cocaine induced myocardial ischemia sean caine grand rounds emergency medicine october 16, 2008
TRANSCRIPT
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 Neurologic
Cardiac 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, CAD
Severe 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.