Calcium channel blocker overdose mimicking an acute myocardial infarction

Resuscitation 59 (2003) 361 /364 www.elsevier.com/locate/resuscitation

Case Report

Calcium channel blocker overdose mimicking an acute myocardial infarction Charles A. Henrikson, Nisha Chandra-Strobos * Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA Received 6 January 2003; received in revised form 4 June 2003; accepted 4 June 2003

Abstract A 42-year-old man presented with shortness of breath, weakness, and diaphoresis, and developed a new left bundle branch block while under evaluation in the Emergency Department. At emergency cardiac catheterization, he was found to have only insignificant coronary disease, and a hyperdynamic ventricle. Despite these findings, he subsequently developed profound bradycardia and hypotension, which were refractory to standard therapies including pressors, calcium, and transvenous pacing. He gradually improved over several days and made a full recovery, after which he admitted to taking multiple calcium channel blockers (CCBs) in an attempt to self-medicate for symptoms he related to his lifelong paroxysmal supraventricular tachycardia. This is the first report of a CCB overdose mimicking an acute myocardial infarction, and highlights the fact that CCB overdose must be considered in the differential diagnosis of some patients who present with apparent acute myocardial infarction. # 2003 Published by Elsevier Ireland Ltd. Keywords: Calcium channel blocker; Electrocardiography; Hypotension; Myocardial infarction; Resuscitation

Resumo Homem de 42 anos vem ao servic¸o de urgeˆncia com dispneia, fraqueza, diaforese e desenvolve um bloqueio completo de ramo esquerdo de novo, durante a observac¸a˜o. Faz cateterismo cardı´aco emergente que mostrou um ventrı´culo hiperdinaˆmico e doenc¸a corona´ria sem significado. Desenvolveu posteriormente bradicardia e hipotensa˜o refracta´rias a´s medidas habituais que incluı´ram vasopressores, ca´lcio e pacing transvenoso. Ao longo dos dias subsequentes foi havendo melhoria progressiva ate´ a´ recuperac¸a˜o completa. Nesta altura o doente refere ter-se auto medicado com antagonistas dos canais do ca´lcio para tratar os sintomas de uma taquicardia supraventricular paroxı´stica. Este e´ o primeiro relato de intoxicac¸a˜o por antagonistas dos canais do ca´lcio que mimetiza enfarte do mioca´rdio, mostrando que esta intoxicac¸a˜o deve ser tida em conta nos diagno´sticos diferenciais de enfarte agudo do mioca´rdio. # 2003 Published by Elsevier Ireland Ltd. Palavras chave: Antagonistas dos canais do ca´lcio; Electrocardiografia; Hipotensa˜o; Enfarte do mioca´rdio; Reanimac¸a˜o

Resumen Un hombre de 42 an˜os se presento´ con dificultad respiratoria, debilidad, diaforesis, y desarrollo´ un nuevo bloqueo de rama izquierda mientras se encontraba en evaluacio´n en el departamento de emergencias. Durante la cateterizacio´n cardiaca de emergencia, se encontro´ que tenı´a enfermedad coronaria insignificante, y un ventrı´culo hiperdina´mico. Pese a estos hallazgos, desarrollo´ una bradicardia profunda e hipotensio´n, las que eran refractarias a las terapias esta´ndar que incluı´an presores, calcio, y uso de marcapasos transvenoso. El mejoro´ gradualmente a lo largo de varios dı´as y llego´ a recuperacio´n completa, despue´s de lo cual el admitio´ que tomo´ mu´ltiples bloqueadores de canales de calcio (CCBs) en un intento de automedicarse para tratar sı´ntomas

* Corresponding author. Johns Hopkins Bayview Medical Center, Division of Cardiology, 4940 Eastern Avenue, Baltimore, MD 21224-2780, USA. Tel.:
/1-410-550-0851; fax: 1-410-550-1183. E-mail address: [email protected] (N. Chandra-Strobos). 0300-9572/03/$ - see front matter # 2003 Published by Elsevier Ireland Ltd. doi:10.1016/S0300-9572(03)00242-9

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que el relacionaba con una taquicardia supraventricular paroxı´stica que ha presentado durante toda su vida. Este es el primer reporte de una sobredosis de CCB que simula un infarto agudo de miocardio, y destaca que la sobredosis de CCB debe ser considerada en el diagno´stico diferencial de algunos pacientes que se presenten con un aparente infarto agudo de miocardio. # 2003 Published by Elsevier Ireland Ltd. Palabras clave: Bloqueador de canales de calcio; Electrocardiografı´a; Hipotensio´n; Infarto de miocardio; Resucitacio´n

1. Introduction Calcium channel blocker (CCB) overdose and acute myocardial infarction (MI) are both common clinical problems. There have been no previous reports directly linking these two phenomena in the same patient. Here, we report a case of CCB overdose whose presentation strongly suggested an acute MI, and which was initially treated as such. Additionally, the overdose was complicated by hypotension refractory to usual treatment with calcium and intravenous pressors, which is atypical for CCB overdose.

2. Case A 42-year-old man with hypertension had been maintained on verapamil for several years for control of his lifelong intermittent supraventricular tachycardia (SVT). He was generally in good health and took no other regular medications. Because of increasing palpitations and dizziness, his primary care physician had recently changed his verapamil to nifedipine, and subsequently to diltiazem on the day prior to admission. He presented with shortness of breath, weakness, and diaphoresis. He appeared ill, his initial vital signs included a heart rate (HR) of 51 beats per minute, blood pressure (BP) of 117/50 mmHg, and his baseline

normal electrocardiogram (EKG, Fig. 1) from the previous day now showed a new intraventricular conduction delay of left bundle branch block (LBBB) morphology (Fig. 2). Because of his symptoms and dynamic EKG findings, the Emergency Department had a high suspicion of an acute MI. Hence, he underwent emergency cardiac catheterization for possible primary percutaneous transluminal coronary angioplasty (PTCA). Coronary angiography demonstrated only nonobstructive lesions, ruling out acute closure of a coronary artery as the cause of his presentation. Additionally, his left ventriculogram revealed no wall motion abnormalities, but rather a markedly hyperdynamic left ventricle with an ejection fraction of 80%. While in the catheterization laboratory his systolic blood pressure ranged from 95 to 115 mmHg, and his pulse from 42 to 50/min. Upon arrival at the Coronary Care Unit he had a HR of 40/min and a BP of 95/40 mmHg. However, over the next 2 h he developed increasing shortness of breath, hypotension, and confusion. Approximately 2 h after leaving the cardiac catheterization lab (6 h after presenting to the Emergency Department) his HR and BP fell: HR of 20 beats per minute, and systolic BP of 60 mmHg. Laboratory studies revealed a marked metabolic acidosis with elevated lactate (16.8 mg/dl), a wide anion gap (37), and marked hypoxemia (pO2 /75 mmHg on FiO2 / 100%). Chest X-ray showed pulmonary edema. A

Fig. 1. Electrocardiogram obtained on the day prior to admission revealed normal sinus rhythm with normal axis and intervals, and no evidence of ischemia or conduction delay.

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Fig. 2. Electrocardiogram obtained on the morning of admission and reveals a junctional rhythm without clear evidence of p waves, and LBBB pattern of conduction.

pulmonary artery catheter revealed a pulmonary capillary wedge pressure of 23 mmHg, cardiac output of 9 l/ min, and a systemic vascular resistance of 400 dynes-seccm 5. Trans-thoracic echocardiography confirmed hyperdynamic left ventricular function, and no pericardial effusion. He was given vigorous supportive treatment with fluid resuscitation, tracheal intubation and ventilatory support, and a transvenous pacemaker. Despite several liters of intravenous fluids, 4 g of calcium gluconate, bicarbonate drip to correct acidosis, and multiple trials of dopamine, epinephrine (adrenaline), norepinephrine (nonadrenaline), phenylephrine, and vasopressin, the patient’s systolic BP remained in the 60/75 mmHg range. Approximately 4 h after the patient’s initial decompensation, his intrinsic rhythm increased to approximately 80/min with a narrow QRS complex, and his BP rose to a systolic of 80 mmHg without pressor agents. The following morning, the patient extubated himself, and although his oxygen saturations remained in the low nineties on 100% inspired oxygen by facemask, his BP remained stable at 80 mmHg without systolic, with no clinical evidence of shock. Pressor agents were not restarted. A diuresis gradually took place and his oxygenation, wedge pressures, and systemic vascular resistance improved over the following 72 h. Serial laboratory studies revealed a grossly elevated total creatinine kinase (CK/2820 IU/l) with a muscle/ brain fraction of less than 1% (MB /24 ng/ml), and a slightly elevated troponin T (0.10 ng/ml (normal 5/ 0.09)). At admission, the patient denied having taken an overdose of his medications, however, after extubation, he admitted taking ‘‘several’’ pills each of long-

acting verapamil, diltiazem, and nifedipine, of unclear dosages, and over an unclear time period.

3. Discussion At presentation, this patient appeared to be having a MI. His shortness of breath, diaphoresis, and hypotension, as well as the new LBBB, justified treatment for an acute ST elevation MI. Thus, he was given usual and appropriate treatment, and taken as an emergency to the cardiac catheterization laboratory. Subsequent findings on angiography, combined with the only slightly elevated cardiac enzymes, indicated that he had not suffered an acute closure of a coronary artery. His presentation in the Emergency Department, however, was fully consistent with MI, and given the available therapies for such, the only prudent clinical course was to treat him as an acute MI. Classically, MI is diagnosed with two of the following three findings: chest pain or other symptoms, EKG changes, and cardiac enzymes. This patient had all three of these */shortness of breath, weakness, and diaphoresis; a new LBBB; and elevated CK and troponin T, albeit a modest rise in troponin T levels. However, angiography showed no significant coronary lesions, both catheterization and echocardiography showed a normal ejection fraction without any wall motion abnormalities, and his markedly elevated CK was less than 1% MB. In retrospect, his presentation and clinical course are fully explained by an overdose of CCBs. He self-administered escalating doses of his CCBs in a misguided attempt to medicate his symptoms of shortness of breath, weakness and diaphoresis. He thought

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that these were due to his longstanding PSVT, however, they were almost certainly due to excessive doses of the CCBs themselves. We suspect that the CCB overdose was not an abrupt event, but rather that he had slowly been increasing the number of pills taken over the preceding days to weeks, and his presentation was the result of these gradually escalating doses. Unfortunately, the patient was unable, or at least unwilling, to provide us with detailed information regarding the doses taken. We do know that the nifedipine was a long-acting preparation, as was the diltiazem. The preparation of verapamil was not available to us. Given that CCB overdose itself was not suspected until the second hospital day, when the patient’s condition was clearly improving, a full workup and investigation for coingestions was not undertaken. The patient’s motivations for taking the CCBs are clear, and thus we doubt that he took any other substances at the same time. He did not have serum or urine toxicology studies. The escalation of the symptoms and the EKG changes seen in the Emergency Department are clearly referable to the CCBs. The profound hypotension which he suffered was most likely due to vasodilation from the CCBs, and this lack of perfusion pressure most likely led to some necrosis of skeletal muscle as reflected by the grossly elevated total CPK with a near-normal MB fraction. The small amount of troponin T present in his serum was most likely due to a similar mechanism, i.e., hypotension and inadequate perfusion pressure in the coronary vasculatures, which led to a small amount of myocardial necrosis. The patient’s main symptoms were SOB, weakness, and diaphoresis. While these are not classic for CCB overdose, they are consistent with hypoperfusion. The primary sites of action of CCBs are on the myocardium, smooth muscle, and cardiac conduction system [1]. Hypotension, bradycardia and conduction delay, mental status changes, and metabolic acidosis are common findings in calcium channel antagonist overdose [2]. Unusual complications include cerebral infarction, bowel infarction, and noncardiogenic pulmonary edema [3]. Presentation mimicking acute MI has not been previously reported. In fact, any evidence of myocardial injury is unexpected in CCB overdose. The coronary vasodilatory effects of CCBs should be pro-

tective against MI, and in fact nifedipine, verapamil, and diltiazem have all been shown to have modest beneficial effects in acute MI. In this case, the patient’s hypotension, which was refractory to both specific treatment with calcium, and nonspecific treatment with sympathomimetics and other pressors, are likely to have overridden any protective effects of CCBs, and produced supply-related ischemia. The usual therapies [4] for hypotension were ineffective in this patient perhaps because the hypotension occurred despite hyperdynamic left ventricular function. The classic findings of CCB overdose should include decreased myocardial contractility. However, the profound reduction in afterload is likely to counteract the direct myocardial effects and facilitate hyperdynamic left ventricular function. Indeed, this patient was found to have a hypercontractile left ventricle, a finding which has been previously reported in CCB overdose [5]. The only effective treatment for the patient reported here was time, and fortunately we were able to support him until the effects of the calcium channel antagonists had begun to dissipate. The hemodynamic effects of CCB overdose can be sustained, devastating, and unresponsive to commonly recommended therapies. This case highlights the fact that the presentation of CCB overdose can mimic acute MI, and thus CCB overdose must be considered in the differential diagnosis of patients presenting with classic signs and symptoms of acute MI.

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