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THE THERAPEUTIC EMPLOYMENT OF BROMIDE OF
BY PROFESSOR BINZ, OF BONN.
THE introduction of bromide of potassium into therapeutics is due to a French physician, Dr. Pourché, an inhabitant of the same town in which bromine had been discovered, ten years earlier, by Balard. If only the half of what is vaunted about it at the present time be true, there is much reason to regret that its popularisation has been so long delayed. A salt so easy of application, and so free from danger, well deserved to have earlier become the panacea for a crowd of neuroses.
There are certain experiments, dating from the most recent period, which give me the opportunity to cast a glance upon the modern bromide of potash treatment. From a much earlier date that of 1838-we possess a series of researches upon men and animals; and (from a contemporary standpoint as to method) some of these researches deserve every acknowledgment. From this time a long-persisting ebb ̧ set in, until the almost universal acceptation of KBr within the last ten years had made a new research upon animals indispensable. I believe that this was first done by myself in Germany. My own labours on this subject give me a right to criticise the foreign researches.
The results obtained by me with puppies and rabbits,2 in contrast to the previous therapeutical assertions, were but little reassuring. Chloride of potassium operated quite as
1 See Hagen, "Die seit 1830 eingeführten Arzneistoffe." Leipzig, 1861. 2 Sitzunsgber. der Nieder-Rhein, Ges. f. Nat. u. Heilk. vom März, 1867.
depressingly as the bromide; but bromide of sodium exhibited, even when the animals were, so to say, impregnated with it, an action equally wanting in any correspondence with the medical statements concerning its action on the heart and nerves with that of chloride of sodium. It appeared to me, on the whole, that as regards the action of KBr on the human organism, the properties of potash described by Grandeau and Claude Bernard were to be considered in the first rank.
At the same time Eulenburg and Guttmann were also occupying themselves with researches on KBr.1 As they very quickly published the results of their researches,2 the communication of my own particular research was delayed. They were the chief cause of the repetition of this research and of others upon the potash salts; since the above-named inquirers also came to the conclusion, from experiments on frogs and rabbits, that KBr, Na Br, and NH Br behaved in the same way with the other salts of these alkalies, and not in any specific manner.
Up to and in the year 1868 there appeared a mass of clinical records, the majority reckoning KBr as a nervine, only some few giving a negative result. W. Sander also preceded experimentally, and indeed on men.3 In his short but clear exposition "Upon the therapeutic employment of KBr and KCl," he comes to the following result:-" KBr is only effective when given in large doses. If we give, at first, 78 grains daily (in 3 ounces of water only), and gradually increase the quantity to half as much again, there occurs in many, but far from universally, an improvement in so far as that the number of the (epileptic) attacks diminishes, and the individual fits abate of their intensity and duration. In some cases, in which the regular and typical occurrence of the attacks had been watched for a long time before the bromide was given, the fits remained absent, under the remedy, for several weeks or even months. The employment of chloride of potassium gave the same results in epilepsy as the bromide of potassium, and I have not, so far, seen any case in which the chloride had failed and the subsequent use of bromide succeeded. The chloride, moreover, possesses the
1 Centralblatt, f. d. Med. Wissenschaften. 1867, 18 Mai.
3 Centralblatt, 1868, 817.
following advantages:-1. It has no injurious extra-effects (such as the acne-like eruption, &c., produced by the bromide); 2. Smaller doses of it are sufficient, since it contains more potassium than the bromide; 3. It is considerably pleasanter."
Sander's clinical experience thus harmonised completely with the above related experiments on animals, yet it was but little heeded.
Lewizky's work, "Upon the action of bromide of potassium upon the nervous system," consists of experiments on frogs, and of clinical observations. The first part proves the same facts which all who had made researches on the potash salts had maintained. From the second I may adduce, as important for us on the present question, the fact that in three cases of insomnia-after dysmenorrhoea, in hemiplegia, and in amenorrhoea-quiet sleep was obtained by bromide of sodium in doses of 54 to 82 grains. That the bromide of potassium was also effective is left to be presumed. In the experiments on frogs it was found that KBr contracted the vessels (p. 192). This cannot, however, by any means be assumed to be proved; for the slower flow of blood from the stumps of amputated toes of a frog which has been "fully poisoned" with KBr may well be referred to the unquestionable poisoning of the heart and a consequent lowering of arterial pressure; and Lewizky's direct observations on the vessels of different parts gave results which were discordant with each other. Purser,2 in the same circumstances, could not verify any alteration in the vessels. Everything is wanting, in this research, for the "rational foundation of the hypnotic action of KBr" on an artifically-produced anæmia of the brain. Lewizky says, also, without giving particulars, that he has observed the hypnotic action of KBr. on rabbits, dogs, and healthy men. Nothing is said about bromide of sodium.
The researches of G. J. Schouten,3 of Leyden, upon the physiological action of KBr on rabbits and dogs give substantially a confirmation of what was known before. Personally, however, I must remark that in his literary introduction he makes me
1 Virchow's Archiv. 45, 183.
2 Dublin Medical Journal, 1869, p. 321.
3 Arch. d. Heilkunde, 1871, p. 97.
say the exact contrary of what will be found printed in the particular passage of mine which he quotes. The mistake is so bad that it must have proceeded from a confusion of names. It would seem that I should express myself, further, against the conclusions of two French experimenters (Martin-Damourette and Pelvet). According to Schouten's own quotation, however, their works1 are of distinctly later date than my communication to the NiederRhein-Gesellschaft. I said, and could say, not one syllable about them.
Schroff, jun., like Lewizky in Kasan, Purser in Dublin, and Saison in Paris, found in KBr an antidote to strychnia poisoning in animals. This is no longer a surprise after all that had been already done on this subject by Guttmann3 and Podcopaew.* Everywhere it is the potassium, and the potassium alone, which encounters us with striking phenomena of depression of nerves and muscles. Meihuizen5 further makes out that the action of large doses of potassium-salts (and bromide among them) in restraining reflex action consists in their controlling or preventing that portion of the reflex act which takes place within the spinal cord. (Compare also Eulenburg, Guttmann, and Lewizky.) Very few, and scarcely needing a commentary, are the experimental results of Laborde. He took large doses of KBr (156 to 234 grains), and expresses himself, at p. 554, on the effect in the following way :
"One feels as if taken with a general stupefaction, which invincibly compels sleep. This sleep is rather a state of heavy somnolence; it is often suddenly interrupted, although there are, properly speaking, no dreams, or no dreams that take a definite shape; it is rather a nightmare, and an indefinite nightmare. However, the state of somnolence is indefinitely prolonged, and waking is accomplished with great difficulty: the will seems as if it were lost, and as if one could not regain possession of one's ideas and one's self-consciousness: one feels plunged in hebetude and stupor."
The pulse was very slow, small, and soft; the extremities were
1 Bull. du Thérap. 1867, pp. 241, 289.
2 Mittheilungen aus d. Pharm. Institut. in Wien.
3 Berliner Klin. Wochensch. 1865, Nos. 34, 35, 36.
4 Virchow's Arch. 33, 505.
6 Gaz. Médicale, 1869, Nos. 42, 45, 49, 52.
cool, and, for some eighteen hours, paretic. Laborde therefore took smaller doses (94 grains). Within an hour he felt “a general sensation of well-being, and of calm which invited to sleep the latter, however, was but half established, so to speak: and in this half-sleep there soon came on, especially if one were lying in one's bed, a more or less intense sexual excitement, according to the circumstances, an excitement which was habitually accompanied by erection and emission; this act, of which there is always perfect consciousness, almost always wakes one. Finally, sleep is definitely established, but with more difficulty or less rapidity than when emission does not take place." Besides this there was strong desire to urinate, and bad dreams: and this interesting scene closes with pains in the limbs and muscles on waking. Thus KBr is also an aphrodisiac. What manysidedness!
If now one takes up a monograph1 on the "physiological and therapeutic action of the bromide of potassium and the bromide of ammonium," of 178 pages, one expects that new light will come to us from it, respecting the extensive scope of its title. That is not the case, however, with the American treatise of Clarke and Amory. The former author experimented on himself: 40 to 50 grains of KBr sometimes produced sleep, and sometimes watching. The explanation seems to him simple. KBr contracts the vessels of the brain: again, sleep is nothing but brain-anæmia; the question therefore is, whether the bromide finds the contents of the cranium hyperæmic or already anæmic; the results will be correspondingly different. The experiments of Hammond serve as a support to this view; he has verified, by direct inspection, the bloodless condition of the brain (in a trephined animal) after the administration of KBr; this was caused by contraction of the vessels. Of the possible heart-paralysis from large doses, and the consequent diminution of the blood-pressure, nothing is hinted. Especially it seems as if all the older observations on the potassium-salts as such had no existence for the two authors, since they are never alluded to. Eulenburg aud Guttmann's researches on KBr are only known to them through a French sub-editor; Lewizky's research (cutting off the toes) is represented as taking place somewhere in Berlin, Bromide of Potassium, &c. Clarke and Amory, Boston, 1872.