eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Cocaine

Lynn Barkley Burnett, EdD, MS, LLB(c), Medical Advisor, Fresno County Sheriff's Department; Attending Consultant-in-Chief and Chairman, Medical Ethics, Clinical Faculty, Community Medical Centers; Adjunct Professor of Forensic Pathology, National University Master of Forensic Science Program
Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Updated: Nov 10, 2008

Introduction

Background

The ancient Incas of Peru believed cocaine to be a gift from the gods. However, it is a modern-day curse to the emergency physician.¹ Aside from alcohol and tobacco, cocaine is the most common cause of drug-related ED visits in the United States, accounting for nearly twice the number of reports to the Drug Abuse Warning Network (DAWN) as does marijuana or hashish, the second leading cause.

Cocaine is the most common reason for illicit drug-related ED visits in the United States. Patients who present to the ED with cocaine toxicity often have a combination of other drugs and cocaine in their system; in fact, the combined use of alcohol and cocaine may be the major cause of drug-related deaths.

The ubiquity of the acute or chronic effects of cocaine may cause patients to voice complaints involving virtually every organ system. Trauma is often associated with cocaine use. Even the absence of cocaine may precipitate an ED visit because patients may seek care for problems resulting from cocaine withdrawal.

History of use and abuse

Use of cocaine spans thousands of years, with a duality of effects noted throughout its history. Knowledge of its mind-altering function dates to at least 2000 BC. For centuries, indigenous mineworkers in Andean countries have used cocaine derived from the chewing of coca leaves as an endurance-enhancement agent. Spanish physicians reported the first European use of coca for medicinal purposes in 1596. Cocaine was not isolated from coca leaves until 1859. Nevertheless, by 1863, a wine fortified with 6 mg of cocaine alkaloid extract per ounce was marketed in France. By 1880, the US pharmaceutical company Parke-Davis sold a fluid extract containing 0.5 mg/mL of crude cocaine.

In 1884, William Stewart Halsted performed the first nerve block using cocaine as the anesthetic. Halsted subsequently became the first cocaine-impaired physician on record. That same year, Sigmund Freud published the essay "Uber Coca," in which he advocated the use of cocaine in the treatment of asthma, wasting diseases, and syphilis. As with Halsted, Freud also became dependent on cocaine. In 1885, John Styth Pemberton registered French Wine Cola in the United States. The popular product, which contained 60 mg of cocaine per 8-oz serving, was later renamed Coca-Cola.

By 1893, occasional reports of fatality were associated with cocaine use, and, in 1895, The Lancet reported a series of 6 deaths. By 1909, more than 10 tons of cocaine was being imported into the United States each year. Many over-the-counter medical products and elixirs had been created. One product for nasal application, called Dr. Tucker's Asthma Specific, contained 420 mg of cocaine per ounce.

The Harrison Narcotics Act of 1914 banned nonprescription use of cocaine-containing products. The resulting reduction in the use of cocaine marked the end of the first American cocaine epidemic. In the 1950s, amphetamine gradually replaced cocaine as the most common stimulant of abuse. However, this trend was reversed in the 1970s, with crack ushering in the second epidemic of US cocaine use in 1985.

Crack, which is generally sold in the form of "rocks," may also be sold in large pieces called slabs. These are approximately the size and shape of a stick of chewing gum and are sometimes scored to form smaller pieces. Users of cocaine in its crack form tend to be young adults aged 18-30 years who live in the central city and who are from low socioeconomic backgrounds. However, in 1986, the National Office of Drug Control Policy reported that young inner-city drug users were beginning to disdain crack as a ghetto drug. In Miami, for example, crack use had become unfashionable, and individuals continuing to use it, particularly African Americans, were trying to hide it from their peers.

Cocaine powder is currently marketed to adults from all ethnic backgrounds and socioeconomic groups, predominated by white men older than 30 years who live in the central city. In several locales, cocaine is mentioned as a club drug, but it is not as prominent as methamphetamine and some hallucinogens in the club environment.

Cocaine transported into the United States originates from coca plants in South America, 75% of which are in Columbia. In 2002, the NationalDrugThreatIntelligenceCenter reported that 353 metric tons of export-quality cocaine was available for US markets, with 75% passing through the Mexican–Central American corridor, 27% passing through the Caribbean, and 1% coming directly from South America.

In 2005, the US Government reported that retail-level prices for cocaine had increased, and purity had decreased. One gram of powder cocaine sold for an average of $100, although variation among major cities was noted: in New York City, for example, powder cocaine sold for $25-35 per gram, whereas in Detroit, a similar amount sold for $75-150. Crack cocaine, sold in the form of 0.1-0.2 g rocks, generally cost $10 per rock, with a price range of $2-40, depending on the size of the rock.

As reflected in the Synonyms, Key Words, and Related Terms, cocaine, alone or in combination, is known by a number of street names. The White House Office of National Drug Control Policy periodically updates street terms in its Drugs and the Drug Trade, a reference that may prove helpful when a patient uses an unfamiliar drug-related term. However, the clinician should always keep in mind the drug that patients believe they purchased may not be what they received and took.

The chemical name for cocaine is benzoylmethylecgonine. It is derived from the leaves of Erythroxylon coca, a shrub indigenous to Peru, Bolivia, Mexico, the West Indies, and Indonesia. Cocaine is a bitter crystalline alkaloid with the molecular formula of C₁₇ H₂₁ NO₄. Ecgonine, an important part of the cocaine molecule, is an ester-type local anesthetic that belongs to the tropane family, which also includes atropine and scopolamine.

The primary effect of cocaine is blockade of norepinephrine reuptake; its secondary effect is marked release of norepinephrine. These effects act synergistically to increase norepinephrine levels at the nerve terminal. Cocaine also causes moderate release and reuptake-blockade of serotonin and dopamine. Its marked local anesthetic effects are caused by blocking the sodium channels, which inhibits the conduction of nerve impulses, decreasing the resting membrane potential and the amplitude of the action potential while simultaneously prolonging the duration of the action potential.

Cocaine also blocks potassium channels. In some cellular membranes, it may block sodium-calcium exchange. The drug is fat soluble and freely crosses the blood-brain barrier. Cocaine appears to stimulate the CNS, with particular activity in the limbic system. There, it potentiates dopaminergic transmission in the ventral basal nuclei, producing the pleasurable behavioral effects that result in its widespread use.

Cocaine enters the United States in the form of a hydrochloride salt, having undergone numerous steps in refinement from the original coca leaf. In its hydrochloride form, cocaine may be absorbed topically across all mucosal membranes, including the oral, nasal (insufflation or snorting), GI, rectal, urethral, and vaginal membranes. It may also be injected intravenously or ingested. Ingested cocaine is poorly absorbed from the stomach because it is a weak base with a pKa of 8.6, but it is readily absorbed from the duodenum. Cocaine may be insufflated through a straw or rolled-up paper currency, or a coke spoon, typically containing 5-20 mg of the drug, may be used to snort cocaine. A 1-inch line typically contains 25-100 mg of the drug.

Crack is produced when the hydrochloride molecule is removed by ether extraction, which frees the basic cocaine molecule, or "freebase.". Heating does not destroy freebase, rather it melts at 98°C and vaporizes at higher temperatures. These physical properties allow it to be smoked. 

Crack is lipid soluble and therefore rapidly absorbed in the pulmonary capillaries. The term crack describes the crackling sound heard when cocaine freebase is smoked. Crack may be smoked in a pipe bowl containing 50-100 mg or in a cigarette with as much as 300 mg. Smoking crack bypasses the vasoconstriction that results when cocaine is snorted; therefore, the effects are similar to taking cocaine intravenously. Crack smokers may aggressively inhale against a small pipe and then perform a Valsalva maneuver before exhaling against pursed lips or forcefully blow the drug into a partner's mouth. These techniques are reputed to enhance the euphoria of cocaine.

All of the cocaine injected intravenously is delivered to the circulatory system, versus 20-30% of cocaine that is ingested or inhaled. With repeated use, tolerance develops so that the intensity and duration of effect decrease. People who use cocaine long term may dose themselves as frequently as every 10 minutes, binge as long as 7 days at a time and use as much as 10 g/d. Reverse tolerance, with onset of seizures and paranoid ideation at decreased doses, has been observed in animals and is thought to occur in humans as well.

Approximately 30-50% of cocaine is metabolized by hepatic esterases and plasma pseudocholinesterase, resulting in the formation of ecgonine methyl ester. Spontaneous nonenzymatic hydrolysis of another 30-40% results in benzoylecgonine. Both products are water-soluble, metabolically active, and capable of increasing blood pressure (BP). Benzoylecgonine, which has a half-life of 7.5 hours, can induce seizures, perhaps even hours to days after the last use.

Approximately 80-90% of injected cocaine is rapidly metabolized. Decreased hepatic perfusion, secondary to conditions, such as hypotension or low-output congestive heart failure (CHF), results in elevation of cocaine levels. A similar result may be observed in pregnant women, fetuses, infants, patients with liver disease, and elderly men, because their plasma cholinesterase activity is decreased. In addition, some people have a genetic deficiency of plasma pseudocholinesterase or a nutritional predisposition to abnormally low pseudocholinesterase levels. Some have postulated that these patients may metabolize cocaine slowly and have increased sensitivity to small doses of cocaine, which places them at risk for increased toxicity and sudden death. Evidence supporting this postulate is scant.

Most of the remaining amount of cocaine is metabolized by hepatic N -demethylation into norcocaine, which is metabolically active. Pregnancy, during which circulating progesterone levels are high, or the exogenous administration of progesterone increase the activity of hepatic N -demethylation. This increased formation of norcocaine, which is more vasoconstrictive than cocaine, may result in women being more sensitive to the cardiotoxic effects of cocaine than men as a result of hormonal potentiation.

Approximately 1-5% of cocaine is excreted, unaltered, through the kidneys within 6 hours of use.

With the multiplicity of physiologic and pharmacologic modifiers cited above, the literature reflects tremendous variability in the reported lethal dose of cocaine in humans. The range is as little as 20 mg IV, to a mean of 500 mg ingested orally, to 1.4 g.

Drug interactions and polypharmacy

More than 38 pharmacologically active substances have reportedly been used with cocaine; alcohol and nicotine are the most common. Although alcohol and nicotine are individually well known for their potential sequelae, their use with cocaine may acutely increase morbidity and mortality risks.

Between 30% and 60% of individuals who take cocaine combine it with alcohol. Clinical data indicate that the concurrent use of alcohol and cocaine is associated with increased mortality and morbidity from cardiovascular complications, hepatotoxicity, and behaviors leading to personal injury. In 74% of cocaine-related fatalities in the United States, another drug, usually ethanol, had been co-ingested. The addition of alcohol to cocaine increases the risk of sudden death 25-fold.

The increased risk from the concomitant use of alcohol and cocaine is enhanced by the formation of a third active compound of toxicologic importance, namely, ethylbenzoylecgonine, commonly known as cocaethylene. Although its behavioral pharmacology and psychomotor stimulant effects are similar to those of cocaine, its toxicity is greater. The plasma half-life of cocaethylene is longer than that of cocaine, and inferential evidence suggests that the lethal dose to kill 50% of subjects (LD50) is lower.

Although most cocaine metabolism involves serum cholinesterase, some of the drug is metabolized in the liver by carboxylesterases. In the presence of alcohol, a nonspecific carboxylesterase catalyses ethyl transesterification of cocaine to cocaethylene. Cocaine is the rate-limiting substrate in this reaction. Cocaethylene can be detected in urine and blood within 100 minutes after a person uses alcohol and intranasal cocaine. Whereas the half-life of cocaine is approximately 40 minutes, the half-life of cocaethylene is 2.5 hours, which may explain why cocaine-related symptoms can continue for some time after cocaine is last used.

The human brain, heart, liver, and placenta bind cocaine and cocaethylene. As with cocaine, cocaethylene binds to dopamine and norepinephrine transporters and inhibits catecholamine reuptake (primarily norepinephrine) into nerve terminals. The increased "high" reported with the concurrent use of alcohol and cocaine may be the result of the additive effect of cocaine and cocaethylene. Yet another reason may be the relationship between these substances and serotonin. The binding of serotonin by cocaine may modulate the high and may be the cause of the dysphoric effects of cocaine. Cocaethylene, which is 40 times less potent than cocaine in binding to the serotonin receptor, does not share this negative property.

In dog studies, cocaethylene was a more potent precipitant of convulsions and cause of lethality than cocaine. This is probably because cocaethylene blocks sodium channels more potently than cocaine. Although the toxic level of cocaethylene in humans is not known, the LD50 in mice was 93 mg/kg for cocaine versus 60 mg/kg for cocaethylene. The process of cocaethylene formation continues for several hours, which may explain why sudden deaths may occur 6-12 hours after cocaine ingestion.

Cocaethylene, which is ultimately metabolized to benzoylecgonine, is not the only factor augmenting the effects of cocaine with ethanol.² Consumption of ethanol before cocaine use also increases the bioavailability of cocaine.

Signs et al present an exception to the weight of the literature in a study based on 57 ED patients who tested positive for both alcohol and cocaine. In these patients, systolic and diastolic BP, heart rate, and body temperature did not significantly differ between those testing positive for both alcohol and cocaine and drug-free control subjects.³ This may be because chronic cocaine users reportedly develop tolerance to the cardiovascular effects of the drug. Signs et al concluded that the incidence of serious cardiovascular complications resulting from simultaneous use of cocaine and ethanol does not appear to be significantly higher than that observed in patients using only cocaine, only ethanol, or no drug.³

Nicotine is the second drug most commonly combined with cocaine. Many of the physiologic effects of nicotine are identical to those of cocaine. Nicotine produces a hypertensive and tachycardic response that is mediated by stimulation of the sympathetic ganglia and the adrenergic medulla. This response is coupled with the discharge of catecholamines from sympathetic nerve endings. Cigarette smoking also causes arterial endothelial desquamation and ultrastructural changes, a reduction of endothelial-cell prostacyclin production, increased serum fibrinogen levels, activation of platelets with enhancement of adhesiveness and aggregability, diminished coronary flow reserve, and an alpha-adrenergically mediated increase in coronary artery tone in patients with coronary atherosclerosis.

Most patients with cocaine-induced myocardial infarction (MI) also smoke cigarettes, a finding which suggests that simultaneous use of cocaine and tobacco may enhance coronary vasospasm. Of patients with cocaine-induced MI, 38% had normal coronary arteries; 77% of this group (average age, 32 y) had an anterior-wall MI. More than two thirds were moderate-to-heavy cigarette smokers (>1-2 packs daily). The average number of additional coronary risk factors, however, was less than 1.

Combining cocaine and heroin into a speedball causes frequent complications, as evidenced by the high-profile cases of actors John Belushi, River Phoenix, and Chris Farley. Speedballing accounts for 12-15% of cocaine-related episodes in patients presenting to EDs in the United States. In speedballing, heroin is injected or snorted, followed immediately by smoking of cocaine. Cocaine is harder to purchase during the summer months than at other times, thus heroin users may speedball with crack in the summer. The effects of heroin last longer than do those of crack, and it modulates symptoms secondary to withdrawal from crack. In both cases, the second drug is used to supplement, rather than substitute, the primary drug.

Persons addicted to crack may also use heroin to dampen the agitation produced by extended crack use. Body packers—smugglers who use their GI tract as a hiding place for large quantities of carefully wrapped packages of cocaine—often use a similar approach. They may take benzodiazepines to prevent becoming too high should a package rupture. Some premedicate themselves with a constipating agent, such as diphenoxylate with atropine, to prevent themselves from having a bowel movement before they arrive at their destination.

Dissolving and injecting crack is less expensive than purchasing enough cocaine powder to produce the same effect. Some users dissolve crack in lemon juice or vinegar before injecting it intravenously, a practice that reportedly produces a more intense rush than smoking the same amount of crack. If the vein is missed, the result is pain and potential abscess formation.

Various agents can heighten the effects of cocaine and contribute to complications. Organophosphates may be taken to deplete pseudocholinesterase, prolonging the effects of cocaine. However, because it produces organophosphate toxicity, the risk of fatality is increased. Cholinesterase inhibitors, such as carbamates, have a similar effect. Another practice involves coabusing crack cocaine and phenytoin to enhance the intoxication. In this practice, unbound phenytoin causes persons with hypoalbuminemia to become symptomatic at lowered drug levels; if death occurs, it usually is the result of respiratory and subsequent circulatory collapse.

The risk of severe effects is increased when cocaine is combined with drugs such as monoamine oxidase inhibitors, tricyclic antidepressants (TCAs), alpha-methyldopa, and reserpine. These drugs alter the metabolism of epinephrine and norepinephrine, potentiating their effects and, in the presence of cocaine, inducing an adrenergic crisis. Serotonin syndrome may result when serotonin selective reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), are taken concurrently with sympathomimetics.

Illicit drugs are frequently admixed with additional chemicals either to increase the apparent quantity of the street drug or to enhance its effect. For example, 8-20% of stimulants available on the street contain cocaine and methamphetamine hydrochloride.

Adulterants are added to cocaine intentionally or are left over from the manufacturing process. Substitutes are compounds that have pharmacologic properties similar to those of cocaine and that are used in its place. The potential for adverse effects is considerably compounded by the presence of adulterants and substitutes. Among the substances used to cut cocaine are local anesthetics (eg, procaine, lidocaine, tetracaine), other stimulants (eg, amphetamine, caffeine, methylphenidate, strychnine), lysergic acid diethylamide (LSD), phencyclidine (PCP), phenytoin, heroin, marijuana, and hashish. Other adulterants may include quinine, talc (ie, magnesium silicate), ascorbic acid, boric acid, chalk, laundry detergent, meat tenderizer, laxatives, plaster of Paris, cornstarch, and lactose. Many of these substances cause pulmonary and systemic reactions when taken intravenously, by insufflation, or by smoking; therefore, they may substantially contribute to the toxicity of cocaine use.

Pathophysiology

Most acute cocaine-related nontraumatic deaths are the result of tachydysrhythmias. Other causes of sudden death associated with cocaine use include stroke, subarachnoid hemorrhage, hyperthermia, and the consequences of agitated delirium. MI can result from acute vasospasm, dysrhythmias, or chronic accelerated atherogenic disease.

Dysrhythmias

The cardiovascular effects of cocaine result primarily from direct actions on the heart and secondarily from effects on the CNS. Cocaine causes central and peripheral adrenergic stimulation by inhibiting the reuptake of norepinephrine and dopamine at preganglionic sympathetic nerve endings. By preventing catecholamine reuptake at presynaptic terminals, cocaine causes catecholamine to accumulate at the postsynaptic membranes.

Without presynaptic reuptake, the action of a neurotransmitter on its receptors becomes sustained. The effects of endogenous catecholamines are thereby potentiated, resulting in tachycardia, hypertension, vasoconstriction, and increased myocardial oxygen consumption. Although cocaine-related tachydysrhythmias result primarily from increases in catecholamine levels, the local anesthetic properties of cocaine can impair impulse conduction in the ventricle, providing a substrate for reentrant ventricular dysrhythmias.

People who abuse cocaine may be exposed to toxic levels of circulating catecholamines. In one study, 48 mg of cocaine more than doubled circulating levels of norepinephrine (420 pg/mL increased to 900 pg/mL).⁴ However, most cocaine-related dysrhythmic fatalities occur in patients with low or modest levels of cocaine use. This finding suggests that the mechanism of death may be different in long-term cocaine users, in whom sudden death is most likely the consequence of adrenergic effects and long-term catecholamine toxicity.

In rat studies, long-term use of cocaine markedly increased norepinephrine content of the left ventricle, raising the possibility that long-term cocaine users should they also accumulate excess norepinephrine may be at risk for a malignant arrhythmia. Of note, coincident with the increase in ventricular catecholamine concentration, the rate of catecholamine synthesis was reduced, reflecting physiologic attempts to decrease sympathetic tone secondary to chronic cocaine stimulation.

Alterations in cardiac histology may produce an arrhythmogenic anatomic substrate. Independent of coronary artery disease or clinically documented MI, cocaine use may induce scattered foci of myocarditis, microfocal fibrosis, and contraction band necrosis, the severity of which is correlated with serum and urine concentrations of cocaine. Although common in the hearts of cocaine and other stimulant abusers, such findings are found in only a minority of hearts examined.

Other conditions providing an anatomic arrhythmogenic substrate include the accessory pathways resulting in Wolff-Parkinson-White (WPW) syndrome, and left ventricular enlargement.

In patients with an arrhythmogenic anatomic substrate, even low levels of cocaine can cause tachydysrhythmias. In a study of 19 people who had survived cocaine-related cardiac arrest, 8 had asystolic arrest (5 because of massive overdose) and the remaining 11 had arrest resulting from ventricular fibrillation (VF). Of the latter group, all had an anatomic substrate for the dysrhythmia: 2 patients had an MI, 3 had WPW, and 6 had left ventricular hypertrophy or cardiomyopathy. On subsequent electrophysiologic testing, several patients had dysrhythmias, which were induced only after they had been given cocaine.⁴

Electrical conduction becomes disorganized in enlarged hearts, a finding that assumes added significance because cardiac enlargement is observed with chronic cocaine use. Rat studies have demonstrated that cocaine causes genetic changes in cardiac myocytes. Hemodynamic overload results in the production of high levels of atrial natriuretic factor (ANF). Increased levels of mRNA coding for ANF were measurable within 4 hours after rats were injected with 40 mg/kg of cocaine. When that same dose was administered to rats over 28 days, levels of mRNA coding for collagen and heavy-chain myosin increased, and left ventricular mass increased by 20%. Increased collagen production and increased left ventricular mass are independent risk factors for sudden death.

Similar findings also are observed in humans. The hearts of cocaine users are 10% heavier than those of nonusers. In a study of 200 asymptomatic patients in a rehabilitation program who had used cocaine long term, one third had increased QRS voltage, which was indicative of left ventricular enlargement. Another study of asymptomatic patients in rehabilitation revealed that more than 40% had an echocardiographically demonstrable increased in left ventricular mass.⁴  

An autopsy study conducted by Darke, Kay, and Duflou (2006) compared cardiovascular and cerebrovascular pathology in decedents dying of cocaine toxicity, opioid toxicity, and those dying of hanging who were toxicologically negative for cocaine or opioids.⁵  With gender, effects of age, and body mass index (BMI) having been controlled for, 1 in 7 cocaine users were found to have left ventricular hypertrophy, two and one-half times the odds of such a pathologic diagnosis being made in either comparison group. In patients with enlarged hearts due to long-term exposure to high levels of cocaine, even low cocaine levels can be lethal.

Cocaine also has quinidinelike direct cardiotoxic effects, causing intraventricular conduction delays, as reflected by widening of the QRS and prolongation of the QT segment. In large doses, blockade of the fast sodium channels prolongs the slope of phase 0 of the cardiac action potential, which may result in a negative inotropic response, bradycardia, and, often as a precursor to death, hypotension from decreased contractility and dysrhythmias.

With high blood levels of cocaine, such as those observed in a body packer or body stuffer when a cocaine packet ruptures, or in a binge user with unlimited cocaine supply, the membrane-stabilizing effects of cocaine may cause cardiac arrest from asystole. In such cases, blood levels may exceed 50,000 ng/mL. Cardiac arrest is even more likely if the patient also has been consuming alcohol, with resultant production of cocaethylene. Tolerance rapidly develops to the euphoriant effects of cocaine but not to its local anesthetic effects of membrane stabilization.

MI and acute coronary syndromes

A 2001 nationally representative study of 10,085 American adults aged 18-45 years found that regular use of cocaine was associated with an increased likelihood of MI. Approximately 1 of every 4 nonfatal MIs was attributable to frequent use of cocaine (defined in this study as >10 uses in a lifetime).⁶

Patients with cocaine-related MI often have fixed atherosclerotic lesions. In addition to these lesions, which may themselves be of clinical significance, cocaine-induced elevations in pulse and BP increase myocardial work. The additional metabolic requirements that result may convert an asymptomatic obstruction into one of clinical significance.

Substantial evidence indicates that cocaine use causes accelerated coronary atherosclerosis. According to a 1995 study of trauma fatalities among men with a mean age of 34 years and an incidental finding of cocaine metabolites, 25% had lesions in 2 or more vessels, and 19% had disease in 3-4 vessels. Of the control subjects, only 6% had 2-vessel disease, and none had 3- or 4-vessel disease. In another study of 22 long-term cocaine users with a mean age of 32 years, all of whom died suddenly with detectable serum cocaine levels, severe narrowing of more than 75% cross-sectional area was found in 1 or more coronary arteries in 36% of patients.⁴

Hollander and Hoffman reviewed and analyzed the literature of 91 patients with cocaine-induced MI. Cardiac catheterization in 54 patients demonstrated that 31% had significant coronary atherosclerosis.⁷ Autopsy studies of patients with cocaine-related MI revealed atherosclerotic lesions in more than one half of patients.⁷ In another review of medical examiners' records, 495 deceased patients had positive toxicologic findings of cocaine; 6 of them, whose mean age was 29 years, had MI with total thrombotic occlusion primarily involving the left anterior descending coronary artery. All of the patients had significant coronary atherosclerosis, with 83% having lesions that caused luminal stenosis of more than 75% cross-sectional area in 1 or more vessels.

Of the patients reviewed by Hollander and Hoffman, 24% had a thrombotic occlusion in the absence of clinically significant coronary disease.⁷ Cocaine's effect of increasing levels of plasma plasminogen activator enhances clot formation. In addition, cocaine activates platelets both directly and indirectly by means of an alpha-adrenergic–mediated increase in platelet aggregation.

Cocaine increases the production of the potent vasoconstrictor endothelin, and simultaneously decreases the production of nitrous oxide, a powerful vasodilator. As a result of alpha-adrenergic stimulation, cocaine may exert a direct vasoconstrictive effect by increasing the influx of calcium across endothelial cell membranes. These factors may produce coronary artery spasm. Although this may occur even in patients who do not have significant coronary artery disease, spasm is most pronounced in portions of the coronary artery that are already narrowed, a phenomenon that is particularly prominent in cocaine users. Therefore, in patients who do have high-grade obstruction, including patients whose stenoses were previously asymptomatic, coronary artery spasm of even modest degree can have a devastating consequence.

In healthy coronary arteries, endothelial cells release endothelium-derived relaxing factor (EDRF) and prostacyclin, which synergistically interact to relax vascular smooth muscle and to inhibit platelet adhesion and aggregation. Mild atherosclerosis and hypercholesterolemia impair endothelium-mediated vasodilation in coronary arteries, and evidence from animal studies suggests that endothelial dysfunction predisposes a person to vasoconstriction and arterial spasm. Hypersensitivity to the vasoconstrictor effects of catecholamines has also been demonstrated in humans with endothelial dysfunction. Therefore, individuals with mild coronary disease who use cocaine may be predisposed to occlusive vascular spasm at the site of early atherosclerotic lesions.

The combination of intimal hyperplasia, accelerated atherosclerosis, and endothelial dysfunction create a prothrombotic milieu.

Cocaine also potentiates platelet thromboxane production and decreases protein C and antithrombin III production, as well as the production and release of prostacyclin. Aggregating platelets are an important source of serotonin. In patients with dysfunctional endothelium, serotonin causes intense vasoconstriction because of its unopposed effects on vascular smooth muscle.

Chronic use of cocaine appears to deplete stores of dopamine in peripheral nerve terminals. In patients undergoing cocaine withdrawal, more than one third have frequent episodes of ST-segment elevation (similar to variant angina), as documented on Holter monitoring. Inhibition of dopamine-mediated coronary vasodilatation secondary to dopamine depletion has been advanced as the hypothetical cause.

Patients with cocaine-related ischemic chest pain, even those who have had MIs, tend to do well after they stop using cocaine.

The effects of cocaine on the heart also include myocarditis and dilated cardiomyopathy. Myocarditis may be 5 times more common in people who use cocaine than in control subjects. It may be the result of microvascular injury, and it is a common autopsy finding in patients dying from cocaine toxicity. The mechanisms producing these effects are unknown, but hypotheses include a direct effect on lymphocyte activity, cytotoxicity of myocardial cells secondary to an increase in the activity of natural killer cells, hypersensitivity reactions (suggested by eosinophilic infiltrate), and induction of focal myocarditis from catecholamine administration.

Cocaine causes a direct negative inotropic effect on cardiac muscle, resulting in transient toxic cardiomyopathy. In one small series, 8 of 10 subjects who used cocaine long term had chest pain without MI but left ventricular ejection fractions less than 50%. In one case report, Jouriles describes a 35-year-old woman who developed hypotension, seizures, and hypoxemia after smoking crack cocaine; she had an ejection fraction of 10%, as observed on echocardiography.⁸

Neurologic effects

Cocaine users have been found to have a 14-fold increase in risk of ischemic or hemorrhagic stroke when compared with matched controls. In the study of Darke, Kaye and Duflou, atherosclerosis of the basal vasculature of the brain was noted in approximately 10% of the cocaine toxicity cases autopsied versus less than 1% noted in either of the comparison groups.⁵

Cocaine acts as a CNS stimulant by inhibiting presynaptic reuptake of norepinephrine, dopamine, and serotonin. It also causes release of epinephrine by the adrenal glands. The intensity and duration of the stimulant effects of cocaine are mediated by the rate at which blood levels of cocaine rise (a function of the route of administration) (see Table 1) and the peak of blood levels.

Cocaine-induced seizure is a severe manifestation of toxicity. Cocaine may cause generalized tonic and clonic convulsions as well as focal seizures. Intense stimulation of sigma and muscarinic receptors by cocaine and increased synaptic concentration of serotonin have been proposed as causal. Cocaine lowers the threshold for seizures and may produce a kindling effect on neurons that promotes convulsions.

The frequency of seizures ranges from a low as 1% to as high as 29%, perhaps a reflection of an increase in cocaine use from one time period to another or the concurrent use of other drugs. Of 474 patients with medical complications of cocaine abuse, 8% experienced first-time seizures and, of these, 85% had seizures during administration of the drug.

Cocaine-associated seizures may occur in naive and long-term users and are mostly single tonic-clonic, resolving without intervention. However, status epilepticus may occur. The first stage of status epilepticus is manifested by generalized tonic-clonic seizures associated with hypertension, hyperpyrexia, and diaphoresis. After approximately 30 minutes, the second stage may occur, in which cerebral autoregulation fails, cerebral blood flow diminishes, and systemic hypotension occurs. During this phase, the only clinical manifestations may be minor twitching, though cerebral electrical seizure activity continues.

Drugs that increase intrasynaptic dopamine change the density and sensitivity of dopamine receptors, with different effects on different receptor subtypes in different areas of the brain.⁹ Excited delirium, cocaine-associated rhabdomyolysis (CAR), and neuroleptic malignant syndrome (NMS) share many common features that can be explained by aberrant dopaminergic function.

Long-term cocaine use decreases the density of dopamine-1 (D1) receptors throughout the striatal reward centers, but it does not affect the number of dopamine-2 (D2) receptors. Antagonism of nigrostriatal dopamine function may cause extrapyramidal motor dysfunction, including dystonic reactions, bradykinesia, akinesia, akathisia, pseudoparkinsonism, and catalepsy. Neuroleptic agents are the principal medications that cause dystonic reactions by means of their blockade of dopamine receptors in the nigrostriatal pathways. Cocaine may increase the risk of neuroleptic-induced dystonias, a problem compounded by the street marketing of substances, such as haloperidol, sold as cocaine.

Over time, the continued use of cocaine may result in a net depletion of dopamine. Therefore, cocaine may be an independent cause of dystonic reactions. Two biochemical events, dopamine receptor blockade by neuroleptics and dopamine depletion by cocaine, result in the same effect, namely, the absence of physiologic dopamine in the nigrostriatal area of the brain. These events may represent the pathophysiologic basis for cocaine-associated dystonias. Intrauterine exposure to cocaine has been suggested as a cause of dystonia in infants.

Agitated (excited) delirium

Agitated delirium, also known as excited delirium, is a common presentation in patients dying from cocaine toxicity. Of cocaine-associated deaths investigated by the Medical Examiner's Department of Metropolitan Dade County, Florida, between 1979 and 1990, excited delirium was the terminal event in approximately 1 of every 6 fatalities. Patients with excited delirium had an immediate onset of bizarre and violent behavior, which included aggression, combativeness, hyperactivity, hyperthermia, extreme paranoia, unexpected strength, and/or incoherent shouting. All of these were followed by cardiorespiratory arrest.⁹

Although heart weight, ventricular hypertrophy, and past MI are not risk factors, repeated binges of cocaine use are associated with fatal excited delirium. The frequency of use that increases risk has not, however, been determined. Individuals with excited delirium may be more sensitive to the life-threatening effects of catecholamine surges than other cocaine users. Excited delirium appears to be generated by increased intrasynaptic dopamine concentrations resulting from a defect in the regulation of the dopamine transporter. Cocaine recognition sites on the striatal dopamine transporter are increased in cocaine users without excited delirium compared with drug-free controls. Persons dying from excited delirium have no such increase; therefore, they may have problems in clearing dopamine from the synapses, a condition that can easily result in agitation and delirium.

Hyperthermia, which may also be caused by downregulation of dopamine receptors, increases the incidence of fatal excited delirium. Death from excited delirium is more common in the summer months than at other times (55% vs 33% for other accidental cocaine toxicity deaths); therefore, high ambient temperature and humidity may play roles in the development of hyperthermia. An independent risk factor for fatal excited delirium is a body mass index (weight in kilograms/height in square meters) in the upper 3 quartiles, with the risk appearing to increase after a threshold is exceeded rather than in a dose-response fashion.

Restraints have been implicated as an exacerbating factor, particularly when the patient is prone. Sudden death occurring during prone restraint of a person in excited delirium appears to be induced by a combination of at least 3 factors that increase oxygen demand and decrease oxygen delivery:

1. The psychiatric or drug-induced state of agitated delirium coupled with police confrontation places catecholamine stress on the heart.
2. The hyperactivity associated with excited delirium coupled with struggling against the police and/or restraints increases oxygen demands on the heart and lungs.
3. A hogtied position impairs breathing by inhibiting chest-wall and diaphragmatic movement.

Hyperthermia

Temperature dysregulation is also a problem with cocaine intoxication, as demonstrated by Callaway and Clark, who reported that patients presented with rectal temperatures as high as 45.6°C.¹⁰ Hyperthermia is a marker for severe toxicity, and it is associated with a number of complications, including renal failure, disseminated intravascular coagulation, acidosis, hepatic injury, and rhabdomyolysis.

Because dopamine plays a role in the regulation of core body temperature, increased dopaminergic neurotransmission may contribute to psychostimulant-induced hyperthermia in cocaine users, including those with excited delirium.

D2 receptors are involved with processes that decrease core temperature. The number of D2 receptors in the temperature regulatory centers of the hypothalamus is substantially reduced in persons with excited delirium. These decreases in D2 receptors lead to unopposed increases in temperature mediated through D1 receptors, which are not affected in individuals who die from excited delirium.

Ruttenber et al hypothesize that hyperthermia may result from extensive muscular activity in the setting of warm ambient temperature and, perhaps, humidity in combination with aberrant thermoregulation in the hypothalamus and mesolimbic system.⁹ Antagonism of central and peripheral catecholamine receptors may be required to protect against psychostimulant-induced hyperthermia because peripherally released catecholamines may directly stimulate muscle or other thermogenic tissue.

Cocaine-induced seizures can also contribute to hyperthermia, though cocaine can induce hyperthermia in the absence of seizures. In animal studies, hyperthermia was the most significant parameter in the lethality of continuous cocaine infusion.

Agitation secondary to intoxication or withdrawal increases motor activity, which increases heat production. The patient's volume needs are thereby increased, and, when not met, they lead to decreased renal perfusion. Heat production may also contribute to increased muscle breakdown, resulting in myoglobinuria. Myoglobinuria, in conjunction with decreased renal perfusion, causes acute tubular necrosis.

Cocaine-associated rhabdomyolysis (CAR)

Excitement, delirium, and hyperthermia frequently precede the onset of CAR. If excited delirium and CAR have a similar cause, the spectrum of severity ranges from rhabdomyolysis with no excited delirium or hyperthermia to various combinations of these 3 conditions.

Long-term, rather than short-term, cocaine use is responsible for persistent changes in dopaminergic function that place users at risk for excited delirium and CAR. Elevations in muscle-enzyme levels are observed in asymptomatic people who use cocaine long term and in untreated persons with schizophrenia. This evidence lends support to the hypothesis that chronic alterations in dopaminergic function can affect the physiology of skeletal muscle.

Acidemia

Acidemia is seen in a clinically significant toxicity and may play an important role in cocaine-related death. In experimental studies, calcium delivery to myofilaments is decreased and contractile proteins become less responsive in the presence of lowered intracellular pH, resulting in depression of myocardial contractility.

Acidosis also potentiates dysrhythmias by repolarization and depolarization abnormalities that lead to reexcitation states. As pH decreases, calcium is spontaneously released from the sarcoplasmic reticulum, resulting in a transient depolarizing current that can precipitate dysrhythmias during diastole. In addition, acidosis decreases conductance between the gap junctions of cardiac cells, which slows propagation of the action potential. In the presence of cocaine, which diminishes sodium conductance, a severe reduction in conduction velocity may occur, increasing the likelihood of dysrhythmia production by means of reentry excitation.

Frequency

United States

The 2006 National Survey on Drug Use and Health found that 35.3 million Americans older than 12 years have used cocaine at least once, with 8.5 million having used cocaine in its crack form. Figures for annual use of cocaine were 6.1 million, of which 1.5 million had used crack. Reports indicate that 2.4 million Americans used cocaine within the previous 30-days, with 702,000 reporting the use of crack.¹¹

Since the early 1970s, in an ongoing national survey of approximately 600 hospital EDs, DAWN has reported the number of episodes of patients seeking treatment related to their use of an illegal drug or their nonmedical use of a legal drug. Although drug-related ED visits declined 6% from 1995-1996, they had previously risen by 65% from 1978-1995, compared with a 24% overall increase in ED visits during the same period.¹² Although the increase in drug-related emergencies may partly result from an increased use of drugs in combination (particularly alcohol), changes in the route of administration, and changes in the amount of drug used per administration, the primary cause appears to be cocaine.

Cocaine-related ED visits increased 78% from 1990-1994, remained statistically level from 1994-1996, and then increased 33% as of 2002.

According to DAWN, in 2005, cocaine was associated with 31% of ED visits related to drug misuse or abuse.¹²  The true relevance of this percentage is best appreciated when it is contrasted with 1978 data showing that cocaine accounted for only 1% of ED visits.

International

In the late 1990s, cocaine was reported to be a major public health issue in at least 3 of 6 major cities in Canada. In Mexico, cocaine was the primary drug of choice reported by patients in drug-treatment programs in 16 cities. In 5 of 7 capital cities of Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panama, and the Dominican Republic, cocaine use increased.

Mortality/Morbidity

• DAWN monitors fatalities reported by Medical Examiners/Coroners (ME/C) in 40 metropolitan areas in the United States. Cocaine was the most frequently reported substance associated with drug abuse or misuse deaths in the DAWN ME/C data for 2003.¹³ Cocaine was reported in 39% of such drug deaths, ranging from 8-70% in various areas. In 75% of the cocaine-associated deaths, 1 or more other drugs were involved. 
• Sequelae of intravenous injection may cause morbidity.
• A "pocket shot" is an attempted injection of the internal jugular vein by directing the needle into the depression in the neck superior to the clavicle and lateral to the sternocleidomastoid. Such attempts can lacerate the apical pleura and/or vasculature resulting in pneumothorax, hemothorax, or hydropneumothorax. This is usually observed in the left side because most people have right-hand dominance, and it is easiest for them to attempt injection into the left side of the neck.
• Intravenous injection may cause aneurysm or pseudoaneurysm of central veins or arteries, and rupture may result in intrathoracic or intra-abdominal hemorrhage, vascular obstruction, and arteriovenous fistulae. A necrotizing angiitis similar to periarteritis nodosa may develop, frequently with severe effects upon the kidneys, such as microaneurysm formation, segmental stenoses, and thromboses. The result is severe hypertension and oliguric renal failure. Similar lesions may occur in the small bowel, liver, and/or pancreas.
• Other sequelae that may be observed with intravenous drug use include AIDS, thrombophlebitis, cellulitis, abscesses, viral and talc-induced hepatitis, subacute bacterial endocarditis (SBE), foreign-particle pulmonary emboli, tetanus, malaria, and cotton fever.
• See also the Physical section below.

Race

Table 2. DAWN Data, 2005  

Sex

• DAWN reports for 2005 reflect that men accounted for 292,402 cocaine-related ED visits, and women, 155,985. This disparity may have a physiologic basis.
• Compared on a milligram-per-kilogram basis, women who use cocaine intranasally have significantly lower plasma cocaine levels than men. Women using cocaine in the luteal phase of their menstrual cycle have peak plasma levels lower than those observed during the follicular phase of the cycle. Notwithstanding these differences, be mindful of the potential for increased cocaine cardiotoxicity in women previously discussed (see The drug and its pharmacology).
• Men detect the effects of cocaine faster and report more episodes of intense good feelings (euphoria) or bad feelings (dysphoria) than women.

Age

Table 3. Cocaine Use in Lifetime, Past Year, and Past Month, by Detailed Age Category: 2006¹¹

• Since 1988, cocaine-related episodes have almost tripled among people older than 35 years. In 1994-1996, the number of cocaine-related ED visits recorded among people aged older than 35 years increased by 21%. In that same period, no significant differences were found in any other age group. The reasons for the increase are not known. However, older people may be seeking emergency care for drug-related problems more often than they have before, or they may be making more frequent visits to EDs than in the past because aging increases their susceptibility to a wide variety of health problems that are exacerbated by drug use, particularly prolonged use and its cumulative effects.
• In a study reported by Hollander et al, the frequency of cocaine positivity for patients aged 41-50 years was 18%. Of patients aged 51-60 years, 3% had positive results for cocaine. The prevalence of cocaine use in older persons was significantly higher than expected in population-based surveys.¹⁴ Older patients are at greatest risk of myocardial ischemia caused by cocaine. Query patients in all age groups about their cocaine use.
• Advanced age does not preclude cocaine as the cause of a patient’s emergent presentation, as is demonstrated by the death of Ike Turner. The Medical Examiner ascribed the 76-year-old musician’s death to acute cocaine toxicity.¹⁵

Clinical

History

The factors addressed below focus on drug use. They supplement the questions and elements of the standard medical-history interview. A drug history is indicated in all patients and should be particularly complete in those presenting with drug reactions, acute anxiety, or other psychological problems, as well as in those with acute cardiovascular, pulmonary, or neurologic symptoms. If the patient is confused or unresponsive, query relatives, friends, or witnesses about antecedent activities, and seizures or syncope. This is crucial, especially if patients are carrying cocaine in their body, because they often have no stigmata of drug abuse.

• History of present illness
  • Did onlookers or other users apply any resuscitation measures that may cause complications?
  • What was used? (Do not accept denial unquestioningly. Street drugs often are not what they are marketed to be. Adulterants markedly increase the potential for complications.)
  • When was the substance used and for how long was it used? What is the patient's tolerance, cross-tolerance, and reverse tolerance? Is evidence of an abstinence syndrome present?
  • What was the total amount of cocaine used? How does this compare with the amount generally used? How long after cocaine use were symptoms noted?
  • By what route was it taken? How long has this route been used?
  • Does the patient have symptoms such as pain (eg, chest, abdominal), dyspnea, altered tactile sensation (eg, cocaine bugs, Magnan sign), or hallucinations (eg, lilliputian hallucination, halo lights around objects)? Do reports of seizures or altered mental status exist?
  • Is the patient pregnant (eg, decreased plasma cholinesterase)?
  • Is the patient a victim of domestic violence? (Substance abuse may develop or worsen as a result of domestic violence. Accordingly, it is appropriate to consider domestic violence when evaluating a patient for alcohol intoxication or drug toxicity and overdose.)
• Review of systems
  • Is the effect of cocaine increased secondary to liver disease or CHF? Is evidence of MI or coronary artery disease present? Is evidence of a dysrhythmogenic substrate (eg, myocarditis, cardiomyopathy, WPW) present?
  • When considering the extent of the review of systems (ROS), be mindful of the wide range of organ systems that cocaine and its routes of administration can affect.
• Medication and drug use history
  • What is the patient's average daily use? What is his or her history of cocaine and other drug use? (The mechanism of fatality differs for long-term cocaine users.)
  • Does the patient smoke (ie, does he or she have coronary vasospasm)? How many packs does the patient smoke per day? When did the patient smoke in relation to using cocaine?
  • Does the patient use alcohol (ie, is cocaethylene formation possible)? If so, did the patient drink before or during cocaine uses? How much alcohol was consumed?
  • What other substances were used? How much was consumed? What route of intake was used?
  • Does the patient have any other drug addictions? Were any drug combinations taken or were drugs taken to increase, prolong, or decrease the effects of cocaine?
  • Could medications taken by the patient potentiate the effects of cocaine? Is the patient in withdrawal?
  • What prompted the visit to the ED? DAWN data for 1998 reflect the reasons for cocaine-related ED visits:
    • Unexpected reaction - 21.9%
    • Overdose - 15.1%
    • Chronic effects - 13.8%
    • Accidental injury - 4.9%
    • Withdrawal - 3.2%
  • Does the patient want help in coping with cocaine use? DAWN data from 2004 reported that 46% of patients presenting to EDs did so for detoxification.¹⁶

Physical

Multisystem effects of cocaine

Cocaine has multisystemic effects, and virtually every organ system may be a site of action. Suspect cocaine use in patients, especially young patients, with altered mental status, new-onset seizures, hypertension, chest pain, myocardial ischemia or infarction, shortness of breath, intracranial hemorrhage, epistaxis, or psychiatric illness. Pay particular attention to the assessment of vital signs and to a detailed examination of the cardiac, pulmonary, and neurologic systems, as listed below.

Association with trauma

Trauma is becoming increasingly associated with use of cocaine. Cocaine can cause agitation, paranoia, distractibility, distorted perception, and depression. All of these may increase the likelihood of violence, suicide, or accidental injury. When cocaine is combined with alcohol, the frequency of ED presentations is substantially greater than when cocaine is used alone.

Differential diagnosis

Cocaine overdose may resemble serotonin syndrome, lithium toxicity, toxicity due to TCAs, neuroleptic malignant syndrome (NMS), thyroid storm, and other hyperadrenergic states.

Consider the diagnosis of phenytoin toxicity in cocaine users who present with lethargy or cerebellar findings. Signs of phenytoin toxicity are correlated with serum levels and include nystagmus, ataxia, dysarthria, lethargy, hypotension, and coma.

• Vital signs and general presentation
• Although bradycardia is reported as an initial effect, the classic presentation of a patient under the influence of cocaine is tachycardia and hypertension.
• When Hollander and Hoffman reviewed the literature concerning 91 patients with cocaine-induced MI, they found that as many patients were bradycardic as tachycardic, and one third were hypertensive.¹⁷ As a result of pathologic vasoconstriction, a patient with hemorrhagic trauma may present with a normal mean arterial pressure.
• Cocaine causes pathologic vasoconstriction, thus hypovolemia secondary to hemorrhage may be delayed in recognition because the patient maintains a normal mean arterial pressure. This combination of pathophysiologic factors, coupled with delayed recognition, increases the potential for cerebral insult.¹⁸
• Chronic cocaine use downregulates adrenergic receptors and decreases endogenous catecholamine stores in the heart. This may affect the patient's presentation, as was observed in a study of patients admitted to a trauma service. Of 84 patients with a systolic BP less than 100 mm Hg, 45% had relative bradycardia (heart rate <100 bpm). Toxicology data were obtained infrequently, but when determined, they demonstrated that cocaine was more frequently reported in patients with bradycardia (76%) than in those with tachycardia (26%).
• The patient's skin may be cool and clammy though the patient is hyperthermic; therefore, obtaining a rectal temperature is advisable.
• Cardiovascular findings
• Cardiopulmonary complaints are the most common presenting manifestations of cocaine abuse and include chest pain (frequently observed in long-term use or overdose), MI, arrhythmias, and cardiomyopathy.
• In individuals with cocaine-associated MI, median times to the onset of chest pain vary with the route or form of cocaine use: 30 minutes for intravenous use, 90 minutes for crack, and 135 minutes for intranasal use.
• Chest pain may be observed in as many as 40% of patients presenting to the ED after admitting to cocaine use. In a study of urban and suburban EDs, cocaine or its metabolites were found in 17% of patients presenting with chest pain. This starkly contrasts with the pretest estimated prevalences of 2-4% for the suburban study site and 10% for the urban sites. The mean age of patients with chest discomfort and positive assays for cocaine was 36 years.
• Include cocaine in the differential diagnosis of any acute vascular problem.
• Vascular spasm may cause blindness, renal infarction, limb ischemia, and intestinal ischemia.
• Limb ischemia may occur after intra-arterial injection. This may be accidental, or intentional due to the unavailability of veins because of sclerosis secondary to repetitive puncture, or due to the desired effects from arterial injection.
• Aortic dissection may also be associated with cocaine use.
• Hypertension occurs frequently.
• Other cardiovascular findings include the following:
• Dysrhythmias (premature ventricular contractions [PVCs], supraventricular tachycardia [SVT], ventricular tachycardias [VT], VF)
• Vasomotor collapse
• High-output heart failure
• Respiratory findings
• As reported in the literature, the primary acute pulmonary complaint associated with cocaine use is cough with black sputum (44% of patients). Chest pain is secondary, affecting 38% (pleurisy in 64% of patients with pain). Of patients with new-onset asthma who present to large urban EDs, 36.4% have urine screens positive for cocaine (compared with 13.6% of control patients without asthma). Hemoptysis accounts for 25% of pulmonary complaints, the result of pulmonary and bronchial constriction and ischemia resulting in interstitial and alveolar hemorrhage.
• Crack lung, a syndrome usually occurring 1-48 hours after cocaine smoking, is a hypersensitivity pneumonitis. It consists of the constellation of chest pain, cough with hemoptysis, dyspnea, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, and pulmonary and systemic eosinophilia.
• Barotrauma, such as pneumothorax and pneumomediastinum, may result from smoking or snorting cocaine and then performing a prolonged Valsalva maneuver to increase the effect of the drug. The increased airway pressure ruptures an alveolar bleb, and free air dissects along peribronchial paths into the mediastinum and pleural cavities.
• The incidence of respiratory complaints in people who use cocaine is not known. The following respiratory toxic reactions are reported in association with cocaine use:
• Barotrauma (eg, pneumothorax, pneumopericardium, pneumomediastinum)
• Pulmonary hemorrhage or infarction
• Diffuse alveolar hemorrhage
• Pulmonary edema
• Wheezing secondary to bronchial muscle constriction
• Airway irritation via damage to bronchial epithelial cells, and stimulation of vagal receptors, inducing bronchospasm, exacerbating asthma
• Eosinophilic lung disease
• Recurrent transient pulmonary infiltrates with peripheral eosinophilia
• Chronic diffuse interstitial pneumonia with mild fibrosis
• CNS stimulant effects (eg, neurogenic pulmonary edema, respiratory depression in overdose or postictal state, abnormal hypoxic response in infants of cocaine-abusing mothers, sudden infant death syndrome (SIDS), and pulmonary hypertension)
• Crack lung or transient pulmonary infiltrates
• Nasal septum perforation and/or aspiration
• Bronchiolitis obliterans organizing pneumonia
• Granulomatosis
• Sinusitis
• Epiglottitis
• Bronchitis
• Cellulose granulomas in lung
• Panlobular emphysema
• Needle or other foreign body aspiration
• Alveolar accumulation of carbonaceous material
• Airway burns or tracheal stenosis
• Tachypnea, irregular breathing
• Respiratory arrest
• Acute lung injury (noncardiogenic [increased permeability] pulmonary edema)
• Eyes, nose, mouth, and throat findings
• Signs include reactive mydriasis, nystagmus (generally vertical but may be bidirectional), epistaxis, atrophic mucosa, ulcerated nasal septa, perforations, acute inflammation or scarring of the tongue, epiglottis, vocal cords, and trachea.
• Hoffman and Reimer list a variety of ophthalmologic complications from cocaine use¹⁹ :
• Cocaine-associated cerebral vasculitis, which may produce gradual decrease in visual acuity or acute blindness
• Central retinal artery occlusion
• Blurring of vision
• Endophthalmitis from systemic or local infection
• Foreign-body granuloma
• Foreign-body embolization
• Optic neuropathy, resulting from chronic sinusitis due to intranasal cocaine use and manifesting as decreased visual acuity
• Corneal ulcerations secondary to direct instillation of cocaine into the conjunctival fornix and vision loss caused by crack-induced corneal ulceration from direct irritation of the smoke, cocaine-induced epithelial disruption, and repeated mechanical disruption from rubbing
• Torticollis, trismus, and laryngospasm may endanger the airway.
• GI findings
• Vomiting, diarrhea, and hyperactive bowel sounds may be present. When evaluating a patient with a history of cocaine use and a complaint of abdominal pain, consider mesenteric ischemia in the differential diagnosis. Patients with abdominal pain must also be evaluated for renal infarction.
• The vascular supply to the intestine has many alpha-adrenergic receptors, and their stimulation may cause mesenteric ischemia. The clinical presentation of mesenteric ischemia includes abdominal pain and possibly tenderness, nausea, vomiting, and bloody diarrhea. Muscarinic receptor blockade results from high concentrations of cocaine, with anticholinergic effects on gastric motility that predisposes the person to ulceration from prolonged exposure to acid.
• Skin, thermoregulatory, and renal findings
• Patients may have sores or linear excoriations; crack pipe burns of the fingers or thumbs; thermal burns of the face and upper airway; and redness, swelling, and tenderness (secondary to phlebitis, vasculitis, cellulitis, and abscess formation).
• Search for track marks in the usual sites, such as the antecubital fossae, and unusual sites, such as under the tongue and on top of the feet.
• Excoriations from pruritus or hallucinations of crawling insects associated with cocaine use may also be found.
• Cocaine affects the anterior hypothalamus, which increases the thermoset point. Agitation secondary to intoxication or withdrawal results in increased motor activity, which causes increased heat production.
• Rule out occult infections in patients with fever.
• Evaluate patients with abdominal or back pain for renal infarction.
• Neurologic and psychiatric findings
• Altered sensorium and acute seizures are the most common cocaine-associated neurologic syndromes observed in the ED, accounting for 52% of related presentations. Other cocaine-related neurologic processes are toxic encephalopathy, ischemic and hemorrhagic stroke, neurogenic syncope, and movement disorders. Use of cocaine also decreases rapid eye movement (REM) sleep.
• Seizures, which can produce hyperthermia and lactic acidosis, are a major determinant of lethality.
• About 3-4% of all strokes occur in patients aged 15-45 years. Cocaine is a common cause of cerebrovascular events, including all varieties of stroke, in young patients. Cocaine-induced hypertension may lead to hemorrhage from cerebral aneurysms or ruptured arteriovenous malformations (AVMs).
• Extrapyramidal phenomena and other movement disorders, though uncommon, are reported in association with cocaine use. These effects are collectively referred to as "crack dancing." In a patient without a history of neuroleptic use such a presentation may be confusing to the ED physician.
• Headaches, some potentially resulting from inhibited serotonin reuptake, are common in people who use cocaine, whereas cerebral vasculitis is rare.
• Approximately 60% of people who regularly use cocaine report psychiatric complications of their drug use, and 18% have had visual or tactile hallucinations; a sensation of something crawling on the skin is most common.
• Psychiatric complications commonly associated with cocaine use include anxiety, depression, paranoia, delirium, psychosis, and suicide. Toxic psychosis might be misdiagnosed as paranoid schizophrenia.
• A crash follows cocaine binging and may result in extreme exhaustion (may be severe enough that the patient appears unresponsive), anxiety, psychomotor retardation, and increased appetite. Of note, the most common problem during a crash is depression that may reach suicidal proportions.
• In withdrawal, depletion of dopamine and norepinephrine leads to dysphoria, depression, and drug craving.
• In short, neurologic and psychiatric findings may include the following:
• Normal sensorium
• Altered mental status (a change in the level of consciousness or the content of consciousness)
• Confusion
• Restlessness
• Severe agitation
• An increase in purposeless psychomotor activity that may be exacerbated by nonspecific stimulation in the setting of cocaine use (commonly called cocaine leaps)
• "Overamped" or "wired" behavior
• Paranoia
• Delirium (a florid abnormal mental state characterized by disorientation, fear, and irritability with misperception of sensory stimuli)
• Headache
• Tremor
• Depression and extreme exhaustion associated with withdrawal following a binge
• Renal findings
• Vascular spasm may cause renal infarction.
• Cocaine may also exacerbate renal susceptibility to rhabdomyolysis by causing hyperthermia, vasoconstriction, and/or hypotension secondary to hypovolemia or MI.
• Endocrine and metabolic findings
• Acute toxic effects of cocaine may include acidosis, hyperkalemia, and hyperglycemia.
• Prolonged use of sympathomimetics, such as in a cocaine binge, may result in hypoglycemia.
• Musculoskeletal findings
• Cocaine use is among the drug-related causes of intrinsic muscle weakness.
• Wilson and Hobbs report a patient with Cori disease in whom cocaine unmasked subclinical skeletal muscle weakness, causing prolonged respiratory muscle insufficiency.
• Cocaine has also been implicated as a cause of impairment of neuromuscular transmission in a patient with myasthenia gravis.
• Packets of illicit drugs may be ingested or inserted into body cavities by "swallowers," "internal carriers," "couriers," or "mules" to intentionally transport drug, a practice called body packing. Another practice, body stuffing, involves swallowing relatively small amounts of loosely wrapped drug, or secreting packets in body cavities because of the fear of arrest. With suspicion of body packing or body stuffing, perform careful cavity searches of the rectum and vagina. Continued drug absorption is likely if toxicity continues for more than 4 hours.
• Altered mental status: A number of etiologic possibilities are possible, including toxic (eg, drug intoxication, withdrawal), metabolic, structural or traumatic, infectious, epileptic, or psychogenic causes.
• A simple toxicologic presentation is rare. Therefore, it is frequently necessary to differentiate agitation secondary to various intoxicants, withdrawal, or possibly both. In the agitated patient with extreme irritability, irrationality, and destructiveness, intoxication or withdrawal should be considered.
• Cocaine causes a sympathomimetic toxidrome, as do amphetamines, hallucinogens, and PCP; PCP causes the most persistent psychophysiologic reactions. Withdrawal from alcohol or sedative-hypnotics may cause the triad of hyperthermia, agitated delirium, and seizures.
• Phases of acute cocaine toxicity: Three phases are reported. In fatal cases, the onset and progression are accelerated, with convulsions and death frequently occurring in 2-3 minutes, though sometimes in 30 minutes. Cocaine stimulates the CNS in rostral-to-caudal fashion, with findings varying with the time since drug use.
• Phase I - Early stimulation
• CNS findings - Mydriasis, headache, bruxism, nausea, vomiting, vertigo, nonintentional tremor (eg, twitching of small muscles, especially facial and finger), tics, preconvulsive movements, and pseudohallucinations (eg, cocaine bugs)
• Circulatory findings - Possible increase in BP, slowed or increased pulse rate (possibly with ventricular ectopy), and pallor
• Respiratory findings - Increase in rate and depth
• Temperature findings - Elevated body temperature
• Behavioral findings - Euphoria, elation, garrulous talk, agitation, apprehension, excitation, restlessness, verbalization of impending doom, and emotional lability
• Phase II - Advanced stimulation
• CNS findings - Malignant encephalopathy, generalized seizures and status epilepticus, decreased responsiveness to all stimuli, greatly increased deep tendon reflexes, and incontinence
• Circulatory findings - Hypertension; tachycardia; and ventricular dysrhythmias (possible), which then result in weak, rapid, irregular pulse and hypotension; and peripheral cyanosis
• Respiratory findings - Tachypnea, dyspnea, gasping, and irregular breathing pattern
• Temperature - Severe hyperthermia (possible)
• Phase III - Depression and premorbid state
• CNS - Coma, areflexia, pupils fixed and dilated, flaccid paralysis, and loss of vital support functions
• Circulatory - Circulatory failure and cardiac arrest (VF or asystole)
• Respiratory - Respiratory failure, gross pulmonary edema, cyanosis, agonal respirations, and paralysis of respiration

Causes

• The National Institute on Drug Abuse (NIDA) estimates that 10% of individuals who begin using cocaine progress to serious, heavy use. After having tried cocaine, people cannot predict the extent to which they continue using the drug. According to 1999 DAWN data, patients visiting EDs for a drug-related cause provide the following reasons for using cocaine:
  • Dependence (49%)
  • Recreational use (37.6%)
  • Other psychic effects (19.7%)
  • Suicide (8.7%)
• A positive family history of substance abuse is related to the speed of developing dependence on cocaine and an earlier age of onset.
• Evidence suggests that cocaine dependence, similar to alcoholism, may have 2 subtypes, A and B (ie, type I and type II in the literature on alcoholism typology). Type A persons may develop cocaine dependence as a function of environmental influences, whereas type B persons may have certain premorbid risk factors that predispose them to a virulent form of cocaine abuse. Ball et al studied 399 patients with cocaine abuse or dependence in the first multidimensional subtyping study of cocaine users.²⁰ The most common presentation, observed in 67%, was type A. Women and African Americans most commonly had type A dependency, whereas men and whites most commonly had type B dependency.
  • Compared with persons with type A dependency, those with type B dependency had more severe abuse of alcohol and other drugs, addiction-related psychological impairment, antisocial behavior, and comorbid psychiatric problems.
  • Persons with type B dependency were more likely to be separated or divorced, to live alone or in an unstable situation, to have a family history of substance abuse, and to have had greater severity of childhood disorder than individuals with type A dependency. They also scored higher than those with type A dependency in assessments of sensation seeking, aggression, criminality, and violence.
  • Those with type B dependency had an early age of onset for antisocial personality disorder and early age of first use, first binge, first regular use, and first daily use of cocaine and alcohol. The quantity, frequency, duration, and severity of cocaine abuse and adverse effects (eg, loss of consciousness, chest pain, misperceived reality, violence, and use to relieve to stress) are greater with type B than with type A.
  • Although the groups do not differ in family history for psychiatric disorders, people with type B dependency had lifetime histories of major depression, suicide attempts, and total treatment episodes for psychiatric disorders as well as for abuse of alcohol and other drugs that were significantly greater than those with type A dependency.
  • No significant differences were found between the subtypes in terms of employment, education, referral source, number of close friends, age, time between the first use and the onset of symptoms of dependence, route of use, previous periods of abstinence from alcohol or other drugs, or the number of strategies used to control use.
• Rivara et al maintain that one half of those who abuse illicit drugs also have a mental disorder. Indeed, cocaine users, along with persons with alcoholism and those who abuse opiates, have elevated rates of antisocial personality, depression, anxiety, and polysubstance abuse. These traits also have been found in their first-degree relatives.²¹

Differential Diagnoses

Other Problems to Be Considered

CNS structural considerations (eg, hematoma, tumor, emboli, abscess, contusion)
Drug withdrawal
Exogenous toxins
Hypoxemia
Intracranial hemorrhage
Mania
Seizures
Serotonin syndrome
Thiamine deficiency
Thyroid storm
Thyrotoxicosis
Xanthine toxicity
Water and electrolyte imbalance

Workup

Laboratory Studies

• No laboratory studies are indicated if the patient has a clear history and mild symptoms.
• If history is absent or if the patient has moderate-to-severe toxicity, appropriate laboratory tests may be ordered to assess the following:
  • Complete blood cell count (CBC)
  • Electrolytes level
  • Glucose level
  • Pregnancy test
  • Calcium level
  • BUN level
  • Creatinine level
  • Arterial blood gases (ABGs) analysis
  • Creatine kinase (CK) level: An elevated CK level is nonspecific. In 19 patients with elevated CK levels, 5 had documented MI, and 14 had intramuscular injections or other muscle trauma. A CK level may be used to help rule out rhabdomyolysis.
  • Urinalysis (UA)
    • A UA should include inspection to detect myoglobinuria. In cocaine-induced rhabdomyolysis, a dipstick UA reveals an orthotoluidine reaction positive for heme in 75% of patients, findings positive for protein in 67%, and microscopic hematuria in some. On a urine drug screen, Drano or bleach can mask cocaine; alkaline urine may raise this suspicion.
    • Desipramine and amantadine, prescribed to reduce cravings for cocaine, may cause false-positive results on urine tests for amphetamines.
  • Toxicology
    • Urine, blood, gastric contents, and unknown substances found on patients or, such as on mustaches, may be sent for toxicologic evaluation. (Include the patient's clinical history and differential diagnosis of the toxins in question to guide the laboratory evaluations). However, high plasma cocaine concentrations are rarely observed because cocaine has a short half-life of 30-45 minutes. Furthermore, numerous studies have demonstrated that toxicology screens rarely change the clinical treatment of patients.
    • Although concentrations higher than 1 mg/L are generally associated with toxicity, deaths have been reported with blood levels of 0.1-20.9 mg/L. Because of this wide range of toxicity, quantitative blood levels of cocaine or metabolites are generally not clinically useful.
  • Half-life
    • Cocaine exhibits first-order kinetics over a wide dose range; therefore, after 5 half-lives (approximately 4 h), virtually all of the cocaine should have been converted to its metabolites. Hollander et al concur, indicating that urinary cocaine may be detected for 4-8 hours after a single intranasal dose. However, Lewin, Goldfrank, and Weisman maintain that most cocaine is excreted in the urine within 24 hours of ingestion.²²
    • Benzoylecgonine may be present in urine for as long as 60 hours after single use and for as long as 22 days after the cessation of heavy cocaine use. If the ratio of benzoylecgonine to cocaine found in the urine is less than 100:1, either the cocaine was ingested less than 10 hours before collection of the sample or ongoing liberation of cocaine is occurring from a body package.
• Also consider tests of the following:
  • Cardiac markers in patients with chest pain
  • Lactate dehydrogenase (LDH) level, aspartate aminotransferase (AST, formerly serum glutamic-oxaloacetic transaminase [SGOT]) level, prothrombin time (PT), activated partial thromboplastin time (aPTT), CSF, and cultures of blood and urine in patients with elevated temperatures
  • Serum osmolality and ketones in patients with altered mental status

Imaging Studies

• General chest radiography
  • Obtain a chest radiograph in patients with chest pain, hypoxia, or moderate-to-severe toxicity. The chest image of drug users may reveal diffuse granulomatous changes resulting from chronic parenteral abuse due to the injection of inert insoluble ingredients of oral preparations or insolubles used to cut cocaine (eg, talc). Septic pulmonary emboli appear round or wedge shaped; they may clear rapidly or cavitate. Aspiration pneumonitis and noncardiogenic pulmonary edema also may be demonstrated. Pulmonary abscesses may become evident after aspiration pneumonitis or after an intravenous injection of bacteria or toxic organic or inorganic materials.
  • Chest images may occasionally reveal a needle, catheter, or fragment thereof, which was lost during drug injection. An aneurysm or pseudoaneurysm may be noted if the person was mainlining, or directly injecting, into a central artery or vein; this finding is an indication for further imaging studies. Up to 50% of posteroanterior (PA) chest images may demonstrate normal findings, with pneumomediastinum demonstrable only on lateral views.
  • To evaluate an inflamed area (abscess or cellulitis) or nonhealing wound in an intravenous drug user, include a radiograph, and look for foreign bodies, such as needles or parts thereof, metal, glass, or painted materials, that may have become imbedded after trauma. A radiograph of the infected area also may reveal subcutaneous emphysema produced by gas-forming organisms in an anaerobic infection.
  • Skeletal images may reveal osteomyelitis or fractures. However, osteomyelitis may not be demonstrable on plain images for 1-2 weeks, and other imaging studies should be performed if such a diagnosis is considered. Fractures are a concern because people under the influence of a drug may have injury that they do not recognize because of their intoxication.
• Chest radiography to investigate body packing
  • Swallowed packets of cocaine may rupture, resulting in acute cocaine poisoning. They may also critically obstruct the esophagus or small bowel, typically at the ileocecal valve. The drug packets typically weigh 1-12 g.
  • Begin with plain images of the abdomen to search for packages. However, the rate of false-negative results is 1.2-33%, which may be because drug packages may not produce a radiographically visible outline or because shadows caused by constipation may obscure the silhouette.
  • Results from ultrasonography are commonly disappointing.
  • Contrast-enhanced study of the bowel or abdominal CT may be the only way of identifying the packages.
  • Regular radiologic examination is imperative to confirm successful transit of packages through the GI tract.
  • McCarron and Wood reported a series of 75 patients with suspected body packing of cocaine who were evaluated with kidneys, ureters, and bladder (KUB) radiography. Cocaine packages (15-175 per individual) were retrieved from 48 patients. In 73%, the KUB images showed foreign bodies. KUB findings were negative in 3% of patients with cocaine packages in the rectum and in another 16% who subsequently passed 15-135 packages.²³
  • McCarron and Wood identified 3 types of packages, with the following physical and radiographic characteristics and risk for rupture²³ :
    • Type 1: Condoms, toy balloons, or fingers of latex gloves contained cocaine in loose white powder form. Typically, the package material was stuffed with cocaine, tied, folded back on itself, and tied again at the opposite end. A variation involved wrapping a package with masking tape to make a small bundle, then covering it with 2 more condoms tied with fishing line. Type 1 packages radiographically appeared as well-defined circular or cigar-shaped white opacities. Ties, if radiographically apparent, had a rosette appearance. If gas halos were observed, they were irregular. This type of cocaine package posed the highest risk for breakage or leaching.
    • Type 2: About 5-7 layers of tubular latex, with a smooth tie on each end, covered white or light yellow matted cocaine powder. On direct inspection of the bundles, they appeared light yellow and were relatively large and uniform in size. These radiopaque bundles were oblong. When viewed radiographically, gas halos were present and regular, but no ties were apparent. Type 2 packages were less susceptible to breaking than type 1 packages.
    • Type 3: Yellow, hardened cocaine paste wrapped in aluminum foil, then wrapped again with 3-5 layers of tubular latex and securely tied at both ends. These packages were hard, smaller than type 1 and type 2 packages, and irregularly sized. They did not appear as foreign bodies on abdominal images. No breakage or leaching of cocaine was reported with this type of package.
  • The risk of bag rupture or leaching increases if the bag remains in the GI tract for a long period. In one series, 2 patients had sloughed pieces of wrapping, and 1 had evidence of leaching. After the container believed to be the last has passed, Perrone and Hoffman recommend imaging (eg, Gastrografin upper-GI series with small-bowel follow through) to ensure that the GI system has been fully purged of all packets.²⁴
• The ACEP recommends brain CT in patients presenting with first-time seizures. Perrone and Hoffman recommend CT scans of the head in all patients with cocaine-associated seizures because intracranial pathology often causes the seizures.²⁴

Other Tests

• Obtain a 12-lead ECG in patients with chest pain; hypoxia; dyspnea; an irregular, rapid, or slow pulse; altered mental status; or moderate-to-severe toxicity.
  • Of 48 patients admitted to an ICU with cocaine-induced chest pain, 86% had abnormal ECG findings, but only 6% were found to have sustained a MI.
  • The Brugada sign has been noted in cocaine users. This finding should prompt consideration of its implications for sudden cardiac death.
• Coma has several possible etiologies in the cocaine-toxic patient, including the second (nonconvulsive) stage of status epilepticus. Therefore, immediate STAT EEG is indicated in patients presenting with unexplained coma in whom this is thought to be a possibility.

Procedures

• Renzi recommends lumbar puncture (LP) to rule out intracranial hemorrhage in patients with persistent headache after the patient's BP is normalized and contraindications are ruled out on head CT.²⁵
  • When LP is considered for this possible indication, remember that headaches are common in cocaine users secondary to decreased uptake of serotonin.
  • Consider LP in all patients with hyperthermia or altered mental status.

Treatment

Prehospital Care

• Establish the patient's airway, breathing, and circulation (ABCs); provide oxygen; obtain intravenous access; monitor and frequently check vital signs; monitor glucose levels (eg, with the Accu-Chek device) in patients with altered mental status; and carefully use naloxone (Narcan) in patients with altered mental status.
• Administer benzodiazepines to manage seizures.
• Patients with cocaine toxicity may be combative, aggressive, and disoriented, and they may have delusions of persecution or hallucinations. Caution is appropriate because the patient may attempt to harm the emergency medical technician (EMT). The patient may have to be restrained, though this should be done with caution and adequate personnel.

Emergency Department Care

Data of DAWN-reporting EDs may provide an impression of the degree of physiologic derangement in cocaine-toxic patients presenting to EDs. Past reports indicated that 52.2% of patients presenting to EDs with cocaine toxicity were treated and released, 44.2% were admitted, and 2.2% left against medical advice. The mortality rate was 0.3%.

General considerations

• Patients presenting with cocaine toxicity initially receive interventions directed at all patients in potentially unstable condition, including attention to ABCs, oxygen, intravenous access, and monitoring (cardiac monitoring and pulse oximetry).
• As assessment is accomplished, the temperature of a hyperthermic patient may continue to rise secondary to agitation and their fighting of the restraints. The temperature may reach critical levels; therefore, early consideration should be given to the potential need to treat hyperpyrexia.
• Remove any residual cocaine from the nasal passages.
• Protect the patient from hypoglycemia, which may present as any neuropsychiatric abnormality.
• Never base treatment on the results of a drug screen; rely on clinical findings instead.
• Reassurance is important if the patient is oriented.
• Avoid physical or pharmacologic restraints if possible. Benzodiazepines are an effective and safe pharmacologic restraint in these patients if one is needed.
• Pregnancy cannot be readily diagnosed or excluded on the basis of the patient's history. The prevalence of unrecognized pregnancy is as high as 6% in ED patients. Therefore, perform routine pregnancy testing in patients with overdose because physiologic changes in pregnancy may increase the patient's susceptibility to drug toxicity. Drug poisoning may induce miscarriage, premature labor, or fetal toxicity, and modifications may be necessary for acute management of the overdose.
• The effects of cocaine are generally short lived. Monitor patients until they are no longer tachycardic and hypertensive (because of the drug) and until they are calm and cooperative. Patients who have normal vital signs and normothermia may be discharged home after observation for 2-6 hours.

Therapeutic dilemmas
 
Medications commonly administered to treat one or more of the pathophysiologic effects of cocaine in emergency cardiovascular care may worsen other adverse effects of cocaine, and therefore raise concerns about their use in treating cocaine poisoning. Conflicting reports and recommendations in the literature compound the controversy surrounding pharmacologic treatment of cocaine toxicity.

As an example, the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care acknowledge that many toxicologic approaches are not based on high levels of research, but rather on case reports, small case series, and data extrapolated from animal studies. Therefore, although the American Heart Association (AHA) recommendations for treatment of individuals with poisoning are class IIb (interventions considered within the standard of care), many represent only expert consensus.

• Epinephrine and vasopressin
• Epinephrine has been the drug of choice for the treatment of cardiac arrest, primarily for its alpha-adrenergic effects. However, epinephrine and cocaine have many similar cardiovascular effects. Furthermore, cocaine prevents the reuptake of exogenously administered epinephrine. Therefore, if epinephrine is used, AHA Guidelines 2005 and the AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider recommend that high-dose epinephrine be avoided and that the interval for its administration be increased (q5-10min).
• If VF or ventricular tachycardia is recurrent or refractory and epinephrine or excessive levels of endogenous catecholamines are the suspected cause, consider withholding further doses of epinephrine.
• Because of this similarity in the cardiovascular effects caused by cocaine and epinephrine, the administration of epinephrine to a patient who arrests in a hyperadrenergic state has been likened to "pouring gasoline on a fire."²⁶
• In theory, vasopressin may offer considerable advantages over epinephrine in cardiac arrest secondary to cocaine toxicity.^27,26
• The hyperadrenergic state caused by cocaine increases myocardial oxygen demand. Epinephrine has the same effect. Vasopressin, on the other hand, increases coronary blood flow, and thereby myocardial oxygen availablity.²⁸
• Cocaine toxicity frequently causes acidosis: epinephrine loses much of its effectiveness in an acidotic milieu²⁸ , whereas vasopressin demonstrates vasoconstricting efficacy even with severe acidosis; vital considerations given that improved coronary perfusion during CPR improves patient survival.²⁹
• Lidocaine
• Lidocaine is one of the primary drugs used to treat ventricular dysrhythmias. Although some animal data indicate that lidocaine can reverse the ECG effects of cocaine and protect against death, others indicate that lidocaine may lower the seizure threshold and potentiate cocaine toxicity.
• Derlet, Tseng, and Albertson caution that lidocaine potentiates the CNS toxicity of cocaine.³⁰ Noting this small "safety window," Derlet states that lidocaine may be used, but advises precautions, such as double or triple checking the total dose, solution concentration, and any infusion pump.³¹
• Cocaine and lidocaine have similar pharmacologic effects. Therefore, the possibility that lidocaine may increase toxicity by potentiating the effects of cocaine on the cardiovascular system has been a concern.
• The AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider cites this similarity for the therapeutic role that lidocaine may play in competing with cocaine at the sodium channel, thereby decreasing the effects of cocaine.
• In the setting of cocaine toxicity, the decision as to whether or not to use lidocaine must be carefully considered, weighing its potential benefit on ventricular rhythm disturbances versus the synergistic toxic effects of lidocaine on seizure risk.
• Beta-blockers
• Strong evidence supports avoidance of nonselective beta-blockers for cocaine-induced ischemia. Echocardiographic data suggest that the antihypertensive effect of propranolol results from depression of cardiac output rather than relief of systemic vascular resistance. Propranolol exacerbates the depression of coronary blood flow induced by cocaine because of unopposed alpha stimulation after beta-blockade. Just before death, cocaine toxicity usually results in hypotension, a condition that use of a beta-blocker further compounds.
• Malbrain et al recommended esmolol for "save use" in managing life-threatening hypertension and tachycardia.³² Esmolol is a selective beta1-adrenergic blocker with rapid onset and short duration of action (elimination half-life, 9 min). They advise that the coadministration of esmolol and sodium nitroprusside should be reserved for severe hypertension that is unresponsive to other treatment and/or complicated by aortic dissection.
• Guidelines 2005 does discuss use of carefully titrated doses of labetalol as a third-line agent for drug-induced hypertensive emergencies.³³ However, labetalol, a combined alpha- and beta-blocking agent, has an alpha-to-beta blockade ratio of 1:7. Therefore, it may not provide enough protection for cocaine-toxic patients from (relatively) unopposed alpha stimulation. Its risk of exacerbating myocardial ischemia parallels the risk of beta-blockers. Labetalol also increased seizures and mortality in animal models; therefore, its use cannot be promoted.

Cardiovascular concerns

• Cocaine-associated VF: Prolonged resuscitative efforts are recommended in AHA Guidelines 2005 for patients with cardiopulmonary arrest in a setting of drug intoxication.³⁴
• Hypotheses about the causes of cocaine-associated VF, if confirmed, have treatment implications. In one study, when the heart rate is held constant, alpha-adrenergic but not beta-adrenergic receptor antagonists prevented cocaine-induced VF. Cocaine activation of myocardial alpha-adrenergic receptors, specifically alpha1A-adrenergic receptors, may substantially contribute to VF during myocardial ischemia. Activation of these receptors elevates cytosolic calcium levels and provokes delayed after-depolarizations. Therefore, calcium overload may be the final common pathway linking enhanced adrenergic activity to cocaine-induced VF.
• This observation raises a question as to the role, if any, of calcium antagonists in cocaine toxicity. Studies supporting the use of calcium channel blockers have been performed only in animal models. Consistent with a local anesthetic mechanism of its toxic effects, calcium channel blockers have not been shown to reduce cocaine toxicity in humans. Furthermore, they increase the lethality of cocaine. This additive lethality may result from the negative inotropic effects shared by these agents. 
• Cocaine-associated cardiac dysrhythmias: Ventricular ectopy is usually transient and is managed with careful observation and escalating doses of benzodiazepine to blunt the hypersympathetic state by modulating cocaine-induced CNS stimulation. Treat malignant ventricular ectopy and perfusing VT by ensuring good oxygenation, by treating the hyperadrenergic state with escalating doses of benzodiazepine, and by administering appropriate antidysrhythmic medications if ventricular arrhythmias persist. Ensure that a defibrillator is readily available.
• Malbrain recommends the use of an antidysrhythmic agent, such as bretylium (though now rarely found on code carts).³² Another pharmacologic option is magnesium sulfate, though caution is necessary because it may cause hypotension.
• Consider sodium bicarbonate for treating dysrhythmias resulting from the direct toxic effects of cocaine,³⁵ such as when sodium channel blockade causes a QRS >100 milliseconds. Dual mechanisms of action have been proposed for its therapeutic effects: (1) Alterations in pH may change the conformation of the sodium channel, and (2) increased extracellular sodium concentrations may override sodium channel blockade. Hourly measurements of blood pH are indicated, with appropriate adjustments until the blood pH is properly controlled. End points of bicarbonate therapy are a serum pH of 7.50-7.55.
• Paroxysmal SVT (PSVT), atrial flutter, and rapid atrial fibrillation are generally short-lived and do not require immediate treatment. Use escalating doses of benzodiazepine to treat hemodynamically stable patients with persistent supraventricular arrhythmias to blunt the hypersympathetic state by modulating cocaine-induced stimulation of the CNS, taking caution not to depress consciousness and create a need for respiratory assistance. In drug-induced hemodynamically significant tachycardia, the pathophysiologic mechanism responsible may be increased automaticity, triggered activity, or reentry phenomenon. Tachycardia caused by increased automaticity will not be responsive to interventions such as adenosine and synchronized cardioversion. Benzodiazepines are generally safe and effective in drug-induced hemodynamically significant tachycardia (HST). 
• Cocaine-associated chest pain and MI: Chest pain may result from musculoskeletal, cardiovascular, pulmonary, or other causes. In patients with cocaine-related chest pain, assume that cardiac ischemia is present until this is proven otherwise. Accordingly, the ED approach to such patients, in addition to oxygen, intravenous access, and monitoring, includes the following steps:
• Perform 12-lead ECG.
• Obtain chest imaging.
• Direct the initial pharmacologic approach to suspected cocaine-related myocardial ischemia at increasing coronary blood flow and decreasing sympathetic output.
• Nitroglycerin (NTG) is appropriate in managing cocaine-associated infarction or ischemia because it reduces cocaine-induced vasoconstriction in healthy and atherosclerotic segments of the coronary arteries.
• Small, incremental doses of benzodiazepines decrease norepinephrine release by the CNS, thereby counteracting the sympathomimetic effects of cocaine on the heart. Similar doses of morphine sulfate (MS) also alter hemodynamics and blood flow dramatically in patients with heightened sympathetic activity. Limiting factors for morphine and benzodiazepines include hypotension, somnolence, and respiratory depression. Kercher cautions that short-acting benzodiazepines (eg, lorazepam) should be prescribed at low doses for patients with hepatic disease, organic brain syndrome, and those taking medications inhibiting the metabolism and clearance of benzodiazepines (eg, those using nicotine or cimetidine [Tagamet]).³⁶
• Although benzodiazepines and NTG are first-line agents in drug-induced acute coronary syndromes, cocaine-induced vasoconstriction also is reversed by phentolamine. Therefore, AHA 2005 Guidelines recommends phentolamine as a second-line agent.³³
• AHA 2005 Guidelines further state that coronary vasodilators administered via the intracoronary route are preferable to peripheral administration, a factor favoring cardiac catheterization, as further addressed below. 
• In a study of MI in the setting of cocaine use, Hollander reports on 246 patients enrolled over 46 months at 6 hospitals. Of patients presenting with cocaine-associated chest pain, 5.7% had MI; other studies have reported rates of 19% and 31% for acute MI in patients admitted with chest pain and cocaine use. Route, length, and frequency of use and interval from last use did not differ between patients with MI and those without MI. Of interest, a history of chest pain was less common in patients with MI than in others.⁷
• In patients with prolonged unexplained chest pain, perform serial ECGs and cardiac-marker measurements to rule out MI. However, in one study, Hollander reports that patients with MI were as likely to present with normal or nonspecific ECG findings as with ischemic ECG findings. The sensitivity of the ECG in predicting MI was only 35.7%; therefore, ECG appears to be less sensitive in patients with cocaine-induced myocardial ischemia than in other patients presenting with ischemic chest pain. Interpretation of cardiac markers in patients with cocaine-induced symptoms may be difficult since levels of creatine kinase (CK) and CK MB-isoform (CK-MB) may be elevated in cocaine users who do not have an MI.
• Be mindful that as many as 43% of patients with cocaine-related chest pain meet standard ECG criteria for fibrinolysis despite being cardiac marker negative for infarction; a high percentage of such patients have early repolarization.
• Of additional importance, an increased incidence of mycotic aneurysms and CNS mass lesions may lead to an increased incidence of hemorrhagic complications in these patients. When evaluating patients for fibrinolytic therapy, remember that a history of intravenous drug use poses a relatively high risk for the possibility of coexisting vascular pathology.³⁵ Obtain a detailed history and perform physical and ancillary testing, as appropriate, directed at identifying endocarditis, septic pulmonary emboli, and pseudoaneurysm.
• AHA 2005 Guidelines state that intracoronary administration of fibrinolytics is preferred to blind peripheral administration in patients with drug-induced acute coronary syndrome. Fibrinolysis in the presence of hypertension or CNS vasculitis may be dangerous, and percutaneous transluminal coronary angioplasty (PTCA) may be a safer alternative when revascularization is indicated.
• In light of the above confounding factors, the AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider indicates that cardiac catheterization is recommended by many experts. 
• Fibrinolysis should thus be reserved for patients who cannot receive percutaneous coronary intervention within the requisite time and who have low risk for cerebrovascular bleeding and other hemorrhagic complications of fibrinolytic therapy.
• Patients may develop chest pain several hours after cocaine use.¹⁷ Recurrent coronary vasoconstriction associated with increased levels of benzoylecgonine and ethyl-methyl ecgonine may be responsible. Furthermore, patients with cocaine withdrawal may have dopamine depletion, resulting in intermittent coronary spasm.²⁴ MI has been attributed to cocaine use several days earlier, and Holter monitoring has documented cocaine-induced ischemia for several weeks after cocaine use.¹⁷ Recurrent ischemic chest pain is reported in patients who do and in patients who do not continue to abuse cocaine.¹⁷ Ischemia may persist for up to 2 weeks after the cessation of cocaine use; therefore, avoiding the use of beta-adrenergic blockade for as long as 2 weeks after withdrawal of the toxin may be prudent.
• Objective assessment may aid decision-making when the patient's treatment or disposition may be altered in the presence of cocaine.¹⁴ For example, beta-blockers are relatively contraindicated in cocaine use, but they are commonly given when cocaine is not considered a factor in myocardial injury or ischemia. However, in one study, 28% of patients with chest discomfort who tested positive for cocaine had denied using it. When beta-adrenergic blockade is being considered, even if cocaine toxicity is not suspected, a rapid bedside test for cocaine use may be appropriate because of its prevalence and the substantial rate of false-negative findings in the history of present illness.
• Hypertension
• Cocaine may cause a hypertensive emergency because of CNS stimulation and its peripheral alpha-agonist effects. Cocaine toxicity may also be superimposed on preexisting hypertension in patients who have become dependent on elevated BP to maintain cerebral perfusion. Carefully consider the patient's clinical status and history when deciding to treat hypertension.
• Hypertension secondary to cocaine is commonly responsive to intravenous benzodiazepines because benzodiazepines minimize the stimulant effects of cocaine on the CNS.
• A vasodilator, such as NTG or nitroprusside, may be titrated to effect if further therapy is indicated. NTG is the drug of choice in patients with chest pain. The use of nitroprusside to control hypertension has the additional advantage of aiding heat loss by peripheral vasodilatation.
• Hypotension: Hypotension may be treated with parenteral fluids and, if refractory to fluids, norepinephrine, a direct-acting pressor, is preferred over indirect agents like epinephrine.
• Aortic dissection: Include type A aortic dissection in the differential diagnosis of cocaine abuse with chest pain. ED care entails close cardiac and hemodynamic monitoring, treatment to reduce the progression of dissection, and administration of narcotics as needed for pain. Sodium nitroprusside should be used to control BP, but it may cause tachycardia, for which esmolol may be considered. Although the goals of therapy are to decrease the heart rate to 60-80 bpm and BP to 100-120 mm Hg, the therapeutic endpoint is the lowest level that permits continued end-organ perfusion.

Pulmonary concerns

• Cocaine affects pulmonary dynamics and may cause pulmonary edema. Other causes of pulmonary edema in the setting of cocaine use include CHF (with or without MI) and subarachnoid hemorrhage or concomitant use of other drugs (eg, heroin). Most patients with cocaine-associated pulmonary edema respond to standard medical treatment. 
• For resistant hypoxemia, positive-pressure ventilation with continuous positive airway pressure (CPAP) or intubation supplemented with positive end-expiratory pressure (PEEP) is usually effective. For patients with respiratory depression intubation may be indicated, as it is for those with apnea.
• Administration of naloxone to a patient who has been speedballing may negate the sedative effect of the opioid and leave the stimulant effect of the cocaine unopposed, precipitating or worsening cocaine toxicity. Naloxone is still indicated in respiratory depression but should be used with caution (ie, slowed rate of administration, lowered doses).
• Administration of flumazenil to patients with benzodiazepine use (eg, to blunt the effects of cocaine) may be dangerous. Cocaine is a gamma-aminobutyric acid (GABA) antagonist that may be blocked by benzodiazepines and potentiated by flumazenil. Use of flumazenil in the cocaine-intoxicated patient may induce seizures.

Neurologic concerns

• Seizures are a concern.
• Cocaine is one of the most common causes of drug- and toxin-associated seizures. Seizures may be a dire sign of toxicity that heralds life-threatening physiologic instability. Cocaine-associated seizures are usually generalized, but they may be partial. They may result directly from toxicity of the CNS or indirectly from hypoxemia, stroke, or other conditions. They may occur after recreational use, long-term abuse, or cocaine overdose. Seizures also occur in people who pack or stuff cocaine in their body, affecting 4% of patients who are body stuffers, with seizures expected in the first 2 hours.
• Seizures occurring from cocaine toxicity are managed as part of comprehensive patient treatment. Seizures and severe agitation require prompt attention to protect the airway and prevent hyperthermia. Although patients with serious compromise may require paralysis and mechanical ventilation, benzodiazepines are first-line therapy. Benzodiazepines directly enhance GABA-mediated neuronal inhibition, affecting the clinical and electrical manifestations. Their overall effectiveness in terminating cocaine-induced seizures is 75-90%.
• Although Perrone and Hoffman recommend head CT in all cases of cocaine-associated seizures because of the risk of associated intracranial lesions,²⁴ Renzi believes that a brief seizure, clearly temporally related to cocaine use, requires no further workup if the patient is otherwise healthy, alert, coherent, without headache, and neurologically intact.²⁵ If patients are not admitted, monitor them in the ED for several hours.

Dystonic reactions

• Emotional distress can exacerbate dystonic reactions, whereas relaxation may reduce the intensity of such attacks. Using a calm reasoned approach in a quiet room markedly complements the effectiveness of pharmacologic interventions.
• Dopamine and acetylcholine have mutually antagonistic functions in the nigrostriatal system. Although diphenhydramine, with its anticholinergic properties, is the drug of choice for most dystonic reactions, it should be used with caution in cocaine toxicity. Antihistamines cause hyperthermia by central (eg, hypothalamic) and peripheral (inhibition of sweating and muscular rigidity) effects; cocaine also causes hyperthermia. Antihistamines and cocaine are sodium channel blockers. Therefore, coadministration of an antihistamine in the setting of cocaine use may potentiate a molecular pathophysiological cascade that exacerbates end-organ dysfunction.
• Benzodiazepines, with their anxiolytic and muscle relaxant properties, are alternative drugs for the treatment of dystonia. Although they only treat the manifestations of dystonias and not the pathophysiology underlying their development; the advantage of using benzodiazepines lies in their safety.

Metabolic concerns

• Hypoglycemia may present as any neuropsychiatric syndrome and is always a consideration in patients who present with altered mental status or convulsions. Rapid diagnosis by meter or Dextrostix prevents the deleterious effects reported for the administration of dextrose in the absence of hypoglycemia. If the adult patient is hypoglycemic, administer thiamine 100 mg followed by 50 mL of 50% dextrose (D50W).
• Acidosis has a profoundly adverse effect on myocardial contractility and may potentiate the effect of catecholamines. The correction of arterial pH, through ventilatory assistance and appropriate use of sodium bicarbonate, may be effective in terminating cocaine-induced dysrhythmias with resulting improvement of hemodynamics.

Hyperthermia

• Recognize and treat hyperthermia as a distinct entity. If psychostimulant-intoxicated patients do not die as a result of cardiac or cerebrovascular complications, the next most important steps in preventing further morbidity are control of hyperthermia and treatment of rhabdomyolysis. Assess the patient's core body temperature and maintain a high index of suspicion for hyperthermia. In the setting of serious hyperthermia, continuously monitor the core body temperature.
• Hyperthermia may be treated with convection cooling, which involves spraying the patient's exposed body with tepid water as fans circulate air. Tepid water prevents maladaptive shivering that may be induced by conduction cooling methods, although ice packs, ice water gastric lavage, or cooling blankets may also be used. Direct efforts at reducing body temperature to 101°F in 30-45 minutes.
• Do not use restraints (physical or pharmacologic) that interfere with dissolution of heat. If necessary, use light hand and foot restraints. Ensure adequacy of hydration and electrolytes. Benzodiazepines are an effective and safe pharmacologic restraint in these patients. Given parenterally, with the usual precautions, they rapidly calm hyperactive patients.
• Do not administer phenothiazines. Goldfrank, Flomenbaum, Lewin, and Weisman apply this injunction to butyrophenones as well.³⁷ Contrary views are, however, expressed in the literature. Callaway and Clark maintain that concerns about the potentiation of drug-induced seizures by butyrophenone neuroleptics (eg, haloperidol) may be exaggerated because such drugs have less effect on human seizure threshold than phenothiazines, and they interfere less with sweat-mediated evaporative cooling in drug-induced hyperthermia.¹⁰ Although Callaway and Clark believe that further studies are necessary to assess the efficacy of butyrophenones in the treatment of psychostimulant overdose,¹⁰ Colucciello and Tomaszewski indicate that haloperidol is effective in treating cocaine-related agitation and that no clinical data proscribe its use, theoretic concerns notwithstanding.³⁸
• Monitor patients with hyperthermia in the ED for several hours if they are not being admitted.

Cocaine-induced rhabdomyolysis

• The reported incidence of rhabdomyolysis in ED patients who use cocaine is 5-30%. Pathophysiologic hypotheses include placement of excessive demands on healthy muscle cells that cannot be met by available energy supplies, direct toxicity of cocaine upon the muscle membrane, cocaine-induced seizures, and the potential concomitant use of other drugs (eg, PCP, amphetamines) that are known to cause this syndrome.
• Risk factors for rhabdomyolysis include altered mental status, hyperactivity, fever, seizures, hypotension, dysrhythmias, and cardiac arrest. Rhabdomyolysis may be associated with hyperphosphatemia, myoglobinuria, nephrotoxicity, hyperkalemia, hypocalcemia, compartment syndromes, or disseminated intravascular coagulation (DIC). The most critical sequelae of rhabdomyolysis are shock and renal failure.
• Rapid fluid resuscitation promotes urine output and alleviates the effect of myoglobin on the kidneys. Generous amounts of intravenous fluids with close monitoring of urine output and pH are indicated for rhabdomyolysis associated with severe psychostimulant toxicity. Fluid resuscitation should maintain urine output of 1-3 mL/kg/h to minimize renal damage from rhabdomyolysis. Patients with rhabdomyolysis may require up to 20 L of fluid in the first 24 hours to achieve these urinary flow rates, and close monitoring of cardiac status and electrolytes is necessary.
• In acid urine, myoglobin is essentially a toxin, and uric acid tends to crystallize at low pH; sodium bicarbonate may be used to alkalinize the urine of patents with rhabdomyolysis. However, without prospective randomized studies to differentiate the role played by volume versus alkalinization, it is possible that volume alone represents maximally effective therapy. This is important because cocaine metabolites are best excreted in acid urine, and it calls into question the role of urinary alkalinization.
• GI concerns: When cocaine has been ingested (not as part of body packing or body stuffing), the patient without altered mental status may be treated by administration of activated aqueous charcoal. Gastric lavage and induction of vomiting via ipecac syrup is not recommended because of the risk of seizure, with the potential for airway compromise and aspiration of vomitus.

Body packing and body stuffing

• In body packers, although a risk for toxicity exists, the drugs are often carefully packaged to prevent rupture or leakage. Carriers often purge the GI tract with a laxative before they ingest the drug packages and then consume only clear liquids until the drugs are delivered. If a constipating agent was used, they ingest a laxative to enhance evacuation when arriving at their destination.
• Conversely, body stuffers quickly ingest drug packages to avoid arrest. Therefore, body stuffers are at increased risk for aspiration because of the rapidity with which they attempt to remove the evidence from police accessibility. Bronchoscopy has been used to successfully remove a drug packet aspirated into the lung.
• Body stuffers have other risks as well. Because they were not planning to ingest the packet (as opposed to the body packer) and because they took no precautions selecting the drug container, the wrapping material often acts as a semipermeable membrane. The hypertonic content of the drug packet attracts water, making the ingested packages especially prone to rupture or leakage resulting in toxicity.
• Potent polypharmaceutic overdose is also common, resulting from an attempt to swallow all of the illegal drugs on site.
• The administration of activated charcoal has been recommended to adsorb any toxins from leaking bags, from ruptured bags, or that were liberated during enhancement of bowel transit (eg, whole-bowel irrigation). Treatment of asymptomatic patients should include laxatives (eg, sodium sulfate, magnesium sulfate, magnesium citrate, psyllium hydrophilic mucilage) or whole-bowel irrigation, several doses of activated charcoal, and close observation.
• If a polyethylene glycol electrolyte lavage solution (eg, GoLYTELY, Colyte) is to be used for whole-bowel irrigation, Malbrain cautions that it must follow the administration of activated charcoal because the maximal adsorptive capacity of activated charcoal is at pH 7 and the polyethylene glycol electrolyte lavage solution has a pH of 8.³² Do not use paraffin-containing laxatives (eg, Lansoyl) because they degrade latex. Avoid endoscopic manipulation and enemas because the drug packet may be ruptured. Contraindications to whole-bowel irrigation include ileus, GI hemorrhage, or bowel perforation.
• Monitor body stuffers for several hours. Body packers may require hours to days of hospitalization until all the packets have been passed. Surgical intervention is needed if patients present with serious signs or symptoms or intestinal obstruction.

Psychiatric concerns

• Individuals using cocaine expect to become euphoric, energetic, and confident. However, with large doses or prolonged use, they may become agitated, anxious, or panicky. A wild, combative patient intoxicated with cocaine may be sedated with lorazepam or midazolam, both of which can be adequately absorbed via the intramuscular route if intravenous access is unobtainable.
• Given the contradictory literature about butyrophenones that was previously addressed, attempt to avoid use of antipsychotics because they may confuse the clinical picture, exacerbate anticholinergic crisis, lower the seizure threshold, or cause a dystonic reaction.

Other considerations

• When treating a traveler who presents with fever, bizarre mental state, or coma, especially if the person has come from West Africa or South America, consider cerebral malaria, treated with intravenous quinine.
• Test patients who inject drugs for HIV and hepatitis (with their permission, if required by state law).
• If a patient with cocaine toxicity is being considered as an organ donor, remember that cocaine preferentially accumulates in the liver and kidney. Therefore, use of these organs may result in the transplantation of a substantial reservoir of the toxin.

Consultations

Consultation with a regional poison control center or a medical toxicologist may be appropriate in complicated cases.

Medication

The general objectives of pharmacotherapeutic intervention in cocaine toxicity are to reduce the CNS and cardiovascular effects of the drug by using benzodiazepines initially and then control clinically significant tachycardia and hypertension while simultaneously attempting to limit deleterious drug interactions.

In a cardiac arrest, vasopressin may offer considerable advantage over epinephrine.

Some patients who abuse cocaine have enhanced sensitivity to benzodiazepines despite a significantly decreased plasma concentration. Be alert to the extreme sedative effects that have been noted after the administration of lorazepam to some patients who used cocaine.

NTG or nitroprusside may be needed to treat severe hypertension. For both of these drugs, an infusion system that ensures a precise rate of flow is needed. Closely monitor the patient's vital signs when vasoactive and antihypertensive medications are used. When vasoactive agents are discontinued, taper them slowly.

Hypotension may compound the patient's status; if present, norepinephrine may be required.

Hypoglycemia is always a possibility in patients presenting with neuropsychiatric syndromes. If bedside glucose results confirm the need, administer thiamine and glucose. Thiamine should be administered before dextrose. Before the intravenous administration of thiamine, administer an intradermal test dose to patients in whom thiamine sensitivity is suspected.

Benzodiazepines

By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, these drugs may depress all levels of the CNS, including the limbic system and reticular formation.

Lorazepam (Ativan)

DOC for status epilepticus because it persists in CNS longer than diazepam. Rate of injection should not exceed 2 mg/min. May be administered IM if unable to obtain vascular access.

Dosing

Adult

0.044 mg/kg (2-4 mg) IV; titrate to effect; single dose not to exceed 4 mg
Status epilepticus: 4 mg IV over 2-5 min; may repeat in 10-15 min prn; not to exceed 8 mg in 12 h

Pediatric

Children: 0.05 mg/kg IV (0.02-0.1 mg/kg); single dose not to exceed 4 mg
Adolescents: Administer as in adults
Status epilepticus:
Neonates: 0.05 mg/kg IV over 2-5 min; may repeat in 10-15 min prn
Infants and children: 0.1 mg/kg IV over 2-5 min; second dose of 0.05 mg/kg IV in 10-15 min prn; not to exceed 4 mg
Adolescents: 0.7 mg/kg IV slowly over 2-5 min; not to exceed 4 mg; second dose in 10-15 min prn

Interactions

Toxicity of benzodiazepines in CNS increases with concurrent alcohol and other CNS depressants

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants at high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or inhibited benzodiazepine metabolism and clearance (eg, those using nicotine or cimetidine)

Midazolam (Versed)

Alternative for termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects; therefore, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors as diazepam. May be administered IM if unable to obtain vascular access.

Dosing

Adult

0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV slowly over several min; may repeat q10-15min until adequate response achieved

Pediatric

<32 weeks: 0.5 mcg/kg/min IV infusion; titrate to effect
>32 weeks: 1 mcg/kg/min IV infusion; titrate to effect
Children: 0.05-0.2 mg/kg IV over 2-3 min then continuous infusion of 1-2 mcg/kg/min; titrate to effect; not to exceed 4 mg per dose
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg IV then continuous infusion 1 mcg/kg/min IV, titrate upward q5min until seizures controlled

Interactions

Theophylline may antagonize sedative effects; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when used together; effects exacerbated by other CNS depressants

Contraindications

Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent) are main contraindications

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in CHF, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lowering dosages in patients with organic brain syndrome or inhibited benzodiazepine metabolism and clearance (eg, those using nicotine or cimetidine)

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing GABA activity. Third-line agent for agitation or seizures because of shortened duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.

Dosing

Adult

5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg

Pediatric

30 days to 5 years: 0.2-0.5 mg IV slowly q2-5min until symptoms resolve; not to exceed 5 mg total dose
>5 years: 1 mg IV slowly q2-5min until symptoms resolve; not to exceed 10 mg total dose

Interactions

Increased toxicity with coadministration of phenothiazines, H1 blockers, barbiturates, alcohols, and MAOIs

Contraindications

Documented hypersensitivity; hypotension; acute narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity)

Cardiovascular agents

Alkalinization may benefit cardiac conduction if a wide QRS is noted. Other treatment for cardiac arrest, dysrhythmias, or acute hypertension may also be required.

Sodium bicarbonate (Neut)

Useful for alkalization of urine in patients with rhabdomyolysis.
Appropriate for dysrhythmias from direct toxic effects of cocaine (ie, QRS >100 ms due to sodium channel blockade).

Dosing

Adult

1 mEq/kg IV bolus; pH (goal, 7.50-7.55) and clinical response guide subsequent doses

Pediatric

Administer as in adults

Interactions

Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may decrease levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine

Contraindications

Documented hypersensitivity; alkalosis; hypernatremia; hypocalcemia; severe pulmonary edema; unknown abdominal pain

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Alkalosis, decreased plasma potassium, hypocalcemia, and hypernatremia; caution in electrolyte imbalances (eg, in CHF, cirrhosis, edema, corticosteroid use, or renal failure); avoid extravasation (can cause tissue necrosis); caution in patients <2 y

Lidocaine (Anestacon, Dilocaine, Xylocaine, Zilactin-L, Dermaflex)

Class IB antiarrhythmic that increases electrical stimulation threshold of ventricle, suppresses automaticity, and slows conduction velocity through ischemic tissue. Indicated for cocaine-induced VF and VT.

Dosing

Adult

1-1.5 mg/kg IV bolus over 2-3 min
VF or pulseless VT: May repeat in 3-5 min
Perfusing VT: Repeat doses of 0.5-0.75 mg/kg in 5-10 min
Not to exceed 3 mg/kg total

Pediatric

Loading dose: 1 mg/kg IV; may repeat in 5-10 min twice
For perfusing VT: 1 mg/kg IV bolus; then may use continuous infusion of 20-50 mcg/kg/min IV

Interactions

Coadministration with cimetidine or beta-blockers increases toxicity; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine

Contraindications

Documented hypersensitivity; Adams-Stokes syndrome and Wolf-Parkinson-White syndrome; severe sinoatrial (SA), atrioventricular (AV), or intraventricular block if artificial pacemaker not in place

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia or shock, respiratory-depression, and bradycardia; may increase risk of CNS and cardiac adverse effects in elderly persons; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities

Bretylium

Class III antiarrhythmic agent for treatment of PVCs. Has catecholamine-releasing properties and adverse effects. Should not be used as initial treatment.

Dosing

Adult

5 mg/kg IV push; may increase to 10 mg/kg IV bolus and repeat q5min; maximum dose 30-35 mg/kg

Pediatric

5 mg/kg IV push; may repeat with second dose of 10 mg/kg IV push

Interactions

Pressor catecholamines and digitalis may increase toxicity; coadministration with ofloxacin may increase risk of cardiotoxicity

Contraindications

Documented hypersensitivity; systemic lupus erythematosus, digitalis-induced arrhythmias, complete heart block or second- or third-degree heart block if pacemaker is not in place; torsade de pointes

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause hypotension especially in fixed cardiac output (eg, aortic stenosis); caution in renal insufficiency, severe pulmonary hypertension, and aortic stenosis; half-life increased in elderly person; with renal clearance of 10-50 mL/min, administer 25-50% of dose; rapid IV injections may cause transient hypertension, nausea, and vomiting; limit injection to 5 mL (undiluted) at each injection site; may exacerbate digitalis toxicity

Esmolol (Brevibloc)

Beta-blockers are generally contraindicated in cocaine toxicity. Some recommend to "save use" together with a vasodilator, only to manage life-threatening hypertension, tachycardia, and aortic dissection unresponsive to other therapeutic interventions. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Dosing

Adult

250-500 mcg/kg/min IV loading dose for 1 min; followed by 50 mcg/kg/min maintenance infusion for 4 min; if adequate therapeutic effect not observed within 5 min, repeat loading dose and follow with maintenance infusion by using increments of 50 mcg/kg/min IV for 4 min; sequence may be repeated as many as 4 times prn; as desired BP approached, omit loading infusion and reduce incremental dose of maintenance infusion from 50 to 25 mcg/kg/min or less; interval between titration steps may be increased 5-10 min prn

Pediatric

Not established; suggested dose is 100-500 mcg/kg IV over 1 min

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents

Contraindications

Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when abruptly withdrawn; withdraw slowly and monitor patient closely

NTG (Deponit, Nitrostat)

Used to treat acute hypertension and cardiac chest pain. Relaxes vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production, decreasing BP. Selection of NTG or sodium nitroprusside based on clinician's preference.

Dosing

Adult

IV: May administer bolus of 12.5-25 mcg IV before continuous infusion; initial infusion rate of 10-20 mcg/min IV may be increased 5-10 mcg/min q5-10min until desired clinical or hemodynamic response achieved; rates of 500 mcg/min IV may be required
SL: 400 mcg; may repeat as needed until therapeutic goal achieved

Pediatric

Not established

Interactions

Aspirin and indomethacin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministered calcium channel blockers (may need to adjust dose of either agent); increased bioavailability of dihydroergotamine (DHE) and decreased coronary vasodilation of NTG may occur when these agents are used concurrently

Contraindications

Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, cerebral hemorrhage, hypovolemia, constrictive pericarditis or pericardial effusion, hypertrophic cardiomyopathy, and sildenafil (Viagra) use within previous 24 h

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in coronary artery disease, low systolic BP, glaucoma, hepatic disease, or hyperthyroidism

Phentolamine (Regitine)

Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension due to catecholamine effects on alpha-receptors.

Dosing

Adult

5-20 mg IV/IM

Pediatric

0.05-0.1 mg/kg/dose IV/IM; repeat prn q2-4h until hypertension controlled

Interactions

Concurrent epinephrine or ephedrine use may decrease effects; ethanol increases toxicity

Contraindications

Documented hypersensitivity; coronary or cerebral arteriosclerosis and renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in tachycardia, peptic ulcer, and gastritis; cerebrovascular occlusions, MIs

Nitroprusside (Nitropress)

Used to treat acute hypertension. Produces vasodilation and increases cardiac inotropic activity. At high dosages, may exacerbate myocardial ischemia by increasing heart rate. Selection of NTG or sodium nitroprusside based on clinician's preference.

Dosing

Adult

0.1 mcg/kg/min IV initially; titrate up q3-5min to effect (up to 5 mcg/kg/min)

Pediatric

1 mcg/kg/min IV initially; uptitrate prn to 8 mcg/kg/min IV infusion

Interactions

Aspirin and indomethacin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministered calcium channel blockers (may need to adjust dose of either agent); increased bioavailability of DHE and decreased coronary vasodilation of NTG may occur when used concurrently

Contraindications

Documented hypersensitivity; subaortic stenosis, idiopathic hypertrophic, and atrial fibrillation or flutter; sildenafil (Viagra) use within previous 24 h

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution with increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; can lower BP and therefore should be used only when mean arterial pressures >70 mm Hg; not first-line drug in pregnant women unless hypertensive emergency; with renal or hepatic insufficiency levels may increase and can cause cyanide toxicity; monitor for thiocyanate and cyanide or to limit use to <24 h; risk of cyanide toxicity increased with infusions >2 mcg/kg/min

Norepinephrine (Levophed)

Stimulates alpha and beta1-adrenergic receptors with alpha-adrenergic predominance which increases cardiac muscle contractility, heart rate, and vasoconstriction; results are increased systemic BP and coronary blood flow. As a vasopressor, useful in hypotension not responsive to IV fluids alone.

Dosing

Adult

0.5-30 mcg/min IV; titrate to effect

Pediatric

0.1-2 mcg/kg/min IV initial; begin low and titrate to effect

Interactions

Chlorpromazine enhances pressor response by blocking bradycardia

Contraindications

Documented hypersensitivity; peripheral or mesenteric vascular thrombosis (may increase ischemia and extend area of infarct)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

If possible, correct blood-volume depletion before therapy; extravasation may cause severe tissue necrosis (should be administered into large vein); caution in occlusive vascular disease

Epinephrine

Considered the single most useful drug in cardiac arrest. Increases coronary perfusion pressure.

Dosing

Adult

1 mg (10 mL of 1:10,000 solution) IVP q3-5min or 0.1 mg/kg IVP q3-5 min during resuscitation; follow each dose with 20 mL flush, elevate arm for 10-20s after dose
Higher doses do not improve survival or neurologic outcome
Endotracheal administration requires 2-2.5 times IV dose

Pediatric

0.01 mg/kg IV/IO (0.1 mL/kg of 1:10,000 standard concentration); administer q3-5min during arrest (maximum dose 1 mg)
0.1 mg/kg ET (0.1 mL/kg of 1:1000 HIGH concentration) administered during arrest q3-5min until IV/IO access achieved; then begin with first IV dose)

Interactions

Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics

Contraindications

Documented hypersensitivity; cardiac arrhythmias, angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; during labor (may delay second stage of labor)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Vasopressin

May improve vital organ blood flow, cerebral oxygen delivery, ability to be resuscitated, and neurologic recovery.

Dosing

Adult

40 Units IV single dose

Pediatric

Not established

Interactions

Lithium, epinephrine, demeclocycline, heparin, and alcohol may decrease effects; chlorpropamide, urea, fludrocortisone, and carbamazepine may potentiate effects

Contraindications

Documented hypersensitivity; coronary artery disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, seizure disorders, nitrogen retention, asthma, or migraine; excessive doses may result in hyponatremia

GI agents

Whole-bowel irrigation with polyethylene glycol promotes the passage of cocaine packets through the GI tract. Activated charcoal may be empirically used to minimize systemic absorption of the toxin.

Polyethylene glycol (Colovage, CoLyte, GoLYTELY, NuLytely)

Laxative with strong electrolyte and osmotic effects. Cathartic actions in GI tract. May be indicated in treatment of cocaine ingestion in people who carry cocaine packages in their body. Must administer after activated charcoal. Liquid reconstituted per package instructions.

Dosing

Adult

240 mL (8 oz) PO/NG q10min, to 4 L total or until rectal effluent clear and packets removed

Pediatric

Not established; recommended dose 25-40 mL/kg/h PO/NG for 4-10 h or until rectal effluent clear and packets removed

Interactions

Reduces effectiveness and absorption of oral medications

Contraindications

Documented hypersensitivity; colitis; megacolon; bowel perforation; gastric retention; GI obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in ulcerative colitis and hot-loop polypectomy; adverse events (eg, fluid and sodium retention) rare

Activated charcoal (Liqui-Char)

Emergency treatment for absorption of drugs or chemicals. Network of pores adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water. Some formulations also contain a cathartic.
For maximum effect, administer within 30 min of poison ingestion. Although value of multiple doses to treat acute drug ingestion not established, in some carefully considered situations, dose may be repeated at half original dose q2-6h until symptoms of toxicity subside, serum drug concentrations return to reference range (if initially elevated) or drug packets eliminated. Repeat doses should not contain cathartic.

Dosing

Adult

5-10 times estimated weight of drug ingested or 1 g/kg body weight PO as single dose

Pediatric

<1 year: 1 g/kg PO without cathartic
1-12 years: 1-2 g/kg or 15-30 g PO without cathartic
>12 years: Administer as in adults

Interactions

May inactivate ipecac syrup if used concomitantly; effectiveness of other medications may decrease if coadministered; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)

Contraindications

Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Protect airway before administration if gag reflex is absent or if development of a decreased level of consciousness, seizures, or other airway risks is a concern
If formulation used contains cathartic, electrolyte abnormalities may occur, particularly in children and with repeated doses.
Can administer in early stages of gastric lavage; gastric lavage returns are black
Monitor bowel sounds and bowel function if repeat administration is considered since repeat administration is contraindicated with ileus; not effective for poisoning with ethanol, methanol, iron-salt poisoning and other nonadsorbed toxins; after emesis induced by ipecac syrup, patient may not tolerate activated charcoal for 1-2 h

Nutrients

Thiamine should be administered before glucose to prevent Wernicke encephalopathy.

Thiamine (Vitamin B1)

Administered before glucose to prevent Wernicke encephalopathy.

Dosing

Adult

100 mg IV over 5 min

Pediatric

10-25 mg IV over 5 min

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Sensitivity reactions; intradermal test dose recommended in suspected sensitivity as anaphylactic deaths due to allergic reactions have resulted from IV use.
Sudden onset or worsening of Wernicke encephalopathy after administration of glucose may occur in thiamine-deficient patients, therefore, administer before or together with dextrose-containing fluids in suspected thiamine deficiency.

Dextrose (D-glucose)

Monosaccharide absorbed from intestine and distributed, stored, and used by tissues. Parenteral injection used in patients unable to sustain adequate oral intake. Direct oral absorption rapidly increases blood glucose concentrations. Effective in small doses and no evidence suggests toxicity. Concentrated infusions provide increased amounts of glucose and increased caloric intake in small volume of fluid.

Dosing

Adult

50 mL D50W (25 g dextrose) IV

Pediatric

0.5-1 g/kg per PALS protocol
Infants: 5-10 mL/kg D10W
Children: 2-4 mL/kg D25W

Interactions

In patients who may have decreased thiamine stores (eg, alcoholics, starvation) administer thiamine before or concomitantly with glucose to avoid precipitation of Wernicke syndrome

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

May cause nausea, which also may occur with hypoglycemia; IV solutions may dilute serum electrolyte concentrations or overhydration in fluid overload; caution in congestion or pulmonary edema; hypertonic dextrose given peripherally may cause thrombosis (use central venous catheter); caution in subclinical diabetes mellitus or carbohydrate intolerance; increased risk of significant hyperglycemia or hyperosmolar syndrome if administered rapidly, especially in chronic uremia or carbohydrate intolerance; do not administer concentrated solutions SC or IM; infusion >0.5 g/kg/h IV may produce glycosuria; at infusion 0.8 g/kg/h IV, incidence of glycosuria is 5%; closely monitor fluid balance, electrolyte concentrations, and acid-base balance; may produce vitamin B-complex deficiency; perform bedside glucose tests to reduce potential for neurologic complications due to inappropriate use of glucose; thiamine should be administered before dextrose

Follow-up

Further Inpatient Care

• Patients with chest pain should be admitted if their pain is severe, sustained, recurrent, associated with significant cardiac risk factors, or associated with any acute cardiopulmonary symptoms accompanied by positive cardiac markers or ECG changes suggestive of ischemia.
• Other indications for admission to a critical care unit may include patients with unresolved moderate-to-severe signs and symptoms, including seizures and focal neurologic deficits and those with suspected ingestion of packages of cocaine.

Further Outpatient Care

• Refer the patient for drug abuse counseling and treatment.
• If domestic violence is identified from the history or physical examination, refer the patient to an appropriate agency that makes referrals for physical and psychological problems and provides safety, treatment, advocacy, and support.
• Provide referral for counseling or testing for HIV and other sexually transmitted disease (STD), as appropriate.

Transfer

• If critical care is not available, transfer patients requiring such care to an appropriate facility, preferably in an advanced life support unit.

Complications

• The principle effect of cocaine, like ethanol, on mortality may be its association with homicide, suicide, and motor vehicle collisions.³⁹ In a study of 14,843 persons who were fatally injured in New York City over 3 years, fatal injury after cocaine use exceeded all deaths associated with other causes in persons aged 15-24 years. Although approximately one third of deaths associated with cocaine use were the result of its direct pharmacologic effects, two thirds were the result of traumatic injuries.
• Cocaine use, determined by detection of its metabolite benzoylecgonine in urine or blood, was found in 26.7% of the above-mentioned patients, with free cocaine, indicating recent use, detected in 18.3%. Ethanol was detected in 28.1% of those who died. For comparison, household surveys of the general population of New York City showed that the estimated frequency of cocaine use in the preceding 30 days was less than 1.3% overall; demographic groups with the highest rates of use were Hispanics and black men, whose rates were 3-4.1%.
• In this study, cocaine use was detected in 69.7% of all cases of accidental poisonings, 29.2% of homicides, 15.3% of suicides, and 9.3% of accidents.
• The use of alcohol and illicit drugs increases the risk of suicide 16-fold, which is substantially higher than the rate observed with either substance alone. A study of suicide cases in New York City demonstrated that 20% of individuals younger than 61 years had used cocaine within days of their death. Nearly one half of Hispanic men who commit suicide have toxicologic screens positive for cocaine. Cocaine users typically choose violent means for self-destruction, especially the use of firearms.
• Illicit use of drugs by members of the household increases a woman's risk of death at the hands of a spouse, lover, or close relative 28-fold.
• According to Brookoff, approximately 45% of assailants in domestic violence had used alcohol or other drugs to the point of intoxication on a daily basis for the previous month.⁴⁰ Approximately 12% were addicted to drugs, and 14% were addicted to alcohol and drugs. On the day of the assault, the most common intoxicant was cocaine. About 30% of assailants had used cocaine and alcohol, and 13% had used alcohol, marijuana, and cocaine.
• In another study of domestic violence, two thirds of assailants had used the combination of alcohol and cocaine on the day of the assault. The active metabolite of this drug combination, cocaethylene, is more intoxicating, longer lived, and possibly more potent in its ability to kindle violent behavior than the parent drugs.
• For individuals with one addictive disorder, the risk of having a second addictive disorder is increased 7-fold.
• People who use cocaine have an increased incidence of acquiring HIV and other sexually transmitted infections.

Patient Education

• The event that prompted this ED visit may provide an opportunity to strongly caution the patient about future use of cocaine and to encourage the patient to seek treatment for drug abuse.
• For excellent patient education resources, visit eMedicine's Substance Abuse Center, Poisoning - First Aid and Emergency Center, and Mental Health and Behavior Center. Also, see eMedicine's patient education articles Cocaine Abuse, Drug Dependence & Abuse, Substance Abuse, Club Drugs, and Poisoning.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider cocaine toxicity in a hyperadrenergic patient, thus precipitating an alpha-adrenergic crisis after administration of a beta-adrenergic blocking drug without addressing the increased alpha-adrenergic activity
• Failure to monitor the patient's core temperature, administer sedation, adequate IV fluids, and cooling measures to prevent or halt the progression of rhabdomyolysis
• Failure to consider drug interactions in a hyperadrenergic patient and contributing to these interactions by administering a drug with potentially detrimental effects (eg, meperidine use in serotonin syndrome)
• Failure to hydrate and alkalinize the urine, thereby increasing the likelihood of renal failure secondary to rhabdomyolysis
• Failure to consider and evaluate all potential causes of agitated delirium, such as trauma or infection
• Failure to consider secondary complications (eg, barotrauma, sepsis, rhabdomyolysis, ischemia or infarction of organs)
• Failure to consider body packing or body stuffing such as in the assessment of patients with prolonged toxicity or in those with otherwise unexplained hyperactivity after arrest or incarceration

Special Concerns

• Pregnant patients
  • A study in the 1990s by NIDA revealed that more than 220,000 women had used an illicit drug during their pregnancy, and more than one fifth of these women had used cocaine in powdered or crack form.
  • Cocaine and its metabolites rapidly cross the placenta. Fetal levels approach 15% of maternal levels in 3-5 minutes. Cocaine plasma levels and vasoconstriction of uterine artery have a dose-dependent inverse relationship, resulting in an increased fetal BP and heart rate and decreased oxygen content (and other nutrients) in fetal blood. Thus, decreased placental blood flow results in chronic fetal hypoxemia. Some studies have demonstrated that cocaine reduces the uptake of nutrient substances in placental villi, even in the absence of vascular tissue. Other findings have suggested that cocaine exerts direct toxic effects on fetal myocytes.
  • Cocaine use in early pregnancy is associated with increased risk of spontaneous abortion or embryonic death with expulsion or resorption.
  • Late pregnancy complications include premature labor and delivery, precipitous delivery, placental abruption (which occurs twice as often as in drug-free control subjects), low birth weight, intrauterine growth retardation, low Apgar scores, meconium staining, fetal demise, and stillbirth.
• Pediatric patients
  • Infants and toddlers have increased susceptibility to cocaine toxicity, possibly secondary to decreased activity of plasma and hepatic cholinesterase.
  • In a study of 43 infants who died within 2 days of birth and whose autopsies failed to reveal an obvious cause of death, 40% had toxicologic evidence of cocaine exposure.
  • Cocaine withdrawal syndrome is common in neonatal intensive care units (NICUs). If the infant is discharged before the problem is recognized, the patient may later present to the ED. Treatment is symptomatic, with use of benzodiazepines.
  • Ostrea, Ostrea, and Simpson report a study of 2964 infants. Of the infants whose mothers denied having a history of illegal drug use, 34.4% screened positive for drugs. A high perinatal morbidity rate was observed in drug-positive infants with significantly low birth weight, head circumference, and length. The incidence of SIDS was not significantly increased among drug-positive infants overall. Low birth weight and prematurity are known consequences of drug use during pregnancy; low-birth-weight babies (2500 g or less) have a significantly increased mortality rate.⁴¹
  • Although a number of structural and developmental abnormalities, including congenital cardiovascular malformations, have been noted in babies with cocaine toxicity, no specific teratogenic syndrome has been identified.
  • Seizure activity is common in neonates with cocaine exposure. These babies are at increased risk for intracerebral and intraventricular hemorrhage; focal seizures may indicate cerebral infarction of the newborn.
  • In neonates, infants, and toddlers, seizures have been precipitated by breastfeeding from a mother using cocaine, passive inhalation of smoke from crack cocaine, and accidental ingestion.
  • Even when the child is no longer exposed to cocaine, his or her cardiovascular abnormalities, including structural and functional abnormalities of the ventricle, intracardiac conduction delays, and dysrhythmias, may persist. These may result in CHF and cardiorespiratory arrest.
  • Cocaine can cause necrotizing enterocolitis in infants.
  • Another risk is child abuse or neglect. In a study of 100 cocaine-exposed infants and socioeconomically matched control infants followed for up for 2 years, 7 were physically injured, 37 were neglected, and 21 were placed in substitute care. The control group of infants not exposed to cocaine had no instances of abuse or neglect.⁴²

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Keywords

cocaine toxicity, cocaine ingestion, cocaine poisoning, benzoylmethylecgonine, blow, coke, crack, snow, toot, nose candy, freebase, club drug, rock, Erythroxylon coca, ecgonine, norcocaine, ethylbenzoylecgonine, cocaethylene, cocaine-induced myocardial infarction, cocaine-induced MI, speedball, ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, hyperthermia, agitated delirium, excited delirium, acute coronary syndromes, cocaine-associated rhabdomyolysis, hyperthermia, ventricular dysrhythmias, myocarditis, microfocal fibrosis, contraction band necrosis, tachydysrhythmias, cardiac arrest, coronary atherosclerosis, dilated cardiomyopathy, cocaine-induced seizures, cocaine-associated seizures, neuroleptic malignant syndrome, NMS, dystonic reactions, bradykinesia, akinesia, akathisia, pseudoparkinsonism, catalepsy, neuroleptic-induced dystonias, sudden death, psychostimulant-induced hyperthermia, myoglobinuria, acute tubular necrosis, acidemia, aortic dissection, pneumothorax, pneumopericardium, pneumomediastinum, pulmonary hemorrhage, pulmonary infarction, diffuse alveolar hemorrhage, neurogenic pulmonary edema, exacerbation of asthma, eosinophilic lung disease, chronic diffuse interstitial pneumonia, sudden infant death syndrome, SIDS, pulmonary hypertension, transient pulmonary infiltrates, crack lung, nasal septum perforation, bronchiolitis obliterans organizing pneumonia, granulomatosis, sinusitis, epiglottitis, bronchitis, cellulose granulomas in lung, panlobular emphysema, alveolar accumulation of carbonaceous material, airway burns, tracheal stenosis, hypersensitivity pneumonitis, toxic encephalopathy, neurogenic syncope, movement disorders, cocaine-induced hypertension, crack dancing, mesenteric ischemia, renal infarction, cocaine-associated cerebral vasculitis, central retinal artery occlusion, blurring of vision, endophthalmitis, optic neuropathy, corneal ulcerations, hallucinations, anxiety, depression, delirium, paranoia, toxic psychosis, cocaine bingeing, pocket shot, necrotizing angiitis, acquired immunodeficiency syndrome, AIDS, thrombophlebitis, cellulitis, talc-induced hepatitis, subacute bacterial endocarditis, SBE, foreign-particle pulmonary emboli, tetanus, cotton fever, malaria

Contributor Information and Disclosures

Author

Lynn Barkley Burnett, EdD, MS, LLB(c), Medical Advisor, Fresno County Sheriff's Department; Attending Consultant-in-Chief and Chairman, Medical Ethics, Clinical Faculty, Community Medical Centers; Adjunct Professor of Forensic Pathology, National University Master of Forensic Science Program
Lynn Barkley Burnett, EdD, MS, LLB(c) is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Association for the Advancement of Science, American Association of Suicidology, American Cancer Society, American College of Sports Medicine, American Heart Association, American Professional Society on the Abuse of Children, American Public Health Association, American Society for Bioethics and Humanities, American Society of Law Medicine and Ethics, American Stroke Association, Association of Military Surgeons of the US, Christian Medical & Dental Society, European Society for Trauma and Emergency Surgery, European Society of Cardiology, European Society of Intensive Care Medicine, European Society of Paediatric and Neonatal Intensive Care, Faculty of Forensic and Legal Medicine of the Royal College of Physicians of London, International Homicide Investigators Association, New York Academy of Sciences, Royal College of Surgeons of Edinburgh, Royal Society of Medicine, Society for Academic Emergency Medicine, Society of Critical Care Medicine, and World Association for Disaster and Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School
Jonathan Adler, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
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Medical Editor

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernandez, MD, FAAEM, FACEP, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD, ABAT is a member of the following medical societies: American Academy of Clinical Toxicology and American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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