Intravenous Adenosine TherapyAccelerating Rateof Paroxysmal Supraventricular Tachycardia STEVEN L. OREBAUGH,
MD, MARK HANDY, MD
Two cases of paroxysmal supraveniricular tachycardia are reported in which the administration of adenosine produced sustained elevation of the rate of parouysmal supraventricular tachycardia. In each case, sinus rhythm was restered readily through the use of intravenous verapamil. This adverse reaction to adenosine has not been previously described. (Am J Emer@Med 1992;10:326-330. This is a US governmentwork. There are no restrictions on its use.) Adenosine is rapidly becoming a first-line therapy for paroxysmal supraventricular tachycardia (PSVT). This agent has a high conversion rate and generally produces transient atrioventricular (AV) block in nonreentrant supraventricular dysrhythmias, such as atria1 fibrillation. Two cases are reported in which intravenous (IV) adenosine administration resulted in sustained elevation of the rate of PSVT. CASE REPORTS CaseNo.1 A 27-year-old woman presented to the emergency department (ED) complaining of palpitations of 1 hour’s duration. She related a history of rapid heart rate, with palpitations experienced in 1985 and in April 1989. Since that time she had been symptom-free until the present episode. The patient complained of mild shortness of breath but denied chest pain, recent use of tobacco, substances containing caffeine, theophylline preparations, illicit drugs, or alcohol. She reported that in 1985 a workup for heart disease (including echocardiagram) had been negative. Significant past medical history consisted only of her episodes of prior palpitations. Physical examination revealed an alert, oriented, healthy-appearing woman who seemed anxious. Her heart rate was 180 beats per minute, respiratory rate 16 breaths per minute, and blood pressure 120/96 mm Hg. Oral temperature was 37.4”C. Her examination was remarkable only for her rapid cardiac rate, with a two out of six systolic murmur at the lower left sternal border. The lungs were clear. No prior electrocardiogram was available. The patient was placed on a cardiac monitor, which revealed a From the Departments of Emergency Medicine and Clinical Investigation, Naval Hospital, San Diego, CA. Manuscript received October 31, 1991; revision accepted January 29.1992. The Chief, Nave Bureau of Medicine and Surgery, Washington, DC, Clinical-Investigation Program sponso;ed- this report #84-l 6-l 968-317. as reauired bv HSETCINST 6000.41. The views expressed in this articie are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. Address reprint requests to LCDR S. L. Orebaugh, MC, USN, % Clinical Investigation Dept, Naval Hospital, San Diego, CA 92134-5000. Key Words: Adenosine, verapamil, paroxysmal supraventricular tachycardia, atrioventricular, cardiac rhythm, hemodynamic. This is a US government work. There are no restrictions on its use. 0735-6757/92/l 004-0012$0.00/O
regular, narrow complex rhythm that remained stable at 180 to 184 beats per minute. Oxygen was begun at 2 L per minute by nasal canula and an IV was established. An electrocardiogram revealed PSVT, and the patient was given 6 mg of adenosine, which was administered rapidly through a peripheral IV catheter. Within seconds, her heart rate increased to 210 beats per minute with a regular rhythm (Figure l), and her blood pressure increased to 190/90 mm Hg. The patient experienced a subjective worsening of her palpitations. Since the initial bolus of adenosine did not result in AV block or conversion, the patient received a second IV dose of 12 mg of adenosine 3 minutes later. The cardiac monitor displayed an acceleration of the heart rate, climbing to as high as 240 beats per minute (Figure 1). The patient became more anxious and noted even worse palpitations with chest pressure and discomfort, lasting less than 30 seconds. After an IV dose of 5 mg of verapamil was administered, her heart rate fell to approximately 110 beats per minute and she converted to sinus rhythm (Figure 2). She noted improvement in her palpitations and appeared much less anxious. Over the next 60 minutes, two further doses of verapamil were required to treat recurrence of the rapid regular rate to 180 beats per minute. Subsequently, she remained hemodynamically stable and in sinus rhythm through 2 hours of observation in the ED. She was referred to the cardiology service for an outpatient evaluation of her PSVT. Subsequent electrocardiograms revealed normal sinus rhythm with no evidence of preexcitation. An echocardiogram was interpreted as a normal study. The patient has had no further symptoms despite declining oral prophylaxis with verapamil.
CaseNo.2 A 55-year-old woman presented to the ED complaining of IO minutes of mild chest pressure and shortness of breath with a sensation of rapid heart beat. The onset of symptoms occurred while dancing, and she noted she had drunk wine and ten cups of coffee that day. She described palpitations occurring three or four times per week for several months, but noted that they generally lasted only a few minutes and resolved spontaneously. They were more frequent when she was anxious or exerting herself. Her past medical history was notable for a reported myocardial infarction which occurred 11 years prior to admission. Since that time, she had had no manifestations of ischemic heart disease and was taking no medication. Examination revealed an obese woman with tachypnea to 32 breaths per minute, a heart rate of 184 beats per minute, and a blood pressure of 164/104 mm Hg. There was no evidence of jugular venous distention, the lungs were clear, and the heart sounds were somewhat distant. The rate was regular with no audible S3, S4, or murmur. There was no edema; the peripheral pulses were full. The electrocardiogram revealed a regular, rapid, narrow complex rhythm interpreted as PSVT at a rate of 184 beats per minute (Figure 3, top). The patient was placed on a cardiac monitor and a pulse oximeter, 2 L of oxygen per nasal canula were given, and an IV of lactated ringers was started. Upon receiving a rapid IV bolus of 6 mg of adenosine, the patient noted a worsening of her shortness of breath and palpitations, and the heart rate was noted to increase to over 200 beats per minute (Figure 3, bottom). Four minutes later a
OREBAUGH AND HANDY n ADENOSINE ACCELERATION OF PSVT
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FIGURE 1. Three electrocardiographic monitoring strips. (Top) Initial strip shows PSVT at rate of about 180 per minute. (Center) Second strip recorded after 6-mg bolus of adenosine administered shows acceleration of rate of PSVT to approximately 200 per minute. (Bottom) Third strip shows further acceleration of rate after 12-mg intravenous adenosine bolus.
12-mg IV bolus of adenosine produced no improvement in the symptoms or the heart rate. There was no deterioration in the blood pressure or the mental status. Immediately, a S-mg IV bolus of verapamil was administered, causing prompt conversion to sinus tachycardia at a rate of 108 beats per minute (Figure 4). There was an immediate cessation of her symptoms. There were no electrolyte
abnormalities, and the chest x-ray was normal. A repeat electrocardiogram revealed only sinus tachycardia without evidence of acute ischemia or prior myocardial infarction. Subsequently, she was treated with oral slow-release verapamil after consultation with the cardiology service. She continued to have symptoms of frequent palpitations. Her therapy was then
FIGURE 2. 1Zlead electrocardiogram recorded after patient no. 2 received 5 mg IV verapamil, displaying sinus tachycardia at rate of I10 per minute.
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changed to 50 mg of oral atenolol daily, which controlled her rhythm and symptoms well 3 months after her ED presentation. An echocardiogram revealed mitral valve prolapse with trace mitral regurgitation and normal systolic function. Thyroid function studies were normal. Rare premature atria1 and ventricular beats were evident on 24-hour Halter electrocardiograph monitoring with no episodes of tachycardia. Repeat electrocardiograms showed no evidence of preexcitation.
DISCUSSION Adenosine is an endogenous adenine nucleoside molecular weight of 267 and, along with adenosine
with a triphos-
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FIGURE 3. (Top) 124ead electrocardiogram shows PSVT at rate of approximately 180 per minute. (Note: leads VI and V3 were reversed when the electrocardiogram was obtained.) (Bottom) Acceleration of rate after 6 mg then 12 mg of IV adenosine.
phate (ATP), has demonstrated efftcacy in the treatment of PSVT when administered as a rapid IV bolus.‘-” In recent years, ATP has become the preferred therapeutic modality
for PSVT in Europe. Its effects on cardiac electrical activity are the same as those of adenosine, to which it is probably metabolized intracellularly.‘2 The half-life of adenosine is quite short: 0.6 to 10 seconds.12v’3 The metabolism of these drugs occurs in the cellular elements of blood and the vascular endothelium, wherein adenosine is phosphorylated to adenosine monophosphate.’ The biologic effects of adenosine are diverse. It contributes to coronary vasodiiation, prostaglandin release, reduc-
OREBAUGH
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FIGURE 4. 12-lead electrocardiogram displaying sinus tachycardia at rate of 108 per minute after patient received 5 mg of IV verapamil.
tion in the size of experimental myocardial infarction,‘2 suppression of ventricular escape rhythms in animals,” and inhibition of platelet aggregation.16 Its most clinically useful effect, however, is its negative chronotropic and dromotropit action at the SA and AV nodes. Sinus node automaticity and AV conduction are both suppressed.’ DiMarco et al4 were able to produce transient complete AV block in 17 patients undergoing electrophysiologic studies with a mean dose of 179 p&kg of adenosine given rapidly IV. During electrophysiologic testing, Favale et al” evaluated the mechanism of action of adenosine on the AV node and reported that the at&l-to-His-bundle interval was lengthened without any change in conduction through the His-Purkinje segment. In almost all patients studied, adenosine has produced slowing of the sinus rate and depression of AV node conduction. l2 Early work by Drury and Szent-Gyorgyi” and Somlo” suggested that adenosine and ATP might be clinically useful in treating PSVT. Various investigators have reported reestablishment of sinus rhythm in 14 to 25 seconds3~“~” This agent has proven efftcacious in spontaneous and induced AV nodal PSVT in adults and children while producing only short-lived AV block in cases of atria1 fibrillation, atria1 flutter, atrial reentrant tachycardia, or automatic atria1 tachycardia.2v8 In direct comparisons of adenosine’s efficacy with that of verapamil in PSVT, this drug has proven comparable in overall effectiveness with fewer adverse hemodynamic effects in both adults and children.‘~5~6~10 Side effects of IV adenosine occur frequently. Flushing and dyspnea have been reported in lS% to 100% of patients.2~‘~8~10~‘2 Also commonly noted are headache, cough,s,9*‘2 and angina-like chest pain.2’ Some patients report a sense of “impending doom.” Adverse cardiovascular effects include sinus bradycardia, sinus arrest, atrial fibrillation, and various degrees of AV block, which are generally short-lived.2”~8-” Ho wever, Reed et al reported sinus arrest with syncope and prolonged bradycardia with hypotension
in two patients after adenosine therapy in the ED.22 DiMarco et al” reported a 36% incidence of undesirable effects in 266 patients receiving this drug for PSVT, all lasting less than 2 minutes, except for one self-limited episode of atria1 fibrillation developing 14 minutes after the dose of adenosine was administered. All episodes of sinus arrest or AV block occurring in this study resolved without therapy in less than 4 seconds. Both of the patients described in this report developed an acceleration of the rate of PSVT within seconds after adenosine was administered. No change in rhythm was evident; atria1 fibrillation did not occur. More disturbing, there was no evidence of AV block produced by adenosine, as has been described in numerous series when adenosine failed to reestablish sinus rhythm.2-5r9-12 The doses of adenosine used in these patients were those recommended by the package insert, though our rates of administration may have been slightly slower (up to 5 seconds instead of the allotted 2 seconds). Similar rates of administration in several of the studies cited in this discussion resulted in no acceleration of heart rate. However, an increase in the sinus rate has been reported with slow infusion (4 mg per minute) of ATP to an average total dose of 40 mg: the sinus rate increased by 10 beats per minute on average, accompanied by anxiety, hyperpnea, and an increased cardiac output. 23Similarly, Reid et al24 noted a 34% increase in the heart rate of 16 patients undergoing cardiac catheterization after infusion of IV adenosine; all were in sinus rhythm. Potential mechanisms include reflex tachycardia in the face of systemic vasodilation and reduced cardiac vagal tone.23s24 Such mechanisms may also have been important in the two cases described, although given the short half-life of adenosine, the persistence of the elevation of the cardiac rate for several minutes is puzzling. In a study of IV adenosine bolus in healthy volunteers, Sylven and colleagues2’ reported a 40% increase in heart rate in those who did not develop AV block, and a similar increase after a 20-second reduction in
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heart rate in those who did. The accelerated rate lasted about 60 seconds, then returned to baseline. Another mechanism which may explain an increase in rate after adenosine administration involves this drug’s effect on accessory conduction pathways. Rinne et al demonstrated AV conduction block in 92% of patients with an 8 mg IV bolus of ATP, while only 3% of accessory pathways were blocked.26 With ventriculoatrial pacing, 16% of accessory tracts and 71% of AV nodal tracts displayed retarded conduction. Atrioventricular conduction delay induced by adenosine administration has been used diagnostically to reveal latent preexcitations of the ventricles in patients who have left free wall accessory pathways.27 These patients often have normal-appearing resting electrocardiograms but are at risk for rapid ventricular response to supraventricular tachydysrhythmias.27.28 Adenosine may thus “unmask” latent preexcitation in patients in sinus rhythm by blocking the AV node. A similar mechanism could be postulated for the two patients described, but one expects obvious widening of the QRS complex as the accessory tract becomes the primary pathway for ventricular depolarization. This was not observed. Finally, methylxanthines, such as theophylline or caffeine, are competitive inhibitors of adenosine at its extracellular receptor site,” and may have inhibited the electrophysiologic response to adenosine in the second case presented. There is nevertheless no theoretic mechanism or experimental data to explain an increase in heart rate with adenosine administration under these circumstances. Regardless of the underlying mechanism for this adverse effect, such an acceleration of rate is hazardous. While neither patient in this report experienced hemodynamic deterioration after adenosine administration, the potential for cardiac ischemia, hypotension, hypoperfusion, and degeneration of the rhythm to ventricular fibrillation is appreciable when supraventricular tachydysrhythmias are accelerated. CONCLUSION Two cases of acceleration of the rate of PSVT after adenosine administration are reported. Neither patient experienced hemodynamic deterioration or a change in cardiac rhythm. In each case, sinus rhythm was restored readily through the use of IV verapamil. This adverse effect of adenosine has not been previously described. REFERENCES 1. Garratt C, Linker N, Griffith M, et al: Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia. Am J Cardiol 1989;64:1310-i316 2. DiMarco JP. Sellers TD. Lerman BE. et al: Diaanostic and therapeutic use of adenosine in patients ‘with supr&entricular tachyarrhythmias. J Am Coll Cardiol 1985;6:417-425 3. Saito D, Ueeda M, Abe Y, et al: Treatment of paroxysmal suoraventricular tachvcardia with intravenous adenosine triphosphate. Br Heart J 1986;55:291-294 4. DiMarco JP. Sellers TD, Berne RM, et al: Adenosine: Electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983;68: 1254-l 262 5. Belhassen B, Glick A, Laniado S: Comparative clinical and electrophysiologic effects of adenosine triphosphate and verapamil on paroxysmal reciprocating junctional tachycardia. Circulation 1988;77:795-805 6. Greco R, Benito M, Arienzo V, et al: Treatment of su-
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praventricular tachycardia in infancy with digitalis, adenosine triphosphate and verapamil: Comparative study. Circulation 1982;66:504-508 7. Somb E: Adenosine triphosphate in paroxysmal tachycardia. Lancet 1955;268:1125 (letter) 8. Overholt ED, Rheuban KS, Gutgesell HP, et al: Usefulness of adenosine for arrhythmics in infants and children. Am J Cardiol 1988;61:336-340 9. Belhasen B, Pelleg A: Electrophysiologic effects of adenosine triphosphate and adenosine on the mammalian heart: Clinical and experimental aspects. J Am Coll Cardiol 1984;4:414424 10. DiMarco JP, Miles W, Akhtar M, et al: Adenosine for paroxysmal supraventricular tachycardia: Dose ranging and comparison with verapamil. Ann Intern Med 1990;113:104-110 11. Munoz A, Leenhardt A, Sassine A, et al: Therapeutic use of adenosine for terminating spontaneous paroxysmal supraventricular tachycardia. Eur Heart J 1984;5:735-738 12. Parkes RB, McCollam PL: Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia. Clin Pharm 1990;9:261-271 13. Moser GH, Schrader J, Dewsen A: Turnover of adenosine in plasma of human and dog blood. Am J Physiol 1989;256: C799C806 14. Schrader J, Berne RM, Rubio R: Uptake and metabolism of adenosine by human erythrocyte ghosts. Am J Physiol 1972; 223:159-166 15. Pelleg A, Mitamura H, Mitsuoka T, et al: Effects of adenosine and adenosine triphosphate on ventricular escape rhythm in the canine heart. J Am Coil Cardiol 1986;8:1145-1151 16. Cusack NJ, Hourani SMO: 5-N-Ethylcarboxamidoadenosine: A potent inhibitor of human platelet aggregation. Br J Pharmacol 1981;72:443-447 17. Favale S, DiBiase M, Riuo U, et al: Effect of adenosine and adenosine triphosphate on atrioventricular conduction in patients. J Am Coll Cardiol 1985;5:1212-1219 18. Drury AN, Szent-Gyorgyi A: The physiologic activity of adenosine compounds with especial reference to their action upon mammalian heart. J Physiol 1929;68:213-217 19. Somlo E: Adenosine triphosphate in paroxysmal tachycardia. Lancet 1955;1:1125 (letter) 20. Watt AH, Bernard MS, Webster J, et al: Intravenous adenosine in the treatment of supraventricular tachycardia. Br J Clin Pharmacol 1986;21:227-230 21. Crea F, Pupita G, Galassi AR, et al: Role of adenosine in pathogenesis of angina1 pain. Circulation 1990;81:164-172 22. Reed R, Falk JL, O’Brien J: Untoward reaction to adenosine therapy for supraventricular tachycardia. Am J Emerg Med 1991;9:566-570 23. Davies DF, Grapper AL, Schroeder HA: Circulatory and respiratory effects of adenosine triphosphate in man. Circulation 1951;111:543-549 24. Reid PG, Fraser AG, Watt AH, et al: Acute hemodynamic effects of intravenous infusion of adenosine in conscious man. Eur Heart J 1990;11:1018-1028 25. Sylven C, Jonzon B, Edlund A: Angina pectoris-like pain provoked by IV bolus of adenosine. Eur Heart J 1989;10:48-54 26. Rinne C, Sharma AD, Klein GJ, et al: Comparative effects of adenosine triphosphate on accessory pathway and AV nodal conduction. Am Heart J 1988;155:1042 27. Garrett CJ, Antonion A, Griffith MJ, et al: Use of intravenous adenosine in sinus rhythm as a diagnostic test for latent preexcitation. Am J Cardiol 1990;65:868-873 28. Belhassen B, Shoshani D, Laniado S: Unmasking of ventricular preexcitation by adenosine triphosphate: Its usefulness in the assessment of the ajmaline test. Am Heart J 1989;1?8:634636 29. Balardinelli L, Fenton RA, West A, et al: Extracellular action of adenosine and the antagonism by aminophylline on the atrioventricular conduction of isolated perfused guinea pig and rat hearts. Circ Res 1982;51-569-579 30. Camm AJ, Garrett CJ: Adenosine and supraventricular tachycardia. N Engl J Med 1991;325:1621-1629
MD, MARK HANDY, MD
Two cases of paroxysmal supraveniricular tachycardia are reported in which the administration of adenosine produced sustained elevation of the rate of parouysmal supraventricular tachycardia. In each case, sinus rhythm was restered readily through the use of intravenous verapamil. This adverse reaction to adenosine has not been previously described. (Am J Emer@Med 1992;10:326-330. This is a US governmentwork. There are no restrictions on its use.) Adenosine is rapidly becoming a first-line therapy for paroxysmal supraventricular tachycardia (PSVT). This agent has a high conversion rate and generally produces transient atrioventricular (AV) block in nonreentrant supraventricular dysrhythmias, such as atria1 fibrillation. Two cases are reported in which intravenous (IV) adenosine administration resulted in sustained elevation of the rate of PSVT. CASE REPORTS CaseNo.1 A 27-year-old woman presented to the emergency department (ED) complaining of palpitations of 1 hour’s duration. She related a history of rapid heart rate, with palpitations experienced in 1985 and in April 1989. Since that time she had been symptom-free until the present episode. The patient complained of mild shortness of breath but denied chest pain, recent use of tobacco, substances containing caffeine, theophylline preparations, illicit drugs, or alcohol. She reported that in 1985 a workup for heart disease (including echocardiagram) had been negative. Significant past medical history consisted only of her episodes of prior palpitations. Physical examination revealed an alert, oriented, healthy-appearing woman who seemed anxious. Her heart rate was 180 beats per minute, respiratory rate 16 breaths per minute, and blood pressure 120/96 mm Hg. Oral temperature was 37.4”C. Her examination was remarkable only for her rapid cardiac rate, with a two out of six systolic murmur at the lower left sternal border. The lungs were clear. No prior electrocardiogram was available. The patient was placed on a cardiac monitor, which revealed a From the Departments of Emergency Medicine and Clinical Investigation, Naval Hospital, San Diego, CA. Manuscript received October 31, 1991; revision accepted January 29.1992. The Chief, Nave Bureau of Medicine and Surgery, Washington, DC, Clinical-Investigation Program sponso;ed- this report #84-l 6-l 968-317. as reauired bv HSETCINST 6000.41. The views expressed in this articie are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. Address reprint requests to LCDR S. L. Orebaugh, MC, USN, % Clinical Investigation Dept, Naval Hospital, San Diego, CA 92134-5000. Key Words: Adenosine, verapamil, paroxysmal supraventricular tachycardia, atrioventricular, cardiac rhythm, hemodynamic. This is a US government work. There are no restrictions on its use. 0735-6757/92/l 004-0012$0.00/O
regular, narrow complex rhythm that remained stable at 180 to 184 beats per minute. Oxygen was begun at 2 L per minute by nasal canula and an IV was established. An electrocardiogram revealed PSVT, and the patient was given 6 mg of adenosine, which was administered rapidly through a peripheral IV catheter. Within seconds, her heart rate increased to 210 beats per minute with a regular rhythm (Figure l), and her blood pressure increased to 190/90 mm Hg. The patient experienced a subjective worsening of her palpitations. Since the initial bolus of adenosine did not result in AV block or conversion, the patient received a second IV dose of 12 mg of adenosine 3 minutes later. The cardiac monitor displayed an acceleration of the heart rate, climbing to as high as 240 beats per minute (Figure 1). The patient became more anxious and noted even worse palpitations with chest pressure and discomfort, lasting less than 30 seconds. After an IV dose of 5 mg of verapamil was administered, her heart rate fell to approximately 110 beats per minute and she converted to sinus rhythm (Figure 2). She noted improvement in her palpitations and appeared much less anxious. Over the next 60 minutes, two further doses of verapamil were required to treat recurrence of the rapid regular rate to 180 beats per minute. Subsequently, she remained hemodynamically stable and in sinus rhythm through 2 hours of observation in the ED. She was referred to the cardiology service for an outpatient evaluation of her PSVT. Subsequent electrocardiograms revealed normal sinus rhythm with no evidence of preexcitation. An echocardiogram was interpreted as a normal study. The patient has had no further symptoms despite declining oral prophylaxis with verapamil.
CaseNo.2 A 55-year-old woman presented to the ED complaining of IO minutes of mild chest pressure and shortness of breath with a sensation of rapid heart beat. The onset of symptoms occurred while dancing, and she noted she had drunk wine and ten cups of coffee that day. She described palpitations occurring three or four times per week for several months, but noted that they generally lasted only a few minutes and resolved spontaneously. They were more frequent when she was anxious or exerting herself. Her past medical history was notable for a reported myocardial infarction which occurred 11 years prior to admission. Since that time, she had had no manifestations of ischemic heart disease and was taking no medication. Examination revealed an obese woman with tachypnea to 32 breaths per minute, a heart rate of 184 beats per minute, and a blood pressure of 164/104 mm Hg. There was no evidence of jugular venous distention, the lungs were clear, and the heart sounds were somewhat distant. The rate was regular with no audible S3, S4, or murmur. There was no edema; the peripheral pulses were full. The electrocardiogram revealed a regular, rapid, narrow complex rhythm interpreted as PSVT at a rate of 184 beats per minute (Figure 3, top). The patient was placed on a cardiac monitor and a pulse oximeter, 2 L of oxygen per nasal canula were given, and an IV of lactated ringers was started. Upon receiving a rapid IV bolus of 6 mg of adenosine, the patient noted a worsening of her shortness of breath and palpitations, and the heart rate was noted to increase to over 200 beats per minute (Figure 3, bottom). Four minutes later a
OREBAUGH AND HANDY n ADENOSINE ACCELERATION OF PSVT
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FIGURE 1. Three electrocardiographic monitoring strips. (Top) Initial strip shows PSVT at rate of about 180 per minute. (Center) Second strip recorded after 6-mg bolus of adenosine administered shows acceleration of rate of PSVT to approximately 200 per minute. (Bottom) Third strip shows further acceleration of rate after 12-mg intravenous adenosine bolus.
12-mg IV bolus of adenosine produced no improvement in the symptoms or the heart rate. There was no deterioration in the blood pressure or the mental status. Immediately, a S-mg IV bolus of verapamil was administered, causing prompt conversion to sinus tachycardia at a rate of 108 beats per minute (Figure 4). There was an immediate cessation of her symptoms. There were no electrolyte
abnormalities, and the chest x-ray was normal. A repeat electrocardiogram revealed only sinus tachycardia without evidence of acute ischemia or prior myocardial infarction. Subsequently, she was treated with oral slow-release verapamil after consultation with the cardiology service. She continued to have symptoms of frequent palpitations. Her therapy was then
FIGURE 2. 1Zlead electrocardiogram recorded after patient no. 2 received 5 mg IV verapamil, displaying sinus tachycardia at rate of I10 per minute.
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changed to 50 mg of oral atenolol daily, which controlled her rhythm and symptoms well 3 months after her ED presentation. An echocardiogram revealed mitral valve prolapse with trace mitral regurgitation and normal systolic function. Thyroid function studies were normal. Rare premature atria1 and ventricular beats were evident on 24-hour Halter electrocardiograph monitoring with no episodes of tachycardia. Repeat electrocardiograms showed no evidence of preexcitation.
DISCUSSION Adenosine is an endogenous adenine nucleoside molecular weight of 267 and, along with adenosine
with a triphos-
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FIGURE 3. (Top) 124ead electrocardiogram shows PSVT at rate of approximately 180 per minute. (Note: leads VI and V3 were reversed when the electrocardiogram was obtained.) (Bottom) Acceleration of rate after 6 mg then 12 mg of IV adenosine.
phate (ATP), has demonstrated efftcacy in the treatment of PSVT when administered as a rapid IV bolus.‘-” In recent years, ATP has become the preferred therapeutic modality
for PSVT in Europe. Its effects on cardiac electrical activity are the same as those of adenosine, to which it is probably metabolized intracellularly.‘2 The half-life of adenosine is quite short: 0.6 to 10 seconds.12v’3 The metabolism of these drugs occurs in the cellular elements of blood and the vascular endothelium, wherein adenosine is phosphorylated to adenosine monophosphate.’ The biologic effects of adenosine are diverse. It contributes to coronary vasodiiation, prostaglandin release, reduc-
OREBAUGH
AND HANDY W ADENOSINE
ACCELERATION
h
II
OF PSVT
n -
SVL
FIGURE 4. 12-lead electrocardiogram displaying sinus tachycardia at rate of 108 per minute after patient received 5 mg of IV verapamil.
tion in the size of experimental myocardial infarction,‘2 suppression of ventricular escape rhythms in animals,” and inhibition of platelet aggregation.16 Its most clinically useful effect, however, is its negative chronotropic and dromotropit action at the SA and AV nodes. Sinus node automaticity and AV conduction are both suppressed.’ DiMarco et al4 were able to produce transient complete AV block in 17 patients undergoing electrophysiologic studies with a mean dose of 179 p&kg of adenosine given rapidly IV. During electrophysiologic testing, Favale et al” evaluated the mechanism of action of adenosine on the AV node and reported that the at&l-to-His-bundle interval was lengthened without any change in conduction through the His-Purkinje segment. In almost all patients studied, adenosine has produced slowing of the sinus rate and depression of AV node conduction. l2 Early work by Drury and Szent-Gyorgyi” and Somlo” suggested that adenosine and ATP might be clinically useful in treating PSVT. Various investigators have reported reestablishment of sinus rhythm in 14 to 25 seconds3~“~” This agent has proven efftcacious in spontaneous and induced AV nodal PSVT in adults and children while producing only short-lived AV block in cases of atria1 fibrillation, atria1 flutter, atrial reentrant tachycardia, or automatic atria1 tachycardia.2v8 In direct comparisons of adenosine’s efficacy with that of verapamil in PSVT, this drug has proven comparable in overall effectiveness with fewer adverse hemodynamic effects in both adults and children.‘~5~6~10 Side effects of IV adenosine occur frequently. Flushing and dyspnea have been reported in lS% to 100% of patients.2~‘~8~10~‘2 Also commonly noted are headache, cough,s,9*‘2 and angina-like chest pain.2’ Some patients report a sense of “impending doom.” Adverse cardiovascular effects include sinus bradycardia, sinus arrest, atrial fibrillation, and various degrees of AV block, which are generally short-lived.2”~8-” Ho wever, Reed et al reported sinus arrest with syncope and prolonged bradycardia with hypotension
in two patients after adenosine therapy in the ED.22 DiMarco et al” reported a 36% incidence of undesirable effects in 266 patients receiving this drug for PSVT, all lasting less than 2 minutes, except for one self-limited episode of atria1 fibrillation developing 14 minutes after the dose of adenosine was administered. All episodes of sinus arrest or AV block occurring in this study resolved without therapy in less than 4 seconds. Both of the patients described in this report developed an acceleration of the rate of PSVT within seconds after adenosine was administered. No change in rhythm was evident; atria1 fibrillation did not occur. More disturbing, there was no evidence of AV block produced by adenosine, as has been described in numerous series when adenosine failed to reestablish sinus rhythm.2-5r9-12 The doses of adenosine used in these patients were those recommended by the package insert, though our rates of administration may have been slightly slower (up to 5 seconds instead of the allotted 2 seconds). Similar rates of administration in several of the studies cited in this discussion resulted in no acceleration of heart rate. However, an increase in the sinus rate has been reported with slow infusion (4 mg per minute) of ATP to an average total dose of 40 mg: the sinus rate increased by 10 beats per minute on average, accompanied by anxiety, hyperpnea, and an increased cardiac output. 23Similarly, Reid et al24 noted a 34% increase in the heart rate of 16 patients undergoing cardiac catheterization after infusion of IV adenosine; all were in sinus rhythm. Potential mechanisms include reflex tachycardia in the face of systemic vasodilation and reduced cardiac vagal tone.23s24 Such mechanisms may also have been important in the two cases described, although given the short half-life of adenosine, the persistence of the elevation of the cardiac rate for several minutes is puzzling. In a study of IV adenosine bolus in healthy volunteers, Sylven and colleagues2’ reported a 40% increase in heart rate in those who did not develop AV block, and a similar increase after a 20-second reduction in
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heart rate in those who did. The accelerated rate lasted about 60 seconds, then returned to baseline. Another mechanism which may explain an increase in rate after adenosine administration involves this drug’s effect on accessory conduction pathways. Rinne et al demonstrated AV conduction block in 92% of patients with an 8 mg IV bolus of ATP, while only 3% of accessory pathways were blocked.26 With ventriculoatrial pacing, 16% of accessory tracts and 71% of AV nodal tracts displayed retarded conduction. Atrioventricular conduction delay induced by adenosine administration has been used diagnostically to reveal latent preexcitations of the ventricles in patients who have left free wall accessory pathways.27 These patients often have normal-appearing resting electrocardiograms but are at risk for rapid ventricular response to supraventricular tachydysrhythmias.27.28 Adenosine may thus “unmask” latent preexcitation in patients in sinus rhythm by blocking the AV node. A similar mechanism could be postulated for the two patients described, but one expects obvious widening of the QRS complex as the accessory tract becomes the primary pathway for ventricular depolarization. This was not observed. Finally, methylxanthines, such as theophylline or caffeine, are competitive inhibitors of adenosine at its extracellular receptor site,” and may have inhibited the electrophysiologic response to adenosine in the second case presented. There is nevertheless no theoretic mechanism or experimental data to explain an increase in heart rate with adenosine administration under these circumstances. Regardless of the underlying mechanism for this adverse effect, such an acceleration of rate is hazardous. While neither patient in this report experienced hemodynamic deterioration after adenosine administration, the potential for cardiac ischemia, hypotension, hypoperfusion, and degeneration of the rhythm to ventricular fibrillation is appreciable when supraventricular tachydysrhythmias are accelerated. CONCLUSION Two cases of acceleration of the rate of PSVT after adenosine administration are reported. Neither patient experienced hemodynamic deterioration or a change in cardiac rhythm. In each case, sinus rhythm was restored readily through the use of IV verapamil. This adverse effect of adenosine has not been previously described. REFERENCES 1. Garratt C, Linker N, Griffith M, et al: Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia. Am J Cardiol 1989;64:1310-i316 2. DiMarco JP. Sellers TD. Lerman BE. et al: Diaanostic and therapeutic use of adenosine in patients ‘with supr&entricular tachyarrhythmias. J Am Coll Cardiol 1985;6:417-425 3. Saito D, Ueeda M, Abe Y, et al: Treatment of paroxysmal suoraventricular tachvcardia with intravenous adenosine triphosphate. Br Heart J 1986;55:291-294 4. DiMarco JP. Sellers TD, Berne RM, et al: Adenosine: Electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983;68: 1254-l 262 5. Belhassen B, Glick A, Laniado S: Comparative clinical and electrophysiologic effects of adenosine triphosphate and verapamil on paroxysmal reciprocating junctional tachycardia. Circulation 1988;77:795-805 6. Greco R, Benito M, Arienzo V, et al: Treatment of su-
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praventricular tachycardia in infancy with digitalis, adenosine triphosphate and verapamil: Comparative study. Circulation 1982;66:504-508 7. Somb E: Adenosine triphosphate in paroxysmal tachycardia. Lancet 1955;268:1125 (letter) 8. Overholt ED, Rheuban KS, Gutgesell HP, et al: Usefulness of adenosine for arrhythmics in infants and children. Am J Cardiol 1988;61:336-340 9. Belhasen B, Pelleg A: Electrophysiologic effects of adenosine triphosphate and adenosine on the mammalian heart: Clinical and experimental aspects. J Am Coll Cardiol 1984;4:414424 10. DiMarco JP, Miles W, Akhtar M, et al: Adenosine for paroxysmal supraventricular tachycardia: Dose ranging and comparison with verapamil. Ann Intern Med 1990;113:104-110 11. Munoz A, Leenhardt A, Sassine A, et al: Therapeutic use of adenosine for terminating spontaneous paroxysmal supraventricular tachycardia. Eur Heart J 1984;5:735-738 12. Parkes RB, McCollam PL: Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia. Clin Pharm 1990;9:261-271 13. Moser GH, Schrader J, Dewsen A: Turnover of adenosine in plasma of human and dog blood. Am J Physiol 1989;256: C799C806 14. Schrader J, Berne RM, Rubio R: Uptake and metabolism of adenosine by human erythrocyte ghosts. Am J Physiol 1972; 223:159-166 15. Pelleg A, Mitamura H, Mitsuoka T, et al: Effects of adenosine and adenosine triphosphate on ventricular escape rhythm in the canine heart. J Am Coil Cardiol 1986;8:1145-1151 16. Cusack NJ, Hourani SMO: 5-N-Ethylcarboxamidoadenosine: A potent inhibitor of human platelet aggregation. Br J Pharmacol 1981;72:443-447 17. Favale S, DiBiase M, Riuo U, et al: Effect of adenosine and adenosine triphosphate on atrioventricular conduction in patients. J Am Coll Cardiol 1985;5:1212-1219 18. Drury AN, Szent-Gyorgyi A: The physiologic activity of adenosine compounds with especial reference to their action upon mammalian heart. J Physiol 1929;68:213-217 19. Somlo E: Adenosine triphosphate in paroxysmal tachycardia. Lancet 1955;1:1125 (letter) 20. Watt AH, Bernard MS, Webster J, et al: Intravenous adenosine in the treatment of supraventricular tachycardia. Br J Clin Pharmacol 1986;21:227-230 21. Crea F, Pupita G, Galassi AR, et al: Role of adenosine in pathogenesis of angina1 pain. Circulation 1990;81:164-172 22. Reed R, Falk JL, O’Brien J: Untoward reaction to adenosine therapy for supraventricular tachycardia. Am J Emerg Med 1991;9:566-570 23. Davies DF, Grapper AL, Schroeder HA: Circulatory and respiratory effects of adenosine triphosphate in man. Circulation 1951;111:543-549 24. Reid PG, Fraser AG, Watt AH, et al: Acute hemodynamic effects of intravenous infusion of adenosine in conscious man. Eur Heart J 1990;11:1018-1028 25. Sylven C, Jonzon B, Edlund A: Angina pectoris-like pain provoked by IV bolus of adenosine. Eur Heart J 1989;10:48-54 26. Rinne C, Sharma AD, Klein GJ, et al: Comparative effects of adenosine triphosphate on accessory pathway and AV nodal conduction. Am Heart J 1988;155:1042 27. Garrett CJ, Antonion A, Griffith MJ, et al: Use of intravenous adenosine in sinus rhythm as a diagnostic test for latent preexcitation. Am J Cardiol 1990;65:868-873 28. Belhassen B, Shoshani D, Laniado S: Unmasking of ventricular preexcitation by adenosine triphosphate: Its usefulness in the assessment of the ajmaline test. Am Heart J 1989;1?8:634636 29. Balardinelli L, Fenton RA, West A, et al: Extracellular action of adenosine and the antagonism by aminophylline on the atrioventricular conduction of isolated perfused guinea pig and rat hearts. Circ Res 1982;51-569-579 30. Camm AJ, Garrett CJ: Adenosine and supraventricular tachycardia. N Engl J Med 1991;325:1621-1629
