eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Opioids: Treatment & Medication

Author: Everett Stephens, MD, Assistant Clinical Professor, Department of Emergency Medicine, University of Louisville
Contributor Information and Disclosures

Updated: Mar 2, 2009

Treatment

Prehospital Care

Adequate prehospital care hinges on aggressive airway control. Expedient endotracheal intubation is indicated for patients who are unable to protect their airway.

• In patients lacking spontaneous respirations, orotracheal intubation is preferred. If advanced life support (ALS) is available, intravenous naloxone (Narcan) may be given to reduce respiratory depression. Exercise caution when giving naloxone in the confines of an ambulance because it can transform a peacefully sleeping patient into an agitated belligerent one. If naloxone is used for a suspected long-term opiate user, only an amount sufficient to return spontaneous respirations is recommended. Judicious application of restraints in a potentially violent patient is advisable in close quarters.
• Alternate routes of naloxone administration include intramuscularly, intranasally, via endotracheal tube, or intralingually. Recommending these routes for routine use in an uncomplicated overdose is difficult because primary attention should be focused on airway maintenance. In the setting of a patient who is unconscious for unknown reasons, naloxone can be administered by EMS judiciously; adequate precautions against violent patients should be taken (eg, application of restraints concurrent or before naloxone administration). Aggressive airway control must take precedence over pharmacologic reversal because the vast majority of morbidity and mortality results from respiratory depression.
• In some instances, treatment in the field with naloxone results in an oriented patient refusing further treatment and transport to the hospital for evaluation and observation. This may require EMS or responsible friends to stay with the patient until they can ensure the continued health of the patient. In these cases, ED physicians should provide direct medical control; it is recommended that ED physicians talk to patients by phone to ensure that they fully understand the risks associated with refusing transport and further evaluation and treatment.

Emergency Department Care

Airway control and adequate oxygenation remain the primary intervention if not already established by EMS. Endotracheal intubation is indicated in patients who cannot protect their airway.

• If occult trauma is suspected, implement cervical spine immobilization. As with all unknown unconscious patients, determination of serum glucose level is mandated.
• Administer naloxone for significant CNS and/or respiratory depression. The usual dose administered by EMS is between 0.4 and 2 mg in the adult and 0.1 mg/kg in the child or infant. In suspected habituated opiate users, if the situation allows, slowly administer 0.1-0.4 mg of IV aliquots every 1-2 minutes for a more controlled and partial reversal of opiate effect. Assisted bag-valve mask breathing can be provided until the patient is ventilating adequately. The onset of effect following IV naloxone administration is 1-3 minutes; maximal effect is observed within 5-10 minutes. A repeat dose is indicated for partial response and can be repeated as often as needed.
• To avoid precipitous withdrawal (nausea, vomiting, agitation) and consequent aspiration, especially in patients suspected of taking another CNS depressant(s) (eg, benzodiazepines, TCAs, ETOH), recommended reversal practice is to start with a very low dose of naloxone of 0.05 to 0.1 mg and titrate it up gradually until reversal of respiratory depression is achieved.
• If an intravenous line cannot be established (eg, in long-term intravenous heroin user with poor intravenous access), administer 2 mg of IM or intranasal naloxone. Clinical reversal occurs within 5-10 minutes.
• The clinical half-life of naloxone is roughly 20-60 minutes, with a duration period of 2-3 hours. Some variation exists because of dosage and route.
• In the patient with nonopiate addiction who has recrudescent opiate toxicity following naloxone administration, naloxone may be administered safely and effectively by continuous intravenous infusion. This practice is dangerous for patients who have opiate addiction because of the concern for precipitating opiate withdrawal. The dose recommended for constant infusion is two-thirds to 1 full reversal dose as a drip rate per hour. Naloxone may be mixed in isotonic saline solution or 5% dextrose in water (D5W) to the desired concentration. This drip may be titrated to the desired effect. Constant infusions are particularly useful for overdoses of long-acting opioids, such as methadone.
• Larger doses of naloxone may be required for diphenoxylate/atropine (Lomotil), methadone, propoxyphene, pentazocine, and the fentanyl derivatives. Repeat doses of 2 mg can be given every 3-5 minutes as needed, up to a total of 10 mg. Reconsider the diagnosis if the patient fails to respond after 10 mg.
• A gradual accumulation of naloxone is preferential to isolated larger doses. The precipitation of withdrawal, while not life threatening, is disconcerting to the patients and the staff. The best way to reverse respiratory depression and coma, while avoiding precipitant withdrawal, is by gradual measured administration of naloxone.
• Activated charcoal is the GI decontamination method of choice for patients with opiate intoxication following ingestion. Because of impairment of gastric emptying and GI motility produced by opiate intoxication, activated charcoal still may be effective when patients present late following ingestion. Decontamination with activated charcoal should be attempted in all symptomatic patients (as long as it is not contraindicated), regardless of the time of ingestion in relation to hospital presentation. Airway has to be protected (ET tube, adequate gag reflex, appropriate level of consciousness) prior to administration of charcoal in order to prevent converting relatively benign opioid overdose into catastrophic charcoal lung aspiration. Although orogastric lavage is not often necessary, it may be considered in addition to activated charcoal when patients present obtunded within 1 hour of ingestion.
• Whole-bowel irrigation should be administered in body packers.
• In a few isolated cases of pure opioid toxicity, patients may fail to respond to aggressive airway control and high-dose naloxone. In the absence of other etiology, prolonged hypoxia may cause a terminal state unresponsive to naloxone. Buprenorphine (Buprenex) has been reported to respond only partially to naloxone.
• Cardiac arrest in the setting of pure opioid toxicity is almost certainly an indication of severe hypoxia and poor neurologic outcome.
• In the pediatric setting, the dose of naloxone is 0.1 mg/kg in patients who weigh less than 20 kg or are younger than 5 years. In patients who weigh more than 20 kg or are older than 5 years, use 0.1-2 mg/dose. Doses may be repeated up to a maximum cumulative dose of 10 mg. Repeat doses may be indicated for relapses caused by the comparatively longer duration of action of most opioids compared with naloxone.
• A naloxone drip may be instituted, administering two thirds of the initial successful dose over 1 hour in a continuous infusion.

Medication

Naloxone is a pure competitive antagonist of opioid receptors and lacks any agonist activity. Adverse effects are rare at therapeutic doses. Naloxone can be given IV, ET, IL, or IM. The use of intranasal naloxone has also been reported. By the ET, IV, or IL route, the onset of action of naloxone is 1-2 minutes. A second dose can be repeated every 2-3 minutes. Discontinue treatment as soon as the desired degree of opioid reversal is achieved. Higher doses may be necessary to reverse methadone, diphenoxylate, propoxyphene, butorphanol, pentazocine, nalbuphine, designer drugs, or veterinary tranquilizers.

Nalmefene (Revex) and naltrexone are newer opioid antagonists that have longer half-lives than naloxone (4-8 h and 8-12 h vs 1 h). The routine use of a long-acting antagonist in the patient who is unconscious for unknown reasons is not recommended. In addition, the fear of precipitating prolonged opioid withdrawal likely prevents the widespread use of these antagonists for emergency reversal of opiate intoxication. In theory, nalmefene may be useful for persons with opiate addiction who accidentally overdose on heroin but refuse to stay for continued observation after an initial reversal dose of naloxone. However, this practice can be fatal to the patient who is discharged and is trying to use an excessive dose of opioids in order to overcome the effects of nalmefene and experience dysphoria. The routine use of this agent is not recommended.

Antidotes for narcotic agonists

These agents reduce or eliminate the effects of opioid agents on their receptors.

Naloxone (Narcan)

Historically, the most commonly used opioid receptor antagonist in the United States. Used to reverse opioid intoxication. Prevents or reverses opioid effects (hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors. Half-life is 1 h.
If patients do not respond to multiple doses of naloxone, consider alternative causes of unconsciousness.

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