AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Pain is arguably the most common reason why patients seek treatment, especially in the ED. The modern physician wields many tools to relieve pain, the most potent of which are narcotics. The term narcotic specifically refers to any substance that induces sleep. In current practice, narcotic refers to any of the many opioids or opioid derivatives. In cultivation since approximately 300 BC, pure opium is a mixture of alkaloids extracted from the sap of unripened seedpods of Palaver somniferous (poppy). Opiates, such as heroin, codeine, or morphine, are natural derivatives of these alkaloids. The term opiate is often used (albeit slightly incorrectly) to refer to synthetic opiate derivatives, such as oxycodone, as well as true opiates.

Although opioids constitute a relatively small percentage of pure overdoses encountered in the ED, they merit particular attention because of the potential mortality they cause when untreated and the relative ease of reversing their effects. The notable prevalence of opioids in current prescribing patterns mandates that physicians maintain a high index of suspicion when treating the patient who is unconscious for unknown reasons.

Narcotic use and abuse have been reported as increasing in frequency in the past few years, a trend that has been blamed in increasing utilization of narcotics by medical personnel, as well as illicit drug abuse (Paulozzi, 2006). While increased availability certainly plays a role in narcotics abuse, the link between legitimate use and abuse is not well proven (Compton, 2006; Joranson, 2006).

Pathophysiology

Activation of opiate receptors results in inhibition of synaptic neurotransmission in the central nervous system (CNS) and peripheral nervous system (PNS). Opioids bind to and enhance neurotransmission at opiate receptors. The physiological effects of opioids are mediated principally through mu and kappa receptors in the CNS and periphery. Mu receptor effects include analgesia, euphoria, respiratory depression, and miosis. Kappa receptor effects include analgesia, miosis, respiratory depression, and sedation. Two other opiate receptors that mediate the effects of certain opiates include sigma and delta sites. Sigma receptors mediate dysphoria, hallucinations, and psychosis; delta receptor agonism results in euphoria, analgesia, and seizures. The opiate antagonists (eg, naloxone, nalmefene, naltrexone) antagonize the effects at all 4 opiate receptors.

Common classifications divide the opioids into agonist, partial agonist, or agonist-antagonist agents and natural, semisynthetic, or synthetic. Opioids decrease the perception of pain, rather than eliminate or reduce the painful stimulus. Inducing slight euphoria, opioid agonists reduce the sensitivity to exogenous stimuli. The GI tract and the respiratory mucosa provide easy absorption for most opioids.

Peak effects generally are reached in 10 minutes with the intravenous route, 10-15 minutes after nasal insufflation (eg, butorphanol, heroin), 30-45 minutes with the intramuscular route, 90 minutes with the oral route, and 2-4 hours after dermal application (ie, fentanyl). Following therapeutic doses, most absorption occurs in the small intestine. Toxic doses may have delayed absorption because of delayed gastric emptying and slowed gut motility.

Most opioids are metabolized by hepatic conjugation to inactive compounds that are excreted readily in the urine. Certain opiates (eg, propoxyphene, fentanyl, buprenorphine) are more lipid soluble and can be stored in the fatty tissues of the body. All opioids have a prolonged duration of action in patients with liver disease (eg, cirrhosis) because of impaired hepatic metabolism. This may lead to drug accumulation and opioid toxicity. Opiate metabolites are excreted in the urine, making urine toxicology useful. Renal failure also leads to toxic effects from accumulated drug or active metabolites (eg, normeperidine).

Frequency

United States

Opioids are prescribed widely, often in concert with other analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) or muscle relaxants. Given all toxicologic presentations, pure opioid ingestions are generally a small proportion of ED overdose cases. The etiology of overdoses presenting to an ED often reflects local prescribing tendencies. Polypharmacy overdoses that include opioids can be a challenge for even the most experienced clinician. Fortunately, pharmacologic reversal of the opioid component can assist in the diagnosis of these potentially complex cases.

Data from the Drug Abuse Warning Network (DAWN) from 1990-1996 indicated that the abuse of opioid analgesics (as recorded from the number of hospital ED visits) is low; compared with the abuse of other drugs, the abuse of opioid analgesics accounts for 3.8-5.1% of ED presentations.

In 1998, a total of 36,848 opiate exposures (pure and mixed preparations) were reported to US poison control centers, of which 1227 (3.3%) resulted in major toxicity and 161 (0.4%) resulted in death.

Mortality/Morbidity

The predominant cause of morbidity and mortality from pure opioid overdoses is respiratory compromise. Less commonly, pulmonary edema, status epilepticus, and cardiotoxicity occur in the overdose setting.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Pertinent history may be obtained from bystanders, family, friends, or EMS providers. Pill bottles, drug paraphernalia, or eyewitness accounts may assist in the diagnosis.
• Occasionally, a trial of naloxone administered by EMS is helpful to establish the diagnosis in the prehospital setting.
• Ingestion time, quantity, and co-ingestants are important aspects of the history and should be ascertained.

Physical

• Opioid toxicity characteristically presents with a depressed level of consciousness. Opiate toxicity should be suspected when the clinical triad of CNS depression, respiratory depression, and pupillary miosis are present. Drowsiness, conjunctival injection, and euphoria are seen frequently. Needle tracks are observed occasionally, depending on the route of abuse. Street users commonly use heroin and morphine by subcutaneous ("skin popping") and intravenous ("mainlining") injection. Raw opium usually is eaten or smoked, and sometimes the powder is sniffed ("snorted"). Transdermal opioid patches, such as fentanyl, also may produce toxicity.
• Other important presenting signs are ventricular arrhythmias, acute mental status changes, and seizures. Reliance on pupillary miosis to diagnose opioid intoxication can be misleading. If sufficiently severe, hypertension and pupillary dilation may present because of CNS hypoxia. Morphine, meperidine, pentazocine, diphenoxylate/atropine (Lomotil), and propoxyphene sometimes are associated with mydriasis or midpoint pupils.
• The respiratory effort frequently is impaired opiate intoxication. Both bradypnea and hypopnea are observed. Rates as slow as 4-6 breaths per minute often are observed with moderate-to-severe intoxication. The body retains the hypoxic drive to breathe but may be overridden by the CNS sedative effects of a severe overdose.
• Mild peripheral vasodilation may occur and result in orthostatic hypotension. However, persistent or severe hypotension should raise the suspicion of co-ingestants and prompt reevaluation. Opioids prolong GI transit times, possibly causing delayed and prolonged absorption. Initial tendencies for nausea and emesis are transient. Pink frothy sputum, muscular rigidity, dyspnea, and bronchospasm strongly suggest pulmonary edema.
• Nightmares, anxiety, agitation, euphoria, dysphoria, depression, paranoia, and hallucinations are encountered infrequently, mainly with high doses. Pruritus, flushed skin, and urticaria may arise because of histamine release. Generalized seizures are infrequent; they occur most commonly in infants and children because of initial CNS excitation. In contrast, seizure activity in adults is suggestive of meperidine or propoxyphene ingestions. Hearing loss has been associated with heroin and alcohol but is generally considered recoverable.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pontine hemorrhage

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Although widely available, drug screens in uncomplicated overdoses rarely alter clinical management. Drug screens are most sensitive when performed on urine. Positive results are observed up to 36-48 hours postexposure, but wide variations are possible depending upon test sensitivity, dose, route, and the patient's metabolism.
• In patients with moderate-to-severe toxicity, performing baseline studies, including a CBC, comprehensive metabolic panel, creatine kinase level, and arterial blood gas determinations, is appropriate.

Imaging Studies

• Obtain chest radiographs if pulmonary edema is suspected. Abdominal films may be helpful when evaluating a suspected body stuffer or body packer. Although the body stuffer (ie, a person who quickly swallows drug packages in an effort to hide evidence from police) is more prone to toxicity from hasty preparation, body packers (ie, individuals who carefully seal large amounts of drugs in packages and then swallow them for transport) have much larger amounts of drug liberated should their packages leak. Films suggestive of ingestion are helpful in making a diagnosis, but films negative for drug packages do not rule out potentially life-threatening ingestions.

Other Tests

• An ECG should be obtained on all patients with intentional overdose (possible cardiotoxic co-ingestants) or those with significant toxicity.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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, 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 remains 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 dose is 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.
• If an intravenous line cannot be established (eg, in long-term intravenous heroin user with poor intravenous access), administer 2 mg of IM 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. 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.
• 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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 versus 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. 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. The routine use of this agent is not recommended; its use should be individualized. Nalmefene is administered as an initial dose of 0.5 mg/70 kg IV or IM. A repeat dose of 1 mg/70 kg may be given after 2-5 minutes if necessary.

Drug Category: Antidotes for narcotic agonists

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

Drug Name	Nalmefene (Revex)
Description	Acts as competitive antagonist at opioid receptor sites, preventing or reversing respiratory depression, sedation, and hypotension induced by opiates. Commercial formulation in United States is available in a less concentrated form for postoperative use (blue label, containing 1 mL of nalmefene 100 mcg/mL). Higher concentration is available for treatment of opioid overdose (green label, containing 2 mL of nalmefene 1 mg/mL). Preferred route of administration is IV. If IV access not available, may be administered IM.
Adult Dose	0.5 mg/70 kg IV/IM; may repeat with 1 mg/70 kg in 2-5 min (0.1 mg/70 kg recommended if opioid dependency suspected); discontinue as soon as desired degree of opioid reversal achieved; if no result is noted after 1.5 mg/70 kg, additional doses are unlikely to provide therapeutic benefit
Pediatric Dose	0.25 mcg/kg IV/IM, followed by increments of 0.25 mcg/kg q2-5 min; discontinue as soon as desired degree of opioid reversal achieved
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use in neonates (clinical experience lacking); caution in cardiovascular disease; has been reported to cause acute pulmonary edema; although elimination half-life is longer than naloxone, patients should still be monitored closely for respiratory depression

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Because the half-life of naloxone is shorter than many opioids, any patient 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 noncardiogenic pulmonary edema (NCPE). 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

• NCPE 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. The clinical findings are similar to those found in cardiogenic pulmonary edema (eg, cyanosis, dyspnea, pink frothy sputum, rales, tachypnea, tachycardia). Unless fatal, the pulmonary edema 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. Naltrexone may be used as an adjunct in long-term avoidance.
• 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 (Weiner, 1998).

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

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. One study evaluated aerosolized fentanyl and found similar plasma concentrations between intravenous and inhaled fentanyl. 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 (Hutchkins, 2000).
• 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 (Olmedo, 2001).

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jan 30, 2007