The Cracked Heart:The Cracked Heart: the cardiac effects of the cardiac effects of

cocainecocaine

Denise WattNov. 6, 2008

CaseCase

22 male22 male Found confused, agitated by momFound confused, agitated by mom 4g cocaine day prior + 4g today4g cocaine day prior + 4g today Combative with EMS, 10mg midazolam Combative with EMS, 10mg midazolam

IMIM PMHx: smoker, asthma, polysubstance PMHx: smoker, asthma, polysubstance

abuseabuse Meds: ventolin, floventMeds: ventolin, flovent

CaseCase

36.5, 180, 60, 88P, 100%, 3.836.5, 180, 60, 88P, 100%, 3.8 Diaphoretic, agitatedDiaphoretic, agitated GCS 11, PERLA 4mmGCS 11, PERLA 4mm CV/CNS nilCV/CNS nil

ECGECG

Case cont.Case cont.

Bolus NS, MidazolamBolus NS, Midazolam ABG: 7.30/30/106/14ABG: 7.30/30/106/14 Agitated, GCS 9Agitated, GCS 9 IntubatedIntubated ?seizure ?seizure Ativan Ativan Labs:Labs:

Cr 164, CK 500/MB 60, TnT 0.07Cr 164, CK 500/MB 60, TnT 0.07 AG 20, urine +ve cocaine, cannabisAG 20, urine +ve cocaine, cannabis

Case contCase cont

CCU consultedCCU consulted Fluids, AtivanFluids, Ativan Extubated 5 hr later – admit CCUExtubated 5 hr later – admit CCU Peak TnT 0.12, CK 14000, LDH >2500Peak TnT 0.12, CK 14000, LDH >2500 Resting Echo:Resting Echo:

low normal LV fn low normal LV fn upper normal sizeupper normal size

Transfer to IMTransfer to IM Uneventful course Uneventful course

OutlineOutline

Overview of cocaineOverview of cocaine Cardiac effectsCardiac effects Cocaine-associated chest pain Cocaine-associated chest pain

DiagnosisDiagnosis MIMI ManagementManagement ControversiesControversies Beyond the EDBeyond the ED

CocaCoca

Coca plant leavesCoca plant leaves South America South America ≥ 1200 years≥ 1200 years CNS stimulant, anestheticCNS stimulant, anesthetic Medicalized 1800sMedicalized 1800s Controlled 1970Controlled 1970 ““epidemic” late 1980sepidemic” late 1980s 22ndnd most common illicit drug most common illicit drug 14% have used (US 2003)14% have used (US 2003) CrimeCrime Highest drug-related Highest drug-related

offenses in Calgaryoffenses in CalgarySource: Wikipedia

Street formsStreet forms CocaineCocaine

Hydrochloride saltHydrochloride salt IV, snortIV, snort Blow, C, marching Blow, C, marching

powder, nose candypowder, nose candy CrackCrack

Alkaloid (free base)Alkaloid (free base) add NaHCO3 add NaHCO3 rock rock smoke smoke cracks cracks

Freebase, rooster, Freebase, rooster, tornadotornado

Source: Wikipedia

PharmacologyPharmacology

NE/Epi/Dopamine/serotonin re-uptake inhibitorNE/Epi/Dopamine/serotonin re-uptake inhibitor Na+ channel blockerNa+ channel blocker Metabolism: hepatic Metabolism: hepatic urine metabolites urine metabolites Peak onsetPeak onset

Seconds inhaled,1-2min IV, 15-30min nasalSeconds inhaled,1-2min IV, 15-30min nasal DurationDuration

5-10min inhale, 15-30min IV, 1 hr nasal5-10min inhale, 15-30min IV, 1 hr nasal tt½: 1hr½: 1hr

Metabolites up to 8 hr Metabolites up to 8 hr

Urine metabolites 4 – 72 hrUrine metabolites 4 – 72 hr Cocaine + ETOH Cocaine + ETOH cocaethylene cocaethylene

Desired EffectsDesired Effects

EuphoriaEuphoria Increased energyIncreased energy

“ “You perceive an increase of self-control and You perceive an increase of self-control and possess more vitality and capacity for work.... possess more vitality and capacity for work.... Long intensive physical work is performed without Long intensive physical work is performed without any fatigue...This result is enjoyed without any of any fatigue...This result is enjoyed without any of the unpleasant after-effects that follow the unpleasant after-effects that follow exhilaration brought about by alcohol” exhilaration brought about by alcohol”

-Sigmund Freud-Sigmund FreudWikipediaWikipedia

Non-cardiac EffectsNon-cardiac Effects

CNS stimulantCNS stimulant agitation, hallucinations, psychosis, seizures, agitation, hallucinations, psychosis, seizures,

ICH, CVAICH, CVA Muscle activityMuscle activity

Rhabdomyolysis, hyperthermiaRhabdomyolysis, hyperthermia AnestheticAnesthetic Appetite suppressantAppetite suppressant VascularVascular

HTN, Aortic dissectionHTN, Aortic dissection Highly addictive, toleranceHighly addictive, tolerance

Cardiac effects:Cardiac effects:acuteacute

HR, HR, BP, BP, contractility contractility Coronary vasoconstrictionCoronary vasoconstriction ThrombosisThrombosis ArrhythmiasArrhythmias

oxygen demand + oxygen demand + oxygen supply oxygen supply

== ischemia ischemia

Cardiac effects:Cardiac effects:chronicchronic

Accelerated atherosclerosisAccelerated atherosclerosis HTNHTN LVHLVH Systolic dysfunctionSystolic dysfunction CardiomyopathyCardiomyopathy MyocarditisMyocarditis

Cocaine-associated chest Cocaine-associated chest painpain

CP most frequent ED presentationCP most frequent ED presentation ““Typical” pt: young, male, smokerTypical” pt: young, male, smoker

DDx:DDx: Cardiac: ischemia/MICardiac: ischemia/MI MSK: rhabdo, traumaMSK: rhabdo, trauma Pulmonary: barotrauma, “crack lung”Pulmonary: barotrauma, “crack lung” Aortic dissectionAortic dissection

Cocaine-associated MI Cocaine-associated MI (CAMI)(CAMI)

6% CP6% CP11

Younger, fewer RFYounger, fewer RF ¼ non-fatal MIs young patients¼ non-fatal MIs young patients 20-50% no CAD 20-50% no CAD Highest risk in 1Highest risk in 1stst hour hour22

24 times baseline24 times baseline up to 4 daysup to 4 days

No predictors of CAMI, TIMI not predictiveNo predictors of CAMI, TIMI not predictive33

In-hospital mortality lowIn-hospital mortality low High incidence recurrent eventsHigh incidence recurrent events

1. Hollander J. Prospective Multicenter Evaluation of Cocaine-associated Chest Pain. 1. Hollander J. Prospective Multicenter Evaluation of Cocaine-associated Chest Pain. Acad Emerg Med.Acad Emerg Med. 1994;1:330-339 1994;1:330-3392. Mittleman M. Triggering of Myocardial Infarction by Cocaine. 2. Mittleman M. Triggering of Myocardial Infarction by Cocaine. CirculationCirculation. 1999;99:2737-2741. 1999;99:2737-27413. Chase . Application of the TIMI risk score in ED patients with cocaine-associated chest pain. 3. Chase . Application of the TIMI risk score in ED patients with cocaine-associated chest pain. Am J Emerg MedAm J Emerg Med 2007;25:1015-10182007;25:1015-1018

Chest pain approachChest pain approach

HistoryHistory Ask!Ask! Timing of use, Timing of use,

route, amount, route, amount, regular useregular use

PEPE Signs of acute Signs of acute

toxicitytoxicity

ECGECG Non-sensitiveNon-sensitive Non-specificNon-specific 43% have STE43% have STE

BER, LVHBER, LVH LabsLabs

AG/ABG, LFTs, Cr, CK, AG/ABG, LFTs, Cr, CK, urine Mburine Mb

CKMB non-specificCKMB non-specific Urine drug screen?Urine drug screen?

27yo male presents with Lt chest 27yo male presents with Lt chest tightness,tightness,

diaphoresis, tachycardia, hypertension.diaphoresis, tachycardia, hypertension.

ECG/CXR normal. Smoker. Denies ECG/CXR normal. Smoker. Denies

cocaine/drugs. RN states anxious.cocaine/drugs. RN states anxious.

Do you:Do you:

a)a) use Guantanamo-style interrogation use Guantanamo-style interrogation

b)b) give him Ativan and send homegive him Ativan and send home

c)c) do a urine drug screendo a urine drug screen

CaseCase

Urine drug screeningUrine drug screening

No studies No studies Widely used in USWidely used in US Why?Why?

Initiate drug counselingInitiate drug counseling May change managementMay change management

Why not?Why not? Low yieldLow yield Takes hour(s)Takes hour(s)

UsefulUseful in some situationsin some situations Young, few RF, high suspicion ACS, MIYoung, few RF, high suspicion ACS, MI Toxic-appearingToxic-appearing

Management of cocaine-Management of cocaine-associated chest painassociated chest pain

Benzodiazepines (I/B)Benzodiazepines (I/B) Animal studiesAnimal studies

Decreases central stimulatory effects Decreases central stimulatory effects decreases CV decreases CV effectseffects

RCTRCT Relieves CPRelieves CP Decreases HR, BPDecreases HR, BP

May be only agent neededMay be only agent needed ASA (I/C)ASA (I/C) Nitrates (I/B)Nitrates (I/B)

2 RCTs2 RCTs Relieves CP, reverses coronary VC, decreases BPRelieves CP, reverses coronary VC, decreases BP

BZD vs. NTGBZD vs. NTG

Small DBRCT diazepam vs. NTG vs. Small DBRCT diazepam vs. NTG vs. diazepam + NTGdiazepam + NTG

40 pt with ischemic-sounding CP40 pt with ischemic-sounding CP Outcomes: cardiac performance Outcomes: cardiac performance

(impedance), hemodynamic, CP(impedance), hemodynamic, CP 3 MI, 5 USA3 MI, 5 USA No differencesNo differences

Bottom line: use either Bottom line: use either If CNS effects present, use BZDIf CNS effects present, use BZD

Baumann B. Randomized, double-blind, placebo-controlled trial of Diazepam, Nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes. Acad Emerg Med. 2000;7:878-885

Management of CACPManagement of CACP

CCB (IIb/C)CCB (IIb/C) Unclear benefitUnclear benefit If no response to BZD/NTGIf no response to BZD/NTG

Phentolamine (IIb/C)Phentolamine (IIb/C) Cath lab study, animal modelsCath lab study, animal models Reverses coronary vasoconstrictionReverses coronary vasoconstriction

HCO3HCO3 Ventricular arrhythmiasVentricular arrhythmias

B-blockers??B-blockers??

ΒΒ-blockers in CACP-blockers in CACP

Contraindicated due to unopposed alphaContraindicated due to unopposed alpha Lange et alLange et al33

30 volunteers elective cath for chest pain work-up30 volunteers elective cath for chest pain work-up Intranasal cocaine vs. placeboIntranasal cocaine vs. placebo Intracoronary propanolol vs. placeboIntracoronary propanolol vs. placebo

Cocaine: coronary vasoconstrictionCocaine: coronary vasoconstriction Worsened by propanololWorsened by propanolol Esmolol, labetolol – mixed resultsEsmolol, labetolol – mixed results AHA III/CAHA III/C3. Lange R. Potentiation of Cocaine-induced coronary vasoconstriction by Beta-adrenergic blockade. 3. Lange R. Potentiation of Cocaine-induced coronary vasoconstriction by Beta-adrenergic blockade. Annals of Int Med.Annals of Int Med.

1990;112:897-9031990;112:897-903

B-blocker controversyB-blocker controversy

Cocaine-associated MI Cocaine-associated MI ≠ ≠ vasospasmvasospasm Thrombosis major causeThrombosis major cause 80% of CAMI had significant CAD80% of CAMI had significant CAD44

Benefits of B-blockersBenefits of B-blockers decrease O2 demanddecrease O2 demand prevent re-infarction and arrhythmiasprevent re-infarction and arrhythmias

4.4. Kontos M. Coronary angiographic findings in patients with cocaine-associated chest pain. Kontos M. Coronary angiographic findings in patients with cocaine-associated chest pain. J Emerg Med.J Emerg Med. 2002;24:9-13. 2002;24:9-13.

Dattilo et al. 2008Dattilo et al. 2008

310 admissions

33B-blockers

277No B-blocker

2 ptB-blocker BEFORE MI

31 ptB-blocker AFTER MI

72 ptMI

• Retrospective cohort study• Telemetry/CCU/ICU admits with +ve urine cocaine

Dattilo et al.Dattilo et al.

6% MI after B-blocker6% MI after B-blocker 26% not receiving B-blocker had MI26% not receiving B-blocker had MI B-blocker reduced risk of MI (OR B-blocker reduced risk of MI (OR

0.06)0.06) No significant mortality differenceNo significant mortality difference Suggest protective effects out ways Suggest protective effects out ways

potential harmpotential harm

LimitationsLimitations

Retrospective, smallRetrospective, small Patient populationPatient population

ICU/CCU/telemetry admissionICU/CCU/telemetry admission ½ patients had CP½ patients had CP

No data on time of ingestionNo data on time of ingestion ?effect after acute ingestion?effect after acute ingestion

No B-blocker group sicker? No B-blocker group sicker? most deaths due to sepsismost deaths due to sepsis

Benefit in ACS is long term useBenefit in ACS is long term use

B-Blockers + cocaineB-Blockers + cocaineBottom LineBottom Line

No great studiesNo great studies Effect in acute cocaine ingestion unknownEffect in acute cocaine ingestion unknown

Likely harmfulLikely harmful Possible long term benefit Possible long term benefit AHA 2008: consider post-discharge in:AHA 2008: consider post-discharge in:

LV dysfunction, ventricular arrhythmiasLV dysfunction, ventricular arrhythmias BUT high recidivism BUT high recidivism No role in the EDNo role in the ED

Thrombolytics in cocaine-Thrombolytics in cocaine-associated STEMIassociated STEMI

No studies showing efficacyNo studies showing efficacy Mortality CAMI lowMortality CAMI low Poor specificity ECGPoor specificity ECG ?Safety?Safety

risk ICHrisk ICH Risks of lytics out way benefitsRisks of lytics out way benefits Use PCI if clear STEMIUse PCI if clear STEMI

Case cont.Case cont.

Patient finally admits to smoking crack Patient finally admits to smoking crack 2 x2 x

week. Pain-free post Ativan.week. Pain-free post Ativan.

What now?What now?

Chest pain unitChest pain unit

Prospective, cohort studyProspective, cohort study 302 moderate-low risk patients with CACP302 moderate-low risk patients with CACP Observed 6-12 hr, serial ECG + TnTObserved 6-12 hr, serial ECG + TnT 158 stress test158 stress test

4 positive (3%) 4 positive (3%) 3 positive angiograms 3 positive angiograms 30 day outcome: 4 MI30 day outcome: 4 MI

All continued to use cocaine, All continued to use cocaine, ≥ 2 RF≥ 2 RF No deathsNo deaths AHA recommends observe x 9-12 hrAHA recommends observe x 9-12 hr

Stress testing “optional”Stress testing “optional”Weber J. Validation of a brief observation period for patients with cocaine-associated chest pain. N Engl J Med. 2003;348:510-7

Risk StratificationRisk Stratification Myocardial perfusion imagingMyocardial perfusion imaging

1 study, 216 patients1 study, 216 patients 100% sensitive for MI100% sensitive for MI Missed 2 significant CADMissed 2 significant CAD

EchocardiographyEchocardiography LVH more commonLVH more common May mask wall motion abnormalitiesMay mask wall motion abnormalities

Stress testingStress testing Case series 6 pt Case series 6 pt + stress tests within 2 weeks post use+ stress tests within 2 weeks post use 5 no CAD, 1- 70% LM 5 no CAD, 1- 70% LM CABG CABG Repeat cath for recurrent CP – patent LM, diffuse vasospasmRepeat cath for recurrent CP – patent LM, diffuse vasospasm

Authors suggest delaying stress test 2-3 weeks post abstinenceAuthors suggest delaying stress test 2-3 weeks post abstinence

AngiographyAngiography

90 high risk patients90 high risk patients 34% MI34% MI

77% had significant CAD77% had significant CAD 32% 1VD, 10% 2VD, 5.6% 3VD32% 1VD, 10% 2VD, 5.6% 3VD Selection biasSelection bias

Kontos, M. Coronary Angiographic findings in patients with cocaine-associated chest pain. J Emerg Med 2003;24:9-13

Disposition/Follow-upDisposition/Follow-up

CAMI – admitCAMI – admit High risk - admitHigh risk - admit Moderate-low risk – observe 9-12 hoursModerate-low risk – observe 9-12 hours

10hr TnT likely reasonable10hr TnT likely reasonable Recurrent visits, other risk factorsRecurrent visits, other risk factors

Out-patient risk stratificationOut-patient risk stratification EducationEducation Drug counseling/cessation programsDrug counseling/cessation programs

AHA recommendationsAHA recommendationsApril 2008April 2008

Take Home PointsTake Home Points Ask about cocaine use in ?ACS patientsAsk about cocaine use in ?ACS patients MI uncommon, low mortalityMI uncommon, low mortality Highest risk first hour post ingestionHighest risk first hour post ingestion Treatment:Treatment:

BZD, ASA, nitrates BZD, ASA, nitrates Brief observation for moderate-low riskBrief observation for moderate-low risk

?out-patient risk stratification?out-patient risk stratification High risk/MIHigh risk/MI

Admit, rule out CADAdmit, rule out CAD Drug cessationDrug cessation

Questions?Questions?