cocaine & beta-blockers

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Cocaine & Beta-Blockers. Liza Halcomb , MD Journal Club 1/17/2008. Cocaine Chest Pain. Common presentation. Human cardiac catheterization studies have shown cocaine to be a powerful coronary vasoconstrictor. - PowerPoint PPT Presentation

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  • Cocaine & Beta-BlockersLiza Halcomb, MD Journal Club 1/17/2008

  • Cocaine Chest PainCommon presentation.Human cardiac catheterization studies have shown cocaine to be a powerful coronary vasoconstrictor.In the case described, there was concern about ongoing tachycardia and hypertension in face of myocardial ischemia.

  • CocaineCauses HTN and tachycardia by inhibiting the reuptake of NE and DA.Sympathetic activation Running away from a dinosaur:Dilated Pupils alpha receptors activatedTachycardia beta receptors activatedHypertension alpha receptors activatedDiaphoresis sympathetic cholinergic

  • CocaineLange et al. showed that cocaine induced coronary artery vasospasm in the cath lab.1Also has type Ia sodium channel blocking effects, can lead to arrhythmias.Accelerates CAD by increasing platelet aggregation and plaque formation.What about MI?

  • Cocaine and MIHollander et al. showed that patients with cocaine related CP had a low incidence of MI.25%On follow up of 203 patients over 408 days after visit for cocaine related CP, only 2 non-fatal MIs were reported in patients who continued to use cocaine.3

  • Cocaine Chest PainUnlikely to have significant mortality or morbidity.

  • Cocaine + UDSUrine remains + for 3 days after use. Tests for benzylecognine, a metabolite.Exceedingly uncommon to have a false + result.

  • Beta- BlockersUsed in ED to treat tachycardia associated with possible ACS.Do not acutely lower BP.Block both Beta 1 and Beta 2 receptors.In asthmatics can cause bronchospasmIn pheochromcytoma can cause unopposed alpha

  • Beta Blockers & AMIPost-MI beta blocker vs. placebo to prevent six-month total mortality for different risk groups:Low risk (no PVCs and no clinical CHF) NNT = 242Medium risk (1-10 PVCs and no CHF) NNT = 217High risk (1-10 PVCs and CHF) NNT = 44Very High risk (> 10 PVCs and CHF) NNT = 30

    For NNH, using the high-risk subset from the COMMIT trial OR = 1.42 and Control Event Rate = 15.7% NNH = 19

  • Beta BlockersWHAT IS UNOPPOSED ALPHA ACTIVATION?

    WHY DONT PEOPLE WHO TAKE BETA-BLOCKERS GET ORTHOSTATIC HYPOTENSION?

  • Beta BlockersBeta 2 receptors are located on the vasculature to the skeletal muscle.No orthostatic hypotension because these vessels constrict when beta-blockers are administered.In the presence of alpha activation, beta-blockade can exacerbate HTN.

  • Beta Blockers and AMIProven mortality benefit in the setting of MIAdopted into quality of care guidelinesHowever, little data on administration in the 1st 12-24 hours of symptoms.COMMIT trial suggests that early administration decreases arrhythmias, however benefit offset by increase in cardiogenic shock.4

  • Cocaine and Beta BlockersPropanolol was routinely used in treatment of cocaine intoxication in the 1970sCatravas conducted a lethality study in dogs all cocaine intoxicated dogs that got propanolol died.5All animals that got diazepam survived.Led to removal of beta-blockers as 1st line treatment for cocaine intoxication.

  • Now were back to square 1

  • Article #1Retrospective review of 348 admissions to telemetry and ICU with + UDS for cocaine.660 people got beta-blockers.Multivariate analysis showed decrease risk of MI in patients who got beta-blockers (1.7% vs. 4.5%)

  • Article #1Lots of fancy stats! Parsimonious multivariate generalized estimating equations.Covariates considered for inclusion were those with a P< 0.25 on bivariate analysis.Propensity scores to address non-randomized administration of beta-blockers.

  • Remember with statistics..

  • Article #1 Problems< 50% of patients presented with CP (165/348).~ 30% of the patients who presented with CP had an MI. (51/165)Beta-blocker use was of borderline significance in reducing the risk of a myocardial infarction (OR 0.05; 95% CI 0.00-2.08)+ UDS cutoff level may remain + for up to 2 weeks in chronic users.

  • Article #1Look at the mortality table and tell me which of those patients should get beta-blockers

  • Article #2Prospective study in 15 patients undergoing cardiac catheteriztation.7All got low dose of intranasal cocaine (1/2 of that used for intranasal anesthesia for ENT)6 got saline.9 got labetalol.Conclusion: Labetalol reduces MAP, but not coronary vasoconstriction.

  • Article #2Look at Table #1Trend to increased vasoconstriction although this is not statistically significant.Conclusion: Not much of a benefit if coronary artery diameter does decrease in size.

  • Article #3Prospective study of 7 patients all under 50 years of age.8All had recent cocaine use or + UDS.Got 0.5 mg/kg esmolol followed by infusion of 0.05 mg/kg/minOutcome: 3 patients had good outcome, 3 patients failed, 1 patient equivocal.Conclusion: Cannot recommend routine use of esmolol.

  • Article #4Randomized double-blind placebo controlled prospective study of 30 patients.915 got intranasal saline, 15 got intranasal cocaine.5/15 in saline group got propanolol15/15 in cocaine group got propanolol

  • Article #4Cocaine decreased coronary-sinus blood flow from 139 to 120 ml per minute. Propranolol further decreased coronary-sinus blood flow to 100 ml per minute.Coronary vascular resistance rose from a base-line value of 0.87 mm Hg /ml/min to 1.05 mm Hg/ml/min after cocaine and 1.20 mm Hg/ml/min after propranolol.

  • Article #4With propranolol one subject had complete coronary-artery occlusion, symptoms of myocardial ischemia, and electrocardiographic changes.

  • Evidence Based Medicine + ToxicologyVery difficult, unable to conduct randomized controlled trial where half the study group is poisoned and half not.How to decide what is best?Physiologic principlesPharmacologic principlesAnimal studiesCase reportsHuman studies

  • Cocaine and Beta BlockersPhysiologic principles suggest that it is contraindicated.Pharmacologic principles suggest that it is contraindicated.Animal studies suggest that it is contraindicated.Case reports suggest that it is contraindicated.Randomized trials in humans suggest that it is contraindicated.

  • ReferencesLange RA, Cigarroa RG, Yancy CW Jr, et al. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med 1989;321:1557-1562. 2. Hollander JE, Hoffman RS, Gennis P, et al. Prospective multicenter evaluation of cocaine associated chest pain (COCHPA) study group. Acad Emerg Med. 1994;1:330-339.Hollander JE, Hoffman RS, Gennis P, et al. Cocaine associated chest pain: one year follow up. Acad Emerg Med 1995;2:179-84.Chen ZM, Pan HC, Chen YP, et al. COMMIT (ClOpidogrel and metoprolol in myocardial infarction trial) collaborative group. Early intravenous then oral metoprolol in45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366;1622-1632.Catravas JD, Waters IW. Acute cocaine intoxication in the conscious dog: studies on the mechanism of lethality. J Pharmacol Exp Ther. 1981;217:350-356.Dattilo PB, Hailpern SM, Fearon K, etal. B-blockers are associated with reduced risk of myocardial infarction after cocaine use. Ann Emerg Med. 2007, IN press.Boehrer JD et al. Influence of Labetolol on Cocaine-Induced Coronary Vasoconstriction in Humans. Am J Med 1993;94:608-6108.Sand IC, Brody SL, Wrenn KD, Slovis CM. Experience with esmolol for the treatment of cocaine-associated cardiovascular complications. Am J Emerg Med 1991;9:161-163. 9.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.

    Think of snorting levophed*You all know this..many of your patients have cocaine on board when the present with CP, few have adverse outcomes.**Remember our goal is to slow down the HR.*The NNT is the number of patients who need to be treated in order to prevent one additional bad outcome. It is the inverse of the Absolute Risk Reduction (ARR). To answer that question, lets ask another.*Unpredictable who is dependent on tachycardia to maintain CO.*NB, not cardiovascular deaths seizures and hyperpyrexia. Diastolic HTN and hyperpyrexia were also reported in cocaine intoxicated patients treated with propanolol.***WHEW!*Garbage in = garbage out*We have no information on the other presenting complaints. *The administration of esmolol decreased mean HR but not hypertension and associated with adverse events in 3/7 patients, including 1 who required intubation.*You know that it is dangerous to jump out of a plane without a parachute. Using a common sense approach and 1st principles, you can make the same argument for many medical decisions. Remember the most important rule is First do no harm..*