Acta med. scand. Vol. 199, pp. 369-371, 1976
Ventricular Fibrillation after Intravenous Atropine for Treatment of Sinus Bradycardia Per Lunde From the Medico1 Deparimeni, Central Hospiial of Rogaland, Stuvcinger, Norway
ABSTRACT. A patient with acute myocardial infarction and sinus bradycardia has been treated with 0.5 mg atropine intravenously. Shortly afier the injection he showed a sinus tachycardia, then developed ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation, which was treated successfully with electrical countershock.
Bradyarrhythmias are a common feature in early myocardial infarction. Incidences of 1 1-27 5% have been reported ( I , 4,8, 1 I ) . These bradyarrhythmias have been considered to represent a potential danger because of hemodynarnic and conduction disturbances, and the use of vagolytic agents, atropine or methylscopolamine i.v., has therefore been recommended. However, the benefit of atropine during bradycardia in acute myocardial infarctions ( A M I ) has been questioned recently by American experimental investigators (3, 6 ) . I t is also well documented that i.v. atropine can actually precipitate serious ventricular arrhythmias (1,9, 10, 16) and increase the area of ischemia during myocardial infarction (14). Atropine might thus aggravate coronary ischemia and precipitate dangerous arrhythmias. This report deals with a patient who developed ventricular fibrillation after i.v. administration of 0.5 mg atropine.
CASE REPORT A 66-year-old man had had myocardial infarction in 1967 and 1971. For the past 2 years he had suffered from angina pectoris. In Oct. 1973 he was admitted to the CCU beAddress for reprints: P. Lunde, Medical Department, Stavanger Hospital, N-4000 Stavanger, Norway 24 - 7629R.s
cause of chest pain. On admission ECG showed sinus rhythm, 52 beatslmin, and evidence of acute diaphragmatic infarction. BP was 110/70. Enzyme changes verified the diagnosis. After 3 hours in hospital the ECG showed increasing bradycardia, but at no time did premature ventricular beats develop. Because of rates between 30 and 35 beatslmin, 0.5 mg atropine was given i.v. BP 105/75. He also received 6.S mg thiethylperazine i.v. because of nausea. During the 12 min following the atropine injection there was a progressive acceleration of the sinus rhythm, and at a rate of 70 beatslmin the patient developed premature ventricular beats followed by ventricular tachycardia and then fibrillation. After 50 mg Xylocaine i.v., defibrillation was achieved by electrical countershock (Fig. I).
DISCUSSION The ventricular fibrillation in this patient might be coincidental with the atropine injection but the following observations speak in favour of a causal relationship. At no time during the bradycardia did premature ventricular beats develop. The fibrillation appeared within 12 min after the administration of atropine and was preceded by frequent premature ventricular beats. The same observation has been reported by others (1, 10, 12, 16). Norris et al. (12) demonstrated recently in a clinical study that major ventricular arrhythmias did not usually occur at the time when bradycardia was present. They also found that the hospital mortality among patients with sinus bradycardia (below 60) was significantly lower (6%) than among those with sinus tachycardia (over 100) (26%). This agrees with earlier reports (5, 8) and tends to indicate that sinus bradycardia is associated with small infarctions and a low incidence of cardiac failure and rhythm disturbances, and thus carries a good prognosis. These observations sugActa med. scand. 199
370
P.Lunde
Fig. 1 . Monitor leads taken continuously. I =the ECG on admission, 2=at the moment the patient received 0.5 mg atropine. At a sinus rate of 70/min there are runs of ventricular beats which are followed by ventricular fibrillation. Strip5 shows the ECG just after the countershock, 2 min later there is sinus rythm. Paper speed 25 mmlsec.
gest a benign course of sinus bradycardia during the hospital phase, and a very recent work by Lie et al. (9) seems to favour such a suggestion. Experimental investigations also support the clinical finding of a benign course of bradycardia in AM1 (2, 15). These investigators found that moderately severe bradycardia accompanying experimental AM1 in dogs did not predispose to serious arrhythmias. On the contrary, bradycardia increased the electrical stability of the myocardium at Actri
med. scanrl. 199
least in a dual way. 1) Increasing heart rates during ischemia reduced the ventricular fibrillation threshold. 2) The disparity of refractory periods is greater at faster rates during ischemia. These effects may indeed explain the potentially dangerous effect of atropine during AMI. The same investigators also found that although atropine was highly effective in abolishing benign ventricular arrhythmias in a bradycardia, it was considerably less effective in eliminating the arrhythmias associated with the subsequent development of ventricular fibrillation (close-coupled premature ventricular contractions). In their model, bradycardia also reduced the ischemia in the myocardium and the extent of myocardial necrosis was always found to be increased by cardioacceleration induced by atropine. These findings might be of therapeutic importance. A recent clinical report (7) suggests that this may be so, as patients with coronary artery disease affecting two and three arteries showed no increase in myocardial blood flow in response to atropineinduced cardioacceleration. Atropine might thus aggravate myocardial ischemia in patients with occlusive artery disease. The possible benefits of cardioacceleration with atropine must therefore be balanced against the potential of the drug for increasing myocardial ischemia. The exact mechanism responsible for the production of ventricular irritability after atropine injection is not entirely clear. Certainly, an increased myocardial oxygen requirement secondary to increased heart rate appears to be an important factor. The fibrillation threshold is lowered and the disparity of refractory periods becomes greater at faster rates when the myocardium is ischemic. This increase in disparity will lead to slow, non-homogenous spread of impulses, resulting in reentrant activity and eventually ventricular fibrillation. Moreover, the efflux of potassium from the myocardial cells associated with tachycardia is also known to promote ventricular irritability by bringing the resting potential down towards the threshold potential. Regardless of the basic mechanism involved in the development of ventricular arrhythmias, our experience suggests, in agreement with reports by others, that i.v. atropine in doses of 0.5 mg and more may be associated with serious arrhythmias in patients with coronary heart disease. Because of this potential danger, atropine should probably be given only if the bradycardia is severe and associated with hypotension or circulatory instability.
Atropine, bradyarrhythmias, ventricularfibrillation
REFERENCES Adgey, A. A. J., Geddes, J. S . , Mulholland, H. C., Keegan, D. A. J . & Partridge, J. F.: Incidence, significance, and management of early bradyarrhythmias complicating acute myocardial infarction. Lancet 2: 1097, 1968. Epstein, S . , Goldstein, R. E., Redwood, D. R., Kent, K . M. & Smith, E. R.: The early phase of acute myocardial infarction: Pharmacological aspects of therapy. Ann. intern. Med. 78:918, 1973. Epstein, S ., Redwood, D. R. & Smith, E. R.: Atropine and acute myocardial infarction. Circulation 45: 1273, 1972. Grauer, L. E., Gershen, B. J., Orlando, M. M. & Epstein, S.: Bradycardia and its complications in the prehospital phase of acute myocardial infarction. Amer. J. Cardiol. 32:607, 1973. Jewitt, D. E., Balcon, R., Raftery, E. B. & Oram, S . : Incidence and management of supraventricular arrhythmias after acute myocardial infarction. Lancet 2:734, 1967. Kent, K. M., Smith, K. M., Redwood, D. R. & Epstein, S.: Electrical stability of acute ischemic myocardium influences of heart rate and vagal stimulation. Circulation 47: 291, 1973. Knobel, S. B., McHenry, P. L., Phillips, J. F. & Widlandsky, S.: Atropine-induced cardioacceleration and myocardial blood flow in subjects with and without coronary artery disease. Amer. J. Cardiol. 33: 321, 1974.
371
8. Lawrie, D. M., Greenwood, T. W., Goddard, M., Harvey, A. C., Donald, K. W., Julian, D. G . & Oliver, M. F.: A coronary care unit in the routine management of the acute myocardial infarction. Lancet 2: 109, 1967. 9. Lie, K. I., Wellens, H. J. & Durrer, D.: Characteristics and predictability of primary ventricular fibrillation. Eur. J. Cardiol. 1/4: 379, 1974. 10. Massumi, R. S . , Mason, D. T., Amsterdam, E. A., De Maria, A., Miller, R. R., Scheinmann, M. M. & Zelis, R.: Ventricular fibrillation and tachycardia after intravenous atropine for the treatment of bradycardias. New Engl. J. Med. 287: 336, 1972. 1 1 . Meltzer, L. E . & Kitchell, J. R.: Symposium on the current status of intensive coronary care. Philadelphia 1966. 12. Mogensen, L. & Orinius, E.: Arrhythmic complications after parasympatholytic treatment of bradyarrhythmias in a coronary care unit. Acta med. scand. 190: 495, 1971. 13. Nonis, R. M., Mercer, C. J. & Yeates, S. E.: Sinus rates in acute myocardial infarction. Brit. Heart J. 34: 901, 1972. 14. Richman, S.: Adverse effect of atropine during myocardial infarction. J.A.M.A. 11: 1414, 1974. 15. Shell, W. E. & Sobel, B. E.: Deleterious effects of increased heart rate on infarct size in the conscious dog. Amer. J. Cardiol. 31: 474, 1973. 16. Zipes, D. P. & Knobel, S. B.: Rapid rate-dependent ventricular ectopy. Chest 62: 255, 1972.
Acta med. scand. 199
Ventricular Fibrillation after Intravenous Atropine for Treatment of Sinus Bradycardia Per Lunde From the Medico1 Deparimeni, Central Hospiial of Rogaland, Stuvcinger, Norway
ABSTRACT. A patient with acute myocardial infarction and sinus bradycardia has been treated with 0.5 mg atropine intravenously. Shortly afier the injection he showed a sinus tachycardia, then developed ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation, which was treated successfully with electrical countershock.
Bradyarrhythmias are a common feature in early myocardial infarction. Incidences of 1 1-27 5% have been reported ( I , 4,8, 1 I ) . These bradyarrhythmias have been considered to represent a potential danger because of hemodynarnic and conduction disturbances, and the use of vagolytic agents, atropine or methylscopolamine i.v., has therefore been recommended. However, the benefit of atropine during bradycardia in acute myocardial infarctions ( A M I ) has been questioned recently by American experimental investigators (3, 6 ) . I t is also well documented that i.v. atropine can actually precipitate serious ventricular arrhythmias (1,9, 10, 16) and increase the area of ischemia during myocardial infarction (14). Atropine might thus aggravate coronary ischemia and precipitate dangerous arrhythmias. This report deals with a patient who developed ventricular fibrillation after i.v. administration of 0.5 mg atropine.
CASE REPORT A 66-year-old man had had myocardial infarction in 1967 and 1971. For the past 2 years he had suffered from angina pectoris. In Oct. 1973 he was admitted to the CCU beAddress for reprints: P. Lunde, Medical Department, Stavanger Hospital, N-4000 Stavanger, Norway 24 - 7629R.s
cause of chest pain. On admission ECG showed sinus rhythm, 52 beatslmin, and evidence of acute diaphragmatic infarction. BP was 110/70. Enzyme changes verified the diagnosis. After 3 hours in hospital the ECG showed increasing bradycardia, but at no time did premature ventricular beats develop. Because of rates between 30 and 35 beatslmin, 0.5 mg atropine was given i.v. BP 105/75. He also received 6.S mg thiethylperazine i.v. because of nausea. During the 12 min following the atropine injection there was a progressive acceleration of the sinus rhythm, and at a rate of 70 beatslmin the patient developed premature ventricular beats followed by ventricular tachycardia and then fibrillation. After 50 mg Xylocaine i.v., defibrillation was achieved by electrical countershock (Fig. I).
DISCUSSION The ventricular fibrillation in this patient might be coincidental with the atropine injection but the following observations speak in favour of a causal relationship. At no time during the bradycardia did premature ventricular beats develop. The fibrillation appeared within 12 min after the administration of atropine and was preceded by frequent premature ventricular beats. The same observation has been reported by others (1, 10, 12, 16). Norris et al. (12) demonstrated recently in a clinical study that major ventricular arrhythmias did not usually occur at the time when bradycardia was present. They also found that the hospital mortality among patients with sinus bradycardia (below 60) was significantly lower (6%) than among those with sinus tachycardia (over 100) (26%). This agrees with earlier reports (5, 8) and tends to indicate that sinus bradycardia is associated with small infarctions and a low incidence of cardiac failure and rhythm disturbances, and thus carries a good prognosis. These observations sugActa med. scand. 199
370
P.Lunde
Fig. 1 . Monitor leads taken continuously. I =the ECG on admission, 2=at the moment the patient received 0.5 mg atropine. At a sinus rate of 70/min there are runs of ventricular beats which are followed by ventricular fibrillation. Strip5 shows the ECG just after the countershock, 2 min later there is sinus rythm. Paper speed 25 mmlsec.
gest a benign course of sinus bradycardia during the hospital phase, and a very recent work by Lie et al. (9) seems to favour such a suggestion. Experimental investigations also support the clinical finding of a benign course of bradycardia in AM1 (2, 15). These investigators found that moderately severe bradycardia accompanying experimental AM1 in dogs did not predispose to serious arrhythmias. On the contrary, bradycardia increased the electrical stability of the myocardium at Actri
med. scanrl. 199
least in a dual way. 1) Increasing heart rates during ischemia reduced the ventricular fibrillation threshold. 2) The disparity of refractory periods is greater at faster rates during ischemia. These effects may indeed explain the potentially dangerous effect of atropine during AMI. The same investigators also found that although atropine was highly effective in abolishing benign ventricular arrhythmias in a bradycardia, it was considerably less effective in eliminating the arrhythmias associated with the subsequent development of ventricular fibrillation (close-coupled premature ventricular contractions). In their model, bradycardia also reduced the ischemia in the myocardium and the extent of myocardial necrosis was always found to be increased by cardioacceleration induced by atropine. These findings might be of therapeutic importance. A recent clinical report (7) suggests that this may be so, as patients with coronary artery disease affecting two and three arteries showed no increase in myocardial blood flow in response to atropineinduced cardioacceleration. Atropine might thus aggravate myocardial ischemia in patients with occlusive artery disease. The possible benefits of cardioacceleration with atropine must therefore be balanced against the potential of the drug for increasing myocardial ischemia. The exact mechanism responsible for the production of ventricular irritability after atropine injection is not entirely clear. Certainly, an increased myocardial oxygen requirement secondary to increased heart rate appears to be an important factor. The fibrillation threshold is lowered and the disparity of refractory periods becomes greater at faster rates when the myocardium is ischemic. This increase in disparity will lead to slow, non-homogenous spread of impulses, resulting in reentrant activity and eventually ventricular fibrillation. Moreover, the efflux of potassium from the myocardial cells associated with tachycardia is also known to promote ventricular irritability by bringing the resting potential down towards the threshold potential. Regardless of the basic mechanism involved in the development of ventricular arrhythmias, our experience suggests, in agreement with reports by others, that i.v. atropine in doses of 0.5 mg and more may be associated with serious arrhythmias in patients with coronary heart disease. Because of this potential danger, atropine should probably be given only if the bradycardia is severe and associated with hypotension or circulatory instability.
Atropine, bradyarrhythmias, ventricularfibrillation
REFERENCES Adgey, A. A. J., Geddes, J. S . , Mulholland, H. C., Keegan, D. A. J . & Partridge, J. F.: Incidence, significance, and management of early bradyarrhythmias complicating acute myocardial infarction. Lancet 2: 1097, 1968. Epstein, S . , Goldstein, R. E., Redwood, D. R., Kent, K . M. & Smith, E. R.: The early phase of acute myocardial infarction: Pharmacological aspects of therapy. Ann. intern. Med. 78:918, 1973. Epstein, S ., Redwood, D. R. & Smith, E. R.: Atropine and acute myocardial infarction. Circulation 45: 1273, 1972. Grauer, L. E., Gershen, B. J., Orlando, M. M. & Epstein, S.: Bradycardia and its complications in the prehospital phase of acute myocardial infarction. Amer. J. Cardiol. 32:607, 1973. Jewitt, D. E., Balcon, R., Raftery, E. B. & Oram, S . : Incidence and management of supraventricular arrhythmias after acute myocardial infarction. Lancet 2:734, 1967. Kent, K. M., Smith, K. M., Redwood, D. R. & Epstein, S.: Electrical stability of acute ischemic myocardium influences of heart rate and vagal stimulation. Circulation 47: 291, 1973. Knobel, S. B., McHenry, P. L., Phillips, J. F. & Widlandsky, S.: Atropine-induced cardioacceleration and myocardial blood flow in subjects with and without coronary artery disease. Amer. J. Cardiol. 33: 321, 1974.
371
8. Lawrie, D. M., Greenwood, T. W., Goddard, M., Harvey, A. C., Donald, K. W., Julian, D. G . & Oliver, M. F.: A coronary care unit in the routine management of the acute myocardial infarction. Lancet 2: 109, 1967. 9. Lie, K. I., Wellens, H. J. & Durrer, D.: Characteristics and predictability of primary ventricular fibrillation. Eur. J. Cardiol. 1/4: 379, 1974. 10. Massumi, R. S . , Mason, D. T., Amsterdam, E. A., De Maria, A., Miller, R. R., Scheinmann, M. M. & Zelis, R.: Ventricular fibrillation and tachycardia after intravenous atropine for the treatment of bradycardias. New Engl. J. Med. 287: 336, 1972. 1 1 . Meltzer, L. E . & Kitchell, J. R.: Symposium on the current status of intensive coronary care. Philadelphia 1966. 12. Mogensen, L. & Orinius, E.: Arrhythmic complications after parasympatholytic treatment of bradyarrhythmias in a coronary care unit. Acta med. scand. 190: 495, 1971. 13. Nonis, R. M., Mercer, C. J. & Yeates, S. E.: Sinus rates in acute myocardial infarction. Brit. Heart J. 34: 901, 1972. 14. Richman, S.: Adverse effect of atropine during myocardial infarction. J.A.M.A. 11: 1414, 1974. 15. Shell, W. E. & Sobel, B. E.: Deleterious effects of increased heart rate on infarct size in the conscious dog. Amer. J. Cardiol. 31: 474, 1973. 16. Zipes, D. P. & Knobel, S. B.: Rapid rate-dependent ventricular ectopy. Chest 62: 255, 1972.
Acta med. scand. 199
