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Propranolol in persistent ventricular fibrillation complicating acute myocardial infarction
Propranolol complicating
in persistent ventricular fibrillation acute myocardial infarction
H. Ikram, M.B., M.R.C.P., London, England
V
M.R.C.P.E.,
entricular fibrillation can usually be terminated by electrical defibrillation following adequate oxygenation, efficient cardiac massage, and the correction of metabolic acidosis. In a small number, particularly those with severe cardiac damage from coronary artery disease, the arrhythmia tends to recur after minutes or hours despite meticulous attention to oxygenation and acid-base balance. In this grave situation, recourse is made to antiarrhythmic drugs such as quinidine, procaine amide, and lidocaine, but successful control of the arrhythmia is infrequent. Sloman and associates6 reported successful control of persistent ventricular fibrillation with propranolol administered by the intravenous route. In the dosage employed by these authors, the adverse effects of this drug on myocardial contractility may have become a serious problem, and the authors attribute one death in their series to this factor. The purpose of this communication is to describe the successful control of persistent ventricular fibrillation occurring in four patients with acute myocardial infarction with intravenous propranolol. The use of l/10 the dose recommended by Sloman and associate9 have enabled us to avoid the undesirable side effect on myocardial contractility while retaining the antiarrhythmic effect. From the Charing Cross Received for publication
795
Hospital, London, June 19, 1967.
F.A.G.S.
Case reports Case 1. J. G., a 54-year-old Canadian business man, was admitted to the hospital with a recent cardiac infarction. The electrocardiogram (ECG) showed the pattern of a massive, fresh anterior infarction. Shortly after admission to the ward, he collapsed. Closed-chest cardiac massage and emergency ventilation were started immediately. Ventricular fibrillation was present on the ECG (Fig. 1). A direct current (D.C.) shock of 200 joules was administered. Following the shock, a ventricular tachycardia developed which reverted to ventricular fibrillation within a few minutes. An infusion of 8.4 per cent NaHC03 was commenced and 100 ml. administered before defibrillation was attempted again. A shock of 300 joules was applied. The fibrillation reverted to a ventricular tachycardia for a few minutes before recurring. The above sequence of events was repeated after two more shocks at 400 joules. A dose of 1 mg. of propranolol was given intravenously and a further shock applied. Following this, a supraventricular tachycardia developed which was sufficient to produce a blood pressure of 100/60. The patient regained consciousness and began to object to the endotracheal tube. Intravenous morphine was given to produce an adequate level of sedation. A little later, sinus rhythm occurred spontaneously. Apart from retrograde amnesia for the duration of the episode, the mental state was quite clear. The postresuscitation ECG showed the changes of an extensive acute anterior infarction. The peak serum glutamic oxalacetic transaminase (SGOT) was 272 Sigma-Frankel units. The patient’s recovery was complicated by congestive cardiac failure which responded to digitalis and diuretics. He has since returned to work in Canada. Case 2. E. G., a .54-year-old man, collapsed in the Casualty Department. External cardiac massage and emergency ventilation were commenced immediately. An ECG showed ventricular fibrillation.
W. C. 2, England
796
Am. Heart
Ikram
Jww.
Fig. 1. ECG’s in Cases 1, 2, and 3 taken just before and shortly in a stable rhythm. Case 2 shows complete heart block which
An infusion of 8.4 per cent sodium bicarbonate was commenced and a total of 250 ml. infused. Two D.C. shocks of 100 and 300 joules were applied to the chest. After each shock, a rhythm capable of producing a pulse at the wrist resulted, but relapsed again into ventricular fibrillation after a few minutes. A dose of 100 mg. of procaine amide was given intravenously, and two further shocks were applied after an interval of ten minutes. The same sequence of arrhythmias was repeated: 1 mg. of propranolol was given intravenously and five minutes later, a further D.C. shock was applied. This resulted in complete A-V block with a ventricular rate sufficient to produce a blood pressure of 100/60 without pressor drugs. The patient rapidly recovered consciousness. The ECG showed an extensive acute posterior infarct. The peak SGOT was 230 Sigma-Frankel units. The patient regained sinus rhythm in about half an hour after the successful defibrillation. His recovery was complicated by congestive failure which responded to diuretics and digitalis. He has now been back at work for six months. Case 3. J. T., a 64-year-old man with a previous history of chronic bronchitis, was admitted to the ward with severe cardiac pain. An ECG showed a massive posterior infarction. Shortly after, he collapsed. Cardiac arrest due to ventricular fibrillation was diagnosed and emergency ventilation and closed chest cardiac massage was commenced. Intravenous infusion of 8.4 per cent sodium bicarbonate was started and a total of 200 ml. administered. Three shocks at 200, 2.50, and 300 joules were administered. After each shock, the ventricular fibrillation reverted to supraventricular rhythm for short periods before relapsing again. A dose of 1 mg. of propranolol was given intravenously and a fourth shock of 400 joules was applied five minutes later. A stable supraventricular tachycardia capable of generating a blood pressure of 90/60 resulted. In view of the
after the final D.C. defibrillation resolved very shortly after.
which
J. 1968
resulted
complicating chronic bronchitis and emphysema, he was ventilated for 12 hours by means of a Bird Mark 8 ventilator. The peak level of SGOT was 300 Sigma-Frankel units. His recovery was complicated by the development of congestive cardiac failure which responded to digitalis and diuretic therapy. He is now back to an active life, though he still requires digitalis and diuretics. Case 4. E. H., a 73-year-old woman, was admitted to the hospital with the changes of a massive posterior infarction. The peak SGOT was 320 SigmaFrankel units. She appeared to be making a satisfactory recovery when she developed a further extension of her cardiac infarction. She was making a slow recovery from this when a further episode of chest pain was followed by a cardiac arrest in ventricular fibrillation. Emergency ventilation and closed-chest massage were commenced immediately. An intravenous infusion of 8.4 per cent NaHC03 was commenced and she was given 150 ml. Two shocks at 250 and 300 joules were applied afterward. In both cases, the shock resulted in a ventricular tachycardia which rapidly relapsed into ventricular fibrillation. A dose of 1 mg. of propranolol was given intravenously and a further shock of 300 joules applied. The same sequence of events recurred. After a further delay of three to four minutes, a further shock was applied. This resulted in a stable rhythm, though the gross deformity of the ECG due to repeated infarctions made it difficult to diagnose the arrhythmia more precisely. A blood pressure of 60/40 resulted and this was boosted to 100/60 by means of an infusion of epinephrine. The blood pressure, however, gradually declined and pulmonary edema developed. Despite all therapy, the patient died 14 hours later. Postmortem examination showed extensive infarction of the left ventricle with only about g of the wall uninvolved by the infarction.
Volume Number
75 6
Propranolol
Discussion The effects of adrenaline on the irritability and contractility of the myocardium are mediated by fi-adrenergic receptors. Many cardiac arrhythmias are adrenergically induced or sustained. Arrhythmias due to cardiac glycosides also have adrenergic mechanisms. The blocking of fl-adrenergic receptors can correct such arrhythmias. Besterman and Friedlander,’ Rowlands and associates,5 and Stock and Dale7 have confirmed the clinical value of ,6-adrenergic blocking agents in various types of arrhythmia. Unfortunately, however, this beneficial action on disorders of rhythm is accompanied by decrease in coronary blood flow and impairment of the force of myocardial contraction, leading to cardiac failure .3,4,7 Thus, great care is required in the use of these drugs in situations where severe myocardial damage exists and it is of vital importance to define as clearly as possible the minimum effective therapeutic dose. These factors are of particular importance in the treatment of persistent ventricular failure complicating myocardial infarction, since extensive muscle necrosis is invariably present. In the only previous paper on the control of persistent ventricular fibrillation by propranolol the authors used doses ranging from 15 to 22 mg. intravenously.6 The cardiodepressant effects of the drug were thought to be responsible for the death of one of their three patients. This led them to recommend an upper limit of 10 mg. intravenously. Our experience suggests that 10 mg. may be unnecessarily high. In all four cases, control of the arrhythmia was achieved by 1 mg. intravenously. In the patients who survived, congestive cardiac failure requiring digitalis and diuretics developed shortly after resuscitation. These patients may well not have survived if larger doses of propranolol had been used. The fact that much smaller intravenous doses of propranolol than previously recommended can be equally effective has been recognized and discussed at a recent symposium.* Our high success rate in controlling this grave complication of acute myocardial infarction in all the cases in which pro-
complicating
acute myocardial
infarction
797
pranolol was used is almost certainly fortuitous. There will be some cases in which neither propranolol nor any other drug in safe doses will control the arrhythmia. The purpose of this paper is to indicate the usefulness and “safe” dose of propranolol in this grave situation and the success rate is meaningful only in this context. The point may be made that the last D.C. shock may well have terminated the arrhythmia without the need for propranolol. In persistent ventricular fibrillation, it is possible to reverse the fibrillation in the majority of cases. The crux of the problem is to maintain the resulting viable rhythm without allowing it to relapse again into ventricular fibrillation after a short period. It is for this specific indication that propranolol is advised. A trial of propranolol is well worth while in this situation since the only other recommended line of therapy seems to be internal cardiac massage and defibrillation.2 This course itself has a great many disadvantages and seems to us to be far more dangerous than the administration of propranolol. Even when the therapeutic aim, namely, the termination of the arrhythmia, has been achieved, a certain proportion of the patients will die of myocardial inadequacy, as in Case 4 of this series. The massive degree of infarction found at postmortem examination confirmed that this patient had died of “pump failure” and that the arrhythmia had been a terminal event. The control of the disorder of rhythm could not be expected to alter the prognosis in such cases. Summary Four cases of persistent ventricular fibrillation complicating acute myocardial infarction are described. In each case, control of the arrhythmia was achieved by the intravenous administration of 1 mg. of propranolol. In this dose, this drug can be used with reasonable safety in controlling a lethal arrhythmia in patients suffering from extensive fresh myocardial infarctions. The author J. L. Edwards
tative
wishes to thank Drs. T. Mitchell and for their prompt initiation of resuscimeasures; the Charing Cross Hospital Clinical
798
Am. Heart J. June, 1968
Ikrclm
Research Committee for financial help, Miss A. Smith, Miss I. L. Wood, and Miss C. S. March for the electrocardiography and monitoring of these patients, and Mrs. J. Caudle for secretarial assistance.
4.
Redding, 1’. T., and Rees, J. R.: Myocardial vascular reactivity, Lancet 1:548, 1966. 5. Rowlands, D. J., Howitt, G., and Markman, P.: Propranolol (Inderal) in disturbances of cardiac rhythm, Brit: M. J. 1:891, 1965. 6. Sloman. G.. Robinson. I. S.. and McLean. K.: Propranolol (Inderal) in persistent ventricular fibrillation, Brit. M. J. 1:895, 1965. 7. Stock, J. P. P., and Dale, N.: Beta-adrenergic receptor blockade in cardiac arrhythmias, Brit. M. J. 2:1230, 1963. 8. Stephen, S. A.: Unwanted effects of propranolol (discussion), Am. J. Cardiol. 18:468, 1966. II
REFERENCES 1.
2. 3.
Besterman, E. M. M., and Friedlander, D. H.: Clinical experiences with propranolol, Postgrad. M. J. 41:526, 1965. Harley, H. R. S.: Reflections on cardiopulmonary resuscitation, Lancet 2:1, 1966. Parrett, J. R., and Grayson, J,: Myocardial vascular reactivity after beta-adrenergic blockade, Lancet 1:338, 1966.
in persistent ventricular fibrillation acute myocardial infarction
H. Ikram, M.B., M.R.C.P., London, England
V
M.R.C.P.E.,
entricular fibrillation can usually be terminated by electrical defibrillation following adequate oxygenation, efficient cardiac massage, and the correction of metabolic acidosis. In a small number, particularly those with severe cardiac damage from coronary artery disease, the arrhythmia tends to recur after minutes or hours despite meticulous attention to oxygenation and acid-base balance. In this grave situation, recourse is made to antiarrhythmic drugs such as quinidine, procaine amide, and lidocaine, but successful control of the arrhythmia is infrequent. Sloman and associates6 reported successful control of persistent ventricular fibrillation with propranolol administered by the intravenous route. In the dosage employed by these authors, the adverse effects of this drug on myocardial contractility may have become a serious problem, and the authors attribute one death in their series to this factor. The purpose of this communication is to describe the successful control of persistent ventricular fibrillation occurring in four patients with acute myocardial infarction with intravenous propranolol. The use of l/10 the dose recommended by Sloman and associate9 have enabled us to avoid the undesirable side effect on myocardial contractility while retaining the antiarrhythmic effect. From the Charing Cross Received for publication
795
Hospital, London, June 19, 1967.
F.A.G.S.
Case reports Case 1. J. G., a 54-year-old Canadian business man, was admitted to the hospital with a recent cardiac infarction. The electrocardiogram (ECG) showed the pattern of a massive, fresh anterior infarction. Shortly after admission to the ward, he collapsed. Closed-chest cardiac massage and emergency ventilation were started immediately. Ventricular fibrillation was present on the ECG (Fig. 1). A direct current (D.C.) shock of 200 joules was administered. Following the shock, a ventricular tachycardia developed which reverted to ventricular fibrillation within a few minutes. An infusion of 8.4 per cent NaHC03 was commenced and 100 ml. administered before defibrillation was attempted again. A shock of 300 joules was applied. The fibrillation reverted to a ventricular tachycardia for a few minutes before recurring. The above sequence of events was repeated after two more shocks at 400 joules. A dose of 1 mg. of propranolol was given intravenously and a further shock applied. Following this, a supraventricular tachycardia developed which was sufficient to produce a blood pressure of 100/60. The patient regained consciousness and began to object to the endotracheal tube. Intravenous morphine was given to produce an adequate level of sedation. A little later, sinus rhythm occurred spontaneously. Apart from retrograde amnesia for the duration of the episode, the mental state was quite clear. The postresuscitation ECG showed the changes of an extensive acute anterior infarction. The peak serum glutamic oxalacetic transaminase (SGOT) was 272 Sigma-Frankel units. The patient’s recovery was complicated by congestive cardiac failure which responded to digitalis and diuretics. He has since returned to work in Canada. Case 2. E. G., a .54-year-old man, collapsed in the Casualty Department. External cardiac massage and emergency ventilation were commenced immediately. An ECG showed ventricular fibrillation.
W. C. 2, England
796
Am. Heart
Ikram
Jww.
Fig. 1. ECG’s in Cases 1, 2, and 3 taken just before and shortly in a stable rhythm. Case 2 shows complete heart block which
An infusion of 8.4 per cent sodium bicarbonate was commenced and a total of 250 ml. infused. Two D.C. shocks of 100 and 300 joules were applied to the chest. After each shock, a rhythm capable of producing a pulse at the wrist resulted, but relapsed again into ventricular fibrillation after a few minutes. A dose of 100 mg. of procaine amide was given intravenously, and two further shocks were applied after an interval of ten minutes. The same sequence of arrhythmias was repeated: 1 mg. of propranolol was given intravenously and five minutes later, a further D.C. shock was applied. This resulted in complete A-V block with a ventricular rate sufficient to produce a blood pressure of 100/60 without pressor drugs. The patient rapidly recovered consciousness. The ECG showed an extensive acute posterior infarct. The peak SGOT was 230 Sigma-Frankel units. The patient regained sinus rhythm in about half an hour after the successful defibrillation. His recovery was complicated by congestive failure which responded to diuretics and digitalis. He has now been back at work for six months. Case 3. J. T., a 64-year-old man with a previous history of chronic bronchitis, was admitted to the ward with severe cardiac pain. An ECG showed a massive posterior infarction. Shortly after, he collapsed. Cardiac arrest due to ventricular fibrillation was diagnosed and emergency ventilation and closed chest cardiac massage was commenced. Intravenous infusion of 8.4 per cent sodium bicarbonate was started and a total of 200 ml. administered. Three shocks at 200, 2.50, and 300 joules were administered. After each shock, the ventricular fibrillation reverted to supraventricular rhythm for short periods before relapsing again. A dose of 1 mg. of propranolol was given intravenously and a fourth shock of 400 joules was applied five minutes later. A stable supraventricular tachycardia capable of generating a blood pressure of 90/60 resulted. In view of the
after the final D.C. defibrillation resolved very shortly after.
which
J. 1968
resulted
complicating chronic bronchitis and emphysema, he was ventilated for 12 hours by means of a Bird Mark 8 ventilator. The peak level of SGOT was 300 Sigma-Frankel units. His recovery was complicated by the development of congestive cardiac failure which responded to digitalis and diuretic therapy. He is now back to an active life, though he still requires digitalis and diuretics. Case 4. E. H., a 73-year-old woman, was admitted to the hospital with the changes of a massive posterior infarction. The peak SGOT was 320 SigmaFrankel units. She appeared to be making a satisfactory recovery when she developed a further extension of her cardiac infarction. She was making a slow recovery from this when a further episode of chest pain was followed by a cardiac arrest in ventricular fibrillation. Emergency ventilation and closed-chest massage were commenced immediately. An intravenous infusion of 8.4 per cent NaHC03 was commenced and she was given 150 ml. Two shocks at 250 and 300 joules were applied afterward. In both cases, the shock resulted in a ventricular tachycardia which rapidly relapsed into ventricular fibrillation. A dose of 1 mg. of propranolol was given intravenously and a further shock of 300 joules applied. The same sequence of events recurred. After a further delay of three to four minutes, a further shock was applied. This resulted in a stable rhythm, though the gross deformity of the ECG due to repeated infarctions made it difficult to diagnose the arrhythmia more precisely. A blood pressure of 60/40 resulted and this was boosted to 100/60 by means of an infusion of epinephrine. The blood pressure, however, gradually declined and pulmonary edema developed. Despite all therapy, the patient died 14 hours later. Postmortem examination showed extensive infarction of the left ventricle with only about g of the wall uninvolved by the infarction.
Volume Number
75 6
Propranolol
Discussion The effects of adrenaline on the irritability and contractility of the myocardium are mediated by fi-adrenergic receptors. Many cardiac arrhythmias are adrenergically induced or sustained. Arrhythmias due to cardiac glycosides also have adrenergic mechanisms. The blocking of fl-adrenergic receptors can correct such arrhythmias. Besterman and Friedlander,’ Rowlands and associates,5 and Stock and Dale7 have confirmed the clinical value of ,6-adrenergic blocking agents in various types of arrhythmia. Unfortunately, however, this beneficial action on disorders of rhythm is accompanied by decrease in coronary blood flow and impairment of the force of myocardial contraction, leading to cardiac failure .3,4,7 Thus, great care is required in the use of these drugs in situations where severe myocardial damage exists and it is of vital importance to define as clearly as possible the minimum effective therapeutic dose. These factors are of particular importance in the treatment of persistent ventricular failure complicating myocardial infarction, since extensive muscle necrosis is invariably present. In the only previous paper on the control of persistent ventricular fibrillation by propranolol the authors used doses ranging from 15 to 22 mg. intravenously.6 The cardiodepressant effects of the drug were thought to be responsible for the death of one of their three patients. This led them to recommend an upper limit of 10 mg. intravenously. Our experience suggests that 10 mg. may be unnecessarily high. In all four cases, control of the arrhythmia was achieved by 1 mg. intravenously. In the patients who survived, congestive cardiac failure requiring digitalis and diuretics developed shortly after resuscitation. These patients may well not have survived if larger doses of propranolol had been used. The fact that much smaller intravenous doses of propranolol than previously recommended can be equally effective has been recognized and discussed at a recent symposium.* Our high success rate in controlling this grave complication of acute myocardial infarction in all the cases in which pro-
complicating
acute myocardial
infarction
797
pranolol was used is almost certainly fortuitous. There will be some cases in which neither propranolol nor any other drug in safe doses will control the arrhythmia. The purpose of this paper is to indicate the usefulness and “safe” dose of propranolol in this grave situation and the success rate is meaningful only in this context. The point may be made that the last D.C. shock may well have terminated the arrhythmia without the need for propranolol. In persistent ventricular fibrillation, it is possible to reverse the fibrillation in the majority of cases. The crux of the problem is to maintain the resulting viable rhythm without allowing it to relapse again into ventricular fibrillation after a short period. It is for this specific indication that propranolol is advised. A trial of propranolol is well worth while in this situation since the only other recommended line of therapy seems to be internal cardiac massage and defibrillation.2 This course itself has a great many disadvantages and seems to us to be far more dangerous than the administration of propranolol. Even when the therapeutic aim, namely, the termination of the arrhythmia, has been achieved, a certain proportion of the patients will die of myocardial inadequacy, as in Case 4 of this series. The massive degree of infarction found at postmortem examination confirmed that this patient had died of “pump failure” and that the arrhythmia had been a terminal event. The control of the disorder of rhythm could not be expected to alter the prognosis in such cases. Summary Four cases of persistent ventricular fibrillation complicating acute myocardial infarction are described. In each case, control of the arrhythmia was achieved by the intravenous administration of 1 mg. of propranolol. In this dose, this drug can be used with reasonable safety in controlling a lethal arrhythmia in patients suffering from extensive fresh myocardial infarctions. The author J. L. Edwards
tative
wishes to thank Drs. T. Mitchell and for their prompt initiation of resuscimeasures; the Charing Cross Hospital Clinical
798
Am. Heart J. June, 1968
Ikrclm
Research Committee for financial help, Miss A. Smith, Miss I. L. Wood, and Miss C. S. March for the electrocardiography and monitoring of these patients, and Mrs. J. Caudle for secretarial assistance.
4.
Redding, 1’. T., and Rees, J. R.: Myocardial vascular reactivity, Lancet 1:548, 1966. 5. Rowlands, D. J., Howitt, G., and Markman, P.: Propranolol (Inderal) in disturbances of cardiac rhythm, Brit: M. J. 1:891, 1965. 6. Sloman. G.. Robinson. I. S.. and McLean. K.: Propranolol (Inderal) in persistent ventricular fibrillation, Brit. M. J. 1:895, 1965. 7. Stock, J. P. P., and Dale, N.: Beta-adrenergic receptor blockade in cardiac arrhythmias, Brit. M. J. 2:1230, 1963. 8. Stephen, S. A.: Unwanted effects of propranolol (discussion), Am. J. Cardiol. 18:468, 1966. II
REFERENCES 1.
2. 3.
Besterman, E. M. M., and Friedlander, D. H.: Clinical experiences with propranolol, Postgrad. M. J. 41:526, 1965. Harley, H. R. S.: Reflections on cardiopulmonary resuscitation, Lancet 2:1, 1966. Parrett, J. R., and Grayson, J,: Myocardial vascular reactivity after beta-adrenergic blockade, Lancet 1:338, 1966.