Opioid overdose and opioid use disorder: workup and management
Opioid overdose presents with respiratory depression, miosis and reduced consciousness. Support ventilation, give naloxone titrated to breathing, observe for recurrent sedation, check for co-ingestants, and use the encounter to start buprenorphine and provide naloxone at discharge.
Working diagnosis
Adult · US guidelines
Draft · awaiting physician review
01Orient
What's new in the evidence
- The federal X-waiver was eliminated in 2023: any clinician with a DEA Schedule III registration can prescribe buprenorphine for OUD
- Fentanyl and xylazine adulterants are now common; xylazine sedation does not reverse with naloxone and causes chronic wounds
- ED-initiated buprenorphine roughly doubles engagement in treatment at 30 days (D'Onofrio, JAMA 2015); low-dose and high-dose induction strategies are used for fentanyl exposure
- Over-the-counter naloxone nasal spray is available in the US since 2023
Differential diagnoses
- Opioid toxicity (heroin, fentanyl, prescription opioids)
- Co-ingestion: benzodiazepines, alcohol, xylazine, gabapentinoids (can't miss)
- Hypoglycemia (can't miss)
- Head injury or intracranial hemorrhage (can't miss)
- Sepsis, CO poisoning, hypercapnic respiratory failure
- Clonidine or other central sedatives
02Assess
Risk scores and decision tools
- Respiratory rate <12/min and miosis with sedation: classic triad
- COWS (Clinical Opiate Withdrawal Scale) to time buprenorphine (typically ≥8–12)
- DSM-5 criteria for opioid use disorder
Key history questions
- Substance, route and time; fentanyl or unknown supply
- Co-ingestants (benzodiazepines, alcohol, stimulants)
- Long-acting opioids (methadone, extended-release) that need longer observation
- Prior overdoses, treatment history, interest in buprenorphine or methadone
- Injection-related infections, pregnancy
Examination findings
- Respiratory rate, SpO₂, end-tidal CO₂
- Pupils, GCS
- Track marks, abscesses, wounds (xylazine), murmurs (endocarditis)
- Trauma, aspiration, compartment syndrome or rhabdomyolysis after prolonged immobility
03Investigate
Initial investigations
- Fingerstick glucose
- ECG (QTc with methadone; QRS with co-ingestants)
- BMP, CK, acetaminophen and salicylate levels
- Pregnancy test
Advanced investigations
- Chest X-ray if hypoxic (aspiration, noncardiogenic pulmonary edema)
- CT head if trauma or focal signs
- HIV, hepatitis B and C screening; blood cultures if febrile and injecting
04Treat
Immediate management
- Airway, bag-valve-mask ventilation and oxygen
- Naloxone 0.04–0.4 mg IV titrated to respiratory effort (not full awakening); 2–4 mg intranasal or 0.4 mg IM if no IV
- Repeat every 2–3 minutes; consider infusion (two-thirds of the effective bolus per hour) for long-acting opioids
First-line treatment
- Observe at least 4–6 hours after the last naloxone dose; longer for methadone or extended-release opioids
- Treat withdrawal symptoms; start buprenorphine when COWS ≥8–12 (e.g., 4–8 mg SL, up to 16–24 mg on day 1)
- Naloxone kit and overdose education for every patient at discharge
Second-line treatment
- Precipitated withdrawal after buprenorphine: give more buprenorphine plus symptomatic treatment
- Low-dose (micro-) induction for patients who cannot tolerate withdrawal
- Methadone via an opioid treatment program; extended-release buprenorphine injection
Specialist referrals
- Addiction medicine or bridge clinic
- Social work and harm reduction services
- Infectious diseases for injection-related infections
05Disposition
Admission criteria
- Recurrent sedation, need for naloxone infusion
- Aspiration, hypoxia, rhabdomyolysis or co-ingestant toxicity
- Long-acting opioid ingestion
Safe discharge criteria
- Normal breathing and mental status ≥4–6 hours after last naloxone
- Naloxone kit given; buprenorphine prescription and follow-up arranged
Follow-up timing
- Treatment follow-up within 72 hours of ED-initiated buprenorphine
Patient instructions
- Never use alone; carry naloxone; use fentanyl test strips
- Avoid combining with alcohol or benzodiazepines
Monitoring
- Continuous SpO₂ and capnography while sedated
- Repeat sedation assessment as naloxone wears off (30–90 minutes)
Clinical pearls and pitfalls
- Naloxone acts for 30–90 minutes; many opioids last longer
- Aim for adequate breathing, not full reversal, to avoid precipitated withdrawal and agitation
- Overdose is the strongest predictor of death from OUD in the following year; start treatment now
RefGuidelines and landmark evidence
For education only. Typical adult starting points; confirm doses against renal function, allergies, interactions and your institution's protocols. Not a substitute for clinical judgment or senior review.