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Cocaine induced myocardial ischemia Sean Caine Grand Rounds Emergency Medicine October 16, 2008 Objectives Epidemiology Pharmacology Review Pathophysiology of CIMI Diagnosis Disposition Management Summary Epidemiology In Alberta 12.3% report use of cocaine/crack in lifetime2 Above the national average of 10.6% 2.4% of patients report using in past year2 Steadily trending upward: 1.3% (1994) 1.1% (1989) Average age of 1st use is 23.81 Epidemiology Cocaine and the ED Detected in 25% of adults age 15-44 suffering fatal injuries7 Cocaine is second only to alcohol for acute drug related ED visits 2% of pts over age 60 tested positive for cocaine at an inner city ED Rates of ED visits for selected illicit drugs: 2005 Epidemiology ED visits for cocaine related phenomenon include: Psychiatric Cardiac Trauma Infectious Disease Genitourinary Neurologic Pulmonary Addiction-related symtoms/comlaints Obstetric/Gynecology MSK Chest pain is the most common presenting complaint of cocaine users in the ED CP accounts for 20-40% of presenting complaints among cocaine users in the ED4,5 Pharmacology Cocaine (benzoylmethylecgonine) Alkaloid from Erythroxylon coca plant Crystalloid form created by dissolving alkaloid in hydrochloric acid Crack cocaine is an unpurified free base “rocks” are obtained from combining cocaine HCl with a base (NaHCO3) and cooking in water Free Base is an ether extracted purified form of Crack Cocaine Pharmacology by Route of Administration Route Formula Onset of Action Peak Effect Duration Inhalation “Crack” 8 sec 2-5 min 10-20min IV Cocaine HCl seconds 10-20 min 30 min Skin popping Cocaine HCl Intranasal/ Mucosal absorbtion Cocaine HCl 2-5 min 5-10 min 30-90 min Modified from Rosen’s Emergency Medicine6 and Levis and Garmel3 Metabolism Ecgonine methylester Cocaine 40% Non-enzymatic hydolysis Benzoylecgonine (Benzoylmethylecgonine) Minor metabolites: -Norcocaine -Ecgonine Mechanism of Action Na fast channel 5HT and DA: Inhibits reuptake Vagal nuclei: moderate blocked Direct stimulation (brief) NE and E: Increased presynaptic release Reuptake inhibition Sympathomimetic toxidrome Hypertension Tachycardia Mydriasis Diaphoresis Hyperthermia CNS excitation/aggitation Cocaine Induced Myocardial Ischemia Case… 26 yo male. Works in Fort McMurray. Back in Calgary for the weekend. Reports new onset CP after using cocaine. DDx of chest pain Noncardiac Pneumothorax Pneumomediastinum Pneumopericardium Aortic dissection Pulmonary infarction Infection MSK Asthma Pneumonitis Cardiac chest pain Endocarditis Pericarditis Ischemia/infarction During acute intoxication After acute intoxication Cocaine Induced Myocardial Ischemia 25% of non-fatal MIs btwn age 18-45 are attributable to frequent cocaine use9 Cocaine-associated CP has a 57% admission rate10 5.7% of pts presenting with cocaine-associated CP will have a MI documented by elevated cadiac enzymes11 Large clinical trials have demonstrated that only 31-67% of cocaine associated MI have atherosclerotic CAD12,13 Risk of AMI is same for all routes of administration15 Risk of MI after cocaine use MI can occur with minutes to days following cocaine use Risk of MI is highest within 1 hours Mittleman, Mintzer, Maclure. Circulation. 199914 Pathophysiology of cocaine associated myocardial ischemia Coronary vasoconstriction and spasm mediated by α-adrenergic receptor stimulation and impaired endothelial dysfunction Human studies show decreases of 8-12% of left coronary artery diameter with doses smaller than typical recreational use17 33%-46% decreases in LAD artery diameter has been demonstrated in animal studies16 This effect further potentiated by presence of cigarette smoking and pre-existing CAD15 Vasoconstriction can be prolonged with coingestion of ethanol due to formation of cocaethylene Increased myocardial oxygen demand Cardiac workload is increased due to increased HR and systemic arterial pressures Negative inotropy also demonstrated in human in vitro studies BOTTOM LINE = the heart is beating FASTER and LESS EFFICIENTLY against GREATER RESISTANCE Thrombogenesis In vitro studies have demonstrated: ↑ platelet activation ↑platelet aggregation ↑thromboxane production Endothelial dysfunction Increased fibrin deposition Coronary Aneurysms Noted commonly among cocaine users undergoing angiography 34% of cocaine users vs 7.6% of control pts Angiogram of a 49 yo male with history of cocaine use. Arrows show a right coronary artery aneurysm. New York Times May 10, 2005 Chronic use… Spont ischemic episodes during withdrawal Accelerated atherosclerosis Left ventricular hypertrophy Systolic dysfunction Dilated cardiomyopathy Jones and Weir. Med Clin N AM. 200515 Diagnosis 26 yo male. New onset CP 2 hours after snorting a line. Investigations? Diagnostic Challenge Difficulty of diagnosis highlighted by high admission rate (57%)10 cocaineassociated chest despite low rate of MI (6%)11 Diagnostic Challenge Patient factors 25% pts will initially deny use of cocaine19 Delayed presentation 19% pts present >24hrs after onset of CP11 ECG Decreased sensitivity to detect MI11 Sensitivity: 35.7% NPV: 95.8% pts with CAMI are as likely to present with normal or nonspecific changes as they are with ischemic changes Higher ED miss rate. With 15% of pts with MI discharged home Increased FP due to presence of LVH and BER11 Specificity: 89.9% PPV: 17.9% Cardiac Enzymes CK & CKMB Decreased sensitivity due to skeletal muscle injury and rhabdo Approx 50% of pts with cocaine-associated CP will have elevated CK CKMB index calculations are distorted in presence of rhabdo Rising serum enzyme more concerning Troponin Troponin I specificity (95%) is comparable to noncocaine using population Preferred cardiac marker for ischemia/infarct in setting of cocaine associated MI 26 yo male with cocaine-associated CP. Initial ECG shows BER. Initial troponin is normal. Chest pain continues. Management ASA Benzodiazepines Decrease central stimulatory effects and aggitation Decrease myocardial O2 demand Shown to decrease HR and BP Nitrates Decrease cocaine induced vasoconstriction in pts with CAD Reduced cocaine-associated CP for 45% of pts20 Management Phentolamine Nonselective alpha antagonist Shown to reverse cocaine induced coronary vasocontriction in humans17 Suggested careful titration 1mg IV q5min Onset is immediate. Duration 15-30min CI: coronary or cerebral arteriosclerosis, phosphodiesterase inhibitors (ie Sildenifil), hypersensitivy Management CCB Less thoroughly evaluated Small study of 10 human volunteers showed verapamil relieved cocaine-induced vasospasm Managment Unfractionated Heparin or LMWH Not well studied Reasonable to give if no clear contraindication Management PCI for cocaine-induced MI Preferred intervention Provides means of diagnosing underlying etiology (ie vasospasm vs. thrombus) Perception of being more safe than lytics in due to case reports of pts w/ICH and aortic dissection Management Thrombolytics Not well studied Only Pts ICH if PCI not readily available at increased risk for aortic dissection and The β-blocker controversy β-blockers ACC/AHA guidelines: “Beta-blockers should not be administered to patients with STEMI precipitated by cocaine because of risk of exacerbating coronary spasm” RDBPCT showed proponolol increased coronary artery resistance and decreased coronary sinus flow21 Labetolol unlikely to offer any benefit and potentially harmful Inceases seizures and death in animal models12 Did not reverse vasoconstriction in human studies12 Dattilo et al. Annals of Emergency Medicine. 2008; 51(2): 117-125 Retrospective cohort study of 363 consecutive pts admitted to ICU or telemetry with positive urine tox Β-blockers given to 60 of 348 admission Reports lower rate of MI (6% vs 26%) and death (1.7% and 4.5%) among pts given B-blockers Dattilo et al. Annals of Emergency Medicine. 2008; 51(2): 117-125 Results have been heavily scrutinized when β-blockers were given during admission Large differences in baseline characteristics btwn cohorts Unclear Greater number of asthmatics among control cohort Greater proportion of B-blocker cohort were male, had higher Cr, and had hx CHF, CAD Severe Only 55% of β-blocker cohort had troponin measured vs. 96% 31/33 limitations with MI cohort. pts were given B-blocker after an MI Only 2 given B blocker – both of home had an MI Management Summary Disposition 26 yo male. Cocaine associated CP. Initial ECG was normal. CP resolved after one hour after given nitro spray x 3 and IV lorazepam. Rpt ECG and troponin normal. Prospective evaluation of 9-12 hour observation of 302 low/intermediate risk pts with cocaine associated CP Discharge criteria: Cocaine use confirmed by urine tox normal troponin, no new ischemic ECG changes CV complications (dysrhythmia, AMI, or recurrent symptoms) All had follow up w/internist or cardiologist within 48hrs Previous Studies Hollander et al. Cocaine-associated chest pain: one year follow up. Acad Emerg Med 1995; 2:179-184. Followed 203 pts discharged from hospital 98% one year actuarial survival 2 No deaths due to MI nonfatal MI No MI or death among pts claiming to have ceased using cocaine Key Points Cocaine-associated CP is a common presentation to ED Majority are NOT due to infarction High risk features: Recent use Hx of CAD Hx of smoking or alcohol use ECG, CKMB, CK are less reliable Low risk disposition can be established following 9-12 hours observations Key Points ASA, Benzo, nitrates are current first-line therapy Very low mortality rate Biggest predictor is continued cocaine use – OFFER contact info for AADAC/rehab Caution to be used with use of less well evaluated meds (CCB and phentolamine) Should continue to avoid B-blocker use No convinving mortality benefit Clearly demonstrated potential harm Any questions? References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Alberta Alcohol and Drug Abuse Commission. Canadian Addiction Survey 2004, Alberta Report. (2006). Edmonton, Alberta, Canada: Author. Adlaf, EM, Begin, P, Sawka E (Eds.). Canadian Addiction Survey (CAS): A national survey of Canadians’ use of alcohol and other drugs: Prevalence of use and related harms: Detailed report. (2005). Ottawa: Canadian Centre on Substance Abuse. Levis JT, Garmel GM. Cocaine-associated chest pain. Emergency Medicine Clinics of North America. 2005; 23:1083-1103. Hoffman RS, Hollander JE. Evaluation of patients with chest pain after cocaine use. Critical Care Medicine. 1997; 13: 809-28. Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive series of 233 patients. American Journal of Medicine. 1990; 88:325-31. Rao RB, Hoffman RS. Cocaine and other sympathomimetics. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6 ed. 2006. Marzuk PM, et al: Fatal injuries after cocaine use as a leading cause of death among young adults in New York City. N Engl J Med 1995; 332:1753 Drug Abuse Warning Network (DAWN). Available online at: dawninfo.samhsa.gov (Accecssed on December 19, 2006). Qureshi, AI, Suri MF, Guterman LR, Hopkins LN. Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Helath and Nutrition Examination Survey. Circulation. 2001; 103:502. Hollander JE. Current concepts: the management of cocaine-associated myocardial ischemia. N Eng J Med. 1995; 333(19):1267-72. References 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. Hollander JE, Hoffman RS, Gennis P, et al. Prospective multicenter evaluation of cocaineassociated chest pain. Cocaine associated chest pain group (COCHPA) study group. Acad Emerg Medi. 1994; 1:330. Hollander JE, Henry TD. Evaluation and management of the patient who has cocaineassociated chest pain. Cardiol Clin. 2006; 24:103-114. Kontos MC, Jesse RL, Tatum JL, et al. Coronary angiographic findings in patients with cocaine associated chest pain. J Emerg Med 2003: 24(1):9-13. Mittleman MA, Mintzner D, Maclure M et al. Triggering of myocardial infraction by cocaine. Circulation. 1999; 99:2737. Jones JH, Weir WB. Cocaine-associated chest pain. Med Clin N Am. 2005; 89:1323-1342. Hayes SN, Moyer TP, Morley D, et al. Intravenous cocaine causes epicardial coronary vasoconstriction in the intact dog. Am Heart J. 1991; 121(6 Pt 1): 1639-48. Lange RA, Cigarroa RG, Yancy CW Jr. et al. Cocaine-induced coronary artery vasoconstriction. N Eng J Med. 1989; 321 (23):1557-62. Satran A, Bart BA, Henry CR, et al. Increased prevalence of coronary artery aneurysms among cocaine users. Circulation. 2005; 111: 2424. Hollander JE, Todd KH, Green G, et al. Chest pain associated with cocaine: an assessment of prevalence in suburban and urban emergency departments. Ann Emerg Med. 1995; 26(6): 671-6. Hollander JE, Hoffman RS, Gennis P, et al. Nitroglycerin in the treatment of cocaine associated CP-clinical safety and efficacy. J Toxicol Clin Toxicol 1994; 32(3):243-256. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med 1990; 112:897-903.