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Serum lipids and cerebrovascular disease
584
13. 14.
15.
16. 17.
18.
19.
20. 21.
Am. Heart J. October, 1968
Annotations
Gimlette, T. M. D.: Thyroid acropachy, Lancet 1:22, 1960. Cullen, D. R., and Maskery, P. J.: Clubbing of the fingers and hypertrophic osteoarthropathy in pregnancy, Lancet 2:473, 1966. Flavell, G.: Reversal of pulmonary hypertrophic osteoarthropathy by vagotomy, Lancet 1:260, 1956. Mendlowitz, M. : Clubbing and idiopathic osteoarthropathy, Medicine 21:269, 1942. Holling, H. E., Danielson, G. K., Hamilton, R. W., Blakemore, W. S., and Brodey, R. S.: Hypertrophic pulmonary osteoarthropathy, J. Thoracic & Cardiovas. Surg. 46:310, 1963. Rimoin, D. L.: Pachydermoperiostosis (idiopathic clubbing and periostosis), New England J. Med. 272:923, 1965. Friedreich, N.: Hyperostose Des Gesammten skelettes, Virchows Arch. path. Anat. 43:83, 1868. Fraentzel, 0.: Uber Akromegalie, Deutsche med. Wchnschr. 14:653, 1888. Jadassohn, J.: Eine eigentumliche Furchung, Erweiterung und Verdickung der Haut am Hinterkopf. IX Kongress Dautschendermatol. Gessellsch., Bern, 1906, page 452.
Serum
lipids
22.
23.
24.
25.
26.
27.
Touraine, A., Solente, A., and Gale, L.: Un syndrome osteodermopatique. La pachydermia plicaturee avec pachyperiostose des extremities, Presse med. 43:1820, 1935. Brugsch, H. G.: Acropachyderma with pachyperiostitis; Report of a case, Arch. Int. Med. 68:687, 1941. Goldbloom, R. B., Stein, P. B., Eisen, A., McSheffrey, J. B., Brown, B. J. St., and Wiglesworth, F. W.: Idiopathic periosteal hyperostosis with dysproteinemia, New England J. Med. 274:873, 1966. Tzoneva-Maneva, M. T., Bosajieva, E., and Petrov, B. : Chromosomal abnormalities in idiopathic osteoarthropathy, Lancet l:lOOO, 1966. Susmano, A., Shah, P., Krompotic, E., and Tashima, C.: Normal sex chromosome complement in a case of familial osteoarthropathy, Lancet 2:131, 1967. Rimoin, L. D., and Borgaonkar, D. S.: Chromosomal abnormalities in idiopathic osteoarthropathy, Lancet 2:860, 1966.
and cerebrevaswlur
The possibility of there being an etiological connection between serum lipids and vascular disease has been most extensively studied in relation to the coronary arterial system. In the early 1950’s, it was reported that the total, free, and esterified plasma cholesterol were elevated in patients with coronary artery disease as compared with normal subjects.‘,2 Sometime later it was demonstrated that the ratio of 01- to P-lipoprotein was less in patients with coronary artery disease than it was in healthy controls.**4 Finally, it was established that the most sensitive indicator of lipid abnormality in coronary artery disease was the serum triglyceride leveL6 These observations were made on subjects with clinical evidence of established coronary disease. More important was the demonstration that the serum lipid level is raised before there are manifestations of clinical disease. The level of lipids in the serum has value, therefore, in predicting that a person is likely to develop coronary arterial disease.B The influence of age must, however, be borne in mind because it has been shown that the triglycerides6 and the (Y- and @-lipoprotein fractions increase with age in normal people. As a result, the significant difference between the serum lipid level of patients who have developed, or who are about to develop clinical manifestations of coronary arterial disease and of normal controls can only be shown in younger age groups. If a patient does not develop myocardial infarction, or other evidence of coronary
disease
arterial disease until later in life, it may not be possible to demonstrate that his serum lipid level is significantly different from his contemporary who is not showing clinical signs or symptoms. Even when patients are grouped, it may still be impossible to demonstrate a significant difference between patients and controls in the older age groups.7 The study of the relationship between serum lipids and cerebrovascular disease is even more complex because the range of disorders afflicting the cerebral arterial system is greater than that affecting the coronary arterial system. The two major pathological processes affecting the cerebral arteries are atherosclerosis and hypertension. In typical cases the effects of these two processes can be clearly separated, the former giving rise to atheromatous lesions in large arteries, such as the carotid and vertebral, whereas the latter affects mainly the smaller arteries, producing medial hypertrophy and leading to the formation of microaneurysms of the Charcot-Bouchard type.s*g The distinction between the effects of these two processes is, however, in practice less sharp for hypertension, besides producing medial hypertrophy, increases the number of atheromatous plaques to be found in the large cerebral vessels, and produces atheroma in smaller vessels than are usually involved in the nonhypertensive patient. In addition, when account is taken of the fact that the differentiation in life between cerebral infarction consequent upon atheroma and cerebral hemorrhagic lesions
Annotations
from hypertension is extremely difficult,lO*n the complexity of the problem is clearly manifested. The comparison of serum lipid levels in patients with cerebrovascular disease or “stroke illness” and controls is in effect a comparison between a number of disorders on the one hand and controls on the other. An attempt was made to distinguish between the effects of atheroma and hypertension by separating patients with a clinically diagnosed cerebral infarction according to their level of blood pressure. The mean serum cholesterol in the patients with a diastolic blood pressure of less than 110 mm. Hg was 228 mg. per 100 ml., whereas in those whose diastolic was 110 mm. Hg, or above, the level was 209 mg., the difference falling just short of the 5 per cent level of significance.r2 In view of the finding in coronary arterial disease that the triglyceride is a more useful indication than cholesterol, the serum levels of triglycerides, as well as total and free cholesterol, phospholipids, and a series of fatty acids was further determined in these two groups of patients,‘3 but none reached the 5 per cent level of significance. The observation that the difference between serum lipid levels of patients with coronary arterial disease and of healthy controls, which is manifest in the younger age groups, disappears with advancing age, is, however, clearly relevant.7 Patients with stroke illness are, on average, older than patients showing signs of coronary arterial disease, hence, it might be expected that any difference between their serum lipids and those of their healthy contemporaries, which might have been present in early adult life, would have disappeared. Evidence that this indeed is the case has recently come from the Framingham study.” Subjects with a high serum cholesterol before 50 years of age were more liable ultimately to develop an atherosclerotic cerebra1 infarction than those whose cholesterol was normal. After the age of 50, this difference could no longer be discerned. This tendency for significant differences between the serum lipid levels of different groups of subjects to disappear with advancing age seems to be a general phenomenon. For instance, the serum triglyceride levels were significantly raised in young, obese female subjects as compared with nonobese subjects, but in the older age groups the difference was no longer apparent, the normals having, as it were, “caught up.“rs Similarly, serum triglycerides and the distribution of subcutaneous fat were found to be significantly related in men below the age of 54, but after this age the correlation was no longer demonstrable.‘G It seems, therefore, reasonable to postulate that the level of serum lipids, particularly triglycerides, before middle age is significantly related to the subsequent development of cerebral atherosclerosis, which is an important predisposing factor in the development of cerebral infarction. By the time infarction occurs, however, this difference in serum lipid levels is no longer apparent, the healthy subjects having caught up with those afflicted with arterial disease. If this postulate is established, it will raise grave problems in the field of preventive medicine. The establishment of some method of screening the population to discover those whose serum lipid level is
58.5
above average in young adult life would be necessary. It would also be necessary to ascertain whether the reduction of the level, in those in whom it is raised, either by diet or by drugs, reduces the risk of the subsequent development of cerebral atherosclerosis and infarction. When it is remembered that cerebrovascular disease is the third largest cause of death in many western countries at the present time, the size of this problem needs no stress. However, the first task is to ascertain the facts, which can only be done by setting up well-designed, longitudinal studies which will establish the relationship, if any, between serum lipids in young, adult life and the subsequent development of cerebrovascular disease. John N. Cumings, M.D. Professor of Chemical Pathology John Marshall, M.D. Reader in Clinical Neurology University of London Institute of Neurology Queen Square London, England
REFERENCES 1. Gertler, M. M., Garn, S. M., and Lerman, J.: The inter-relationships of serum cholesterol, cholesterol esters and phospholipids in health and coronary artery disease, Circulation 2:205, 1950. 2. Oliver, M. F., and Boyd, G. S.: The plasma lipids and coronary artery disease, Brit.. Heart 1. 15:38?, 1953. 3. bliver, Ivl. F., and Boyd, G. S.: Serum Iipoprotein patterns in coronary sclerosis and associated conditions, Brit. Heart J. 17:299, 1955. 4. Mills, G. L., and Wilkinson, P. A. : Plasma lipid levels and the diagnosis of coronary arteriosclerosis in England, Brit. Heart J. 28:638, 1966. M. J., and Man, E. B.: Serum 5. Albrink, triglycerides in coronary artery disease, Arch. Int. Med. 103:4, 1959. effort of the Technical Group of the 6. Joint Committee on Lipoproteins and Atherosclerosis and the Committee on Lipoproteins and Atherosclerosis of the National Advisory Heart Council: Evaluation of serum lipoprotein and cholesterol measurements as predictions of clinical complications of atherosclerosis, Circulation 14:691, 1956. A., and Bersohn, I.: Serum triglycer7. Antonis, ide levels in South African Europeans and Bantu in ischaemic heart disease, Lancet 1:998, 1960. 8. Ross Russell, R. W.: Observations on intracerebral aneurysms, Brain 86:425, 1963. 9. Cole, F. M., and Yates, P. 0.: The occurrence and significance of intracerebral micro-aneurysms, J. Path. & Bact. 93:393, 1967. 10. Dalsgaard-Nielsen, T. : Some clinical experience in the treatment of cerebral apoplexy (1,000 cases), Acta psychiat. Scandinav. Suppl. 108:101, 1956. 11. Heasman, M. A., and Lipworth, L.: Accuracy of certification of causes of death, General Register Office, Studies on Medical and Population Subjects No. 20, H. M. Stationery Office, 1966.
586
12. 13.
14.
Am. Hcne J. October, 1968
Annotations
Prineas, J., and Marshall, J.: Hypertension and cerebral infarction, Brit. M. J. 1:14, 1966. Cumings, J. N., Grundt, I. K., Holland, J. T., and Marshall, J.: Serum-lipids and cerebrovascular disease, Lancet 2:194, 1967. Kannel, W. B.: An epidemiologic study of cerebrovascular disease. From cerebral vascular diseases, Transactions of the Fifth Conference held by the American Neurological Association
Lidocaine
in acute
15.
16.
myocardial
Experience in monitoring of patients with acute myocardial infarction in a coronary care unit (CCU) has shown that diverse arrhythmias recur sporadically during the initial 48 to 72 hours of illness. Ventricular rhythm disorders are the most frequent, with ectopic beats (VPB) observed in 70 per cent and ventricular tachycardia (VT), usually at a slow rate, in 28 per cent of the patients. These arrhythmias generally do not compromise cardiac function nor are they perceived by the patient. However, they reflect an underlying electrical instability of the heart and may augur development of catastrophic derangements of the heart beat. Indeed, in a recent study; when minor arrhythmias were abolished, not a single enisode of ventricular fibrillation resulted in 130 consecutive patients with acute myocardial infarction. The drug employed to control the minor ventricular rhythm abnormalities was lidocaine
(2%). Lidocaine is a synthetic local anesthetic agent first employed by Southworth and associate@ in 1950 for its antiarrhythmic properties. Its effectiveness in combating ventricular arrhythmias has been corroborated.3.6 The clinical use of lidocaine has been reviewed in this JOURNAL.” When given intravenously, an effect is observable within 15 to 30 seconds; this is due to rapid diffusion and cell membrane nenetration. Within 20 minutes it is cleared from the circulation. The primary pathway of elimination is by hepatic degradation to free and conjugated phenols: Less than 10 per cent of this unaltered drue is found in the urine. Unlike procaine amide, lidocaine does not decrease arterial pressure nor reduce right ventricular contractile force.’ Its antiarrhythmic action is probably due to a reduction in Purkinje fiber automaticity. Lidocaine is admirably suited for suppressing ventricular ectopic mechanisms in the patient with acute infarction. The ventricular arrhythmias develop unpredictably and need to be controlled promptly. Lidocaine can be administered intravenously in a single bolus with expectation of almost instantaneous effective action. Once the arrhythmia is abolished, a continuous intravenous infusion can be readily adjusted to a level just adequate for control. The most serious complication of myo-
and American Heart Association at Princeton, N. J., in January, 1966, New York and London, 1966, Grune & Stratton, Inc., page 53. Rifkind, B. M., Gale, M., and Jackson, I. D.: Serum lipid levels and body fat distribution in obese females, J. Clin. Path. 20:249, 1967. Evans, J. G., and Ostrander, L. D.: Fasting serum triglycerides concentration and distribution of subcutaneous fat, Lancet 1:761, 1967.
Mar&on
cardial infarction is hypotension leading to shock. Antiarrhythmic drugs such as quinidine and procaine amide impair cardiac contractility and reduce peripheral resistance, thereby, contributing to this condition. Therapeutically, adequate doses of lidoCaine are less likely to compromise cardiac hemodynamics. Furthermore, lidocaine does not depress conduction, induce intraventricular or bundle branch block (BBB). In the critically ill patient with low cardiac output and reduced renal blood flow, the accumulation of antiarrhythmic drugs in the body deleteriously affect ventricular performance. Since lidocaine is eliminated by the liver, it can be employed even in the patient with oliguria. If untoward effects develop, cessation of infusion permits prompt assessment as to whether the drug is implicated. The transient action of lidocaine also allows frequent cessation of drug administration to determine whether antiarrhythmic measures are still required. In the patient with acute myocardial infarction, treatment with lidocaine is initiated for suppressing VPB’s if they present any of the following: (1) occurrence early in the cycle with interruption of the T wave. esueciallv if the 0-R’/O-T,is less than 0.85. where Q-R’ represents-the interval between the onset of QRS and VPB; (2) salvos of two or more successive ectopic beats; (3) multiform configuration; and (4) a frequency of VPB’s greater than 5 per minute. Lidocaine is given initially as an intravenous bolus of 25 to 50 mg.; if ineffective it may be immediately followed with 100 mg. If the VPB’s are abolished, the drug is administered by continuous intravenous infusion in a concentration of 4 mg. per cubic centimeter at a rate of 1 to 4 mg. per minute. If ectopic mechanisms recur increasingly, the rate of infusion may be inadequate, but once again the arrhythmias can be eliminated by an appropriate bolus injection and then recurrencecan be-prevented with a sliahtlv higher infusion rate. Treatment is the same for ,aroxysmal VT. Lidocaine was employed in 64 of 125 consecutive patients with myocardial infarction admitted to a CCU during the past year. In 88 per cent it completely abolished ectopic activity. In 10 per cent ventricular mechanisms recurred and were controlled either by the addition of another antiarrhythmic
13. 14.
15.
16. 17.
18.
19.
20. 21.
Am. Heart J. October, 1968
Annotations
Gimlette, T. M. D.: Thyroid acropachy, Lancet 1:22, 1960. Cullen, D. R., and Maskery, P. J.: Clubbing of the fingers and hypertrophic osteoarthropathy in pregnancy, Lancet 2:473, 1966. Flavell, G.: Reversal of pulmonary hypertrophic osteoarthropathy by vagotomy, Lancet 1:260, 1956. Mendlowitz, M. : Clubbing and idiopathic osteoarthropathy, Medicine 21:269, 1942. Holling, H. E., Danielson, G. K., Hamilton, R. W., Blakemore, W. S., and Brodey, R. S.: Hypertrophic pulmonary osteoarthropathy, J. Thoracic & Cardiovas. Surg. 46:310, 1963. Rimoin, D. L.: Pachydermoperiostosis (idiopathic clubbing and periostosis), New England J. Med. 272:923, 1965. Friedreich, N.: Hyperostose Des Gesammten skelettes, Virchows Arch. path. Anat. 43:83, 1868. Fraentzel, 0.: Uber Akromegalie, Deutsche med. Wchnschr. 14:653, 1888. Jadassohn, J.: Eine eigentumliche Furchung, Erweiterung und Verdickung der Haut am Hinterkopf. IX Kongress Dautschendermatol. Gessellsch., Bern, 1906, page 452.
Serum
lipids
22.
23.
24.
25.
26.
27.
Touraine, A., Solente, A., and Gale, L.: Un syndrome osteodermopatique. La pachydermia plicaturee avec pachyperiostose des extremities, Presse med. 43:1820, 1935. Brugsch, H. G.: Acropachyderma with pachyperiostitis; Report of a case, Arch. Int. Med. 68:687, 1941. Goldbloom, R. B., Stein, P. B., Eisen, A., McSheffrey, J. B., Brown, B. J. St., and Wiglesworth, F. W.: Idiopathic periosteal hyperostosis with dysproteinemia, New England J. Med. 274:873, 1966. Tzoneva-Maneva, M. T., Bosajieva, E., and Petrov, B. : Chromosomal abnormalities in idiopathic osteoarthropathy, Lancet l:lOOO, 1966. Susmano, A., Shah, P., Krompotic, E., and Tashima, C.: Normal sex chromosome complement in a case of familial osteoarthropathy, Lancet 2:131, 1967. Rimoin, L. D., and Borgaonkar, D. S.: Chromosomal abnormalities in idiopathic osteoarthropathy, Lancet 2:860, 1966.
and cerebrevaswlur
The possibility of there being an etiological connection between serum lipids and vascular disease has been most extensively studied in relation to the coronary arterial system. In the early 1950’s, it was reported that the total, free, and esterified plasma cholesterol were elevated in patients with coronary artery disease as compared with normal subjects.‘,2 Sometime later it was demonstrated that the ratio of 01- to P-lipoprotein was less in patients with coronary artery disease than it was in healthy controls.**4 Finally, it was established that the most sensitive indicator of lipid abnormality in coronary artery disease was the serum triglyceride leveL6 These observations were made on subjects with clinical evidence of established coronary disease. More important was the demonstration that the serum lipid level is raised before there are manifestations of clinical disease. The level of lipids in the serum has value, therefore, in predicting that a person is likely to develop coronary arterial disease.B The influence of age must, however, be borne in mind because it has been shown that the triglycerides6 and the (Y- and @-lipoprotein fractions increase with age in normal people. As a result, the significant difference between the serum lipid level of patients who have developed, or who are about to develop clinical manifestations of coronary arterial disease and of normal controls can only be shown in younger age groups. If a patient does not develop myocardial infarction, or other evidence of coronary
disease
arterial disease until later in life, it may not be possible to demonstrate that his serum lipid level is significantly different from his contemporary who is not showing clinical signs or symptoms. Even when patients are grouped, it may still be impossible to demonstrate a significant difference between patients and controls in the older age groups.7 The study of the relationship between serum lipids and cerebrovascular disease is even more complex because the range of disorders afflicting the cerebral arterial system is greater than that affecting the coronary arterial system. The two major pathological processes affecting the cerebral arteries are atherosclerosis and hypertension. In typical cases the effects of these two processes can be clearly separated, the former giving rise to atheromatous lesions in large arteries, such as the carotid and vertebral, whereas the latter affects mainly the smaller arteries, producing medial hypertrophy and leading to the formation of microaneurysms of the Charcot-Bouchard type.s*g The distinction between the effects of these two processes is, however, in practice less sharp for hypertension, besides producing medial hypertrophy, increases the number of atheromatous plaques to be found in the large cerebral vessels, and produces atheroma in smaller vessels than are usually involved in the nonhypertensive patient. In addition, when account is taken of the fact that the differentiation in life between cerebral infarction consequent upon atheroma and cerebral hemorrhagic lesions
Annotations
from hypertension is extremely difficult,lO*n the complexity of the problem is clearly manifested. The comparison of serum lipid levels in patients with cerebrovascular disease or “stroke illness” and controls is in effect a comparison between a number of disorders on the one hand and controls on the other. An attempt was made to distinguish between the effects of atheroma and hypertension by separating patients with a clinically diagnosed cerebral infarction according to their level of blood pressure. The mean serum cholesterol in the patients with a diastolic blood pressure of less than 110 mm. Hg was 228 mg. per 100 ml., whereas in those whose diastolic was 110 mm. Hg, or above, the level was 209 mg., the difference falling just short of the 5 per cent level of significance.r2 In view of the finding in coronary arterial disease that the triglyceride is a more useful indication than cholesterol, the serum levels of triglycerides, as well as total and free cholesterol, phospholipids, and a series of fatty acids was further determined in these two groups of patients,‘3 but none reached the 5 per cent level of significance. The observation that the difference between serum lipid levels of patients with coronary arterial disease and of healthy controls, which is manifest in the younger age groups, disappears with advancing age, is, however, clearly relevant.7 Patients with stroke illness are, on average, older than patients showing signs of coronary arterial disease, hence, it might be expected that any difference between their serum lipids and those of their healthy contemporaries, which might have been present in early adult life, would have disappeared. Evidence that this indeed is the case has recently come from the Framingham study.” Subjects with a high serum cholesterol before 50 years of age were more liable ultimately to develop an atherosclerotic cerebra1 infarction than those whose cholesterol was normal. After the age of 50, this difference could no longer be discerned. This tendency for significant differences between the serum lipid levels of different groups of subjects to disappear with advancing age seems to be a general phenomenon. For instance, the serum triglyceride levels were significantly raised in young, obese female subjects as compared with nonobese subjects, but in the older age groups the difference was no longer apparent, the normals having, as it were, “caught up.“rs Similarly, serum triglycerides and the distribution of subcutaneous fat were found to be significantly related in men below the age of 54, but after this age the correlation was no longer demonstrable.‘G It seems, therefore, reasonable to postulate that the level of serum lipids, particularly triglycerides, before middle age is significantly related to the subsequent development of cerebral atherosclerosis, which is an important predisposing factor in the development of cerebral infarction. By the time infarction occurs, however, this difference in serum lipid levels is no longer apparent, the healthy subjects having caught up with those afflicted with arterial disease. If this postulate is established, it will raise grave problems in the field of preventive medicine. The establishment of some method of screening the population to discover those whose serum lipid level is
58.5
above average in young adult life would be necessary. It would also be necessary to ascertain whether the reduction of the level, in those in whom it is raised, either by diet or by drugs, reduces the risk of the subsequent development of cerebral atherosclerosis and infarction. When it is remembered that cerebrovascular disease is the third largest cause of death in many western countries at the present time, the size of this problem needs no stress. However, the first task is to ascertain the facts, which can only be done by setting up well-designed, longitudinal studies which will establish the relationship, if any, between serum lipids in young, adult life and the subsequent development of cerebrovascular disease. John N. Cumings, M.D. Professor of Chemical Pathology John Marshall, M.D. Reader in Clinical Neurology University of London Institute of Neurology Queen Square London, England
REFERENCES 1. Gertler, M. M., Garn, S. M., and Lerman, J.: The inter-relationships of serum cholesterol, cholesterol esters and phospholipids in health and coronary artery disease, Circulation 2:205, 1950. 2. Oliver, M. F., and Boyd, G. S.: The plasma lipids and coronary artery disease, Brit.. Heart 1. 15:38?, 1953. 3. bliver, Ivl. F., and Boyd, G. S.: Serum Iipoprotein patterns in coronary sclerosis and associated conditions, Brit. Heart J. 17:299, 1955. 4. Mills, G. L., and Wilkinson, P. A. : Plasma lipid levels and the diagnosis of coronary arteriosclerosis in England, Brit. Heart J. 28:638, 1966. M. J., and Man, E. B.: Serum 5. Albrink, triglycerides in coronary artery disease, Arch. Int. Med. 103:4, 1959. effort of the Technical Group of the 6. Joint Committee on Lipoproteins and Atherosclerosis and the Committee on Lipoproteins and Atherosclerosis of the National Advisory Heart Council: Evaluation of serum lipoprotein and cholesterol measurements as predictions of clinical complications of atherosclerosis, Circulation 14:691, 1956. A., and Bersohn, I.: Serum triglycer7. Antonis, ide levels in South African Europeans and Bantu in ischaemic heart disease, Lancet 1:998, 1960. 8. Ross Russell, R. W.: Observations on intracerebral aneurysms, Brain 86:425, 1963. 9. Cole, F. M., and Yates, P. 0.: The occurrence and significance of intracerebral micro-aneurysms, J. Path. & Bact. 93:393, 1967. 10. Dalsgaard-Nielsen, T. : Some clinical experience in the treatment of cerebral apoplexy (1,000 cases), Acta psychiat. Scandinav. Suppl. 108:101, 1956. 11. Heasman, M. A., and Lipworth, L.: Accuracy of certification of causes of death, General Register Office, Studies on Medical and Population Subjects No. 20, H. M. Stationery Office, 1966.
586
12. 13.
14.
Am. Hcne J. October, 1968
Annotations
Prineas, J., and Marshall, J.: Hypertension and cerebral infarction, Brit. M. J. 1:14, 1966. Cumings, J. N., Grundt, I. K., Holland, J. T., and Marshall, J.: Serum-lipids and cerebrovascular disease, Lancet 2:194, 1967. Kannel, W. B.: An epidemiologic study of cerebrovascular disease. From cerebral vascular diseases, Transactions of the Fifth Conference held by the American Neurological Association
Lidocaine
in acute
15.
16.
myocardial
Experience in monitoring of patients with acute myocardial infarction in a coronary care unit (CCU) has shown that diverse arrhythmias recur sporadically during the initial 48 to 72 hours of illness. Ventricular rhythm disorders are the most frequent, with ectopic beats (VPB) observed in 70 per cent and ventricular tachycardia (VT), usually at a slow rate, in 28 per cent of the patients. These arrhythmias generally do not compromise cardiac function nor are they perceived by the patient. However, they reflect an underlying electrical instability of the heart and may augur development of catastrophic derangements of the heart beat. Indeed, in a recent study; when minor arrhythmias were abolished, not a single enisode of ventricular fibrillation resulted in 130 consecutive patients with acute myocardial infarction. The drug employed to control the minor ventricular rhythm abnormalities was lidocaine
(2%). Lidocaine is a synthetic local anesthetic agent first employed by Southworth and associate@ in 1950 for its antiarrhythmic properties. Its effectiveness in combating ventricular arrhythmias has been corroborated.3.6 The clinical use of lidocaine has been reviewed in this JOURNAL.” When given intravenously, an effect is observable within 15 to 30 seconds; this is due to rapid diffusion and cell membrane nenetration. Within 20 minutes it is cleared from the circulation. The primary pathway of elimination is by hepatic degradation to free and conjugated phenols: Less than 10 per cent of this unaltered drue is found in the urine. Unlike procaine amide, lidocaine does not decrease arterial pressure nor reduce right ventricular contractile force.’ Its antiarrhythmic action is probably due to a reduction in Purkinje fiber automaticity. Lidocaine is admirably suited for suppressing ventricular ectopic mechanisms in the patient with acute infarction. The ventricular arrhythmias develop unpredictably and need to be controlled promptly. Lidocaine can be administered intravenously in a single bolus with expectation of almost instantaneous effective action. Once the arrhythmia is abolished, a continuous intravenous infusion can be readily adjusted to a level just adequate for control. The most serious complication of myo-
and American Heart Association at Princeton, N. J., in January, 1966, New York and London, 1966, Grune & Stratton, Inc., page 53. Rifkind, B. M., Gale, M., and Jackson, I. D.: Serum lipid levels and body fat distribution in obese females, J. Clin. Path. 20:249, 1967. Evans, J. G., and Ostrander, L. D.: Fasting serum triglycerides concentration and distribution of subcutaneous fat, Lancet 1:761, 1967.
Mar&on
cardial infarction is hypotension leading to shock. Antiarrhythmic drugs such as quinidine and procaine amide impair cardiac contractility and reduce peripheral resistance, thereby, contributing to this condition. Therapeutically, adequate doses of lidoCaine are less likely to compromise cardiac hemodynamics. Furthermore, lidocaine does not depress conduction, induce intraventricular or bundle branch block (BBB). In the critically ill patient with low cardiac output and reduced renal blood flow, the accumulation of antiarrhythmic drugs in the body deleteriously affect ventricular performance. Since lidocaine is eliminated by the liver, it can be employed even in the patient with oliguria. If untoward effects develop, cessation of infusion permits prompt assessment as to whether the drug is implicated. The transient action of lidocaine also allows frequent cessation of drug administration to determine whether antiarrhythmic measures are still required. In the patient with acute myocardial infarction, treatment with lidocaine is initiated for suppressing VPB’s if they present any of the following: (1) occurrence early in the cycle with interruption of the T wave. esueciallv if the 0-R’/O-T,is less than 0.85. where Q-R’ represents-the interval between the onset of QRS and VPB; (2) salvos of two or more successive ectopic beats; (3) multiform configuration; and (4) a frequency of VPB’s greater than 5 per minute. Lidocaine is given initially as an intravenous bolus of 25 to 50 mg.; if ineffective it may be immediately followed with 100 mg. If the VPB’s are abolished, the drug is administered by continuous intravenous infusion in a concentration of 4 mg. per cubic centimeter at a rate of 1 to 4 mg. per minute. If ectopic mechanisms recur increasingly, the rate of infusion may be inadequate, but once again the arrhythmias can be eliminated by an appropriate bolus injection and then recurrencecan be-prevented with a sliahtlv higher infusion rate. Treatment is the same for ,aroxysmal VT. Lidocaine was employed in 64 of 125 consecutive patients with myocardial infarction admitted to a CCU during the past year. In 88 per cent it completely abolished ectopic activity. In 10 per cent ventricular mechanisms recurred and were controlled either by the addition of another antiarrhythmic