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Cocaine-induced chest pain Focus on Acute coronary syndromes Daniel Brouillard, R3 McGill Emergency Medicine December 12 2001 Objectives What is the prevalence of ACS/AMI in cocaine users? What is the role of the EKG in the diagnosis of ACS in this particular patient population? What is the most beneficial approach to management based on the current litterature? What is the role of reperfusion therapy in these patients? Plan 1) Cocaine 2) Cocaine associated-C/P 3) Cocaine-related myocardial ischemia Cocaine Erythroxylon coca Benzoylmethylecgonine (cocaine) Primarly grown in South America Hydrochloride salt « free base » History 3000 B.C. Coca leaves are chewed in South America, believed to be a gift from God. 1400’s Coca plantations operated by Incas. 1662 First indepedent mention of coca in the English litterature: « A legend of Coca » by Abraham Coley. 1850 Coca tinctures used in throat surgery. 1855 Cocaine is first extracted from coca leaves. 1870 Vin Mariani is for sale in Europe, in contains 6mg of cocaine per ounce of wine. History (continued) 1884 Sigmund Freud publishes « On Coca » in witch he recommends the use of cocaine in the treatment of various conditions. 1886 Introduction of Coca-Cola: contains cocaine syrup. 1895 First cases of associated deaths reported in the Lancet. 1912 5000 cocaine related fatalities per year 1914 Harrison’s Narcotics Act 1970’s -80’s Days of Glory Mid-80’s Freebase cocaine( crack) Presentation and pharmacology . Erythroxylon Coca Cocaine salt « freebase » cocaine Snorted Ingested Injected Heat stable Smoked Onset and duration of action ROUTE ONSET Inhalation or Seconds Iv Insufflation GI DURATION PEAK (min) (min) 3-5 15-30 1-3 min 20-30 60-90 Variable 60-90 Over 180 Effects 1) Sodium channel blocking properties (Quinidine-Like) 2) Systemically, blocks the re-uptake of amines in the synapse. Excretion Metabolised by liver and plasma esterase Ecgonyl methyl ester (30-50%) Benzylecgonine (40%) Detection possible in urine - Free cocaine : 6h - Benzylecgonine : up to 72 h. Cocaethylene 2 substances often consummed together Product of combination of cocaine and ET-OH in the liver. Dose related myocardial depression in dogs. Longer half life Could account for delayed presentation. Part II Cocaine and people 30 million American at least one time users 5 million current users 160,000 visits per year in the USA Statistiques Canada 1994: close to 2% of Canadian population are current users Prevalence-Questions In cocaine users who present to the ED, how many will have a major complaint of C/P ? How many of these patients have ACS ? How many of these patients have AMI ? Hollander and al. Annals of emergency medicine 1994 Prevalence of cocaine use in patients older then 18 y presenting with C/P 359 patients Anonymous urine collection on everybody Found 20 % prevalence in urban area Prevalence of 7% at the rural sites 28% of positives denied use when questioned Rich, Annals of EM, June 1991 « Cocaine related Symptoms in patients presenting to the ED » 146 patients Retrospective chart review Overall prevalence 16% for C/P (23 patients) Total of 3 patients admitted Stronger association with nasal route (11/23) Brody, Am. Journal of medicine, 1990 « Cocaine-related medical problems » 233 patients Retrospective chart review 40% prevalence of C/P Most had acute complaints(3 h<) Overall mortality 1% Cocaine related complaints Brody,1990 Rich, 1991 CVS 40% 16% Neuro 21% 25% Psychiatric 27% 31% Trauma - 11% GI 10% 8% MSK 9% 3% Differential diagnosis Cardiomyopathy Myocarditis Pulmonary embolus or thrombus Pneumonia Endocarditis Aotic dissection Pneumothorax, pneumopericardium, pneumomediastinum ACS Differential diagnosis(2) Most articles discuss the prevalence of AMI/ACS. Case reports Most C/P will, in the end, have a benign diagnosis. Prevalence studies-Cocaine MI 40 35 30 25 20 % 15 10 5 0 Amin 1990 Zimmerman 1991 Hollander 94 Weber 2000 Feldman2000 Problems Subjected to reporting bias All studies done on inpatients. No studies use Troponin. Small amount of long term follow-up. Population difficult to follow as outpatient AMI vs ACS All studies essentially look at incidence of MI. Questions: Acute event in a otherwise normal coronary? Prevalence of actual CAD ? Prevalence of Acute Coronary Syndromes? Reversible ischemia? People with chest pain Users vs non-users American Survey 1995-1996 4639 chest pain visits In the general population( ages 25-40) 5.6% of C/P in ED will be ACS 2.5% prevalence of AMI Burt, Am. Jour. Of Emerg. Med, October 1999 Epidemiology High proportion is male ( 70-80%) Mostly African-American Median age : 35 yo Cardiac risk similar vs control High concommitant use of cigarettes More likely to be admitted to ICU/CCU Cost of 83 millions $$$$$$ Dangers of body-packing Frequent vs non-frequent users Third Nationnal Health and Nutrition survey 10 085 patients aged 18-45 yo 731 infrequent users 532 frequent users ( about 5% of population) 46 non fatal MI’s HNADES III ’88-’94 Results: 1) OR 6.9 for frequent users. CI95% 1.3 to 58 2) OR 0.1 infrequent users. CI95% 0.002 to 0.8 *More smokers, HTN Time to presentation Mittleman and al., Circulation 99 - 3946 MI patients - 38 admitted to cocaine use - 9 within 1h of MI - 1within 2h of MI - 1 within 3h of MI - RR 23.7 in the first hour Prevalence of ACS Feldman, Annals of emergency med. 1999 -241 patients over 2 years. - High risk (69) went directly to CCU. - Moderate and low risk had tehcnicium99 sestamibi done in the following 90 min. - 6 MI’s (6/218= 2.5%) or 8.7% of CCU patients - Stress studies on 70 patients: 6 reversible ischemia (6/67= 8.6%) at follow-up. - No recurrence at 30 days CAD vs Non-CAD events ? Review articles : 31 to 67% have CAD. Hollander , Meta-analysis, 1997 - 66 patients with cocaine-associated MI - Angio-proven CAD in 41% of patients - Presence of other risk factors NOT associated with greater incidence of CAD. Complications/ short term Reported in the prospective studies: 5-10% One study designed to look at complications: - Hoffman, Archives of internal med, 1995 - Retrospective study of 130 patients with MI. - 36% had complications - 90% within 12 h of presentation - 48% on arrival to the ED Complications CHF 7% Nonsustained VT 13% Sustained VT 4% SVT 4% Bradydysrhythmias 19% Mortality Feldman 2000 : 0% Weber 2000: 0% Hoffman 1995: 0% Hollander 1994: 0% -No study reports death following arrival to the hospital. In summary Up to 40% of cocaine-related complaints Young population Smokers Delayed presentation Frequent users are more at risk Most complications occur within 12h Very low mortality In summary(2) 6% prevalence of AMI in most studies. Prevalence of ACS is not known Maybe close to 9-10% 30 to 67% of these patients have CAD PART III Animal testing Part III Cocaine- related ACS Pathophysiology Diagnosis Treatment Conclusion Pathophysiology 1) Increased workload on the heart - Sympathomimetic state - Increased afterload - Increased myocardial O2 needs. Impact: Rise in BP of 20/10mmHg Rise in HR of 30 beats/min Equivalent to mild exercise at recretionnal doses. ( 2 mg/kg). Pathophysiology(2) - Coronary vasoconstriction Most human studies use doses 2mg/kg Effect starts at 3-5 min 1-4 - Decrease in diameter of 4% to 29% Effect is worse on diseased arteries. Presence of temporal variations 1. 1)Lange and al., N Engl J Med 1989;321:1557-62.2 )Flores ED, Am Coll Cardiol 1990;16:74-9.3)Molnerto DJ, N - . 5 Engl J Med 1994;330:454-9. 4)Majid MJ, Clin Cardiol 1992;15:253-8 5)Daniel WC, Am J Cardiol 1996;78:288-91 Pathophysiology(3) Thrombosis and platelet aggregation. - Cocaine associated to thrombus in coronary arteries in some of the AMI cases. - Angiographic and pathologic evidence.1-4 - Mecanism is believed to be expression of thrombogenic substances in-situ 1)Simpson RW, Arch Pathol Lab Med 1986;110:479-84. 2)Cooke CT, Pathology 1988;20:242, 305-6 3)Patel GQ, Circulation 1988;78(II Suppl):II436 4)Steinberg RG,Arch Pathol Lab Med 1989;113:521-4 Pathophysiology (4) Accelerated intracoronary atherosclerosis - Wilson and al, J Emerg Med 1998;16:631-4. - Review of previous series and 2 new cases. #1 Significant LAD lesion over 10 months #2 Significant 3 vessel disease over 16 months - Rapid progression in chronic abusers. - Recurrence of ACS with continuous use. Pathophysiology Evaluation History and physical examination. EKG Cardiac enzymes History and physical exam Unable to differentiate between the various causes on the basis of the clinical evaluation. - Localisation - Quality - Associated symptoms - Pleuritic component * 28% of patients with MI had a pleuritic component. *Hofffman, Academic emergency med, 1994 EKG Primary determinent to thrombolysis in AMI. Sensitivity: 54-89% ( 95% CI ) Specificity: 67-96% Do these findings apply to cocaine-induced chest pain? EKG (2) Gitter and al., Annals of int. Medicine, 1991 - Serie of 101 patients with cocaine-C/P - 43% met TIMI criteria for reperfusion. - NO AMI found Tokarski, Ann. of emerg. Med, 1990 - Serie of 42 patients - All normal EKG’s - 19% of patients had CK-MB elevation EKG (3) Pitfalls : - High prevalence of repolarisation abnormalities in young population. (BER). - Presence of repolarisation abnormalities in cocaine users without C/P. - Higher incidence of left ventricular hypertrophy in cocaine users. EKG(4) Are abnormal EKG’s in cocaine-induced C/P due to normal variants? Study of 112 patients ( 56 per group) Young (mean 28yo), Non-caucasian Few other risk factors for CAD 2 independent physicians Kappa 0.70 Hollander, Acad. Emerg med, 1994 EKG(5) 9-16% of controls had Normal EKG (4-13%) 5-18% of controls had Ischemic ( 13-25%) 5% of controls met TIMI criterias (13%) Conclusion: - High prevalence in « normal » population - Further increase in cocaine users « ischemic » ( 22 vs 13%) EKG Sensitivity and specificity Hollander, Hoffman, « Prospective multicenter evaluation of Cocaine-associated chest pain. », Acad. Emerg. Med., 1994 Sensivity: 35.7% Specificity: 89.9% PPV: 17.9% NPV: 95.8% Cardiac enzymes All studies reviewed are using CK-MB. Is the specificity of cardiac markers changed in cocaine users ? Answer: 1) Mildly for CK-MB ( 75% users vs 88% in nonusers) 2) Troponin I : not affected (94% in both group) Hollander, Am. Jour. of Cardiology, 1998 Treatment ASA Nitrates β- blockers α- blockers Calcium channel blockers Benzodiazepines Anticoagulants Reperfusion strategies ASA First line agent in ACS NO formal studies in the context of cocainerelated ACS Makes sense to give for its antiplatelet activity. Caution against its use if SAH is suspected. Hollander, NEJM, 1995. Lange and Hillis, NEJM, 2001 Hoffman, Emerg. Med clinics, 2001 Benzodiazepines Works by stimulation of GABA receptors. Agent of choice to control agitation and other sympatomimetic symptoms. Protects against seizures. Anxiolytic effect Mechanism of action in cocaine-induced C/P??? Benzodiazepines Decreases the adrenergic state Decreases O2 requirements and workload. No demonstrated effect on coronaries. Are benzos better then nitro in cocaine-induced chest pain ? Baumann, Acad. Emerg Med, 2000 Randomised double-blind placebo controlled study. 40 patients, Diazepam, Nitro, or both. Outcomes: chest pain score, vital signs and hemodynamic monitoring Results: - No difference between the 2 drugs - No beneficial effect of combination of both Nitroglycerin Standard of care in ACS Coronary vasodilator in ACS. Experimental evidence of reversal of coronary vasospam caused by cocaine. Good to lower BP. No advantage over benzos ( Baumann 2000) Place in therapy β-Blockers UGE controversy in the literature 2000 AHA TOX-ACLS recommendations Good quality evidence to exclude nonselective β-blockers. Selective β-blockers and mixed α/β (labetalol) are not recommended but not C-I α-Blockers Prototype drug is phentolamine. AHA 2000 : Class IIb Reverses vasoconstriction Based on animal and human studies. No RDM clinical trial or safety studies. Use of a low dose is recommended. Hollander JE, Carter WA, Hoffman RS. Use of phentolamine for cocaineinduced myocardial ischemia. N Engl J Med 1992;327:361-361 Calcium channel blockers Coronary artery vasodilator. Decreases afterload. Not reviewed in Tox-ACLS. One human study (10 patients).1 Conclusion: Cannot recommend routinely 1.Negus BH, Willard JE, Hillis LD, et al. Alleviation of cocaine-induced coronary vasoconstriction with intravenous verapamil. Am J Cardiol 1994;73:510-513 Antiarythmics Cocaine acts as Class Ia Tox-ACLS : H2CO3 is first line Safety of Lidocaine? -RD Shih, Annals of Emergency Medicine Volume 26 • Number 6 • December 1995 - Risk is high based on animal studies. - Time from last cocaine consumption seems important. Thrombolysis Pros: - Proven thrombotic component - Improved mortality/morbodity in traditionnal AMI - Available in most centers Thrombolysis Cons - Low mortality in this patient population. - No proven benefit in cocaine-AMI. - Risk of hemorrhage. - Difficult EKG interpretation in this population. Thrombolysis- complications « traditionnal AMI » risk of intracranial bleed is 0.95% in a serie of 71 000 AMI patients. 3 case reports in the literature. Reported thrombolysis complication rate for cocaine-related AMI is 0 to 12% (95%CI). Thrombolysis-Safety Hollander/ Hoffman, Chest, 1995 Serie of 67 patients with Cocaine-MI 25 received thrombolysis 14/21 had evidence of reperfusion No complications Summary-Treatment Agressive first line treatment is recommended. If no response : trial of second line medications and arrange for possible Cath-Lab. If doubt on the diagnosis try to get rapid confirmation of diagnosis (Echo, Technicium99) Consider thrombolysis Conclusion Chest pain is the most common chief complaint of cocaine users. High prevalence of CAD in this population. Up to 10% will have an acute coronary syndrome History and EKG may be misleading. Conclusion(2) Observe and obtain serial enzymes. Treat keeping in mind the pathophysiology of cocaine related AMI. Disposition: - 12h observation period - Close follow-up for stress-testing Treat the addiction. Thank YOU ?