REMARKS UPON THE PHYSIOLOGICAL AND THERAPEUTICAL EFFECTS OF IODINE, GIVEN IN VERY LARGE DOSES,
In the forms of Iodide of Starch, Hydriodic Acid, and Iodide of Potassium.
By Andrew Buchanan, M.D.
Junior Surgeon to the Glasgow Royal Infirmary.
The following remarks upon iodine comprehend the principal results of clinical observations on the use of that medicine, made during the last nine months in the surgical wards of the Glasgow Royal Infirmary. It was about the beginning of the period just mentioned, that I first became aware of the very large doses in which iodine admitted of being administered. Many of the patients treated took from a quarter to half a pound of it in the course of a month or six weeks; and yet so large a quantity, all of which it was ascertained was absorbed and passed through the body, to be discharged chiefly by the kidneys, produced no injurious effects upon the general health, and in many instances exerted a most salutary influence upon the diseases for which it was proscribed. Struck with a result so much at variance with the commonly received opinions as to the poisonous nature of the preparations of this substance, I prescribed it in every ease in which the use of it was at all admissible, with the view of throwing light both on its physiological and its therapeutical effects. In making known the result of these investigations, I shall first describe the preparations of iodine which were employed; I shall next state the most remarkable physiological effects observed; and, lastly, mention the principal diseases in which it was prescribed, and the opinion I was led to form of its curative influence.
Iodide of Starch
When iodine is given in the form of tincture or of Lugol’s solution, or in any of the other forms in which it is usually administered in the unconmbined state, the dose may be pushed as far as gr. iij. or gr. iv. in the course of the twenty-four hours; but if that dose be increased, and frequently even before attaining it, pain of the stomach and bowels, vomiting, and other symptoms of gastric irritation, are induced. If, however, Lugol’s solution be given in a state of great dilution, and in divided doses, a larger quantity may be taken — even to the extent of gr. vi. of iodine in the course of the day. This last observation, and the nature of the symptoms induced when iodine was found to disagree, led me to believe that the disagreement was to be ascribed to the irritant local action of the preparations employed, and not to any effects produced by the medicine subsequent to absorption. Under these impressions, I was led to look out for some new medicinal preparation of iodine, which might be less acrimonious in its local action, while its absorbability and alterant virtues were not diminished. The iodide of starch suggested itself to me as a substance likely to answer the euds in view. Judging from its taste, I thought it was not likely to prove an irritant preparation, for the acrimonious qualities of the iodine are so blunted by combining with the starch, that the compound tastes much more of starch than of iodine; and on reflecting still further on the digestibility of the starch in the stomach, I thought the combination was not likely to impede, but, on the contrary, rather to promote the absorption of the iodine, and its consequent efficacy as an alterant. These anticipations were fully confirmed by the trials made of the iodide of starch as a medicine.
Iodine and starch appear to be capable, like water and alcohol, of combining together in all proportions. In the receipt given above, the proportions employed are a scruple of starch to a grain of iodine. These were the proportions I tried in the first instance, and I have adhend to them ever since, finding them to answer well. The iodine should be first triturated with a little water, gradually adding the starch, and continuing the trituration till the compound assumes an uniform blue colour, so deep as to approach to a black. The iodide should lie dried with a heat so gentle as to run no risk of driving off' the iodine; and it ought afterwards to be kept in a well-stopped bottle.
Not knowing what change of physiological effects might be induced upon the iodine by combining it with starch, I commenced the use of the new medicine in the very cautious dose of ten grains, equivalent to half a grain of iodine. This dose was gradually increased to 3:v. or 4 grains of iodine in the course of the day, without exciting any unpleasant symptom.
Proceeding, therefore, in the same gradual manner, the dose was augmented to 3iv., equivalent to 12 grains of iodine daily, and still no symptom of gastric irritation was induced, while the secretions were deeply impregnated with iodine. I did not, for some time, judge it prudent to increase the dose further, because, though I felt satisfied that no bad effects were likely to arise from the irritant local action of the iodide of starch, I did not know what might he the consequence of impregnating the system with so large a quantity of iodine. It was only, therefore, after continuing the dose of 3iv. daily for a considerable period, and trying it in various cases, that I ventured to proceed further; no bad consequence of any kind having resulted from these trials.
The dose taken by the patient to whom the medicine had been first given was now increased by degrees, first to 3ss and at length to 3i., three times a day, equivalent to 72 grains of iodine daily; still no symptoms of gastro-intestinal irritation, and no other symptoms of an unpleasant kind, shewed themselves, while the secretions, and more especially the urine, were very deeply impregnated with iodine, becoming as black as ink on the addition of nitro-muriatic acid and starch. I have occasionally exceeded the last-mentioned dose, but not often, both because I thought that dose in all probability sufficient to produce whatever alterant effects could be expected from iodine, and because the bulk of the dose was so great that the patients objected to it, as being more like a meal than a medicine. Having satisfied myself, by many trials, of the safety of these doses of the iodide of starch, I have been in the habit, in persons not labouring under any dyspeptic ailment or constitutional delicacy of habit, and whom I wished to put under the influence of iodine, of commencing the use of the medicine with half-ounce doses, and increase them immediately afterwards to ounce doses, if necessary. As there is no great occasion for nicely apportioning the doses, a heaped teaspoonful, dessert-spoonful, or table-spoonful, are convenient enough measures for smaller quantities in private practice. I have always directed the medicine to be taken in a draught of water gruel.
Some medical friends to whom I mentioned the large doses in which I gave the iodide of starch, were of opinion that it must necessarily be an inert substance. I could, however, see no grounds for that opinion. To say nothing in the meantime of its effects in cases of disease, it is certainly not one of those substances, the inertness of which arises from their passing along the alimentary canal unchanged. This is rendered obvious by the iodine appearing abundantly in the secretions, which shews that it must have been absorbed and pervaded the tissues of the body; and since it is found in the secretions in the same state of chemical combination, as when free iodine in any other form is introduced into the stomach, there seems to be no reason why it should not produce the same alterant effects as the tincture of iodine, only with a degree of energy proportionate to the much larger quantity in which it admits of being introduced into the system.
Thinking it possible, however, that a portion of the medicine might pass undecomposed through the bowels, I have more than once examined the stools of patients taking it in full doses, and never could discover any traces of the dark colour which would, in that case, have been communicated. On the contrary, the stools were, for the most part, of a paler colour than usual. To be still more certain, I had the feces voided by a patient taking the medicine in 3i. doses, subjected to a chemical examination. Water digested over them gave no trace of free hydriodic acid, or soluble iodides. To detect the presence of any undecomposed iodide of starch, the mass was next treated with a solution of potass; but on neutralising the potass, not one particle of starch was precipitated. It follows, then, that the whole iodine given in combination with starch undergoes the same changes in the first passages as free iodine given in any other vehicle, and that it is wholly absorbed into the system; and the only difference between the iodide of starch and other preparations of free iodine, is, that the former exerts no irritant or corrosive action on the stomach and bowels, and admits, therefore, of being introduced into the body in vastly larger quantities.
