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History
1884 Sigmund Freud publishes On Coca ; 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 Harrisons Narcotics Act:"An Act To provide for the registration of, with
collectors of internal revenue, and to impose a special tax on all persons who produce, import, manufacture, compound, deal in, dispense, sell, distribute, or give away opium or coca leaves, their salts, derivatives, or preparations, and for other purposes."
Pathophysiology
Cocaine users have elevated levels of C-reactive protein, von Willebrand factor, and fibrinogen that may also contribute to thrombosis Cocaine, therefore, causes myocardial ischemia or MI in a multifactorial fashion that includes: (1) increasing myocardial oxygen demand by increasing heart rate, blood pressure, and contractility; (2) decreasing oxygen supply via vasoconstriction; (3) inducing a prothrombotic state by stimulating platelet activation and altering the balance between procoagulant and anticoagulant factors; and (4) accelerating atherosclerosis.
The incidence of CAA ranges from 0.2% to 5.3% with the largest antemortem series found in the Coronary Artery Surgery Study (CASS) registry (4.9% of 20 087 patients referred for coronary angiography). CAAs are most commonly associated with atherosclerosis but also are reported with Kawasakis disease, arteritis (polyarteritis nodosa, syphilis, systemic lupus erythematosis, Takayasus arteritis), mycoses, trauma, connective tissue disorders (Marfans and Ehlers-Danlos syndromes), metastatic tumors, polycystic kidney disease After observing the presence of severe coronary ectasia in several young cocaine users, the authors hypothesized that cocaine use increases the prevalence of CAA The study population included 112 consecutive patients over a 10-year period with a history of cocaine use and coronary angiography. Of the patients with reliable documentation regarding frequency and method of cocaine abuse, 66% reported at least weekly use.
Cont
Sixty-nine percent reported smoking or intranasal use; 7%, intravenous use; and 24%, multiple routes of administration. To provide a control group, a cohort of 79 patients of similar age and risk factors was selected from a preexisting angiographic database of 300 consecutive patients within the time period of the study group.
To provide a similar age distribution, all patients <52 years of age were included, with cocaine use the only exclusionary criterion. Although the control group was similar in nearly all clinical characteristics, there was a higher rate of diabetes (33% vs 16%, p=0.01) in controls and a higher rate of cigarette smoking (95% vs 71%, p<0.001) in cocaine users. Indications for angiography among the cocaine users were as follows: 34% acute coronary syndromes, 20% stable angina/positive stress test, 27% congestive heart failure/cardiomyopathy, 16% atypical chest pain, and 4% arrhythmias/valvular disease. Indications for angiography among the control group included 47% acute coronary syndromes, 34% stable angina/positive stress test, 5% congestive heart failure/cardiomyopathy, 9% atypical chest pain, and 5% arrhythmias/valvular disease.
In the COCaine Associated CHest PAin (COCHPA) study, cocaine-associated MI occurred in 6% of patients who presented to the ED with chest pain after cocaine use Overall incidence of cocaine-associated MI varies between studies from 0.7% to 6% of those presenting with chest pain after cocaine ingestion (some of the variance may relate to differences in MI diagnostic criteria), cocaine appears to be an important contributor to MI among the young
Hollander JE, Hoffman RS, Gennis P, Fairweather P, DiSano MJ, Schumb DA, Feldman JA, Fish SS, Dyer S, Wax P, Whelan C, Schwartzwald E. Prospective multicenter evaluation of cocaine-associated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group. Acad Emerg Med. 1994; 1: 330339.
146 patients Retrospective chart review Overall prevalence 16% for CP (23 patients) Total of 3 patients admitted Stronger association with nasal route (11/23)
233 patients Retrospective chart review 40% prevalence of CP Most had acute complaints (3 h<) Overall mortality 1%
Prevalence studies-Cocaine MI
Cocaine-associated MI appears to occur most often soon after cocaine ingestion. In one study, two thirds of MI events occurred within 3 hours of cocaine ingestion Survey of 3946 patients with recent MI, 38 patients admitted to cocaine use in the preceding year, and 9 patients reported ingestion in the 60 minutes preceding the onset of MI symptoms This survey reported a striking 24-fold higher risk of MI in the first hour after cocaine use, with a rapid decrease in risk after this time
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
EKG
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, which may be interpreted by physicians as an abnormal ECG finding Gitter and colleagues reported an early repolarization pattern in 32% of patients with cocaine-associated chest pain, a left ventricular hypertrophy pattern in 16%, and a normal ECG in only 32% of patients.
Overall, 42% of patients in their cohort of 101 patients manifested electrocardiographic ST-segment elevation, although all of them eventually had MI excluded by cardiac marker testing
In the COCHPA (Cocaine Associated Chest Pain) study, the sensitivity of an ECG revealing ischemia or MI to predict a true MI was only 36%
Gitter MJ, Goldsmith SR, Dunbar DN, Sharkey SW. Cocaine and chest pain: clinical features and outcome of patients hospitalized to rule out myocardial infarction. Ann Intern Med. 1991;115:277282.
Cardiac Biomarkers
Hollander, Am. J. of Cardiology, 1998
All studies reviewed using CK-MB Is the specificity of cardiac markers changed in cocaine users ? Answer: 1) Mildly for CK-MB ( 75% users vs 88% in non-users) 2) Troponin I : not affected (94% in both group)
Cocaine ingestion may cause rhabdomyolysis with consequent elevation in myoglobin and total creatine kinase levels, which may confound the diagnosis of cocaine-associated MI
Treatment
ASA Benzodiazepines Nitrates
- blockers
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 CP; more related to its neuro effects that subsequently affect the CVS (decrease adrenegic response) Decreases O2 requirements and workload No demonstrated effect on coronaries
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)
Negus BH, Willard JE, Hillis LD, et al. Alleviation of cocaine-induced coronary vasoconstriction with intravenous verapamil. Am J Cardiol 1994;73:510-513
Beta Blockers
Controversy in the literature 2000 AHA TOX-ACLS recommendations: Good quality evidence to exclude non-selective -blockers Selective -blockers and mixed contraindicated / (labetalol) are not recommended but not
Propranolol exacerbates the depression of coronary blood flow induced by cocaine because of unopposed alpha stimulation after beta-blockade Esmolol is a selective beta1-adrenergic blocker with rapid onset and short duration of action (elimination half-life, 9 min) Coadministration of esmolol and sodium nitroprusside should be reserved for severe hypertension that is unresponsive to other treatment and/or complicated by aortic dissection
Beta Blockers
Third-line agent for drug-induced hypertensive emergencies However, labetalol, a combined alpha- and beta-blocking agent, has an alpha-to-beta blockade ratio of 1:7 Therefore, it may not provide enough protection for cocaine-toxic patients from (relatively) unopposed alpha stimulation Its risk of exacerbating myocardial ischemia parallels the risk of other beta-blockers
-Blockers
phentolamine
AHA 2000 : Class IIb Reverses vasoconstriction Based on animal and human studies No randomized clinical trials or safety studies
Hollander JE, Carter WA, Hoffman RS. Use of phentolamine for cocaineinduced myocardial ischemia. N Engl J Med 1992;327:361-361
Cocaine-associated VF
Cocaine activation of myocardial alpha-adrenergic receptors, specifically alpha1A-adrenergic receptors, may substantially contribute to VF during myocardial ischemia Activation of these receptors elevates cytosolic calcium levels and provokes delayed after-depolarizations Therefore, calcium overload may be the final common pathway linking enhanced adrenergic activity to cocaineinduced VF
Thrombolysis
Pros: - Improved mortality/morbidity in traditionnal AMI - Available in most centers
Thrombolysis
Cons - 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 series of 71 000 AMI patients Reported thrombolysis complication rate for cocaine-related AMI is 0 to 12% (95%CI)
Therefore, they recommend using a bare-metal stent over a drug-eluting one to reduce the
Conclusion
Chest pain is the most common chief complaint of cocaine users High prevalence of CAD and CAA in this population Up to 10% will have an acute coronary syndrome History and EKG may be misleading
Conclusion
Observe and obtain serial enzymes Treat keeping in mind the pathophysiology of cocaine related AMI, avoid BB, use BDZ Disposition: 12h observation period Close follow-up for stress-testing Treat the addiction Avoid DES and Thrombolysis