Transcript Cocaine induced chest pain - Hatzalah of Miami-Dade

Cocaine-induced chest pain
Focus on Acute coronary
syndromes
Daniel Brouillard, R3
McGill Emergency Medicine
December 12 2001
Objectives
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What is the prevalence of ACS/AMI in cocaine users?
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What is the role of the EKG in the diagnosis of ACS in this
particular patient population?
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What is the most beneficial approach to management based on
the current litterature?
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What is the role of reperfusion therapy in these patients?
Plan
1)
Cocaine
2)
Cocaine associated-C/P
3) Cocaine-related myocardial ischemia
Cocaine
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Erythroxylon coca
Benzoylmethylecgonine
(cocaine)
Primarly grown in
South America
Hydrochloride salt
« free base »
History
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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)
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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
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.
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
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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
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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
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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
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In cocaine users who present to the ED, how
many will have a major complaint of C/P ?
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How many of these patients have ACS ?
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How many of these patients have AMI ?
Hollander and al. Annals of
emergency medicine 1994
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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 »
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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 »
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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
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11%
GI
10%
8%
MSK
9%
3%
Differential diagnosis
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Cardiomyopathy
Myocarditis
Pulmonary embolus or thrombus
Pneumonia
Endocarditis
Aotic dissection
Pneumothorax, pneumopericardium,
pneumomediastinum
ACS
Differential diagnosis(2)
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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
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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
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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
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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
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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
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HNADES III ’88-’94
Results:
1) OR 6.9 for frequent users.
CI95% 1.3 to 58
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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
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CAD vs Non-CAD events ?
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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
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Reported in the prospective studies: 5-10%
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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
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Feldman 2000 : 0%
Weber 2000: 0%
Hoffman 1995: 0%
Hollander 1994: 0%
-No study reports death following arrival to the
hospital.
In summary
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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)
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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
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Pathophysiology
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Diagnosis
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Treatment
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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)
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Coronary vasoconstriction
Most human studies use doses 2mg/kg
Effect starts at 3-5 min
1-4
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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
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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
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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.
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#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
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History and physical examination.
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EKG
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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.
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*Hofffman, Academic emergency med, 1994
EKG
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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
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 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.
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EKG(4)
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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)
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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
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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)
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Hollander, Am. Jour. of Cardiology, 1998
Treatment
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ASA
Nitrates
β- blockers
α- blockers
Calcium channel blockers
Benzodiazepines
Anticoagulants
Reperfusion strategies
ASA
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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
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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
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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
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Nitroglycerin
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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
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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
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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
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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
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Cocaine acts as Class Ia
Tox-ACLS : H2CO3 is first line
Safety of Lidocaine?
-RD Shih, Annals of Emergency Medicine Volume 26 •
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Number 6 • December 1995
- Risk
is high based on animal studies.
- Time from last cocaine consumption seems
important.
Thrombolysis
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Pros:
- Proven thrombotic component
- Improved mortality/morbodity in traditionnal
AMI
- Available in most centers
Thrombolysis
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Cons
- Low mortality in this patient population.
- No proven benefit in cocaine-AMI.
- Risk of hemorrhage.
- Difficult EKG interpretation in this
population.
Thrombolysis- complications
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« 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
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Hollander/ Hoffman, Chest, 1995
Serie of 67 patients with Cocaine-MI
25 received thrombolysis
14/21 had evidence of reperfusion
No complications
Summary-Treatment
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Agressive first line treatment is recommended.
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If no response : trial of second line medications
and arrange for possible Cath-Lab.
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If doubt on the diagnosis try to get rapid
confirmation of diagnosis (Echo, Technicium99)
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Consider thrombolysis
Conclusion
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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.
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Thank YOU
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