We now arrive at our third fact, which will require more extensive elaboration.

Third Fact

The pharmaco-dynamic potency of stimulants, sedatives, analgesics, and probably of all remedies which possess a chemical affinity for nervous matter, is enhanced by exhibiting them (the remedies) in solution or soluble form - hypodermically, by the mouth, or per rectum - while the subject remains in a condensed atmosphere. And, as a corollary, it may be stated that this increase, this enhancement of the potency of the remedy is, within certain limits, in the ratio of the atmospheric condensation.

To express this truth mathematically is not difficult. Thus, when a represents the amount of blood of the whole body, b the amount of the remedy, e the amount of atmospheric compression, and x the pharmaco-dynamic potentiality which we are seeking, we shall then have the simple formula:

x = ( b x e ) / a

A definite conception of the truth of this proposition will, I think, be more readily attained by the presentation of the steps which led me to its discovery.

Let me begin, then, by stating that my attention was attracted several years ago by that unique complex of symptoms known as the "caisson or tunnel disease." As most physicians are aware, the caisson disease is an affection of the spinal cord, due to a sudden transition from a relatively high atmospheric pressure to one much lower. Hence, those who work in caissons, or submerged tunnels, under an external pressure of two atmospheres or even more, are liable to be attacked by the disease shortly after leaving the tunnel. The seizure never, however, occurs while the subject is in the caisson, or in other words, while he remains under pressure. Moreover, when the transition from the condensed atmosphere to that of ordinary density is gradually accomplished, which may be done by letting the air escape from the lock very slowly, the caisson disease is rarely if ever set up. It is the systematic disregard of this principle by those who work in compressed air that is responsible, or largely responsible, for the occurrence of the disease.

The chief clinical features of the caisson disease are pain, which may be relatively mild, as when confined to a circumscribed area of one extremity, or of frightful intensity, as when it appears in the ears, knees, back, or abdomen; anaesthesia and paralysis, usually of paraplegic type; bladder symptoms, assuming the form of retention or incontinence; and, more rarely, rectal disturbances (usually incontinence).

These phenomena, or rather some of them, appear some time within half an hour after the subject has left the compressed atmosphere. It was while investigating this most interesting affection as it occurred in the course of the construction of the Hudson River tunnel, that I was able, at the same time, to study the effects of compressed air upon the organism, and especially upon the nervous system, as exhibited in a large number of persons.

The results of these studies I now submit without hesitation, and in all candor, to the judgment of the profession, believing, as I certainly do, that their practical significance from a neuro-therapeutic standpoint is assured. Without anticipating, however, let me state that the first thing which impressed me about compressed air was its extraordinary effect upon cerebral and cerebro-spinal function.

Those who remain for a certain length of time, not too long, however, in the condensed atmosphere, exhibit a most striking exacerbation of mental and physical vigor. They go up and down ladders, lift heavy weights, are more or less exhilarated, and, in short, behave as though under the influence of a stimulant.

Hardly had I observed these things, which are perfectly well known to those who have been able to familiarize themselves with the ordinary effects of compressed air as used in caissons and submarine works of various kinds, when my attention became attracted by what at first appeared to be a phenomenon of trivial importance. In a word, I observed that some of the men exposed to the effects of the compressed air were more exhilarated by it than others. Upon superficial reflection one might have supposed that this discrepancy in physiological effect was to be accounted for merely on the basis of constitutional idiosyncrasy; maturer thought, however, convinced me that the exaggerated effects of the condensed air were both too numerous and too constant to be amenable to such an explanation. This led me to study the habits of the men; and thus it was that I arrived at a discovery of real practical value to neurotherapy. To be brief, I found that a certain percentage of the men, before entering the compressed air employed in the construction of the Hudson River tunnel, were in the habit of drinking a quantity of alcohol, usually in the form of whisky. So long as these men remained outside the tunnel, where the atmospheric conditions were normal, they were not visibly affected by their potations.

When, however, they entered the compressed air of the tunnel, but a short time elapsed before they became exhilarated to an inordinate degree, acting, as one of the foremen graphically expressed it, "as though they owned the town."

On the other hand, when the customary draught of alcohol was withheld from them, these same men were no more, if as much, exhilarated on entering the compressed air as were their fellows.

The effects of alcohol, then, are enhanced by exposing the subject to the influence of an atmosphere condensed to a considerable degree beyond that of the normal atmosphere.

Acting on the hint derived from this discovery, I proceeded to administer absinthe, ether, the wine of coca, vermouth, champagne, and other stimulants, before exposing the subject to the influence of the condensed atmosphere, and invariably observed analogous effects, i.e., palpable augmentation of the physiological effects of the remedy.

Upon what principle does this augmentation of physiological effect depend? how is it to be accounted for?

In my opinion, the answer to this question may be given as follows: In the first place, we know that the primary effect of the compressed air upon the organism must be to force the blood from the surface of the body toward the interior, and especially into the cerebro-spinal canal. Or, to express it more succinctly, the blood will be forced in the direction of the least resistance, that is, into the soft organs inclosed by bony walls, which latter completely shut out the element of counter-pressure. Now, when the blood stream is freighted with a soluble chemical of some sort - let us say, for the present, with alcohol - this medicated blood will exert its greatest chemical effect where the tension - the pressure - is greatest, that is, in the cerebro-spinal canal. The reason for this is found in the fact that endosmosis is most pronounced where the blood pressure is greatest. This explanation of why the effects of alcohol are enhanced by exposing the individual who has taken it to the effects of a condensed atmosphere will, I believe, appeal to the physiological conceptions of most medical men.

It was the above course of reasoning which, at this stage of the argument, led me to the idea that, just as the effects of stimulating substances are enhanced by exposing the subject to the influence of compressed air, so, inversely, sedatives and analgesics, when brought in solution into the blood stream, either hypodermically or by the stomach, might be greatly enhanced in effect by causing the subject to remain, while under their influence, in a condensed atmosphere.

When I came to investigate the validity of these predictions, as I did shortly after the introduction of antipyrin, phenacetin, and the other members of the same group of compounds, I found my predictions verified, and, indeed, exceeded. To summarize the whole matter, I ascertained that not only could therapeutic effects be obtained from much smaller doses by exposing the subject to the influence of a condensed atmosphere, but, what was of equal interest, I found that the analgesic influence of the remedies was much more permanent, was prolonged, in short, by this mode of administration. When we consider how great must be the nutritive changes in the nervous system, and especially in the cerebro-spinal axis, consequent upon increasing the blood pressure in this way, I hardly think that these things should be matters of astonishment.

Concerning The Practical Application Of The Foregoing Facts

Truths like the foregoing possess, however, much more than a theoretical interest, and we should be greatly lacking in perspicuity did we not seek to derive from them something further than a foundation for mere speculation. Indeed, the whole tenor of these facts is opposed to such a course, for, view them as we may, the thought inevitably arises that here are things which contain the germ of some practical acquisition. This, at least, is the impression which they engendered in my own mind - an impression which, being unable to rid myself of, I have allowed to fructify. Nor has regret followed this tenacity of purpose, since, by the combination of the three principles previously enunciated, I have been able to devise a procedure which, in my hands, has yielded flattering results in the treatment of a wide range of nervous affections, and notably so in melancholia, chorea, insomnia, neurasthenia, and painful conditions of various kinds.

Recapitulation Of Argument

The method in question consists, then, in the combination of the three facts already elucidated. To recapitulate, they are:

1. That the effects of remedies upon the cerebro-spinal axis may be enhanced by the sequestration of the blood contained in one or more extremities, previous to the administration of the medicament. This is only another way of saying that the quantity of a remedy required to produce a given physiological effect may be reduced by any expedient which suspends, or sequestrates, the blood in one or more extremities. As has been previously said, however, care should be exercised to avoid dangerous exsanguination of the trunk, and consequently of the respiratory and cardiac centers contained in the medulla. This may be done by compressing the central portion of both artery and vein; but I shall presently indicate a better way of accomplishing the same thing.

2. The duration of the effect of a remedy upon the cerebro-spinal axis is in the inverse ratio of its volatility. For this reason the anaesthetic effects of ether disappear shortly after removal of the inhaler, whereas solutions of antipyrin, phenacetin, morphine, and other salts possessing an affinity for nervous tissue exert much more permanent effects upon the cerebro-spinal system.

It is evident, therefore, that the administration of remedies designed to exert an influence upon the central nervous system in the form of gases must be far inferior to the exhibition of potent solutions hypodermically or by the mouth.

3. The pharmaco-dynamic potency of stimulants, sedatives, analgesics, and probably of all remedies possessing a chemical affinity for nervous matter, is enhanced by exhibiting them (the remedies) in solution, or at least in soluble form while the subject remains in a condensed atmosphere.

And, as a corollary to this, it may be stated that this increase - this enhancement of therapeutic effect - is, within physiological limits, in the ratio of the atmospheric condensation. By physiological limits we mean simply that there is a degree of atmospheric condensation beyond which we cannot go without jeopardizing the well-being of the subject.

(To be continued.)

Paper Read Before The British Association

Elec. Engineer.

On the "Effective and Rapid Induction of General Anaesthesia," the New York Medical Journal, October 22 and December 24, 1887.