Using Digitalis to the Best Advantage



Fockes Frog Heart Method.- The heart of a normal frog is exposed, the digitalis injected, and the time required for the heart to stop in systole is observed. If this is not between seven and twenty minutes a larger or smaller dose must be given. Four such frogs are weighed after the heart stops, and the averages are taken. The weight divided by the minutes multiplied by the dose in cubic centimeters is the standard, and should be about 10 (e.g., weight, 0.30 gram, dose 0.3 cc.; time, ten minutes for a 10 per cent infusion).

Reed and Vanderkleeds Guinea-pig Method.- Guinea pigs of any size are used, a dose based on that for a 250-gram pig, and adjusted to the weight, being injected subcutaneously into the abdomen. The smallest amount of the preparation which will kill 250 grams of guinea pig in twenty-four hours is the unit.

Hatcher and Brody Cat Method.- A cat is anesthetized and an amount of digitalis less than enough to cause death is injected into a vein. Injection is then discontinued and a standard solution of ouabaine, the value of which is known, is injected until death occurs. The amount less 0.1 mgm. per gram required represents the value of digitals previously given. The amount which would have been required without the ouabaine is calculated by a simple proportion. The test may be modified by giving 0.075 mgm. of ouabaine per kilo, and continuing with the unknown solution until death supervenes, which must take place in one to two hours after beginning the injection. The quantity which represents the activity corresponding to the additional 0.025 mgm. of ouabaine is multiplied by four to give the fatal dose per kilo, which is termed cat unit. The cat method of Hatcher and Brody is considered the best. The cat being a warm-blooded animal, its heart more closely resembles that of man.

It has been proven that investigators working independently in different parts of the country get results that vary less than 10 per cent when assaying samples from the same lot of digitalis by the cat method.

To insure more accurate observations through the use of digitalis of a known and constant behavior a plan was adopted by the Adult Clinic of Bellevue Hospital and the Department of Pharmacology of Cornell University Medical College. This consists in obtaining a quantity of digitalis leaf sufficient to last for a period of two to three years. It is first standardized by the cat unit method and a sample is tested on several patients to determine its clinical effectiveness.

This lot of digitalis leaf is placed in a suitable container sufficient to hold the entire amount. Withdrawals for manufacturing purposes do not exceed a maximum of 10 per cent of the whole amount of the drug. Immediately on withdrawal of a portion of the lot for manufacturing, an equal amount of biologically and clinically standardized digitalis leaf is added to replace the amount withdrawn. After each addition of a new lot the old and the new are intimately mixed. By following this procedure the essential potency of the powdered digitalis leaf remains practically unchanged. At no time can the variation, if any, be more than 10 per cent.

The chief use of digitalis is in the relief of congestive heart failure. In this condition the most striking results are obtained, and benefit is derived regardless of the rhythm of the heart. Clinical and experimental data have brought out the fact that in the presence of heart failure digitalis causes an increase in the cardiac output, in this way creating a more efficient circulation. Digitalis should be given in cases of congestive heart failure, no matter what the cause of the failure is. Relief can be obtained in the presence of active rheumatic carditis, even when the carditis is obviously the cause of the failure. This has been demonstrated by Sutton and Wyckoff. Even in the congestive heat failure which occurs after coronary thrombosis digitalis may be give with benefit to the patient.

Although the most striking results with digitalis therapy are obtained in congestive heart failure, the uses of this drug are by no means limited to this condition. When the ventricular rate in patients having auricular fibrillation is high and it is evident that the high rate may cause symptoms of cardiac insufficiency, digitalis may then be given to keep the ventricular rate down to within normal limits. This from of treatment is more prophylactic than curative, for it is essentially aimed at preventing heart failure. It is also known that digitalis will as times change auricular flutter to auricular fibrillation, in which condition the treatment of the patient can be handled more effectively, and possibly with quinidine.

Gold and Otto have shown that digitalis is capable of diminishing the number of ventricular premature contractions and occasionally cause them to disappear completely. Before digitalis is employed in such conditions, the toxic factor responsible must first be eliminated, and the toxic agent have may be tobacco, alcohol, coffee, etc. If the premature contractions persist, then digitalis may be given.

Digitalis is also of value in preventing the occurrence of attacks of paroxysmal auricular or nodal tachycardia. This, however, should be postponed until quinidine has been thought of and ruled out as contra- indicated. Quinidine, of course, is the specific in these conditions, but quite often, due to certain circumstances, cannot be used without too great danger to the patient.

In the past, and even today, some clinicians give digitalis to support the heart in pneumonia and other infections disease. Recent clinical and laboratory reports have come out which caution against this practice. Digitalis in pneumonia is of no value. In fact, it is harmful in quite a few cases. Increased body temperature increases also the bodys susceptibility to the toxic effects of digitalis. It is best not given at all.

Digitalis is indicated in aortic insufficiency of whatever type. In the stage of decompensation, of mitral involvement, digitalis should be given in its fullest doses. Once the stage of compensation has set in the usefulness of digitalis is diminished. It may be continued for a short time in small doses for its vasodilator effect.

In mitral disturbances, such as mitral insufficiency, digitalis gives very effective relief. In mitral stenosis where there is but a slight closing of the mitral valves and with no tendency to heart block, digitalis may be given with benefit. In those cases where the stenosis is marked and where there is a tendency to heart block, digitalis should not be administered.

In chronic myocarditis small doses of digitalis may be used over long periods of time (not more than twenty days at a time, however) with intervening pauses of five days if of benefit to the patient.

When digitalis is given to a patient with cardiac insufficiency it has a variable action on the systolic pressure; it may lower, raise, or have a no effect on it whatsoever. But it always lowers the diastolic pressure. The diuretic action of digitalis is one of its most valuable properties. It is at once a direct diuretic through heart tonic action and an indirect diuretic through renal vasodilator action. Diuresis produced by digitalis is relatively slow when compared to other diuretic drugs. It begins, on the average, twenty-four to thirty-six hours after administering the drug, and usually continues for several days.

The patient under digitalis medication should be watched at all times for signs of toxicity. These are:.

(1) Persistent nausea or vomiting coming after appreciable amounts of digitalis, and not appearing immediately after the administration of the drug.

(2) The appearance of frequent ventricular premature contractions or bigeminal rhythm in a heart which had not shown these irregularities previously.

(3) Disturbances of vision, usually of color vision, accompanied frequently by a band-like headache.

(4) In auricular fibrillation the slowing of the ventricular rate to below 50 per minute.

(5) The appearance of auricular fibrillation or signs of tachycardia in a heart which had not previously shown them.

Digitalis is perhaps the only drug in the materia medica concerning the dosage of which there seems to be a great deal of mystery. This is more apparent then real, for digitalis can be given for varying degrees of heart damage, which naturally requires different doses. Thus, in cases where digitalis is to the given for its tonic effect and where digitalization is not an immediate problem it may be given in the form of powder or tablets in 12 grain doses, or as the tincture in sixteen minimum cases, three to four times a day.

In cases where digitalization is required there are three methods available:.

(1) The slow method in which digitalization is obtained in from four to six days.

(2) The rapid method in which digitalization is obtained in from one to two days.

(3) The intensive Eggleston body-weight method for use in urgent conditions in which digitalization is obtained in a few hours.

Edward Podolski