Medical Complications of Cocaine Use
Medical Complications of Cocaine Use
Authors:
Anna Marie Chang, MD, Research Fellow, Hospital of the University of Pennsylvania, Philadelphia.
Judd E. Hollander, MD, Professor, Clinical Research Director, Hospital of the University of Pennsylvania, Philadelphia.
Peer Reviewer:
Christine Murphy, MD, Carolinas Medical Center/Carolinas Poison Center.
Cocaine is a natural product from the leaves of Erythroxylon coca, a shrub that grows in Mexico, South America, the West Indies, and Indonesia. In the 6th century, natives of Peru chewed or sucked on the leaves.1,2 In the 1100s, the Incas used cocaine as part of ritual trephinations.1,2 In 1855, "erythroxylon" was isolated from the coca plant3 and was first used as a local anesthetic in 1884.1,4 In the 1890s, cola drinks were marketed with cocaine as an ingredient.3 In the early 20th century, cocaine was labeled as a narcotic,1,3-5 but despite this, cocaine use has either increased or remained steady since the 1970s.1,6
Epidemiology
Estimates in the past 10 years have consistently reported about 6 million Americans aged 12 or older using cocaine in the past year.6 Behind marijuana, cocaine is the second most commonly used illicit substance in the United States.6 During 2008, the Drug Abuse Warning Network (DAWN) estimated that cocaine was involved in more than 400,000 ED complaints, the most of any illicit substance.7
Cocaine Processing
Cocaine (benzoylmethylecgonine) exists in several forms: cocaine hydrochloride, the salt powder form; "crack," made by dissolving the salt in water; or "freebase," a free-base alkaloid.5 It can be used by insufflation (snorting), intravenous (IV) injection, smoking, ingestion, or mucosal application. Its half-life is approximately 0.5-1.5 hours depending on the dose and route of administration.1,5,8,9
Cocaine is extracted from the E. coca plant and treated with hydrochloric acid to form cocaine hydrochloride salt powder.1 This form is water-soluble and can be snorted and injected, but cannot be smoked. Crack cocaine is made by dissolving the salt form in water, mixing with sodium bicarbonate, and heating.5 The cracking sound heard when the drug is heated gives "crack" its name.5 Crack cocaine is cheap to make, is highly addictive, and has the highest profit margin. It is the most commonly used form of cocaine.5 Freebase cocaine is made using ether to dissolve the salt form.1 Freebase is not as popular because if the ether is not completely extracted, it is highly flammable and may cause facial burns when smoked.5,10
Metabolism and Detection
Cocaine is hydrolyzed via liver and plasma esterases to ecgonine methylester (EME), which is approximately one-third to one-half of the metabolites. It is believed that EME does not have pharmacologic activity. Hydrolysis converts cocaine to benzoylecgonine (BE), which accounts for 40% of the metabolism of the parent compound.1,5 BE does not cross the blood-brain barrier but has peripheral vasoconstrictive properties.1,5 Hepatic N-demethylation forms norcocaine, which is less than 5% of the absorbed drug. Norcocaine does cross the blood-brain barrier and causes vasoconstriction as well.1,5 In the presence of alcohol, cocaine is metabolized to cocaethylene, which also has potent effects.11
Because of the short half-life of cocaine, drug assays typically measure its BE.1,5,10 Testing can be performed on urine, blood, or hair.5 In the ED, urine testing can be done via point-of-care assays. Urine immunoassays detect as little as 300 ng/mL of BE. Positive results are usually confirmed with gas chromatography/mass spectroscopy (GC/MS), which has a lower detection limit of 1 ng/mL of BE. Confirmatory testing is not typically done for clinical purposes, but rather due to legal implications of a positive test result. A positive urine test result typically indicates that cocaine was last used within 1 to 3 days.1,5,10 However, patients who are chronic users of cocaine can occasionally have positive urine screens for weeks after their last use.12 A few substances can cause false positives or false negatives. False positives are seen with prilocaine13, coca tea sold over the Internet14, and if bleach or Drano are added to urine specimens.5,10 A false negative can also occur if urine is tested very shortly after use, prior to the formation of BE.5
Pharmacology
Cocaine is both an anesthetic and a stimulant.1,5,10 Cocaine blocks voltage-gated sodium channels in the neuronal membrane.
In the central nervous system (CNS), cocaine affects the cortex, lower motor centers, and even the medulla via neurotransmitters. Cocaine inhibits dopamine reuptake, which is believed to cause psychostimulatory effects including euphoria, increased self-confidence and alertness, aggressiveness, disorientation, and hallucinations.
Cocaine causes vasopressor effects through norepinephrine, and the tachycardia is via epinephrine.1 It also blocks fast sodium channels within the myocardium, which interferes with cardiovascular conduction.1,5,10 Cocaine and its metabolite norcocaine have vasoconstrictive effects, most likely secondary to increased circulating norepinephrine. All major metabolites other than EME cause cerebral vasoconstriction.1,5,10
The phamarcology and hemodynamic effects of cocaethylene are similar to the effects of other cocaine metabolites. Enhanced blockade of dopamine reuptake by cocaethylene causes enhanced euphoria when alcohol is used simultaneously with cocaine. Despite its increased psychostimulatory effects, cocaethylene has a direct myocardial depressant effect,1 which leads to transient decreases in left ventricular function.1
The combination of sodium channel blockade and increased circulating catecholamines causes numerous complications. A list of the more common complications is included in Table 1.
Table 1: Complications Associated with Cocaine
|
Cardiac |
Neurologic |
Pulmonary |
Psychiatric |
|
Myocardial infarction |
Seizure |
Pneumothorax |
Anxiety |
|
Arrhythmia |
Cerebral hemorrhage |
Pneumomediastinum |
Depression |
|
Aortic dissection |
Cerebral infarction |
Crack lung |
Delirium and psychosis |
|
Cardiomyopathy |
Cerebral vasculitis |
Bronchiolitis obliterans |
Suicide |
|
Myocarditis |
Pulmonary edema |
Addiction |
|
|
Head and Neck |
Obstetric |
Renal |
Gastrointestinal |
|
Septal perforation |
Placental abruption |
Renal infarction |
Gastric perforations |
|
Dental and gingival decay |
Prematurity |
Rhabdomyolysis |
Intestinal ischemia |
|
Chronic sinusitis |
Cocaine-Related Chief Complaints Seen in the ED by Organ System
The foundation for treatment of all cocaine-associated complaints includes supportive care and benzodiazepines.
Neurological Complaints
Cocaine is associated with an increased risk of cerebrovascular events including subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, transient ischemic attacks, dystonic reactions, toxic leukoencephalopathy, migraine-type headache syndromes, seizures, cerebral vasculitis, and varied psychiatric manifestations.1,5,15-17 Most cocaine-toxic patients are anxious or agitated, which can be secondary to the effects of cocaine or underlying pathology.
A recent study at a tertiary stroke center identified patients with cocaine use; almost half were given a diagnosis of ischemic stroke or transient ischemic attack, a quarter intracerebral hemorrhage (ICH), and another quarter subarachnoid hemorrhage. Current users were more likely to have ICH compared with previous users (37.7% v 8.6%) and less likely to have ischemic stroke or TIA (36.1% v 65.7%).16 An epidemiologic study indicated that cocaine abuse was associated with both hemorrhagic (OR, 2.33; 95% CI, 1.74-3.11) and ischemic (OR, 2.03; 95% CI, 1.48-2.79) stroke.16
Some patients with neurologic complaints have had predisposing cerebrovascular disease (for example, aneurysms or arteriovenous malformations), but most do not. Cocaine-related ischemic stroke may be due to vasospasm, enhanced platelet aggregation, cerebral vasculitis, and cardioembolism from cocaine-induced myocardial infarction or cardiomyopathy. Hypertensive surges causing a disturbance of cerebral autoregulation and blood flow may play a part in cocaine-induced hemorrhagic stroke.1,5
Seizures may occur in the presence or absence of infarction or hemorrhage. Most seizures are single and generalized without any lasting neurologic deficits.1,10 Smoking crack or injecting intravenous cocaine are more likely to be associated with seizures.1,10 Multiple seizures or focal seizures are usually associated with concomitant drug use or an underlying seizure disorder. Seizures occur in upwards of 20% of cocaine-using populations.18 In the patient with an acute neurological complaint, the initial evaluation should rule out central nervous system events such as bleeding, edema, trauma, and infection, including a head CT and laboratory tests. EEG and lumbar puncture should be considered. The diagnosis of cocaine-induced seizures or intracranial abnormality is a diagnosis of exclusion.18 If a patient is diagnosed with a neurological emergency, guidelines for those conditions should be followed. In patients with known cocaine-associated seizures, an extensive workup may not be necessary. Benzodiazepines are the first-line treatment for ongoing seizures, to prevent further seizures, and to reduce blood pressure, anxiety, and agitation. Start with lorazepam, 2-4 mg intravenously, or diazepam, 5-10 mg1,18 and titrate up for effect. Very large doses of benzodiazepines may be required.18 Antipsychotic agents are not used, as they may lower the seizure threshold. If benzodiazepines do not achieve sedation, barbiturates such as phenobarbital (a dose of 10-20 mg/kg at 25-50 mg/min) are used.18
A decreased level of consciousness and profound lethargy characterizes a "washed out" syndrome secondary to acute cocaine use.1 It is thought that repetitive use of cocaine depletes dopamine stores and causes this syndrome. Patients may appear to be in a post-ictal state except that they have normal mentation when aroused. "Washed out" patients assume normal sleep postures and can be aroused to full orientation. Supportive care is instituted until the patient resumes normal consciousness.
Renal Complaints
Acute renal disease after cocaine abuse can be due to vasoconstriction, rhabdomyolysis, glomerular diseases, and acute interstitial nephritis. Cocaine causes severe vasoconstriction by blocking the re-uptake of catecholamines by adrenergic nerve terminals. Cocaine can also cause endothelial cell surface activation and platelet buildup leading to thrombus formation.5,19
Renal infarction is rare and presents 1-4 days after cocaine use.19 Presenting symptoms include flank pain, nausea, vomiting, and fever. Leukocytosis or hematuria, and an elevated LDH can be seen.20 Unlike acute tubular necrosis caused by rhabdomyolysis, serum creatine phosphokinase is not elevated. The diagnosis is made by CT scan with contrast or a renal scintigram; ultrasound is not sensitive.19,20
There are no evidence-based therapies for cocaine-induced renal infarction.19 Thrombolytic and anticoagulant therapy has been used but is cautioned in these patients as they may have other sources of bleeding. Blood pressure control with benzodiazepines, followed by nitroglycerin or nitroprusside is appropriate.5,19
Rhabdomyolysis. The increased psychomotor activity seen in cocaine use increases heat production.1 Vasoconstriction inhibits heat loss.1 Both of these processes and hypothalamic dysregulation lead to hyperthermia. It is believed that alterations in dopamine function can lead to muscle ischemia. Rhabdomyolysis, renal failure, and myoglobinuria occur as sequelae. Hyperthermia can cause disseminated intravascular coagulation (DIC), acidosis, hepatic injury, and renal failure.1,5
Excited delirium is defined as a prolonged period of mental and physiological hyperarousal commonly associated with the use of cocaine.5 Patients at risk for excited delirium often have a history of repeated cocaine binges. This condition can lead to hyperthermia, rhabdomyolysis, bizarre psychotic behavior, and hyperactivity.21 Those with excited delirium can be extremely hostile and violent.21 A physical struggle with police or medical personnel can be fatal.21
Treatment of cocaine-associated rhabdomyolysis and excited delirium is twofold.5 To prevent the precipitation of myoglobin, urine output is maintained at greater than 3 mL/kg/hr using IV fluids, mannitol, and urine alkalinization.5 As in all patients with cocaine-associated symptoms, benzodiazepines are first-line agents.5,22 Hyperthermia and psychomotor agitation are treated with rapid cooling and benzodiazepines. If seizures occur and benzodiazepines are ineffective, barbiturates may be used.5 If this fails, intubation and neuromuscular blockade are recommended. Non-depolarizing agents such as vecuronium are preferred in cases of rhabdomyolysis.1,5
Pulmonary Complaints
Cocaine may cause new lung problems or exacerbate pre-existing pulmonary disease. Acute respiratory complaints include cough with black sputum, chest pain and shortness of breath, hemoptysis, and wheezing. The differential is broad, ranging from pneumothorax to pulmonary edema and acute respiratory distress syndrome. Pneumothorax, pneumomediastinum, pneumopericardium, and hemothorax are the main acute complications of inhaling crack cocaine vapor.1,5,15,22-26 Crack lung is a phenomenon described in patients with pulmonary symptoms after inhalation of freebase cocaine. Patients present with fever, chest pain, shortness of breath, hemoptysis, hypoxemia, or respiratory failure.22,23 Chest radiography may be normal or reveal diffuse alveolar infiltrates.25 This is a hypersensitivity-mediated condition and will improve with systemic corticosteroids. Milder cases usually resolve spontaneously within 36 hours.23,25 Patients with pre-existing pulmonary conditions such as asthma may have exacerbations associated with cocaine use.15,26
Cocaine use is associated with pulmonary edema. Chest X-rays will usually show bilateral perihilar, interstitial, and alveolar infiltrates.23,25 In rare and severe cases, crack users may develop adult respiratory distress syndrome and end-stage respiratory failure due to crack-associated interstitial pneumonitis and bronchiolitis obliterans with organizing pneumonia (BOOP).10,22,25 The pathogenesis of this condition is unclear, but may be due to the negative inotropic effect of cocaine.5 Treatment for these conditions is similar to patients with other etiologies of pulmonary edema with diuretics, nitrates, and oxygen followed by mechanical ventilation, if necessary.22
Upper Airway. Freebase cocaine is highly flammable, and severe facial and body burns have been reported. The upper airway, including the epiglottis, may be affected.5,23 Patients may present with dysphagia, drooling, and hoarseness. On soft-tissue neck radiography, findings may be similar to those with infectious epiglottitis. On nasopharyngolaryngoscopy (NPL), a swollen erythematous epiglottis and eschar of the posterior pharyngeal wall may be visualized.5 The treatment for this condition includes immediate airway management, antibiotics, and steroids.5,22 On occasion, metal pieces from crack cocaine pipes are inhaled.
Cardiac Complaints
Chest discomfort accounts for up to 40% of ED cocaine-related visits, and it is the most frequently seen complaint.1,5,27 Cocaine can induce dysrhythmias from sinus tachycardia to ventricular tachycardia. However, the initial response to cocaine is stimulation of the vagal nuclei, which causes bradycardia.1
Dysrhythmias. Narrow Complex Tachycardia. Sinus tachycardia is most likely caused by central nervous system activation and increased catecholamine release.5 In one case series, 5% of patients had supraventricular tachycardia, and there are case series of patients who present with atrial fibrillation.28 The psychomotor agitation, psychiatric distress, hyperthermia, and volume depletion that occur with cocaine use enhance these rhythm disturbances.5 Supportive care is used to treat sinus tachycardia in the acutely cocaine-intoxicated patient. This should include oxygen, cooling, and volume resuscitation. Benzodiazepines are the mainstays of treatment.28 Midazolam (1-2 mg IV) or lorazepam can be used and titrated to effect, and may be more beneficial than diazepam because they can be given intramuscularly without erratic absorption patterns.28 Beta-blockers are contraindicated to control sinus tachycardia as they may exacerbate coronary vasoconstriction. Supraventricular tachycardia or atrial fibrillation can be rate controlled with a calcium channel blocker.27,28
Wide Complex Tachycardia/Ventricular Tachycardia. The blockade of fast sodium channels by cocaine can best be described as a class Ic effect. The effects can be subtle or resemble electrocardiogram (ECG) changes seen with tricyclic antidepressant overdoses. Notably, the ECG will show a rightward shift of the terminal 40 ms of the QRS complex, and an S wave in leads I and aVL, and an R wave in lead aVR, with an incomplete right bundle-branch block. Case reports indicate that cocaine may cause the manifestation of a Brugada ECG pattern in those who are predisposed.25-31
Lidocaine has been used to treat dysrhythmias from other sodium channel blockers such as propoxyphene and tricyclic antidepressants, and can compete with cocaine for binding to sodium channels. However, lidocaine may decrease the seizure threshold.28,32,33 Animal data show reversal of QRS prolongation with the instillation of hypertonic sodium bicarbonate.34 In patients who are acutely ill with hypertension, tachycardia, and cocaine toxidrome, oxygenation, rapid cooling, and benzodiazepines followed by 1-2 mEq/kg bolus of hypertonic sodium bicarbonate (1-2 amps in normal saline for a normal-sized adult) is recommended.28 The boluses can be repeated or isotonic sodium bicarbonate can be given at twice the patient's fluid maintenance rate. This can be continued until cocaine is metabolized or the QRS duration and other physiologic parameters normalize.28 Clinicians need to be cautious of acid-base status and electrolyte abnormalities with this solution. Although clinical improvement with its use has been reported in humans, the patient picture often is confounded by the presence of acidosis and other concurrent therapies.35 If hypertonic sodium bicarbonate fails, anti-arrhythmic doses of lidocaine should be administered, followed by a continuous infusion.28 All Ia and Ic anti-dysrhythymic agents are contraindicated;28 there are no data to support the use of amiodarone.36
Cocaine also affects the potassium channels and impairs repolarization of the cardiac cell membranes. This leads to prolongation of the QT interval on ECG, in addition to the widened QRS already seen with sodium channel blockade.28 On occasion, abnormal T waves, U waves or extra P waves may be seen due to accumulation of calcium ions within the membrane. These small extra depolarizations are proposed as one possible mechanism for the origin of ventricular tachycardia or torsades des pointes.37 For those patients presenting with QT prolongation and acute cocaine toxicity, treatments for other causes of QT prolongation must be used, as there are insufficient data to make specific recommendations.28 Electrolyte abnormalities should be corrected. If patients present with unstable wide complex tachycardia, cardioversion or defibrillation and ACLS should be instituted. Use of magnesium, overdrive packing, and lidocaine to successfully convert cocaine-associated torsades des pointes have been reported, but there is not enough data to support protocols.28
Patients presenting as stable ventricular tachycardia will need oxygen and perhaps mechanical ventilation. Benzodiazepines are given to decrease agitation and heart rate, and they may have anti-anginal effects in patients with cocaine-associated acute coronary syndromes (ACS).38-40 Lidocaine is the preferred drug, and hypertonic sodium bicarbonate is used only if lidocaine fails. All Ia and Ic anti-dysrhythymic agents and beta-blockers are contraindicated. Amiodarone use is not well studied. In the unstable or refractory patient, electrical cardioversion may be used.28
Myocardial Ischemia/Acute Coronary Syndrome. The first reports of cocaine-associated myocardial infarction came in the early 1980s.41 Even for patients at low risk by traditional risk stratification, the risk of acute myocardial infarction is increased by a factor of 24 during the first 60 minutes after the use of cocaine.1,5,27,42,43 Despite this fact, the amount of cocaine used, route of administration, and frequency of use does not change the likelihood of AMI in patients with cocaine-associated chest pain. In patients who present with chest pain, cocaine or its metabolites may be found in up to 25%.44
The overall incidence of cocaine-associated MI varies from 0.7% to 6% (some of the difference may be due to differences in MI diagnostic criteria).27 In the COCaine Associated CHest PAin (COCHPA) study, the MI incidence was 6%.45 Other studies of cocaine-associated chest pain have reported lower rates of MI, including the Acute Cardiac Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI) study (0.7%);46 another study documented a 2.8% rate of MI in a series of 218 patients.47 However, in all studies, cocaine appears to be an important contributor to MI, especially among the young. In one study, the average age was only 38 years. The classic patient with cocaine-related myocardial infarction is a young, nonwhite, male, cigarette smoker with few other risk factors for atherosclerosis who has a history of repeated use of cocaine.27,42
The pathophysiology of cocaine-associated myocardial ischemia is multi-factorial. Chronic cocaine users develop left ventricular hypertrophy, coronary aneurysms and ectasia, and atherosclerosis.5,27,42 Acutely, cocaine causes coronary arterial vasoconstriction, in-situ thrombus formation, platelet aggregation, and increased myocardial oxygen demand. The combination of increased demand and decreased blood flow results in myocardial ischemia. Furthermore, cocaine users often are cigarette smokers, and the combination of tobacco and cocaine has a synergistic vasoconstrictive effect on the epicardial coronary arteries.5,27,42,44
In a classic demonstration of the cardiopathophysiology of cocaine, 29 patients were given intranasal cocaine during cardiac catheterization. The dose of cocaine used was less than what a recreational cocaine user would use. With administration of intranasal cocaine, heart rate and systemic arterial pressure increased; coronary sinus blood flow decreased; left coronary arterial diameters decreased 8-12%. No patient had chest pain or electrocardiographic evidence of myocardial ischemia following cocaine administration.48
The AHA recommends self-reporting as the primary means for evaluation of cocaine use. This especially applies to younger patients.27 It recommends urine testing when the patient is unable to communicate and no other reliable source of history is available or when a young patient with no or few risk factors presents with an MI.27 In our experience, more broad urine testing for cocaine identifies more patients with cocaine-associated symptoms, especially in patients without clinical suspicion. Like any patient who presents with chest pain, an ECG and serial cardiac markers should be done with a history and physical examination.
An abnormal ECG has been reported in 56% to 84% of patients with cocaine-associated chest pain; however, many of these patients are young and commonly have the normal variant of early repolarization.27 ECG findings specific for ischemia or infarction were present in only a minority of patients; 2% had changes typical for ST-segment elevation MI.27 Cocaine ingestion may cause rhabdomyolysis with elevation in total creatine kinase levels.49 Cardiac troponins are the most sensitive and specific markers for the diagnosis of cocaine-associated MI.24
In the absence of ECG changes or elevated cardiac markers, low- and intermediate-risk patients can be managed safely in a chest pain observation unit for 9-12 hours. The likelihood of underlying coronary artery disease or adverse cardiac events in patients in whom MI is ruled out is low.47,50 In one study, no differences in 30-day outcomes among patients managed with or without stress testing before discharge were seen.50 The AHA recommends that stress testing be performed at the time of observation or on an outpatient basis, and it should be considered based on other cardiac risk factors.27 Figure 1 shows AHA-recommended treatment of potential cocaine-induced acute coronary syndrome. Patients with a brief period of observation in the ED found to have normal coronary arteries by CT angiography are at very low risk for complications and will not require further provocative testing.51
Figure 1: Management of Cocaine-associated Chest Pain Based on the 2008 AHA Guidelines
Antithrombotic and antiplatelet agents
Outpatient: ASA, clopidogrel, statin
therapy, and consider beta-blockers
For All Patients:
If persistently hypertensive, consider nitroglycerin, nitroprusside, or phentolamine.
Avoid beta-blockers in the acute setting.
Drug abuse counseling.
Primary PCI
STEMI
Benzodiazepines
Cocaine-associated Chest Pain
ECG/Cardiac enzymes
Unstable angina/ACS
Cardiac catheterization
Aspirin
Low/moderate risk chest pain
Observation/serial cardiac markers
Inpatient or outpatient stress test
Aortic Dissection. Cocaine use also has been implicated as a cause of aortic dissection. Although it occurs in only 2.6-3.5 per 100,000 patient years, cocaine may be a causative factor in up to 37% of cases.52,53 Untreated, the mortality rate climbs to 33% within 24 hours and 90% at 1 year.54-56 The sudden and severe elevation of blood pressure induced by the sympathomimetic action of cocaine produces increased shear stress on the aorta, tearing the intimal layer. Chronic cocaine users may already have impaired elastic properties. Patients complain of chest pain or back pain. Hypertension is present in 75-80% of cases.52 Retrograde dissection into the coronary artery may produce ACS. Neurological abnormalities may occur, as well as pericardial hemorrhage or sudden death. Diagnostic imaging options include transesophageal echocardiography, computed tomography (CT) imaging, magnetic resonance imaging, or invasive contrast aortography.53 Both Stanford types A and B aortic dissection have been reported with cocaine use. While definitive therapy may be surgical or medical, the mainstay of treatment in the emergency department is pain relief and heart rate and blood pressure control. The goal systolic blood pressure should be between 100-120 mm Hg.53 In patients in whom cocaine use is confirmed or suspected, the use of beta-blockers is contraindicated. Similar to cocaine-induced acute coronary syndromes, benzodiazepines are considered first-line treatment; phentolamine (an alpha adrenergic blocking agent) may be useful to provide vasodilatation and further blood pressure control. Nitroglycerin either as a sublingual or intravenous form also may be an option. Nitroprusside may be another agent to effectively lower blood pressure.57 Immediate surgical consult is recommended for a type A dissection; both surgical and medical options are available for type B dissections.53
Other Cocaine Complaints
Cocaine can cause a myriad of other diseases throughout the body. Nasal insufflation of cocaine has caused nasal septal perforations and chronic rhinitis.10 Oral application of cocaine has led to dental erosions and gingival ulcerations.5,10
Cocaine has been reported to cause gastric and intestinal perforations, mesenteric ischemia, and ischemic colitis.15 In one review, the average age of patients with cocaine-induced ischemic colitis was 32.6 years old, with a mortality of 28.5%.52 Like other acute abdominal processes, CT is useful to make the diagnosis.52 Women who use cocaine and are pregnant may develop placental abruption, abnormal labor, spontaneous abortion, or premature rupture of membranes.5,10
Cocaine crosses the placental barrier. Infants born to mothers who use cocaine are more likely to be of low birth weight and have increased risk of sudden infant death syndrome, necrotizing enterocolitis, congenital abnormalities, and behavioral disorders.5,10,15
Table 2: Treatment for Cocaine-related Medical Conditions
|
Medical Condition |
Treatments |
Doses |
|
Cardiovascular |
||
|
Aortic dissection |
Benzodiazepines to effect Surgical consultation Consider nitroglycerin, phentolamine, nitroprusside |
Diazepam: 5-10 mg IV or lorazepam 2-4 mg IV Nitroglycerin 10-20 mcg/min IV, max 200 mcg/min Nitroprusside 0.3-0.5 mcg/kg/min, max 10 mcg/kg/min Phentolamine 5-20 mg IV |
|
Arrhythmia Supraventricular tachycardia |
Benzodiazepines Consider diltiazem or verapamil If hemodynamically unstable: ACLS protocol |
Diazepam 5-10 mg IV or lorazepam 2-4 mg IV Diltiazem 20 mg IV or verapamil 5 mg IV |
|
Ventricular dysrhythmias |
Benzodiazepines Consider sodium bicarbonate and/or lidocaine If hemodynamically unstable: defibrillation |
Lidocaine: 1.5 mg/kg IV bolus, 2 mg/min infusion Sodium bicarbonate: 1-2 mEq/kg IV bolus |
|
Acute coronary syndrome |
Aspirin Benzodiazepines Nitroglycerin Heparin For ST segment elevation (STEMI): Percutaneous intervention (angioplasty, stent placement) preferred. Consider fibrinolytic therapy (increased risk of bleeding) Consider morphine sulfate, phentolamine, verapamil, or glycoprotein IIb/IIIa inhibitors |
Aspirin: 325 mg PO Diazepam: 5-10 mg IV or lorazepam 2-4 mg IV Nitroglycerin: 3 sublingual tablets to reduce MAP by 10%, followed by 10-20 mcg/min IV, max 200 mcg/min Heparin: IV push: 60 units/kg, max 4000 U, followed by 12 units/kg/hour, max 1000 U/hour |
|
Hypertension |
Benzodiazepines Consider nitroglycerin, phentolamine, nitroprusside |
Diazepam: 5-10 mg IV or lorazepam 2-4 mg IV Nitroglycerin: 10-20 mcg/min IV, max 200 mcg/min Nitroprusside: 0.3-0.5 mcg/kg/min, max 10 mcg/kg/min Phentolamine: 5-20 mg IV |
|
Pulmonary edema |
Furosemide and nitroglycerin Consider morphine sulfate or phentolamine |
Furosemide: 20-40 mg IV Nitroglycerin: 10-20 mcg/min IV, max 200 mcg/min Morphine sulfate: 2 g IV titrated to effect Phentolamine: 5-20 mg IV |
|
Hyperthermia |
Benzodiazepines Cooling methods If agitated, consider paralysis and intubation |
Etomidate 0.3 mg/kg Non-depolarizing paralytic agents such as vecuronium or rocuronium |
|
Adapted from: Dart's Medical Toxicology 3rd edition. (Continued.) |
||
Table 2: Treatment for Cocaine-related Medical Conditions (continued)
|
Medical Condition |
Treatments |
Doses |
|
Neuropsychiatric |
||
|
Anxiety and agitation |
Benzodiazepines |
Diazepam: 5-10 mg IV or lorazepam 2-4 mg IV |
|
Seizures |
Consider phenobarbital if benzodiazepines fail |
Phenobarbital: 10-20 mg/kg IV |
|
Intracranial hemorrhage |
Surgical consultation |
|
|
Rhabdomyolysis |
IV hydration Consider sodium bicarbonate or mannitol If acute renal failure, hemodialysis |
Mannitol: 50-100 g dose |
|
Cocaine washout syndrome |
Supportive care |
|
|
Body packers |
Activated charcoal Whole-bowel irrigation Laparotomy or endoscopic retrieval |
Activated charcoal: 25-50 g as single dose 20-30 min prior to WBI Polyethylene-glycol: 1.5 L/h oral |
|
Adapted from Dart's Medical Toxicology 3rd edition. |
||
Cocaine Contaminants
Adulterants are often used by drug dealers to increase profit by diluting the quantity of real drug.5 Some adulterants include prescription drugs such as diltiazem, lidocaine, acetaminophen, clenbuterol, fentanyl, arsenic, strychnine, and over-the-counter agents such as baking soda, caffeine, multi-vitamins, or sugar.5 A recent report from France indicated that the median cocaine content was 22%, and 75% contained at least one adulterant.59 The most frequent adulterants were phenacetin (54%), caffeine (17%), paracetamol (14%), diltiazem and lidocaïne (11%).59 When benzocaine is used as an adulterant, it can cause methemoglobinemia.60
More recently, cocaine has been contaminated with levimasole. Levamisole was found in 30% of the cocaine recently seized by the U.S. Drug Enforcement Agency.61 Levamisole is a veterinary antihelminthic previously used as an immunomodulator in rheumatoid arthritis or adjuvant therapy in the treatment of colorectal cancer. It is currently available in the United States and South America only for veterinary use. Serious side effects have been reported, including neutropenia, allergic reactions, airway difficulties, and nervous system problems (confusion, fatigue, memory loss, muscle weakness, numbness or tingling, seizure, and speech disturbances).62 Levimasole-adulterated cocaine has been shown to cause occlusive necrotizing vasculitis of end digits, ears, and skin.63
Since June 2006, 108 episodes of neutropenia and 60 cases of neutropenia associated with tainted cocaine (NATC) have been identied in Alberta and British Columbia.64 Cases typically present with bacterial/fungal infections and fever. Clinicians should be aware that severe neutropenia may be caused by levamisole in cocaine. If fever or infection is present, treatment should include empiric intravenous broad-spectrum antibiotics, and granulocyte-colony stimulating factor (G-CSF or filgastrim) should be considered. Based on previous reports, the majority of patients respond within days of treatment, but neutropenia may recur on subsequent exposure.64 If neutropenia is found, clinicians need to ask about patients' recent cocaine use and request levamisole testing if urine can be obtained within 48 hours of cocaine use.64
Cocaine Body Packing
In the 1970s, body packing grew as a way for drugs to be smuggled into countries.65 Body pushers insert drug packets into the rectum or vagina, and body stuffers swallow unwrapped or inadequately wrapped drugs to escape capture by law enforcement.66 These are different from "body packers" or "mules," who are individuals who swallow (or insert into a body cavity) containers or packages filled with illegal drugs for the purpose of smuggling past customs. Often, the packaging material is not as well done as it is for "professional" body packers. General characteristics of a body packer include: returning from a trip abroad in a location with a history of illicit drug exporting; history of frequent trips; high-profit drugs such as cocaine or heroin; and packaging material made of high-grade latex, aluminum foil, or condoms.67 To postpone natural evacuation, especially for long flights, the body packers take anticholinergic medications and may decline to eat or drink. Although body packers once were predominantly young men, the practice now crosses demographic groups, including children and pregnant women.65
Initially, the literature reported surgical management to remove the packets prior to rupture. In the 1980s, a growing body of evidence suggested that conservative management was feasible in cocaine body packers.67,68 Between 2000 and 2005, Beckley et al collected data regarding suspects detained at Heathrow Airport for body packing. During that time, more than 2500 suspected body packers were detained. About one-quarter were brought to the local hospital, and 60% of those had visible packets on plain abdominal radiographs. The mean number of cocaine packets swallowed was 70 (range 3-169), with 3-15 g of cocaine per packet.67 Despite the large number of packets, this case series had no deaths. Cocaine body packing and stuffing carries heavy morbidity but not mortality.
In the ED, body packers should have a full history and physical exam, focusing on the abdominal exam including rectal and vaginal exams, and signs of cocaine intoxication including chest pain, arrhythmia, and neurological symptoms. The patient should be asked about the drug packets (the type of drug, the number of packets, and the nature of the wrapping). Recent reports suggest that packages are now increasingly well crafted, probably via an automated process, making them far less susceptible to rupture.65 As with all cocaine toxicities, benzodiazepines should be given for agitation and seizures, the administration of hypertonic sodium bicarbonate and lidocaine for ventricular dysrhythmias, and the administration of phentolamine or sodium nitroprusside for severe hypertension. Beta-blockers and mixed alpha and beta-blockers, such as labetalol, are contraindicated. Blood tests, including a complete blood count, comprehensive metabolic panel, and liver function tests should be requested, as it is important to have baseline values should the patient deteriorate. An ECG should also be performed to detect any arrhythmias or evidence of cardiac ischemia.65,67,70 In the series of patients reported by Beckley et al, only 6 patients showed signs of cocaine toxicity; only 4 had chest pain or ECG changes.67
The current treatment recommended for asymptomatic body packers is whole bowel irrigation with polyethylene-glycol at a rate of 1.5 L/h orally until all packets are passed. There is no limit on the volume that can be given. Whole bowel irrigation is contraindicated with bowel obstruction, bowel perforation, clinically important gastrointestinal hemorrhage, hemodynamic instability, and an unprotected compromised airway. Polyethylene glycol has proven to be safe and effective and does not have any adverse effects on the patient's fluid balance or electrolyte status. In the large Beckley case series, the average volume given was 6 L per day. There were no deaths reported in this group.67 Literature also suggests that activated charcoal can be given 20-30 minutes prior to whole bowel irrigation, at a dose of 1 gram per kilogram (max 50 grams) as it may reduce the potential mortality from cocaine.65
Conclusion
Emergency physicians will treat cocaine-intoxicated patients throughout their careers and need to understand care of the acute patient. The mainstays of treatment of the cocaine-intoxicated patient are benzodiazepines and supportive care.
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Estimates in the past 10 years have consistently reported about 6 million Americans aged 12 or older using cocaine in the past year.Subscribe Now for Access
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