Oe K Prolonged AV block with ATP

Case Report

Prolonged Atrioventricular Block and Ventricular Standstill Following Adenosine Triphosphate Injection in a Patient Taking Dipyridamole and Antiarrhythmic Agents: A Case Report

Kotaro Oe MD1, Tsutomu Araki MD1, Kenshi Hayashi MD2, Masakazu Yamagishi MD2 1Division of Internal Medicine, Saiseikai Kanazawa Hospital 2Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine

An 83-year-old woman was admitted to our hospital because of palpitation. She had hypertension and paroxysmal atrial fibrillation, treated with digoxin and cibenzoline, and took dipyridamole for microalbuminuria. Before admission, she had taken pilsicainide pills in addition. On admission, electrocardiogram showed regular tachycardia with mildly prolonged QRS width. For the purpose of terminating tachycardia, 10 mg of adenosine triphosphate (ATP) was rapidly injected. About 20 sec later, atrioventricular block and ventricular standstill occurred. She presented loss of consciousness and convulsion, and chest compression was performed. About 30 sec later, the QRS complex reappeared, and she became alert. Serum concentration of digoxin, cibenzoline and pilsicainide was within therapeutic level, respectively. We should be cautious in using ATP for a patient taking dipyridamole and antiarrhythmic agents. (J Arrhythmia 2009; 25: 219–222)

Key words: Adenosine, Cardiac arrest, Antiarrhythmia agents

Introduction Case Report Adenosine has been commonly used to treat An 83-year-old woman was admitted to our patients with supraventricular tachycardia (SVT). hospital because of palpitation. She had been Because of the very short half-life of adenosine, diagnosed with hypertension and paroxysmal atrial serious adverse effects are rarely seen with adeno- fibrillation and was being treated with antihyperten- sine used to treatment of SVT.1–3) We report an sive agents (candesartan 8 mg/day, nifedipine 20 elderly women who took dipyridamole and antiar- mg/day), digoxin (0.125 mg/day) and cibenzoline rhythmic agents, and presented with prolonged (50 mg/day) since she was 76-year-old. In addition, atrioventricular (AV) block and ventricular standstill she took dipyridamole (300 mg/day) for microalbu- after adenosine triphosphate (ATP) injection. minuria related to hypertension. Previous electro-

Received 5, June, 2009: accepted 24, September, 2009. Address for correspondence: Kotaro Oe MD, Division of Internal Medicine, Saiseikai Kanazawa Hospital, Akatsuchimachi Ni 13-6, Kanazawa 920-0353 Japan. Telephone: +81-76-266-1060 Fax: +81-76-266-1070 E-mail: [email protected]

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aVF V6 aVF V6 Figure 2 Figure 1 Electrocardiogram on admission showed regular tachycardia with Electrocardiogram about one year before admission. mildly prolonged QRS width. cardiogram had showed frequent atrial premature digoxin was 1.1 ng/ml (therapeutic level: 0.8–2.0), complexes and mild ST depression in II, III, aVF, V5 cibenzoline was 117.3 ng/ml (70.0–250.0) and pilsi- and V6 leads (Figure 1). Echocardiography showed cainide was 0.85 mg/ml (0.20–0.90). Dipyridamole normal contractility (ejection fraction 74%) of the was discontinued, but digoxin (0.125 mg/day) and left ventricle without hypertrophy and dilatation, and cibenzoline (50 mg/day) were continued for treat- left atrial diameter was normal (34 mm). Previous ment of arrhythmia. Atrial flutter reverted to sinus Holter recordings did not show sinus node dysfunc- rhythm during the first day. Holter recording on the tion or atrioventricular block. Cardiac catheterization second day did not show sinus node dysfunction, was performed when she was 77-year-old. Coronary atrioventricular block and paroxysmal atrial fibrilla- angiography showed no organic stenosis of the left tion. Thereafter, her clinical course was uneventful. and right coronary arteries, and left ventriculography We have prohibited the use of ATP in this patient. showed normal contractility. Before admission, she took two additional pills of pilsicainide (100 mg Discussion total), which were prescribed for her husband in other hospital. On admission, her height was 150 cm, Adenosine is an endogenous nucleoside present body weight was 56 kg, blood pressure was 106/ throughout the body and has been commonly used 66 mmHg, and heart rate was 114 beats per minute to treat patients with SVT. Adenosine triphosphate and regular. Laboratory data indicated normal serum (ATP) is rapidly converted to adenosine after creatinine level (0.72 mg/dl) and mild reduction of exogenous administration and adenosine functions estimated glomerular filtration ratio (58 ml/min/ through its receptor. Adenosine is removed from the 1.73 m2). Serum creatine kinase concentration was extracellular space by washout, enzymatically by within normal range. Electrocardiogram showed degradation to inosine, by phosphorylation to ad- regular tachycardia with mildly prolonged QRS enosine monophosphate, or by reuptake into cells width (Figure 2). For the purpose of terminating through nucleoside transport system.4) Because of tachycardia, 10 mg of ATP was rapidly (within a few the very short half-life (1 to 6 seconds) of adenosine, seconds) injected from right cephalic vein. About serious adverse effects were rare in using adenosine 20 sec later, AV block and ventricular standstill for treatment of SVT.1–3) occurred (Figure 3). Atrial flutter was identified by Several serious adverse effects of adenosine were its characteristic sawtooth waveform. She presented reported.5) Atrial fibrillation is occasionally observed loss of consciousness and convulsion, and chest with adenosine administration,4) and hemodynamic compression was performed. About 30 sec later, deterioration by preexcited atrial fibrillation was QRS complexes reappeared during chest compres- reported in a patient with WPW syndrome.6) Accel- sion, and she became alert. Serum concentration of eration of ventricular response to atrial flutter were

220 Oe K Prolonged AV block with ATP

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Figure 3 Electrocardiogram after injec- tion of adenosine tiphosphate showed atrioventricular block and ventricular standstill. Atrial flutter was identified by its characteristic sawtooth convulsion waveform. reported in some patients.2,7,8) Adenosine-induced patient who was given adenosine while taking polymorphic ventricular tachycardia9–11) and ven- dipyridamole.16) Because our patient also took tricular fibrillation12) were reported in a few patients. dipyridamole, 10 mg of ATP might have been an To our knowledge, this is the second case report of overdose for her. Potentiated effect of adenosine prolonged AV block induced by adenosine. Harvey may cause prolonged AV block and ventricular et al. reported an elderly woman who presented standstill in this patient. prolonged complete AV block requiring intubation For prevention of serious adverse effect of ATP, and temporary pacemaker after administration of we have discontinued dipyridamole and prohibited adenosine for atrial flutter during the treatment with the use of ATP in this patient. When atrial flutter metoprolol and diltiazem.13) In our patient, digoxin recurs, we would recommend catheter ablation for and cibenzoline were used daily, and she took this patient. pilsicainide temporarily. Although the serum con- centrations of these agents were all within the Conclusion therapeutic level, drug interactions might be related to this complication. Both cibenzoline and pilsicai- We report an elderly women who presented nide block the sodium channel, digoxin and cibenzo- prolonged AV block and ventricular standstill line affect muscarinic receptor subtype 2,14) and following ATP injection while taking dipyridamole pilsicainide potentiates the effect of digoxin. The and antiarrhythmic agents. We should be cautious potentiated inhibitory effect of these agents on the in using ATP for patients taking dipyridamole and AV node and the His-Purkinje system may relate to antiarrhythmic agents. prolonged AV block and ventricular standstill. In this patient, electrocardiogram on admission showed intraventricular conduction delay which might be References due to the effects of sodium channel blockers 1) Rankin AC, Brooks R, Ruskin JN, et al: Adenosine and (cibenzoline and pilsicainide). Because adenosine the treatment of supraventricular tachycardia. Am J Med 15) suppresses His-Purkinje automaticity, it may cause 1992; 92: 655–664 prolonged ventricular standstill in patients with 2) Riccardi A, Arboscello E, Ghinatti M, et al: Adenosine in intraventricular conduction delay. the treatment of supraventricular tachycardia: 5 years of Dipyridamole is a nucleoside transport blocker experience (2002–2006). Am J Emerg Med 2008; 26: that blocks reuptake of adenosine, delaying its 879–882 4) 3) Innes JA: Review article: Adenosine use in the emer- clearance and potentiating its effect. In patients gency department. Emerg Med Australas 2008; 20: 209– taking dipyridamole, a lower dose of adenosine is 215 5) recommended for treatment of SVT. Prolonged 4) Miller JM, Zipes DP: Therapy for cardiac arrhythmia, bradycardia (approximately 35 sec) was reported in a Heart disease 8th edition, Braunwald E, editor,

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Philadelphia, Saunders, 2008, 799–800 11) Kaplan IV, Kaplan AV, Fisher JD: Adenosine induced 5) Mallet ML: Proarrhythmic effects of adenosine: a review atrial fibrillation precipitating polymorphic ventricular of the literature. Emerg Med J 2004; 21: 408–410 tachycardia. Pacing Clin Electrophysiol 2000; 23: 140– 6) Cowell RPW, Paul VE, Ilsley CDJ: Haemodynamic 141 deterioration after treatment with adenosine. Br Heart J 12) Shah CP, Gupta AK, Thakur RK, et al: Adenosine- 1994; 71: 569–571 induced ventricular fibrillation. Indian Heart J 2001; 53: 7) Rankin AC, Rae AP, Houston A: Acceleration of 208–210 ventricular response to atrial flutter after intravenous 13) Harvey MG, Safih S, Wallace M: Adenosine-induced adenosine. Br Heart J 1993; 69: 263–265 complete heart block: Not so transient. Emerg Med 8) Slade AKB, Garratt CJ: Proarrhythmic effect of adeno- Australas 2007; 19: 559–562 sine in a patient with atrial flutter. Br Heart J 1993; 70: 14) Kodama I, Ogawa S, Inoue H, et al: Profiles of aprindine, 91–92 cibenzoline, pilsicainide and pirmenol in the framework 9) Romer M, Candinas R: Adenosine-induced non-sus- of the Sicilian Gambit. Jpn Circ J 1999; 63: 1–12 tained polymorphic ventricular tachycardia. Eur Heart J 15) Lerman BB, Wesley RC, DiMarco JP, et al: Antiadre- 1994; 15: 281–282 nergic effects of adenosine on His-Purkinje automaticity. 10) Smith JR, Goldberger JJ, Kadish AH: Adenosine induced J Clin Invest 1988; 82: 2127–2135 polymorphic ventricular tachycardia in adults without 16) Brady WJ, DeBehnke DJ, Wickman LL, et al: Treatment structural heart disease. Pacing Clin Electrophysiol 1997; of out-of-hospital supraventricular tachycardia: adeno- 20: 743–745 sine vs verapamil. Acad Emerg Med 1996; 3: 574–585

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