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Opioid Toxicity Treatment & Management

  • Author: Everett Stephens, MD; Chief Editor: Asim Tarabar, MD  more...
Updated: Jul 14, 2016

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 intraosseusly, intramuscularly, intranasally, or via endotracheal tube. Recommending these routes for routine use in an uncomplicated overdose is difficult because primary attention should be focused on airway maintenance. Intranasal (IN) route of administration of naloxone is of similar effectiveness to the (IM) route as a first-line treatment for isolated opioid overdose in the prehospital setting.[19]

In November 2015, the US Food and Drug Administraiton approved intranasal naloxone for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. The ready-to-use single-dose sprayer delivers a 4-mg dose by intranasal administration. Approval was based on pharmacokinetic studies that compared IM and intranasal dosage forms. The National Institute on Drug Abuse also was crucial to the approval by forming a public-private partnership by designing and conducting the clinical trials required to determine that the intranasal formulation delivered naloxone as quickly and as effectively as an injection.[20, 21]

In the case of a patient who is unconscious for unknown reasons, naloxone can be administered judiciously by emergency medical services (EMS) personnel; 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 central nervous system (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 typically 1-2 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, tricyclic antidepressants, ethanol), 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 a long-term intravenous heroin user with poor intravenous access), administer 2 mg of IM or intranasal naloxone. Clinical reversal occurs within 5-10 minutes. An intranasal dosage form (Narcan Nasal Spray) was approved in November 2015 that delivers 0.4 mg per single-dose spray.[20, 21]

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 non–opiate-addicted patient 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 to reverse toxicity from 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.

In a California report of an outbreak of fentanyl toxicity, one of the 18 patients had recurrent toxicity 8 hours after naloxone discontinuation and four required prolonged naloxone infusions (26-39 hours). The outbreak resulted from fentanyl-adulterated tablets that were purchased on the street as hydrocodone/acetaminophen and were virtually indistinguishable from authentic hydrocodone/acetaminophen tablets.[22]

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.

The 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 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 can be considered for removal of ingested drug packets in body packers, but data from controlled trials documenting improvement in clinical outcome after whole-bowel irrigation are lacking. Contraindications to whole-body irrigation include bowel obstruction, perforation, or ileus; hemodynamic instability; and a compromised unprotected airway.[23]

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, with two thirds of the initial successful dose given over 1 hour in a continuous infusion.

Case reports have surfaced of laypersons using buprenorphine/naloxone intravenously to reverse a heroin overdose.[24] Use of buprenorphine/naloxone has also been reported being used sublingually to reverse acute narcotic overdose. A combined overdose can potentially provide false reassurance to the practitioner, and caution should be exercised in patients receiving both medications.

Narcotic bowel syndrome is also a possible manifestation of opiate toxicity, characterized by abdominal pain that worsens with short- or long-term use of escalating doses of narcotic pain medication. It may occur in patients who have no preexisting gastrointestinal problems, either in acute settings in which opiates are administered for another injury or when the potential hyperalgesic effects of long-term opiate use are not recognized.

Methadone, a long-acting narcotic often used to attenuate withdrawal symptoms and used in narcotics recovery programs, also has extensive potential for abuse. It can be ingested orally or pills can be crushed and used intravenously or intranasally.[25] In studies by the US Centers for Disease Control and Prevention (CDC) from 1999-2010, methadone accounted for 4.5-18.5% of narcotics sold in the United States and was involved in 31% of opioid deaths in the 13 states involved in the study. In addition, CDC analysis of data collected from 2004-2009 revealed a significant increase in the nonmedical use of methadone alone or in combination with other drugs.[26]

In recent years, methadone has also been used increasingly for treatment of chronic pain. However, patients using methadone face serious risks related to risk of overdose and cardiac arrhythmias, and consequently require careful dose initiation and titration, along with diligent monitoring and follow-up.[27]



In March of 2015, the United States Department of Health and Human Services identified expanded use and distribution of naloxone as a priority area to reduce opioid use disorders and overdose. Both prescribers and pharmacists can play a role in overdose prevention.[28]

Coprescribing naloxone to primary care patients prescribed opioids for pain may reduce the risk of opioid toxicity. Coffin and colleagues reported that patients who received a naloxone prescription had 47% fewer opioid-related emergency visits per month in the 6 months after receipt of the prescription and 63% fewer visits after 1 year, compared with patients who did not receive naloxone. The study was not randomized; naloxone was more likely to be prescribed to patients receiving higher doses of opioids and those with an opioid-related ED visit in the past 12 months.[29]

A New Mexico program that allows pharmacists to prescribe naloxone offers a possible model for expanding access to opioid overdose prevention. Of the 133 naloxone rescue kits prescribed, the majority 89.5%) were first-time prescriptions. The most common reason for a prescription was patient request (56.4%), followed by a pharmacist's recommendation due to prescription high-dose opioids (28.6%) and history of opioid misuse or abuse (15.0%).[30]



Contributor Information and Disclosures

Everett Stephens, MD Assistant Clinical Professor, Department of Emergency Medicine, University of Louisville School of Medicine

Everett Stephens, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Mark Louden, MD Assistant Professor of Clinical Medicine, Division of Emergency Medicine, Department of Medicine, University of Miami, Leonard M Miller School of Medicine

Mark Louden, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

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