eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Opioids: Follow-up

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

Updated: Mar 2, 2009

Follow-up

Further Inpatient Care

• Because the half-life of naloxone is shorter than many opioids, in addition to the patients with history of exposure to the long-acting opioids, any patient who is exhibiting significant respiratory depression, recurrent sedation, or any other complicating factors of opioid ingestion should be admitted for a minimum of 12-24 hours of observation. Appropriate cardiorespiratory monitoring should be initiated until the effects of opioid toxicity subside.
• Most physicians recommend admission of any patient who requires a second dose of naloxone or who fails a 6-hour observation period in the ED. Some authorities recommend admission of patients with heroin overdose who present with significant respiratory depression caused by the increased risk of acute lung injury. However, this complication usually is evident within minutes of patient arrival. Thus, the patient who is asymptomatic following heroin overdose and has not demonstrated recrudescent toxicity during a 6-hour period of observation may be discharged safely.

Complications

• Acute lung injury (ALI) is a well-documented sequelae of heroin overdose. It also is associated with propoxyphene and methadone and almost always is present in fatal cases of opioid overdose. Although the etiology is still unclear, the putative culprit is hypoxia and hypoventilation. The clinical findings are similar to those found in cardiogenic pulmonary edema (eg, cyanosis, dyspnea, pink frothy sputum, rales, tachypnea, tachycardia). Unless fatal, the ALI clears in 24-48 hours with vigorous airway control and oxygen. Typical pulmonary edema therapy (eg, vasodilators, cardiac glycosides) is not necessary, and diuretics actually may contribute to severe hypotension.
• Intravenous drug abuse (IVDA) carries an additional list of complications. Cellulitis and abscesses are frequent complications of IVDA, usually with staphylococcal or streptococcal infection; however, anaerobic bacteria are observed occasionally. Hematogenous dissemination of bacteria, commonly to the epidural space, can cause spinal epidural abscess. This also may occur from spread of vertebral osteomyelitis. Staphylococcus aureus is the most common organism, but gram-negative bacilli may be observed. Osteomyelitis in IVDA is well known; if a patient with long-term IVDA presents with back pain, this diagnosis should be added to the differential.
• Site-specific sequelae, such as Horner syndrome from patients injecting into the neck region, may be observed. Particulate matter poses a threat because of embolic phenomena. Pulmonary emboli and peripheral emboli are two common complications. Thrombi initiated by vessel intimal damage from the needle may lead to similar syndromes. Inadvertent intra-arterial injection is another potential complication, possibly resulting in necrosis of the affected extremity. Intraneural injection may cause transient or permanent neuropathy.
• Endocarditis is the most serious complication of IVDA. The diagnosis is difficult to make in the ED and requires a high index of suspicion. Although either side of the heart may be affected, the right side is involved more commonly than the left. The tricuspid valve is the most frequent site of endocardial infection. Murmurs may be heard. Repeated septic pulmonary emboli may be the only presenting signs, usually involving S aureus as the etiologic agent. Left-sided endocarditis can result from a variety of pathogens, including Escherichia coli or Streptococcus, Klebsiella, or Pseudomonas species. Physical findings consistent with endocarditis are observed more frequently in left-sided disease than in right-sided disease.
• Pneumonia often is observed, particularly in the long-term abuser. Normal pathogens should be considered, but aspiration should be added in patients who have been unconscious. Tuberculosis should be added early to the differential diagnosis to avoid unnecessary exposure to health care workers and other patients and to ensure timely and adequate treatment.
• Rhabdomyolysis, with or without a compartment syndrome, should be sought in patients who have experienced a potentially long period of unconsciousness. Necrotizing fasciitis is a life-threatening infection that is characterized by septic necrosis. A dusky, erythematous, tender, confluent rash that spreads rapidly and is associated with fever, chills, tachycardia, tachypnea, and leukocytosis should prompt aggressive resuscitation, aggressive therapy, and surgical consultation.
• Certain medications can increase the risk of seizures; however, this is not common. Meperidine, propoxyphene, heroin, pentazocine, intravenous fentanyl, or sufentanil may cause grand mal seizures. Prolonged or unusual seizure activity should prompt reevaluation and consideration of intracranial injury or prolonged hypoxia.
• Withdrawal from opioids is a complication that is not observed universally. Generally, the withdrawal syndrome is not nearly as severe as that observed with barbiturates or alcohol. The onset depends on the drug of abuse, varying 8-12 hours with meperidine and 2-4 days with methadone. Symptoms include piloerection, lacrimation, yawning, sweating, rhinorrhea, nasal congestion, myalgia, emesis, diarrhea, and abdominal cramping. Symptoms peak between 36 and 48 hours and subside after 72 hours. Occasionally, symptoms last as long as 7-10 days. Treatment of withdrawal is symptomatic. The use of opioids on an outpatient basis to alleviate symptoms should be avoided. Alternate therapy may include clonidine, particularly when methadone is inappropriate, unsuccessful, or unavailable. The involvement of local substance abuse programs is key in avoiding long-term relapse.
• The administration of naloxone to patients with true opioid dependence may precipitate withdrawal. Signs and symptoms similar to typical withdrawal are observed. The onset of action is often within 5 minutes and subsides in 1-2 hours. Symptomatic treatment is recommended. Opiate withdrawal is not usually life-threatening. Opiate withdrawal has been reported after the use of buprenorphine, an agonist/antagonist.
• Adulterants, contaminants, and diluents are often added to illicit narcotics, often without the knowledge of the end user. In certain cases, these additives can be biologically active. In 1995, an epidemic of this nature was noted in New York City when heroin adulterated with scopolamine was circulated among heroin users. The intravenous use of the heroin was associated with severe anticholinergic toxicity; 370 cases were reported to local poison centers. Anticholinergic toxicity has also been reported as a complication of inhaled cocaine.⁷

Patient Education

• For excellent patient education resources, visit eMedicine's Drug Overdose Center, Poisoning - First Aid and Emergency Center, and Substance Abuse Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Narcotics Abuse, Activated Charcoal, Drug Dependence and Abuse, and Substance Abuse.

Miscellaneous

Medicolegal Pitfalls

• Illicit use of narcotics for recreation or the use of methadone for opioid dependence can be associated with co-ingestants including cocaine, benzodiazepines, tricyclics,⁸  or other substances. A 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.
• Failure to admit patients who were exposed to the long-acting opioids for observation
• Failure to recognize cardiac dysrhythmias due to sodium channel blockade (eg, propoxyphene)
• Failure to aggressively treat hypoxia and protect the airway
• Failure to ventilate the patient prior to administration of naloxone can precipitate acute lung injury
• Precipitation of opioid withdrawal, nausea, vomiting, and aspiration in patients who co-ingested CNS depressants
• Aspiration of charcoal in unconscious patients or in patients with precipitated withdrawal
• Use of pin-point pupils as a cardinal sign of opioid exposure
• Failure to recognize body stuffer and body packer and appropriately decontaminate it

Special Concerns

• 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. Two studies have evaluated inhaled morphine and found it similar in onset and duration.^9,10 One study evaluated aerosolized fentanyl and found similar plasma concentrations between intravenous and inhaled fentanyl.¹¹ However, all of these studies used a proprietary delivery mechanism and currently limits this potentially useful vehicle.
• Transdermal delivery of opioids, specifically fentanyl, is becoming a more prevalent 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) has been the subject of at least one report stating that overdose has required the use of naloxone. Although classified as a nonopioid analgesic, it 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 prolonged QRS on ECG 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.¹²
• 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.¹³

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