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.