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Cocaine Beta-Blockers

Cocaine Chest Pain. Common 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.. Cocaine. Causes HTN and tachycardia by inhibiting the reuptake of NE and DA.Sympathetic activation

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Cocaine Beta-Blockers

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    1. Cocaine & Beta-Blockers Liza Halcomb, MD Journal Club 1/17/2008

    2. Cocaine Chest Pain Common 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.

    3. Cocaine Causes HTN and tachycardia by inhibiting the reuptake of NE and DA. Sympathetic activation – Running away from a dinosaur: Dilated Pupils – alpha receptors activated Tachycardia – beta receptors activated Hypertension – alpha receptors activated Diaphoresis – sympathetic cholinergic Think of snorting levophedThink of snorting levophed

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

    5. Cocaine and MI Hollander et al. showed that patients with cocaine related CP had a low incidence of MI.2 5% 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

    6. Cocaine Chest Pain Unlikely to have significant mortality or morbidity. You all know this…..many of your patients have cocaine on board when the present with CP, few have adverse outcomes.You all know this…..many of your patients have cocaine on board when the present with CP, few have adverse outcomes.

    7. Cocaine + UDS

    8. Beta- Blockers Used 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 bronchospasm In pheochromcytoma can cause unopposed alpha Remember our goal is to slow down the HR.Remember our goal is to slow down the HR.

    9. Beta Blockers & AMI Post-MI beta blocker vs. placebo to prevent six-month total mortality for different risk groups: Low risk (no PVC’s and no clinical CHF)        NNT = 242 Medium risk (1-10 PVC’s and no CHF)           NNT = 217 High risk (1-10 PVC’s and CHF)                     NNT = 44 Very High risk (> 10 PVC’s 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 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). 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).

    10. Beta Blockers WHAT IS UNOPPOSED ALPHA ACTIVATION? WHY DON’T PEOPLE WHO TAKE BETA-BLOCKERS GET ORTHOSTATIC HYPOTENSION? To answer that question, lets ask another….To answer that question, lets ask another….

    11. Beta Blockers Beta 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.

    12. Beta Blockers and AMI Proven mortality benefit in the setting of MI Adopted into quality of care guidelines However, 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 Unpredictable who is dependent on tachycardia to maintain CO.Unpredictable who is dependent on tachycardia to maintain CO.

    13. Cocaine and Beta Blockers Propanolol was routinely used in treatment of cocaine intoxication in the 1970s Catravas conducted a lethality study in dogs – all cocaine intoxicated dogs that got propanolol died.5 All animals that got diazepam survived. Led to removal of beta-blockers as 1st line treatment for cocaine intoxication. NB, not cardiovascular deaths – seizures and hyperpyrexia. Diastolic HTN and hyperpyrexia were also reported in cocaine intoxicated patients treated with propanolol.NB, not cardiovascular deaths – seizures and hyperpyrexia. Diastolic HTN and hyperpyrexia were also reported in cocaine intoxicated patients treated with propanolol.

    14. Now we’re back to square 1

    15. Article #1 Retrospective review of 348 admissions to telemetry and ICU with + UDS for cocaine.6 60 people got beta-blockers. Multivariate analysis showed decrease risk of MI in patients who got beta-blockers (1.7% vs. 4.5%)

    16. Article #1 Lots 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.

    17. WHEW!WHEW!

    18. Remember with statistics….. Garbage in = garbage outGarbage in = garbage out

    19. 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.

    20. Article #1 Look at the mortality table and tell me which of those patients should get beta-blockers We have no information on the other presenting complaints. We have no information on the other presenting complaints.

    21. Article #2 Prospective study in 15 patients undergoing cardiac catheteriztation.7 All 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.

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

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

    24. The administration of esmolol decreased mean HR but not hypertension and associated with adverse events in 3/7 patients, including 1 who required intubation.The administration of esmolol decreased mean HR but not hypertension and associated with adverse events in 3/7 patients, including 1 who required intubation.

    25. Article #4 Randomized double-blind placebo controlled prospective study of 30 patients.9 15 got intranasal saline, 15 got intranasal cocaine. 5/15 in saline group got propanolol 15/15 in cocaine group got propanolol

    26. Article #4 Cocaine 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.

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

    28. Evidence Based Medicine + Toxicology Very difficult, unable to conduct randomized controlled trial where half the study group is poisoned and half not. How to decide what is best? Physiologic principles Pharmacologic principles Animal studies Case reports Human studies 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…..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…..

    29. Cocaine and Beta Blockers Physiologic 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.

    30. References Lange 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;94:608-610 8. 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.

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