Chapter 5

By way of introduction, I may recall the fact that my attention was directed several years since to the advisability of devising some means by the aid of which medicinal substances, and more especially anæsthetics, might be made to localize, intensify, and perpetuate their action upon the peripheral nerves. The simple problem in physiology and mechanics involved in this question I was fortunate enough to solve quite a long time ago; and I must confess that in the retrospect these undertakings in themselves do not seem to me of great magnitude, though in their practical application their significance appears more considerable. Herein lies, it may be, the explanation of the interest which these studies excited in the profession at the time of their publication. These things are, however, a part of medical history; and I merely refer to them at this time because they have led me to resume the solution of a far greater problem--that of intensifying, perpetuating, and (to some extent at least) localizing the effects of remedies upon the brain and spinal cord. I speak of resuming these studies because, as far back as 1880 and 1882, I made some attempts--albeit rather abortive--in the same direction.

In constructing the argument for the following study, I am beholden more especially to three facts, the knowledge of which came to me as the direct result of experimental tests. One may place confidence, therefore, in the procedure which I have based upon these premises, for at no point, I think, in the following argument will mere affirmation be found to have usurped the place of sound induction. Without anticipating further, then, let me specify as briefly as may be the nature of these facts.

PREMISES OF ARGUMENT. _First Fact._--The amount of ether, chloroform, chloral hydrate, the bromides, strychnine, and many other remedies, required to produce physiological effects upon the cerebro-spinal mechanism may be reduced by first securing a ligature around the central portion of one or several of the limbs of an animal, so as to interrupt both the arterial and venous circulation.

The proof and explanation of this may be thus presented:

In the first place, it is well known that children and small animals are affected by much smaller quantities of anæsthetics and other medicinal substances than are required to produce equal effects in men and large animals.

At first sight, there appears to exist a certain definite relation between the weight of the animal and the quantity of medicament required to produce physiological effects. On closer inquiry, however, we find behind this proposition the deeper truth that the real proportion is between the magnitude of the blood-mass and the amount of medicament. Thus, if we withdraw a considerable amount of blood from a large dog, we may be able to affect him by much smaller doses than those required under ordinary circumstances; and, among human beings, we find the anæmic much more susceptible to remedies than the full-blooded of equal weight.

The degree of saturation of the blood-mass with the remedy is obviously, then, the principal thing; the greater the amount of blood, the more remedy--everything else being equal--we shall have to give in order to obtain definite results.

If we wish to embody the proposition in a mathematical statement, we may do so in the following simple manner:

Let a represent the total quantity of blood, _b_, the amount of remedy exhibited, and _x_ the magnitude of the physiological effect. We shall then have the simple formula, x = b / a.

Again, if we withdraw a certain quantity of blood from the circulation by venesection, and call that amount _d_, we shall then have the formula x = b / (a-d).

But, if we wish to act upon the organs of the trunk, and more especially upon those contained within the cerebro-spinal canal, it is not necessary to resort to such a drastic expedient as copious blood-letting; for, in place of this, we may dam up and effectually eliminate from the rest of the body a certain amount of blood by passing a ligature around the central portion of one or several extremities, so as to interrupt the circulation in both artery and vein. When this has been done it is clear that we may introduce a remedy into the system by way of the stomach, or hypodermically into some portion of the trunk; and it is equally certain that a remedy so introduced will be diluted only in the ratio of the amount of blood freely circulating, and more especially by that contained within the trunk and head. That which is incarcerated behind the ligatures is as effectually withdrawn from the realm of physiological action as though it had been abstracted by the surgeon's knife. Elimination by the knife and elimination by the ligature are, for present purposes, then, one and the same thing. Hence, if we let _d'_ represent the amount of blood incarcerated behind the ligatures, _x_ the magnitude of the physiological effect which we are seeking, _b_ the amount of remedy exhibited, and a the total amount of blood contained in the whole organism, we shall have the formula,

b b x = ------ = ----- a - d' a - d

Several years since, I had an excellent opportunity of proving the truth of the foregoing, in connection with the administration of ether in the case of a patient who resisted all attempts to anæsthetize him in the ordinary way.

The case in question was a man under treatment at the Manhattan Eye and Ear Hospital, upon whom it was deemed advisable to perform an operation. As has been said, the ordinary means of inducing anæsthesia had proved ineffectual, for the man was a confirmed drunkard; and it was at this juncture that I was called in consultation and requested by my friend, Dr. David Webster, one of the surgeons of the hospital, to endeavor to devise some means of getting the man under the influence of the anæsthetic.

The procedure which I suggested was this:[3] Around the upper part of each thigh a flat rubber tourniquet was tightly drawn and secured in place in the usual manner. By this means the sequestration of all the blood contained in the lower limbs was accomplished; but, inasmuch as both artery and vein were compressed, only the amount of blood usually contained in each limb was shut off from the rest of the body--which would not have been the case had we contented ourselves with merely compressing the veins, as some have done.

[Footnote 3: On the "Effective and Rapid Induction of General Anæsthesia," the New York _Medical Journal_, October 22 and December 24, 1887.]

In subsequently commenting on my published report of this case, that most accomplished writer and physician, Henry M. Lyman--than whom there is no greater authority on anæsthesia--observes that the plan proposed and adopted by me on this occasion (that of compressing both vein and artery) is far preferable to compression of the vein alone.

The reason for this is not far to seek. When we compress the veins alone there is a rapid accumulation of blood in the extremities through the accessions derived from the uninterrupted arteries. Now, as this blood is derived from the trunk, and consequently also from the organs contained within the cerebro-spinal canal, there is danger of syncope and even heart failure. When, on the other hand, both artery and vein are compressed no such derivative action occurs, and all danger is, consequently, removed. With an apology for this brief digression, I now return to the interesting case which has given rise to it.

Having, as previously stated, applied tourniquets to the central portion of the lower limbs, the ether cap was placed over the mouth and nose of the patient, and in an incredibly short time he was unconscious, and the surgeons were able to go on with the operation.

The late Dr. Cornelius R. Agnew and many other members of the staff of the hospital were present, and gave emphatic expressions of approval.

Dr. F.W. Ring, assistant surgeon to the Manhattan Eye and Ear Hospital, declared that both the amount of ether and the time consumed in its administration were infinitesimal when compared with what had been expended in previous efforts at inducing anæsthesia in the usual way. The facts brought out on this occasion with regard to the administration of ether have since been repeatedly verified by different observers; so that at the present day their validity cannot be questioned. I will merely add, however, that I have long known that the dosage of phenacetin, antipyrine, morphine, chloralamid, chloral, the bromides, and many other remedies might be reduced by resort to the same procedure; all of which is merely equivalent to stating that their pharmaco-dynamic energy may be increased in this way. And this brings us to the second fact, which requires no special elaboration, and may be stated thus:

_Second Fact._--The duration of the effect of a remedy upon the cerebro-spinal axis is in the inverse ratio of its volatility; and this is equally true whether the remedy be given with or without the precautions previously detailed. For example, the anæsthetic effects of ether disappear shortly after removal of the inhaler, whether we apply tourniquets to the extremities or not; but, on the other hand, the analgesic influence of antipyrin, phenacetin, morphine, and other like remedies lasts very much longer, and their dose may be reduced, or--what is the same thing--their pharmaco-dynamic potency may be enhanced by the sequestration of the blood contained within the extremities. So far as I know, I was the first to announce this fact. In so far as a simple expression of the above truth is concerned, we may employ the following formula:

Let _a_ represent the normal blood-mass contained in the entire body, _d_ the amount of blood sequestrated by the ligatures, _b_ the amount of the remedy, _c_ the volatility of the remedy, and _x_ the pharmaco-dynamic potency of which we are in search; we shall then have

b x = ----------- (a - d') × c

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:

b x e x = ----- 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; anæsthesia 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 anæsthetic 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_.)

* * * * *

EYESIGHT: ITS CARE DURING INFANCY AND YOUTH.[1]

[Footnote 1: A lecture delivered before the Franklin Institute, December 5, 1890.--_From the Journal of the Institute_.]

By L. WEBSTER FOX, M.D.

Medical science, as taught in our medical colleges to-day, has two objects in view: (1) the prevention of disease; (2) the amelioration of disease and its cure. Some of our advanced thinkers are suggesting a new mode of practice, that is the prevention of disease by proper hygienic measures. Chairs are being established and professors appointed to deliver lectures on hygiene. Of what value is the application of therapeutics if the human economy is so lowered in its vital forces that dissolution is inevitable? Is it not better to prevent disease than to try the cure after it has become established, or has honeycombed the constitution?

These few preliminary remarks are _apropos_ to what is to follow in the subject which I have selected as the topic for discussion this evening.

Vision is the most useful of all the senses. It is the one gift which we should cherish and guard the most. And at no time in one's life is it more precious than in infancy and youth.