Cocaine induced myocardial ischemia

Sean Caine

Grand RoundsEmergency 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 NeurologicCardiac PulmonaryTrauma Addiction-related symtoms/comlaintsInfectious Disease Obstetric/GynecologyGenitourinary 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 AdministrationRoute Formula Onset of

ActionPeak 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

Cocaine(Benzoylmethylecgonine)

Ecgonine methylester

Benzoylecgonine

Minor metabolites:

-Norcocaine

-Ecgonine

30-50%

40%

DETECTED IN

URINE TOX

SCREEN

plasma cholinesterase

Non-enzymatic hydolysis

Mechanism of Action Na fast channel

moderate blocked

5HT and DA: Inhibits reuptake

Vagal nuclei: 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 co-ingestion 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 cocaine- associated 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

CCBLess 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 MIPreferred 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

ThrombolyticsNot well studied

Only if PCI not readily available

Pts at increased risk for aortic dissection and ICH

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

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 scrutinizedUnclear when β-blockers were given during

admissionLarge differences in baseline characteristics

btwn cohorts Greater number of asthmatics among control cohort Greater proportion of B-blocker cohort were male, had

higher Cr, and had hx CHF, CADSevere limitations with MI cohort.

Only 55% of β-blocker cohort had troponin measured vs. 96%

31/33 pts were given B-blocker after an MI Only 2 given B blocker – both of home had an MI

Dattilo et al. Annals of Emergency Medicine. 2008; 51(2): 117-125

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

Cocaine use confirmed by urine tox

Discharge criteria: 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

No deaths due to MI 2 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?

References1. Alberta Alcohol and Drug Abuse Commission. Canadian Addiction Survey 2004,

Alberta Report. (2006). Edmonton, Alberta, Canada: Author. 2. 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.

3. Levis JT, Garmel GM. Cocaine-associated chest pain. Emergency Medicine Clinics of North America. 2005; 23:1083-1103.

4. Hoffman RS, Hollander JE. Evaluation of patients with chest pain after cocaine use. Critical Care Medicine. 1997; 13: 809-28.

5. Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive series of 233 patients. American Journal of Medicine. 1990; 88:325-31.

6. Rao RB, Hoffman RS. Cocaine and other sympathomimetics. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6 ed. 2006.

7. 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

8. Drug Abuse Warning Network (DAWN). Available online at: dawninfo.samhsa.gov (Accecssed on December 19, 2006).

9. 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.

10. Hollander JE. Current concepts: the management of cocaine-associated myocardial ischemia. N Eng J Med. 1995; 333(19):1267-72.

References11. Hollander JE, Hoffman RS, Gennis P, et al. Prospective multicenter evaluation of cocaine-

associated chest pain. Cocaine associated chest pain group (COCHPA) study group. Acad Emerg Medi. 1994; 1:330.

12. Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiol Clin. 2006; 24:103-114.

13. 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.

14. Mittleman MA, Mintzner D, Maclure M et al. Triggering of myocardial infraction by cocaine. Circulation. 1999; 99:2737.

15. Jones JH, Weir WB. Cocaine-associated chest pain. Med Clin N Am. 2005; 89:1323-1342.16. 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): 1639-48.17. Lange RA, Cigarroa RG, Yancy CW Jr. et al. Cocaine-induced coronary artery

vasoconstriction. N Eng J Med. 1989; 321 (23):1557-62.18. Satran A, Bart BA, Henry CR, et al. Increased prevalence of coronary artery aneurysms

among cocaine users. Circulation. 2005; 111: 2424.19. 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.

20. 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.

21. 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.