Complicaciones cardiovasculares por consumo de cocaína. Dolor torácico

inducido por cocaína. Arritmias cardíacas.

Robert S. Hoffman, MD

Cocaine-Related Chest Pain Cocaine-Related Chest Pain

History / Epidemiology Clinical Presentation Mechanism Differential Diagnosis Evaluation Treatment Disposition

1886 British Medical Journal

Cocaine Chest PainCocaine Chest Pain

175,000 cocaine-related ED visits each year

Chest pain is the most common complaint• 40% of the patients• 57% admitted to the hospital• Average LOS = 3 days• Cost exceeds $83 million in hospital expenses

alone• Most rule out for MI• Most continue to use cocaine after discharge

Cocaine-Chest PainCocaine-Chest Pain

Most common chief complaints can be easily associated with CV disease• Chest pain 39.5%• Short of breath 21.9%• Palpitations 20.6%• Diaphoresis 6.4%

– Brody SL: Am J Med 1990;88:325 (n=233)

Cocaine-Myocardial InfarctionCocaine-Myocardial Infarction

First case of cocaine related MI was in 1982• Coleman DL: West J Med 1982;136:444

91 MI’s reviewed from existing reports81 males, average age 32.8, all routes of use

Time to onset: Mean 30 min, Max 24 hours

Tobacco in 87%, other risk factors rare

ASHD 31%, thrombosis without ASHD 24%

• Hollander and Hoffman: J Emerg Med 1992;10:169

Qureshi A: Circulation 2001;103:502-506Cocaine accounts for 25% of MIs in young adults

FarmacologíaVía Absorción máxima Duración

(minutos) (horas)

Intravenoso 0,5-2,0 0,25-0,5

Intranasal 30 1-2

Gastrointestinal 60-90 >3

Fumada 0,5-1 0,25-0,5

Mecanismo de acción

Bloqueo de la recaptación• Dopamina• Noradrenalina• Serotonina

Aminoácidos excitadores agonistas Efecto antiarritmico Tipo I Otros

Ratones que faltan el transportista de dopamina

Giros B, et al: Nature 1996;379:606-612.

Homocigotos• Agitación psicomótora

• Pobre ganacia de peso

• Mueren jovenes

Heterocigoto• Comportamiento intermedio

– Giros B, et al: Nature 1996;379:606-612.

Agitación Psicomótora y Dopamina

Homocigotos

Adrenalina de la glándula suprrenal y taquicardia

Adrenalina de la glándula suprrenal y taquicardia

Tella SR, et al: J Pharmacol Exp Ther 1993;267:153-162

Noradrenalina y hipertensiónNoradrenalina y hipertensión

PathophysiologyPathophysiology

Increased Oxygen DemandIncreased Oxygen Demand

Increased catecholamines in patients with cocaine related cardiac symptoms• Karch: Ann Emerg Med 1987;16:481

Norepinephrine (345-622 g/L)• normal (0-90 g/L)

Epinephrine (135-202 g/L)• normal (0-55 g/L)

Hypertension and tachycardia result

Cocaine-induced VasospasmCocaine-induced Vasospasm Human volunteer study of patients given

intranasal cocaine during cardiac cath• Coronary sinus blood flow decreases

• Left coronary artery diameter decreases

• Coronary vascular resistance increases

• Effects reversed by phentolamine

• Effects exacerbated by propranolol– Lange RA: NEJM 1989;321:1557

– Lange RA: Ann Intern Med, 1990;112:897

Accelerated AtherogenesisAccelerated Atherogenesis

Animal data• Normal rabbits never develop ASHD• Rabbits fed a high cholesterol diet never

develop ASHD• Rabbits fed a high cholesterol diet plus cocaine

develop atherosclerotic heart disease– Langner RO: FASEB 1989;3:297

Accelerated AtherogenesisAccelerated Atherogenesis

High incidence of ASHD (for age) in patients with cocaine related MI who undergo catheterization

– Hollander and Hoffman: J Emerg Med 1992;10:169

62-77% of patients with cocaine related myocardial infarctions will have some abnormality of their coronary arteries

– Minor RL: Ann Intern Med 1991;115:797– Kontos MC: J Emerg Med 2003;24:9-13

Enhanced CoagulationEnhanced Coagulation

Endothelial effects• Denuded endothelium

– Surface exposed to trigger coagulation

• Loss of EDRF (nitric oxide)– Impaired relaxation

– Impaired inhibition of platelet aggregation

• Reduced prostacycline – Impaired relaxation

Enhanced CoagulationEnhanced Coagulation

Platelet effects• Increased responsiveness to thromboxane and

prostacycline– Increased aggregation

• Increased aggregation releases serotonin• Serotonin constricts dysfunctional endothelium

– Tonga G: Haemostasis 1985;15:100

Enhanced CoagulationEnhanced Coagulation

Human study of plasma constituents after receiving intranasal cocaine• Moliterno DJ: Am J Med 1994;96:492

No effect seen on fibrinogen, plasminogen, lipoprotein, or plasminogen activator

Cocaine use resulted in an increase in tissue plasminogen activator inhibitor activity IMPAIRED THROMBOLYSIS

Effects of Cigarette SmokingEffects of Cigarette Smoking

Smoking exacerbates myocardial oxygen demand and vasoconstrictive effects of cocaine• Moliterno: NEJM 1994;330:454

In 51 cocaine chest pain patients the time to onset of pain was related to the interval between tobacco and cocaine use• Hollander JE: VHT 1994;36:349

HistologyHistology

Classic myocardial infarction

Contraction band necrosis

Inflammatory infiltrate

Differential DiagnosisDifferential Diagnosis

Ischemia or infarction Dysrhythmia Dissection Pneumothorax, mediastinum, pericardium Pulmonary infarction or alveolar injury Musculoskeletal Esophageal

EvaluationEvaluation

History• Cocaine use• Tobacco use, other cardiac risk factors• Pain

– Onset

– Duration

– Quality

• Associated factors

Screening Value of the ECGScreening Value of the ECG

Some patients with normal or nondiagnostic ECG’s will develop myocardial infarction

Many patients with very abnormal ECG’s will never develop an MI

There is a high incidence of “abnormal” ECG’s in this population. This usually represents early repolarization• Hollander JE: J Emerg Med 1994;12:144

COCHPACOCHPA

Prospective study of patients who presented to the ED with cocaine-related chest pain• Hollander and Hoffman: Acad Emerg Med

1994;1:330 Six emergency departments Consecutive enrollment protocol 46 month study 246 patients enrolled

COCHPA ResultsCOCHPA Results

14 MI’s (5.7%, 95% CI 2.7%-8.7%) Median age 33 71.5% male Median onset to chest pain 60 minutes 12 arrhythmias, 4 CHF, 2 deaths 92.9% tobacco use Other cardiac risk factors were low

COCHPA ResultsCOCHPA Results

ECG utility• Sens 35.7% Spec 89.9% • PPV 17.9% NPV 95.8%

History, physical examination or laboratory factors useful for predicting MI• NONE

COCHPA One Year Follow-upCOCHPA One Year Follow-up Prospective study of COCHPA patients

• Hollander and Hoffman: Acad Emerg Med 1995;2:179

203 patients followed for a mean of 408 days• 6 deaths (none from MI): 98% 1 year survival• 2 nonfatal MI’s• Continued cocaine use common (60%)• Recurrent chest pain was more common in

continued users (75% vs 31%)

TreatmentTreatment Oxygen Sedation Aspirin, Heparin Nitrates NO Beta adrenergic antagonists Phentolamine Thrombolysis Lidocaine

NitratesNitrates

12 patients were given cocaine during routine cardiac catheterization• Brogan WC: J Am Coll Cardiol 1991;18:581-6

Normal arteries constricted 22% Diseased arteries constricted 45% (p<0.02) All vessels responded to sublingual

nitroglycerin

Nitrates - COCHPANitrates - COCHPA

83 patients given nitrates by various routes• J Toxicol Clin Toxicol 1994;32:243

37 (45%): relief or reduction of chest pain 4 (5%): other benefits (CHF) 1 adverse effect:

• hypotension in a patient with a documented right ventricular infarction

Saland KA: Am J Cardiol 2002;90:810-1.

PhentolaminePhentolamine

38 year old male with 2 hours of chest pain after using cocaine• Hollander and Hoffman: NEJM 1992;327:361

Agitated, 140/90, 120 ST elevations in V2-V4 No response to oxygen, nitrates, aspirin or

diazepam Symptoms and ECG resolved with

phentolamine

Phentolamine Phentolamine

Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS. Phentolamine therapy for cocaine-association acute coronary syndrome. J Med Toxicol. 2006 Sep;2(3):108-11.

Beta Blockers - Human DataBeta Blockers - Human DataParameter Cocaine Cocaine + Inderal

Coronary sinusblood flow + decrease ++ decrease

Left coronaryartery diameter + decrease ++ decrease

Coronary vascularresistance + increase ++ increase

Lange RA: Ann Intern Med 1990;112:897

Before Esmolol After Esmolol BP HR BP HR

112/60 150 104/60 98140/80 133 110/70 100144/88 150 124/84 107194/128 104 184/136 88100/72 210 80/70 210200/120 124 230/180 88190/90 107 140/90 107

Sand CI: Am J Emerg Med 1991;9:161

Beta Blockers - Human DataBeta Blockers - Human Data

J Med Toxicol 2007;3:169-172

Thrombolysis - COCHPAThrombolysis - COCHPA

Retrospective study of 136 cocaine-related myocardial infarctions• Hollander and Hoffman: Chest 1995;107:1237

Thrombolysis given in 25 cases No significant adverse effects Insufficient data to judge efficacy Recommended use with cautions

ResultsResults

342 patients evaluated• 42 direct admissions• 302 in final study group

No patient died of a cardiovascular event • 95% CI 0-0.99%

4 of the 256 with good follow up had nonfatal myocardial infarction • 95% CI 0.1-3.1%. • All 4 continued to use cocaine.

ImplicationsImplications

Cocaine chest pain does not equal admission

Low risk patients can be safely discharged after a period of evaluation

Most important intervention is to offer cocaine detoxification / counseling

Dysrhythmic EffectsDysrhythmic Effects

Sodium Channel Blockade Sodium Channel Blockade

Wide complex arrhythmia• Terminal 40 msec rightward axis deviation• Right bundle branch block morphology

Heart rate• Tachycardia: catecholaminergic effects• Bradycardia: initially or following massive

overdose Brugada pattern

Winecoff AP, et al: Pharmacotherapy 1994;14:698-703

Bicarbonate and Type I Toxicity

Beckman KJ, et al: Circulation 1991;83:1799-1807.

Type I Antidysrhythmic Effect

Clinical Effect of Bicarbonate

Lidocaine and Bicarbonate

Winecoff AP, et al: Pharmacotherapy 1994;14:698-703Bicarbonate Lidocaine

Retrospective study of 155 cocaine-related myocardial infarctions• Shih RD: Vet Hum Toxicol 1994;36:349

29 patients treated with lidocaine• 31% for prophylaxis• 31% for PVC’s• 38% for V-tach or V-fib

No arrhythmogenesis or seizures

Lidocaine - COCHPALidocaine - COCHPA

Potassium Channel BlockadePotassium Channel Blockade

QTc 582 msec

Schrem SS, et al. Am Heart J. 1990;120:980-4.

J Addict Dis. 2005;24(1):53-60.

CardioversionMagnesiumEpinephrineLidocaine

QT Prolongation and TdPQT Prolongation and TdP

Cardioversion if unstable Magnesium Overdrive pacemaker Subsequent options unclear

Chest Pain SummaryChest Pain Summary

ACLS / AHA• Minus beta blockers

Absence of complication• Short period of observation• Clinical stability• Stable ECG + Negative marker(s)

Referral for detoxification