The anæsthetics, chloroform and ether, have been frequently administered, but although muscular relaxation and sleep have been thereby secured, the natural progress of the disease toward a fatal termination has not been materially affected: death has at times been directly and suddenly produced, and not infrequently, though the inhalations have lessened suffering, they have seemed to hasten the end.
Curare, which “powerfully impairs and destroys the conductivity of motor nerves,” and of which, consequently, much was hoped at one time, has proved to be of but little value.15 In order that benefit may follow its administration the agent must be given in large doses and until a decided impression is made upon the innervation of the muscles of respiration, great danger meanwhile existing of producing asphyxia, for the relief of which artificial respiration must be instituted. McArdle of Dublin, in reporting recently a successful case of the acute variety in which gr. ⅔ was given every fifth hour, suggested the combination of curare and pilocarpine, “in the hope that the cardiac and respiratory trouble produced by the former might be prevented by the latter.” Uncertain in composition, cumulative in action, “dangerous, difficult to manage, and variable in its effects,” curare is not, so far as has as yet been determined, an agent to be recommended in the treatment of tetanus.
15 Of Demme's 22 cases, 14 died (63.6 per cent.); of Busch's 11 cases, 6 died (54.5 per cent.); and in 51 cases collected by Knecht the mortality-rate was 49 per cent.
Conium, the action of which is much akin to that of curare, and which primarily is upon the terminal portions of the motor nerves, has been occasionally employed—successfully in two cases by Christopher Johnson of Baltimore, who gave it hypodermically in doses of from 1/6 to 2 minims every one, two, or three hours. In two other cases under the care of the same surgeon death took place, but the remedy seemed to have acted beneficially in relieving the spasms and relaxing the tonic rigidity.
Calabar bean—which produces a paralyzing action on the spinal cord, abolishing its reflex functions, and later “diminishes and destroys the conductivity of the motor nerves”—though apparently of service in certain cases (almost all of them, however, in young subjects and of chronic character), has proved to be of little or no more value than other less dangerous agents. It was first clinically employed by Vella in the Italian war of 1859. Of the 39 cases in Yandell's table, 39 per cent. recovered; of the 60 in Knecht's, 45 per cent.; and of the 60 collected by H. C. Wood, 55 per cent. It may be administered by the mouth, the rectum, or subcutaneously in doses (of the extract) of from ⅓ gr. to 2 grs. every quarter hour, half hour, hour, or two hours (Ringer gave 4 grs. in an hour),16 according to the violence of the symptoms, being stopped when there is produced “vomiting, diarrhœa, or a rapid small pulse and clammy sweat.” Yet its beneficial action in severe cases is only manifested when it has been “pushed to the extent of rendering the patient collapsed, the temperature of his body falling perhaps to 94° or 95° F., the pulse being hardly perceptible at the wrist” (Macnamara); under which circumstances there is about as great risk of death from the treatment as from the disease itself. Always, fever is a contraindication to its employment.
16 E. Watson gave to a patient in the course of forty-three days the equivalent of 1026 grs. of the solid extract, a tincture of the powdered bean being largely employed.
Cannabis indica, originally used by the East Indian surgeons, and believed by them to have a powerful influence in controlling the tetanic spasms, has proved much less efficacious in cases occurring in Europe and this country, perhaps because of the unreliable character of the extract used; though of 42 cases of the traumatic variety treated in the Chadnie Hospital at Calcutta in five years (1865-69), 62 per cent., and of 39 idiopathic cases 40 per cent., died, and of Chuckerbutty's 13 cases in India, 6 (i.e. 46 per cent.) died. Of the 25 cases in Yandell's table, the mortality-rate was 36 per cent. If given, it should be in doses of from ½ to 2, or even 4, grs. of the extract, or minim 15 to drachm j of the tincture, every two or three hours. Having a strong hypnotic action, it is to this probably that the beneficial effects of its administration are due, rather than to its secondary influence upon sensation and muscular movements.
Of all the sedatives and narcotics, opium has been longest and most often used, and in so far as it relieves pain and causes sleep it is of service. Like the other agents, it must be administered in large doses, reference being had to the effect produced and not to the number of grains given. The difficulty of swallowing even the liquid preparations has of late years made the hypodermic injections of morphia the favorite mode of administering the drug. Demarquay has advised that the solution (1 part to 50 of water) should be thrown deeply into the substance of the affected muscles, as near as possible to the place of entrance of their supplying nerves; the result being to especially relieve the trismus and allow of the taking of food. Fayrer in India found opium-smoking of advantage. The mortality-rate of the 185 cases tabulated by Yandell treated with opium was 43 per cent., but, as is true of the other drugs that have been referred to, it is chiefly if not wholly in the mild and chronic cases that the beneficial effects have been observed.
So far as has yet been determined, chloral is our most valuable drug in the treatment of tetanus, as it is in that of the allied condition of strychnia-poisoning—not because of any direct antidotal action, but by reason of its producing sleep, lessening the reflex irritability of the spinal cord, and diminishing the violence and frequency of the muscular spasms, thus enabling the patient to keep alive until the morbid state can spontaneously disappear. Given usually by the mouth or the rectum, it has been administered hypodermically (as much as 5 grs. at a time by Salter) or, as proposed by Oré, thrown directly into a vein. If it is true, as has been claimed, that its beneficial effect is due entirely to the sleep secured (not infrequently after waking up the spasms return with increased violence), the drug should be administered in doses sufficiently large and repeated to maintain a continuous slumber. Verneuil (whose therapeutic formula has three terms, rest, warmth, sleep) has found that while with certain patients a drachm a day is enough, to others four times as much must be given, and directs that the chloralic coma be continued for about twenty days. Further experience may show that small doses may suffice to secure the needed quiet—as, e.g., the 40 grs. at bedtime, with, if necessary, 30 grs. more at midday, recommended by Macnamara. Such small doses are far safer than the enormous ones that have at times been employed,17 since chloral can exert a powerful toxic influence upon the circulatory and respiratory centres, death being almost always due to arrest of respiration, though in tetanic cases it may be the effect of slight spasm upon a heart the enfeebled state of which is indicated by a very rapid and thready pulse. The intravenous injections expose the patient further to the risk of the formation of clots and plugging of the pulmonary artery, several instances of which accident have already been reported, though this method of treatment has but seldom been employed. The death-rate of those treated by chloral alone was 41 per cent. in the 134 cases analyzed by Knecht, and 41.3 per cent. of the 228 tabulated by Kane.
17 Beck is reported to have given 420 grs. in three and a half hours, and Carruthers 1140 grs. in six days; both patients recovered—Beck's after a continuous sleep of thirty hours. In one case the chloral sleep was maintained without interruption for eight days, from 250 to 300 grains a day being given; and in another, which also recovered, over 3000 grs. were taken in the course of thirty-eight days.