Part 46

Tetany is more commonly localized in particular groups of muscles, and shows longer and more irregular intervals between paroxysms than does tetanus. It is improved by thyroid extract, and may be roused at will to contraction by pressing on the nerve going to the affected muscles.

Laminitis in its most violent form and early stages, may be confounded at first glance with tetanus, but the high fever, the standing on the heels, the advance of the hind legs under the body, the great heat and tenderness of the feet, the impossibility of standing on one fore foot when the other is lifted and the strong pulsation of the digital arteries, are sufficiently distinctive.

Treatment. For fully developed tetanus no known resort of therapeutics can be relied on. In slight cases that have shown a long incubation and a slow increase and extension of spasm and in those having trismus only, a recovery may be expected. Treatment has been conducted largely on theoretic lines and may be divided into antispasmodic, eliminating and antidotal or antiseptic.

Rest, darkness and absolute quiet are the first and main considerations. A dark stall, with no straw litter, the rustling of which often excites the patient, but rather a little chaff, saw dust or even earth to prevent noise from the feet, and the exclusion of all visitors are essential. As a rule slings should be put under the patient so that he cannot lie, nor drop down, and this becomes more imperative as the disease advances. The aggravation of the spasms when down, and the danger of their extension to the respiratory muscles are far more to be dreaded than the temporary excitement caused by the application of slings. Food should be sloppy mashes, of bran, middlings, oat meal, linseed meal, gruels or milk, or green food may be allowed in moderate amount if the jaws are still movable. It must not be forgotten that digestion is impaired and food that is indigestible, especially fermentescible, or in excess, may arouse fatal colics and bloating, yet in a protracted exhausting disease like tetanus, the strength must be sustained by all means in our power. Pure water should always be accessible. Food and water should be furnished in buckets at a level which will not necessitate either raising or dropping the head to get to them (about 4 feet). The food must be given often, in small quantity to avoid fermentation and spoiling. If noise cannot be wholly excluded it may be an advantage to put cotton wool in the ears. I have seen a mare recover when completely covered with cotton wool under blanket and hoods.

Local antiseptic treatment. Theoretically this is of great value since the microbe is confined to the inoculation wound and by the time the first symptoms appear, the spores have developed into bacilli and are in a condition to be easily destroyed by disinfectants. We can, therefore, by caustics or active disinfectants destroy the infecting microbian colony, and prevent the further entrance of any toxins into the circulation and nerve centres. The principle has been shown experimentally successful in cases of inoculation in the tails of cats and Guinea pigs, and the amputation of these members as soon as tetanic symptoms appear (Kitasato, Babes). Unfortunately in too many cases, when first seen, too much of the marvelously potent toxin has already reached the nerve centres, and these have already undergone such changes, that the disease is likely to go on to a fatal issue in spite of the cutting off of future supplies of toxin. Yet the principle is sound and proves helpful in proportion as it is applied nearer to the time of infection. The most thorough method is the amputation of the infected member, if like the tail or ear it can be excised without ruining the animal. In 1875, Barbillon had success in again amputating the tail, in a case of tetanus after docking. Next to this comes the excision of the wounded tissues, but this can too seldom be effectually and certainly accomplished, and we must fall back on caustics and antiseptics. The actual cautery if thoroughly applied may be trusted to destroy the bacillus along with the tissues, but most of the chemical escharotics unite with the albumen to form an impermeable film, which protects the tissues in the deeper part of the wound against the antiseptic action. Of the different antiseptic applications carbolic acid should be especially recommended as being not only antiseptic, but also an antidote to the toxins as shown below. It has the further advantage of acting as a local anæsthetic, and of not coagulating albumen. Creosote, creolin, lysol or other antiseptic may be used instead and should be applied thoroughly to all parts of the depth of the wound on a pledget of surgeon’s cotton or through a tube. When agents so little destructive are employed they may be continuously applied to the sores for a length of time.

Recoveries have taken place after neurectomy, and after stretching the nerve going to the wounded part, the theory being to check the afferent (sensory) nervous current, and arrest the reflex spasms. The new irritation, however, caused by the surgical wound is to be dealt with, and may itself turn the balance against recovery.

Nervous derivation appears to have been beneficial in some advanced, or partially convalescent cases. One horse after 14 days illness (Taffanel) and another after 21 days (Prud’homme), were castrated, bled freely and slowly recovered. Tisserand gives another case without mentioning the stage of the disease. A horse with advanced tetanus was taken to the seashore and shot. He fell into deep water, swam ashore and made a recovery. But whatever virtue may be in elimination of the toxins by bleeding, in nervous derivation or in the shocking of an unbalanced nervous system, these can hardly be recommended as regular methods of treatment. Yet the older veterinary records contain many instances of alleged benefit from bleeding.

Internal treatment. The whole list of antispasmodics have been tried, with no very satisfactory result. Opium has been extensively employed in spite of its tendency to encrease constipation, and morphia given hypodermically has checked spasm and induced sleep. Hydrocyanic acid and potassium cyanide have shown a decided reducing action on the spasms with the same drawback of favoring constipation. Potassium and other bromides are useful in mild and chronic cases, and may be given in full doses in combination with chloral hydrate. Calabar bean and eserine have been given for their physiological action on the nerve centres, and recoveries have followed their use, but they have little effect on the spasms until the system has been saturated to the point of threatening collapse. Chloroform has the advantage that it can be easily given by inhalation, but while it may be pushed to the extent of temporarily checking the spasms, yet these return at once when the action of the drug is exhausted. Chloroform is always dangerous to a weak or exhausted heart and cannot be given for any great length of time continuously. It is, therefore, very unsatisfactory. Sulphonal and trional have similarly checked the spasms. Gelsemium has given good results in certain mild cases, but it must be pushed to the extent of coming just short of poisonous doses, and the fear of an overdose, together with its failure in severe cases, have prevented its general acceptance. The same end has been sought by the use of nauseating antispasmodic agents, as tartar emetic, tobacco, apomorphia, and lobelia, but though useful in individual cases, these are on the whole no more successful than other agents. Phenacetin, antipyrin, acetanilid and cocaine have respectively received credit for some recoveries.

Chloral hydrate commends itself as being at once a most potent antispasmodic and hypnotic, and an antiseptic. It can, moreover, be conveniently given as a rectal injection, thus avoiding the irritation and excitement of administration by the mouth. Given in this way too, it tends to relaxation of the bowels, instead of constipation. Carbolic acid which can be conveniently given by enemata has an anæsthetic action.

Antiseptic and Antidotal or Antitoxin treatment is more promising, yet it has failed to come up to the full measure of expectation, mainly because the nervous changes have already reached a stage which cannot be undone speedily or at all. Under this heading would come phenic acid (½ oz.) and probably chloral hydrate (1 oz.), already referred to, and the various compounds of iodine which may be here noted.

Iodine Terchloride. Iodine. Behring and Kitasato secured immunity of two months duration, by injecting the animal with a filtrate of a culture of tetanus bacillus, and then injecting at the same point 3cc. daily, for five days, of a 1 per cent solution of iodine terchloride. Roux and Chamberland had similar results by using iodine instead of the iodine terchloride, and maintained the full measure of immunity by repeating the inoculation every fortnight. Here it is evident that the action of the iodine is directly antitoxic or antidotal, when introduced along with the toxins and before they can reach the nerve centres.

Iodide of Potassium. In an experimental case of general tetanus in the dog, Babes had a recovery in ten days, by injecting subcutem 5cc. of Lugol’s solution and thereafter for eight days 10 to 30cc. daily. This suggests the use of this agent along with phenic acid, or as an alternate, in any case in which phenol appears to be losing its effect by use. It may be used hypodermically, or in the drinking water or by rectal injection. It has an advantage over phenic acid in being actively diuretic and eliminating, while phenic acid has the recommendation that it tends to lower nervous excitability and moderate the reflex spasm. Theoretically the combination of the two agents, which do not mutually decompose each other, should give the best results.

These experiments have been often repeated showing clearly the antidotal action of the iodine compounds when mixed with the virus before inoculation, or injected with the virus into the seat of the wound. When employed later when the symptoms have developed, everything depends on the changes already accomplished in the nerve centres, and the severity and generalization of the spasms.

Serum Antitoxin Orrotherapy. Babes appears to have been the first (1889) to use the serum of animals (rat) recovered from tetanus in mitigating and curing tetanus in experimental cases. An attempt on a well developed case in man failed. His method of preparing the serum is as follows: A horse of 900 lbs. (461 kgm.), is inoculated with a mixture composed of 0.5cc. toxin (of which 0.001 mgm. kills a mouse) and 0.5cc. iodo-potassium iodide, and then at intervals of four or five days of 2.5cc., 4, 5 and 10cc. of the iodine mixture. Then stronger mixtures are used: first 2 parts of toxin to 1 part of the iodine mixture; dose 10cc.; then 3:1 dose 10cc.; then 4:1 dose 5cc.; then 15:1 dose 10cc.; then 30:1 dose 25cc.; and finally virulent cultures in progressively encreasing doses 10, 20, 30 and 50cc. One week after the last injection 1cc. of the blood serum will antidote 50cc. of toxin. Injection of toxin is however continued and the dose is gradually raised to 200cc. Eight or fourteen days after the last injection the blood serum may be taken for protective purposes. He has prepared antitoxin from cows in the same way, and Brieger and Ehrlich have prepared it from the goat. Chickens being naturally refractory to tetanus toxin can bear large doses and a potent antitoxin is more speedily secured from them. In the case of the cow the milk is rich in antitoxin.

Other methods of preparing an animal for producing the antitoxin have been resorted to as injecting it with a mixture of toxin and antitoxin in increasing doses, or again injecting with a mixture of toxin and thyroid extract in increasing doses. The extract of the normal thyroid contains a natural antitoxin.

It may be fairly inferred that the antitoxin is not formed in the nerve cells alone in their resistance to the toxin, but also in the thyroid, the liver (bile having an antitoxic action), and perhaps in other organs or liquids.

The blood of the immunized animal drawn through the sterilized cannula and aspirating syringe is coagulated in vessels set on ice, and the serum when separated is mixed with 0.5 per cent. carbolic acid and 1 per cent. chloroform, and kept in the dark in well closed bottles. It will usually keep for years.

Early experiments with antitoxins showed that when mixed with the toxin before injection it could be trusted to neutralize it. Ehrlich, Tizzoni and Cattani even claimed success in all experimental subjects if employed as soon as the slightest symptoms of tetanus were shown. They found, however, that it required 1000 to 2000 times the amount of antitoxin in such cases than was required when it was mixed with the toxin prior to injection. They found, moreover, that when the disease is fully developed the dose must be 150 times more than is required when the first symptoms are shown. It should be added that when the disease has developed rapidly, after a short incubation, and is well advanced the antitoxin treatment is usually of little avail. The changes in the nerve centres are already too great to allow hope of recovery. In man the ratio of recoveries are about as follows: After incubation of 10 days or under, 3 to 4.5 per cent. recover. After an incubation of 11 to 15 days 50 per cent. recover (Woodhead). Lambert claims 46 per cent. recoveries in 114 cases, and 38.71 per cent. recoveries in acute cases with an incubation of 8 days and under.

On the whole the ratio of recoveries is greater under the antitoxin treatment than before, though far from sustaining the optimistic views of Behring and other early experimenters. Babes draws attention to the fact that spore laden splinters of wood, in the wound render the antitoxin useless as a continuous succession of fresh spores, bacilli and toxins are thereby supplied. As this is one of the most common forms of casual infection it interferes seriously with the success of antitoxin treatment.

Roux and Borrel found that in animals, intracranial injection of the antitoxin was the most effective method. Recovery also followed its injection into the cerebrum of a tetanic boy. Babes had recoveries in two cases out of three with cerebral or intracranial injections. As the reflex spasms depend on the spinal centres these would seem to be the ideal points of injection.

Babes who has done a large amount of subcutaneous and intraperitoneal injection of antitoxin, employed for man doses of 300 to 500cc., which would represent 8 to 10 ozs. as the dose for an ordinary horse. As the antitoxin is rapidly eliminated from the body, these should be repeated daily or every other day. Nor should this supercede other curative measures. The leading principles may be thus stated: 1st. Antitoxin should be used at the earliest possible moment. 2nd. The infected wound area must be thoroughly disinfected or destroyed by caustics, and that at once. 3rd. The antidotal treatment by phenol and iodine must not be omitted. 4th. Palliative treatment by antispasmodics, narcotics or soporifics must go hand in hand with antitoxic treatment. 5th. Measures should be taken to secure elimination of the toxins present in the blood.

Treatment by brain emulsion. Wassermann and Takaki (Berlin Klin. Woch. Jan. 3d, 1898) have in a number of cases, mixed 1cc. of brain substance of a warm-blooded animal with ten times the lethal dose of tetanus toxin and injected without producing any symptoms of tetanus. They obtained a similar immunity by injecting the brain emulsion 24 hours after the injection of three times, and in other cases of five times the lethal dose of tetanus toxin. Control cases uniformly died of tetanus. The brain matter was obtained from Guinea pigs, pigeons, rabbits, horses, and men. They accordingly advanced the theory that brain matter is a direct antidote to the tetanus toxin, uniting with it chemically and rendering it innocuous. The liver, spleen, kidney, bone marrow and blood serum gave no such protection.

Marie, in a series of experiments, injected the brain emulsion and tetanus poison at different parts of the body of Guinea pigs and found that fatal tetanus ensued. It would appear, therefore, that the brain emulsion acts by direct contact, and that it is only by its meeting and combining with the toxin before the latter reaches the spinal cord that tetanus can be prevented.

Roux and Borrel (Ann. de l’Instit. Pasteur, 1898) demonstrated this union between the poison and brain matter, by making an emulsion of the two, and putting in a centrifuge, which will separate the brain substance from the clear liquid. The fluid obtained in this way was shown by injection on the living animal to contain almost no toxin. Knorr and Blumenthal reached the same conclusion as to a chemical union with the brain matter which robbed the toxin of its toxicity.

Knorr, and Tizzoni, and Cattani and Morax showed indeed, that if the tetanus toxin is injected subdurally or into the surface layers of the cerebrum, it produces not tetanus, but a characteristic cerebral disease. A dose of ¹⁄₂₀th or ⅒th cc. of tetanus toxin produces in the rabbit, in 10 to 12 hours, restlessness, constant change of place, and signs of great fear like hiding the head, turning rapidly round, attempting to escape, polyuria, grinding the teeth, epileptoid convulsions. The toxin in this case had manifestly united with the brain substance while the cord suffered little.

Metchnikoff (Ann. de l’Inst. Past., April, 1898) holds that the brain matter is only valuable in holding the toxin until it can be destroyed by the leucocytes. He showed that the injection of the tetanus toxin in chickens or Guinea pigs greatly encreased the production of leucocytes. He injected tetanus toxin into the aqueous humor of the rabbit without producing much effect, but when the same agent mixed with cerebral substance was injected, the result was a great accumulation of leucocytes, and hypopion. If the mixture of brain substance and tetanus toxins were injected on the brain, little encrease of leucocytes occurred, but if thrown into the peritoneum, a most remarkable leucocytosis took place. In twenty minutes after the injection the fluid withdrawn from the abdomen showed large numbers of leucocytes filled with brain substance, but no free cerebral matter.

The present status of the treatment by brain substance is therefore somewhat uncertain. The value of that agent in holding the toxin is allowed, but like the antitoxin it must be employed before the toxin has reached the nerve centres and united with the living ganglion cells. Its use would be called for therefore at the earliest possible moment and it should be continued so long as there is reason to suspect the production of fresh toxin in the wound. Its direct action on the toxin would suggest its injection around an infected wound, or even as a dressing for the wound in connection with antiseptics. When tetanus has already set in it cannot be expected to undo the evil already accomplished by the union of the toxin with the cells of the cord, though it might in part arrest and hold new supplies of this poison coming from the wound to the nerve centres.

Prevention. In a disease so deadly as tetanus and so refractory to treatment even by antitoxin when it is once developed, prophylactic measures are of the greatest importance. With the extensive adoption of antiseptic surgery there has already been a material diminution in the number of cases, yet a greater attention is demanded to the prevention of casual cases which result from ordinary wounds. Dirty, grimy wounds filled with the dust of stable yard or garden soil, and such as contain splinters of wood, stones, thorns, straw and the like can only be considered quite safe after thorough disinfection. It has been shown that the toxin is easily neutralized at the time of infection, whereas, after the disease is developed it will require 1,000 or 100,000 times as much antitoxin to produce the same effect. In the case of soiled wounds, therefore, in a valuable animal, a harmless injection of antitoxin or of phenic acid or iodine solution before the development of tetanic symptoms is not an unwise precaution. A succession of such injections might be given to ward off the disease until after a lapse of time exceeding the short and dangerous incubation.