By J. LEONARD CORNING, A.M., M.D., New York, Consultant in Nervous
Diseases to St. Francis Hospital, St. Mary's Hospital, the Hackensack
Hospital, etc.
To merely facilitate the introduction of medicinal agents into the
system by way of the air passages, in the form of gases, medicated or
non-medicated, has heretofore constituted the principal motive among
physicians for invoking the aid of compressed air. The experiments of
Paul Bert with nitrous oxide and oxygen gas, performed over fourteen
years ago, and the more recent proposals of See, are illustrations in
point.
The objects of which I have been in search are quite different from
the foregoing, and have reference not to the introduction of the
remedy, but to the enhancement of its effects after exhibition. Let me
be more explicit on this point, by stating at once that, in
contradistinction to my predecessors, I shall endeavor to show that by
far the most useful service derivable from compressed air is found in
its ability to enhance and perpetuate the effects of soluble remedies
(introduced hypodermically, by the mouth, or otherwise) upon the
internal organs, and more especially upon the cerebro-spinal axis.
Some chemical affinity between the remedy employed and the protoplasm
of the nerve cell is, of course, assumed to exist; and it is with the
enhancement of this affinity--this bond of union between the medicinal
solution and the nervous element--that we shall chiefly concern
ourselves in the following discussion.
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_.)
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