Complications from the use of thrombolytic agents in patients with cocaine associated chest pain

The Journal of Emergency Medicine. Vol 14. No 6, pp 7?i -7%. 1996 copyright $ 1996 8lscv1er Science Inc. Printed in the USA. All rights reserved r173w(,74/!xl

bl5

00 -

.oo

PI1 SO736-4679(96) 00187-4

ELSEVIER

TUpiCS: Ca

COMPLICATIONS

agy CommeWwy

FROM THE USE OF THR LYTIC AGEt4TS CN PATiEt4TS WITH COCAINE ASSOCIATED CHEST PAIN

Judd E. Hollander,

MD,*

Lance D. Wilson, tm,t

Paul J. Leo, DO,* and Richard D. Shih, MD§

*Department of Emergency Medicine, Universiv Medical Center, Stony Brook, New York, @epartment of Emergency Medicine, Mount Sinai Medical Center, Cleveland, Ohio, *Department of Emergency Medicine, New York Methodist Hospital, Brooklyn, New York, and §New Jersey Poison Information and Education System, Newark-Beth Israel Medical Center, Newark, New Jersey Reprint Address: Judd E. Hollander, MD, Department of Emergency Medicine, University Medical Center, Room t-4.,515, State University of New York, Stony Brook, NY 11794-8350.

0 Abstract-Previous investigators have noted that patients with cocaine associated chest pain frequently have abnormal electrocardiograms, including ST segment elevation, in the absence of ongoing myocardhl ischemia. The effects of these nonischemic ST segment elevations have not been evaluated. We report two patients with cocaine associated chest pain and ST segment elevations who received thrombolytic agents in the absence of myocardial ischemia. Neither patient sustained a myocardial infarction, nor had clinical evidence of reperfusion. The ST segment elevations persisted after resolution of chest pain in both patients, and both of the patients experienced complications of thrombolytic therapy. One patient sustained a hemorrhagic stroke and one had minor oral-pharyngeal bleeding. Given the lack of documented efficacy, concerns about safety, and poor specificity of the electrocardiogram for myocardial ischemia in patients with cocaine associated chest pain, thrombolytic therapy should be used with caution in these patients. 0 1996 Elsevier Science Inc.

is the most common cocaine related medical complaint (2). The recognition

0 Keywords-electrocardiogram, cocaine, thrombolysis, myocardial &hernia, myocardial infarction

INTRODUCTION Cocaine is the most common illicit drug of abuse seen in Emergency Department patients ( 1) , and chest pain _I_ RECEIVED: ACCEPTED

Cardiology Commentary is coordinated by Steven R. Lowenstrin, Sciences Center, Denver, Colorado

30 January 1996; FINAL :

SUBMISSION

that cocaine use can result in

myocardial &hernia and infarction has ahered the evaluation and triage of young patients with chest pain. Although most patients with cocaine associated chest pain do not sustain a myocardial infarction (3-7), clinical series have not been able to identify low risk patients who can safely be discharged from the emergency department (7 ) . The electrocardiogram is the single best predictor of a high risk of myocardial infarction in patients who present to the emergency department with chest pain unrelated to cocaine (8)) however, it is less useful in patients with cocaine associated chest pain. Clinical series of patients with cocaine associated chest pain have found that most patients have abnormal electrocardiograms, despite the fact that few have myocardial infarction (3-$7). Some 29-43% of patients have ST segment elevation in the absence of myocardial ischemia (3-5,7). These “false-positive” ST segment elevations have been attributed to early repolarization in young patients and left ventricular hypertrophy in chronic cocaine users (4,9). Additionally, T-wave inversions secondary to a “persistent juvenile pattern” may also be confused with ischemia. Although commonly noted, the clinical relevance of

RECEIVED:

6 May 1996 731

MD, MPH,

19 April 1996;

of the University of Colorado Health

-..----.2_-.------.----- --

732

J. E. Hollander et al.

these false-positive ST segment elevations is unclear. Some investigators have advocated a cautious approach to the use of thrombolytic agents in patients with cocaine associatedchest pain, since it is possible that they may be inadvertently administered in the absence of myocardial infarction (9,lO). We report two patients with cocaine associated chest pain and ST segment elevation who received treatment with thrombolytic agents in the absenceof myocardial infarction.

CASE REPORTS Case I A 55-year-old male presented 6 h after onset of severe left-sided chest pain occurring at rest. The pain was described as a severe substernal burning sensation that radiated down the left arm and was associated with diaphoresis, nausea,and emesis. The patient had a past medical history significant for 14 years of insulin-dependent diabetes mellitus and 10 years of hypertension. He had no prior history of chest pain, coronary artery disease, or cerebrovascular events. He had a 20 pack/ year smoking history and reported recent cocaine use. Medications were insulin, hydrochlorothiazide, and enalapril. There was no family history of cardiac disease. The patient was an obese male who appeared diaphoretic and anxious. Initial vital signs were: temperature, 36.7”C (98°F) ; heart rate, 88 beats per min; respirations, 16 breaths per min; and blood pressure, lOO/ 70 mmHg. The patient had bibasilar tales, without jugular venous distention or peripheral edema.The cardiac examination was significant for an S3 gallop and the neurological examination, including pupillary response and funduscopic examination, was normal. The initial electrocardiogram showed marked ST segment elevations in leads V2-V6 (Fig. 1) , consistent with an acute anterior lateral wall myocardial infarction. Chest x-ray study demonstrated mild pulmonary edema. Laboratory studies revealed normal platelets and coagulation profile. After sublingual nitroglycerin, intravenous morphine, and intravenous nitroglycerin, the patient had continued chest pain and persistent ST segment elevations. The blood pressure remained controlled and there were no contraindications to thrombolytics, thus he received tissue plasminogen activator with an initial 8 mg IV bolus, followed by an 80 mg infusion over 1 h. Approximately 30 min following onset of the infusion, sudden onset of right-sided hemiparesis and aphasia occurred. Subsequent laboratory assays revealed creatine kinase values of 931, 3638, and 2943 IU/L without de-

tection of MB fractions. The urine toxicology screen revealed cocaine metabolites. A head computed tomography (CT) scan without intravenous contrast obtained within 1 h of the onset of the neurologic symptoms was normal. The patient’s aphasia and denseright hemiparesis persisted. Other than a short self-limited run of ventricular tachycardia, the patient suffered no cardiovascular complications. A two-dimensional echocardiogram performed on the second day of admission showed mildly reduced left ventricular function and dyskinesis of the distal cardiac septum and apex. Neither intracardiac thrombus nor valvular vegetations were identified. Repeatelectrocardiograms over the first 2 hospital days showed persistent 1-2 mm ST segment elevations (Fig. 2). A head CT scan 6 days after presentation demonstrated a hemorrhagic infarct involving the left frontal, anterior temporal, and parietal lobes with mass effect compressing the left lateral and third ventricles. Neurologic symptoms improved minimally over the subsequent 2 weeks, and the patient was discharged on hospital day 23 to a rehabilitation facility.

Case 2 A 29-year-old male without prior medical history presented with 1 h of crushing substernal chest pain that radiated to the left arm. He had accompanying dyspnea, palpitations, and diaphoresis. Symptoms began 2 h after smoking 6 g of crack cocaine. Initial blood pressure was 1lo/70 mmHg; heart rate, 108 beats per min; respiratory rate, 18 breaths per min; temperature 36.7”C (98°F). The initial electrocardiogram revealed upsloping ST segmentelevations in the anterior precordial leads (Fig. 3 ) . The patient continued to have chest pain after the administration of nitrates, morphine sulfate, aspirin, and heparin. The electrocardiogram showed persistent ST segment elevations and tissue plasminogen activator was administered as a 15 mg bolus followed by 50 mg to be infused over 30 min. Ten minutes after commencement of the tissue plasminogen activator infusion, oral-pharyngeal bleeding developed. The infusion was terminated. Emergency coronary arteriography revealed normal coronary arteries, global hypokinesis, and an ejection fraction of 45%. Creatine kinase values were 630, 536, and 321 U/L with MB fractions of 1.4, 1.4, and 1.2%, respectively. A repeat electrocardiogram 24 h after presentation was unchanged. There was no evidence of focal myocardial ischemia. The patient had an otherwise uneventful hospital course and was discharged 2 days later.

Thrombolytics

in Cocaine-Induced

MI

Figure 1. Presenting

electrocardiogram

in Case 1 that appears

DISCUSSION The present cases once again raise concerns about the safety of thrombolytic agents in patients with cocaine associated chest pain. Although myocardial infarction following cocaine use is associatedwith thrombus formation, the poor specificity of the electrocardiogram for acute myocardial ischemia; a lack of documented efficacy; and concerns about safety must be taken into account when treating patients with cocaine associated chest pain. Acutely, cocaine causes increased thrombus formation in addition to coronary artery vasoconstriction (including spasm) and increased myocardial oxygen demand ( IO). Cocaine enhances platelet aggregation ( 11- 13) and increasesendogenoustissue plasminogen activator inhibitor ( 14). Furthermore, thrombus has been noted in the coronary arteries of patients with cocaine associated myocardial infarction with or without underlying coronary artery disease ( 15- 17). As such, there is theoretical rationale for the use of thrombolytic agents in patients with cocaine associatedmyocardial infarction. Initial concerns surrounded the safety of these

to show antero-lateral

ischemia.

agents becausecocaine is associated with neurovascular complications such as subarachnoid hemorrhage, intraparenchymal bleeding, and bland cerebral infarcts ( 18-21). Additionally, the use of intravenous drugs may predisposepatients to mycotic aneurysm and other central nervous system infections that may be more prone to hemorrhagic complications (22 ) . Bland cerebral infarcts have occurred concomitantly with cocaine associated myocardial infarctions (23). Bush ( 22) reported a fatality secondary to intracranial hemorrhage in a patient who received tissue plasminogen activator following the use of cocaine. The patient presented with chest pain and ST segment elevation, but did not sustain a myocardial infarction. The largest series to examine this issue found no major complications in 25 patients who received thrombolytic agents for the treatment of cocaine associated myocardiai infarction (24). Prior to the present cases. only one jntracranial hemorrhage had occurred in the 36 reported patients who received thrombolytic agents for the treatment of cocaine associated myocardial infarction, An additional concern regarding the use of thrombolytic agents in patients with cocaine associated chest pain is the poor specificity of the electrocardiogram

734

J. E. Hollander et al.

Figure 2. Repeat electrocardiogram

in Case 1 showing persistent ST segment elevations.

Figure 3. Presenting electrocardiogram

in Case 2.

Thromboiytics

in Cocaine-Induced

,735

MI

(9,24). Clinical series have found that 56-84% of patients with cocaine associatedchest pain have abnormal electrocardiograms, and ST segment elevations are one of the most common abnormalities ( 3 - 5,7 ) . Gitter et al. (4) reported 101 patients admitted to monitored beds with cocaine associated chest pain. Although none of these patients sustained a myocardial infarction. 43% had ST segmentelevation that met TIM1 criteria for the administration of thrombolytic agents. Hollander et al. (9) found that the electrocardiograms of young patients with cocaine associated chest pain ( in the absenceof myocardial infarction) met electrocardiographic TIMI criteria in 5- 13% of cases.Additionally, they found that emergency physicians and cardiologists determined that 7% of hedthy volunteers (with or without recent cocaine use) under 35 years of age met TIM1 electrocardiographic criteria (26). The presence of ST segment elevation in these young patients was attributed to early repolarization. Although ST segment elevations can also occur in patients with left ventricular hypertrophy, left ventricular aneurysms. and pericarditis, these entities are less common than early repolarization. Our cases illustrate the difficulty in identifying electrocardiographic evidence of ischemia in this patient population. The efficacy of thrombolytic agents for the treatment of cocaine associated myocardial infarction has not been well studied. They may have limited benefit. The largest incremental reduction in mortality from the use of thrombolytic agents for myocardial infarction (unrelated to cocaine) occurs in the elderly, however, most patients with cocaine associated myocardial infarction are 40 years of age or under (16,17,25). The mortality in this group of patients is generally quite low (5.16,17,25). The CAMI study, a retrospective study of 136 patients with myocardial infarction secondary to cocaine: found a mortality of 0% (25). Reviews of case reports yield a mortality rate less than 5% ( 1617). Since most deaths and cardiovascular complications secondary to cocaine occur prior to, or shortly after, hospital arrival (7,25 ), administration of thrombolytic agents is unlikely to have a significant effect on important outcome parameters such as survival. One series was unable to demonstratea reduction even in softer end points. such as peak CK, peak CKMB, or time until peak enzyme levels with the use of thrombolytic agents (24). Whether thrombolytic agents can improve left ventricular function and patient functional class still needsto be determined,but moderateto severe congestive heart failure and cardiogenic shock appear to be rare after cocaine associatedmyocardial infarction ( 16,25) . As a result of the difficulty in electrocardiographic determination of acute myocardial infarction in young

patients with cocaine associated chest pain, a lack of demonstrated efficacy in patients with cocaine associated myocardial ischemia, and the potential for hemorrhagic complications, the use of thrombolytic agents in patients with cocaine associated myocardial &hernia must be approachedwith caution. Where cardiac catheterization with mechanical reperfusion ( i.e., angioplasty) can be performed, this option may be a better choice than the administration of thrombolytic agents. When mechanical reperfusion is not feasible. adjunctive testing may be useful. Possibly, noninvasive diagnostic studies such as bedside echocardiography to detect wall motion abnormalities. rest sestamibi imaging to detect ischemia (27), or review of prior electrocardiograms to confirm that the ST segment elevation is new can be expeditiously performed prior to administration of thrombolytic agents. Our approachto the managementof patients with cocaine associatedchest pain and ST segment elevation is to provide initial treatment with benzodiazepinesto decreasecentral adrenergic stimulation ( lo,28 ). Aspirin should be used to reduce thrombus formation ( 10,28). and nitroglycerin should be the preferred choice to reverse coronary vasoconstriction ( 10,29). Patients with continued ischemia can be treated with either low doses of phentolamine, or verapamil (10,30,31). If ischemia continues after treatment with these agents, mechanical reperfusion should be performed in centerswith capabilities for rapid intervention. Thrombolytic therapy should be reservedfor patients with clinical evidence of continued myocardial ischemia. It should be considered on an individual basis. The present report illustrates several of the difficult issuesregarding thrombolytic usein the settingof cocaine associatedchest pain. Both patients had electrocardiographic evidence of infarction even though neither sustained a myocardial infarction. Although total creatine kinase levels were elevated, this is unlikely to represent acute myocardial infarction. Cocaine users may get elevatedcreatinekinasefrom both acuteand chronic skeletal muscle disease (32,33). These elevations are common in patients with cocaine associatedchest pain in the absenceof infarction (7.10,34). It is unlikely that the use of thrombolytic agentscausedreperfusion and resolution of infarction as both chest pain and electrocardiographic ST elevations persisted.Both patients had complications secondary to thrombolytics, one a minor pharyngeai bleed that resolved after cessation of infusion. and the other a hemorrhagic stroke. SUMMARY We present two patients with both clinical and electrocardiographic indications for thrombolysis in the set-

J. E. Hollander et al.

ting of presumed cocaine associated myocardial infarction. Since myocardial infarction secondary to coCaine use is much less common than ST segment elevations in the absence of myocardial infarction, more exhaustive measuresto confirm the diagnosis of

a myocardial infarction in the setting of cocaine use are indicated prior to the initiation of thrombolytic therapy. Furthermore, since cocaine associated myocardial infarction has a very low mortality, the need for thrombolytic therapy should be carefully considered.

REFERENCES 1. U.S. Department of Health and Human Services. Annual Emergency Room Data, 1992. Data from the Drug Abuse Warning Network. DHHS number (SMA) 94-2080, 1994. 2. Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive series of 233 patients. Am J Med. 1990; 88:325-31. 3. Zimmerman JL, Dellinger RP, Maiid PA. Cocaine associated chest pain. Ann EmergMed. 1991;~20:611-15. 4. Gitter MJ. Goldsmith SR. Dunbar DN. Sharkev SW. Cocaine and chest pain: clinical features and outcome of patients hospitalized to rule out myocardial infarction. Ann Intern Med. 1991; 115:277-82. 5. Amin M, Gableman G, Karpel J, Buttrick P. Acute myocardial infarction and chest pain syndromes after cocaine use. Am J Cardiol. 1990:66:1434-7. 6. Tokarski GN,‘Paganussi P, Urbanski R, Carden D, Foreback C, Tomlanovich MC. An evaluation of cocaine induced chest pain. Ann Emerg Med. 1990;19:1088-92. 7. Hollander JE. Hoffman RS. Gennis P. et al. Prosoective multicenter evaluation of cocaine associated chest pain. Acad Emerg Med. 1994; 1:330-9. 8. Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest pain in the emergency room: identification and examination of low-risk patients. Arch Intern Med. 1985; 145:65-9. 9. Hollander JE, Lozano M Jr, Fairweather P, et al. Abnormal electrocardiograms in patients with cocaine-associated chest pain are due to “normal” variants. J Emerg Med. 1994;12:199205. 10. Hollander JE. Management of cocaine associated myocardial ischemia. N Engl J Med. 1995;333:1267-72. 11. Togna G, Tempesta E, Togna AR, et al. Platelet responsiveness and biosynthesis of thromboxane and prostacyclin in response to in vitro cocaine treatment. Haemostasis 1985; 15:100-7. 12. Rezkalla S, Mazza JJ, Kloner RA, Tillema V, Chang SH. The effect of cocaine on human platelets. Am J Cardiol. 1993; 72243-6. 13. Kugelmass AD, Shannon RP, Yeo EL, Ware A. Intravenous cocaine induces platelet activation in the consciousdog. Circulation 1995;91:1336-40. 14. Molitemo DJ, Lange RA, Gerard RD, Willard JE, Lackner C, Hillis LD. Influence of intranasal cocaine on plasma constituents associated with endogenous thrombosis and thrombolysis. Am J Med. 1994;96:492-6. 15. Pate1R, Haider B, Ahmed S, Regan TJ. Cocaine related myocardial infarction: high prevalence of occlusive coronary thrombi without significant obstructive atherosclerosis.Circulation 1988; 78: (suppl II) B-436. 16. Hollander JE, Hoffman RS. Cocaine induced myocardial infarction: an analysis and review of the literature. J Emerg Med. 1992; 10:169-77.

17. Minor RL, Scott BD, Brown DD, Winniford MD. Cocaineinduced myocardial infarction in patients with normal coronary arteries. Ann Intern Med. 1991;115:797-806. 18. Levine SR, Brust JCM, Futrell N, et al. Cerebrovascular complications of the use of the crack form of the alkaloidal cocaine. N Engl J Med. 1990;323:699-704. 19. Wojak JC, Flamm ES. Intracranial hemorrhage and cocaine use. Stroke 1987;18:712-15. 20. Lichtenfeld PJ, Rubin DB, Feldman RS. Subarachnoid hemorrhage precipitated by cocaine snorting. Arch Neurol. 1984; 411223-4. 21. Daras M, Tuchman AJ, Marks S. Central nervous system infarction related to cocaine abuse. Stroke 1991;22:1320-5. 22. Bush HS. Cocaine associated myocardial infarction: a word of caution about thrombolytic therapy. Chest. 1988;94:878. 23. Sloan MA, Mattioni TA. Concurrent myocardial infarction and cerebral infarctions after intranasal cocaine use. Stroke 1992; 23~427-30. 24. Hollander JE, Burstein JL, Shih RD, et al. Cocaine associated myocardial infarction: clinical safety of thrombolytic therapy. Chest 1995;107(5):1237-41. 25. Hollander JE, Hoffman RS, Burstein J, et al. Cocaine associated myocardial infarction. Mortality and complications. Arch Intern Med. 1995;155:1081-86. 26. Hollander JE, Lozano M Jr, Goldstein E, et al. Variations in the electrocardiograms of young adults: Are revised criteria for thrombolysis necessary?Acad Emerg Med. 1994;1(2):94- 102. 27. Yuen-Green MS, Yen CK, Lin AD, Lull RJ. Tc-99 sestamibi myocardial imaging at rest for evaluation of cocaine induced myocardial ischemia and infarction. Clin Nucl Med. 1992; 17:923-5. 28. Goldfrank LR, Hoffman RS. The cardiovascular effects of cocaine. Ann Emerg Med. 1991;20:165-75. 29. Brogan WC, Lange RA, Kim AS, Molitemo DJ, Hillis LD. Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin. J Am Co11Cardiol. 1991;18:581-6. 30. Hollander JE, Carter WC, Hoffman RS. Use of phentolamine for cocaine induced myocardial ischemia (letter). N Engl J Med. 1992;327:361. 31. Negus BH, Willard JE, Hillis LD, et al. Alleviation of cocaine induced coronary vasoconstriction with intravenous verapamil. Am J Cardiol 1994;73:510-513. 32. Warrian WG, Halikas JA, Crosby RD, Carlson GA, Crea F. Observations on increased CPK levels in asymptomatic cocaine abusers. J Add Dis. 1992; 11:83-95. 33. Swartz CM, Breen KJ. Elevated serum CK in long abstinent cocaine abusers. Am J Drug Alcohol Abuse 1993;19:327-35. 34. McLaurin MD, Henry TD, Apple FS, Sharkey SW. Cardiac troponin I, T and CK-MB in patients with cocaine related chest pain (abstract). Circulation 1994;9O(suppl):I-278.