Overview
Opioid Overdose
Quick Reference
Critical Alerts
- Airway and ventilation first: BVM before and during naloxone
- Naloxone reverses opioid overdose: Titrate to respiratory drive
- Fentanyl may require higher doses: More potent, may need repeated dosing
- Observe for renarcotization: Opioid may outlast naloxone
- Consider polysubstance use: Benzos, alcohol, stimulants common
- Harm reduction saves lives: Prescribe take-home naloxone at discharge
Classic Toxidrome
| Feature | Finding |
|---|---|
| Mental status | Depressed (drowsy to comatose) |
| Pupils | Pinpoint (miosis) |
| Respirations | Slow, shallow, apnea |
| Skin | Cyanosis if hypoxic |
Emergency Treatments
| Route | Naloxone Dose | Notes |
|---|---|---|
| Intranasal | 4 mg (2 mg per nostril) | First-line prehospital |
| Intramuscular | 0.4-2 mg | If no IV |
| Intravenous | 0.04-0.4 mg initial | Titrate; start low in opioid-dependent |
| Repeat | q2-3 min if no response | Up to 10 mg total |
Definition
Overview
Opioid overdose is a life-threatening emergency characterized by CNS and respiratory depression due to excessive opioid effect. It is a leading cause of drug-related death in the United States, with synthetic opioids (primarily illicit fentanyl) now responsible for most overdose fatalities. Prompt recognition and naloxone administration save lives.
Classification
By Opioid Type:
| Category | Examples |
|---|---|
| Natural | Morphine, codeine |
| Semi-synthetic | Heroin, oxycodone, hydrocodone, hydromorphone |
| Synthetic | Fentanyl, methadone, tramadol |
| Partial agonist | Buprenorphine |
By Setting:
| Type | Context |
|---|---|
| Illicit drug use | Heroin, illicit fentanyl |
| Prescription misuse | Opioid analgesics |
| Iatrogenic | Hospital setting, post-operative |
| Accidental (pediatric) | Ingestion of medications |
Epidemiology
- US overdose deaths: >100,000/year total; >70,000 involve opioids
- Fentanyl predominates: Most opioid deaths involve synthetic opioids
- Rising trend: Overdose deaths continue to increase
- Risk populations: IVDU, chronic pain patients, post-incarceration, polysubstance users
Etiology
Risk Factors:
| Factor | Mechanism |
|---|---|
| Fentanyl contamination | Unpredictable potency |
| Tolerance loss | After abstinence (detox, incarceration) |
| Combining with sedatives | Additive CNS/respiratory depression |
| High-dose prescription | Exceeding tolerance |
| Opioid-naïve | No tolerance |
| Respiratory comorbidities | COPD, sleep apnea |
Pathophysiology
Mechanism of Opioid Toxicity
- Mu-opioid receptor binding: CNS, respiratory centers
- Respiratory depression: Decreased drive, rate, depth
- Hypoxia: Leading to loss of consciousness
- Apnea and death: If untreated
Other Opioid Effects
| System | Effect |
|---|---|
| CNS | Sedation, euphoria, coma |
| Respiratory | Hypoventilation, apnea |
| Cardiovascular | Bradycardia, mild hypotension |
| GI | Decreased motility, nausea |
| Pupils | Miosis (pinpoint) |
| Urinary | Retention |
Duration of Action
| Opioid | Duration |
|---|---|
| Heroin | 4-6 hours |
| Fentanyl (IV) | 30-60 minutes |
| Methadone | 24-36 hours |
| Extended-release formulations | 12-24+ hours |
Naloxone duration: 30-90 minutes → Risk of renarcotization
Clinical Presentation
Classic Opioid Toxidrome
Triad:
- Depressed level of consciousness
- Miosis (pinpoint pupils)
- Respiratory depression
Other Findings
History (Often Limited)
Key Information:
Physical Examination
| Finding | Significance |
|---|---|
| Unresponsive | Severe overdose |
| Apnea/Agonal breathing | Imminent death |
| Pinpoint pupils | Classic; may be absent with coingestants |
| Cyanosis | Hypoxia |
| Track marks | IVDU |
| Pulmonary crackles | NCPE possible |
Hypoxia (low SpO2)
Common presentation.
Cyanosis
Common presentation.
Bradycardia
Common presentation.
Hypotension (usually mild)
Common presentation.
Hypothermia
Common presentation.
Decreased bowel sounds
Common presentation.
Pulmonary edema (non-cardiogenic, NCPE)
Common presentation.
Needle marks (IVDU)
Common presentation.
Red Flags
Life-Threatening Features
| Finding | Concern | Action |
|---|---|---|
| Apnea | Respiratory arrest | Immediate BVM + naloxone |
| Cyanosis | Severe hypoxia | Ventilate, high-flow O2 |
| Unresponsive | Profound overdose | Full resuscitation |
| Cardiac arrest | Hypoxic arrest | CPR + naloxone + ACLS |
| Pulmonary edema | NCPE | Ventilatory support |
| No response to naloxone | Polysubstance, wrong diagnosis | Reassess |
Complications
- Aspiration pneumonia
- Hypoxic brain injury
- Rhabdomyolysis (prolonged immobility)
- Compartment syndrome
- Death
Differential Diagnosis
Other Causes of Depressed LOC with Respiratory Depression
| Diagnosis | Features |
|---|---|
| Benzodiazepine overdose | Similar; may have mixed use |
| Ethanol intoxication | Alcohol on breath |
| GHB/Sedative-hypnotics | Similar presentation |
| Hypoglycemia | Low glucose; reverses with dextrose |
| Stroke | Focal deficits |
| Head trauma | Mechanism, focal findings |
| Sepsis | Fever, infection source |
| Hypothermia | Low temperature |
| Carbon monoxide | Exposure history |
Diagnostic Approach
Clinical Diagnosis
- Opioid overdose is a clinical diagnosis
- Classic toxidrome + response to naloxone = diagnostic
Bedside Assessment
| Test | Purpose |
|---|---|
| SpO2 | Assess hypoxia |
| Fingerstick glucose | Rule out hypoglycemia |
| Temperature | Hypothermia |
| ECG | Arrhythmia (methadone: QT prolongation) |
Laboratory Studies
| Test | Purpose |
|---|---|
| ABG/VBG | Hypercapnia, acidosis |
| BMP | Renal function (for rhabdomyolysis) |
| CK | Rhabdomyolysis |
| Urine drug screen | Confirms opioid (may miss fentanyl) |
| Acetaminophen, salicylate | Rule out coingestants |
| Lactate | Perfusion status |
Important Note on Urine Drug Screens
- Fentanyl often NOT detected on standard screens
- Do NOT rely on UDS to rule out opioid overdose
- Treat based on clinical presentation
Treatment
Principles
- Airway and ventilation first: BVM before/during naloxone
- Naloxone administration: Titrate to respiratory drive
- Supportive care: IV access, monitoring
- Observe for renarcotization: Opioid may outlast naloxone
- Address polydrug use: Other substances may require treatment
Airway Management
Before and During Naloxone:
- Head tilt-chin lift or jaw thrust
- Suction if needed
- BVM with 100% O2
- Avoid hyperventilation
Intubation Indications:
- Persistent apnea despite naloxone
- Unable to protect airway
- Aspiration
- Refractory hypoxemia
Naloxone (Narcan)
Mechanism: Competitive mu-opioid receptor antagonist
Dosing by Route:
| Route | Dose | Notes |
|---|---|---|
| Intranasal | 4 mg (2 mg per nostril) | Easiest prehospital |
| Intramuscular | 0.4-2 mg | If no IV |
| Intravenous | 0.04-0.4 mg initial | Start low in opioid-dependent |
| Subcutaneous | 0.4-2 mg | Alternative |
| Endotracheal | 2-4 mg (diluted) | If no other access |
Titration Strategy:
- Start low (0.04-0.1 mg IV) in opioid-dependent patients
- Goal: Restore respiratory drive, NOT full arousal
- Repeat every 2-3 minutes up to 10 mg
- If no response after 10 mg: Reconsider diagnosis
Fentanyl Overdose:
- May require higher and repeated doses
- Maintain ventilation while titrating
Observation Period
| Opioid Type | Duration |
|---|---|
| Short-acting (heroin) | 4-6 hours |
| Long-acting (methadone) | 12-24 hours |
| Fentanyl patch | Prolonged |
| Extended-release | 12-24+ hours |
Naloxone Infusion
Indication: Recurrent respiratory depression
Preparation: 2/3 of effective bolus dose per hour
- Example: 0.4 mg reversed → Infuse ~0.25-0.3 mg/hour
Managing Precipitated Withdrawal
| Symptom | Management |
|---|---|
| Agitation | Reassurance, benzodiazepines if severe |
| Vomiting | Antiemetics, protect airway |
| Diaphoresis | Supportive |
| Pain | Non-opioid analgesics if possible |
Supportive Care
| Intervention | Details |
|---|---|
| IV fluids | For hypotension, rhabdomyolysis |
| ECG | QT prolongation (methadone) |
| Monitoring | Continuous SpO2, cardiac |
| Chest X-ray | If aspiration suspected |
| CK monitoring | If prolonged immobility |
Disposition
Discharge Criteria
- Observed minimum 4-6 hours (longer for long-acting opioids)
- No recurrent respiratory depression after naloxone wears off
- Stable mental status
- No complications
- Safe discharge plan
- Naloxone kit prescribed
Admission Criteria
- Long-acting opioid ingestion
- Repeated naloxone doses required
- Naloxone infusion needed
- Respiratory complications
- Rhabdomyolysis
- Persistent altered mental status
- Unknown coingestants
ICU Admission
- Intubated patient
- Hemodynamic instability
- Severe complications
Leaving AMA
- Document capacity
- Provide naloxone kit
- Harm reduction counseling
- Provide addiction treatment resources
Harm Reduction at Discharge
- Prescribe naloxone (Narcan) for patient and family
- Overdose prevention education
- Offer treatment for opioid use disorder (buprenorphine initiation)
- Connect with addiction services
Patient Education
For Patient
- "You had an opioid overdose—the drug slowed your breathing and you could have died."
- "Naloxone saved your life."
- "Please carry naloxone and teach others how to use it."
- "Treatment for opioid use disorder is available and works."
Overdose Prevention
- Never use alone
- Start low after tolerance break
- Avoid mixing opioids with benzos/alcohol
- Test substances (fentanyl test strips)
- Carry naloxone
How to Use Naloxone (Teach Patient/Family)
- Check responsiveness
- Call 911
- Give naloxone (nasal spray or injection)
- Perform rescue breathing
- Place in recovery position
- Stay until help arrives
Warning Signs of Overdose
- Unresponsive, can't wake up
- Slow or stopped breathing
- Gurgling or snoring sounds
- Blue lips or fingertips
Special Populations
Opioid-Dependent Patients
- Start with lower naloxone doses (0.04-0.1 mg)
- Titrate to respiratory drive, not full alertness
- Avoid severe withdrawal (agitation, vomiting → aspiration)
Pregnancy
- Naloxone is safe and indicated
- May precipitate fetal withdrawal
- OB consultation
- Monitor for fetal distress
Pediatric
- Accidental ingestion common
- Naloxone: 0.1 mg/kg IV/IM/IN (max 2 mg)
- Repeat as needed
Cardiac Arrest
- Standard ACLS + Naloxone 2 mg IV/IO
- Airway and ventilation critical
- Continue CPR
Quality Metrics
Performance Indicators
| Metric | Target | Rationale |
|---|---|---|
| Naloxone given for suspected OD | 100% | Life-saving |
| Observation adequate for opioid duration | 100% | Prevent renarcotization |
| Naloxone kit prescribed at discharge | >0% | Harm reduction |
| OUD treatment offered | 100% | Reduce future overdoses |
Documentation Requirements
- Suspected substance and route
- Prehospital naloxone and response
- Hospital naloxone doses and response
- Observation period
- Discharge plan and harm reduction
Key Clinical Pearls
Diagnostic Pearls
- Classic triad: Depressed LOC + miosis + respiratory depression
- Miosis may be absent: Meperidine, coingestants, hypoxia
- UDS misses fentanyl: Treat clinically
- Response to naloxone is diagnostic
- Polysubstance is common: May have atypical features
Treatment Pearls
- Ventilate first, then give naloxone: BVM is life-saving
- Start low in dependent patients: Avoid severe withdrawal
- Titrate to respiratory drive, not consciousness
- Fentanyl may need high/repeated doses: Keep ventilating
- Renarcotization is real: Observe 4-6+ hours
Disposition Pearls
- Must observe after reversal: Opioid outlasts naloxone
- Prescribe take-home naloxone: To every overdose patient
- Offer OUD treatment: ED-initiated buprenorphine saves lives
- Document, counsel, connect: Comprehensive approach
References
- Boyer EW. Management of Opioid Analgesic Overdose. N Engl J Med. 2012;367(2):146-155.
- Schiller EY, et al. Opioid Overdose. StatPearls. 2024.
- Chou R, et al. Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings. Ann Intern Med. 2017;167(12):867-875.
- CDC. Opioid Overdose Prevention. 2024.
- SAMHSA. Opioid Overdose Prevention Toolkit. 2018.
- American College of Emergency Physicians. Naloxone Prescribing Policy Statement. 2019.
- D'Onofrio G, et al. Emergency Department-Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence. JAMA. 2015;313(16):1636-1644.
- UpToDate. Acute opioid intoxication in adults. 2024.