Opioid Toxicity Differential Diagnoses

Updated: Oct 06, 2017
  • Author: Everett Stephens, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
  • Print
DDx

Diagnostic Considerations

Illicit use of narcotics for recreation or the use of methadone for opioid dependence can be associated with co-ingestants including cocaine, benzodiazepines, cyclic antidepressants, [25] or other substances. Suspicion of co-ingestants should be nurtured when the patient's clinical course does not conform closely to known opiate effect profiles, especially given the cardiac toxicity of the tricyclics.

The delivery of narcotics via inhalation is a relatively new methodology with limited mechanism but potentially significant clinical impact. Butorphanol, a combined agonist-antagonist, is currently available in an intranasal form but is not entirely aerosolized. Fentanyl is available in an intranasal form that is indicated for breakthrough cancer pain in adults who are tolerant to opioid therapy for their underlying persistent cancer pain.

Transdermal delivery of opioids, specifically fentanyl, has become a mechanism of analgesia. A prolonged time to peak effect and a long elimination half-life are characteristics of this delivery mechanism. Because of the relatively prolonged onset, this route is rarely the sole precipitant of overdose. However, transdermal patches can contribute to the toxicity of orally or parentally administered opioids.

Dextromethorphan is widely available in many over-the-counter cough preparations, which increases the chances of abuse. It is an opioid derivative with specific antitussive properties. Although high doses may cause sedation, the other components of the preparation (eg, antihistamines) often require additional treatment. Observation for 3-4 hours in uncomplicated overdoses is sufficient. One documented case of respiratory depression in an adult overdose was reversed with naloxone. Administration of dextromethorphan or meperidine in patients taking monoamine oxidase inhibitors (MAOIs) should be strictly avoided. Serious manifestations of the serotonin syndrome may result, in some cases, compromising cardiovascular function.

Tramadol (Ultram), although classified as a nonopioid analgesic, uses a dual mode of action through opioid and nonopioid receptors. Tramadol has a relatively long duration of action of 5-6 hours. In a known overdose of tramadol, a trial of naloxone is suggested; however, repeat doses of naloxone may be required.

Efforts by back-room chemists have brought very potent and potentially deadly opioid derivatives to the street. Normal toxicologic screens cannot detect such designer drugs because of the extremely low dose involved. Synthetic fentanyl derivatives, such as china white (alpha-methylfentanyl), are extremely potent. Abusers have been found dead with needles still in their arms. Even more powerful derivatives, such as 3-methylfentanyl, have been synthesized and are estimated to be 2000 times more potent than morphine. These drugs may require unusually high doses of naloxone to reverse. Deaths from such highly potent drugs often occur in clusters as the new product or batch reaches the street for use.

Pentazocine is a combined agonist-antagonist. Although the effects of pentazocine can be reversed by naloxone, high doses (10-15 mg) of naloxone frequently are required. Similarly, propoxyphene can be reversed by high doses of naloxone. Propoxyphene is known for its rapid onset of toxic effects, and prolonged observation is recommended. Cardiac effects also may be observed with propoxyphene toxicity because of its quinidinelike effects. Naloxone is not effective in treating propoxyphene-induced arrhythmias.

Propoxyphene and its metabolite norpropoxyphene impair cardiac conduction and contractility. These agents are quinidinelike type IA antidysrhythmic agents that block fast-sodium channels. Clinical effects may include sinus bradycardia, prolonged PR, QRS, and QTc intervals on ECG; hypotension; bundle-branch blocks; and ventricular dysrhythmias. Sodium bicarbonate is effective treatment and recommended for patients who are hypotensive or have a prolonged QRS segment following propoxyphene ingestion.

The combination drug diphenoxylate/atropine (Lomotil) can produce signs of anticholinergic toxicity in addition to opioid toxicity. Because of the prolonged duration of action, respiratory depression may occur as late as 14 hours postingestion. Any child younger than 5 years who has ingested Lomotil should be observed for up to 24 hours. Adults and children older than 5 years should be given gastric decontamination and observed for 6 hours in the ED. They may be discharged home if asymptomatic.

The transport of illegal drugs may involve so-called body packers, or people who intentionally ingest packets of drugs for purposes of evading police. These packets are usually well wrapped, but they can still cause unintended complications such as intestinal obstruction. Three cases of intestinal perforation in this setting have been reported. [26]

In contrast to body packers, so-called body stuffers are created in the stress of pursuit, usually by police. In an effort to avoid prosecution, hurriedly packaged drugs are ingested without the careful preparation characteristic of body packers. Such persons who body stuff are much more likely to experience the consequences of drug overdose and should be treated very aggressively. Surgical removal may be indicated in those patients who are symptomatic or show evidence of obstruction. Even aggressive surgical treatment is not without sequelae. [27]

Differential Diagnoses