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“Salvage the pacemaker” at autopsy
Letters to the Editor
Needed:
An F.D.A.
for surgery?
To the Editor: If heart attacks were caused by germs, it properly would be said that we the people are in the midst of a raging epidemic of a highly lethal disease. If the medical profession advised for the treatment of this epidemic the widespread use of an incredibly expensive, painful treatment having a small but definite mortality rate of its own, and yet a treatment which had not yet been proved to prolong life in the great majority of cases, it properly could (and would) be said of us that we are a bunch of fools. This precisely is the state of affairs today for coronary bypass surgery. If a wise and dispassionate onlooker were to say that there must be a better way, he would be.right. There is. Much public agitation occurred recently when the popular press reported the results of a scientific study which purported to demonstrate that coronary bypass surgery does not prolong life. While the validity of this conclusion is open to some question, what ie not open to question is that thii kind of proof is being sought years too late. Insofar as drugs are concerned, the medical community long has taken the position, and rightly so, that the burden of proof is on the protagonist who claims safety and efllcacy for a new drug. Right from the beginning, it is up to the drug manufacturer to prove that his drug works, and that the risk of taking the drug is less than the risk of having the untreated disease. Until he does so, the drug is prohibited by the F.D.A. from being sold on the open market. Undoubtedly, some lives may be lost by such a cautious approach, but the attitude of our profession is: when in doubt, an error of omission is better than an error of commission. “Above all, do no harm,” is a venerable and deeply held medical axiom. Unfortunately, this policy rarely, if ever, is followed for surgical procedures A new operation, no matter how bizarre, often can be championed by a surgeon without any proof whatsoever other than his intuitive (and often erroneous) “experience,” if the hospital medical staff and administration are compliant. As first tens, then hundreds, and finally thousands upon thousands of these operations are done, bits and pieces of positive and negative information are accumulated, but, more often than not, even then a firm scientific foundation for the operation still cannot be given. This is the present sad state of affairs for coronary bypass surgery. Ten years down the line, and after tens of thousands of operations have been performed, only recently are we asking for the kind of rigid scientific proof that should have been demanded right from the start. If (as seems probable) a suitable animal model could not have been fashioned, then the procedure should have been labeled an experimental procedure and handled in the same way as a new and unproved drug would have been handled: The initial trials should have been limited to a few authorized hospitals which were prepared to conduct these trials under strict scientific conditions, conditions calculated to yield the maximum amount of information with the least risk to the patients. Let this experience be a lesson to us. Henceforth, we should
540
require of new surgical procedures what we now require of new drugs. Our bull-dog posture should be: “Show me!” Myron R. Schoenfeld, M.D. 2 Overhill Rd. Scarsdale, N. Y. 10583 ‘The author is a cardiologist who prefers to make as few errors of commiseion
Fructeee
as possible.
and triglycerides
To the Editor: In an Annotation in your JOURNAL of December, 1974, Roberts calls attention to the relation between dietary sucrose and triglyceride levels. It is intereating to note that papers published by other authors show that this action is due to fructose.‘~ z Our previous work showed that it is possible to know the reaction of the patients by means of a load of 199 gm. of fiucto!~.~~ ’ With this procedure it is possible to know if the patients need a restriction of sucrose in the diet. M. J. Halpern Department of Biochemistry Institute of Biomedical Sciences Campo de Santana Lisbon, Portugat 1. Cook, G. C.: Absorption and metabolism of D(--) fructose in man, Am. J. Clin. Nutr. 24:1302, 1971. 2. MacDonald, I., and Turner, L. J.: Serum glucose and fructoas levels after sucrose meal5 in atherosclerosis, Nutr. Metab. 13:168, 1971. 3. HaIpem, M. J., and Miguel, M. J.: Fructose and uric acid, Lancet 1:670, 1973. 4. Halpem, M. J.: Saccharides and triglycerides, Am. J. Clin. Nutr. 26637, 1973.
“Salvsge
the pacemaker”
at autopsy
To the Editor: Frequently I receive autopsy material from various sonrces, both Italy and abroad, for cllnicopathologlc control of the conducting system. It is most diatreaaing to note how often serious injury has been inflicted on the cardiac specific tisaue by the customary postmortem procedures in the hands of patkologiata who have not been warned or who do not specialize in cardiac tissue. All too often the ainoatrial (SA) node (Fig. 1) has been badly slashed by the traditional handbook in&ion,l~ * driven along&de the right atrioventricular (AV) walla, and positioned laterally in the anperior vena cava. Often there is a lengthwise cut in the intercaval bridge as well.
April,
I978, Vol. 95, No. 4
Letters to the Editor
Fig. 1. Mutilation of SA nodes which occurred during autopsy, thereby impairing the study of two interesting cases-one from Italy and one from Portugal. (Hematoxylin and eosin; x 10.)
Thorough histologic study of the pacemaker is always hampered by these injuries, and sometimes impeded. Surely it is nonsensical to sacrifice the very “heart’s heart” on the autopsy table to mere manual habit. One can avoid any damage to the SA node by simply extending the lateral incision of right ventricle and AV ring posteriorly into the ostium of the inferior vena cava, instead of the superior. Through this wide gap the inner atria1 wall can be inspected; it can be turned inside out; the intercaval bridge can be further cut lengthwise as medially as possible. Suggestions have been put forward on the matter without apparent succes@; a strong, authoritative, and far-reaching plea to “salvage the pacemaker” at autopsy is needed in order to secure basic morphologic knowledge in the field of arrhythmias. Lino Rossi Via Annunciata 23/4 Milan, Italy REFERENCES
1. American Hospital Association: Postmortem procedures, 1970. .2. Redaelli, P.: Guida all’autopsia Milan, 1950. 3. Rossi, L.: Histopathologic features of cardiac arrhythmias, Milan, 1969. Reactions
to furosemide
To the Editor: In the July, 1977, issue of THIS JOURNAL (94:6, 1977) Dr. Greenblatt and colleagues conclude that furosemide is a “relatively safe diuretic in a wide range of clinical situations,” based on the observation of a 10.1 per cent incidence of “adverse reactions” among 2,367 hospitalized patients in whom only two deaths were felt to be furosemide related. They found the data “re~uring, since serious toxicity was unusual.” While not necessarily disagreeing with their conclusions, we would like to point out that the authors’ criteria for “serious toxicity” are not mentioned in the article. In addition, it is not clear how aggressively possible “reactions” were sought. Were audiograms routinely performed before and after furosemide
American Heart Journal
therapy, or was the patient required to complain of hearing difficulties? There is abundant literature implicating furosemide as a potentially ototoxic drug.‘-3 Were the drugs whose toxicities are known to be potentiated by furosemide, such as cephaloridine, lithium, aminoglycoside antibiotics, and curariform drugs,’ included in the tabulation? There were 320 patients in the report who carried a diagnosis of “congestive heart failure” and 164 patients, “acute myocardial infarction.” As is pointed out in a recent article edited by one of the investigators,” patients with chronic congestive heart failure have been noted to have decreased blood pressure and cardiac output with elevated systemic vascular resistance; “diuretics may be effective but are very likely to decrease cardiac output further and to impair renal function still more.” In acute myocardial infarction, sudden massive diuresis in patients with normal filling pressures might be expected to reduce cardiac output and adversely affect the myocardial oxygen supply/demand balance. We wonder how carefully hemodynamic parameters were monitored in the reported patients. Volume depletion was cited as the commonest “adveme reaction,” based on the finding of elevated blood urea nitrogen in many cases. Were indices of creatinine clearance monitored too? Patients with many of the illnesses represented have, in our experience, diminished appetite and protein intake. Consequently, blood urea nitrogen might not be a sensitive measure of volume status or nephrotoxicity. In summary, we do not disagree with Dr. Greenblatt and associates’ enthusiasm for furosemide as a “safe diuretic.” However, we do not feel that their article has proved the conclusions stated. It should be recalled that 16.3 per cent of their patients died during hospitalization. Moreover, how many receiving furosemide as outpatients suffered consequences in the unsupervised milieu of home is not clear. We believe that the potent “loop diuretics” should still be respected and that appropriate monitoring for adverse effects should accompany their use. Lieutenant S. E. Warren (MC) USNR Commander S. M. Steinberg (MC) USN Nephrology Division Department of Internal Medicine Naval Regional Medical Center San Diego, California 92134 The opinions and sesertions contained herein sre those of the authors and are not to be construed ss official or necessarilyretlecting the view of the Medical Department of the Navy or the Naval Service at large. REFERENCES
1. Vargish, T., Benjamin, R., and She&man. L.: Deafness from furosemidei Ann. Intern. Med. 72:761, 1970. 2. Schwartz. G. H.. David. D. S.. Rieaio. R. R.. et al.: Ototoxicity induced by ‘furosemide.“N, Engl. J. Med. 282:1413, 1970. 3. Wigand, M. E., et al.: Ototoxic side effects of high doses of furosemide in patients with uraemia, Postgrad. Med. J. 47(Suppl):54, 1971. 4. The Medical Letter, 19: No. 2, Jan. 28, 1977. 5. Cohn, J. N., and Franciosa, J. A.: Drug therapy: Vasodilator therapy of cardiac failure (edited by Koch-Weser, J.), N. Engl. J. Med. 297:255, 1977.
541
Needed:
An F.D.A.
for surgery?
To the Editor: If heart attacks were caused by germs, it properly would be said that we the people are in the midst of a raging epidemic of a highly lethal disease. If the medical profession advised for the treatment of this epidemic the widespread use of an incredibly expensive, painful treatment having a small but definite mortality rate of its own, and yet a treatment which had not yet been proved to prolong life in the great majority of cases, it properly could (and would) be said of us that we are a bunch of fools. This precisely is the state of affairs today for coronary bypass surgery. If a wise and dispassionate onlooker were to say that there must be a better way, he would be.right. There is. Much public agitation occurred recently when the popular press reported the results of a scientific study which purported to demonstrate that coronary bypass surgery does not prolong life. While the validity of this conclusion is open to some question, what ie not open to question is that thii kind of proof is being sought years too late. Insofar as drugs are concerned, the medical community long has taken the position, and rightly so, that the burden of proof is on the protagonist who claims safety and efllcacy for a new drug. Right from the beginning, it is up to the drug manufacturer to prove that his drug works, and that the risk of taking the drug is less than the risk of having the untreated disease. Until he does so, the drug is prohibited by the F.D.A. from being sold on the open market. Undoubtedly, some lives may be lost by such a cautious approach, but the attitude of our profession is: when in doubt, an error of omission is better than an error of commission. “Above all, do no harm,” is a venerable and deeply held medical axiom. Unfortunately, this policy rarely, if ever, is followed for surgical procedures A new operation, no matter how bizarre, often can be championed by a surgeon without any proof whatsoever other than his intuitive (and often erroneous) “experience,” if the hospital medical staff and administration are compliant. As first tens, then hundreds, and finally thousands upon thousands of these operations are done, bits and pieces of positive and negative information are accumulated, but, more often than not, even then a firm scientific foundation for the operation still cannot be given. This is the present sad state of affairs for coronary bypass surgery. Ten years down the line, and after tens of thousands of operations have been performed, only recently are we asking for the kind of rigid scientific proof that should have been demanded right from the start. If (as seems probable) a suitable animal model could not have been fashioned, then the procedure should have been labeled an experimental procedure and handled in the same way as a new and unproved drug would have been handled: The initial trials should have been limited to a few authorized hospitals which were prepared to conduct these trials under strict scientific conditions, conditions calculated to yield the maximum amount of information with the least risk to the patients. Let this experience be a lesson to us. Henceforth, we should
540
require of new surgical procedures what we now require of new drugs. Our bull-dog posture should be: “Show me!” Myron R. Schoenfeld, M.D. 2 Overhill Rd. Scarsdale, N. Y. 10583 ‘The author is a cardiologist who prefers to make as few errors of commiseion
Fructeee
as possible.
and triglycerides
To the Editor: In an Annotation in your JOURNAL of December, 1974, Roberts calls attention to the relation between dietary sucrose and triglyceride levels. It is intereating to note that papers published by other authors show that this action is due to fructose.‘~ z Our previous work showed that it is possible to know the reaction of the patients by means of a load of 199 gm. of fiucto!~.~~ ’ With this procedure it is possible to know if the patients need a restriction of sucrose in the diet. M. J. Halpern Department of Biochemistry Institute of Biomedical Sciences Campo de Santana Lisbon, Portugat 1. Cook, G. C.: Absorption and metabolism of D(--) fructose in man, Am. J. Clin. Nutr. 24:1302, 1971. 2. MacDonald, I., and Turner, L. J.: Serum glucose and fructoas levels after sucrose meal5 in atherosclerosis, Nutr. Metab. 13:168, 1971. 3. HaIpem, M. J., and Miguel, M. J.: Fructose and uric acid, Lancet 1:670, 1973. 4. Halpem, M. J.: Saccharides and triglycerides, Am. J. Clin. Nutr. 26637, 1973.
“Salvsge
the pacemaker”
at autopsy
To the Editor: Frequently I receive autopsy material from various sonrces, both Italy and abroad, for cllnicopathologlc control of the conducting system. It is most diatreaaing to note how often serious injury has been inflicted on the cardiac specific tisaue by the customary postmortem procedures in the hands of patkologiata who have not been warned or who do not specialize in cardiac tissue. All too often the ainoatrial (SA) node (Fig. 1) has been badly slashed by the traditional handbook in&ion,l~ * driven along&de the right atrioventricular (AV) walla, and positioned laterally in the anperior vena cava. Often there is a lengthwise cut in the intercaval bridge as well.
April,
I978, Vol. 95, No. 4
Letters to the Editor
Fig. 1. Mutilation of SA nodes which occurred during autopsy, thereby impairing the study of two interesting cases-one from Italy and one from Portugal. (Hematoxylin and eosin; x 10.)
Thorough histologic study of the pacemaker is always hampered by these injuries, and sometimes impeded. Surely it is nonsensical to sacrifice the very “heart’s heart” on the autopsy table to mere manual habit. One can avoid any damage to the SA node by simply extending the lateral incision of right ventricle and AV ring posteriorly into the ostium of the inferior vena cava, instead of the superior. Through this wide gap the inner atria1 wall can be inspected; it can be turned inside out; the intercaval bridge can be further cut lengthwise as medially as possible. Suggestions have been put forward on the matter without apparent succes@; a strong, authoritative, and far-reaching plea to “salvage the pacemaker” at autopsy is needed in order to secure basic morphologic knowledge in the field of arrhythmias. Lino Rossi Via Annunciata 23/4 Milan, Italy REFERENCES
1. American Hospital Association: Postmortem procedures, 1970. .2. Redaelli, P.: Guida all’autopsia Milan, 1950. 3. Rossi, L.: Histopathologic features of cardiac arrhythmias, Milan, 1969. Reactions
to furosemide
To the Editor: In the July, 1977, issue of THIS JOURNAL (94:6, 1977) Dr. Greenblatt and colleagues conclude that furosemide is a “relatively safe diuretic in a wide range of clinical situations,” based on the observation of a 10.1 per cent incidence of “adverse reactions” among 2,367 hospitalized patients in whom only two deaths were felt to be furosemide related. They found the data “re~uring, since serious toxicity was unusual.” While not necessarily disagreeing with their conclusions, we would like to point out that the authors’ criteria for “serious toxicity” are not mentioned in the article. In addition, it is not clear how aggressively possible “reactions” were sought. Were audiograms routinely performed before and after furosemide
American Heart Journal
therapy, or was the patient required to complain of hearing difficulties? There is abundant literature implicating furosemide as a potentially ototoxic drug.‘-3 Were the drugs whose toxicities are known to be potentiated by furosemide, such as cephaloridine, lithium, aminoglycoside antibiotics, and curariform drugs,’ included in the tabulation? There were 320 patients in the report who carried a diagnosis of “congestive heart failure” and 164 patients, “acute myocardial infarction.” As is pointed out in a recent article edited by one of the investigators,” patients with chronic congestive heart failure have been noted to have decreased blood pressure and cardiac output with elevated systemic vascular resistance; “diuretics may be effective but are very likely to decrease cardiac output further and to impair renal function still more.” In acute myocardial infarction, sudden massive diuresis in patients with normal filling pressures might be expected to reduce cardiac output and adversely affect the myocardial oxygen supply/demand balance. We wonder how carefully hemodynamic parameters were monitored in the reported patients. Volume depletion was cited as the commonest “adveme reaction,” based on the finding of elevated blood urea nitrogen in many cases. Were indices of creatinine clearance monitored too? Patients with many of the illnesses represented have, in our experience, diminished appetite and protein intake. Consequently, blood urea nitrogen might not be a sensitive measure of volume status or nephrotoxicity. In summary, we do not disagree with Dr. Greenblatt and associates’ enthusiasm for furosemide as a “safe diuretic.” However, we do not feel that their article has proved the conclusions stated. It should be recalled that 16.3 per cent of their patients died during hospitalization. Moreover, how many receiving furosemide as outpatients suffered consequences in the unsupervised milieu of home is not clear. We believe that the potent “loop diuretics” should still be respected and that appropriate monitoring for adverse effects should accompany their use. Lieutenant S. E. Warren (MC) USNR Commander S. M. Steinberg (MC) USN Nephrology Division Department of Internal Medicine Naval Regional Medical Center San Diego, California 92134 The opinions and sesertions contained herein sre those of the authors and are not to be construed ss official or necessarilyretlecting the view of the Medical Department of the Navy or the Naval Service at large. REFERENCES
1. Vargish, T., Benjamin, R., and She&man. L.: Deafness from furosemidei Ann. Intern. Med. 72:761, 1970. 2. Schwartz. G. H.. David. D. S.. Rieaio. R. R.. et al.: Ototoxicity induced by ‘furosemide.“N, Engl. J. Med. 282:1413, 1970. 3. Wigand, M. E., et al.: Ototoxic side effects of high doses of furosemide in patients with uraemia, Postgrad. Med. J. 47(Suppl):54, 1971. 4. The Medical Letter, 19: No. 2, Jan. 28, 1977. 5. Cohn, J. N., and Franciosa, J. A.: Drug therapy: Vasodilator therapy of cardiac failure (edited by Koch-Weser, J.), N. Engl. J. Med. 297:255, 1977.
541