On Snake-Poison: Its Action and Its Antidote

Part 2

Chapter 23,397 wordsPublic domain

All other objections to the treatment require but to be glanced at to show their absurdity. Certain crude experiments on dogs made many years ago in India, and put forward as irrefutable at first, have been abandoned of late, and my learned opponents have now taken up a position in their stronghold of statistics, supposed to be impregnable, but in reality only the last refuge of the destitute, a position from which, by dexterous handling of alleged facts, anything and everything can be proven, in short, to use a strong expression, not my own, a convenient and respectable form of lying. By means of these statistics they try to prove, in the first place, that Australian snake-poison is not at all the insidious death-dealing agent it is supposed to be, since, according to statistics, only 126 persons died from it in three colonies within the last ten years. Further study of these statistics leads them to the inference that a strong healthy adult will recover from snakebite _without any treatment_, and thus they finally arrive at the conclusion aimed at, that persons cured by strychnine injections would probably have recovered without them. These are the inferences drawn by men, who, practising in towns, have probably never seen a case of snakebite. How do they tally with the facts of the case? It is true that the mortality among those bitten by snakes is small here as compared with India, though the poison of our snakes, quantity for quantity, has been proven to be quite as deadly as that of the Indian ones. Our greater immunity is due to our snakes giving off less poison at a bite, and with their short and (excepting those of the death adder) merely grooved poison fangs injecting it very superficially, thus making the process of elimination of the poison by ligature and incision or excision of the punctures much more easy and successful. It is to this treatment, which, as a rule; is immediately adopted in the bush, that our small mortality is due. Our children are taught it in school, and the most illiterate bushman knows how to carry it out. Where it is omitted by persons not knowing that they are bitten until the poison has been absorbed recovery is as rare as it is with the ox and the horse left to themselves without any treatment. But it requires a prodigious stretch of the logical faculty to understand what our small mortality from snakebite has to do with the intrinsic merits of the strychnine treatment. Even if nobody died at all its effects in doing away with the misery and suffering, which, before its introduction, invariably followed snakebite, and often was never got rid of completely, would still be sufficiently beneficial to render the senseless opposition to it on the part of a small section of medical men little short of criminal; for these effects are a matter of constant observation, and cannot, like the rescues from death, be called into question.

The statistics brought forward to prove that the treatment has not reduced the death-rate are also most faulty. Until it is thoroughly understood and in every instance properly applied it is manifestly foolish as well as unfair to lay non-success and failures at its door. When a medical man is called upon to treat a serious case, and instead of boldly addressing himself to the task of combating the symptoms by injecting the antidote irrespective of the quantity he may require until it has conquered the snake-poison, becomes nervous and ceases to inject, when, after what in ordinary practice would be a dangerous dose, he sees but little effect, or if from the first he injects small doses at long intervals, the cause of failure surely lies with him and not with the antidote, which rarely fails where it is properly applied. The duty of disseminating a sound knowledge of the principles of the strychnine treatment unquestionably devolves on our health authorities, who ought, by this time, to have taken some notice of it. But officialdom remains obtuse and issues circulars on the treatment of snakebite, recommending, _inter alia_, the free use of alcohol.

The literature on the subject of snake-poison is very voluminous, but those who seek for enlightenment in it will be as disappointed as the writer was after wading through it. The toilers in this barren field of research were numerous, but with few exceptions, they toiled in vain. FONTANA may be looked upon as the founder of that hideous experimentalism by which, in his hands alone, four thousand animals were tortured to death without a single tangible result except that in his great work, "Reserche Fisiche sopra il Veneno della Vipera," which he wrote at the conclusion of his cruel labours, he left us a grotesque monument of patient, but ill-guided research. Other Italians, following his method, Redi, Mangili, Metaxa, &c., were equally unsuccessful in shedding one ray of light on the vexed and obscure problem.

Among the Germans who contributed to the subject may be mentioned:--

WAGNER.--"Erfahrungen über den Biss der gemeinen Otter."

PRINZ MAXIMILIAN VON WIEDD.--"Beiträge zur Geschichte Brasiliens."

LENZ.--"Schlangenkunde."

HEINZEL.--"Ueber Pelias Berus und Vipera Ammodytes."

Among the French:--

SOUBEIRAN.--"Rapport sur les Vipéres de France."

BULLET.--"Etude sur la Mosure de Vipére."

British and American Workers are the most numerous. Commencing with the century we have:--

RUSSELL.--"An Account of Indian Serpents, collected on the Coast of Coromandel." Later on,

S. WEIR MITCHELL.--"Researches upon the Venom of the Rattlesnake."

HALFORD--"On Australian Snakes, and the Intravenous Injection of Ammonia, in _British Medical Journal_, _Medical Times_, and _Australian Medical Journal_."

JONES.--"On Trigonocephalus Contortrix."

NICHOLSON.--"On Indian Snakes."

SIR JOSEPH FAYRER.--"The Tanatophidia of India." Also, "Researches in conjunction with Richards, Brunton and Eward."

WALL.--"On the Difference in the Physiological Effects produced by the Poison of Indian Venomous Snakes." Proc. Royal Soc., 1881, vol. xxxii., p. 333.

Among those enumerated above Wall is the only one who formulated a correct and thoroughly scientific theory of the action of snake-poison, which has since been confirmed by Australian research and by Feoktistow's elaborate experiments. It is strange that, after finding the theory that explained all the phenomena, he did not follow it up by applying the antidote to which his theory should have led him.

SNAKE-POISON AND ITS ACTION.

The poison gland of snakes is the analogue of the parotid gland of mammals, both in position and structure. Its acini or alveoli are lined with a layer of secretory, columnar, finely granular cells and arranged with great regularity along the excretory duct, which is straight and cylindrical and opens with vipers into the hollow poison fang, with our colubrines into the groove on the anterior surface of it. Snake-poison, as it leaves this gland, is a thin, albuminoid, yellow liquid of neutral reaction. On exposure to the air it becomes viscid and slightly acid. Of its chemical composition we know as yet but little, and it is very questionable whether the most perfect chemical analysis of its constituents would ever have given us a clue to its action or will enrich our present knowledge of it. Like all albuminoid secreta it becomes putrid after prolonged exposure and then, through ammonia production, loses its acid, and assumes an alkaline reaction, still, however, though in a modified degree, retaining its toxic properties, which are completely lost only after an exposure of many months. Feoktistow found that freezing at 1° R. caused the poison to separate into a solid mass and a thin, very yellow liquid, which, even at a temperature of 4° R., remained liquid, and the poisonous properties of which greatly exceeded those of the solid mass. Boiling diminishes and, continued for any length of time, completely destroys the potency of the poison.

The microscope has done good service in the investigation of snake-poison. It has, in the first place, informed us with absolute certainty that there are no micro-organisms or germs of any kind in the fresh poison immediately after it leaves the gland. But a still more important revelation we owe to it is the fact that these organisms, when we introduce them into a 2% solution of the poison, do not die, but live, multiply, and enjoy their existence most lustily, as they do in any other non-poisonous albuminoid liquid, whilst animals of a higher type--say a snail or a frog--soon perish in it. In watching the movements of the latter we find that they get slower and slower, and finally cease. We now follow up the interesting research, and take two frogs. Under the skin of one of them we inject a few drops of the poison solution, the other one for comparison we leave intact, and place both into a glass globe partly filled with water. In a very short time we have no difficulty to identify the poisoned frog. Its hind legs begin to drop and their movements become sluggish. This difficulty increases from minute to minute, until at last all motion ceases, and the legs hang down completely paralysed. At the same time we observe that the animal shows increasing difficulty of breathing, that, even when taken out of the water, and placed on the table before us it gasps for breath and is unable to move. At last respiration ceases altogether and the frog dies.

Two problems now present themselves for solution. In the first place we have to account for the fact of the snake-poison leaving the lower forms of animal life intact and being fatal to the higher ones. The symptoms we have observed in the frog point unmistakably to an affection of the nervous system as their cause. Now we know that the lower forms which the poison does not affect have no such system, and we are justified to infer that to the absence of this system they owe their immunity. This inference leads us on to a second one equally justifiable, namely, that there is a certain unaccountable attraction between the delicate nerve tissue and the subtle ophidian poison, which renders the latter a specific nerve poison.

Our second problem is to ascertain the nature of the change in the nerves, to find out, if possible, whether it is merely functional or an actual interference with the structure of either cells or fibres. With this end in view we once more consult the microscope. We make two preparations, one of nerve fibres and of nerve cells of the poisoned frog, and, under the microscope, compare them carefully with an analogous one from the killed healthy frog. The result is purely negative as regards structural change. Both present identical and perfectly normal pictures of apparently healthy cells and fibres. There being no visible structural change we are driven to the conclusion that only a functional one has been effected by the poison, and with the symptoms observed all pointing in that direction, that it is of central origin.

The writer's theory as to the action of snake-poison, formed, in the first instance from observations made at the bedside of his patients only, is thus confirmed by experiments specially instituted by him for that purpose. Further proof of its correctness we have in the brilliant results of the strychnine treatment of snakebite in Australia, which is the outcome and practical application of this theory. In those desperate cases more especially, reported from all parts of the colonies, in which death was imminent, and pulse at wrists as well as respiration had already ceased, the strychnine injections could not possibly have effected complete recovery within a few hours if the structure of the nerve centres had been impaired or blood changes brought about incompatible with life.

Feoktistow's experiments, made with viper poison, fully bear out the correctness of the writer's theory, besides proving that there is no essential difference between the action of the viperine and colubrine poisons. He proved conclusively that snake-poison does not destroy protoplasm or interfere with infusorial life, that injected into the heart of a mollusc it causes an almost immediate cessation of its action, that hypodermic injections of it in fish produce contraction of the pigment cells and bleaching of the integuments, followed by asphyxial respiration, general paralysis and death. Similar results were observed on frogs. In mammals the symptoms were: dyspnoea, asphyxia, paresis and paralysis of the lower extremities with succeeding general paralysis, sometimes tonic and clonic convulsions, hæmorrhages from bowels, lungs, nose and bladder, and finally complete paralysis of respiration and of heart.

Action of Snake-Poison on Special Nerve Centres.

It must be borne in mind that the symptoms as about to be detailed are successive only to some extent in the order presented. They commence generally at the lower part of the spinal cord, but immediately afterwards, if not simultaneously, are ushered in with great rapidity from other centres, masking each other and rendering it extremely difficult to observe and analyse them separately. They are also very variable through the poison concentrating its action on special centres, leaving others comparatively intact, and this not only when from different varieties of snakes, but also from snakes of the same variety. Another element increasing the difficulties of correct analysis are the depressing effects of fear, inseparable in all but the strongest minds from the consciousness of having been bitten, and so similar in appearance to those of snake-poison, that sometimes it is by no means easy to decide which of the two is in operation, and that only those cases are of real value to the observer from which this element of fear is completely excluded.

A.--Action on the Anterior Cornua of the Spinal Cord.

The anterior cornua are almost invariably the first of the motor-centres attacked by the snake-poison, the affection (commencing with paresis and in serious cases generally culminating in paralysis) beginning in the lumbar ganglia and taking an upward course. The lower extremities feel unnaturally heavy and a paretic condition of the muscles supervenes _simultaneously on both sides_. The walk becomes unsteady and staggering, very similar to that of persons under the influence of large doses of alcohol. By a powerful effort of the will, however, persons in this condition are often able to walk and even run for some distance, especially if by prompt ligature the absorption of the poison has been checked. As the affection proceeds, though still able to move the legs in a sitting posture, they are unable to rise again. Ere long even sitting up becomes impossible and they collapse helplessly. At this stage sensation is still intact, and reflex action, by pricking the skin, &c., still takes place. The upper extremities generally retain the power of voluntary motion, even after the muscles of the neck have become paretic and the head is held up with difficulty or sinks to one side.

With birds, according to Feoktistow, the reverse is the case. The wings are usually first attacked, or paresis comes on in wings and legs at the same time.

B.--Action on the Medulla Oblongata.

a.--The Vaso-Motor Centre.

Whilst the voluntary muscles are thus brought under the influence of the poison, symptoms denoting the invasion of the oblongata are rapidly developing. The first of these is the deadly pallor and ashy hue of the cold skin, evidently due to the blood receding from the surface, a condition not unlike that obtaining in extreme anæmia. As persons in this state complain of an agonising feeling about the heart and of deadly faintness, a paretic condition of the heart suggests itself as the most obvious cause, more especially when taken in conjunction with the small, frequent, and compressible pulse. But though the heart muscle is no doubt participating in the general paresis, the condition of the surface of the body is in reality one of anæmia. The blood, even at this early stage, begins to accumulate in the large veins of the abdomen, which expand gradually in consequence of the diminishing motor force supplied by the splanchnicus, keeping them in the normal state of contraction when intact and having its centre in the medulla oblongata. When this large vaso-motor nerve is cut in animals anywhere in its course, the veins of the abdomen become distended enormously. The animal is, so to say, bled into its own belly.

By a series of most interesting experiments Feoktistow has shown conclusively that snake-poison has the same effect on the abdominal circulation as section of the splanchnicus. Even slight intravenous injections of the poison produced quickly a high degree of paresis of the nerve and a corresponding engorgement of the veins of the abdomen, whilst after lethal doses, the paresis culminated in a few minutes in complete paralysis, followed by rapid collapse, excessive weakness of the bloodless heart, and death from paralysis of the latter and anæmia of the nerve-centres. One experiment deserves special record, as it also shows the untenability of the blood-poison theory.

The whole vascular system of an animal poisoned by intravenous injection was thoroughly washed out with the warm defibrinised blood of four animals of the same species, the blood being infused into an external jugular vein and allowed to flow out of a crural artery. Although blood exceeding its normal quantity was left in the animal, when the vessels named were closed, the nerve affection remained unchanged. The blood pressure raised during the infusion sank at once again to zero, when it ceased, and the paralysed veins of the abdomen became engorged once more with the whole, or nearly the whole, of the blood-mass, leaving the rest of the body anæmic as before. This interesting experiment also shows how strong a hold the snake-poison has on the nerve-cells when they are thoroughly under its influence, and how independent this paralysing action is of the blood, persisting, as it was in this case, after all the poison had been washed out of the animal.

The heart in vaso-motor paresis and paralysis is weakened in the first instance by the direct action of the poison on the medulla oblongata and the intracardiac ganglia. Its pulsations, at first retarded in frequency, become accelerated soon after the introduction of the poison, the pulse rate increasing rapidly and the waves becoming smaller and more easily compressible in proportion to the frequency of the pulse, which generally counts from 100 to 120 and more per minute at a comparatively early stage of the poisoning process. But an equally potent cause of heart failure is its depletion by the simultaneous stagnation of the blood mass in the veins of the abdomen. Finally, to complete the mischief, we have not only anæmia of the semi-paralytic oblongata, but the scanty blood supply this important centre receives becomes also surcharged with carbonic acid. Oxyhæmaglobin disappears almost entirely from the blood under the circumstances detailed, as both pulmonary and internal respiration are greatly interfered with, the blood tending more and more towards that thin dark condition which it presents after death, and which has been taken as _prima facie_ evidence of the direct blood-poisoning action of snake virus by one and all of previous investigators.

That under the powerful combination of causes, each of which is in itself sufficient to endanger life, and greatly intensified as paresis gradually deepens into paralysis, the heart, even of large animals, succumbs in a comparatively short time, may be readily understood.

The _blood-pressure_, under the circumstances just detailed, must necessarily be _nil_. Observations by means of the sphygmograph at the bedside of a person suffering from snake-poison are scarcely feasible, except, perhaps, in a hospital, and thus far are not on record. We must, therefore, once more fall back on Feoktistow's experiments, which show that even the smallest doses (0.02 to 0.04 mllgr.) of the dried poison _per kilo_ injected into the vein of a cat caused a fall in the blood-pressure almost immediately, without influencing either pulse or respiration, but that two to four mgr. were sufficient to reduce the blood-pressure to zero and bring on collapse, infusions of blood only raising it temporarily. Of drugs raising the blood-pressure he found ammonia the most effective, but only after slight doses of the poison; after lethal ones it had no effect whatever on the blood pressure but greatly increased the hæmorrhagic process in all internal organs. This important observation should be kept in mind by those who inject ammonia in serious snakebite cases, and it probably applies likewise to _the excessive use of alcohol_.