vomiting, diarrhea, abdominal cramping
• Musculoskeletal: myalgias, arthralgias
• Autonomic: diaphoresis, piloerection ("goose flesh"), rhinorrhea, lacrimation, yawning
• Neuropsychiatric: restlessness, insomnia, anxiety, irritability, cravings
• Vital signs: tachycardia, hypertension (mild)
• Opioid withdrawal is extremely uncomfortable but NOT life-threatening in otherwise healthy adults (unlike alcohol or benzodiazepine withdrawal)
  • Exception: neonatal abstinence syndrome, medically frail/pregnant patients — withdrawal may be dangerous in these populations

Complications of Chronic OUD

• Infective endocarditis (right-sided > left-sided in IVDU; Staphylococcus aureus most common)
• Soft tissue abscess, cellulitis, necrotizing fasciitis
• Sepsis / bacteremia
• DVT, septic thrombophlebitis
• Hepatitis B, hepatitis C, HIV
• Septic pulmonary emboli, lung abscess
• Wound botulism (especially skin-popping black tar heroin)
• Rhabdomyolysis (prolonged immobilization during intoxication)
• Non-cardiogenic pulmonary edema (post-overdose)
• Xylazine ("tranq")-associated skin wounds: necrotic, non-healing ulcers at sites distant from injection; not reversed by naloxone

Differential Diagnosis

For Opioid Intoxication/Overdose

• Other toxidrome: sedative-hypnotics, clonidine / centrally-acting alpha-2 agonists, organophosphate poisoning (miosis + altered mental status)
• Hypoglycemia
• Stroke, intracranial hemorrhage
• Sepsis / meningitis
• Hypothermia
• Carbon monoxide poisoning
• Polysubstance ingestion (fentanyl commonly mixed with xylazine, benzodiazepines, stimulants)

For Opioid Withdrawal

• Gastroenteritis
• Sepsis / infection
• Thyrotoxicosis
• Stimulant intoxication (cocaine, amphetamine)
• Other withdrawal syndromes (alcohol, benzodiazepines)
• Anxiety / panic disorder

Evaluation

Workup

• No labs are required before initiating buprenorphine — do not delay treatment for test results
• Focused evaluation for common complications:
  • Point-of-care glucose (rule out hypoglycemia)
  • ECG (if concern for QTc prolongation from methadone, co-ingestions, or endocarditis)
  • CBC, BMP (if febrile, ill-appearing, or significant comorbidities)
  • Lactate, blood cultures (if sepsis concern)
  • LFTs (not required prior to buprenorphine initiation but may be helpful for outpatient follow-up)
  • Urine drug screen: may inform clinical picture but should not be used as a prerequisite for treatment; note that standard immunoassays do NOT detect fentanyl (requires specific fentanyl assay)
  • Pregnancy test (informs formulation choice: buprenorphine monoproduct preferred in pregnancy)
• Screening for associated infections in IVDU patients when clinically indicated: hepatitis C, HIV, hepatitis B (can be performed as outpatient if not acutely relevant)

Diagnosis

• DSM-5 criteria: ≥2 of 11 criteria within a 12-month period (see below)
  • Mild: 2-3 criteria; Moderate: 4-5 criteria; Severe: ≥6 criteria
• In the ED, a formal 11-criterion assessment is not necessary — a clinical diagnosis based on history is sufficient to initiate treatment
• Key ED diagnostic clues: recurrent overdoses, needle marks, withdrawal symptoms, requests for OUD treatment, opioid-positive UDS in clinical context
• Clinical Opioid Withdrawal Scale (COWS) — 11-item scoring tool to quantify withdrawal severity and guide induction timing:
  • 0-4: No withdrawal
  • 5-12: Mild withdrawal
  • 13-24: Moderate withdrawal
  • 25-36: Moderately severe withdrawal
  • >36: Severe withdrawal
• COWS ≥8 is the traditional threshold for buprenorphine induction, though emerging protocols allow initiation at lower scores or without formal COWS scoring

Management

Acute Opioid Overdose

• See Opioid overdose for complete management
• Naloxone 0.04-0.4 mg IV (titrate to respiratory effort, not consciousness) — higher doses (2-4 mg) may be needed for fentanyl
• Bag-valve mask ventilation is the primary intervention; naloxone is an adjunct
• Post-reversal: observe for re-sedation (fentanyl's duration may exceed naloxone's half-life of 30-90 min)
• Post-overdose is an ideal time to initiate buprenorphine — see below

Opioid Withdrawal Symptom Management

• Buprenorphine is the treatment of choice — treats withdrawal AND initiates OUD treatment simultaneously
• See
• 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

for induction strategies

Adjunctive symptom management (if buprenorphine not initiated or as supplemental therapy):

• Clonidine 0.1-0.2 mg PO/SL q4-6h for autonomic symptoms (max 0.8 mg/day; monitor for hypotension)
• Ondansetron 4 mg IV/PO for nausea/vomiting
• Loperamide 4 mg PO initially, then 2 mg after each loose stool (max 16 mg/day)
• NSAIDs or acetaminophen for myalgias
• Dicyclomine 10-20 mg PO for abdominal cramping
• Hydroxyzine 25-50 mg PO for anxiety/insomnia (avoid benzodiazepines if possible)
• IV fluids for dehydration
• Avoid: phenothiazines (lower seizure threshold), chronic benzodiazepine prescriptions

ED-Initiated Buprenorphine for OUD

This is the cornerstone of ED OUD management.

• Three induction strategies exist depending on withdrawal status — standard, high-dose (macro), and low-dose (micro)
• See Buprenorphine page and
• 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

for detailed induction protocols

Key principles:

• Any patient with OUD who is willing to accept treatment should be offered buprenorphine
• Do not delay initiation for lab results, urine drug screen, or social work evaluation
• COWS ≥8 is traditional threshold; post-overdose patients can be inducted earlier while naloxone is still active
• Precipitated withdrawal is managed with more buprenorphine (not less), plus adjunctive medications
• Discharge with buprenorphine/naloxone prescription (16 mg/day × 7-14 day bridge supply)
• No X-waiver required

Methadone in the ED

• Full mu-opioid agonist; available for OUD only through registered opioid treatment programs (OTPs)
• ED physicians may administer (not prescribe) methadone for up to 72 hours for acute withdrawal under the 72-hour rule (21 CFR §1306.07(b)) while arranging referral to an OTP
• Starting dose: 20-30 mg PO; may give additional 5-10 mg after 2-4 hours if withdrawal persists (max 40 mg day 1)
• Caution: QTc prolongation risk, full agonist (no ceiling effect for respiratory depression), unpredictable half-life (8-59 hours)

Naltrexone

• Long-acting mu-opioid antagonist; blocks opioid effects
• Must be opioid-free for 7-10 days before initiation (risk of precipitated withdrawal)
• Not practical for ED initiation but may be referenced in follow-up planning
• Available as oral (50 mg daily) or IM depot (Vivitrol 380 mg monthly)

Harm Reduction

• Naloxone kit — prescribe or provide to every patient with OUD at discharge (and to household contacts)
• Fentanyl test strips — where legal, offer to patients who use illicit substances
• Counsel on safer use practices (never use alone, carry naloxone, avoid mixing with benzodiazepines/alcohol)
• Provide information on syringe services programs and supervised consumption sites where available
• Offer hepatitis C and HIV testing or referral

Disposition

Discharge

• Most patients with uncomplicated OUD or opioid withdrawal can be discharged from the ED
• Discharge with:
  • Buprenorphine/naloxone prescription (7-14 day supply, typically 16 mg/day)
  • Naloxone kit (or prescription for naloxone)
  • Outpatient follow-up appointment with addiction medicine, primary care, or federally qualified health center that provides MOUD
  • Written withdrawal management instructions (if home induction planned)
  • Harm reduction resources
• Ensure patient has had resolution or improvement of withdrawal symptoms before discharge

Admit

• Medically complicated withdrawal (significant dehydration, electrolyte abnormalities, comorbid medical illness)
• OUD-related complications requiring inpatient management: endocarditis, epidural or deep abscess, osteomyelitis, sepsis, necrotizing fasciitis
• Post-overdose with persistent respiratory depression, non-cardiogenic pulmonary edema, or aspiration
• Concurrent alcohol or benzodiazepine withdrawal requiring monitored detoxification
• Pregnancy with uncontrolled withdrawal (risk to fetus)
• Suicidal ideation or acute psychiatric emergency co-occurring with OUD
• Failed outpatient management or patient without safe discharge plan

Post-Overdose Observation

• Patients reversed with naloxone should be observed for at least 1 hour after last naloxone dose (longer if sustained-release opioid or fentanyl suspected, where re-sedation risk is higher)
• Use the observation period to engage patient in OUD treatment discussion and buprenorphine initiation

Follow-Up Resources

• SAMHSA National Helpline: 1-800-662-4357 (referral and information, 24/7)
• PEPline (buprenorphine clinical questions): 1-888-448-4911
• SAMHSA Buprenorphine Practitioner Locator: https://www.samhsa.gov/medications-substance-use-disorders/find-help

See Also

• Opioid overdose
• Opioid withdrawal
• Buprenorphine
• Naloxone
• Methadone
• Naltrexone
• Endocarditis
• Toxidromes

External Links

• Yale ED-Initiated Buprenorphine Resource Center
• ACEP Opioid Use Disorder Resources
• COWS Score Calculator (MDCalc)
• SAMHSA Medications for Substance Use Disorders