DESCRIPTION

• Pharmaceutical preparations for oral administration include morphine (MS-Contin, Roxanol), hydromorphone (Dilaudid), levorphanol (Levo-Dromoran), methadone (Dolophine), meperidine (Demerol), fentanyl (Sublimaze), codeine, hydrocodone (Vicodin, Hycodan), dihydrocodeine (Synalgos-DC), paregoric, oxycodone (Percocet, Percodan), propoxyphene (Darvon), and oxymorphone (Numorphan). Numerous other products are available and many are combination products containing acetaminophen or aspirin, and occasionally caffeine.
• Heroin is covered in a separate chapter.

FORMS AND USES

• Narcotics are used for the oral treatment of pain.
  • Morphine is administered at 2.5 to 20 mg orally every 2 to 6 hours as required.
  • Hydromorphone is administered at 2 to 4 mg orally every 4 to 6 hours as required.
  • Meperidine is administered at 50 to 100 mg orally every 3 to 4 hours as required.
• Narcotics are also present in selected cough preparations.

TOXIC DOSE

• Codeine. The lethal dose for adults is 7 to 14 mg/kg.
• Hydrocodone. The lethal dose for adults is 100 mg.
• A tolerant individual may require much larger doses for toxicity.
• Children may have unusual sensitivity to opioids and may develop toxicity near the therapeutic dose.

PATHOPHYSIOLOGY

• The primary effects in overdose are mediated by µ, kappa-, and sigma- opioid receptors.
• µreceptor stimulation produces agonist-type supraspinal analgesia, respiratory depression, euphoria, and decreased gastrointestinal motility.
• kappa-receptor stimulation produces agonist-antagonist type spinal analgesia, sedation, and miosis.
• sigma-receptor activation produces antagonist activity such as dysphoria and psychotomimetic effects (e.g., hallucinations).
• Opioids lose receptor specificity when given at high doses.
• The onset of effects may occur immediately after intravenous injection or inhalation, minutes to hours after ingestion.
• Direct pulmonary injury may produce noncardiogenic pulmonary edema.

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following exposure are typically moderate, with death occurring from respiratory depression.

CAUSES

• Use is typically intentional in adults, accidental in children.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

Persistent pain (e.g., severe toothache or headache) may lead to overuse.

DRUG AND DISEASE INTERACTIONS

• Narcotics potentiate CNS depression of sedative-hypnotic drugs and other respiratory depressants.
• Meperidine and monoamine oxidase inhibitors may cause serotonin syndrome.
• Methadone serum levels are decreased by chronic use of carbamazepine, phenytoin, and rifampin, resulting in withdrawal.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category. Pregnancy risk is category B for nearly all narcotics; however, the risk factor is category D for prolonged use or in high doses at term.
• Category D. Despite positive evidence that human fetal risk exists, benefits in certain situations (e.g., life-threatening situations or serious diseases) may make use of the drug acceptable despite its risks.
• Newborns of addicted women often suffer symptoms of withdrawal.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Other toxicologic causes of miosis include cholinergic agonist drugs such as pilocarpine or the organophosphate insecticides, but these also may cause salivation, lacrimation, urination, defecation, and bronchorrhea.
• Other toxicologic causes of CNS and respiratory depression are numerous; of note, olanzapine appears to produce miosis and altered mental status.
• Other causes. Pontine hemorrhage (which occurs rarely) may cause sudden loss of consciousness, pinpoint pupils, and cardiovascular instability.

SIGNS AND SYMPTOMS

Rapid onset of miosis, respiratory depression, and decreased mental status suggest opioid overdose.

Vital Signs

Hypothermia or hyperthermia and hypotension may develop.

HEENT

The pupils are normally pinpoint but may be dilated when acidosis or hypoxia is severe.

Cardiovascular

• Hypotension, bradycardia, pulmonary hypertension, cardiac dysrhythmia, and cyanosis can occur with all opioids.
• Norpropoxyphene, the metabolite of propoxyphene, may cause heart block, conduction delays, and ventricular dysrhythmia.
• Pentazocine overdose can cause ventricular dysrhythmia.

Pulmonary

• Respiratory depression, noncardiogenic pulmonary edema, respiratory arrest, hypoxia, bronchoconstriction, acute asthma, and pneumonitis may occur.
• Butorphanol overdose is associated with pulmonary hypertension induced by naloxone administration.

Gastrointestinal

Constipation, decreased intestinal motility, and ileus occur commonly.

Renal

Urinary retention, myoglobinuria, proteinuria, glomerulonephritis, acute tubular necrosis, and nephropathy may occur during chronic abuse.

Musculoskeletal

Rhabdomyolysis may cause acute renal failure.

Neurologic

• Lethargy and coma are common and responsive to naloxone.
• Normeperidine, a metabolite of meperidine, can cause tremors and seizures.
• Seizures can occur with propoxyphene or high doses of fentanyl.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests may be needed for asymptomatic patients.

Recommended Tests

• Serum electrolytes, BUN, and creatinine are recommended to assess the causes of altered mental status, seizure, or cardiac effects.
• Serum creatine kinase may be elevated due to repeated seizures or rhabdomyolysis.
• An ECG and continuous cardiac monitoring for symptomatic patients are advised to detect the effects of cardiotoxic medication such as propoxyphene.
• Urinalysis is used to assess injury from rhabdomyolysis or hypotension.
• Serum acetaminophen and aspirin levels should be checked in an overdose setting to detect occult ingestion.
• Head CT, blood and CSF cultures, and lumbar puncture should be performed as needed to rule out other causes of coma or seizures.
• Chest radiography is used to evaluate persistent hypoxia.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on airway management, naloxone administration, and hemodynamic support.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Seizures, dysrhythmia, hypotension, acidemia, or other severe effects are present.
• Toxic effects are not consistent with narcotic poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• The patient or caregiver seems unreliable.
• Any toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient admission to an intensive care setting is warranted for patients with persistent altered mental status, persistent hypoxia, seizures, hypotension, or dysrhythmia.

DECONTAMINATION

Out of Hospital

Emesis should not be induced because coma or seizure may develop abruptly.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

• Naloxone should be administered for respiratory depression from known opioid overdose.
  • The dose is 2.0 mg intravenous push; if the patient does not respond, the dose can be repeated in 2.0-mg increments to a total dose of 10 mg.
  • Although these methods are less desirable, naloxone also may be administered by endotracheal, intramuscular, intralingual, intraosseous, or subcutaneous injection.
  • If a reversal response occurs, patients should be observed for 4 hours after the final dose to avoid resedation.
  • Patients with persistent or recurrent effects may be treated with a constant infusion of naloxone.
• Nalmefene may be substituted for naloxone if prolonged antagonist effect is desired. The starting dose is 0.5 mg by intravenous push; if no effect is seen, an additional 1 mg may be given.
  • Higher doses of nalmefene appear to give prolonged activity; 1.5 mg of nalmefene blocks opioid activity up to 8 hours.
  • If repeated dosing is required, the patient should be admitted to an ICU setting.

ADJUNCTIVE TREATMENT

Pulmonary Edema

• Adequate ventilation and oxygenation should be maintained.
• Positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) should be considered if adequate oxygenation cannot be maintained on 60% FiO₂.
• Care should be taken to avoid fluid overload.

Hypotension

• The primary treatment is correction of narcotic effects and dysrhythmia.
• Also, 10 to 20 ml/kg 0.9% saline should be administered, and the patient should be placed in the Trendelenburg position and given a vasopressor, if needed.

Seizures

• A patent airway must be ensured.
• A benzodiazepine is administered for initial control. If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Pulmonary Edema
  • Hypotension
  • Seizures

PATIENT MONITORING

• Respiratory and cardiac function should be monitored continuously.
• Possible complications include renal failure and CNS injury secondary to prolonged seizure, and myocardial or CNS injury from hypoxia.

EXPECTED COURSE AND PROGNOSIS

The prognosis is determined by the hypoxic injury that occurred before treatment or the muscle injury from lying on an extremity for a prolonged period.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. For most narcotics, asymptomatic patients may be discharged following decontamination, a 6-hour observation period, and psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged after mental status, ECG, and vital signs return to normal, and decontamination and psychiatric evaluation are completed, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

• Pinpoint pupils may be obscured by hypoxia or agents that produce mydriasis, such as scopolamine.
• Many tablets containing narcotics also contain acetaminophen or aspirin.

FOLLOW-UP

Discharge of the patient immediately after naloxone treatment may allow the recurrence of respiratory depression outside of the emergency department.

Section Outline:

• DIAGNOSIS
• FOLLOW-UP

Poisoning by analgesics, antipyretics, and antirheumatics: opiates and related narcotics.

See Also: SECTION II, Body Packer/Body Stuffer, Hypotension, Pulmonary Edema, and Seizures chapters; SECTION III, Naloxone chapter; and SECTION IV, Heroin, Acetaminophen, and Salicylates chapters.

RECOMMENDED READING

Goldfrank LR, Weisman RS. Opioids. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. Goldfrank's toxicologic emergencies, 6^th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Robin Millin

Reviewer: Richard C. Dart