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Intravenous propranolol in the treatment of repetitive ventricular tachyarrhythmias during resuscitation from sudden death
Volume Number
110 1, part
Rripf (‘ommunirations
1
cardia was no longer inducible, either by atrial pacing (rate 96/min) or right atrial extrastimulus. Atria1 pacing at a higher heart rate (lOO/min) was still able to induce only very short bursts of tachycardia. Many authors5 have reported that Am, given intravenously during EPS, did not significantly change ventricular and accessory Kent-like bundle refractoriness. In contrast, its main effect is on the AV node in prolonging refractory periods and conduction time. Lengthening of the conduction time through the retrograde limb of the reentry circuit, as we have achieved in our case, giving Am as an intravenous bolus, may be suggestive of the presence of an accessory pathway with nodal-like property. As a further proof of the drug efhcacy, a continuous 24-hour ECG recording was obtained after 4 weeks of oral treatment with Am (400 mg/day). The continuous ECG recording did not reveal any episode of AVNRT. Therefore, the role of intravenous and oral Am in the control of incessant AVNRT should be critically evaluated. REFERENCES
1. Coumel P, Attuel P, Leclerq JF: Permanent form of junctional reciprocating tachycardia: Mechanism, clinical and therapeutic implications. In Narula OS, editor: Cardiac arrhvthmias; electrophysiology, diagnosis and management. Baltimore, 1979, The Williams and Wilkins Co. D 347. 2. Sung RJ, Waxman HL, Saksena S, Juma Z: Sequence of retrograde atria1 activation in patients with dual atrioventricular nodal pathways. Circulation 64:1059, 1981. 3. Farre J, Ross D, Wiener I, Bar FW, Vanagt EJ, Wellens HJJ: Reciprocal tachycardia using accessory pathways with long conduction times. Am J Cardiol44:1099, 1979. 4. Gruppo di Studio di Elettrofisiologia delle Aritmie: Protocollo di studio elettrofisiologico della sindrome di WPW. G Ital Cardiol 7:740, 1977. 5. Rowland E, Krikler DM: Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias. Br Heart J 44:82, 1980.
Intravenous propranolol in the treatment repetitive ventricular tachyarrhythmias during resuscitation from sudden death
of
JamesR. Mason, M.D., Joseph C. Marek, M.D. Henry S. Loeb, M.D., and Patrick J. Scanlon, M.D. Maywood
and Hines,
Ill.
We have observed dramatic improvement shortly after administering intravenous propranolol in the setting of recurrent ventricular tachyarrhythmias during resuscitation from sudden cardiac death. Though this application of beta blockers was reported when propranolol first became available,’ the indications for their use in this From the Department of Medicine, Section of Cardiology, Loyola University Medical Center; and Hines Veterans Administration Hospital. Reprint requests: James R. Mason, M.D., Section of Cardiology, 2160 South First Ave., Maywood, IL 60153.
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situation remain unclear. This report contains our experience with three casesfollowed by a discussionof possible mechanismsand clinical profiles of the patient most likely to benefit with intravenous therapy. Cam No. 1. This 66-year-old man with diabetes melhtus, rheumatoid arthritis, and a prior cerebrovascular accident denied any cardiac symptoms. A routine ECG performed prior to elbow surgery revealed an old inferior wall myocardial infarction (MI). A few months later his ECG showedevidence of a recent anterior wall infarction, even though he had not experienced interim symptoms.A thallium threadmill test was ordered to assessthe presence of jeopardized myocardium. Three minutes into the study the patient exhibited 2 mm of ST segmentdepression in associationwith ventricular triplets, in the absence of symptoms. The test was terminated on the basisof his ventricular arrhythmias, and within a few minutes after cessationof exercise the patient demonstrated sustained ventricular tachycardia. He remained asymptomatic and maintained a normal blood pressure. A 100 mg bolus of lidocaine was given, but his rhythm deteriorated to ventricular flutter, with lossof consciousness and no palpable pulse. Cardioversion was promptly delivered, resulting in sinus tachycardia. However, the rhythm quickly deteriorated into sinus tachycardia with brief runs of nonsusmined ventricular tachycardia. His blood pressure was 220/106 mm Hg. He regained consciousnesswith spontaneous,normal respirations, and a seconddoseof lidocaine, 75 mg intravenously, wasgiven. Approximately 5 minutes after his initial cardioversion, he developed ventricular flutter (Fig. 1). The subsequentcoursewasone of repeated cardioversion to sinustachycardia with hypertension followed by rapid deterioration to sustained ventricular tachycardia, followed by ventricular flutter. During the next 15 minutes, cardiopulmonary resuscitation was carried out, including intubation, chest conpression,and 1 mg intravenous epinephrine given to support circulation after unsuccessfulcardioversions. Normal arterial blood gases were obtained after administration of oxygen and sodium bicarbonate, A lidocaine infusion at 4 mg/min wasstarted and bretylium, 500mg intravenously over 10 minutes, was given without significant effect. Over the next 20 minutes the patient received 500mg of procainamide with continuous infusion at 4 mg/min. This regimen decreasedthe rate of the ventricular tachycardia with a concomitant 25% widening of the QRS complex; it did not prevent the recurrence of ventricular flutter, which becamemore resistant to cardioversion, performed at least 10 times. At this time, propranolol, 2 mg intravenously wasgiven over 3 minutes, during which the patient again developed ventricular flutter. On cardioversion, he converted to normal sinusrhythm and had a normal blood pressure (Fig. 1). No complex ventricular arrhythmias were seenin the following hour. Repeat ECG waswithout significant changes.Cardiac catheterization and angiography were performed the following day. which demonstrated severe three-vesselcoronary artery diseaseand an ejection fraction of 25% . Case No. 2. The patient is a 59-year-old man with a
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Fig. 1. The first two panels demonstrate the frequent episodesof nonsustainedventricular tachycardia accompaniedby sinus tachycardia, hypertension, and ST segmentdepression.The second panel shows deterioration to ventricular flutter. Panel three exhibits the slowedventricular tachycardia and widened QRS following procainamide, and the fourth panel was obtained following intravenous propranolol administration.
history of an old MI. He had been feeling well without symptoms of chest pain, dyspnea, palpitations, or syncope, and he was not taking any medications. On the day of admission,he developed the suddenonset of diaphoresis followed by loss of consciousness.He arrived in the emergency room in cardiac arrest and cardiopulmonary resuscitation was performed. The first rhythm recorded was ventricular fibrillation, which on cardioversion converted to a wide QRS tachycardia, rate of 150/min, with a systolic blood pressure of 190 mm Hg. This rhythm spontaneously degenerated to ventricular fibrillation, which was again cardioverted to a wide QRS tachycardia accompaniedby an elevated blood pressure.The patient’s rhythm degeneratedinto ventricular fibrillation following eachcardioversion, and in someinstanceswasprecededby a polymorphic ventricular tachycardia (Fig. 2). During the courseof an hour the patient wasintubated and received 100% oxygen and sodiumbicarbonate, resulting in correction of his initial hypoxia and acidosis. He required cardiopulmonary resuscitation (CPR) and received epinephrine during periods when cardioversion did not successfully convert his ventricular fibrillation. Lidocaine wasgiven with a loading doseof 200mg over 15 minutes in addition to a continuous infusion at 3 mglmin. Following lidocaine, the patient received bretylium, 500 mg intrave-
nously over 10 minutes and a continuous infusion of 2 mg/min, and 10 minutes later an additional 100 mg bolus of lidocaine. His arrhythmias were not altered by these interventions, and he continued to have recurrent ventricular fibrillation, following short periods in a wide QRS tachycardia with hypertension. After 1 hour the patient received his eighteenth cardioversion and he wasgiven 3 mg of propranolol intravenously over 5 minutes. There were no further episodesof ventricular fibrillation over the next few hours. He was transferred to the coronary care unit (CCU), where he was noted to have converted his wide QRS tachycardia to sinus rhythm, associatedwith mild hypotension. Subsequent evaluation disclosed a mild reduction in the patient’s ionized serum calcium, while the rest of his electrolytes, including potassium and magnesium,were normal. An ECG in the CCU demonstrated new prolongation of the QT interval. Serial cardiac enzymes and a technetium pyrophosphate scan were negative. Calcium supplements were given and after a slow recovery, the patient was gradually weaned from all drugs. His only medication at dischargewasa beta blocker. A radionuclide ventriculogram revealed an ejection fraction of 24% and ECG prior to dischargedemonstrated a normal QT interV&d.
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Fig. 2. The first two panels demonstrate the recurring episodesof uniform ventricular tachycardia (top panel) and polymorphous ventricular tachycardia (middle panel) which precededventricular fibrillation. The bottom panel showsthe sinus rhythm and prolonged QT interval following intravenous propranolol
administration.
Fig. 3. The top panel shows an episode of atria1 fibrillation with rapid ventricular responseseen following cardioversion from ventricular tachycardia. The middle panel demonstratesthe rapid, uniform ventricular tachycardia. The third panel was obtained following administration of 5 mg of intravenous propranolol.
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Case NO. 3. This 72-year-old female had no prior cardiovascular problemsexcept for hypertension. She had experienced exertional angina intermittently, but did not seek medical attention. On the day of admission, she experienced chest pain while shopping and fell to the floor. Upon presentation to the emergencyroom, she was in ventricular fibrillation. Cardioversion resulted in supraventricular tachycardia, but frequent episodesof ventricular tachycardia occurred. The ventricular tachycardia was a rapid, unifocal rhythm, with a rate of 22O/min, during which no pulse was palpable. Cardioversion was performed numerous times and resulted in supraventricular tachycardia and episodesof atria1 fibrillation, with ventricular rates of 140to 17O/min (Fig. 3). While her heart wasin a supraventricular rhythm, the systolic blood pressurewas consistently in excessof 200 mm Hg. Over the first hour, the patient received full loading dosesof lidocaine with continuous infusion at 2 mg/min, followed by bretylium and then procainamide, and she required 14 cardioversions. There was no significant change in the pattern of her recurrent ventricular tachycardia. During this time, she received 2 mg of intravenous verapamil in an attempt to better control her supraventricular tachycardia and severe hypertension. Approximately 80 minutes after her arrival, intravenous propranolol was administered, 0.5 mg/min, to a total dose of 5 mg; there were no further episodesof ventricular tachycardia. The patient was transferred to the CCU in sinus rhythm at approximately 6O/min, and her blood pressurewas 130/160 mm Hg. Subsequent hemodynamic measurementsrevealed a pulmonary capillary wedgepressure of 18 mm Hg and a cardiac output of 2.5 L/min. The patient’s hemodynamicsimproved and stabilized over the following 24 hours on dobutamine infusion at 5 pg/kg/min. The ECG revealed minor nonspecific ST abnormalities and was otherwise normal. The routine laboratory data including electrolytes and cardiac enzymes were normal and a radionuclide ventriculogram revealed an ejection fraction of 50%. Discussion. These three casescontain a pattern of “malignant,” repetitive rhythms unresponsiveto multiple antiarrhythmic agents and general supportive measures. In addition, all three casesdemonstrated clinical evidence of heightened sympathetic activity. In each case,prompt suppression of recurrent ventricular tachyarrhythmias followed the administration of intravenous propranolol, and it seemslikely that beta blockade provided the major antiarrhythmic mechanism. Beta receptor stimulation enhances pacemaker activity in cardiac fibers, and enhanced activity of latent pacemaker sites in the ventricle may result in ventricular arrhythmias.2 However, reentry is a more common mechanism for recurrent, sustained ventricular tachycardia, and nonuniform lengthening or shortening of refractory periods, referred to as dispersion, provides the proper substrate3s4Catecholamines can produce dispersion of refractoriness in patients with coronary artery diseaseor in other cardiac diseasesby shortening the refractory period in somefibers but not in adjacent fibers, thereby establishinga reentrant
American
July, 1985 Heart Journal
pathway and the potential for ventricular tachyarrhythmiasZ4 Adrenergic stimulation may also initiate and worsenischemia.Therefore, increasedsympathetic activity may establisha cycle of,worseningischemia,ventricular arrhythmias, and cardiac arrest, which then results in a further increase in adreneigic tone and more refractory arrhythmias. This cycle may be perpetuated by the exogenous catecholamines frequently given during cardiac pulmonary resuscitation, which may have been a factor in our cases. All three of our patients exhibited signs of increased adrenergic tone, manifested by an elevated heart rate and blood pressure.Also, casesNos. 1 and 3 had evidence of ischemia. These interrelating factors provide a situation ideally suited for treatment with beta blockers and may have accounted for the responsesseen in these patients. Of specialinterest is caseNo. 2. Reentry due to dispersion of refractoriness has been postulated to be a cause of ventricular arrhythmias, syncope, and sudden death in patients with prolonged QT intervals, and propranolol has been successfulin reducing syncopal episodesin these patients5 Although the etiology of the transient QT interval prolongation in caseNo. 2 wasnot clearly determined and may have been related to hypocalcemia, the potential benefits of beta blockade remain. There remains the important issueof safety in using intravenous propranolol in these unstable patients. The safe useof intravenous beta blockade during acute MI has been documented in large, carefully designed studies.Bs 7 However, it is more relevant to this discussionto review the effects of beta blockade in cardiac arrest. There is a common misconception that epinephrine’s efficacy in cardiopulmonary resuscitation dependson beta-adrenergic stimulation of the heart. Animal studies8sg have shown that it is the alpha effect of epinephrine that is important for successful resuscitation. Alpha-receptor stimulation increasesaortic diastolic pressureand redirects flow from low priority tissues(muscularand cutaneouscirculations) to the heart and brain. Therefore, despite the underlying rhythm, the administration of epinephrine is recommended during cardiopulmonary arrest in order to maximize the effects of external cardiac massage.Based on these studies, beta blockade should not interfere with the beneficial actions of epinephrine during cardiopulmonary resuscitation. In Ikram’s series* involving successfully resuscitated patients treated with intravenous proprano101,one patient had an episodeof atrioventricular block, which was well tolerated, and another patient had hypotension, which responded well to epinephrine.’ Ikram’s other two patients did not seem to have any adverse effects from beta blockade. In the only other serieswhich reported control of persistent ventricular fibrillation by propranolol,10the authors used dosesranging from 15 to 22 mg intravenously with prompt, effective suppressionof the ventricular fibrillation. However, one patient died from circulatory failure, leading these investigators to recommend lower dosages. lo In our series, one of our patients exhibited mild hypotension and another developed a significantly reduced cardiac output, though she
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also received intravenous verapamil. Both of these patients responded well to low doses of an inotropic agent. In summary, intravenous propranolol appeared to be quite valuable in our three patients with recurrent lifethreatening ventricular tachyarrhythmias. We feel that patients with cardiac arrest who during resuscitation develop refractory ventricular tachyarrhythmias following cardioversion, should be considered for treatment with intravenous propranolol, particularly in the presence of signs of increased adrenergic tone. However, caution must be employed, since adverse effects can occur. REFERENCES 1.
2.
3.
4. 5. 6.
7.
8.
9.
10.
Ikram H: Propranolol in persistent ventricular fibrillation complicating acute myocardial infarction. AM HEART J 75:795, 1968. Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiologic effects on beta adrenergic receptor stimulation and blockade (Part A). AM HEART J 90:521, 1975. Josephson ME, Horowitz LN, Farshidi A, Kastor JA: Recurrent sustained ventricular tachycardia. Circulation 57:431, 1978. Han J, Moe GK: Non-uniform recovery of excitability in ventricular muscle. Circ Res 14:44, 1964. Garza LA, Vick RL, Nora JJ, McNamara DG: Heritable QT prolongation without deafness. Circulation 41:39, 1970. Hjalmarson A, Herlitz J, Holmberg S, et al: The Goteborg metoprolol trial effects on mortality in acute myocardial infarction. Circulation 67(suppl I):I-26, 1983. Muller HS, Ayres SM, Religa A, Evans RG: Propranolol in the treatment of acute myocardial infarction (effect on myocardial oxygenation and hemodynamics). Circulation 49:1078, 1974. Yakaitis RW, Otto CW, Blitt CD: Relative importance of alpha and beta adrenergic receptors during resuscitation. Crit Care Med 7:293, 1979. Otto CW, Yakaitis RW, Blitt CD: Mechanism of action of epinephrine in resuscitation from asphyxial arrest. Crit Care Med 9:364, 1981. Sloman G, Robinson JS, McLean K: Propranolol in persistent ventricular fibrillation. Br Med J 1:895, 1965.
Rate-dependent, pacemaker-related, concealed ventricular extrasystoles: Entrainment of an ectopic ventricular focus Herman 0. Klein, M.D., Pinhas Sareli, M.D., Elieser Kaplinsky, M.D., and Leo Schamroth, M.D., D.Sc., F.R.C.P. F.R.S.(SA). Haifa,
Israel,
and Johannesburg,
S. Africa.
From the Department of Cardiology, Rambarn Medical Center and Faculty of Medicine, Tech&m-Israel Institute of Technology; and the Department of Medicine, Baragwanatb Hospital and the University of the Witwatersrand. Reprint requests: Herman 0. Klein, M.D., Dept. of Cardiology, Rambam Medical Center, P.O. Box 9602, 31096 Haifa, Israel.
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Most ventricular extrasystoles respond to increasingelectrical pacing rates by decreasingin frequency (“overdrive suppression”).’A paradoxic responseto electrical stimulation in man was first reported in 1976.’ Another case is presented here, where slight increases in the rate of electrical stimulation resulted in the appearance of and increasein the frequency of ventricular extrasystoles. In addition, the manifestation of “concealed bigeminy”3 was also elicited by pacing, the first such case reported in man. Ventricular pacing was instituted at a rate of 83 bpm in a 72-year-old man hospitalized becauseof complete atrioventricular (AV) block. This rate was accompanied by ventricular quadrigeminy-a ventricular extrasystole after every three paced beats. The pacing rate was decreasedto 64 bpm, with the immediate cessationof all ventricular extrasystoles. The top strip of Fig. 1 shows that with a pacing cycle length of more than 0.72 second (rats below 83/min), the ECG was free of extrasystoles. Extrasystoles appeared at a pacing cycle length of 0.72 secondin the form of quadrigeminy (strip 2 of Fig. 1). At a cycle length of 0.68 second(88fmin; strips 3 and 4 of Fig. l), they increasedin frequency, manifesting in the form of bigeminal rhythm. As the cycle length was shortened to 0.64/set (94/min), a ventricular couplet, characterized as two consecutive uniform extrasystoles, appeared (top strip of Fig. 2), in addition to the bigeminal rhythm. When the cycle length was again increased to 0.72 and 0.76 second(rates of 83 and 79/min, respectively; strips 2 and 3 of Fig. 2), sustained bigeminy persisted. Finally, as the pacing cycle length wasincreasedto 0.90 second(67/min), the extrasystoles decreasedin frequency, with five pacemaker beats between extrasystoles (strip 4). These extrasystolesdisappearedcompletely with a further increasein the cycle length (strip 5). The sequencesdescribed above repeated themselves during 30 minutes of observation, ever so slight variations in the rate of stimulation repeatedly producing a changein the manifest frequency of the extrasystoles. The extrasystoles in Fig. 2 varied slightly in morphology; suchchanges in morphology are not unusual in unifocal extrasystoles, especially when the basic rate and coupling intervals change. AS long as bigeminy was manifest, the coupling interval of the extrasystoles changed in a direct relationship to the pacing interval (strips 2 and 3 of Fig. 2). At a cycle length of 0.64 second (top strip of Fig. 2), the coupling interval ranged from 0.52 to 0.56 second.As the cycle length was increased to 0.72 to 0.76 second, the coupling interval also increased to 0.60 and 0.68 second, respectively. Three major mechanismshave been proposed for the genesisof ventricular extrasystoles that are coupled t,o normal beats: (1) entrainment of an automatic focus by the preceding normal impulse3,“;(2) reentry of a normal impulse through an area of depressed conductions; (3) triggered afterdepolarizations The combination of the three salient features of this case (paradoxic responseto pacing, manifestation of concealed extrasystoles, and shortening of the coupling interval with faster pacing
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cardia was no longer inducible, either by atrial pacing (rate 96/min) or right atrial extrastimulus. Atria1 pacing at a higher heart rate (lOO/min) was still able to induce only very short bursts of tachycardia. Many authors5 have reported that Am, given intravenously during EPS, did not significantly change ventricular and accessory Kent-like bundle refractoriness. In contrast, its main effect is on the AV node in prolonging refractory periods and conduction time. Lengthening of the conduction time through the retrograde limb of the reentry circuit, as we have achieved in our case, giving Am as an intravenous bolus, may be suggestive of the presence of an accessory pathway with nodal-like property. As a further proof of the drug efhcacy, a continuous 24-hour ECG recording was obtained after 4 weeks of oral treatment with Am (400 mg/day). The continuous ECG recording did not reveal any episode of AVNRT. Therefore, the role of intravenous and oral Am in the control of incessant AVNRT should be critically evaluated. REFERENCES
1. Coumel P, Attuel P, Leclerq JF: Permanent form of junctional reciprocating tachycardia: Mechanism, clinical and therapeutic implications. In Narula OS, editor: Cardiac arrhvthmias; electrophysiology, diagnosis and management. Baltimore, 1979, The Williams and Wilkins Co. D 347. 2. Sung RJ, Waxman HL, Saksena S, Juma Z: Sequence of retrograde atria1 activation in patients with dual atrioventricular nodal pathways. Circulation 64:1059, 1981. 3. Farre J, Ross D, Wiener I, Bar FW, Vanagt EJ, Wellens HJJ: Reciprocal tachycardia using accessory pathways with long conduction times. Am J Cardiol44:1099, 1979. 4. Gruppo di Studio di Elettrofisiologia delle Aritmie: Protocollo di studio elettrofisiologico della sindrome di WPW. G Ital Cardiol 7:740, 1977. 5. Rowland E, Krikler DM: Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias. Br Heart J 44:82, 1980.
Intravenous propranolol in the treatment repetitive ventricular tachyarrhythmias during resuscitation from sudden death
of
JamesR. Mason, M.D., Joseph C. Marek, M.D. Henry S. Loeb, M.D., and Patrick J. Scanlon, M.D. Maywood
and Hines,
Ill.
We have observed dramatic improvement shortly after administering intravenous propranolol in the setting of recurrent ventricular tachyarrhythmias during resuscitation from sudden cardiac death. Though this application of beta blockers was reported when propranolol first became available,’ the indications for their use in this From the Department of Medicine, Section of Cardiology, Loyola University Medical Center; and Hines Veterans Administration Hospital. Reprint requests: James R. Mason, M.D., Section of Cardiology, 2160 South First Ave., Maywood, IL 60153.
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situation remain unclear. This report contains our experience with three casesfollowed by a discussionof possible mechanismsand clinical profiles of the patient most likely to benefit with intravenous therapy. Cam No. 1. This 66-year-old man with diabetes melhtus, rheumatoid arthritis, and a prior cerebrovascular accident denied any cardiac symptoms. A routine ECG performed prior to elbow surgery revealed an old inferior wall myocardial infarction (MI). A few months later his ECG showedevidence of a recent anterior wall infarction, even though he had not experienced interim symptoms.A thallium threadmill test was ordered to assessthe presence of jeopardized myocardium. Three minutes into the study the patient exhibited 2 mm of ST segmentdepression in associationwith ventricular triplets, in the absence of symptoms. The test was terminated on the basisof his ventricular arrhythmias, and within a few minutes after cessationof exercise the patient demonstrated sustained ventricular tachycardia. He remained asymptomatic and maintained a normal blood pressure. A 100 mg bolus of lidocaine was given, but his rhythm deteriorated to ventricular flutter, with lossof consciousness and no palpable pulse. Cardioversion was promptly delivered, resulting in sinus tachycardia. However, the rhythm quickly deteriorated into sinus tachycardia with brief runs of nonsusmined ventricular tachycardia. His blood pressure was 220/106 mm Hg. He regained consciousnesswith spontaneous,normal respirations, and a seconddoseof lidocaine, 75 mg intravenously, wasgiven. Approximately 5 minutes after his initial cardioversion, he developed ventricular flutter (Fig. 1). The subsequentcoursewasone of repeated cardioversion to sinustachycardia with hypertension followed by rapid deterioration to sustained ventricular tachycardia, followed by ventricular flutter. During the next 15 minutes, cardiopulmonary resuscitation was carried out, including intubation, chest conpression,and 1 mg intravenous epinephrine given to support circulation after unsuccessfulcardioversions. Normal arterial blood gases were obtained after administration of oxygen and sodium bicarbonate, A lidocaine infusion at 4 mg/min wasstarted and bretylium, 500mg intravenously over 10 minutes, was given without significant effect. Over the next 20 minutes the patient received 500mg of procainamide with continuous infusion at 4 mg/min. This regimen decreasedthe rate of the ventricular tachycardia with a concomitant 25% widening of the QRS complex; it did not prevent the recurrence of ventricular flutter, which becamemore resistant to cardioversion, performed at least 10 times. At this time, propranolol, 2 mg intravenously wasgiven over 3 minutes, during which the patient again developed ventricular flutter. On cardioversion, he converted to normal sinusrhythm and had a normal blood pressure (Fig. 1). No complex ventricular arrhythmias were seenin the following hour. Repeat ECG waswithout significant changes.Cardiac catheterization and angiography were performed the following day. which demonstrated severe three-vesselcoronary artery diseaseand an ejection fraction of 25% . Case No. 2. The patient is a 59-year-old man with a
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Fig. 1. The first two panels demonstrate the frequent episodesof nonsustainedventricular tachycardia accompaniedby sinus tachycardia, hypertension, and ST segmentdepression.The second panel shows deterioration to ventricular flutter. Panel three exhibits the slowedventricular tachycardia and widened QRS following procainamide, and the fourth panel was obtained following intravenous propranolol administration.
history of an old MI. He had been feeling well without symptoms of chest pain, dyspnea, palpitations, or syncope, and he was not taking any medications. On the day of admission,he developed the suddenonset of diaphoresis followed by loss of consciousness.He arrived in the emergency room in cardiac arrest and cardiopulmonary resuscitation was performed. The first rhythm recorded was ventricular fibrillation, which on cardioversion converted to a wide QRS tachycardia, rate of 150/min, with a systolic blood pressure of 190 mm Hg. This rhythm spontaneously degenerated to ventricular fibrillation, which was again cardioverted to a wide QRS tachycardia accompaniedby an elevated blood pressure.The patient’s rhythm degeneratedinto ventricular fibrillation following eachcardioversion, and in someinstanceswasprecededby a polymorphic ventricular tachycardia (Fig. 2). During the courseof an hour the patient wasintubated and received 100% oxygen and sodiumbicarbonate, resulting in correction of his initial hypoxia and acidosis. He required cardiopulmonary resuscitation (CPR) and received epinephrine during periods when cardioversion did not successfully convert his ventricular fibrillation. Lidocaine wasgiven with a loading doseof 200mg over 15 minutes in addition to a continuous infusion at 3 mglmin. Following lidocaine, the patient received bretylium, 500 mg intrave-
nously over 10 minutes and a continuous infusion of 2 mg/min, and 10 minutes later an additional 100 mg bolus of lidocaine. His arrhythmias were not altered by these interventions, and he continued to have recurrent ventricular fibrillation, following short periods in a wide QRS tachycardia with hypertension. After 1 hour the patient received his eighteenth cardioversion and he wasgiven 3 mg of propranolol intravenously over 5 minutes. There were no further episodesof ventricular fibrillation over the next few hours. He was transferred to the coronary care unit (CCU), where he was noted to have converted his wide QRS tachycardia to sinus rhythm, associatedwith mild hypotension. Subsequent evaluation disclosed a mild reduction in the patient’s ionized serum calcium, while the rest of his electrolytes, including potassium and magnesium,were normal. An ECG in the CCU demonstrated new prolongation of the QT interval. Serial cardiac enzymes and a technetium pyrophosphate scan were negative. Calcium supplements were given and after a slow recovery, the patient was gradually weaned from all drugs. His only medication at dischargewasa beta blocker. A radionuclide ventriculogram revealed an ejection fraction of 24% and ECG prior to dischargedemonstrated a normal QT interV&d.
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Fig. 2. The first two panels demonstrate the recurring episodesof uniform ventricular tachycardia (top panel) and polymorphous ventricular tachycardia (middle panel) which precededventricular fibrillation. The bottom panel showsthe sinus rhythm and prolonged QT interval following intravenous propranolol
administration.
Fig. 3. The top panel shows an episode of atria1 fibrillation with rapid ventricular responseseen following cardioversion from ventricular tachycardia. The middle panel demonstratesthe rapid, uniform ventricular tachycardia. The third panel was obtained following administration of 5 mg of intravenous propranolol.
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Case NO. 3. This 72-year-old female had no prior cardiovascular problemsexcept for hypertension. She had experienced exertional angina intermittently, but did not seek medical attention. On the day of admission, she experienced chest pain while shopping and fell to the floor. Upon presentation to the emergencyroom, she was in ventricular fibrillation. Cardioversion resulted in supraventricular tachycardia, but frequent episodesof ventricular tachycardia occurred. The ventricular tachycardia was a rapid, unifocal rhythm, with a rate of 22O/min, during which no pulse was palpable. Cardioversion was performed numerous times and resulted in supraventricular tachycardia and episodesof atria1 fibrillation, with ventricular rates of 140to 17O/min (Fig. 3). While her heart wasin a supraventricular rhythm, the systolic blood pressurewas consistently in excessof 200 mm Hg. Over the first hour, the patient received full loading dosesof lidocaine with continuous infusion at 2 mg/min, followed by bretylium and then procainamide, and she required 14 cardioversions. There was no significant change in the pattern of her recurrent ventricular tachycardia. During this time, she received 2 mg of intravenous verapamil in an attempt to better control her supraventricular tachycardia and severe hypertension. Approximately 80 minutes after her arrival, intravenous propranolol was administered, 0.5 mg/min, to a total dose of 5 mg; there were no further episodesof ventricular tachycardia. The patient was transferred to the CCU in sinus rhythm at approximately 6O/min, and her blood pressurewas 130/160 mm Hg. Subsequent hemodynamic measurementsrevealed a pulmonary capillary wedgepressure of 18 mm Hg and a cardiac output of 2.5 L/min. The patient’s hemodynamicsimproved and stabilized over the following 24 hours on dobutamine infusion at 5 pg/kg/min. The ECG revealed minor nonspecific ST abnormalities and was otherwise normal. The routine laboratory data including electrolytes and cardiac enzymes were normal and a radionuclide ventriculogram revealed an ejection fraction of 50%. Discussion. These three casescontain a pattern of “malignant,” repetitive rhythms unresponsiveto multiple antiarrhythmic agents and general supportive measures. In addition, all three casesdemonstrated clinical evidence of heightened sympathetic activity. In each case,prompt suppression of recurrent ventricular tachyarrhythmias followed the administration of intravenous propranolol, and it seemslikely that beta blockade provided the major antiarrhythmic mechanism. Beta receptor stimulation enhances pacemaker activity in cardiac fibers, and enhanced activity of latent pacemaker sites in the ventricle may result in ventricular arrhythmias.2 However, reentry is a more common mechanism for recurrent, sustained ventricular tachycardia, and nonuniform lengthening or shortening of refractory periods, referred to as dispersion, provides the proper substrate3s4Catecholamines can produce dispersion of refractoriness in patients with coronary artery diseaseor in other cardiac diseasesby shortening the refractory period in somefibers but not in adjacent fibers, thereby establishinga reentrant
American
July, 1985 Heart Journal
pathway and the potential for ventricular tachyarrhythmiasZ4 Adrenergic stimulation may also initiate and worsenischemia.Therefore, increasedsympathetic activity may establisha cycle of,worseningischemia,ventricular arrhythmias, and cardiac arrest, which then results in a further increase in adreneigic tone and more refractory arrhythmias. This cycle may be perpetuated by the exogenous catecholamines frequently given during cardiac pulmonary resuscitation, which may have been a factor in our cases. All three of our patients exhibited signs of increased adrenergic tone, manifested by an elevated heart rate and blood pressure.Also, casesNos. 1 and 3 had evidence of ischemia. These interrelating factors provide a situation ideally suited for treatment with beta blockers and may have accounted for the responsesseen in these patients. Of specialinterest is caseNo. 2. Reentry due to dispersion of refractoriness has been postulated to be a cause of ventricular arrhythmias, syncope, and sudden death in patients with prolonged QT intervals, and propranolol has been successfulin reducing syncopal episodesin these patients5 Although the etiology of the transient QT interval prolongation in caseNo. 2 wasnot clearly determined and may have been related to hypocalcemia, the potential benefits of beta blockade remain. There remains the important issueof safety in using intravenous propranolol in these unstable patients. The safe useof intravenous beta blockade during acute MI has been documented in large, carefully designed studies.Bs 7 However, it is more relevant to this discussionto review the effects of beta blockade in cardiac arrest. There is a common misconception that epinephrine’s efficacy in cardiopulmonary resuscitation dependson beta-adrenergic stimulation of the heart. Animal studies8sg have shown that it is the alpha effect of epinephrine that is important for successful resuscitation. Alpha-receptor stimulation increasesaortic diastolic pressureand redirects flow from low priority tissues(muscularand cutaneouscirculations) to the heart and brain. Therefore, despite the underlying rhythm, the administration of epinephrine is recommended during cardiopulmonary arrest in order to maximize the effects of external cardiac massage.Based on these studies, beta blockade should not interfere with the beneficial actions of epinephrine during cardiopulmonary resuscitation. In Ikram’s series* involving successfully resuscitated patients treated with intravenous proprano101,one patient had an episodeof atrioventricular block, which was well tolerated, and another patient had hypotension, which responded well to epinephrine.’ Ikram’s other two patients did not seem to have any adverse effects from beta blockade. In the only other serieswhich reported control of persistent ventricular fibrillation by propranolol,10the authors used dosesranging from 15 to 22 mg intravenously with prompt, effective suppressionof the ventricular fibrillation. However, one patient died from circulatory failure, leading these investigators to recommend lower dosages. lo In our series, one of our patients exhibited mild hypotension and another developed a significantly reduced cardiac output, though she
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Brief Communications
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also received intravenous verapamil. Both of these patients responded well to low doses of an inotropic agent. In summary, intravenous propranolol appeared to be quite valuable in our three patients with recurrent lifethreatening ventricular tachyarrhythmias. We feel that patients with cardiac arrest who during resuscitation develop refractory ventricular tachyarrhythmias following cardioversion, should be considered for treatment with intravenous propranolol, particularly in the presence of signs of increased adrenergic tone. However, caution must be employed, since adverse effects can occur. REFERENCES 1.
2.
3.
4. 5. 6.
7.
8.
9.
10.
Ikram H: Propranolol in persistent ventricular fibrillation complicating acute myocardial infarction. AM HEART J 75:795, 1968. Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiologic effects on beta adrenergic receptor stimulation and blockade (Part A). AM HEART J 90:521, 1975. Josephson ME, Horowitz LN, Farshidi A, Kastor JA: Recurrent sustained ventricular tachycardia. Circulation 57:431, 1978. Han J, Moe GK: Non-uniform recovery of excitability in ventricular muscle. Circ Res 14:44, 1964. Garza LA, Vick RL, Nora JJ, McNamara DG: Heritable QT prolongation without deafness. Circulation 41:39, 1970. Hjalmarson A, Herlitz J, Holmberg S, et al: The Goteborg metoprolol trial effects on mortality in acute myocardial infarction. Circulation 67(suppl I):I-26, 1983. Muller HS, Ayres SM, Religa A, Evans RG: Propranolol in the treatment of acute myocardial infarction (effect on myocardial oxygenation and hemodynamics). Circulation 49:1078, 1974. Yakaitis RW, Otto CW, Blitt CD: Relative importance of alpha and beta adrenergic receptors during resuscitation. Crit Care Med 7:293, 1979. Otto CW, Yakaitis RW, Blitt CD: Mechanism of action of epinephrine in resuscitation from asphyxial arrest. Crit Care Med 9:364, 1981. Sloman G, Robinson JS, McLean K: Propranolol in persistent ventricular fibrillation. Br Med J 1:895, 1965.
Rate-dependent, pacemaker-related, concealed ventricular extrasystoles: Entrainment of an ectopic ventricular focus Herman 0. Klein, M.D., Pinhas Sareli, M.D., Elieser Kaplinsky, M.D., and Leo Schamroth, M.D., D.Sc., F.R.C.P. F.R.S.(SA). Haifa,
Israel,
and Johannesburg,
S. Africa.
From the Department of Cardiology, Rambarn Medical Center and Faculty of Medicine, Tech&m-Israel Institute of Technology; and the Department of Medicine, Baragwanatb Hospital and the University of the Witwatersrand. Reprint requests: Herman 0. Klein, M.D., Dept. of Cardiology, Rambam Medical Center, P.O. Box 9602, 31096 Haifa, Israel.
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Most ventricular extrasystoles respond to increasingelectrical pacing rates by decreasingin frequency (“overdrive suppression”).’A paradoxic responseto electrical stimulation in man was first reported in 1976.’ Another case is presented here, where slight increases in the rate of electrical stimulation resulted in the appearance of and increasein the frequency of ventricular extrasystoles. In addition, the manifestation of “concealed bigeminy”3 was also elicited by pacing, the first such case reported in man. Ventricular pacing was instituted at a rate of 83 bpm in a 72-year-old man hospitalized becauseof complete atrioventricular (AV) block. This rate was accompanied by ventricular quadrigeminy-a ventricular extrasystole after every three paced beats. The pacing rate was decreasedto 64 bpm, with the immediate cessationof all ventricular extrasystoles. The top strip of Fig. 1 shows that with a pacing cycle length of more than 0.72 second (rats below 83/min), the ECG was free of extrasystoles. Extrasystoles appeared at a pacing cycle length of 0.72 secondin the form of quadrigeminy (strip 2 of Fig. 1). At a cycle length of 0.68 second(88fmin; strips 3 and 4 of Fig. l), they increasedin frequency, manifesting in the form of bigeminal rhythm. As the cycle length was shortened to 0.64/set (94/min), a ventricular couplet, characterized as two consecutive uniform extrasystoles, appeared (top strip of Fig. 2), in addition to the bigeminal rhythm. When the cycle length was again increased to 0.72 and 0.76 second(rates of 83 and 79/min, respectively; strips 2 and 3 of Fig. 2), sustained bigeminy persisted. Finally, as the pacing cycle length wasincreasedto 0.90 second(67/min), the extrasystoles decreasedin frequency, with five pacemaker beats between extrasystoles (strip 4). These extrasystolesdisappearedcompletely with a further increasein the cycle length (strip 5). The sequencesdescribed above repeated themselves during 30 minutes of observation, ever so slight variations in the rate of stimulation repeatedly producing a changein the manifest frequency of the extrasystoles. The extrasystoles in Fig. 2 varied slightly in morphology; suchchanges in morphology are not unusual in unifocal extrasystoles, especially when the basic rate and coupling intervals change. AS long as bigeminy was manifest, the coupling interval of the extrasystoles changed in a direct relationship to the pacing interval (strips 2 and 3 of Fig. 2). At a cycle length of 0.64 second (top strip of Fig. 2), the coupling interval ranged from 0.52 to 0.56 second.As the cycle length was increased to 0.72 to 0.76 second, the coupling interval also increased to 0.60 and 0.68 second, respectively. Three major mechanismshave been proposed for the genesisof ventricular extrasystoles that are coupled t,o normal beats: (1) entrainment of an automatic focus by the preceding normal impulse3,“;(2) reentry of a normal impulse through an area of depressed conductions; (3) triggered afterdepolarizations The combination of the three salient features of this case (paradoxic responseto pacing, manifestation of concealed extrasystoles, and shortening of the coupling interval with faster pacing