Venoms: Venomous Animals and Antivenomous Serum-therapeutics

CHAPTER XV.

Chapter 202,870 wordsPublic domain

_TREATMENT OF POISONOUS SNAKE-BITES IN MAN AND ANIMALS._

_OBJECTS OF THE TREATMENT: TECHNIQUE OF ANTIVENOMOUS SERUM-THERAPY._

In all countries the remedies recommended for the bites of poisonous snakes are innumerable, and native pharmacopœias abound in so-called infallible recipes.

Pliny himself wrote on this subject as follows:--

“For poisonous bites, it is customary to employ a liniment made of fresh sheep-droppings, cooked in wine. Rats cut in two are also applied; these animals possess important properties, especially at the epoch of the ascension of the stars, seeing that the number of a rat’s fibres wax and wane with the moon.

“Of all birds, those that afford most assistance against snakes are vultures. The black ones are the weaker. The odour of their feathers when burnt puts snakes to flight. Provided with a vulture’s heart one need not fear encounters with snakes, and can also defy the wrath of wild beasts, robbers, and princes.

“Cock’s flesh, applied while still warm, neutralises the venom of snakes. The brains of the bird, swallowed in wine, produce the same effect. The Parthians, for this purpose, make use of chicken’s brains. The fresh flesh of the pigeon and the swallow, and owls’ feet burned, are good against snake-bites.

“If one has been bitten by a snake or by any venomous animal, another method of cure is to take salt fish and wine from time to time, so as to vomit in the evening. This remedy is chiefly efficacious against the bite of the _Chalcis_, _Cerastes_, _Seps_, _Elaps_ and _Dipsas_.”

* * * * *

In Equatorial America, and especially in India, a multitude of plants are credited with marvellous properties, which they possess only in the imagination of the snake-charmers or medicine-men by whom they are employed. None of them stand the test of experiment, any more than the more or less compound drugs, numbers of specimens of which from all sources have passed through my hands.

It cannot, however, be denied that certain chemical substances, of well-defined composition, are very useful, not as physiological antidotes to venoms, but as agents for their modification or destruction in the poisoned wounds, when they have not yet been absorbed. In this way _permanganate of potash_, _chromic acid_, _chloride of gold_, and the _alkaline hypochlorites_, especially _hypochlorite of lime_, may be extremely useful under many circumstances.

_Permanganate of potash_ was recommended in 1881 by Professor de Lacerda,[104] of Rio de Janeiro, as the result of experiments made by him with venoms of Brazilian snakes. When a few cubic centimetres of a 1 per cent. solution of permanganate of potash are quickly injected into the actual wound caused by the bite and around the point of inoculation, there can be no doubt that the venom not yet absorbed is destroyed. When mixed _in vitro_ with venom, permanganate renders the latter innocuous.

Here, however, it is a case of actual destruction by direct contact. If we inject a lethal dose of venom into the right thigh of an animal, for example, and several cubic centimetres of permanganate solution into different parts of the body, or beneath the skin of the left thigh, neither the general intoxication nor the local effects of the venom are modified.

The same may be said with regard to _chromic acid_ (1 per cent. solution), recommended by Kaufmann[105] for the bite of the common viper.

No other effect is produced by a 1 per cent. solution of _chloride of gold_, or the _alkaline hypochlorites_, which I have shown to possess a strong oxidising action on the different venoms, even on those that are most rapidly diffusible, such as cobra-venom (see Chapter V.). They possess, however, owing to their slight causticity, the advantage of not producing severe local disorders, and in this respect they are to be preferred.

The chemical reagent most to be recommended is _hypochlorite of lime_, in a fresh solution of 2 grammes per cent., and containing about 90 c.c. of chlorine per 100 grammes. It immediately and surely destroys the venom by simple contact, and the chlorine gas that it gives off, owing to its great diffusibility, acts at a fairly long distance from the point of inoculation on the venom which is already beginning to be absorbed.

Professor Halford, of Melbourne, advises the direct injection into the patient’s veins of from 10 to 20 drops of ammonia, diluted with an equal quantity of distilled water. This is a means of reviving nervous excitability in certain subjects at the commencement of intoxication; but torpor soon reappears, and, if the dose of venom inoculated is sufficient to cause death, a fatal ending takes place notwithstanding. Experimentally the effects of ammonia are _nil_.

No better results are obtained by injections of strychnine, as recommended by Dr. Mueller, in Australia. Moreover, the statistics published by Raston Huxtable[106] positively condemn this therapeutic method. They show that, in 426 cases of snake-bite, out of 113 treated by strychnine 15 proved fatal, the ratio of mortality being 13·2 per cent., while the 313 cases not treated by strychnine only resulted in 13 deaths, or a mortality of 4·1 per cent.

In the case of animals intoxicated by venom, injections of strychnine, morphia, nicotine, or curare in small doses always prove ineffective; they even considerably assist the progress of the intoxication and hasten death. The use of these drugs in the case of human beings should therefore be absolutely forbidden.

It appears, on the other hand, that alcohol and coffee, or tea, absorbed by ingestion, are very often beneficial. Indeed, it was long ago observed that the swallowing of alcohol until symptoms of drunkenness appear retards or diminishes the phenomena of torpor and paresis that precede the ultimate phase of the intoxication. Its use may therefore be recommended when it is impossible to have recourse to the only treatment really specific that modern science places in our hands--_antivenomous serum-therapy_. It is important, however, to state that, _when serum is used, alcohol must be forbidden_. The latter hinders the effects of the former.

In practice, the rational treatment of the bite of a venomous snake must be directed towards:--

(1) Preventing the absorption of the venom.

(2) Neutralising, by the injection of a sufficient quantity of antitoxic serum, the effects of the venom already absorbed.

In order to prevent the absorption of the venom introduced into the wound, the first precaution to be taken is to compress the bitten limb by means of a ligature of some kind, such as a handkerchief, as close as possible to the bite, and between it and the base of the limb. The ligature must be tightly twisted, and, by compressing the tissues around the bite, an attempt should be made to squeeze out the venom that may have been introduced into them. The expulsion of the poison should be hastened, either by making an incision 2 or 3 cm. in length and 1 cm. in depth in the direction taken by the fangs of the reptile and also parallel to the axis of the bitten member, or by sucking the wound hard.

The ligature on the limb should not be applied for more than half an hour; if it were kept on longer it would interfere with the circulation to a dangerous degree, and would certainly injure the vitality of the tissues. The period in question also usually affords sufficient time for taking the patient to a place where help can be obtained, and for the preparation of everything necessary for his subsequent treatment.

The wound should then be freely washed with a fresh 2 _per cent._ solution of _hypochlorite of lime_, or with a 1 in 1,000 solution of _chloride of gold_. In default of hypochlorite of lime or chloride of gold, either _eau de Javel_, diluted with tepid water to a strength of 1 in 10, or a 1 per cent. solution of permanganate of potash, may be employed. These reagents should be made to penetrate as deeply as possible into the tissues, and a few cubic centimetres of them should even be injected with a Pravaz syringe into the punctures caused by the bite and all round them.

The wound being then covered with a damp dressing by means of compresses saturated with hypochlorite of lime, or at least with pure alcohol, the next thing to be done is to prepare to apply the serum-therapic treatment in order to arrest the general intoxication, if this has already commenced to take effect, or to prevent it from setting in.

For the employment of serum it is necessary to be in possession of a sterilisable syringe of the capacity of 10 c.c., similar to those used in the treatment of diphtheria.

If the life of the patient be not immediately in danger, care should first be taken to have the syringe boiled, or at least to rinse it out with boiling water, making sure that the piston fits tightly, and that the syringe itself is in good working order.

Should a syringe of 10 c.c. not be available, any kind of Pravaz syringe, previously washed out with boiling water, may be employed, but in this case the use of so small an instrument renders it necessary to give several painful injections.

The entire contents of a bottle of serum (10 c.c. of liquid serum, or 1 gramme of dry serum dissolved in 10 c.c. of boiled water) should be injected into the subcutaneous areolar tissue of the abdomen, on the right or left side. There is no advantage in making the injection at the actual spot bitten; the serum is best and most rapidly absorbed when injected into the loose tissues of the abdominal wall (fig. 95).

If it has been impossible to apply the treatment until several hours after the bite, and if the latter has been inflicted by a poisonous snake of large size or belonging to a very dangerous species, such as the Cobra or Indian Krait, it is preferable to inject into the patient three whole doses of serum at once.

In cases in which the phenomena of serious intoxication have already appeared, and when asphyxia threatens, one must not hesitate to inject 10 or even 20 c.c. of serum directly _into a vein_. For such an injection it is most convenient to choose a superficial vein at the elbow or wrist, or on the back of the hand.

The introduction of serum into the veins is never dangerous if good care be taken not to allow either bubbles of air or particles of precipitated albumin to enter.

It is not advisable to repeat the injections beneath the skin or into the veins unless the general symptoms appear to become more acute.

In most cases the local pain, excitement, and attacks of cramp and nausea disappear within a few minutes after the first injection. Improvement progresses very rapidly, and by the following day the patient has recovered.

The administration of ammonia, alcohol, morphia, or ether by the mouth is entirely superfluous. These drugs, as I have already stated, may even be harmful to the patient and hinder the effects of the serum. All that should be done is to give copious hot drinks, tea or coffee, and to cover up the patient warmly in order to induce abundant perspiration.

The bitten member should not be cauterised with red hot iron or with chemical agents of any kind, since such cauterisations only lead to injuries which are too often prejudicial to the normal action of the affected organs.

_Treatment of Poisonous Bites in the Case of Domestic Animals._--It often happens that dogs, horses, or cattle are bitten and succumb to the poisoning in a few hours or in two or three days. Such accidents are especially frequent among sporting dogs, even in Europe, in regions in which _vipers_ are found.

In most cases, dogs, horses, and cattle are bitten on the nose, and such bites are immediately followed by a very painful swelling, which arouses the suspicion of the owners of the animals. It is then necessary, as soon as possible, to inject subcutaneously in the right or left flank, or at the base of the neck, one or two doses of antivenomous serum, according to the gravity of the effects observed.

The injection of the serum and the dressing of the wound should be performed as in the case of poisonous bites in human beings.

_Influence of the Doses of Antivenomous Serum injected, and of the Time that has elapsed since the Venomous Bite._--I have stated above that antivenomous serum possesses a preventive and curative power of such intensity, that it is capable in a few minutes of rendering animals into which it has been injected absolutely insensible to the most strongly neurotoxic venoms, such as those of _Naja_ or _Bungarus_. On the other hand, I have established the fact that, the more sensitive are the animals to intoxication by venom, the greater is the quantity of antivenomous serum necessary to immunise them passively or to cure them.

In experimenting upon mice, guinea-pigs, and rabbits, it is found that in order to preserve, let us say, a mouse of 25 grammes against inoculation with half a milligramme of venom, which is ten times the lethal dose for this little animal, it is necessary to give a preventive injection of 1 c.c. of serum; while half a cubic centimetre of the same serum is sufficient to render the dose of half a milligramme of venom innocuous, when venom and serum are mixed _in vitro_ before being injected.

In the case of the guinea-pig, it is likewise found that the dose of serum to be injected preventively, in order to protect the animal from intoxication by ten times the lethal dose of venom, is about _twice as much_ as the quantity of the same serum that it is sufficient to mix _in vitro_ with venom, in order to render ten times the lethal dose of venom innocuous.

If we inject into animals first venom, in doses calculated to kill the controls of the same weight in from two to three hours, and the serum _fifteen minutes afterwards_, it is found that the quantity of serum that must be injected in order to prevent death is about _thrice as great_, as that which neutralises _in vitro_ the dose of venom inoculated.

It is also found that _the amount of curative serum that an animal intoxicated by venom must receive is inversely proportional to its weight_.

The experiments upon dogs, performed at the Pasteur Institute at Lille by my collaborator C. Guérin, are highly demonstrative in this respect.[107]

A dog of 12 kilogrammes, inoculated with 9 milligrammes of venom (a dose lethal to controls of the same weight in from five to seven hours), is completely cured on receiving, _two hours after inoculation with the poison_, 10 c.c. of serum.

When the treatment does not take place until _three hours after the injection of the venom_, it is necessary to inject 20 cc. of serum in order to prevent the animal from dying. With a longer delay than this, death is inevitable, since the bulbar centres are already affected, and paralysis of the respiratory muscles commences to appear.

These facts show that:--

(1) _The more sensitive animals are to venom, the greater is the quantity of serum necessary in order to prevent their intoxication by a given dose of venom._

(2) _For a given species of animal and a given dose of venom, the longer the delay in applying the remedy, the greater is the quantity of serum that must be injected in order to arrest the poisoning._

It will be understood from what has been already stated, that a man weighing 60 kilogrammes, if bitten by a snake which injects, let us say, what would amount to 20 milligrammes of venom if collected in the dry state (the mean quantity that a _Naja_ is able to inoculate in a single bite), would only require, in order to escape death, to receive the quantity of antivenomous serum sufficient to neutralise the portion of venom in excess of the amount that he could tolerate without dying.

Let us suppose, for the sake of example, that the man of 60 kilogrammes can withstand intoxication by 14 milligrammes of _Naja_-venom. It follows that, in the case with which we are dealing, we must inject sufficient serum to neutralise 20-14 (=6) milligrammes of venom; that is to say, the injection of serum being made immediately after the bite, 6 _c.c._, if the serum employed neutralises _in vitro_ 1 milligramme of venom per cubic centimetre.

Of course, if the serum is more powerful, less of it will be necessary, while more will be required if the remedy is applied later, or if the quantity of venom inoculated by the snake is supposed to have been greater.

For this reason, in practice, but very little serum is usually necessary in order to augment the natural resistance of a man of average weight or of a large animal; it is sufficient in most cases to give an injection of 10 or 20 c.c. in order to cure human beings who have been bitten. The clinical proof of this is, moreover, to be found in the cases, already very numerous, that have been published in the course of the last few years in the scientific journals of all countries. I have gathered together a few of these in the concluding pages of this book, and I would beg the reader to be good enough to refer to them.