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longer time, would be serviceable in sustaining a slight narcotism. It is probable that in some chronic diseases of the throat or bronchial passages, where the effect of a local narcotic would be desirable, this mode of practice may find favour from its success. Again, it may be that in disease of the lungs themselves, where there is loss of structure (cavity), anhydrous chloral may be inhaled in minute quantities with advantage. I name these points in order to call the attention of fellow physicians to the mode of administration I have ventured to suggest.

Connected also with anhydrous chloral is another reasonable suggestion; I mean the plan of applying the agent as a narcotic caustic to unnatural growths and ulcerating fungoid surfaces. I find that by applying the fluid to my arm freely there is destruction of the epidermis (scarf skin), so that without any pain the epidermis peels off, almost dry, at the point where the fluid has been placed; and that when on this exposed surface some of the fluid is applied, the true skin is in turn affected, so that in a day or two what the ancients called an issue may be developed, the tissues destroyed coming away in the form of scales. The surgeon will at once see the practical utility of an agent possessing these properties, and he may in some instances subcutaneously inject the fluid if the outward employment of it be too slow.

It is a very curious experiment to subject freshly drawn blood to anhydrous chloral, and to observe microscopically the changes that ensue. The action of the chloral is to extract water both from the liquor sanguinis and the corpuscles, and to form crystalline chloral hydrate. Into this formation the shrinking corpuscles sink, while the fibrine remains free from precipitation; but if water be added, so as to dissolve and remove the hydrate that has been formed, the corpuscles are to some extent restored, and the fibrine coagulates and separates in the usual way.


Under favouring conditions anhydrous chloral is converted into an insoluble substance, to which the name of "metachloral" has been applied. The change sometimes occurs spontaneously, as it has done in a specimen now on the table; but it is always effected when chloral is brought into contact with sulphuric acid. Dr. Versmann has made for me some beautiful specimens of metachloral by this last-named process.

Metachloral is a white substance, easily reducible into a fine powder, but insoluble in water and in alcohol. It is isomeric with chloral itself, being merely different in respect to physical condition. When it is treated with an alkali it yields, as chloral does, an alkaline formate and chloroform. These facts led me to ask whether, in the animal body, metachloral would undergo decomposition and produce specific narcotic effects; and here, again, a series of results were obtained of great interest. Administered to birds in the form of pilule, and to other animals either in the same form or in suspension in gum emulsion, the metachloral, so insoluble in water, is found to undergo solution in the animal secretions, and to produce the same narcotic effects as the chloral hydrate, viz. narcotism, muscular prostration, and decrease of animal temperature.

In the pigeon from ten to fifteen grains are sufficient to take full effect. The animal in the course of an hour becomes drowsy, and in an hour and a half is in a perfect sleep, from which, nevertheless, it may be roused, to fall back again into sleep with great rapidity: the sleep lasts from three to four

hours. The temperature of the body undergoes considerable change, falling, in the pigeon, full five degrees Fahrenheit, and remaining so reduced that a period of eight and even nine hours is required for its complete restoration to the natural standard. On frogs the effect of metachloral is equally marked. A frog weighing ten drachms is fairly narcotized in thirty minutes by a dose of a quarter of a grain, the insensibility continuing many hours and closely simulating death. During the period of deep insensibility the muscles remain in the most extreme state of flaccidity, but do not fail to respond to the galvanic stimulus.

To rabbits comparatively larger doses of metachloral may be administered by the mouth without exciting any effect whatever. To a large rabbit weighing eight pounds, ten grains may be given with absolute freedom from symptoms of narcotism; but when the dose is increased to twenty grains a very distinct effect is produced. About one hour following upon the administration the animal sinks into sleep precisely as if he had taken chloral hydrate, and passes through all the stages of narcotism and recovery in the same way.

The action of metachloral is full of interest in a physiological point of view, and goes far, I think, to sustain Liebreich's original view of the action of chloral hydrate, viz. that the narcotism produced by it is due to the action of chloroform liberated within the body. On this view metachloral is first changed in the body, under the influence of alkali, into the soluble condition, after which it passes into the hydrate, and then into alkaline formate and chloroform. It is thus slower than the hydrate and slower than the anhydrous chloral in its action, but in the end the effects from it are the same. Metachloral admits of being employed medicinally; it may be combined with morphia, quinine, and other alkaloids, and will, I think, be found to possess many useful medicinal qualities.


When bromine is made to act upon chlorine, a substance called bromal is the product. It is an oily substance like chloral, and when acted upon by alkalies is decomposed into formiate of the alkali employed, and into bromoform, the analogue in the bromine of chloroform in the chlorine series. The composition of bromal is C, HBr,O. When it is treated with water a crystalline substance, bromal hydrate, is produced. The composition of bromal hydrate is C, H Br, O 2H, O; it is the analogue in the bromine of the chloral hydrate in the chlorine series. Bromal hydrate has an odour somewhat like chloral hydrate; its crystals are very soluble in water, and it may be administered in solution by the mouth or by hypodermic injection.

Very soon after the discovery of the action of chloral hydrate I commenced a research on the physiological properties of the bromal hydrate. Two other observers also moved in the same path, and have preceded me in recording what they had observed. One of these is Dr. Steinann, of Berlin, the other Dr. John Dougall, of Glasgow. In their researches nearly the same class of inquiries were instituted as in my own, the same animals were subjected to observation, and practically the same results were obtained.

In order to produce marked effects from bromal hydrate, much smaller doses are required than of the corresponding chloral compound; five grains of the former are equivalent to ten of the latter. After an efficient dose the symptoms produced resemble in many respects the symptoms that follow chloral; i. e. there is great muscular prostration and a kind of narcotism, attended, however, with very slight insensibility, except in cases in which the dose has been dangerously large, In extreme cases only is there really deep

anæsthesia; in all cases there is sudden and extreme decrease of the animal temperature. In birds, rabbits, guineapigs, as well as in the human subject, these phenomena are observable. But there are other symptoms belonging to bromal hydrate which are peculiar to it, and which render its practical utility, according to our present knowledge of it at any rate, doubtful. It is intensely irritating; it causes great difficulty of respiration; it so suddenly and effectually reduces the animal temperature that the accumulation of fluid in the bronchial canals, from condensation, is a source of positive danger, and altogether its internal employment would be unwise. I agree with Drs. Steinann and Dougall as to the mode of its action, and, with them, attribute the phenomena to the effects of the bromoform that is liberated in the body after the dose has been administered; I agree also with Dougall that the cause of death, when the dose is fatal and slow, is due to asphyxia. I attribute the asphyxia primarily to the fall of temperature of the body, and secondarily to condensation of water in the bronchial passages.

One- condition I have noticed which seems not to have fallen under the attention of the learned observers I have named, viz. that in birds a large dose of the bromal hydrate may destroy life almost instantaneously by an intense convulsion, amounting, in fact, to suddenly developed tetanus.

The chief interest at this moment attaching to bromal hydrate is the difference that is seen in its action, in comparison with the action of chloral hydrate. It illustrates how a difference of chemical elementary constitution and of weight modifies physiological action; how the heavier bromine in combination with carbon, hydrogen, oxygen, and water differs in action from chlorine in similar combination. The science of therapeutics will ultimately rest on these distinctions.


At the Meeting of the Association held at Newcastle-on-Tyne in 1863, I introduced this curious and potent substance to the notice of the Association, and explained, as best I could, its history and its physiological properties. Every year since then some new fact of interest has attached to the substance, and the immediate past year is not different in this respect from those that have preceded it. The first observer of the action of nitrite of amyl on the animal functions was Professor Guthrie, F.R.S., then of Edinburgh, and now of the School of Mines, London. Professor Guthrie observed, while working in the laboratory with nitrite of amyl, that the inhalation of its vapour produced flushing of the face, rapid action of the heart, a peculiar breathlessness, such as occurs after fast running, and disturbance of cerebral action. These facts, most ably described by the Professor, became known to Mr. Morison, a dentist in Edinburgh, who thought from them that the substance might be made of service for the treatment of persons who were suffering from faintness. He therefore brought some of the compound to the College of Dentists, a Society then existing in London, and the Council of that institution referred the whole subject to me, with a request that I would report to them. The task was readily undertaken, and the study connected with it has not been completed at this hour.

I take the liberty of mentioning these details for the sake of historical accuracy. From the circumstance that I have introduced nitrite of amyl greatly into medical practice, and have been year after year treating of its action, it has been all but universally believed that I made the earliest observations upon it; I would correct this error: I have worked industriously with nitrite of amyl, have studied carefully its mode of action, and have sug

gested many new applications of it; but the credit of the earliest observations, as I stated at Newcastle, belongs strictly to Professor Guthrie.

It will be remembered by some that in one of my early papers on nitrite of amyl I pointed out that the effects observed were clearly due to an induced paralysis of the vascular system, of the terminal part of that system, and that the heart passed into vehement motion, not, as I at first had thought, because it was excited by the agent, but because the resistance to its action being removed, it ran down like a clock in which the resistance to the spring is broken by the removing of the pendulum or the pallets. I further explained that the seeming over-action produced by the nitrite was in truth no evidence of power or tension of muscle, but that in truth, under the influence of the nitrite, the muscular system is brought into extreme relaxation, so that the substance might be used as a remedy for the relief even of tetanic spasm. These views have been sustained by later observation. It remained, however, still to discover how far the relaxation of vessels from nitrite of amyl extended to the functions of special organs of the body; and during the present year I have followed up this line of research in respect to the changes producible by it in the pulmonary organs, the lungs. The study has been most fruitful, and will, I think, as it is followed up, open quite a new field of accurate and sound observation as to the mode in which many diseases of the lungs take their origin.

As there may be many here who are not conversant with the nature and properties of nitrite of amyl, I may say briefly, in respect to it, that it is an amber-coloured fluid, having the odour of ripe pears, and, although requiring a high temperature for ebullition, volatilizing very readily on exposure to the air.

When taken into the body nitrite of amyl produces intense flushing of the face, throbbing and sensation of fulness in the head, rapid action of the heart, and in time a sense of breathless exhaustion. In my previous Reports I have entered at length into details of its action, of which the following is a summary.

The nitrite, though insoluble in water, will enter the body and produce its specific action by any channel of the body, by the cellular tissue, stomach, blood. It produces general muscular paralysis, affecting directly or indirectly

all the motor centres.

It exerts no primary action on the sensory centres, and therefore does not produce anæsthesia.

Its paralyzing action seems first to be directed to the organic nervous centres, by which the vascular tension is reduced. It acts, in fact, after the manner of an emotional shock, leading quickly to paralysis of the minute vessels.

It prevents oxidation by its presence, and possesses distinct antiseptic powers. It produces a peculiar tarry condition of the blood, but does not materially impede coagulation.

It neutralizes the tetanic action of strychnia, and removes tetanic spasm. On reviewing these inferences of former years, as thus detailed, I see no occasion to change one of them; indeed I believe they have, on the whole, all been confirmed by other observers. The admirable experiments of Dr. Brunton on the action of the nitrite on vascular tension call for special recognition. There is, however, one observation in my Report of 1864 I would like to correct. Speaking at that time of the action of the nitrite on the muscles, I remarked that it first excites the muscular system, and then paralyzes it. I am in doubt now whether the muscular excitement of which I

spoke in 1864 is a true excitement due to the influence excited by the agent on the motor centres. I think, from my own sensations, it is rather due to an indirect or mental impression, that it indicates a vehement desire to escape from the influence of the agent, like the excitement of fear or frenzy.

Let me from these points turn to the observations of the past year. I observed long ago, in making dissections of the bodies of animals that had died from amyl nitrite, that the condition of the lungs varied much, that sometimes the lungs were of milky whiteness, sometimes of leaden hue, and again of deep dark red hue. It occurred to me at last that these differences were not accidental, but that they depended upon the mode in which the agent destroyed the life of the animal. Thereupon I made direct inquiry into this subject, and was led to discover that I could, practically, modify the circulation of the blood, passing over the lung from the right to the left heart, as I pleased; in other words, I learned that the vessels of the lungs are influenced by the nitrite in the same manner as the vessels of the skin.

The observation thus stated led me naturally a step further. I inquired as to results of different temporary lesions that might be inflicted on the pulmonary organs by the nitrite, and what extremity of lesion could be recovered from under conditions favourable to recovery. I commenced this research in February last, and have carried it on without intermission from that time the results of the labour have been most instructive.

There are four distinct conditions of lung producible by nitrite of amyl; there may be more, but I know of these:

1. If the animal be destroyed by an overwhelming dose of the agent, so that it dies instantly, as it might die from syncope, the lungs are left absolutely bloodless and of pure whiteness. The right side of the heart is in this case paralyzed; but exposed to the air immediately after death it often recovers its power of contraction. In this instance the death is really by syncope; the nervous paralysis is extended immediately to the heart, probably from paralysis of the sympathetic supply, and the right ventricle failing to pour out its blood to the lung, the death is so instantaneous that there is no time left for the production of any organic change.

2. If the death be comparatively slow, if it be preceded by a short interval of muscular prostration, and if it occur from paralysis of the muscles of respiration, then the lungs are left charged with dark tarry blood, but they contain air and are free of congestion. Here the lungs and heart have failed together, and the balance of the pulmonary circulation has been fairly maintained.

3. If the effect of the nitrite be more definitely prolonged, there is produced intense general congestion of the pulmonary vascular system, a congestion so intense that the lungs, full of blood, dark and heavy, will not float in water. The cause of death in this instance is progressive neural paralysis of the pulmonary vessels; it is the equivalent of congestion of the lungs from long expose to extreme cold.

4. The above may all be considered as acute changes in the pulmonary structures, and the two first-named changes are immediately fatal. The last need not be; as it occurs from prolonged and sustained action of the nitrite, in quantities insufficient to kill directly, the effects of sustained congestion may be traced out from day to day for many weeks.

To be accurate in the observations made on this subject, I constructed a glass house or chamber of a capacity of three cubic feet, and so ventilated it that the air could be kept charged with the vapour of the nitrite. In this chamber rabbits and guineapigs were housed. They were carefully fed,

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