Transcript Cocaine induced myocardial ischemia

Cocaine induced
myocardial ischemia
Sean Caine
Grand Rounds
Emergency 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
Cardiac
Trauma
Infectious Disease
Genitourinary

Neurologic
Pulmonary
Addiction-related symtoms/comlaints
Obstetric/Gynecology
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
Administration
Route
Formula
Onset of
Action
Peak
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
Ecgonine methylester
Cocaine
40%
Non-enzymatic hydolysis
Benzoylecgonine
(Benzoylmethylecgonine)
Minor metabolites:
-Norcocaine
-Ecgonine
Mechanism of Action

Na fast channel


5HT and DA:


Inhibits reuptake
Vagal nuclei:


moderate blocked
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 coingestion 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 cocaineassociated 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

CCB
 Less
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 MI
 Preferred
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

Thrombolytics
 Not
well studied
 Only
 Pts
ICH
if PCI not readily available
at increased risk for aortic dissection and
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

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Inceases seizures and death in animal models12
Did not reverse vasoconstriction in human studies12
Dattilo et al. Annals of Emergency Medicine. 2008; 51(2): 117-125

Retrospective cohort study of 363
consecutive pts admitted to ICU or
telemetry with positive urine tox
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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 scrutinized
when β-blockers were given during
admission
 Large differences in baseline characteristics
btwn cohorts
 Unclear
Greater number of asthmatics among control cohort
 Greater proportion of B-blocker cohort were male, had
higher Cr, and had hx CHF, CAD

 Severe

Only 55% of β-blocker cohort had troponin measured vs.
96%
 31/33

limitations with MI cohort.
pts were given B-blocker after an MI
Only 2 given B blocker – both of home had an MI
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


Discharge criteria:

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
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Cocaine use confirmed by urine tox
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

2
No deaths due to MI
nonfatal MI
 No MI or death among pts claiming to have ceased
using cocaine
Key Points


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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?
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Alberta Alcohol and Drug Abuse Commission. Canadian Addiction Survey 2004,
Alberta Report. (2006). Edmonton, Alberta, Canada: Author.
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.
Levis JT, Garmel GM. Cocaine-associated chest pain. Emergency Medicine
Clinics of North America. 2005; 23:1083-1103.
Hoffman RS, Hollander JE. Evaluation of patients with chest pain after cocaine
use. Critical Care Medicine. 1997; 13: 809-28.
Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive
series of 233 patients. American Journal of Medicine. 1990; 88:325-31.
Rao RB, Hoffman RS. Cocaine and other sympathomimetics. Marx: Rosen’s
Emergency Medicine: Concepts and Clinical Practice, 6 ed. 2006.
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
Drug Abuse Warning Network (DAWN). Available online at: dawninfo.samhsa.gov
(Accecssed on December 19, 2006).
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.
Hollander JE. Current concepts: the management of cocaine-associated
myocardial ischemia. N Eng J Med. 1995; 333(19):1267-72.
References
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Hollander JE, Hoffman RS, Gennis P, et al. Prospective multicenter evaluation of cocaineassociated chest pain. Cocaine associated chest pain group (COCHPA) study group. Acad
Emerg Medi. 1994; 1:330.
Hollander JE, Henry TD. Evaluation and management of the patient who has cocaineassociated chest pain. Cardiol Clin. 2006; 24:103-114.
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.
Mittleman MA, Mintzner D, Maclure M et al. Triggering of myocardial infraction by cocaine.
Circulation. 1999; 99:2737.
Jones JH, Weir WB. Cocaine-associated chest pain. Med Clin N Am. 2005; 89:1323-1342.
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.
Lange RA, Cigarroa RG, Yancy CW Jr. et al. Cocaine-induced coronary artery
vasoconstriction. N Eng J Med. 1989; 321 (23):1557-62.
Satran A, Bart BA, Henry CR, et al. Increased prevalence of coronary artery aneurysms
among cocaine users. Circulation. 2005; 111: 2424.
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.
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.
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.