Part 4

E. Action of the Motor Cortical Centres of the Cerebrum.

In all but the very lightest cases of snakebite-poisoning there are always symptoms manifested that cannot be referred to any other cause than an invasion of the centres now under consideration. They range from mere stupor, confusion of thought and delirium to the deepest coma, with complete extinction of consciousness and insensibility to all external impressions. Coma is a frequent and in serious cases an almost invariable symptom in Australia. After the bite of our death adder only we find persons sometimes collapse and expire suddenly, when still conscious and able to answer questions rationally. Coma invariably develops from sleep. It is, in fact, sleep intensified. An almost irresistible desire to sleep is one of the first symptoms to be observed. If the dose of poison imparted by the snake has been small, the desire may pass off or the sleep may not assume the form of coma, but in all serious cases it quickly assumes that form. Vice versa the deepest coma becomes sleep again, when the suspended function of the cortical centres is roused by strychnine injections. The insensible and completely paralysed patient usually announces the gradual return of consciousness by a few groans and uneasy movements and not unfrequently begins to snore, as in ordinary sleep, when a smart shake at the shoulder will rouse him into full consciousness. At other times this transition from coma back to sleep does not take place and consciousness returns quite suddenly, the persons opening their eyes and looking around them, dazed and bewildered, but perfectly conscious at once. When coma is fully established and the largest and most powerful motor-centres have succumbed to the insidious poison, general paresis becomes general paralysis and all the motor-centres of the body are in a condition of more or less suspended functional activity. This and this only is the condition of the centres, the whole secret of snake-poison, that has puzzled the human mind for ages and yet appears so simple when discovered at last. It is beautifully and strikingly illustrated in the phenomena before us. We have coma and complete general paralysis, every motor-nerve cell, from the highest psycho-motor one downwards, is thrown into a state of torpor and has ceased to discharge the life force that regulates every process of life and the entire absence of which inevitably must be death. Only weak, lingering currents are sent forth yet and put off the inevitable finale for a time. But the strychnine is injected and mark the change. It courses quickly to every one of the sleepers, for whom it also has an affinity, but the direct opposite to that of the deadly venom that has overpowered them. It touches them as if with the wand of a magician and orders them to awake and do their work. There is no disobeying the mandate, for it is founded on one of nature's unchangeable laws. Almost immediately the cells begin their work again, the life streams flow afresh, coma and paralysis vanish and within a very short time the subject of this beautiful experiment is snatched from the brink of the grave and restored to life and health.

The phenomena of sleep and coma as the result of a poison acting as a depressant of motor nerve force afford food for some interesting speculations, which, however, as more concerning the psychologist, the writer can only glance at here. It is evident that in the highest of psycho-motor centres, the organs of thought and of consciousness, the paresis of the lower centres assumes the form of sleep, and paralysis that of coma. Sleep, as a partial, and coma, as a complete, obliteration of thought and consciousness must, therefore, be intimately connected with motor nerve function, sleep being a reduction, coma a suppression of the function, or a suspension of thought. Ideation, to use J. S. Mill's very appropriate term for the thought process, appears to be effected by motor nerve currents or, at all events, to be accompanied by them and suspended with their suspension. The thinking principle, the nous within us, is no doubt more than mere nerve action, but it can, apparently, not manifest its presence without motor nerve cells in healthy action. Every thought, though not synonymous, is evidently synchronous with a current of motor nerve force, and it is not improbable that, by means of these currents, that silent transference of thought is effected from brain to brain, which modern psychology has demonstrated to be not only possible but actual under certain conditions. But further speculation on these interesting mysteries it would be out of place here to indulge in.

F. Action on Sensory Centres and the Reflexes.

The sensory sphere remains comparatively unaffected in mild cases, and in the early stages of more serious ones, but when paresis has deepened into paralysis, sensation becomes ever more blunted, and with the advent of coma, of course, quite extinct. Reflexes, both superficial and deep ones, are also completely abolished at this period of the poisoning process, and the nerves of special sense do not react against any, even the strongest possible stimulation. The eye stares vacantly into a glaring light held close before it, and the widely dilated pupil shows no sign of reaction. The ear also appears deaf to any noise, and strong ammonia vapour is inhaled through the nose like the purest air, whilst pricking, beating, and even burning the skin elicit not a quiver of a muscle.

Feoktistow's experiments with regard to reflexes, more especially their restoration by strychnine, differ in their results entirely from Australian observations. Whilst we have no difficulty in restoring them with the drug on man as well as the domestic animals, his experiments on frogs were a failure, and merely showed a decided antagonism between the two poisons. He did not succeed in restoring the reflexes, and, instead of following up with experiments on the higher animals, he trusted implicitly to his results on frogs, and thus lost his opportunity.

G. Irregularities in the Action of Snake-poison.

There is in the whole range of toxicology not a single condition known to us in which the symptoms, both in chronological order and in their strength and relation to each other, show as much variety as those of snake-poison. Experienced observers will agree with the writer that it is but rarely we find two cases of snakebite exactly alike in the symptoms they present. Some of these puzzling variations have already been alluded to, but it is necessary to consider them a little more in detail. Apart from quantitative differences in the poison imparted, they arise principally from the strange capriciousness with which the poison concentrates its action on special nerve centres and leaves others comparatively intact.

The nearest approach to regularity and orderly sequence of the symptoms, as described in the foregoing pages, we find in Australia after the bite of the tiger snake (Hoplocephalus curtus) and the brown snake (Diemenia superciliosa), more especially that of Queensland. Here we can trace the action of the poison distinctly from centre to centre, from the lowest part of the anterior cornua up to the cortex cerebri, and even throughout the sympathetic ganglia as far as they are patent to observation. The poison of these snakes is extremely diffusible and quickly absorbed. It spreads with rapidity and nearly equal force over all the motor centres, the symptoms following each other so quickly as almost to appear simultaneous, though, in reality, successive. But even the poison of these snakes leaves the arms only slightly paretic, when paralysis in all the other voluntary muscles is well pronounced, and does not paralyse them until coma has set in. It also touches the respiratory centre but slightly. Sometimes coma is light and the patients can be roused for a little while, at other times it is deep and lasts till death. But even greater variations are observed occasionally. In one very extraordinary case of tiger snakebite, the patient, a child of 9 years, remained conscious to the last, and after vomiting blood freely died under symptoms of heart failure. In rare cases the symptoms resemble those of cobra poison.

If we turn from these to the black snake (Pseudechis porphyriacus) a different picture presents itself. Its poison does not produce so deep a coma and often none at all. The patients generally feel drowsy and fall asleep, but are easily roused and sometimes awake spontaneously. There is also not the same amount of muscular paralysis. They are frequently able to walk a few steps with assistance and can move in bed, the arms especially being almost free from paresis. But the insidious poison none the less does its work, though its effects are less patent. It concentrates its action on the vaso-motor centre. The victims from hour to hour become more anæmic in appearance through increasing engorgement of the abdominal veins. Anæmia of the nerve-centres hastens the collapse, and from the combined effects of this and heart failure death takes place suddenly and quickly as if in a fainting fit. Here then we have an approach to the effects of viper poison which is also shown in the greater amount of swelling and effusion around the bite and in the bitten limb.

This approach is still closer in the poison of the death adder (Acantophis antarctica). There is generally much extravasation of blood locally. Muscular paralysis is also less pronounced, but sudden collapse from vaso-motor paralysis not unfrequently takes place, when the patients fully conscious are still able to sit up. That leading feature of viper poison, diapedesis with hæmorrhage, does not occur with either.

If we turn from Australian to Indian snakes, the peculiar tendency of the poison to concentrate its action on special nerve-centres becomes still more marked. The predilection of the cobra poison for the respiratory centre has already been dwelt on. More remarkable and strange is the action of the Indian viper-poison on the minute ganglia in the vaso-motor nerve ends, which control the capillary circulation, and by their paralysis bring about extensive hæmorrhage through diapedesis.

It is quite impossible for us with our present scanty knowledge to account for these peculiarities and irregularities in the action of a poison, which we know now to accomplish its destruction of animal life by one uniform design and principle of action. That the protean forms under which the poison-symptoms present themselves are one and all the result of reduction and suspension of motor nerve currents may now be accepted as a well proven and fully established scientific fact. But why the effects of one and the same cause are so varying in their appearance, why the poison of different varieties of snakes, and even that of the same variety under different circumstances, make such a capricious selection among the various motor nerve-centres we can not explain and probably never will. Chemical analysis of the dead poison, no matter how minutely and elaborately it may be effected, will probably never throw much light on the "why" of this strange puzzle, for the subtle phenomena of life are apt to elude the grasp of the analyst. We have to do with a poison transferred from one living organism into another one and modified in its action by the condition of the giver and the constitution and peculiarities of the recipient quite as much probably as by slight variations in its chemical composition. Accepting the "why" of these phenomena like that of many other ones, simply as a fact not to be accounted for at present, we must be content to know "how" they are effected, and, what is of more immediate and paramount importance to know, that we now have an antidote that will deal successfully with them all, that the convulsions and hæmorrhages of the Indian viper-poison and the asphyxia of that of the cobra will yield as readily to strychnine, when properly and boldly applied, as the coma and general paralysis following the bite of the deadly tiger snake.

THE ANTIDOTE.

The theory of the action of snake-poison as that of a specific nerve-poison, depressing and more or less suspending the function of the motor nerve-centres throughout the body, has in the foregoing pages received a double proof of its correctness.

In the first place, all the symptoms the snake-poison produces have been passed in review, and shown to be fully explainable by this theory. On this ground alone it may be claimed to have been fully established; for it is an axiom in science that a theory on any subject must be accepted as correct, if it accounts satisfactorily for all the phenomena observable in connection with that subject by showing them to result from the operation of one law. The second inductive proof of the correctness of the writer's theory has been rendered by the experiments of Feoktistow on animals.

Science, however, demands that a theory thus established inductively must also stand the test of practical application or deduction. It says in the present case:--"Granting your theory to be correct, it is but a theory, which, however valuable it may be as a contribution to science, is of little value to mankind if you cannot apply it practically. If snake-poison merely acts as a depressant on motor nerve-cells without interfering with their structure, you must be able to counteract it by administering some drug or substance which acts as a powerful stimulant on these cells, if such a substance can be found."

It is another illustration of that wise adaptation of means to ends which, throughout the domain of nature, denotes the presence and rule of a Supreme Intelligence, that this substance has been provided for us by nature, though we have been long in finding it. Its discovery in strychnine, and its successful application as the long and vainly sought antidote to snake-poison, are glorious triumphs of scientific deduction.

Strychnine is the exact antithesis to snake-poison in its action. Under its influence every motor nerve-cell throughout the system sends forth stronger currents of nerve force than it does in its normal state. These currents run alike from cell to cell, and from cell to peripheral fibre, and act by means of the latter on all contractile, and especially all muscular tissue, causing contractions, which, after poisonous doses of the drug, assume the form of tetanic convulsions, provoked by the slightest touch or even noise in consequence of highly intensified reflex action.

Whilst, then, snake-poison, as we have seen, turns off the motor-batteries and reduces the volume and force of motor-nerve currents, strychnine, when following it as an antidote, turns them on again, acting with the unerring certainty of a chemical test, if administered in sufficient quantity. Purely physiological in its action, it neutralises the effects of the snake-poison, and announces, by unmistakable symptoms, when it has accomplished this task, and would, if continued, become a poison itself. Previous to this announcement its poisonous action is completely neutralised by the snake-poison, and the latter would therefore be equally as efficacious in strychnine-poisoning as strychnine is in snake-poisoning. Strychnine, in short, is the antidote par excellence of snake-poison, and cannot be surpassed by any other substance known to us.

With the symptoms following the introduction of the subtle ophidian virus into the human and animal system so markedly pointing to strychnine as the antidote, it appears a matter of surprise that it was not used as such before and that it was left to the writer to discover the antagonism between the two poisons. Misleading experiments with the drug on animals erroneously considered to be final in their results, together with confused and contradictory notions about the action of snake-poison, were the chief factors, already pointed out, that caused research on this important subject to remain for centuries so barren of results, and made even able investigators with more correct views than the rest, postpone the discovery of a physiological antidote to a more advanced state of science, when all the time it was lying ready at their hands.

It is self-evident from preceding statements, that in the treatment of snakebite with strychnine the ordinary doses must be greatly exceeded, and that its administration must be continued, even if the total quantity injected within an hour or two amounts to what in the absence of snake-poison would be a dangerous if not a fatal dose. Timidity in handling the drug is fraught with far more danger than a bold and fearless use of it. The few failures among its numerous successes recorded during the last four years in Australia were nearly all traceable to the antidote not having been injected in sufficient quantity. Even slight tetanic convulsions, which were noticed in a few cases, invariably passed off quickly. It should be borne in mind that of the two poisons warring with each other that of the snake is by far the most insidious and dangerous one, more especially in its effects on the vaso-motor centres. The latter are wrought very insidiously, and where they predominate require the most energetic use of the antidote, for whilst the timid practitioner after injecting as much strychnine as he deems safe stands idly by waiting for its effects, the snake virus, not checked by a sufficient quantity of it, continues its baneful work, drawing the blood mass into the paralysed abdominal veins and finally by arrested heart action bringing on sudden collapse. In such cases even some tetanic convulsions are of little danger and may actually be necessary to overcome the paralysis of the splanchnicus and with it that of the other vaso-motor centres.

Whilst then it must be laid down as a principle that the antidote should be administered freely and without regard to the quantity that may be required to develop symptoms of its own physiological action, the doses in which it is injected and the intervals between them must be left to the practitioner's judgment, as they depend in every case on the quantity of snake-poison absorbed, the time elapsed since its inception and the corresponding greater or lesser urgency of the symptoms. If the latter denote a large dose to have been imparted and it has been in the system for hours, delay is dangerous and nothing less than 16 minims of liq. strychnine P.B., in very urgent cases even 20 to 25 minims should be injected to any person over 15 years of age. Even children may require these large doses, as they are determined by the quantity of the poison they have to counteract and are kept in check by it. The action of the antidote is so prompt and decisive that not more than 15 to 20 minutes need to elapse, after the first injection, before further measures can be decided on. If the poisoning symptoms show no abatement by that time, a second injection of the same strength should be made promptly, and unless after it a decided improvement is perceptible, a third one after the same interval. As the action of strychnine when applied as antidote is not cumulative, no fear needs to be entertained of violent effects suddenly breaking out after these large doses repeated at short intervals. They are, so to say, swallowed up by the snake-poison and remain latent except in counteracting the latter. This has now been proven abundantly by scores of qualified observers in all parts of Australia, and still more by Banerjee in India. No hesitation, therefore, should be felt by medical men in other snake-infested countries to adopt the Australian treatment. It is seldom that more than half a grain of strychnine administered in 16m. doses of liq. strychniæ is required here to effectually counteract the venom and place its intended victim out of danger. Ligature and excision of the bitten skin have usually been practised and much of the poison eliminated before the antidote is applied. Our snakes, however, as already pointed out, with their shorter and merely grooved fangs, do not perforate the cellular tissue to such depth nor instil as large a quantity of poison as the cobras, kraits and vipers of India or the rattlesnake of America, all having perforated and much longer fangs and much more productive poison glands. Even if after the bite of a vigorous cobra, for instance, a ligature has been applied and the bitten part deeply excised, a comparatively large quantity of poison will probably be absorbed requiring much larger quantities of the antidote, perhaps grains of it, to effect a cure.

If under the influence of these large doses the symptoms abate, or if the latter are comparatively mild from the first, smaller doses of strychnine should be injected, say from 1/15th to 1/10th of a grain, but under all circumstances the rule that, distinct strychnia symptoms must be produced before the injections are discontinued, should never be departed from. This rule is a perfectly safe one, for its observance entails no danger, a few muscular spasms or even slight tetanic convulsions being easily subdued and harmless as compared with that most insidious condition exemplified in case No. 1, cited below, the first one treated with strychnine by the writer, who, having no experience in the treatment, did not administer quite enough strychnine. The patient, after apparently recovering from a moribund condition and being able to walk and even to mount a horse, remained partly under the influence of the poison and succumbed to it during sleep, when, according to subsequent experience, one more injection would have saved him.

The tendency to relapses is always great when much snake-poison has been absorbed. Apparently yielding to the antidote for a time, the insidious venom, after a shorter or longer interval, during which it appears to have been conquered, all at once re-asserts its presence, and has to be met by such fresh injections, regardless of the quantity of strychnine previously administered, but the amount required in most relapses is not a large one. The writer formerly inclined to the belief that the strain thus put on the delicate nerve-cells would limit the usefulness of the antidote to cases requiring not much above a grain. Knowing the Indian snakes to impart to their victims such comparatively large quantities of venom, he had strong misgivings as to his method standing the severe test of Indian practice; and it was most fortunate for this method that its first practical application in India was made by a gentleman who, whilst thoroughly familiar with its principles and convinced of their correctness, had the courage to apply them fearlessly by injecting what to us Australians appear enormous quantities, ranging as they do up to three and four grains per patient. Dr. Banerjee's eight cases, all successful, and of which the most important one, relating to the much and justly dreaded Duboia Russellii, was published in the November number of the Australasian Medical Gazette, settled the treatment of snakebite in India as well as elsewhere. If the poison of Bungarus coeruleus, Echis carinata, and Duboia Russellii can be successfully counteracted, and if for this purpose four grains of strychnine can be injected with perfect impunity, it may be inferred with certainty that the poison of the cobra, fer-de-lance, and the rattlesnake--in fact, of any snake known to us will be found amenable to the antidote, and that, if four grains can be injected with safety, we may venture on six and eight grains, if they are required. In those cases only where the long fangs of these snakes perforate into a vein, and a large quantity of the venom injected into the blood-stream overpowers the nerve-centres so as to make death imminent, if not almost instantaneous, the subcutaneous injections may be found of little use. Here intravenous injections of half a grain and even one grain doses would appear to be indicated, and might yet fan the flame of life afresh, even when respiration and pulse at wrist have already ceased. We have seen both these functions extinct in Australia and restored by comparatively small doses of the antidote, and can see no reason why a more energetic use of it should not restore them in India.

Considering the terrible mortality from snakebite in India, Dr. Banerjee's merit in being the first to introduce the strychnine treatment there is of a very high order, and his grateful countrymen will ever cherish his memory. When his Excellency the Viceroy had been appealed to in vain by the writer, and the adoption of his method in India urged through two Australian Governors, a native of India has stepped forward and taken the first step towards alleviating an evil that has hurried over two millions of his countrymen in every century to an untimely grave.

The cases as reported by him to the Australasian Medical Gazette are cited below.

CASES.