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THE CARDIAC ASPECT OF SURGICAL RISK
1164
the medical profession have been inadequately tested for therapeutic potency, while some have little or no curative value. In the case of the arsphenamines small differences in methods of
given. Of the 230 patients, 55 were in the primary and secondary stages of syphilis, 154 suffered from tertiary and late syphilis (including 71 without symptoms or signs, in whom the diagnosis was lead to extreme toxicity, and the based on positive serum tests alone), and 21 were synthesis may careful tests regarded as essential include estimates congenital syphilitics. The continuous alternating of trypanocidal power that afford some guide to method of treatment was adopted and the patients therapeutic potency. In this country all new with early syphilis received six weeks’ intensive preparations of the arsphenamine group are tested medication with arsphenamine followed by twelve clinically under the auspices of the Therapeutic weekly injections of bismuth ethyl camphorate, Trials Committee of the Medical Research Council before they are issued for general use. On the other hand, the practitioner has no means of estimating the value of the various bismuth preparations and must choose from a bewildering variety. It is now recognised that a high content of elemental bismuth is not a useful index of the potency of such products, and that various other factors, including rate of absorption and ability to penetrate, must be taken into consideration. TYTLER BURKE,1 endeavouring to overcome such difficulties, has recommended an ingenious method of estimating the relative values of the various antisyphilitic remedies by which a chemotherapeutic index is obtained for each of them by dividing the maximum tolerated dose by the minimum curative dose in the experimental rabbit. In this way he has evolved an efficiency scale in which the bismuth preparations, and other accessory medicaments, are rated in proportion to arsphenamine, the drug of choice : the doses of all available drugs have their therapeutic unit values, which provide a reasonably accurate guide to their relative efficiency. But this scheme, which appears to provide a method of restoring order out of chaos, has not been generally adopted. Of the various bismuth preparations the suspensions of the metal and of its insoluble salts have been most widely used. They are slowly absorbed and are believed to maintain a steady therapeutic attack that supplements the action of the rapidly absorbed and rapidly eliminated arsenicals. The water-soluble bismuth preparations are quickly absorbed and excreted in such quantity by the kidney that they are apt to cause nephritis. Intermediate in rate of absorption are the fat-soluble products which LEVADITI considers to be the most effective and which in BuRgE’s efficiency scale It is, therefore, are ranked above the others.
interesting
to have TgrxMON’s2
fat-soluble salt, bismuth
report
on a new
camphorate,
that ethyl clinic in his tested carefully during the This months. past eighteen preparation contains about 23’5 per cent. of elemental bismuth and its solution contains 40 mg. of the metal in the recommended dose of 1 c.cm.-a relatively low bismuth content. Experiments in rats showed the drug to compare favourably as regards toxicity with other fat-soluble preparations in general use, and it was applied to 230 out of a total of 1800 patients under active treatment for, syphilis, providing ample opportunity for detailed comparison. In all, 2444 intramuscular injections of the drug were
has been
Burke, E. T. : Brit. Med. Jour., 1931, i., 306. 2 Thurmon, F. M. : New Eng. Jour. Med., 1936, ccxv., 315. 1
of treatment. This at least twice. In cases of repeated the treatment standing began with twelve
which constituted
one course
course was
longer weekly injections of the bismuth preparation and was usually followed by a course of arsphenamine injections, or, in the case of neurosyphilitics, by Tryparsamide. In a few patients who were
intolerant of the arsenicals and of mercury, the bismuth was used alone for considerable periods -in one case for as long as twenty-nine weeksand in others, with indications for more intensive therapy, heavier dosage was employed. Bismuth ethyl camphorate proved very efficacious in its action both on visible lesions and on serological tests. In the earlier manifestations of syphilis there were no clinical or serological relapses during the administration of this drug after the preliminary In the later manifestacourse of arsphenamine. tions, where the bismuth was used first, the response to treatment was prompt and in some cases remarkable. Occasional " bugbear " cases, which had proved resistant to or intolerant of other forms of treatment, responded well to this preparation. TnunMON claims that the effect of bismuth ethyl camphorate in producing serological changes is one of the strongest points in favour of its use, but both as regards local pain or discomfort and more general toxic effects it compared very favourably with the standard insoluble bismuth salt-bismuth salicylate, suspended in oil-which was in routine use on other patients in the clinic. These findings are particularly interesting as. introducing a valuable preparation and as setting a useful standard for the clinical trial and assessment of new antisyphilitic remedies. <
THE CARDIAC ASPECT OF SURGICAL RISK
problems which arise when operation is. required by a patient who suffers also from cardiovascular disease are never simple. Nor can they be satisfactorily solved by any formula or any opinion based merely on statistical and theoretical THE
evidence. Each case must be faced on its own merits. There can be little help in the knowledge that a surgeon found that seventy-five patients, who underwent operation in similar circumstances. to those now present, recovered, if the practitioner can see no reason to place a patient among the seventy-five rather than among the other unlucky twenty-five. Similarly the formulated guides for determining the operative risk of everypatient according to an equation worked out regarding blood pressure-the formula and rule of’ BARACH and of MOOTS-cannot be relied on except
1165 a generalised probability. Even the operation so completely satisfying. Generally the breath-holding test of myocardial effi- patient is a woman who, if relieved, has still many ciency is, according to KIRSCHNER,1 not to be years of happy life before her, and the disability trusted. " These tests," he says, " give little or from which she is rescued is most distressing. But there is one respect in which the thyrotoxic no indication as to the capacity of the heart to withstand operative procedures." The only safe patient is peculiar. Generally, when assessing the guide is a complete judgment which embraces the risk of operation, the worse the heart the more mental and physical qualities of the patient as chary will the surgeon be of interfering. Faced well as his definite organic troubles, and the with a patient suffering from thyrotoxicosis the prognosis for him if no operation is performed, surgeon has to take a different view, for the operation is designed to relieve the heart condition as well as an estimate of the probable result, immediate and remote, of performing it. itself, and it is often safer for a patient thus affected Sometimes the problem is simplified by the to face operation than avoid it. As has been extreme nature of one or other of the factors written,3 " It is commonly believed that when which enter into it. The surgical state, for example, the heart is seriously affected an operation should which calls for operation may be such that it can be delayed. In general this view is unwise and be said with certainty, " This man will die shortly unsafe ; the affection of the heart is another reason if he is not relieved." This certainty must then for thyroidectomy." For these patients, also, be weighed against the probability of the patient modern anaesthetic technique has greatly improved dying on the table from the combined effect of the chance of safe operation ; the risk is very operation and anaesthetic. In holding the scales different from what it was before premedication the ansesthetist’s help should be called in on and non-toxic gases were at the surgeon’s disposal. occasions of this kind, for not only will the immeValvular disease of itself, if fully compensated, diate outcome rest largely on how well he does has long ceased to be regarded as adding much to his part, but also, if the worst occurs, it is more the operative risk, except in the eyes of the general than likely to be attributed to the anaesthetic. public to whom " heart disease " spells inevitable Yet so far as the anaesthetic is concerned it is disaster at operation. Most irregularities of cardiac remarkable how comparatively innocuous cardio- action and extrasystole are regarded with equanivascular troubles are, and it is rarely indeed that mity by surgeon and anaesthetist, although their the anaesthetist will seek to veto an operation presence should lead to careful examination, includwhich the surgeon wishes to perform on a patient ing electrocardiography. Generally the symptom of suffering from heart disease. This is not because heart disease which is of most import from the the effects of general anaesthetics on the heart can surgical standpoint is shortness of breath. When be disregarded. On the contrary, recent cardio- this is present risk is always increased, and especiof the heart2 show plainly ally if the operation or anaesthetic involves any investigations graphic that no less than 75 per cent. of subjects under element of asphyxia. Advanced arterio-sclerosis anesthesia show some type of arrhythmia; but is often associated with other physical qualities the normal heart is more affected than the abnormal. which render the subject an unfavourable one for Moreover, the subjects of cardiovascular affections operation. In the presence of these the surgeon stand the induction of anaesthesia particularly will commonly recommend operation only when well, because impaired circulation is accompanied this is needed as a life-saving measure. How by muscular development below the normal, and successful it may be even in highly unfavourable these subjects are little liable to the excitement conditions of the patients’ cardiovascular systems and spasm which constitute a prime danger in is well illustrated by three histories recently narcosis. But the comparative immunity from recorded.4 It might almost equally well be said risk of these patients does not extend to those of cardiovascular conditions as it was of head who have myocardial defect. Here is the real injuries, that none is slight enough to be ignored peril, for a heart may be, through its muscular nor serious enough to be despaired of. It is also degeneration, ill-fitted to withstand the extra clear that correct judgment of the risk of operating strain of any operation, and yet may have given on a patient suffering from heart disease requires but little evidence beforehand of its imperfection. the collaboration of physician and surgeon. The These are the patients whose true state will only latter can scarcely be expected to estimate the be revealed by searching preliminary examina- kind or duration of life which the patient’s cardiac tion, both verbal and physical. Fortunately, condition will allow him to lead if no operation modern improvements in anaesthetic practice have is performed. Yet this consideration must obvireduced the risks in this class of patient, for it ously affect the decision, and, on the other hand, was they who provided the principal source of the physician is less well qualified than the surgeon fatalities under chloroform. to judge the immediate risks of operation. On Whether to operate or not on the patient suffer- this point in. many instances the experienced ing from Graves’s disease is often a difficult ques- anaesthetist should also be consulted, for what tion. These subjects offer some of the worst risks he will give and how he will give it may play the which the surgeon is called on to undertake but, dominating part in ensuring the success of the on the other hand, in few conditions is a successful operation and a smooth recovery from it.
as
giving
excellent
1 Kirschner, M. : Lippincott. 1931.
Operative Surgery. Philadelphia: J. B.
2 Jour. Amer. Med. Assoc., Feb. 8th, 1936, p. 434.
3
Thomson, p. 221.
A. P. :
Birmingham Med. Rev., September, 1936,
4 Proc. Staff Meetings Mayo Clinic, Sept.
30th, 1936.
the medical profession have been inadequately tested for therapeutic potency, while some have little or no curative value. In the case of the arsphenamines small differences in methods of
given. Of the 230 patients, 55 were in the primary and secondary stages of syphilis, 154 suffered from tertiary and late syphilis (including 71 without symptoms or signs, in whom the diagnosis was lead to extreme toxicity, and the based on positive serum tests alone), and 21 were synthesis may careful tests regarded as essential include estimates congenital syphilitics. The continuous alternating of trypanocidal power that afford some guide to method of treatment was adopted and the patients therapeutic potency. In this country all new with early syphilis received six weeks’ intensive preparations of the arsphenamine group are tested medication with arsphenamine followed by twelve clinically under the auspices of the Therapeutic weekly injections of bismuth ethyl camphorate, Trials Committee of the Medical Research Council before they are issued for general use. On the other hand, the practitioner has no means of estimating the value of the various bismuth preparations and must choose from a bewildering variety. It is now recognised that a high content of elemental bismuth is not a useful index of the potency of such products, and that various other factors, including rate of absorption and ability to penetrate, must be taken into consideration. TYTLER BURKE,1 endeavouring to overcome such difficulties, has recommended an ingenious method of estimating the relative values of the various antisyphilitic remedies by which a chemotherapeutic index is obtained for each of them by dividing the maximum tolerated dose by the minimum curative dose in the experimental rabbit. In this way he has evolved an efficiency scale in which the bismuth preparations, and other accessory medicaments, are rated in proportion to arsphenamine, the drug of choice : the doses of all available drugs have their therapeutic unit values, which provide a reasonably accurate guide to their relative efficiency. But this scheme, which appears to provide a method of restoring order out of chaos, has not been generally adopted. Of the various bismuth preparations the suspensions of the metal and of its insoluble salts have been most widely used. They are slowly absorbed and are believed to maintain a steady therapeutic attack that supplements the action of the rapidly absorbed and rapidly eliminated arsenicals. The water-soluble bismuth preparations are quickly absorbed and excreted in such quantity by the kidney that they are apt to cause nephritis. Intermediate in rate of absorption are the fat-soluble products which LEVADITI considers to be the most effective and which in BuRgE’s efficiency scale It is, therefore, are ranked above the others.
interesting
to have TgrxMON’s2
fat-soluble salt, bismuth
report
on a new
camphorate,
that ethyl clinic in his tested carefully during the This months. past eighteen preparation contains about 23’5 per cent. of elemental bismuth and its solution contains 40 mg. of the metal in the recommended dose of 1 c.cm.-a relatively low bismuth content. Experiments in rats showed the drug to compare favourably as regards toxicity with other fat-soluble preparations in general use, and it was applied to 230 out of a total of 1800 patients under active treatment for, syphilis, providing ample opportunity for detailed comparison. In all, 2444 intramuscular injections of the drug were
has been
Burke, E. T. : Brit. Med. Jour., 1931, i., 306. 2 Thurmon, F. M. : New Eng. Jour. Med., 1936, ccxv., 315. 1
of treatment. This at least twice. In cases of repeated the treatment standing began with twelve
which constituted
one course
course was
longer weekly injections of the bismuth preparation and was usually followed by a course of arsphenamine injections, or, in the case of neurosyphilitics, by Tryparsamide. In a few patients who were
intolerant of the arsenicals and of mercury, the bismuth was used alone for considerable periods -in one case for as long as twenty-nine weeksand in others, with indications for more intensive therapy, heavier dosage was employed. Bismuth ethyl camphorate proved very efficacious in its action both on visible lesions and on serological tests. In the earlier manifestations of syphilis there were no clinical or serological relapses during the administration of this drug after the preliminary In the later manifestacourse of arsphenamine. tions, where the bismuth was used first, the response to treatment was prompt and in some cases remarkable. Occasional " bugbear " cases, which had proved resistant to or intolerant of other forms of treatment, responded well to this preparation. TnunMON claims that the effect of bismuth ethyl camphorate in producing serological changes is one of the strongest points in favour of its use, but both as regards local pain or discomfort and more general toxic effects it compared very favourably with the standard insoluble bismuth salt-bismuth salicylate, suspended in oil-which was in routine use on other patients in the clinic. These findings are particularly interesting as. introducing a valuable preparation and as setting a useful standard for the clinical trial and assessment of new antisyphilitic remedies. <
THE CARDIAC ASPECT OF SURGICAL RISK
problems which arise when operation is. required by a patient who suffers also from cardiovascular disease are never simple. Nor can they be satisfactorily solved by any formula or any opinion based merely on statistical and theoretical THE
evidence. Each case must be faced on its own merits. There can be little help in the knowledge that a surgeon found that seventy-five patients, who underwent operation in similar circumstances. to those now present, recovered, if the practitioner can see no reason to place a patient among the seventy-five rather than among the other unlucky twenty-five. Similarly the formulated guides for determining the operative risk of everypatient according to an equation worked out regarding blood pressure-the formula and rule of’ BARACH and of MOOTS-cannot be relied on except
1165 a generalised probability. Even the operation so completely satisfying. Generally the breath-holding test of myocardial effi- patient is a woman who, if relieved, has still many ciency is, according to KIRSCHNER,1 not to be years of happy life before her, and the disability trusted. " These tests," he says, " give little or from which she is rescued is most distressing. But there is one respect in which the thyrotoxic no indication as to the capacity of the heart to withstand operative procedures." The only safe patient is peculiar. Generally, when assessing the guide is a complete judgment which embraces the risk of operation, the worse the heart the more mental and physical qualities of the patient as chary will the surgeon be of interfering. Faced well as his definite organic troubles, and the with a patient suffering from thyrotoxicosis the prognosis for him if no operation is performed, surgeon has to take a different view, for the operation is designed to relieve the heart condition as well as an estimate of the probable result, immediate and remote, of performing it. itself, and it is often safer for a patient thus affected Sometimes the problem is simplified by the to face operation than avoid it. As has been extreme nature of one or other of the factors written,3 " It is commonly believed that when which enter into it. The surgical state, for example, the heart is seriously affected an operation should which calls for operation may be such that it can be delayed. In general this view is unwise and be said with certainty, " This man will die shortly unsafe ; the affection of the heart is another reason if he is not relieved." This certainty must then for thyroidectomy." For these patients, also, be weighed against the probability of the patient modern anaesthetic technique has greatly improved dying on the table from the combined effect of the chance of safe operation ; the risk is very operation and anaesthetic. In holding the scales different from what it was before premedication the ansesthetist’s help should be called in on and non-toxic gases were at the surgeon’s disposal. occasions of this kind, for not only will the immeValvular disease of itself, if fully compensated, diate outcome rest largely on how well he does has long ceased to be regarded as adding much to his part, but also, if the worst occurs, it is more the operative risk, except in the eyes of the general than likely to be attributed to the anaesthetic. public to whom " heart disease " spells inevitable Yet so far as the anaesthetic is concerned it is disaster at operation. Most irregularities of cardiac remarkable how comparatively innocuous cardio- action and extrasystole are regarded with equanivascular troubles are, and it is rarely indeed that mity by surgeon and anaesthetist, although their the anaesthetist will seek to veto an operation presence should lead to careful examination, includwhich the surgeon wishes to perform on a patient ing electrocardiography. Generally the symptom of suffering from heart disease. This is not because heart disease which is of most import from the the effects of general anaesthetics on the heart can surgical standpoint is shortness of breath. When be disregarded. On the contrary, recent cardio- this is present risk is always increased, and especiof the heart2 show plainly ally if the operation or anaesthetic involves any investigations graphic that no less than 75 per cent. of subjects under element of asphyxia. Advanced arterio-sclerosis anesthesia show some type of arrhythmia; but is often associated with other physical qualities the normal heart is more affected than the abnormal. which render the subject an unfavourable one for Moreover, the subjects of cardiovascular affections operation. In the presence of these the surgeon stand the induction of anaesthesia particularly will commonly recommend operation only when well, because impaired circulation is accompanied this is needed as a life-saving measure. How by muscular development below the normal, and successful it may be even in highly unfavourable these subjects are little liable to the excitement conditions of the patients’ cardiovascular systems and spasm which constitute a prime danger in is well illustrated by three histories recently narcosis. But the comparative immunity from recorded.4 It might almost equally well be said risk of these patients does not extend to those of cardiovascular conditions as it was of head who have myocardial defect. Here is the real injuries, that none is slight enough to be ignored peril, for a heart may be, through its muscular nor serious enough to be despaired of. It is also degeneration, ill-fitted to withstand the extra clear that correct judgment of the risk of operating strain of any operation, and yet may have given on a patient suffering from heart disease requires but little evidence beforehand of its imperfection. the collaboration of physician and surgeon. The These are the patients whose true state will only latter can scarcely be expected to estimate the be revealed by searching preliminary examina- kind or duration of life which the patient’s cardiac tion, both verbal and physical. Fortunately, condition will allow him to lead if no operation modern improvements in anaesthetic practice have is performed. Yet this consideration must obvireduced the risks in this class of patient, for it ously affect the decision, and, on the other hand, was they who provided the principal source of the physician is less well qualified than the surgeon fatalities under chloroform. to judge the immediate risks of operation. On Whether to operate or not on the patient suffer- this point in. many instances the experienced ing from Graves’s disease is often a difficult ques- anaesthetist should also be consulted, for what tion. These subjects offer some of the worst risks he will give and how he will give it may play the which the surgeon is called on to undertake but, dominating part in ensuring the success of the on the other hand, in few conditions is a successful operation and a smooth recovery from it.
as
giving
excellent
1 Kirschner, M. : Lippincott. 1931.
Operative Surgery. Philadelphia: J. B.
2 Jour. Amer. Med. Assoc., Feb. 8th, 1936, p. 434.
3
Thomson, p. 221.
A. P. :
Birmingham Med. Rev., September, 1936,
4 Proc. Staff Meetings Mayo Clinic, Sept.
30th, 1936.