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1238 SECTION 15: Toxicology Patients with mild opioid withdrawal are treated with symptomatic therapy, usually antiemetics and antidiarrheals as needed. Symptoms of moderate opioid withdrawal can be rendered more tolerable by the administration of the central α 2-agonist clonidine.77 Clonidine should not be used if the patient is hypotensive or bradycardiac. A test dose of clonidine 75 to 100 micrograms PO should be given first with reassess ment of the patient after 30 minutes. If there is no drop in the blood pressure and the patient is not dizzy, then treatment with 150 micro grams PO three times a day is begun, continued for 3 days and then tapered and discontinued after the fifth day. Opioid replacement therapy, usually with buprenorphine or metha done, should be considered for moderately severe withdrawal and is recommended for severe withdrawal. 78 To treat withdrawal, standard doses of buprenorphine or methadone are initiated, titrated over with next 2 to 3 days as withdrawal symptoms peak, and then tapered. 78,79 The management of opioid-dependent individuals hospitalized for medical or surgical reasons can be challenging. Detoxification from opioids during the course of an acute medical illness is usually unsuccessful, so alleviation of withdrawal symptoms with opioid replacement is gen erally the goal. For patients already enrolled in an outpatient buprenor phine or methadone program, daily administration of the verified dose is recommended to inhibit withdrawal symptoms and reduce craving. A patient who uses high doses of opioids but who is not enrolled in methadone maintenance therapy can be given methadone 20 to 30 milligrams PO or 10 milligrams IM; this dose should inhibit withdrawal symptoms but not induce euphoria. Buprenorphine, 0.3 to 1.2 milligrams IV or IM every 6 hours or 2 to 4 milligrams sublingual, can safely be administered to a medically ill opioid-dependent patient experiencing withdrawal who is being admitted to the hospital. 79 No methadone or buprenorphine should be administered to an opioid-dependent patient until withdrawal symptoms appear. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Cocaine and Amphetamines Rachel S. Wightman Jeanmarie Perrone INTRODUCTION Historical records of indigenous cultures in South America describe early stimulant use by chewing leaves of the Erythroxylum coca plant, a practice that continues today. Cocaine was first used therapeutically in 1884 for ophthalmologic procedures, accompanied closely by reports of severe toxicity. Amphetamines were synthesized in 1887, and in 1932, they were marketed medicinally in an inhaler form as a bronchodilator. Use of methamphetamine to enhance physical and intellectual perfor mance began in the 1930s. Amphetamines were widely used as an alertness aid for troops by both Allied and Axis powers during World War II. Today, cocaine and amphetamines have limited therapeutic roles but are widely used as drugs of abuse. Clinical effects and toxicity are due to sympathetic nervous system stimulation. PHARMACOLOGY  COCAINE Cocaine is the naturally occurring alkaloid found in E. coca , a plant indigenous to South America.

World War II. Today, cocaine and amphetamines have limited therapeutic roles but are widely used as drugs of abuse. Clinical effects and toxicity are due to sympathetic nervous system stimulation. PHARMACOLOGY  COCAINE Cocaine is the naturally occurring alkaloid found in E. coca , a plant indigenous to South America. The water-soluble hydrochloride salt is absorbed across all mucosal surfaces, including oral, nasal, GI, and CHAPTER TABLE 187-1 Pharmacokinetics of Cocaine Route of Exposure Onset of Action Peak Action Duration of Action IV <1 min 3–5 min 30–60 min Nasal insufflation (snorting) 1–5 min 20–30 min 60–120 min Inhalation (smoking) <1 min 3–5 min 30–60 min GI 30–60 min 60–90 min Unknown Source: Reproduced with permission from Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR: Goldfrank’s Toxiciologic Emergencies, 10th ed. © 2015 by McGraw-Hill, Inc., New York. vaginal epithelium; cocaine can thus be topically applied, swallowed, or injected IV . The hydrochloride salt (powder) form is most often insufflated (snorted) or dissolved in water and injected IV; it degrades rapidly when pyrolyzed. Freebase cocaine can be smoked because it melts at a much lower temperature and can be prepared in many ways. A common method uses an alkali, such as sodium bicarbonate, to produce “crack cocaine, ” which, when smoked, produces the popping sound that characterizes its name. The onset and duration of action vary with the route of administration (Table 187-1). When cocaine is insufflated nasally, the delayed and prolonged effect is a result of vasoconstrictive properties that limit mucosal absorption followed by swallowing a portion of the insufflated cocaine, which is then absorbed from the stomach. GI absorption is also prolonged by vasoconstriction, producing delayed peak effect. Cocaine is primarily metabolized to ecgonine methyl ester by plasma cholinesterase. Relative deficiency of this enzyme may predispose affected patients to life-threatening toxicity. 1 Benzoylecgonine is the other major metabolite excreted in the urine and is the target compound detected in routine urine toxicology screens. Cocaethylene is a longacting metabolite formed when cocaine is used in combination with ethanol. Cocaethylene has vasoconstrictive properties similar to those of cocaine. Cocaine is both a CNS stimulant and a local anesthetic. 2,3 Central effects are mediated by enhancement of excitatory amino acids and blockade of presynaptic reuptake of norepinephrine, dopamine, and serotonin. The excess of neurotransmitters at postsynaptic receptor sites leads to sympathetic activation, producing the characteristic physical findings of mydriasis, tachycardia, hypertension, and diaphoresis, and predisposing to dysrhythmias, seizures, and hyperthermia. Cocaine use produces a euphoria associated with enhanced alertness and a general sense of well-being. It is thought that the psychological addiction, drug craving, and withdrawal effects are mediated by interference with dopamine and serotonin balance in the CNS. Subsequent dopamine depletion at the nerve terminals may account for the dysphoria and depression associated with long-term abuse. Like other local anesthetics, cocaine inhibits conduction of nerve impulses by blocking fast sodium channels in the cell membrane. In cardiac myocytes, cocaine inhibits rapid inward sodium channels caus ing QRS prolongation and can also block potassium channels resulting in QT c prolongation. Thus, in large doses, cocaine may exert a direct toxic effect on the myocardium, resulting in negative inotropy and widecomplex dysrhythmias.  AMPHETAMINES Amphetamines compose a broad class of structurally similar derivatives of phenylethylamine.

n and can also block potassium channels resulting in QT c prolongation. Thus, in large doses, cocaine may exert a direct toxic effect on the myocardium, resulting in negative inotropy and widecomplex dysrhythmias.  AMPHETAMINES Amphetamines compose a broad class of structurally similar derivatives of phenylethylamine. The derivative methamphetamine, also known as “ice, ” is abused by ingestion, IV injection, inhalation, or nasal insuffla tion. Absorption and peak effects vary with the route ( Table 187-2). Modification of the basic amphetamine structure produces substances with additional psychoactive properties. 4,5 More than 50 such “designer” amphetamines have been created ( Table 187-3), primarily for halluci nogenic effects (see Chapter 188, “Hallucinogens”). Methamphetamine and the designer amphetamines may have effects that persist for up to 12 hours or longer. Amphetamines enhance the release and block the reuptake of cat echolamines at the presynaptic terminal and may also directly stimulate Tintinalli_Sec15_p1187-1332.indd 1238 8/2/19 8:39 PM

ter 188, “Hallucinogens”). Methamphetamine and the designer amphetamines may have effects that persist for up to 12 hours or longer. Amphetamines enhance the release and block the reuptake of cat echolamines at the presynaptic terminal and may also directly stimulate Tintinalli_Sec15_p1187-1332.indd 1238 8/2/19 8:39 PM CHAPTER 187: Cocaine and Amphetamines 1239 and antagonized by phentolamine, which suggests mediation through stimulation of α-adrenergic receptors. 20 This effect is potentiated by cigarette smoking, and risk is heightened in patients with preexisting coronary artery disease. 21,22 In addition to promoting vasospasm and causing increased myocardial oxygen demand, cocaine predisposes to acute coronary syndrome by increasing atherogenesis through increased platelet aggregation, thrombogenesis, and accelerated atherosclerosis. Most patients who suffer cocaine-associated acute coronary syn drome are nonwhite men between the ages of 20 and 40 years who smoke cigarettes and regularly use cocaine. These demographic char acteristics encompass the majority of patients presenting with cocaineassociated chest pain, making it difficult to predict those at greatest risk for myocardial infarction. 23-25 However, a recent study of a nationwide inpatient sample of 363,143 admissions for cocaine-induced chest pain suggests female sex, age >50 years, history of heart failure, supraven tricular tachycardia, endocarditis, tobacco use, dyslipidemia, coronary artery disease, or renal failure as predictors of myocardial infarction. All routes of cocaine administration are associated with chest pain, acute coronary syndrome, ST-segment elevation myocardial infarction, and non–ST-segment elevation myocardial infarction. Atypical chest pain is common. Acute coronary syndromes and aortic dissection are also reported in association with ephedrine, phenylpropanolamine, and amphetamine use. 27 Mitral and aortic valve abnormalities associated with use of the amphetamine combination phentermine-fenfluramine prompted a voluntary recall of these appetite-suppressant drugs. Cardiopulmonary toxicity from other amphetamine diet aids has also been reported. Dysrhythmias induced by cocaine can result from sympathomimetic stimulation, blockade of the sodium channel during depolarization, inhibition of the potassium channel during repolarization, and effects on calcium channel current. 18,28 Sympathomimetic-induced dysrhythmias are tachycardias, such as sinus tachycardia, reentrant supraventricular tachycardia, and atrial fibrillation and flutter. Sodium channel blockade produces a rightward shift of the terminal portion of the QRS complex as seen on the frontal plane ECG leads (aVr with terminal R wave >3 mm and R/S ratio >0.7), a pattern similar to that of cyclic antidepressants. Progressive toxicity may induce a complete right bundle branch block or a prolonged QRS >120 milliseconds that, when combined with sinus tachycardia, produces a wide-complex tachycardia. Cocaine can induce the ECG appearance of the Brugada pattern, although it is not clear whether this is strictly a toxic effect or if the sodium channel–blocking effect of cocaine unmasks an underlying genetic predisposition to the Brugada syndrome. Potassium channel blockade impairs repolarization, prolonging the QT interval on the ECG. 29 The effects of cocaine on calcium channel current are dose dependent and complex, but at concentrations asso ciated with clinical toxicity, prolongation of both depolarization and repolarization is seen, as well as enhanced dispersion in repolarization. Delayed repolarization and enhanced dispersion promote early after potentials that can trigger reentrant dysrhythmias, such as ventricular tachycardia and a variant, torsades de pointes.

clinical toxicity, prolongation of both depolarization and repolarization is seen, as well as enhanced dispersion in repolarization. Delayed repolarization and enhanced dispersion promote early after potentials that can trigger reentrant dysrhythmias, such as ventricular tachycardia and a variant, torsades de pointes. Takotsubo syndrome, transient apical ballooning of the left ventricle, has been associated with cocaine use. The physiology is not clearly understood, but has been attributed to the effects of a sympathomimetic surge on the myocardium after cocaine use. 31,32  CNS Neurologic syndromes associated with cocaine abuse include seizures, cerebral infarctions, and hemorrhages. Hyperadrenergic tone induces severe transient hypertension, hemorrhage, or focal vasospasm, and, sometimes, exacerbation of underlying abnormalities of cerebral blood vessels. Cerebral vasoconstriction following cocaine administration has been observed using magnetic resonance angiography. Other CNS manifestations reported after cocaine use include spinal cord infarctions, cerebral vasculitis, and intracranial abscesses. Cho reoathetosis and repetitive movements (termed “crack dancing”) are associated with cocaine and amphetamine intoxication and appear related to dopamine dysregulation. Acute dystonic reactions following cocaine use and withdrawal are also observed. Unilateral blindness has TABLE 187-3 Commonly Abused Designer Amphetamines Abbreviation Chemical Name MDMA 3,4-Methylenedioxymethamphetamine MDA 3,4-Methylenedioxyamphetamine MDEA 3,4-Methylenedioxyethamphetamine PMA Paramethoxyamphetamine DOB 4-Bromo-2,5-dimethoxyamphetamine 2CB 4-Bromo-2,5-dimethoxyphenylethylamine STP or DOM 4-Methyl-2,5-dimethoxyamphetamine Fenethylline (Captagon® ) Amphetaminoethyltheophylline TABLE 187-2 Pharmacokinetics of Methamphetamine Route of Exposure Onset of Action Peak Action Duration of Action IV 15–30 s 30 min 10–12 h Nasal insufflation (snorting) 3–5 min 1–2 h 10–12 h Inhalation (smoking) 10–30 s 5–10 min 8–12 h GI 15–20 min 2–3 h 10–12 h catecholamine presynaptic and postsynaptic receptors. 6 Some amphet amine metabolites inhibit monoamine oxidase, increasing cytoplasmic concentrations of norepinephrine. Certain amphetamine derivatives can also induce release of serotonin and affect central serotonin receptors. These serotonergic effects account for the hallucinogenic properties of some amphetamine derivatives such as MDMA (3,4-methylenedioxy methamphetamine) and mescaline (3,4,5-trimethoxyphenethylamine). Downregulation of dopamine receptor activity with long-term use may contribute to the withdrawal phenomenon. Mortality from amphetamine toxicity is a result of hyperthermia, dysrhythmias, seizures, hypertension (intracranial hemorrhage or infarction), and encephalopathy. Stimulants such as methylphenidate, ephedrine, pseudoephedrine, and phenylpropanolamine produce toxic syndromes similar to but generally less severe than those caused by cocaine and amphetamines. 8-13 The U.S. Food and Drug Administration–approved prescription stim ulant medications for attention-deficit/hyperactivity disorder, such as methylphenidate and dextroamphetamine, are available in both immediate- and extended-release formulations. Abusers may crush the extended-release tablet to separate the active agent from the extendedrelease matrix to achieve a rapid onset of action after insufflation or injection. Synthetic (or substituted) cathinones, often termed “ bath salts, ” are designer drugs derived from naturally occurring amphetamine analogs found in the Catha edulis plant. Cathinones stimulate the release and block the reuptake of norepinephrine, dopamine, and serotonin at synapses in the brain, producing stimulant effects similar to cocaine and amphetamines.

en termed “ bath salts, ” are designer drugs derived from naturally occurring amphetamine analogs found in the Catha edulis plant. Cathinones stimulate the release and block the reuptake of norepinephrine, dopamine, and serotonin at synapses in the brain, producing stimulant effects similar to cocaine and amphetamines. 15-17 Commonly abused substituted cathinones include mephedrone, methylenedioxypyrovalerone, and methylone, although the composition in bath salts sold for abuse varies widely. CLINICAL FEATURES The clinical features of cocaine and amphetamine toxicity are the result of their sympathomimetic, vasoconstrictive, psychoactive, and local anesthetic properties affecting a variety of organ systems. 2-4,6  CARDIOVASCULAR Cocaine induces dysrhythmias, myocarditis, cardiomyopathy (including takotsubo), and acute coronary syndromes. 18 Other vascular compli cations include aortic rupture and aortic and coronary artery dissec tion. Even at relatively low doses, cocaine induces vasoconstriction in coronary arteries, contributing to cocaine-induced chest pain. Coronary vasoconstriction is exacerbated by β-adrenergic blockade Tintinalli_Sec15_p1187-1332.indd 1239 8/2/19 8:39 PM 1240 SECTION 15: Toxicology TABLE 187-4 Differential Diagnosis of Cocaine or Amphetamine Toxicity Toxicologic Phencyclidine toxicity Hallucinogen toxicity Anticholinergic toxicity Sedative-hypnotic withdrawal Serotonin syndrome Neuroleptic malignant syndrome CNS Ischemic stoke Intracranial hemorrhage Traumatic brain injury Encephalitis or meningitis Cerebral vasculitis Neoplasm Endocrine Hypoglycemia Pheochromocytoma Hyponatremia Thyrotoxicosis Psychiatric Acute psychosis Other

Phencyclidine toxicity Hallucinogen toxicity Anticholinergic toxicity Sedative-hypnotic withdrawal Serotonin syndrome Neuroleptic malignant syndrome CNS Ischemic stoke Intracranial hemorrhage Traumatic brain injury Encephalitis or meningitis Cerebral vasculitis Neoplasm Endocrine Hypoglycemia Pheochromocytoma Hyponatremia Thyrotoxicosis Psychiatric Acute psychosis Other Heatstroke Hypoxia been reported secondary to central retinal artery occlusion, and bilateral blindness can be caused by diffuse vasospasm. A syndrome of corneal abrasions and ulcerations secondary to smoke and irritation is known as “crack eye. ” Keratitis caused by methamphetamine use has been described as well. “Cocaine washout” is a syndrome that may occur in patients after a prolonged crack binge and results from depletion of neurotransmitters. Patients have a depressed level of consciousness but can be aroused to normal with stimulation. Resolution of lethargy can take up to 24 hours. Amphetamine, phenylpropanolamine, and ephedrine use are asso ciated with intracranial hemorrhage, infarction, encephalopathy, and seizures. 4,6 Amphetamines can also cause a CNS vasculitis, resulting in focal neurologic deficits. A profound paranoid psychosis can be seen with long-term amphetamine abuse and withdrawal.  PULMONARY Respiratory effects of cocaine use are more common in patients who smoke crack cocaine. Pulmonary hemorrhage, barotrauma, pneumonitis, asthma, and pulmonary edema have been observed. 34 Pneumomediastinum, pneumothorax, and pneumopericardium result from barotrauma secondary to performance of the Valsalva maneuver after inhalation or nasal insufflation in an attempt to enhance drug effect. Pneumonitis, asthma, and bronchiolitis may be an immunologic phenomenon or may result from numerous adulterants in illicit preparations. Inhalation of crack cocaine is associated with new-onset broncho spasm, likely the result of local airway irritation. 35,36 Acute lung injury associated with cocaine use is multifactorial and may be catecholamine mediated. A similar syndrome has been described in patients with adrenergic excess from pheochromocytoma and intracranial hemor rhage. Upper airway irritation and a “thermal” uvulitis can occur in patients smoking crack cocaine.  GI Cocaine-induced mesenteric vasospasm may produce intestinal ischemia, bowel necrosis, ischemic colitis, and splenic infarctions. In addi tion, GI ulceration, bleeding, and perforation occur in association with cocaine use. Advanced tooth decay (termed “meth mouth”) is common in habitual methamphetamine users. The reasons are presumably multifactorial and are related to poor oral hygiene, persistent dry mouth, jaw clenching, and tooth grinding. The belief that contamination with acidic or corrosive substances from the manufacturing process is responsible for this condition is not supported by analysis of illicitly produced methamphetamine.  ENDOCRINE MDMA users may develop hyponatremia due to drug-induced secretion of vasopressin in the setting of overhydration with water, which has been associated with several deaths. There is limited evidence suggesting that synthetic cathinones may cause similar effects.  RENAL Cocaine or amphetamine use may cause traumatic and nontraumatic rhabdomyolysis. 37-39 In cocaine-induced rhabdomyolysis, up to one third of patients develop acute kidney failure. 39 Risk factors for rhab domyolysis include altered mental status, seizures, dysrhythmias, and hemodynamic instability. Stimulants may further exacerbate renal injury by producing hyperthermia, vasoconstriction, hypotension, and hypovolemia. Renal infarction has been described following IV cocaine use.  PREGNANCY Cocaine is a potent vasoconstrictor that affects uteroplacental blood flow.

ures, dysrhythmias, and hemodynamic instability. Stimulants may further exacerbate renal injury by producing hyperthermia, vasoconstriction, hypotension, and hypovolemia. Renal infarction has been described following IV cocaine use.  PREGNANCY Cocaine is a potent vasoconstrictor that affects uteroplacental blood flow. Cocaine abuse during pregnancy is associated with an increased incidence of spontaneous abortions, abruptio placentae, fetal pre maturity, and intrauterine growth retardation. 40-43 Both spontaneous abortions and abruptio placentae appear to occur from placental vasoconstriction and increased uterine contractility, with concomitant maternal hypertension. A breastfed infant can become intoxicated secondary to maternal cocaine use. Methamphetamine abuse during pregnancy has detrimental effects on fetal growth. DIAGNOSIS Cocaine or amphetamine intoxication can usually be suspected based on the symptoms and signs of the sympathomimetic toxidrome: agita tion, mydriasis, diaphoresis, tachycardia, tachypnea, hypertension, and possibly hyperthermia. Mental status can range from normal to severely agitated and paranoid. Lethargy or coma suggests a postictal state or intracranial hemorrhage. Symptoms such as chest pain, palpitations, dyspnea, headache, or focal neurologic complaints suggest end-organ toxicity. Without a history of cocaine or other stimulant use, it may be difficult to distinguish this presentation from other conditions with catecholamine excess, such as withdrawal from alcohol or sedativehypnotic drugs (Table 187-4). Lactic acidosis may be present following seizures or as a result of vasoconstriction and hypoperfusion. As with all intoxicated patients, consider occult trauma and hypoglycemia. Concomitant use of alcohol and other drugs frequently alters the clinical presentation. For example, a patient using both opioids and stimulants may present with a decreased level of consciousness and few, if any, other diagnostic features of catecholamine excess. When the opioid effects are reversed with naloxone, the stimulant effects are unmasked, often with impressive findings.  LABORATORY EVALUATION Laboratory studies and imaging are directed by clinical findings. Obtain a chemistry panel and creatine kinase level in a patient with agitation or elevated temperature to evaluate for possible metabolic acidosis, renal failure, or rhabdomyolysis. Hyponatremia, often with altered mental status, occasionally occurs after the use of hallucinogenic amphetamines such as MDMA or mescaline. For chest pain, obtain an ECG and serum levels of cardiac biomarkers. If the patient is hyperthermic (>104°F or 40°C), coagulation and liver function studies should be performed. Altered mental status typically requires neuroimaging. Urine drug screens to confirm cocaine or amphetamine use are readily available, but interpretation requires knowledge of pharmacology and the testing method. 44 Most of the rapid urine screening tests for cocaine are highly specific for cocaine metabolites (such as benzoylecgonine) and Tintinalli_Sec15_p1187-1332.indd 1240 8/2/19 8:39 PM

to confirm cocaine or amphetamine use are readily available, but interpretation requires knowledge of pharmacology and the testing method. 44 Most of the rapid urine screening tests for cocaine are highly specific for cocaine metabolites (such as benzoylecgonine) and Tintinalli_Sec15_p1187-1332.indd 1240 8/2/19 8:39 PM CHAPTER 187: Cocaine and Amphetamines 1241 exhibit little cross-reactivity to the parent compound or other metabo lites. Commonly available urine drug screens for the cocaine metabolite benzoylecgonine are sensitive at very low levels, and cocaine use within the past 24 to 72 hours is typically detected, depending on dose. Cocaine can be detected in habitual users by more sensitive techniques (radioimmunoassay, gas chromatography) for up to 2 weeks after last use of the drug. Most urine amphetamine screens detect amphetamine, dextro amphetamine, methamphetamine, and, with decreasing sensitivity, 3,4-methylenedioxymethamphetamine, MDMA, and 3,4-methylene dioxyamphetamine. Synthetic cathinones may be detected, but results are too variable to be clinically useful due to variation in both laboratory analyzers as well as “bath salt” preparations. Commercial urine drug screens for amphetamine are sensitive to 1000 nanograms/mL, and amphetamine use within the past 48 hours is usually detected. How ever, interfering substances and other phenylethylamine compounds cross-react with amphetamine immunoassays, which limits their speci ficity. For example, excessive use of certain nasal inhalers that contain cross-reacting stimulant-class drugs may lead to positive results on immunoassays. Patients who take the nonprescription decongestants pseudoephedrine or phenylephrine or use prescription stimulants for attention-deficit/hyperactivity disorder or narcolepsy can have a positive urine amphetamine result. Many drugs, such as bupropion, chlorpromazine, promethazine, thioridazine, trazodone, desipramine, and doxepin, have metabolites that react with the amphetamine immunoassay. Other drugs, such as labetalol, isometheptene, ranitidine, ritodrine, and trimethobenzamide, possess enough structural similarity to the basic amphetamine form to react with the immunoassay as well. TREATMENT Follow the standard protocol for poisoned patients (see Chapter 176, “General Management of Poisoned Patients”). Establish IV access, and provide oxygen administration for hypoxia. The cornerstone of therapy is monitoring of vital signs, treatment of complications, supportive care, and adequate sedation to prevent self-harm and allow for testing and imaging (Table 187-5). 45 Treat hyperthermia with an ice bath or cool ing blankets (see Chapter 210, “Heat Emergencies”). 46 Aggressive IV hydration is the primary treatment for rhabdomyolysis (see Chapter 89, “Rhabdomyolysis”). Seizures are initially treated with benzodiazepines, and status epilepticus requires aggressive treatment (see Chapter 171, “Seizures and Status Epilepticus in Adults”). Obtain a head CT to iden tify intracranial pathology as the cause of seizures.  SEDATION Benzodiazepines are the cornerstone of therapy for sedation. Loraz epam, 2 milligrams IV , or diazepam, 5 milligrams IV , can be adminis tered and titrated with repeated doses to decrease the excess autonomic and neural stimulation. Antipsychotics such as haloperidol, droperidol, and chlorpromazine are not first-line therapy because they may lower the seizure threshold, contribute to hyperthermia, and increase QT prolongation and the risk of ventricular dysrhythmias. However, if benzodiazepines are ineffective, antipsychotics may be necessary to control agitation and dangerous behavior.  CHEST PAIN Chest pain characteristics in cocaine users are no different than in patients with atherosclerotic heart disease.

and increase QT prolongation and the risk of ventricular dysrhythmias. However, if benzodiazepines are ineffective, antipsychotics may be necessary to control agitation and dangerous behavior.  CHEST PAIN Chest pain characteristics in cocaine users are no different than in patients with atherosclerotic heart disease. Question chest pain patients about the use of cocaine. 47 Cocaine users with suspected acute coronary syndrome are managed with aspirin and nitroglycerin (see Chapter 49, “ Acute Coronary Syndromes”).47,48 Additional therapy is guided by the ECG. IV calcium channel blockers (diltiazem, 5 to 20 milligrams IV) are recommended as adjunctive therapy for patients with ST-segment elevation or depression. 47 Use of β-adrenergic antagonists (“β-blockers”) in the management of cocaine-associated myocardial ischemia or infarction is controversial. 47-50 Case reports suggested that β-blockers may create the potential for unopposed stimulation of α-adrenergic receptors that worsens coronary and peripheral vasoconstriction, hypertension, and possibly ischemia. 47,48 Conversely, large observational studies of patients with cocaine-related chest pain did not find an increased incidence of adverse effects in patients who received a β-blocker in the ED. 51-53 Labetalol (a mixed α-adrenergic and β-adrenergic antago nist) has been suggested for use by some in cocaine-associated chest pain because it does not appear to induce coronary artery vasocon striction, even though β-adrenergic–blocking activity predominates over α-adrenergic–blocking activity. 50,54-57 The 2014 American Heart Association/American College of Cardiology guidelines recommend that β-blockers not be administered to patients with signs of acute cocaine intoxication. 48 Although there are no definitive data to guide treatment of tachycardia in the setting of cocaine-related chest pain, available evidence from the emergency medicine literature supports use of labetalol when clinical judgment dictates a need for heart rate reduction. Emergent coronary angiography is recommended if ST segments remain elevated despite nitroglycerin and calcium channel–blocker therapy. 47 Fibrinolytics may be used for cocaine-induced ST-segment elevation myocardial infarction if no other contraindications exist and coronary angiography is not available. 47 Based on limited observational data demonstrating cardiac toxicity and similarities in patho physiology between cocaine and amphetamines, the current American Heart Association/American College of Cardiology guidelines recom mend therapy similar to that of cocaine-induced chest pain for chest pain in the setting of amphetamine use. 48,56 For patients without evidence of acute cocaine intoxication or STsegment elevation on ECG and a negative initial troponin, risk stratifi cation using the HEART Pathway (history, ECG, age, risk factors, and troponin) or other risk stratification tools including serial ECGs and a minimum of two troponin assessments is reasonable.  DYSRHYTHMIAS Target antidysrhythmic therapy according to the probable pathogenesis of the dysrhythmia. 21,59,60 Sinus tachycardia is generally responsive to sedation, cooling, and IV fluid rehydration; β-blocker therapy should be avoided if possible, and labetalol should be used if β-blockade is judged necessary. Use a calcium channel blocker to treat reentrant supraven tricular tachycardia as well as to control the ventricular rate in atrial fibrillation or flutter. A wide-complex tachycardia with clinical evidence of cocaine toxic ity can be assumed to be due to sodium channel blockade and treated with sodium bicarbonate, a 1 to 2 mEq/L IV bolus followed by either intermittent boluses or an infusion.

ia as well as to control the ventricular rate in atrial fibrillation or flutter. A wide-complex tachycardia with clinical evidence of cocaine toxic ity can be assumed to be due to sodium channel blockade and treated with sodium bicarbonate, a 1 to 2 mEq/L IV bolus followed by either intermittent boluses or an infusion. 60,61 The frequency of boluses or the rate of infusion is guided by clinical response and serum pH; do not alkalinize the serum above a pH of 7.55 with sodium bicarbonate. Lidocaine in standard doses can be used in refractory cases of wide-complex tachycardia; theory and animal models suggest harmful interaction, but clinical experience has documented safety. Magnesium, lidocaine, and overdrive pacing have all been reported to be successful in cocaine-induced torsades de pointes. It seems reasonable, although of unproven benefit, to administer magnesium in an attempt to prevent torsades in patients with a prolonged corrected QT interval >500 milliseconds or who fall above the QT–heart rate pair nomogram.  HYPERTENSION Severe hypertension not responding to sedation with benzodiazepines should be treated with phentolamine (initial dose, 2.5 to 5.0 milligrams IV), TABLE 187-5 Management of Sympathomimetic Toxicity •  Vital  signs and continuous cardiac monitoring •  Supportive  care and prevent self-harm •  Benzodiazepines  for sedation •  Aggressive  cooling for hyperthermia •  IV  fluid for rhabdomyolysis •  Benzodiazepines  for seizures •  Evaluate  chest pain and treat ACS •  Phentolamine  for uncontrolled hypertension •  Targeted  therapy for dysrhythmias Abbreviation: ACS = acute coronary syndrome. Tintinalli_Sec15_p1187-1332.indd 1241 8/2/19 8:39 PM