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Authors: Gary Hals, MD, PhD, Attending Physician, Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Columbia, SC; William Richardson, MD, Resident Physician, Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Columbia, SC.
Peer Reviewer: Albert C. Weihl, MD, FACEP, Director for Education, Section of Emergency Medicine, Yale University School of Medicine, New Haven, CT.
In emergency departments (EDs) across the country, patients are treated nearly every day for complications resulting from drug abuse; drug abuse, by definition, is illicit. Emergency physicians must treat patients who present with altered mental status caused by drug abuse, intentional and accidental overdoses, and withdrawal syndromes, as well as patients requesting help for drug addiction and its related depression. The drug-seeking patient can rely on the ED as a source of his or her drugs. Attempting to identify these patients from the "legitimate" ED patient population can cause considerable stress for the emergency physician. Patients abusing drugs also are delivered to the ED by authorities for medical clearance before psychiatric admission or jail stays.
Traumatic injuries related to drug abuse are reaching epidemic proportions. Each year, thousands of patients suffer from trauma as a result of motor vehicle accidents in which the driver is "under the influence." Alcohol use is a well-known factor in motor vehicle accidents, with 40-70% of traffic fatalities related to alcohol use.1,2 However, illicit drug use also is highly correlated with traumatic injury. A report on 516 major trauma patients from 1998 in Los Angeles found that 71% of patients had positive screens for drugs and/or alcohol, with 42% of patients having positive drug screens.3 Another series of 169 patients from Philadelphia demonstrated an even greater correlation, with 74% of the trauma patients having positive drug screens.2 The frequency of drug use was as follows: cocaine, 54%; marijuana, 37%; benzodiazepines, 10%; opiates, 9%; barbiturates, 7%; and amphetamines, 5%.2 When violent patients involved in crimes with or without blunt trauma were identified, the effects of drug use were highlighted—only 6% of these patients had positive screens for alcohol, while 80% were positive for illicit drugs.2 Accidents may occur when patients abuse drugs in the workplace, as well as from gang violence that is related to drug transactions.
Other patients have medical disorders that are directly related to their drug abuse, but the patient may be unable or unwilling to verify that illicit drugs are involved. For example, a significant number of patients who abuse crack cocaine will have ischemic and hemorrhagic stroke, myocardial infarction (MI), or seizure. Patients with cocaine-associated MI may not benefit from thrombolytics to the same degree as patients with noncocaine-related MIs. However, if they do not give a history of cocaine use, ED physicians may not be able to treat them appropriately. The number of complications caused by cocaine abuse is astounding. Up to 30% of strokes in young adults are cocaine-related.4 Approximately 10% of patients presenting to the ED with cocaine toxicity will exhibit seizures.5 Finally, in one series cocaine was found to be the cause in as many as 40% of ED patients complaining of chest pain.6
Intravenous drug abusers (IVDAs) have been found to die at seven times the rate of comparable age groups of non-drug users.7 Complications experienced with IVDA include obvious disorders such as cellulitis and skin abscesses, as well as more cryptic and life-threatening problems like endocarditis. Since patients with a history of IVDA may not be forthcoming about their drug use, their problems may be difficult to detect and treat appropriately. For example, one may not think to include oral pathogens in selecting an antibiotic to treat cellulitis, but many IVDA patients are known to lick the needle before use and thereby need broader coverage for their abuse-related cellulitis. Further, without knowing that a history of IVDA exists, most emergency physicians would not put endocarditis at the top of the differential in a seemingly healthy young adult who presents with fever without a source. However, when endocarditis goes undiagnosed, the patient may have severe and even fatal consequences.
Finally, the pediatric patient can be exposed to adults abusing drugs in the home. Cocaine is passed from mother to infant in breast milk; as a result, irritability, vomiting, diarrhea, hyperactivity, and hyperventilation in infants have been reported.8 A recent study of 122 inner city children younger than age 1 presenting for emergency care found that an alarming 16-33% of these patients had positive drug screens, presumably from passive cocaine smoke exposure.9 Older children also have begun to present to EDs with needlestick injuries from abandoned needles left in public places.10 ED visits for complications of drug abuse in the 12- to 17-year-old age group accounted for 10% of all visits to the ED for drug abuse.11
Unfortunately, time has shown that the problems of drug abuse will not disappear quietly. The United States annually budgets an impressive $40 billion for the Drug Enforcement Agency (DEA). Despite the substantial efforts to curb both demand for drugs and drug importation to the United States, patients continue to abuse drugs and present to the ED with drug-related complaints. According to data from the Drug Abuse Warning Network (DAWN), visits to EDs for drug abuse have increased 49% from 1990 to 1999.11 Part one of this two-part series will discuss the clinical manifestations and initial management of patients affected by commonly abused illegal drugs.— The Editor
Illicit drug abuse is considered by some to be the number one health problem in the United States. At face value this may seem extreme, but the following data may help one appreciate this point of view. It was estimated that in 1995 substance abuse cost the United States $276 billion, or $1,050 per each man, woman, and child.12 This figure includes alcohol abuse, but illicit drug use accounts for 40% of the estimated costs. Costs are incurred not only from medical treatment, but also from lost productivity, law enforcement intervention, the justice system, welfare, etc. In 1995, substance abuse was estimated to cost Medicare, Medicaid, the Food Stamp Program, and Unemployment Compensation $77 billion.12 The costs to Medicaid alone are expected to top $1 trillion during the next 20 years if current trends in illicit drug use persist. When including deaths from overdose, suicide, homicide, motor vehicle accidents (MVAs), and medical complications, it is estimated that more than 20,000 people die from illicit drug use every year in the United States.13 Nearly 33% of all justice system costs are related to untreated substance abuse, and this does not include the $250 billion in property losses in victims of drug-related crimes. The Justice Center reports that a national average of 64% of males arrested in 1999 had positive urine drug screens. The national average for positive cocaine screens was 32%, 40% for marijuana, and 7% for both opiates and methamphetamine. Variability from city to city was quite high, indicating regional differences for specific drug use. The highest numbers for any one city were 51% for marijuana, 20% for opiates, and 27% for methamphetamine. The link between crime and substance abuse is underscored by these statistics.
There also is a strong connection with psychiatric diagnoses and substance abuse. In one study of 266 patients presenting for emergency psychiatric services, 41% had positive urine drug screens.14 Of these, 26% were positive for cocaine. Further, fewer than 50% of these patients revealed their current drug use during their interviews. Also, the highs and lows of cocaine use can simulate bipolar disorder. To further confuse the matter, up to 60% of patients with bipolar disorder also report substance abuse.15 Schizophrenics also have a high incidence (50%) of alcohol and substance abuse.
Medical costs associated with domestic violence total $44 million each year, and 50% of domestic abusers are believed to have illicit drug problems.16 Fully 80% of all child abuse cases are believed to involve parental substance abuse.16 Three million people are admitted each year for treatment of substance abuse, but the National Household Survey on Drug Abuse (NHSDA) estimates that in 1997, 27.8 million Americans needed treatment. Generally, most individuals who enter these treatment programs are severely and chronically addicted. Even so, a recent review of illicit drug abuse suggests that drug dependence primarily still is viewed as a social problem, and that treatment of drug addiction should be evaluated and insured like other chronic medical problems.17 Clearly, substance abuse is a costly problem and a significant national health threat.
There are several yearly attempts to gather data on substance abuse in the United States: DAWN, National Household Survey on Drug Abuse (NHSDA), and the annual data summary by the American Association of Poison Control Centers (AAPCC) across the United States. DAWN is a yearly data summary of U.S. ED visits in which drugs are involved. It is sponsored by the Substance Abuse and Mental Health Service Administration (SAMHSA), a division of the Department of Health and Human Services. DAWN numbers do not necessarily reflect the popularity of a drug, but rather the incidence of ED visits based on the drug’s use/abuse. The NHSDA is another yearly data summary collected from thousands of households (70,000 in 1999) across the United States, and also is sponsored by SAMHSA. Numbers from this survey do reflect popularity of specific drugs, but are extrapolated from the survey answers. The AAPCC has published its yearly summary of data from U.S. poison control centers, and now has more than 24 million drug exposure cases. The most recent relevant data from these three sources are summarized in Tables 1, 2, and 3.
|Table 1. 1999 DAWN Data: Top 20 Drugs Causing ED Visits*|
|Drugs||Street Names||Route of Use|
|2. Cocaine||Coke, rock, crack||Inject, smoke, sniff|
|3. Marijuana/hashish||Blunts, grass, pot, reefer, weed||Smoke, ingest|
|4. Heroine/morphine||Smack, horse, junk||Inject, smoke, sniff|
|5. Alprazolam (Xanax)||Ingest|
|7. Acetaminophen (Tylenol)|
|8. Diazepam (Valium)||Ingest|
|9. Lorazepam (Ativan)||Ingest|
|10. Methamphetamine||Crank, crystal, ice, speed, meth||Inject, ingest, smoke, sniff|
|11. Fluoxetine (Prozac)|
|12. Oxycodone (Tylox)||Ingest, inject|
|13. Propoxyphene (Darvocet)|
|14. Amitriptyline (Elavil)|
|15. Diphenhydramine (Benadryl)|
|17. LSD||Acid, microdot, blotter||Ingest|
|18. OTC sleep aids|
|19. Phencyclidine (PCP)||Angel dust, embalming fluid, rocket fuel||Inject, ingest, smoke|
|*Data from 1999 DAWN calculation of ED episodes — episode defined as "an ED visit that was induced by or related to the use of an illegal drug(s) or the nonmedical use of a legal drug for patients older than age 6.11|
|Table 2. 1999 National Household Survey on Drug Abuse: Top 10 Drugs of Abuse*|
|Past year||Past month||
|8. PCP||7,600,000||340,000||no estimate||—|
|*Data from 1999 NHDSA — represents estimates extrapolated from voluntary survey of 70,000 households across the United States.21|
|Table 3. 1999 Annual Poison Control Center Data*|
| % Deaths/
|Chloral hydrate||305||2 0||.6%|
|* Numbers above may underestimate drug usage and deaths, as episodes may go unreported.19|
Several points from these studies bear mention. In 1998 the NHSDA estimated that 36% of the U.S. population (78 million people) has used at least one illicit drug in their lifetimes, 11% (23 million) had used in the past year, and 6% (14 million) had used in the last month.20 This compares to 105 million lifetime users of alcohol (47% of the U.S. population) and 67 million lifetime users of tobacco (30% of the U.S. population). The highest level of current drug use was recorded in 1979, when 25.4 million people were estimated to have used an illicit drug in the month prior to the survey. The 18- to 20-year-old age group has the highest rate of current drug use, with an estimated 21% using at least one illicit drug in the last year. The 12- to 17-year-old age group represents the youngest surveyed, and in 1999 10.9% were current drug users (used in the last month). From Table 3 it should be noted that while benzodiazepines were the most commonly abused illicit drug in 1999, cocaine and narcotics are much more dangerous. A much higher percentage of patients abusing cocaine and narcotics (particularly heroin) suffer fatal consequences. Even in the AIDS era, drug overdose remains the leading cause of death among IVDAs.18
Many physicians are aware that drugs are "scheduled" by the government, but may not know exactly how each drug is categorized. The Comprehensive Drug Abuse Prevention and Control Act was created in 1970, partially in response to the increased illicit drug use of the 1960s. Title II of this document is known as the Controlled Substances Act and forms the basis of drug scheduling. Drugs are divided into five schedules based on the drug’s medical use, potential for abuse, safety, and potential for dependence. Penalties for individuals caught with illicit drugs vary with this schedule system.
Schedule I. These are drugs with a very high potential for abuse, with no currently accepted medical use in the United States. They are considered dangerous when used without medical supervision. Examples of Schedule I drugs are heroin, lysergic acid diethylamide (LSD), methaqualone, quaaludes, gamma-hydroxybutyrate (GHB), and marijuana. Although exact penalties vary with the amounts involved, individuals convicted for possession of 100 grams of pure Schedule I or II drugs can be fined up to $4 million individually and sentenced to 10 years or more (but not life) for their first offense. The second offense requires an $8 million fine, with a mandatory 20-year sentence. Penalties for marijuana differ in accordance with the quantity of drug (penalties above apply for 1000 kg or 1000 plants).
Schedule II. These drugs also have very high potential for abuse, but do have some accepted medical uses in the United States. Abuse leads to physical and/or psychological dependence, and is considered dangerous. Examples include: morphine, phencyclidine (PCP), cocaine, methadone, and methamphetamine.
Schedule III. Drugs in this category also have potential for abuse, but less than that of drugs in the previous two categories. There are accepted medical treatment uses for these drugs in the United States. Abuse can lead to mild or moderate physical dependence or great psychological dependence. Examples include: anabolic steroids, codeine, hydrocodone, and barbiturates. Penalties for those with first-time offenses are sentences of fewer than five years and fewer than $250,000 in individual fines.
Schedule IV. These are drugs with relatively low potential for abuse, and they have accepted medical uses in the United States. Abuse leads to limited physical or psychological dependence. Examples include: benzodiazepines and oral opiates. First-time offenders can be sentenced to fewer than three years and be required to pay fewer than $250,000 in individual fines.
Schedule V. These drugs have a low potential for abuse and accepted medical uses in the United States. Abuse may lead to limited physical or psychological dependence; examples include over-the-counter cough and diarrhea medicines. First-time offenders can be sentenced to less than one year and be required to pay fewer than $100,000 in individual fines.
Background. Cocaine has been used in South America for hundreds of years, and Colombia remains the world’s leader in cocaine production. Cocaine use in the United States was legal until the Food and Drug Act of 1906 and the Harrison Narcotic Act of 1914 were passed. Cocaine is an alkaloid compound found in leaves of Erythroxylon coca, a small tree that is native to the mountains of northern South America. Its leaves are dissolved in hydrochloric acid to make cocaine hydrochloride. This is then mixed with ether to form freebase cocaine, or it is extracted with sodium bicarbonate and water to form crack cocaine. Production of crack cocaine is easier and cheaper than that of freebase cocaine. The name "crack" comes from the popping sound this form of cocaine makes when smoked.
Cocaine is arguably one of the most popular and most dangerous illicit drugs used. Estimates as to the total number of users peaked in 1985 at 20 million.22 The NHSDA estimates 1.5 million Americans, 0.7 % of the population older than age 12, are current cocaine users. Cocaine use is the number one complaint of patients admitted to drug treatment centers.23 Cocaine abuse also results in a large number of ED visits. Recent data from the Drug Abuse Warning Network show that cocaine use remains the most common cause for drug-related visits to the ED. In 1999, cocaine use was responsible for 30% of visits to the ED for drug abuse.11 Cocaine also is one of the most common illicit drugs associated with traumatic injury. In a 1989 study on 169 trauma patients from New York, 54% tested positive for cocaine (compared to 35% testing positive for alcohol).2 For patients involved in violent crime injuries, alcohol was found in only 6.2% of cases, whereas 80% of these patients tested positive for illicit drugs. More recent data confirm this trend. Data from 1998 on 516 traumatically injured patients from Los Angeles found that cocaine and opiates were responsible for 91% of the positive drug screens.3
The economics of cocaine trafficking are staggering. According to data from the U.S. DEA from Los Angeles in 1994, a kilogram of cocaine costs between $950 and $1200 dollars in South America.24 American importers are charged between $12,000 and $14,000 per kilogram, and in turn receive between $25,000 and $35,000 when they divide the kilogram into 1-ounce packets. If the kilogram is made into crack, the profit change is dramatic. On the street, a 0.2-gram rock costs around $20, yielding around $100,000 from a single kilogram. If cut with procaine, lidocaine, lactose, or mannitol, profits can be as much as $200,000 per kilogram. The average user smokes between seven and eight rocks a day, producing a $1050 habit per week, or $54,600 per year.
In addition to the economic attraction of crack cocaine trafficking, the effect on the user also is strong. Smoking either form of cocaine rapidly yields high blood levels and affects the user similarly to intravenous (IV) use of cocaine. Typically, ingesting cocaine nasally yields a peak effect in 15-20 minutes and lasts 60-90 minutes. Smoking or injecting cocaine gives a peak effect in 5-10 minutes and lasts only 30 minutes. As the high the user gets depends on the rate of rise and the peak blood level, smoking cocaine leads to rapid, intense highs that quickly are followed by crashes. This rapid crash can promote frequent cocaine use to the point of binging to avoid the crash. Further, tolerance to cocaine develops with this repeated use, increasing the amount of cocaine necessary to produce the same high. Cocaine is metabolized by the liver into benzoylecgonine and ecgonine, which are then excreted in the urine. A single dose of cocaine can lead to positive urine drug screens for the next 24-36 hours.25 When the user also ingests alcohol, cocaine is metabolized into cocaethylene. Cocaethylene has a much longer half-life than benzoylecgonine and ecgonine, and is believed to play a part in the increased risk of sudden death by users of both alcohol and cocaine. In patients using both cocaine and alcohol, risk of sudden cardiac death is increased 25-fold compared to users of cocaine only.26
Cocaine binds to specific proteins, inhibiting the reuptake of dopamine, norepinephrine, and serotonin. The increases in dopamine and serotonin levels in the brain are associated with the euphoria (i.e., feelings of increased energy and lowered inhibitions) observed in the user. As the dopamine levels fall, the user experiences depression and cravings for more cocaine.26 Cocaine also is associated with the direct release of catecholamines from the adrenal gland.26 How these changes specifically affect different organ systems will be discussed under the following sections.
Cardiovascular. Dysrhythmias. Cocaine use can cause multiple dysrhythmias in the user, including sinus tachycardia, atrial fibrillation, idioventricular rhythm, ventricular tachycardia or fibrillation, sinus arrest, atrioventricular blocks, asystole, and prolonged QT interval that may lead to Torsades de Pointes.27,28 Cocaine acts as a type Ia sodium channel blocker like quinidine or procainamide, and prolongs the QT interval by prolonging the action potential duration. Mechanisms of other dysrhythmias are less well understood, but also may involve direct sympathetic stimulation and ischemia.29 Lethal ventricular arrhythmias are thought to be responsible for sudden cardiac death in cocaine users who do not have coronary artery disease.30
Management of cocaine-induced dysrhythmias depends, in part, on the rhythm that is found. It is important to remember that beta-blockers are contraindicated, as they will worsen cocaine-induced coronary artery vasospasm.31 Likewise, procainamide and quinidine are contraindicated in these patients as they will aggravate the situation by their type 1a action. If the patient has a rhythm due to cocaine’s 1a effects (i.e., supraventricular tachycardia with QRS widening), sodium bicarbonate may be helpful to overcome the sodium channel blockade.32 If the rhythm is caused by catecholamine excess (i.e., sinus tachycardia), sedation with benzodiazepines can be helpful. At times, the etiology of the dysrhythmia may be unclear or multifactorial. Dysrhythmias associated with chest pain should be assumed to be caused by ischemia and treated as such until proven otherwise. Lidocaine should be used when indicated, and at least one study found no complications with its use in patients with cocaine-related MI.33
Ischemia. Cocaine can produce ischemic effects on the heart in both direct and indirect ways. Direct mechanisms include coronary vasoconstriction, increased platelet aggregation, and thrombus formation leading to MI. Cocaine also causes increased cardiac demand for oxygen, a result of adrenergic stimulation (increased heart rate, cardiac output, and increased peripheral vascular resistance) that worsens any ischemia. Cocaine also may have direct myocardial toxicity.34 Indirectly, repeated cocaine use accelerates atherosclerotic development as well as nonatherosclerotic plaque growth.35
The emergency physician, therefore, is presented with a significant dilemma when patients using cocaine come to the ED complaining of chest pain. Chest pain is the most common reason for ED presentation after cocaine use, and is seen in 20-40% of ED patients using cocaine.6,36 In 1997, it was estimated that 64,000 cocaine-related chest pain patients were evaluated in the ED. One-half of these were admitted, costing an estimated $80 million for health care.36 However, repeated studies show that only 6% of patients with cocaine-induced chest pain will later be shown to have an MI.37,38 The difficulty facing the ED physician is identifying which patients will be in this 6%. Many factors complicate this issue. Cocaine-related MI and sudden death can occur in the chronic user as well as first-time users, and can occur with use of large or small amount of cocaine.
Patients frequently are reluctant to admit cocaine use. One study of 359 patients found that only 72% admitted cocaine use when questioned.39 Often, the patient’s description of his or her chest pain after using cocaine is worrisome. They complain of retrosternal pressure associated with shortness of breath, diaphoresis, and sometimes nausea and/or vomiting. However, clinical complaints alone are not useful for identifying patients with MI after cocaine use.36,40 The route of administration also is not useful; MI is known to follow cocaine use by nasal, IV, or inhalation routes.41 The electrocardiogram (ECG) is nondiagnostic in 60% of patients who are later proven to have cocaine-induced MI.37 Creatine kinase (CK) levels often are elevated in patients who complain of chest pain in the absence of MI after cocaine use as a result of cocaine-induced rhabdomyolysis.27 One study of 40 patients presenting after cocaine use found an average CK level of 1071 IU/L.42 As with MI that is not related to cocaine use, a persistently elevated isoenzyme of creatine kinase (CK-MB) level may be diagnostic of MI. A recent study of 97 patients with cocaine-related chest pain found that only myoglobin levels were significantly altered by recent cocaine use.43 CK-MB levels and troponin I levels were not changed by cocaine use and, therefore, still should be accurate for diagnosis of MI in these patients.
The consensus in the literature is that patients presenting to the ED with complaints of persistent chest pain after cocaine use should be observed for 12 hours. During this time, they should have serial ECGs and serial CK and CK-MB testing. This recommendation is based on the finding that patients with cocaine-related chest pain who do not meet criteria for diagnosis of MI during that time are at very low risk for developing it later. Only 0.2% of these patients will present with cardiovascular complications after the 12-hour observation.40 It is important to note, however, that some authors report that up to 33% of patients who are diagnosed with cocaine-induced MI will develop complications, including ventricular dysrhythmia and congestive heart failure, during the first 12 hours after presentation.27 Therefore, it is necessary to closely monitor patients who are being held for observation. Recently, a six-hour observation period has been proposed.44 During this time cardiac enzymes (CEs) are checked at zero, three, and six hours, and ST segments are continuously monitored. More than 197 patients have been evaluated with this protocol; if CEs are normal and no ST segment abnormalities are found, the authors suggest patients may be discharged safely. Prospective verification of this protocol may establish it as a guideline to follow in these patients.
Specific treatment for patients who can be diagnosed with acute MI on initial presentation can be focused on typical treatment for MI (i.e., nitrates, aspirin, etc.). With the hope of reducing vasospasm, some authors recommend low doses of phentolamine or verapamil for patients who continue to have chest pain after standard treatment.41 A recent randomized, double-blind, placebo-controlled study attempted to show which treatment was more effective in the setting of chest pain secondary to cocaine.38 Treatment with benzodiazepines alone, nitroglycerin alone, or both in combination showed no difference based on chest pain improvement or on changes in cardiac performance.38 This paper supports the addition of benzodiazepines to the medications used to treat ischemia in these patients and reports they may be beneficial or may be an acceptable alternative treatment alone. It is hoped that further investigation will clarify these issues. While treatment with thrombolytic agents is standard for noncocaine-associated MIs, their use in these patients is controversial.45 Some studies report an increased risk of intracranial hemorrhage in these patients,46 but this is based on a single case report.29,47 Other studies support the safety of thrombolytic use in cocaine-associated MI.48 Still others report both minor and major hemorrhagic complications and recommend thrombolysis with caution.49 What remains unclear is the efficacy of thrombolytic use in these patients; with their low mortality rate, it is difficult to show a beneficial effect from thrombolytic use.27 One author suggests that additional studies, including echocardiography and angiography, should be used to identify which patients would clearly benefit from thrombolysis.29 Case reports of angioplasty for treatment of cocaine-associated MI also are being described.50
Seizures. Seizures resulting from cocaine use are seen in 2-10% of ED patients.5 Cocaine-induced seizures are defined as seizures that occur within 90 minutes of cocaine use. Generalized tonic-clonic seizures have been reported up to 12 hours after cocaine use.51 Typically, cocaine-induced seizures occur in patients with no history of seizures, and are single, self-limiting events. Patients often will have normal computed tomography (CT) scans and normal electroencephalograms.5 As cocaine-induced strokes are not rare, CT scan should be used liberally in these patients to rule out these complications. If the patient has no further seizure activity in the ED, treatment with benzodiazepines may not be necessary. Patients with a previous history of noncocaine-related seizures can experience repetitive focal motor seizures. Status epilepticus has been seen in patients without previous seizures who have used large amounts (2-8 g) of cocaine.5 Treatment with benzodiazepines (i.e., lorazepam 2 mg IV) is the first line of treatment. Patients in status epilepticus who do not respond to repeated doses may require the use of phenobarbitol or general anesthesia. Children who present with unexplained seizures may need urine drug screens to rule out accidental cocaine exposure as a cause of their seizure.
Strokes. Unfortunately, both headache and cerebrovascular accidents are common in cocaine users. Up to 60% of them report headache after cocaine use, and 12% of patients who present to the ED after cocaine use list headache as their chief complaint.6 Use of cocaine may trigger migraine headaches, and headache also can be a feature of cocaine withdrawal. Patients presenting to the ED with headache should be asked about cocaine use, and a drug screen obtained if this information would alter their management. Patients with stroke from cocaine use typically develop objective neurological symptoms during the first 3-6 hours after their last use of it.52 Therefore, one could argue that unless the presentation is particularly concerning, patients who present more than six hours after their last use of cocaine and have no neurological findings are at lower risk for stroke.
At least one author suggests that CT and lumbar puncture are not indicated in all patients with cocaine-induced headache.27 However, the decision to not perform CT scan and lumbar puncture in low-risk patients who present with cocaine-associated headache may be difficult in today’s legal climate. Cocaine users are at high risk for HIV infection and traumatic injuries, and their headaches could be from complications of these other entities as well. Further, the clinical history reported by a cocaine user may be less than complete for many reasons. To truly define a patient with cocaine-induced headache as low-risk (no work-up needed), one should add a verified, negative HIV status and no history/evidence of head trauma to the low risk criteria. All other patients with cocaine-associated headaches should be evaluated with CT scan and lumbar puncture (unless a competent patient refuses) to rule out more serious causes of their headaches
Cocaine use causes 90% of strokes in young adults (3rd and 4th decades of life),52 and is the most common cause of drug-associated stroke. Stroke associated with cocaine use can occur with first-time use or in chronic users. Cocaine use may cause subarachnoid hemorrhage, intracerebral bleed, or ischemic stroke. Although 80% of patients with hemorrhage will be found to have an aneurysm or arteriovenous malformation on further examination, fully 20% will not.5 While crack abuse is associated with both ischemic and hemorrhagic stroke, IV use more commonly causes hemorrhage.53 Patients who present with sudden, severe headache after cocaine use may have a subarachnoid hemorrhage; the presence of stiff neck, syncope, nausea, vomiting, and photophobia on exam markedly increase their risk. Patients who have altered mental status and focal neurological findings are more likely to have an intracerebral bleed.
Central nervous system (CNS) ischemia after cocaine use may present as a transient ischemic attack (TIA) or ischemic stroke. Vasospasm of cerebral arteries after cocaine use is not rare, especially in the middle cerebral and vertebrobasilar arteries.54 Serotonin is a potent vasoconstrictor, and may be the cause of vasospasm as cocaine blocks serotonin reuptake. Patients present with typical hemiplegia, paresthesia, aphasia, and dysarthria. TIAs often are resolved by the time the patient reaches the ED, and subsequent CT and lumbar puncture are likely to be normal. Phentolamine is recommended with caution by at least one author as a potential reversal agent for cocaine-induced cerebral artery vasospasm.27 Cocaine-induced cerebral vasculitis also has been implicated in ischemic stroke in these patients, and may be diagnosed by arteriogram.55 Anterior spinal artery syndrome,55 lateral medullary syndrome,55 and embolic stroke56 all also have been reported after crack use.
Respiratory. Crack cocaine use has multiple effects on the respiratory system as well, and 20% of cocaine users presenting for treatment will complain of shortness of breath.27 Reported complications include: increased asthma symptoms, pneumothorax, pneumomediastinum, noncardiogenic pulmonary edema, and pulmonary hemorrhage/infarction. One study that compared asthma symptoms and severity in cocaine users and non-cocaine users found that asthma severity, when measured by length of stay, was significantly longer in cocaine users.57 Upper airway burns also have been reported, and even led to four cases of acute epiglottitis in one report.58 An entity labeled "crack lung" also been has reported.59 It consists of fever, dyspnea, hemoptysis, hypoxia, chest pain, infiltrates, and even respiratory failure. The symptoms develop within 1-12 hours after crack use. Treatment of crack lung patients with corticosteroids may be beneficial, as eosinophilia has been noted in samples of pulmonary tissue.60
Body Stuffer/Packers. People who ingest cocaine (or other drugs) for the purpose of hiding them from authorities can be divided into two categories: body "stuffers" and body "packers." Body stuffers are people who consume smaller amounts of unprepared drugs than body packers, to avoid imminent danger (e.g., arrest by the police). Body packers swallow meticulously packaged drugs to transport them in smuggling operations. Each type of drug ingestion has its own problems and recommendations.
Body stuffers more commonly are encountered. Because they spontaneously ingest drugs without preparation, the packages they eat typically consist of small plastic bags or vials of crack cocaine. These packages are not put together with the intention of ingestion, and often leak their contents. Patients also may eat unwrapped crack. Patients can be asymptomatic at the time of exam, as they often are seen just after ingestion. Histories are very inaccurate, and because the lethal oral dose of cocaine is only 1 gram,5 all patients suspected of body stuffing should be treated as if they have ingested a dangerous amount. Drug testing is not indicated, as the patient should be treated the same regardless of the result. Plain films are typically negative, and even CT scans may have false-negative results.61,62 Activated charcoal followed by whole bowel irrigation is recommended in all cases until rectal effluent is clear, and plain abdominal films show no foreign bodies on a scout film. One study of 98 cases of crack body stuffers found that crack was unwrapped 28% of the time, and wrapped in plastic baggies in 29% of the cases.63 Fortunately, these patients usually ingest smaller amounts of cocaine, and while they often have signs of cocaine toxicity, morbidity and mortality are rare. The same study of 98 cases confirms this; symptoms of mild cocaine toxicity were common, with tachycardia in 54%, hypertension in 23%, agitation in 22%, and 19% requiring sedation.63 No patients exhibited dysrhythmias, but 4% did have generalized seizures within two hours of ingestion that responded to treatment.63 Another study of 34 body stuffers found 74% remained asymptomatic, but the two patients who developed seizure and dysrhythmia both died despite treatment.64 Although serious complications are less common, deaths have been reported by others as well;65 physicians should be aware that serious injury can occur. Further, delayed toxicity also can occur, and at least one author recommends admission for observation.27
Body packers (termed "mules") usually ingest large amounts of drug in well-prepared packets, and are encountered less commonly in most EDs. One body packer was documented to have swallowed 143 packets of cocaine and heroin.66 With each packet containing from 5 to 7 grams of cocaine, rupture of just one is potentially fatal. Patients may present with sudden, fatal collapse during transport, but more often are brought to the ED when authorities suspect drug smuggling. Another presentation is that of acute bowel obstruction in a young patient with no risk factors. Plain x-ray may reveal evidence of body packing as the packets themselves or air trapped in them can be seen, but more systematic evaluation with contrast studies, serial x-rays, or CT scan may be needed to visualize the packets.67 With the patient often denying the offense, and if initial plain films are negative, the ED physician is faced with the difficult decision of when to pursue further evaluation.
Digital rectal exam may reveal the presence of packets, but one author found a high correlation with a positive urine drug test and the presence of internal packets.68 They examined 120 mules and found a higher than 95% correlation with a positive drug screen and the presence of both cocaine- and heroin-filled packets. Thus, if plain films do not reveal their presence, a positive drug screen for cocaine (or heroin) should prompt a more extensive evaluation to ensure patient safety. Once the packets have been detected, asymptomatic patients should be given activated charcoal followed by polyethylene glycol electrolyte solution until rectal effluent is clear and all packets have been retrieved. Again, any history about the number of packets ingested is very unreliable, and follow-up imaging studies are needed to ensure that all packets have been passed. All body packers should be admitted for observation and potential treatment during packet retrieval. If complications appear that suggest packet failure, immediate surgery for removal is indicated. Endoscopy is contraindicated, as packet rupture has occurred with both upper and lower retrieval attempts.69
Miscellaneous. Acute rhabdomyolysis is a well-known complication of cocaine abuse, and may be seen in users with no other risk factors (trauma, seizure, hyper- or hypotension, hyperthermia, or coma).70 As many as 30% of patients with rhabdomyolysis from cocaine use will progress to renal failure.5 While cocaine can lead to direct renal injury,71 initial case reports found a correlation of the presence of hyperthermia, hypotension, and delirium with more severe cases of rhabdomyolysis.72 A syndrome known as agitated delirium is characterized by extreme agitation, delirium, hyperthermia, and sudden death in physically restrained cocaine users, and also has been described.73 Recently, one author has suggested that agitated delirium and rhabdomyolysis in cocaine users actually are different stages of the same syndrome.74 They suggest that intense, chronic cocaine use disrupts dopamine processing by the body and that excitement, physical restraint, and hyperthermia triggered both syndromes. Both syndromes were more common in young, black, male patients who smoked or injected cocaine in the summer months.74 One should be aware of these risk factors and liberally use benzodiazepines and active cooling to help prevent both fatal agitated delirium and rhabdomyolysis in patients at risk for them. Once suspected, acute rhabdomyolysis should be treated with 1 Amp sodium bicarbonate diluted in 1 L normal saline followed by IV fluids at 200 cc/hr, dopamine (3 mcg/kg/min), and furosemide (60 mg tid) to help prevent renal failure.
A unique condition can follow a cocaine binge called "cocaine washed-out" syndrome. Described in case reports, it consists of a dramatically decreased level of consciousness following extended cocaine use. Patients can be essentially comatose, and do not respond to painful stimuli and invasive procedures. One patient was described who presented after a two-week cocaine binge and tolerated placement of Foley catheter, IVs, arterial blood gas (ABG), and even orotracheal intubation without any response.75 All tests obtained were negative, and he slowly woke up over the next 24 hours. The proposed mechanism of this state is catecholamine depletion, but no data exist to support or dispute this idea. Even though they spontaneously recover in 12-24 hours, patients with this level of coma require many tests to prove other conditions are not responsible. Cocaine washed-out syndrome remains a diagnosis of exclusion.
Cocaine use by pregnant women is associated with many complications both with their pregnancy and in their children. Complications of pregnancy associated with cocaine use include increased preeclampsia, eclampsia, vaginal bleeding, premature labor, placental abruption, and fetal death.76 These mothers also have increased risk of spontaneous miscarriage. One study of 400 miscarriages found a 29% increase in mothers using cocaine.77 Another case report described a patient with spontaneous uterine rupture along a previous Cesarean section scar.78 Virtually every fetal organ system has associated anomalies from in utero cocaine exposure.79 Specific disorders that are increased in these infants include higher rates of apnea and neonatal necrotizing enterocolitis.80 ED physicians should be aware of the increased risks associated with cocaine use in pregnant women and their children and screen for these complications when treating these patients.
Acute gastrointestinal complications of crack use also have begun to surface. One case report, published in 1999, described a patient who developed acute ischemia of his colon after IV cocaine use.81 The patient underwent emergent surgical repair and survived. Another recent paper describes three patients in whom bowel ischemia led to resection of gangrenous segments.82 All of these patients were otherwise healthy men ages 20-40 years. The mechanism of bowel injury is thought to be ischemia from acute vasospasm. Although not exceedingly common, one should keep in mind that history of recent cocaine/crack use is a risk factor for serious abdominal pathology in otherwise healthy patients.
Finally, when treating patients in the ED for cocaine dependence, one can be discouraged by the perception that cocaine addiction is notoriously difficult to treat and has a high potential for relapse. However, data support that treatment efforts are important and more successful than one may appreciate. The costs of crime associated with cocaine abuse were compared in 502 cocaine-dependent people for the year before and the year after treatment. The patients were treated in outpatient (28%) and inpatient settings (78%), and significant reductions were reported in crime after treatment from both groups.83 A large study of 1605 cocaine-dependent people in 11 U.S. cities found cocaine use dropped 60% in the year after treatment.84 Higher relapse rates were correlated with higher severity of use before treatment and shorter inpatient stays (< 90 days).84 The search continues for adjunctive treatments that will be helpful for the treatment of cocaine dependence. Many compounds have been evaluated for effectiveness in treating cocaine addiction, including carbamazepine,85 respiridone,86 amantadine,87 and most recently, dopaminergic drugs.88 Unfortunately, no drug tested thus far has proven effective.89
Opiates are a class of drugs that have been used for thousands of years to reduce pain, sedate, treat diarrhea, and produce euphoria. Heroin was first synthesized from morphine in 1874, and commercial production began in 1898. No controls were placed on its use until the Harrison Narcotic Act of 1914. As a class, their abuse remains popular, with a 181% increase in new users since 1990.21 This is the largest increase for any class of drugs, with the next highest increases for stimulants (165%) and inhalants (154%). Data from the 1999 NHSDA indicate that there are around 200,000 current heroin users, representing only 0.1% of the nation’s population older than age 12.21 The same survey estimates there were 149,000 new users in 1999. The estimated number of new users per year has not changed significantly from 1996 to 1999. Combining data from 1996 to 1999, the mean age of heroin abusers remains young, with 25% of new users being younger than age 18, and another 49% ages 18-25 years at the time of first use. Together, nearly 80% of new users are younger than age 26.
Approximately 2.1% of 8th-, 10th-, and 12th-graders in the United States report at least one lifetime use.90 The availability of less expensive, higher-quality heroin and increased usage by middle-class sectors are responsible for these changes. Among heroin users, there was an increase from 55% to 82% between 1994 and 1996 in those who had either snorted or smoked heroin. The percentage of users who injected remained about the same at 50%.21 The purity of heroin on the streets has risen from about 1-10% a decade ago to 1-98% today with a national average of 41%.91 The desired high that only could be obtained by needle injection 10 years ago now can be obtained by nasal insufflation or smoking. Increased purity also results in more deaths from inadvertent overdose. For example, the Medical Examiner’s Commission reports heroin-related deaths climbed more than 600% in Florida from 1993 to 1998.
Heroin still disproportionately affects impoverished minorities, but the largest increase in heroin use has come from 14- to 19-year-old Caucasians during the past five years. Because of these recent changes, heroin-related ED visits have doubled from 1990 to 1995.11 The 1999 AAPCC report found 30 deaths that year from heroin abuse, which was second only to sedative-hypnotics and cocaine.19 Compared to the other two drugs, though, the percentage of patients who die using heroin is several fold higher; this illustrates the risk of heroin abuse. While 3% of patients in the AAPCC report died from heroin abuse, only 1% died from using cocaine, and only 0.1% from sedative-hypnotic abuse.19 Looking further, opiates are found in combination with other drugs in nearly 10-20% of deaths reported to poison control centers.92 In addition, some areas of the country have a much higher percentage of these cases. Up to 50% of drug-related deaths reported to medical examiners have been attributed to opiates.92 While patients abusing other drugs may die from a variety of causes, almost every death from opiate abuse is caused by respiratory depression. Theoretically, this means that if temporary ventilatory support was given to these patients until their own respiratory drive returned, none of them would have died.
In San Francisco, where deaths from heroin abuse were particularly high in 1999, an organization called You Find Out (UFO) was started to help reduce deaths from accidental heroin overdose. The organization actually began when researchers tried to examine the incidence of HIV and hepatitis in San Francisco heroin abusers. They found that the majority of these people were not dying from HIV or hepatitis infection, but from accidental overdose. A surprising 50-75% of heroin users they interviewed had either overdosed or witnessed a heroin overdose among friends. Overdoses were defined as the user becoming obviously cyanotic. UFO also attempts to reduce other complications from heroin abuse. For example, San Francisco General Hospital lost $18 million from IVDA skin abscesses in 1999 alone.
Pharmacology. Morphine and codeine are the only two opiates that directly are derived from the juice of the poppy, Papaver somniferum. Other opiates are semisynthetic, and are produced from morphine; these include hydromorphone (Dilaudid), heroin (diacetylmorphine), and oxycodone (Tylox, Percocet). Heroin can be a white powder with a bitter taste, or a black, sticky substance (black tar, from Mexico). Purely synthetic opiates include meperidine (Demerol), propoxyphene (Darvocet), diphenoxylate (Lomotil), fentanyl, methadone, buprenorphine (Buprenex), and pentaxocine (Talwin). Opiates can be taken orally, nasally, or by injection. On average, peak effects are reached in 1-2 hours when taken orally, 90 minutes if by subcutaneous injection, 30 minutes if by intramuscular (IM) injection, and in 10 minutes when taken via IV. As a large amount of the dose is broken down in the liver, oral doses, in general, need to be much larger to produce the same effect as IV or IM doses. For example, 200 mg of codeine needs to be given orally to produce the same effect as 10 mg of morphine IM.
The volume of distribution for opiates is large, so blood levels carry little clinical significance and dialysis will not substantially reduce their serum levels. With the exception of methadone, diphenoxylate, buprenorphine, and propoxyphene, all of the opiates have a relatively short duration of action (< 8 hours). Rapid hepatic metabolism accounts for this effect. The exceptions mentioned above can have effects for 24 hours, and patients overdosing on these opiates will need significantly longer observation to ensure their safety.
Opiate receptors have been well studied, and mu, kappa, and delta subtypes have been identified. Mu and kappa receptors are the most clinically relevant, as the delta receptor does not interact with commonly used opiates but with endorphins (endogenous morphine). The most potent opiates act as agonists at mu receptors, while the agonist-antagonists act as agonists at kappa receptors and antagonists at the mu receptor. It had been hoped that specific opiate effects could be linked to certain receptors, and therefore, a drug designed that had the analgesic effects of morphine without respiratory depression. It was found that analgesia and respiratory depression can be linked to all three receptors and that many drugs have effects at more than one receptor type. Two recently developed opiates, butorphanol (Stadol) and tramadol (Ultram), were developed as non-addictive drugs to be used in pain treatment. While not causing significant respiratory depression, some authors question the abuse potential of butorphanol.93 While abuse potential for tramadol is reported by some authors as very high in opiate addicts,94 tramadol remains a non-scheduled drug.95
Pure antagonists for the opiate receptors include naloxone, naltrexone, and nalmefene. Naloxone is a pure antagonist and blocks all opiate receptors. The primary difference between these drugs is their half-life. Naloxone is effective in 1-2 minutes when given IV, but effects last for only 60 minutes. Nalmefene lasts for 4-8 hours, and naltrexone last up to 72 hours. Naltrexone is used for long-term management of opiate addiction, and controversy exists about the use of nalmefene for treatment of ED patients. One author cautioned that although its longer half-life is useful in some situations, prolonged withdrawal in the opiate addict can be problematic.96 Another study used both naloxone and nalmefene randomly in ED patients suspected of narcotic overdose.97 Although the authors state no significant differences were found in using the two drugs this way, the number of adverse events was nearly double using nalmefene (30% of study patients) compared to naloxone (15% of study patients).97 Clinical use of naloxone will be discussed in the treatment section.
Clinical Effects. Opiates produce a variety of effects in humans, including depressed respiratory drive, euphoria, sedation, miosis, mild hypotension, decreased gastrointestinal (GI) tone, and seizure.
Respiratory. The most significant effect clinically is that of respiratory depression. In overdose, opiates produce hypoventilation by decreasing the rate of respiration (2-4 breaths/minute) without affecting tidal volume, whereas overdose with sedative-hypnotics will produce shallow respirations with a normal rate. They appear to blunt the responsiveness of the medullary respiratory center to rising arterial carbon dioxide levels. In contrast to sedative-hypnotics, opiates produce significant analgesia and respiratory depression before causing notable reduction in level of consciousness. Even though they often are conscious, patients often are unaware of the respiratory distress they are experiencing.
Opiates also can cause noncardiogenic pulmonary edema. This seems to be most common with IV heroin use, but also can be seen with oral or nasal use. It most commonly is associated with opiate overdose, and is found in 50% of heroin overdose cases98 and in 90% of fatal opiate overdose cases.99 Apparently, hypoxia is the indirect cause. Hypoxia causes extreme pulmonary vasoconstriction that directly damages pulmonary capillary beds, resulting in leak of fluid from the capillaries. It typically appears immediately following injection, but can be delayed for 24 hours. The edema usually is bilateral, but also can be unilateral; the heart size often is normal. In contrast to cardiogenic pulmonary edema, treatment with digitalis, diuretics, ACE inhibitors, etc., is not effective.100 Use of naloxone and supportive treatment is all that usually is needed, and opiate-induced pulmonary edema typically clears rapidly in 24-36 hours.
Other than the obvious decrease in level of consciousness, opiate abuse can cause CNS excitation, including seizures. All opiates initially cause CNS excitation, and in children this effect can produce seizures with almost any opiate. When seizure is present in adults with opiate intoxication, it implicates use of meperidine, tramadol, or propoxyphene.
Miosis. Miosis is a well-known side effect of opiate use, and will be seen in 90% of overdose cases. It occurs due to an enhanced pupillary response to light. Together with decreased respiratory rate, the two clinical features are the hallmark of opiate intoxication. It is important to remember that not all patients with opiate overdose have miosis. Meperidine is known to cause mydriasis instead, and patients overdosing with "speedballs" (cocaine and heroin IV) may have normal, miotic, or mydriatic pupils. Patients add heroin to a cocaine IV, as the effects from direct IV injection of cocaine are too strong for most users. Further, the presence of head trauma or brain injury from prolonged hypoxia also can cause pupils to not be pinpoint in opiate overdose.
Cardiovascular. In general, opiate intoxication is without significant cardiovascular effects. Cardiovascular effects that are seen with opiate overdose are rare and limited to mild hypotension from histamine release. Mild orthostatic hypotension may be produced, but when the patient is supine his or her blood pressure should remain normal. Resting hypotension or notable clinical effects of hypotension indicate co-ingestion(s) with other dangerous drugs, or a preterminal state. Hypertension also may be present, but if found it is secondary to hypoxic CNS damage. Nearly 25% of heroin abusers may have other ECG changes, most commonly atrial fibrillation.92 Reflexive bradycardia may be seen as well; it occurs in response to dangerous levels of hypoxia.
Gastrointestinal. Opiates depress smooth muscle contraction in the GI tract, and this effect does not diminish with increasing tolerance to opiate use. This fact accounts for the long history of opium as a treatment of diarrhea. This effect can be significant in mixed ingestions in which drugs can remain in the GI tract for prolonged periods of time. It also is important to remember that many oral opiate preparations are combined with acetaminophen (Percocet, Vicodin, etc.), and that serious acetaminophen toxicity may be present with overdose of these drugs. The delayed GI transit times can affect the absorption of acetaminophen, and perhaps enhance the usefulness of activated charcoal or gastric lavage. In some patients, choledochoduodenal sphincter spasm can occur with opiate use, creating abdominal pain similar to that experienced with biliary colic.
Treatment. The mainstay of treatment in opiate overdose is respiratory support, commonly through endotracheal intubation. As most opiate-related deaths occur outside the hospital, prehospital respiratory support and treatment with naloxone can save many lives. Once in the ED, several clues may guide the emergency physician to identify opiate overdose. The following commonly are seen in symptomatic opiate overdose: depressed respiratory rate of 2-4 breaths/minute, pinpoint pupils, needle tracks (scars from repeated injection over the same sites), pink frothy sputum, bradycardia, hypothermia, and coma. Remember that, as mentioned above, pupils also may be midpoint or dilated. Also, needle tracks can be well hidden, as in the case in femoral vein injection.
After airway protection is accomplished or respirations are supported to prevent hypoxia, reversal with naloxone may be attempted. Although 1 mg of naloxone temporarily can neutralize 25 mg of heroin, much larger amounts (15 mg) may be needed in overdose with pentazocine (Talwin) or propoxyphene (Darvocet). Even large amounts of naloxone safely can be used in ED patients with only the side effect of precipitation of acute withdrawal reaction. Physicians should never withhold naloxone therapy for fear of withdrawal, as it is not clinically unsafe. However, abruptly causing acute withdrawal can be very unpleasant, and results in agitation, emesis, abdominal cramping, diarrhea, sweating, etc.
One should resist the temptation to give an additional opiate to stop withdrawal symptoms, as a vicious cycle of overdose and reversal can ensue. Withdrawal symptoms should fade as naloxone wears off in fewer than 60 minutes. Use of smaller increments of naloxone can help prevent precipitation of withdrawal. A 0.4 mg IV initial test dose should be given. If no response is observed, one should give 2 mg doses every three minutes up to 10 mg total IV. If a response is observed with the test dose, continue to titrate 0.4 mg IV for the desired clinical effect. Alternatively, if the patient is a known opiate addict, one can titrate with 0.1 mg IV doses for finer control of the response. As the clinical effects of opiate reversal with naloxone will wane over 30-60 minutes, the patient should be closely monitored for return of the overdose symptoms. One can begin a naloxone drip by giving two-thirds of the initial total dose needed for response hourly.
Several items deserve special mention in the treatment of opiate overdose. First, it is important to remember substantial differences are found when opiates are ingested orally compared to IV injection. Clinical effects are much slower to appear and slower to wear off. Activated charcoal is indicated in oral opiate overdose, and gastric lavage may be beneficial because of the delayed gastric emptying seen in opiate use. Even when the opiate component of a mixed overdose is not clinically apparent (i.e., no respiratory depression, etc.), there will be effects on gastric emptying and potentially increased absorption of other toxins taken. Naloxone therapy will help reduce the delays in intestinal transit time, and is indicated if history suggests opiate use along with other potentially dangerous drugs. Further, oral opiates often are combined with acetaminophen or acetylsalicylic acid and serum levels of these two compounds always should be checked in suspected cases of oral opiate overdose.
Oral Opiates. Propoxyphene (Darvocet) is notable in that overdose can lead to a rapid and sudden collapse within 15 minutes to two hours of ingestion. It has a rather narrow therapeutic range, with toxicity found at five times the normal dose (roughly 10 tablets) and death commonly seen at 15 times the normal dose (30 tablets). Pulmonary edema and seizures frequently are seen in cases of dangerous overdose. The effects of propoxyphene overdose can last much longer than typical opiate overdose, and it is recommended to observe these patients for 24 hours before discharge. Importantly, while successful in propoxyphene overdose, naloxone must be given in relatively high doses (10-15 mg) to work.
Diphenoxylate (Lomotil) is an oral agent used for the treatment of diarrhea. Diphenoxylate reduces GI motility more and causes less respiratory depression proportionally than other opiates. Overdose with diphenoxylate causes only minor problems in adults, but has caused fatalities in children younger than age 2.101 The clinical picture can include anticholinergic signs and symptoms, as diphenoxylate also contains atropine. Further, signs of respiratory depression can be delayed up to 14 hours, and has been known to recur up to 72 hours post-ingestion. With these numbers in mind, any child younger than age 5 who ingests diphenoxylate needs to be observed for at least 24 hours for delayed symptoms. Children older than age 5 are at much less risk, and only need observation for six hours; they may be discharged if they are symptom free by this time.
Fentanyl and its analogs are very short-acting opiates, and can be up to 6000 times as potent as morphine.102 This difference in potency has lead to many deaths when users unintentionally inject fentanyl (street name "China White") believing it to be heroin.103 Fentanyl and its derivatives are not detected on many urine or serum drug screens. Due to its potency, patients may require high doses (10-20 mg) of naloxone to reverse its effects. Fentanyl is available in IV and transdermal preparations. There are reports of fatal overdose from transdermal use as well.104
Pentazocine hydrochloride (Talwin) is an opiate agonist-antagonist, and is similar to morphine in overdose except that dysphoric reactions are common. Although partial agonists generally produce less respiratory depression, deaths have occurred when combined with other drugs of abuse. Non-cardiogenic pulmonary edema has not been reported with overdose, and naloxone will reverse all but the dysphoria—although high doses (up to 15 mg) may be required. Patients who exhibit no significant symptoms after four hours of observation may be safely discharged.
Methadone commonly is found in areas with widespread heroin abuse, and is used in maintenance programs designed to keep addicts from injecting opiates. It has a very long half-life compared to other opiates, and overdose symptoms may not appear for up to three hours. It may take 12 hours for the symptoms to become severe. All cases of methadone overdose need admission for observation and often require naloxone infusion to prevent return of symptoms. Activated charcoal and whole bowel irrigation also are recommended.
While not an opioid, clonidine is used to treat acute withdrawal symptoms, and patients with clonidine overdose share some symptoms with opiate overdose. Patients may have respiratory depression and hypotension, both of which have been reported to respond to naloxone therapy. The response to naloxone is variable, with some patients having no response and others having partial response (i.e., only respiratory depression or only hypotension responding). Some patients have significant hypertension in response to naloxone, and naloxone is reserved for patients with significant symptoms in cases of clonidine overdose. It is important to realize many children are now being prescribed clonidine for treatment of attention deficit disorder, and that clonidine overdose is becoming more common in the pediatric population.105
The withdrawal syndrome in opiate abusers produces a combination of symptoms that are opposites of the acute effects. These symptoms include: nausea, diarrhea, coughing, yawning, lacrimation, mydriasis, rhinorrhea, sweating, piloerection (goose bumps, the origin of the term quitting "cold turkey"), myoclonic leg muscle contractions ("kicking the habit"), dysphoria, and intense drug craving. Most patients require nearly a month of daily opiate use before withdrawal symptoms will occur with cessation of use or with naloxone treatment. The symptoms are uncomfortable, but no deaths or serious complications have been reported in otherwise healthy patients. The acute syndrome can last for nearly a week, and mild symptoms may persist for months. When given to an opiate addict, naloxone can precipitate acute withdrawal in five minutes, symptoms peak in 30 minutes, and resolve in 1-2 hours. One should resist the temptation to use opiates in this setting, as very large amounts are required to displace naloxone from the opiate receptor and this would certainly result in serious overdose symptoms when naloxone effects cease. Treatment of opiate withdrawal from the ED usually consists of clonidine (5 mcg/kg up to 0.3 mg bid to qid), but caution is urged because simultaneous use of clonidine and opiates produce dramatic sedation and hypotension. More effective treatment of opiate withdrawal consists of gradually decreasing doses of methadone over 5-10 days to blunt withdrawal symptoms, but this is not normally done from the ED. An acute withdrawal syndrome is recognized in newborns whose mothers were addicted to opiates. Symptoms appear on the second day, and consist of irritability, crying, tremor, increases in respiratory rate, reflexes, diarrhea, yawning, and vomiting.
Rehabilitation of opiate addicts is conducted in two modes: inpatient detoxification and outpatient methadone maintenance. With inpatient detoxification, patients typically are withdrawn from opiates over several days and given support from organizations like Narcotics Anonymous. Recently, another approach, termed Ultra Rapid Opiate Detoxification (UROD), has been employed with some success. UROD consists of administering a combination of naloxone, naltrexone, and clonidine to patients under general anesthesia to rapidly (over several hours) withdraw the patient from opiates.106 One recent follow-up study of patients undergoing this treatment method found 55% of 123 patients were relapse-free six months after treatment.107 Outpatient methadone can be used to maintain opiate addicts or to gradually withdrawal them over several months. Patients enrolled in these programs receive their methadone only from designated program centers, and ED physicians are cautioned against giving prescriptions to patients who state they "ran out" or "missed their dose."
IVDA Complications. The majority of substance abusers who inject their drugs are opiate (heroin) addicts, and they suffer a multitude of medical complications that are unique to IVDAs. Complications are related to infections (e.g., HIV, hepatitis, cellulitis, abscesses, endocarditis, tetanus, pneumonia) or to problems with injection technique (e.g., intra-arterial injection, neuropathies). Renal failure from rhabdomyolysis also can occur when patients are in drug-induced "coma" for extended periods.
Infectious complications from IVDA can be occult and deadly. HIV infection is common among opiate addicts, with one 1993 study providing a hint to the high risk these individuals have for seroconversion. The authors examined 255 opiate addicts in Philadelphia, and found a baseline rate of HIV of 12%.108 During the next 18 months, 22% of patients not in a methadone treatment program seroconverted. As many of these patients may not be aware of their HIV status, any patient with history of IVDA who has not had a recent negative HIV test should be considered at very high risk for occult HIV infection. The many complications of HIV infection should be kept in mind when evaluating these patients. Likewise, hepatitis is common among IVDAs and complications of chronic hepatitis infection should be kept in mind in these patients as well. Some heroin addicts also heavily abuse alcohol, and this may accelerate damage to their livers.
Skin infections commonly are seen in IVDAs. Cellulitis and abscesses often are seen on the forearms and hands. Staphylococci are the most common organism causing these infections, but anaerobic bacteria also are seen. When needed, antibiotic therapy should be given that covers anaerobic organisms. Infections of the hands or fingers should prompt consultation, and typically result in admission to a hand specialist, as gangrene rapidly can destroy tissue and lead to permanent disability or even amputation. Abscesses in the neck, axilla, or groin should be drained in the operating room due to the proximity of major vessels. Mycotic aneurysms should be considered when treating abscess in these areas, and ultrasound or angiography may be required to rule these out.
Endocarditis is a dangerous complication of IVDA, and morality remains unchanged during the past two decades.109 The incidence of bacterial endocarditis remains constant at around two cases per 1000 addicts. Any patient with a history of IVDA and fever needs to be evaluated for endocarditis, and admission often is necessary. Endocarditis is diagnosed by persistently positive blood cultures with cardiac valve involvement. Infections can affect the right or left side of the heart, although right-sided infections are most common in addicts. In right-sided infection, the clinical picture will be one of pneumonia and sepsis. Staphylococcus aureus is the most common organism, but also attacks left-side valves with equal frequency. Left-sided infections may present with systemic septic embolization of the brain, extremities (Osler’s nodes, Janeway lesions), and viscera. Streptococcus sp. are the second most common bacteria in endocarditis, and more commonly affect left-sided valves. Acute aortic insufficiency is a deadly complication that may be difficult to diagnose, as classic markers of chronic aortic insufficiency (wide pulse pressure, diastolic murmur) often are absent. Patients have dyspnea, tachycardia, and hypotension without another obvious source. Patients in whom the diagnosis of endocarditis is in question should be admitted to the intensive care unit. Up to 20% of patients with endocarditis will require surgical intervention, most commonly for congestive heart failure.
Spinal epidural abscess is another complication of IVDA that may be difficult to diagnose. Symptoms include a progression from backache to radicular symptoms, followed by weakness and eventually paraplegia. Plain films may reveal signs of osteomyelitis, but most often are negative. CT scan or magnetic resonance imaging (MRI) is the most useful imaging technique to make the diagnosis. To further add to the confusion, transverse myelitis can be seen in heroin abusers who restart injections after abstaining from use for six months to one year.
Necrotizing fasciitis is seen with IM injection, and should be suspected in any IVDA with sepsis and extremity pain. The involved extremity often has poor capillary refill, is swollen, and is tender to touch out of proportion to physical findings. The disease is characterized by very rapid progression, and emergent surgical debridement in combination with antibiotics (covering Staphylococcus, Streptocococcus, and gram-negative organisms) is mandatory. Even with treatment, the mortality rate is 30%.100 Long periods of muscle compression also can lead to rhabdomyolysis and renal failure in IVDAs. Septic arthritis and osteomyelitis should be suspected in any IVDA with bone or joint pain. Patients are at risk for careless injection of a joint space when using antecubital or wrist veins. Addicts also are affected by hematogenous spread to their bones, and seem to have a high incidence of spread to the sternoclavicular joint. Pseudomonas aeruginosa and Serratia marcescens are organisms commonly seen in IVDA infections, but are much less common in patients who do not inject. Finally, tetanus still is seen in two populations in the U.S.: the elderly and IVDAs. Heroin addicts with tetanus have a very high mortality,100 and cases have even been reported in previously immunized patients.110 In the 1950s, 8.3% of deaths among addicts were caused by tetanus.111 The diagnosis is based on clinical grounds, and prompt treatment with IV penicillin, hyperimmune globulin, and supportive therapy does not ensure survival.
Inadvertent intra-arterial injection causes immediate pain in the affected extremity, and patients often present with few physical findings. While more often seen in the brachial, radial, and femoral arteries, it also has been reported in the subclavian artery.112 Ultimately, ischemic necrosis of the entire limb can occur, but fasciotomy has been successful if the problem is recognized early in its course.113 Injections also can produce immediate pain from nerve damage, and this initially may be confused with intra-arterial injection. These patients often have signs of peripheral neuropathy progressing distally from the injection site. The brachial plexus, ulnar, and radial nerves commonly are affected sites.
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