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THE USE OF DIGITALIS.

Le Roy Crummer, M. D., Omaha, Neb.

HE time of our meeting is so usually taken up with the new and startling in medicine that it may seem somewhat incongruous to devote attention to such a time-worn subject as digitalis, but the new and startling is so often forgotten before the time of the next medical meeting, and digitalis has held its place and value for so long that I have no apology for drawing your attention to this classic drug.

The pharmacopeia directs that the source of all preparations of digitalis shall be the leaves of the fox-glove, picked in August of the second year of the growth of the plant. From these leaves we have the following officinal preparations, the powdered leaf, the solid extract, the fluid extract, and the infusion. The activity of all of these preparations depends directly upon the strength of the original leaves, and for this reason the sources of the leaves must be above suspicion, so that the first rule in the use of digitalis is to be sure that you are using a reliable preparation made from leaves of unquestionable source and proved activity. Digitalis gives its name to a group which contains the following less important drugs, strophanthus, scilla, hellebore, convalaria and apocynum.

The active principle of digitalis has never been isolated with the accuracy desired. Various investigators have described and named several so-called active principles, among which are digitalin, digitalein, digitoxin, digitonen, which are not alkaloids but glucosides. These various active principles are on the market under the above names, but probably none of them are chemically pure substances agreeing in toto with the chemical names given them. Furthermore, none of these isolated principles produce the effect of the leaves themselves.

In addition to the pharmacopeial preparations above mentioned various manufacturing houses have endeavored to make preparations of digitalis for commerce with the idea of presenting the benefits of the officinal preparations without their defects. Among these may be mentioned dialgen, digitalinum verum and digitalone. The deficiency in all of these active principles and commercial articles will be appreciated if we study for a moment the solubility of the glucosides themselves. Nature has combined in the digitalis leaves a series of active principles which meet in an ideal manner the indications for its use. Certain of these principles are soluble in alcohol and not in water, and some are soluble in water and not in alcohol. Consequently all preparations made from the leaves themselves by any of the pharmacopeial methods are deficient in certain active principles and contain proportionately a greater amount of other active principles than they should. In certain cases this is an advantage, as for instance in the use of the infusion of digitalis, which is a stronger diuretic than any other preparation of the drug. In the majority of instances, however, when we wish the well-balanced action of digitalis we are forced to rescrt to the use of the powdered leaf itself.

According to the best observers digitalis increases the power of the cardiac systole by direct action upon the heart muscle. In addition to this it slows the rate of the heart by action by the vagus center, and so prolongs diastole. The result of this combined action is to better fill the

ventricle with blood during diastole and propel a greater portion of the contained blood forward by reason of the increased force of systole. A further action is that of influence upon the vasomotors causing increased arterial tension throughout the peripheral circulation. While the total effect of digitalis, and particularly of its various glucosides, is still the subject of considerable discussion among the pharmacologists I think we can accept the above details as sufficiently proven for clinical purposes.

The indications for the use of digitalis can be summed up in a few words. In cardiac incompensation digitalis is the ideal drug. Cardiac incompensation most frequently results from valvular disease, though it may also originate from disease of the heart muscle itself. In the latter case digitalis is not so reliable, because it can only act upon the muscle fibers which are still comparatively healthy. If the degeneration has proceeded to any great extent digitalis will prove harmful rather than beneficial. This is so true that we may use it as a test of the progress of degeneration, and can say that in the process of degeneration of the heart muscle the cautious use of digitalis gives us the best measure of the extent of the degeneration. When we analyze incompensation from valvular defect we at once meet valvular defects originating from two distinct and separate causes. First, valvular defects dependent upon previous infectious disease or inflammatory conditions of the endocardium. Second, valvular defects dependent upon arterio-sclerotic or other degenerations of the valves or their enviroment.

This degenerative endocarditis is most generally accompanied by arterio-sclerosis, and further degenerative changes within the cardiac walls, consequently digitalis must be used with greater caution. There is no other drug which can replace it, and at the same time, it is here that we experience the bad effects of digitalis more frequently than in any other condition. As I said above, digitalis offers us a true measure of the extent of degeneration, so if the case is not too far advanced we are occasionally enabled to bring about wonderful improvement. It is in this class of cases that the vaso-constrictor action of digitalis is much to be feared, and the drug must never be adminstered in these cases unless we use at the same time the vaso-dilators. As a method of control the sphygmomanometer can be used, and if digitalis increases blood-pressure it must be stopped.

Incompensation due to inflammatory valvular disease is the most favorable of all cardiac conditions to treat by digitalis, but here the location of the valvular defect, or with multiple valvular defects, the location of the predominant lesion, determines to a certain extent the reliability of our treatment.

The best effect of digitalis treatment is found in incompensation due to mitral insufficiency. In fact the number of times recurrent incompensation due to mitral insufficiency can be corrected by the proper use of digitalis is practically without number. When a mitral insufficiency cannot be corrected it means advanced muscular degeneration. Mild grades of mitral stenosis are almost always benefited by digitalis, but button-hole stenosis frequently not only proves refractory to digitalis treatment, but, in fact, cardiac pain and precardial distress may be added to other symptoms and force us to adopt treatment along other lines. Theoretically considered the lesions at the aorta are not to be benefited by the use of

fox-glove, but frequently practice is here opposed to theory, and a sufficient number of cases of aortic regurgitation are benefited so directly that it is always allowable to make a careful attempt to overcome the incompensation due to this lesion by the use of digitalis, and frequently our results surpass expectation. Aortic stenosis of a true physiological nature is very rare indeed, and incompensation here always means an advanced dilatation of the left ventricle, so that we may reasonably expect results from digitalis. However, we must be careful here not to use digitalis too long, as it is sometimes a dangerous drug after the dilatation has been overcome. In general' digitalis must be discontinued when a previously rapid pulse comes down to 72. In the nervous diseases of the heart digitalis has freqently been advocated, but it is usually disappointing in paroxysmal tachycardia and in the rapid heart of Grave's disease. In aneurasthenia cordis, on the other hand, that portion of the digitalis action is which is exercised on the vagus frequently permits us to relieve many of the distressing symptoms. This action is so positive that it may be used from a differential diagnostic standpoint, and when the irritable heart responds at once to the proper exhibition of digitalis it shows us the symptoms have no definite pathological foundation.

While diigtalis will do a great deal in the treatment of heart disease along the lines I have just discussed we cannot expect it to do everything. Certain adjuvants, synergists, and antagonists can be frequently used in combination with digitalis with benefit. The greatest synergist to digitalis action is absolute rest, so that in the beginning stage of incompensation absolute rest is essential to bring about the best effects of digitalis. In fact, we might almost make it a rule that digitalis should never be used with an ambulatory patient. It is too much to expect digitalis to straighten up an incompensated heart in the presence of a large amount of edema. In these cases the edema must be treated as a preliminary to the treatment with digitalis. Here the diuretics and hy. drogogue cathartics aid materially in the subsequent digitalis medication.

In the peculiar form of dropsy which occurs in these cases which have not been able to lie down, and where there is but little accumulation of fluid elsewhere, but extreme edema of the legs, we must frequently resort to puncture of the ankles to get rid of the excessive amount if fluid. I have seen 300 ounces drain from the ankles in the course of twenty-four hours in these cases with an immediate subsequent effectiveness of digitalis, which had previously exerted no influence.

When orthopnea is a prominent symptom with cardiac incompensation morphine is absolutely indispensable. A hypodermic of a grain administered in the evening will almost always secure rest for the patient, and even a few hours sleep will double the effect of our digitalis medication. It is not usually necessary to continue the morphine for more than three or four nights, because within this time the heart power has been improved sufficiently so that the annoying symptom or orthopnea disappears. When digestive disturbance and a swollen liver are the main features of incompensation the preliminary treatment with hydrogogue cathartics is an absolute essential. This form of venous congestion yields better than any other to the depleting effects of catharsis, and with the removal of fluid for the body the digitalis can reach the heart in more concentrated solution and brace up the heart muscle much more rapidly.

With albuminuria due to incompensation, in addition to the digitalis and rest we must enforce strong dietetic measures to bring about relief. The pure milk diet does not deserve the prominence usually accorded it in these cases. In order to administer sufficient calories for the body needs excessive amounts of fluid must be given, if straight milk diet is ordered, which has a tendency to overwhelm an already overworked heart. In these cases with a restriction of fluid to 36 ounces per day, and the calorie needs made up of carbohydrates and fats, results are achieved much easier than with the straight milk diet.

When arterio-sclerosis and degenerative changes are a factor in the case it is absolutely essential to overcome the vaso-constrictor action of digitalis by the simultaneous administration of vaso-dilators. For this purpose we can use the nitrites, either as nitro glycerin or sodium nitrite, or the caffein group. When using these drugs the dosage must be rather larger than is usually given. If the patient has never been a user of alcohol we can accomplish arterial widening more easily with small doses of good whiskey than in any other way. But usually the time will come in these cases where digitalis is no longer effective in doses which can be used without fear of cerebral hemorrhage.

In the majority of cases iron is one of our most useful adjuncts to digitalis medication. The heart muscle is nourished only by the blood flowing through it, and when this blood is deficient in hemoglobin muscular nutrition must suffer, so that we find iron a valuable aid, not only in picking up the individual attack of incompensation, but also as a prophylactic against subsequent attacks.

The Nauheim treatment is a most valuable adjunct to the treatment by digitalis. It is difficult but not impossible to carry out the treatment in this country by the artificial baths, and any good masseur can be instructed in the resistance movements. There is no question but that recompensation can be more firmly established by using this Nauheim treatment than by any other means. In this country at least it must be considered an adjuvant to rather than a substitute for the digitalis treatment.

Digitalis is by some supposed to have a cumulative action. This point is not proven, however, but nevertheless the drug is not one which can usually be continued over long periods. Nothing is more useless than the chronic administration of small doses of tincture of digitalis or heart tablets. In one class of cases is this continuous administration advisable, and that is where the line between compensation and incompensation is very easily broken. In a certain number of these cases, but not in all we can keep the patient up and around by the continuous use of digitalis, but even here it would be better to try and increase the reserve power of the heart by a systematic course of resistance movements.

One of the frequent drawbacks to the use of digitalis is irritation of the stomach. This exists more frequently in fancy than in fact when digitalis is properly given. I have never seen irritation of the stomach follow the administration of the powdered leaf. The Germans in such cases use the infusion given by rectum with reported good success. I have never seen benefit from the hypodermic administration of digitalis or its active principles.

It naturally follows from what I have already said that I consider the best method of administering digitalis is to use pulvis digitalis foliorium, unless there are definite indications for the use of some other preparation. I use the following method: From grain to 13 grains of powdered leaves is administered in capsule form twice daily for four days, using the smaller dose when the leaves are fresh in October, and gradually increasing the dose throughout the year. This gives us not only the maximum of digitalis action, but enables us to measure the chance of recovery with the individual patient. After this period of four days, if deemed advisable, the digitalis can be continued longer, although usually it is wise to withdraw digitalis medication at this time for a period of three or four days, when it may be administered again for a similar time. Ordinarily we begin to get the effect of the drug in eighteen to twenty-four hours, and the effect lasts to a certain extent over three to four days, after being withdrawn. This good effect is manifest not only in improvment in symptoms, but also by demonstrable changes in the size and shape of the heart and in the quality of the auscultatory phenomena. These periods alternate until the desired result is achieved, or until we are convinced that there is nothing gained by doses of this size.

In these bad cases after an interval of two or three weeks of other treatment we can again attempt the use of digitalis, but with an increased dosage, usually doubling the dose, and with the other details of the treatment the same. This may be tried the third time.

When a patient with incompensation is not benefited by digitalis given in this way it is indeed a serious case, and the prognosis is almost hopeless. Occasionally, it is true, the use of other members of the digitalis group will be effective when digitalis itself is not, but these cases are extremely rare, and we can say that, as a general rule, the cases which are not benefited by the above scheme, with intelligent administration of other forms of cardiac tonics in the interval, are not to be benefited by any treatment whatever.

I could cite cases to confirm each point made, but will not take the time of the society for such a purpose. In conclusion, I wish to reiterate briefly the main points that I have brought out above.

Of all drugs of the so-called digitalis group, digitalis itself is the best. Of all forms of digitalis nothing has yet been able to replace the pulvis digitalis foliorium.

Digitalis should always be used in a definite form and a definite dosage, so that we may be able to judge directly of its effects in the individual case, and so form the proper diagnosis.

While digitalis is of benefit in most cases of incompensation its action frequently has to be controlled by the simultaneous administration of synergists and antagonists.