Cocaine-induced chest pain Focus on Acute coronary syndromes

1
Cocaine-induced chest painFocus on Acute
coronary syndromes

• Daniel Brouillard, R3
• McGill Emergency Medicine
• December 12 2001

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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?

3
Plan

• Cocaine
• 2) Cocaine associated-C/P
• 3) Cocaine-related myocardial ischemia

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Cocaine

• Erythroxylon coca
• Benzoylmethylecgonine (cocaine)
• Primarly grown in South America
• Hydrochloride salt
•  free base 

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History

• 3000 B.C. Coca leaves are chewed in South
  America, believed to be a gift from God.
• 1400s 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.

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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 Harrisons Narcotics Act
• 1970s -80s Days of Glory
• Mid-80s Freebase cocaine( crack)

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Presentation and pharmacology

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Onset and duration of action
ROUTE ONSET PEAK (min) DURATION (min)
Inhalation or Iv Seconds 3-5 15-30
Insufflation 1-3 min 20-30 60-90
GI Variable 60-90 Over 180
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Effects

• 1) Sodium channel blocking properties
  (Quinidine-Like)
• 2) Systemically, blocks the re-uptake of amines
  in the synapse.

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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.

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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.

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Part II
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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

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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 ?

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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

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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)

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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 hlt)
• Overall mortality 1

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Cocaine related complaints
Brody,1990 Rich, 1991
CVS 40 16
Neuro 21 25
Psychiatric 27 31
Trauma - 11
GI 10 8
MSK 9 3
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Differential diagnosis

• Cardiomyopathy
• Myocarditis
• Pulmonary embolus or thrombus
• Pneumonia
• Endocarditis
• Aotic dissection
• Pneumothorax, pneumopericardium,
  pneumomediastinum
• ACS

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Differential diagnosis(2)

• Most articles discuss the prevalence of AMI/ACS.
• Case reports
• Most C/P will, in the end, have a benign
  diagnosis.

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Prevalence studies-Cocaine MI
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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

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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?

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People with chest painUsers 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

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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

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Dangers of body-packing
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Frequent vs non-frequent users

• 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

• 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 MIs
• HNADES III 88-94

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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

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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 MIs (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

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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.

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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

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Complications
CHF 7
Nonsustained VT 13
Sustained VT 4
SVT 4
Bradydysrhythmias 19
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Mortality

• Feldman 2000 0
• Weber 2000 0
• Hoffman 1995 0
• Hollander 1994 0
• -No study reports death following arrival to the
• hospital.

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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

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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

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PART III
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Animal testing
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Part III Cocaine- related ACS

• Pathophysiology
• Diagnosis
• Treatment
• Conclusion

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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).

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Pathophysiology(2)

• Coronary vasoconstriction
• Most human studies use doses 2mg/kg 1-4
• Effect starts at 3-5 min
• Decrease in diameter of 4 to 29
• Effect is worse on diseased arteries. 5
• Presence of temporal variations
• 1)Lange and al., N Engl J Med 19893211557-62.2
  )Flores ED, Am Coll Cardiol 19901674-9.3)Molnert
  o DJ, N Engl J Med 1994330454-9. 4)Majid MJ,
  Clin Cardiol 199215253-8.5)Daniel WC, Am J
  Cardiol 199678288-91

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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
  1986110479-84.
• 2)Cooke CT, Pathology 198820242, 305-6
• 3)Patel GQ, Circulation 198878(II Suppl)II436
  
• 4)Steinberg RG,Arch Pathol Lab Med 1989113521-4

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Pathophysiology (4)

• Accelerated intracoronary atherosclerosis
• - Wilson and al, J Emerg Med 199816631-4.
• - 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.

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Pathophysiology
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Evaluation

• History and physical examination.
• EKG
• Cardiac enzymes

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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

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EKG

• Primary determinent to thrombolysis in AMI.
• Sensitivity 54-89 ( 95 CI )
• Specificity 67-96
• Do these findings apply to cocaine-induced chest
  pain?

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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 EKGs
• - 19 of patients had CK-MB elevation

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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.

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EKG(4)

• Are abnormal EKGs 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

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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)

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EKGSensitivity 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

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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
  non-users)
• 2) Troponin I not affected (94 in both group)
• Hollander, Am. Jour. of Cardiology, 1998

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Treatment

• ASA
• Nitrates
• ß- blockers
• a- blockers
• Calcium channel blockers
• Benzodiazepines
• Anticoagulants
• Reperfusion strategies

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ASA

• First line agent in ACS
• NO formal studies in the context of cocaine-
  related 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

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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???

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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 ?

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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

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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

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ß-Blockers

• UGE controversy in the literature
• 2000 AHA TOX-ACLS recommendations
• Good quality evidence to exclude non-selective
  ß-blockers.
• Selective ß-blockers and mixed a/ß (labetalol)
  are not recommended but not C-I

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a-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 cocaine-induced myocardial
  ischemia. N Engl J Med 1992327361-361

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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 199473510-513

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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.

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Thrombolysis

• Pros
• - Proven thrombotic component
• - Improved mortality/morbodity in traditionnal
  AMI
• - Available in most centers

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Thrombolysis

• Cons
• - Low mortality in this patient population.
• - No proven benefit in cocaine-AMI.
• - Risk of hemorrhage.
• - Difficult EKG interpretation in this
  population.

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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 (95CI).

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Thrombolysis-Safety

• Hollander/ Hoffman, Chest, 1995
• Serie of 67 patients with Cocaine-MI
• 25 received thrombolysis
• 14/21 had evidence of reperfusion
• No complications

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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

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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.

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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.

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Thank YOU

• ?