II. Indications: Opioid Overdose management

  1. Respiratory Depression (Hypoxia, apnea)
  2. Severe sedation (e.g. comatose)

III. Epidemiology

  1. Opioid Overdose is the leading cause of death in U.S. for those under age 50 years old
  2. Opioids have been implicated in 16,000 deaths per year in U.S. as of 2013
    1. (2015) MMWR Morb Mortal Wkly Rep 64(1): 32 [PubMed]

IV. Risk Factors

  1. Morphine Equivalents >50 mg/day doubles risk, contrasted with <20 mg/day (e.g. Hydrocodone 5 mg every 6 hours)

VI. Findings: Symptoms and Signs

  1. Altered Level of Consciousness (CNS depression or sedation)
    1. Coma
    2. Lethargy
    3. Stupor
  2. Miosis
    1. Miosis consistently occurs even after tolerance and Chronic Opioid use
    2. Exception: Demerol causes Mydriasis
  3. Injection site track marks
    1. See Skin changes suggestive of chemical dependency
  4. Hypotension
  5. Pulmonary Edema
  6. Respiratory depression
  7. Seizures

VII. Precautions

  1. Close monitoring must be continued after antidote
    1. Opioid Half-Life might exceed that of Naloxone
  2. Consider Very Low Dose Naloxone Protocol
    1. Indicated for Cancer Pain or Chronic Pain (prevents severe Rebound Pain)
  3. Heroin and other Illicit Drugs are often adulterated with synthetic Opioids at inconsistent doses
    1. Fentanyl (most common)
    2. Alpha-methylfentanyl
    3. Carfentanil
  4. Other adulterants mixed with Opioids
    1. Xylazine
      1. Clonidine-like agent added to Opioids to intensify and prolong euphoria
      2. Increases risk of fatal Overdose and has a duration of action from 8 to 72 hours
      3. May result in apnea, Bradycardia, Hypotension refractory to Naloxone
      4. Vega (2023) Am Fam Physician 108(3): 229-30 [PubMed]
  5. Children
    1. Buprenorphine effects in children is similar to that of full opioid Agonists

VIII. Differential Diagnosis: Suspected Opioid Overdose not reversing with Naloxone

  1. Clonidine Overdose
  2. Drugs of Abuse often have very high potency
    1. Krokodil (use Naloxone 2 mg)
    2. Fentanyl derivative (may require Naloxone up to 10 mg )

IX. Labs

  1. Toxicology labs
    1. See Toxin Ingestion
  2. Creatinine Phosphokinase (CPK)
    1. Risk of Rhabdomyolysis

X. Diagnostics

  1. Electrocardiogram
    1. Certain Opioids (i.e. Methadone) will prolong QTc Interval

XI. Management: General

  1. See Unknown Ingestion
  2. ABC Management
    1. Ensure adequate respiration and oxygenation
    2. Consider 1 or 2 Nasal Trumpets (Nasopharyngeal Airways)
    3. Consider Endotracheal Intubation if persistent respiratory depression despite Naloxone
    4. Monitoring
      1. EtCO2 and Oxygen Saturation
        1. Oxygen Saturation alone is insufficient
        2. Supplemental Oxygen can result in Apneic Oxygenation with normal O2Sat but rising carbon dioxide
  3. Antidotes
    1. Naloxone (Narcan)
      1. See Naloxone for dosing protocols for adults and children as well as per clinical circumstance
      2. See doses below (or see Naloxone)
      3. Indicated for hypoventilation <9 breaths/min or increased EtCO2
        1. Not indicated for a mentating patient with normal Vital Signs
      4. Caution in Opioid Dependence (risk of Opioid Withdrawal)
      5. Caution in pregnancy (risk of Preterm Labor, Hypertensive Crisis, neonatal abstinence syndrome)
    2. Consider longer acting antidotes for long acting Opioids (Oxycontin, MS Contin, Methadone, Zohydro)
      1. Naloxone continuous infusion
      2. Nalmefene (Revex)
        1. Caution using Nalmefene due to risk of prolonged Opioid Withdrawal
  4. Observation Stay indications
    1. Young Children (age <5 years old)
    2. Long acting Opioid
    3. Intentional Overdose (and evaluate for psychiatric admission)
  5. Observe in Emergency Department for at least one hour (some prefer 4 hour observation)
    1. Naloxone effect lasts 45 minutes (opiod effects may last longer)
    2. Observe longer for long acting agents (e.g. Methadone) or suspected dual ingestion (e.g. with Fentanyl)
    3. Monitoring after heroin Overdose
      1. May discharge if asymptomatic for 3-6 hours after Overdose and >1 hour after last dose of Naloxone
      2. Deblieux and Swadron in Majoewsky (2012) EM:RAP 12(6): 2
      3. Vilke (2003) Acad Emerg Med 10(8): 893-6 [PubMed]
      4. Willman (2017) Clin Toxicol 55(2): 81-87 +PMID: 27849133 [PubMed]

XII. Management: Naloxone (Narcan)

  1. Adults (and children age >5 years, weight >20 kg)
    1. Initial
      1. No respiratory depression: 0.1 to 0.4 mg IV, IO or IM
      2. Respiratory depression: 1 to 2 mg IV, IO or IM
      3. Naloxone may also be administered intranasal or via Endotracheal Tube
      4. Alternative initial protocol (minimizes withdrawal effects in longterm use)
        1. Very Low Dose Naloxone Protocol (slow titration method)
        2. Prepare Naloxone 1 ml (0.4 mg/ml ampule) in 9 ml Normal Saline (0.04 mg/ml)
        3. Inject at 1-2 ml/dose (0.04 mg/ml) titrating and observe for increased responsiveness
    2. Next, if no response or incomplete response (synthetic Opioids may require high Naloxone dose)
      1. Give 2 mg IV or IM every 3-5 minutes to a total of 10-20 mg
    3. Infusion
      1. Naloxone 2 mg in 500 ml D5W or NS (0.004 mg/ml) titrating to response
  2. Children (age <5 years or weight <20 kg or 44 lbs)
    1. Initial
      1. Respiratory depression: 0.1 mg/kg IV or IM
      2. No respiratory depression: 0.01 mg/kg IV or IM
    2. Next, if no response or incomplete response
      1. Give 0.1 mg/kg IV or IM every 2 to 3 minutes as needed

XIII. Complications

  1. Death
    1. More than 50,000 Opioid Overdose deaths in 2016 (U.S.)
    2. Non-fatal Overdose is associated with a 10% mortality within the next year
  2. Pulmonary Edema
    1. Typically follows Opioid reversal (unclear etiology)
    2. May require Endotracheal Intubation

XIV. Prevention: Prescribed Chronic Opioids

  1. Best prevention is to keep Opioid naive patients naive
    1. See Emergency Department Pain Management
  2. Identify alternatives to Opioids in Chronic Pain Management
  3. Prescribe Home Naloxone in case of Overdose or for those on high dose Opioids
  4. Keep equianalgesic doses in mind when administering ParenteralOpioids
    1. Hydromorphone (Dilaudid) 1 mg is equivalent to up to 10 mg of Morphine Sulfate
  5. Exercise caution when combining agents that blunt respiratory drive (e.g. Opioids with Benzodiazepines)
    1. Benzodiazepines
    2. Muscle relaxants
  6. Analgesic tolerance occurs before tolerance to respiratory depression
    1. Opioid tolerant patients are at increased risk of apnea due to high dose Opioids
  7. Exercise caution in already compromised respiratory status
    1. COPD
    2. Sleep Apnea

XV. Prevention: Opioid Abuse

  1. See Opioid Abuse for protocol
  2. Prescribe Home Naloxone
  3. Needle exchange program
  4. Infectious disease screening (e.g. HIV, Hepatitis C, as well as STDs)
  5. Offer Chemical Dependency treatment
    1. Treatment is often declined, as patients walk out of ED prior to discharge process
      1. Reassure patient that the Naloxone withdrawal wears off in one hour
      2. Offer Opioid Withdrawal symptomatic management (e.g. Clonidine, Ondansetron)
      3. Patient waiting until withdrawal symptoms subside opens window for discussion of Buprenorphine, prevention
      4. Non-fatal Opioid Overdose patients are at very high risk that the next Overdose will be fatal
    2. Sample script (modified from Reuben Strayer, MD, in reference below)
      1. I know you have a complicated life and wish things could be different
      2. When you are ready to make a change, we can help
      3. Come back anytime; we are here all day, every day
    3. Buprenorphine (Suboxone) prescription
      1. See Opioid Abuse
      2. Requires practitioner waiver (X DEA number)
      3. See Buprenorphine for precautions (including precipitating withdrawal)
      4. Reframe Buprenorphine for addiction, as similar to Insulin in Diabetes Mellitus

XVI. References

  1. Mason and Armenian in Herbert (2018) EM:Rap 18(7):8-9
  2. Strayer in Herbert (2020) EM:Rap 20(6):10-2
  3. Strayer and Swaminathan in Herbert (2018) EM:Rap 18(9): 3-6
  4. Swaminathan, Hayes, LaPoint in Herbert (2017) EM:Rap 17(5): 2-3
  5. Vega (2024) Am Fam Physician 109(2): 143-53 [PubMed]

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