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Effect of methylprednisolone on myocardial preservation during coronary artery surgery
Effect of Methylprednisolone
on Myocardial Preservation
during Coronary Artery Surgery Jeremy R. Morton, MD, Portland, Maine Clement A. Hiebert, MD, Portland, Maine Chris A. Lutes, MD, Portland, Maine Richard L. White, MD, Portland, Maine
Nearly one tenth of patients demonstrate electrocardiographic changes of myocardial infarction after coronary bypass surgery [I]. More significantly, fully one third of patients have significant elevations in postoperative cardiac enzyme levels, suggesting a lesser degree of intraoperative myocardial damage. These changes occur despite the use of intraoperative systemic and local hypothermia to promote myocardial preservation. Recent experimental work by Libby et al [2] suggests that a single dose of corticosteroids may significantly reduce the extent of myocardial injury induced by ischemia. In light of these observations, we have undertaken a prospective, randomized, double blind study of the effect of a single large dose of corticosteroids on intraoperative myocardial preservation during coronary artery surgery. Material and Methods Ninety-five consecutive patients undergoing aortocoronary bypass grafts without associated valve replacement or ventricular aneurysmectomy were included. Four cardiac surgeons participated in the study. Surgical technic was essentially the same in every case. The heart was exposed through a median sternotomy incision and simultaneously the required length of lower saphenous vein was harvested from one or both legs. All of the proximal anastomoses were then completed using an exclusion clamp on the ascending aorta prior to initiation of cardiopulmonary bypass. A disposable pump oxygenator was employed with a single right atria1 venous cannula and an arterial cannula in the ascending aorta. A left atria1 sump was inserted through the right superior pulmonary vein. The patient was cooled to 32V.
From the Department of Surgery. Maine Medical Center. Portland, Maine. Reprint requests should ba addressed to Jeremy R. Morton, MD, 321 Srackett Street, Portland, Maine 04102. Presented at the Fifty-Sixth Annual Meeting of the New England SwgiCal Society. Portsmouth, New Hampshire, September 25-27, 1975.
volum. 131, Apru 4976
For each distal anastomosis, the ascending aorta was cross-clamped and the heart locally chilled with Ringer’s lactate solution at 5°C. Distal anastomoses were performed using 6-O polypropylene suture. On completion of each distal anastomosis, the aorta was declamped and the heart defibrillated and allowed to recover for 5 minutes. This procedure was repeated for each additional anastomosis. Aortic occlusion times varied from 12 to dit minutes. The patients ranged in age from thirty-one to seventy-six years with an average of fifty-three years. Fifty patients had had a previous myocardial infarct, thirtysix had unstable angina, and sixty-five had some degree of impaired ventricular function as determined by ventriculography. Thirteen patients had single, thirty-eight double, thirty-one triple, and thirteen quadruple bypass grafts. The mean pump time for a triple graft was 98 minutes. The mean value for the longest period of continuous aortic occlusion in each patient was 23.5 minutes. The corticosteroid used was methylprednisolone given in a single dose of 2 gm or approximately 30 mg/ kg. Half the patients received the drug and half received a placebo. The drug and placebo were supplied, packaged, and randomly coded by the Upjohn Company. The code was not revealed until the study was completed and all the data had been collected and interpreted. The test drug was administered by intravenous injection immediately prior to induction of anesthesia, which was approximately 2 hours prior to the institution of cardiopulmonary bypass. Serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase (SGOT) were measured on the first three days postoperatively. Electrocardiograms were obtained on the second and fifth postoperative days or more often if indicated. Midway through the study the technic for separating CPK and LDH into isoenzyme fractions became available and was used thenceforth. Some elevation in cardiac enzymes, particularly CPK and LDH, occurred in all patients operated on. It became necessary, therefore, in evaluating those patients in whom isoenzymes were not available, to determine the level for each enzyme above which it was likely that
419
Morton et al
the elevation represented significant myocardial injury. It was apparent that all patients with electrocardiographic evidence of infarction and nearly all patients with isoenzyme patterns suggestive of myocardial injury, as seen subsequently herein, exhibited total CPK values in excess of 300 U (international units per liter), LDH values greater than 300 U, and SGOT values greater than 100 U. These figures were therefore used to define “significant enzyme elevation.” Only rarely was one enzyme greater than the significant elevation level and the others not. Then, it was usually the LDH value and represented hemolysis. In evaluating relatively minor degrees of irreversible myocardial damage in a group of patients undergoing cardiac’surgery, it is necessary to employ a very sensitive test with a high degree of specificity. Although total CPK is a sensitive indicator, the enzyme is produced by the skeletal muscle and brain as well as myocardial muscle and lacks specificity in surgical patients. LDH is also a very sensitive indicator, but again because of its presence in virtually all tissues including red blood cells, its specificity is limited. SGOT is considerably less sensitive and also nonspecific. Recent investigators have found that by examining the electrophoretically separated isoenzyme fraction of CPK and LDH, the specificity of each can be increased and by applying both tests together a predictive value of nearly 100 per cent can be obtained. If the second or MB fraction of CPK is elevated on the first postinjury day and the first LDH fraction becomes greater than the second (inverted) on the second or third day, myocardial infarction can be diagnosed with virtually complete certainty. If only the CPK change occurs, it suggests severe but reversible myocardial ischemia, and an inverted LDH isoenzyme pattern alone suggests hemolysis. Postoperative electrocardiograms were read by one of eight cardiologists. Interpretations of these tracings were often made difficult by nonspecific changes from the surgery itself; frequently, it was impossible to determine if a given change was indicative of myocardial injury or perioperative reaction. In an effort to augment the information gained from the electrocardiograms, they were all reviewed by one cardiologist with the aims of the study in mind. Results
One death occurred in the series, this patient dying suddenly 6 hours after operation from unexplained hemorrhage. All the remaining patients are alive to date. Only one has had recurrence of angina during the follow-up period of eighteen months. Significant elevations of cardiac enzymes CPK, LDH, and SGOT, as defined herein, or positive isoenzyme patterns of CPK and LDH suggesting myocardial injury were observed in thirty of ninety-four patients. Of these, fourteen were in the
420
patients receiving the steroid and sixteen in the control group. If only those forty-three patients whose isoenzymes were measured are considered, thirteen (30 per cent) had positive patterns; of these, eight had received the steroid and five had not. (Table I.) The mean value of total CPK in all patients receiving the steroid was 250 U compared with a mean value of 284 U in the controls. Application of Student’s t test (Table II) demonstrated no significant difference between the two populations (p > 0.05). If the absolute value of the MB fraction of CPK is determined in those patients in whom it was present, the mean values of the two groups again did not differ significantly. Finally, as Table II illustrates, no difference was noted in the mean value of either LDH or SGOT. Ten patients demonstrated fairly conclusive electrocardiographic evidence of either transmural or subendocardial infarction in conjunction with significant enzyme elevation. Of these, five were in the steroid-treated and five in the control group. Several other less specific parameters noted in the study are listed in Table I. After completion of the final distal anastomosis, most patients could be weaned from cardiopulmonary bypass within 10 minutes of the time the aortic clamp was released. The number of patients in each group requiring more than this period of weaning was noted; although there are a few more patients in the control group, the difference is not significant. Six patients required the assistance of an intra-aortic counterpulsation balloon before they could be weaned successfully from cardiopulmonary bypass and of these, four had received the steroid. No difference in the incidence of postoperative arrhythmias was noted between the two groups. Respiratory insufficiency enough to require ventilatory assistance for more than one day postoperatively developed in only six patients. These patients were equally distributed between the steroid-treated patients and the controls. A few more patients in the steroid-treated group required more than fourteen days in the hospital after surgery, but again the significance of this difference is doubtful. Comments
A considerable research effort has been directed at defining the effect or corticosteroids on the myocardium and peripheral vasculature. Evidence has been accumulated by Dietzman et al [3] that
The American Journal of Surgery
hkthylprednisolone
TABLE I
Relative Incidence of Abnormal Postoperative Factors in Steroid-Treated versus Control Patients Number of Patients Factors
Steroid Group
Control Group
14 8 5 8 4 4 13 3 12
16 5 5 14 2 6 16 3 9
Significant enzyme elevation Positive isoenzyme profile Enzyme rise and electrocardiographic evidence of infarct
Prolonged wean from cardiopulmonary Intra-aortic balloon required Postoperative bleeding over 1,000 cc
bypass
Arrhythmia Respirator required more than 1 day In hospital more than 14 days postoperatively
suggests rather convincingly that single large doses of corticosteroids produce a gradual systemic vasodilatation that is effective in the treatment of the low cardiac output syndrome. The same investigators noted some inotropic effects of the drug in a few younger patients under the age of thirty years. A direct effect of corticosteroids on the myocardium in which the extent of myocardial damage after infarction was reduced, was suggested by Johnson and co-workers [41 using modest doses of cortisone during a two to three week period. Other investigators [5,6], however, were unable to confirm these findings. Using a more sensitive experimental model, Libby et al [2] demonstrated a significant reduction in myocardial infarction in dogs treated with a single large dose of hydrocortisone (50 mg/kg). This difference was reflected in electrocardiographic changes, tissue levels of CPK, and histologic changes, and on the basis of previous work by Weissman and Thomas [7], it was surmised that the drug possibly exerted its effect by stabilizing the lysosomal membranes within the myocardial muscle cell and preventing disruption of these organelles in response to hypoxia. In view of this excellent experiment, we were surprised to discover no electrocardiographic or enzyme differences between the steroid-treated and control groups in our study. In the experiment by Libby et al [2], however, the ischemic steroidtreated changes seen after occlusion of the coronary artery improved dramatically within 30 minutes after administration of the steroid. This suggests that the reduction in the size of the infarct seen in their steroid-treated animals, rather than reflecting an intracellular effect of the drug, may have been the result of other factors such as coronary vasodilatation with increased collateral blood flow to the ischemic area. Recently, Dietzman et al [B] reported on an apparently retrospective study in which they demon-
vohuna131, *prll1978
TABLE II
Comparison of Mean Values of Postoperative Cardiac Enzymes in Steroid-Treated versus Control Patients with Application of Student’s t Test
Enzymes CPK Steroid Control CPK-MB Steroid Control
Mean
Standard Deviation t Value
p Value
250 284
254 220
0.69
0.25
20 15
28 23
0.65
0.25
LDH Steroid Control
330 276
145 128
1.91
0.06
SGOT Steroid Control
99 82
75 61
1.18
0.15
fraction
strated less vasoconstriction and improved perfusion during cardiopulmonary bypass in steroidtreated patients. They observed that, presumably as a result of better tissue perfusion, the steroidtreated patients seemed to fare better clinically during the immediate postoperative period. In our study, we did not detect any qualitative difference in the recovery of the patients in the steroid-treated group. Summary
It has been proposed that a single preoperative dose of a corticosteroid may protect the myocardium from ischemic injury during open heart surgery. To test this hypothesis, a prospective, randomized, double blind study was carried out in ninety-five patients undergoing coronary bypass surgery using intermittent ischemic arrest with systemic and local hypothermia. Half the patients received 2 gm (approximately 30 mg/kg) of
421
methylprednisolone 2 hours prior to the initiation of cardiopulmonary bypass and the other half received a placebo. Postoperative electrocardiograms and blood levels of serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase @GOT) were compared in the two groups. No apparent difference was noted in the number of patients with significantly elevated levels of CPK, LDH, or SGOT or in the number with positive isoenzyme patterns of CPK and LDH. Moreover, there was no significant difference in the mean values of CPK, LDH, or SGOT between the two groups. The number of patients with electrocardiographic evidence of myocardial injury (10 per cent) was the same in both groups and no difference was noted in (1) the ease with which patients could be weaned from cardiopulmonary bypass, (2) postoperative arrhythmias, (3) postoperative bleeding, (4) postoperative respiratory insufficiency, and (5) length of hospital stay. It is concluded that a single preoperative dose of 2 gm of methylprednisolone offers no demonstrable protection to the myocardium from the effects of ischemia during coronary artery bypass surgery. References 1. Kansal S, Roitman 0, Kouchoukos N. Sheffield LT: lschemic myocardial injury following aorta-coronary bypass surgery. Chest 67: 20, 1975. 2. Libby P, Maroko PR, Bloor CM, Sobel BE, Braunwald E: Ra duction of experimental myocardial infarct size by corticosteroid administration. J C/in lnwest 52: 599. 1973. 3. Dietzman RH, Ersek RA, Lillehei CW. Castaneda AR. Lillehei RC: Low output syndrome: recognition and treatment. J Thorac Caniiovasc Surg 57: 136, 1969. 4. Johnson AS, Scheinberg SR. Gerisch RA, Saltstein HC: Effect of cortisone on the size of experimentally produced myocard&l infarcts. C/rcu/atbn 7: 224, 1953.
422
5. Opdyke DF, Lambert A, Stoerk HC, Zanetti ME. Kuna S: Failure to reduce the size of experimentally produced myocardial infarcts by cortisone treatment. CircuWon 8: 544, 1953. 6. Galen RS: The enzyme diagnosis of myocardial infarction. Human Pathot6: 141. 1975. 7. Weissman 0, Thomas L: The effects of cotticosteroids upon connective tissue and lysosomes. Recent Prog Honn Res 20: 215,1964. 6. Dietzman RH, Lunseth JB, Goott B, Berger EC: The use of methylprednisolone during cardiopulmonary bypass: a review of 427 cases. J 7horac Canliovasc Sura 69: 670. 1975.
Discussion Wilford B. Neptune (Boston, MA): There are presently a number of services around the country with an excellent record in coronary artery bypass surgery. We have had less than 1 per cent mortality among the last nearly 400 consecutive cases. Despite a low mortality, however, most services without exception report a distressingly high incidence of intra- or perioperative myocardial infarction. This presents a real stumbling block in our discussions with our medical colleagues. I have been using methylprednisolone with this technic in all cases of open heart surgery for the last fifteen years and have never seen any adverse effects. It is going to be difficult to ignore the experimental evidence of Doctor Richard C. Lillehei in demonstrating the advantages of vasodilatation, and, in particular, the protective benefits on the lung as shown by Doctor Sabiston and his group at Duke. Moreover, the experimental and clinical observations reported by Braunwald over the last number of years are impressive. Despite similar statistics, there remains a great variation in regard to technic and conduct of perfusion. With all due respect, I doubt if this relatively small series completely answers the question concerning the protective value of methylprednisolone. It is certain, however, that this type of data must be presented if we are to clear up some of the mystery that still surrounds cardiopulmonary perfusion.
Ths Amarkan Journal of Sur9ary
on Myocardial Preservation
during Coronary Artery Surgery Jeremy R. Morton, MD, Portland, Maine Clement A. Hiebert, MD, Portland, Maine Chris A. Lutes, MD, Portland, Maine Richard L. White, MD, Portland, Maine
Nearly one tenth of patients demonstrate electrocardiographic changes of myocardial infarction after coronary bypass surgery [I]. More significantly, fully one third of patients have significant elevations in postoperative cardiac enzyme levels, suggesting a lesser degree of intraoperative myocardial damage. These changes occur despite the use of intraoperative systemic and local hypothermia to promote myocardial preservation. Recent experimental work by Libby et al [2] suggests that a single dose of corticosteroids may significantly reduce the extent of myocardial injury induced by ischemia. In light of these observations, we have undertaken a prospective, randomized, double blind study of the effect of a single large dose of corticosteroids on intraoperative myocardial preservation during coronary artery surgery. Material and Methods Ninety-five consecutive patients undergoing aortocoronary bypass grafts without associated valve replacement or ventricular aneurysmectomy were included. Four cardiac surgeons participated in the study. Surgical technic was essentially the same in every case. The heart was exposed through a median sternotomy incision and simultaneously the required length of lower saphenous vein was harvested from one or both legs. All of the proximal anastomoses were then completed using an exclusion clamp on the ascending aorta prior to initiation of cardiopulmonary bypass. A disposable pump oxygenator was employed with a single right atria1 venous cannula and an arterial cannula in the ascending aorta. A left atria1 sump was inserted through the right superior pulmonary vein. The patient was cooled to 32V.
From the Department of Surgery. Maine Medical Center. Portland, Maine. Reprint requests should ba addressed to Jeremy R. Morton, MD, 321 Srackett Street, Portland, Maine 04102. Presented at the Fifty-Sixth Annual Meeting of the New England SwgiCal Society. Portsmouth, New Hampshire, September 25-27, 1975.
volum. 131, Apru 4976
For each distal anastomosis, the ascending aorta was cross-clamped and the heart locally chilled with Ringer’s lactate solution at 5°C. Distal anastomoses were performed using 6-O polypropylene suture. On completion of each distal anastomosis, the aorta was declamped and the heart defibrillated and allowed to recover for 5 minutes. This procedure was repeated for each additional anastomosis. Aortic occlusion times varied from 12 to dit minutes. The patients ranged in age from thirty-one to seventy-six years with an average of fifty-three years. Fifty patients had had a previous myocardial infarct, thirtysix had unstable angina, and sixty-five had some degree of impaired ventricular function as determined by ventriculography. Thirteen patients had single, thirty-eight double, thirty-one triple, and thirteen quadruple bypass grafts. The mean pump time for a triple graft was 98 minutes. The mean value for the longest period of continuous aortic occlusion in each patient was 23.5 minutes. The corticosteroid used was methylprednisolone given in a single dose of 2 gm or approximately 30 mg/ kg. Half the patients received the drug and half received a placebo. The drug and placebo were supplied, packaged, and randomly coded by the Upjohn Company. The code was not revealed until the study was completed and all the data had been collected and interpreted. The test drug was administered by intravenous injection immediately prior to induction of anesthesia, which was approximately 2 hours prior to the institution of cardiopulmonary bypass. Serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase (SGOT) were measured on the first three days postoperatively. Electrocardiograms were obtained on the second and fifth postoperative days or more often if indicated. Midway through the study the technic for separating CPK and LDH into isoenzyme fractions became available and was used thenceforth. Some elevation in cardiac enzymes, particularly CPK and LDH, occurred in all patients operated on. It became necessary, therefore, in evaluating those patients in whom isoenzymes were not available, to determine the level for each enzyme above which it was likely that
419
Morton et al
the elevation represented significant myocardial injury. It was apparent that all patients with electrocardiographic evidence of infarction and nearly all patients with isoenzyme patterns suggestive of myocardial injury, as seen subsequently herein, exhibited total CPK values in excess of 300 U (international units per liter), LDH values greater than 300 U, and SGOT values greater than 100 U. These figures were therefore used to define “significant enzyme elevation.” Only rarely was one enzyme greater than the significant elevation level and the others not. Then, it was usually the LDH value and represented hemolysis. In evaluating relatively minor degrees of irreversible myocardial damage in a group of patients undergoing cardiac’surgery, it is necessary to employ a very sensitive test with a high degree of specificity. Although total CPK is a sensitive indicator, the enzyme is produced by the skeletal muscle and brain as well as myocardial muscle and lacks specificity in surgical patients. LDH is also a very sensitive indicator, but again because of its presence in virtually all tissues including red blood cells, its specificity is limited. SGOT is considerably less sensitive and also nonspecific. Recent investigators have found that by examining the electrophoretically separated isoenzyme fraction of CPK and LDH, the specificity of each can be increased and by applying both tests together a predictive value of nearly 100 per cent can be obtained. If the second or MB fraction of CPK is elevated on the first postinjury day and the first LDH fraction becomes greater than the second (inverted) on the second or third day, myocardial infarction can be diagnosed with virtually complete certainty. If only the CPK change occurs, it suggests severe but reversible myocardial ischemia, and an inverted LDH isoenzyme pattern alone suggests hemolysis. Postoperative electrocardiograms were read by one of eight cardiologists. Interpretations of these tracings were often made difficult by nonspecific changes from the surgery itself; frequently, it was impossible to determine if a given change was indicative of myocardial injury or perioperative reaction. In an effort to augment the information gained from the electrocardiograms, they were all reviewed by one cardiologist with the aims of the study in mind. Results
One death occurred in the series, this patient dying suddenly 6 hours after operation from unexplained hemorrhage. All the remaining patients are alive to date. Only one has had recurrence of angina during the follow-up period of eighteen months. Significant elevations of cardiac enzymes CPK, LDH, and SGOT, as defined herein, or positive isoenzyme patterns of CPK and LDH suggesting myocardial injury were observed in thirty of ninety-four patients. Of these, fourteen were in the
420
patients receiving the steroid and sixteen in the control group. If only those forty-three patients whose isoenzymes were measured are considered, thirteen (30 per cent) had positive patterns; of these, eight had received the steroid and five had not. (Table I.) The mean value of total CPK in all patients receiving the steroid was 250 U compared with a mean value of 284 U in the controls. Application of Student’s t test (Table II) demonstrated no significant difference between the two populations (p > 0.05). If the absolute value of the MB fraction of CPK is determined in those patients in whom it was present, the mean values of the two groups again did not differ significantly. Finally, as Table II illustrates, no difference was noted in the mean value of either LDH or SGOT. Ten patients demonstrated fairly conclusive electrocardiographic evidence of either transmural or subendocardial infarction in conjunction with significant enzyme elevation. Of these, five were in the steroid-treated and five in the control group. Several other less specific parameters noted in the study are listed in Table I. After completion of the final distal anastomosis, most patients could be weaned from cardiopulmonary bypass within 10 minutes of the time the aortic clamp was released. The number of patients in each group requiring more than this period of weaning was noted; although there are a few more patients in the control group, the difference is not significant. Six patients required the assistance of an intra-aortic counterpulsation balloon before they could be weaned successfully from cardiopulmonary bypass and of these, four had received the steroid. No difference in the incidence of postoperative arrhythmias was noted between the two groups. Respiratory insufficiency enough to require ventilatory assistance for more than one day postoperatively developed in only six patients. These patients were equally distributed between the steroid-treated patients and the controls. A few more patients in the steroid-treated group required more than fourteen days in the hospital after surgery, but again the significance of this difference is doubtful. Comments
A considerable research effort has been directed at defining the effect or corticosteroids on the myocardium and peripheral vasculature. Evidence has been accumulated by Dietzman et al [3] that
The American Journal of Surgery
hkthylprednisolone
TABLE I
Relative Incidence of Abnormal Postoperative Factors in Steroid-Treated versus Control Patients Number of Patients Factors
Steroid Group
Control Group
14 8 5 8 4 4 13 3 12
16 5 5 14 2 6 16 3 9
Significant enzyme elevation Positive isoenzyme profile Enzyme rise and electrocardiographic evidence of infarct
Prolonged wean from cardiopulmonary Intra-aortic balloon required Postoperative bleeding over 1,000 cc
bypass
Arrhythmia Respirator required more than 1 day In hospital more than 14 days postoperatively
suggests rather convincingly that single large doses of corticosteroids produce a gradual systemic vasodilatation that is effective in the treatment of the low cardiac output syndrome. The same investigators noted some inotropic effects of the drug in a few younger patients under the age of thirty years. A direct effect of corticosteroids on the myocardium in which the extent of myocardial damage after infarction was reduced, was suggested by Johnson and co-workers [41 using modest doses of cortisone during a two to three week period. Other investigators [5,6], however, were unable to confirm these findings. Using a more sensitive experimental model, Libby et al [2] demonstrated a significant reduction in myocardial infarction in dogs treated with a single large dose of hydrocortisone (50 mg/kg). This difference was reflected in electrocardiographic changes, tissue levels of CPK, and histologic changes, and on the basis of previous work by Weissman and Thomas [7], it was surmised that the drug possibly exerted its effect by stabilizing the lysosomal membranes within the myocardial muscle cell and preventing disruption of these organelles in response to hypoxia. In view of this excellent experiment, we were surprised to discover no electrocardiographic or enzyme differences between the steroid-treated and control groups in our study. In the experiment by Libby et al [2], however, the ischemic steroidtreated changes seen after occlusion of the coronary artery improved dramatically within 30 minutes after administration of the steroid. This suggests that the reduction in the size of the infarct seen in their steroid-treated animals, rather than reflecting an intracellular effect of the drug, may have been the result of other factors such as coronary vasodilatation with increased collateral blood flow to the ischemic area. Recently, Dietzman et al [B] reported on an apparently retrospective study in which they demon-
vohuna131, *prll1978
TABLE II
Comparison of Mean Values of Postoperative Cardiac Enzymes in Steroid-Treated versus Control Patients with Application of Student’s t Test
Enzymes CPK Steroid Control CPK-MB Steroid Control
Mean
Standard Deviation t Value
p Value
250 284
254 220
0.69
0.25
20 15
28 23
0.65
0.25
LDH Steroid Control
330 276
145 128
1.91
0.06
SGOT Steroid Control
99 82
75 61
1.18
0.15
fraction
strated less vasoconstriction and improved perfusion during cardiopulmonary bypass in steroidtreated patients. They observed that, presumably as a result of better tissue perfusion, the steroidtreated patients seemed to fare better clinically during the immediate postoperative period. In our study, we did not detect any qualitative difference in the recovery of the patients in the steroid-treated group. Summary
It has been proposed that a single preoperative dose of a corticosteroid may protect the myocardium from ischemic injury during open heart surgery. To test this hypothesis, a prospective, randomized, double blind study was carried out in ninety-five patients undergoing coronary bypass surgery using intermittent ischemic arrest with systemic and local hypothermia. Half the patients received 2 gm (approximately 30 mg/kg) of
421
methylprednisolone 2 hours prior to the initiation of cardiopulmonary bypass and the other half received a placebo. Postoperative electrocardiograms and blood levels of serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase @GOT) were compared in the two groups. No apparent difference was noted in the number of patients with significantly elevated levels of CPK, LDH, or SGOT or in the number with positive isoenzyme patterns of CPK and LDH. Moreover, there was no significant difference in the mean values of CPK, LDH, or SGOT between the two groups. The number of patients with electrocardiographic evidence of myocardial injury (10 per cent) was the same in both groups and no difference was noted in (1) the ease with which patients could be weaned from cardiopulmonary bypass, (2) postoperative arrhythmias, (3) postoperative bleeding, (4) postoperative respiratory insufficiency, and (5) length of hospital stay. It is concluded that a single preoperative dose of 2 gm of methylprednisolone offers no demonstrable protection to the myocardium from the effects of ischemia during coronary artery bypass surgery. References 1. Kansal S, Roitman 0, Kouchoukos N. Sheffield LT: lschemic myocardial injury following aorta-coronary bypass surgery. Chest 67: 20, 1975. 2. Libby P, Maroko PR, Bloor CM, Sobel BE, Braunwald E: Ra duction of experimental myocardial infarct size by corticosteroid administration. J C/in lnwest 52: 599. 1973. 3. Dietzman RH, Ersek RA, Lillehei CW. Castaneda AR. Lillehei RC: Low output syndrome: recognition and treatment. J Thorac Caniiovasc Surg 57: 136, 1969. 4. Johnson AS, Scheinberg SR. Gerisch RA, Saltstein HC: Effect of cortisone on the size of experimentally produced myocard&l infarcts. C/rcu/atbn 7: 224, 1953.
422
5. Opdyke DF, Lambert A, Stoerk HC, Zanetti ME. Kuna S: Failure to reduce the size of experimentally produced myocardial infarcts by cortisone treatment. CircuWon 8: 544, 1953. 6. Galen RS: The enzyme diagnosis of myocardial infarction. Human Pathot6: 141. 1975. 7. Weissman 0, Thomas L: The effects of cotticosteroids upon connective tissue and lysosomes. Recent Prog Honn Res 20: 215,1964. 6. Dietzman RH, Lunseth JB, Goott B, Berger EC: The use of methylprednisolone during cardiopulmonary bypass: a review of 427 cases. J 7horac Canliovasc Sura 69: 670. 1975.
Discussion Wilford B. Neptune (Boston, MA): There are presently a number of services around the country with an excellent record in coronary artery bypass surgery. We have had less than 1 per cent mortality among the last nearly 400 consecutive cases. Despite a low mortality, however, most services without exception report a distressingly high incidence of intra- or perioperative myocardial infarction. This presents a real stumbling block in our discussions with our medical colleagues. I have been using methylprednisolone with this technic in all cases of open heart surgery for the last fifteen years and have never seen any adverse effects. It is going to be difficult to ignore the experimental evidence of Doctor Richard C. Lillehei in demonstrating the advantages of vasodilatation, and, in particular, the protective benefits on the lung as shown by Doctor Sabiston and his group at Duke. Moreover, the experimental and clinical observations reported by Braunwald over the last number of years are impressive. Despite similar statistics, there remains a great variation in regard to technic and conduct of perfusion. With all due respect, I doubt if this relatively small series completely answers the question concerning the protective value of methylprednisolone. It is certain, however, that this type of data must be presented if we are to clear up some of the mystery that still surrounds cardiopulmonary perfusion.
Ths Amarkan Journal of Sur9ary