This is a companion case to that reported by Graham, where ligation of the limb proved to be of great practical importance.
An interesting series of experiments, bearing directly upon the use of the ligature in such cases, were made by Mr. Georges,[29] at the Paris Society of Practical Medicine, some of which were conducted for this gentleman by M. Claude Bernard. These experiments consisted in “injecting poisonous substances into the cellular tissue, with the view of showing the far greater safety and certainty of the hypodermic method as a means of administering, medicinally, highly-poisonous substances. He injected quantities of codeine, atropine and especially strychnine, which would surely cause death in the absence of precautions for preventing the too rapid introduction of the poisons. These injections were practiced without danger in the dog’s paw, the passage of the poison into the veins being checked by the forcible application of a ligature around the paw. To render the experiment still more striking, he resolved to employ injections of the most dangerous of poisons—curare—and M. Claude Bernard conducted them for him. A solution containing about five centigrams of curare (sufficient to kill more than fifty dogs of the size of the one operated upon), was injected into the paw, and in twenty minutes the animal fell on its side. The paw was now firmly tied, and at the end of about twenty minutes the animal arose. Whenever the ligature was loosened he again fell down, sometimes at the end of ten minutes, and sometimes in a shorter period,[30] and in this way it became possible to dose with complete certainty, according to the effect desired to be produced, the quantity of poison to be absorbed. The next day the dog was found on his three paws, only suffering from the swelling caused in the fourth by the injections. The ligature was removed and he was soon all right.
“The same experiment performed on another dog was followed by the same results, the animal being caused to fall or rise at the end of five, ten, or fifteen minutes, accordingly as the paw was tied or untied. This dog, however, next morning, on the removal of the ligature, fell down again, all the poison not having had time to become eliminated by the urine, so that it was necessary to reapply the ligature. M. Georges points out the superiority of the endermic method, when we have to administer powerful substances, as we may apportion the dose with an exactitude, according to the tolerance of the disease and idiosyncrasy of the patient, quite unattainable when administered internally.”
Dr. Alonzo Clark, Professor of Theory and Practice of Medicine and Clinical Medicine in the College of Physicians and Surgeons, New York, kindly gives me the details of the following case: “There was brought into Bellevue Hospital, some years ago, during his term of service, a young woman, aged about twenty-five, suffering from trismus. The jaws were so firmly locked that it was necessary to break out a tooth, in order to administer food and medicine. All ordinary medicine failing, on the evening of the second day the house physician determined to treat the case with hypodermic injections of morphia. He gave three injections of fifteen minims of Magendie’s solution, with two hours’ interval between the doses, and finding that no effects of the morphia were apparent at 2 A.M., he gave an injection of twenty minims. When he returned to the ward, at 4 A.M., the patient was dead. The nurse, on being questioned, stated that the patient was “asleep” before the doctor left the ward. The arm in which the puncture had been made was examined by Dr. Clark and others, and over the point of the last puncture a little discoloration, as from extravasated blood, was apparent, and which, on careful dissection, was found to mark the track of the needle, which had opened directly into a vein.”
In this case the patient probably died almost immediately, the action of the morphia being shock-like, and its effect the more intense as one grain and a half had already entered the system by the skin.
Prof. Wm. T. Lusk, of this city, writes me of a case of syncope following immediately upon the injection. No blood appeared at the point of puncture.
Another case of death from injection into a vein is reported to me by Professor Willard Parker. An injection of morphia, to relieve the severe pain of neuralgia, was made into the temporal region of an apparently healthy young man. Death was almost immediate. The case was in the hands of a physician in Connecticut. I have repeatedly written, asking for full particulars, but cannot get them. It is a strange fact that all the cases where injection into the temporal or infra-orbital region is mentioned by correspondents and by some authors, have been attended by either intense narcotism or death. This is, of course, not a uniform occurrence, but it has happened sufficiently often to call our attention to it, and urge caution in its use in this situation.
In this connection, and in point of history, the following quaintly worded extract from a diary, which appears in Pepy’s Journal,[31] of May 16th, 1664, is of interest. “With Mr. Pierce, the surgeon, to see the experiment of killing a dog by letting opium into its hind leg. He and Dr. Clark did fail mightily in hitting the vein, and in effect did not do the business after many trials; but with the little they got in, the dog did presently fall asleep and so lay till we cut him up.”
The different effects produced by the same accident on different persons seems to be due to some peculiarity of constitution with reference to morphine. The drug is thrown so rapidly into the circulation that it carries everything before it, seeming to instantly overwhelm the vital powers. The brunt of its action seems to be exerted on the heart, and the key to proper treatment is thereby afforded. To whatever cause due, the effect is essentially the same, the difference being only one of degree. That syncope and vaso-motor disturbances are ever due to the injection of air into a vein with the solution, I very much doubt. In the first place the morphia itself is quite sufficient to produce the symptoms, and in the second place not more than a bubble of air is ever left, by carelessness, in a syringe, and this is not sufficient to produce these symptoms. To settle this matter, I purposely injected into the median cephalic vein of my own arm twice as much air as this, with a solution of warm water, and without any bad effects; in fact, no effect whatever. My arm, above the point of puncture, was protected by a ligature that could have been drawn tight at a moment’s notice, had there been any untoward symptoms. The following day I injected one-sixteenth of a grain of the sulphate of morphia into another vein, with the effect of producing sudden dizziness, a feeling as if the head would burst, pricking and tingling of the nose, suffusion of the face and eyeballs, dilatation of the pupils, faintness and nausea. The pulse was first greatly accelerated, and then fell to about 65, and remained so all that day. My pulse in health is 74. This was done at 10.30 A.M., and I did not fully recover until about 3 P.M. It may be well to state that morphia, either by the mouth or skin, always has a very unpleasant effect on me, while opium has not. Instead of causing sleep and soothing irritation, the former makes me nervous, “twitchy” and somewhat light-headed. In both cases the needle entered the vein, as it was made prominent by the ligature, and blood appeared at the point of puncture. As soon as the injection was made the ligature was loosened, I being ready to pull it tight at a moment’s notice.
M. Calvet[32] presents a physiological research of the action of morphine upon the various functions of the organism. A clinical study of morphine as a therapeutical agent, especially in the relations of acute to chronic morphinism. In the first he observes that both intravenous as well as subcutaneous injection of the hydrochlorate of morphine accelerates respiratory movements, succeeded by a period of retardation, and produces sometimes a momentary arrest or respiratory syncope. The same relative effects occur with the cardiac movements; at first accelerated, followed by retarded pulsations; sometimes even by cardiac syncope. During this time animal heat exhibits analogous phenomena, namely, the elevated is followed by lowered temperature. In fact, the absorption of morphine, whether by intravenous or subcutaneous injection, produces a very marked influence upon the reflex actions. In certain cases the period of exaltation does not occur, but the temperature becomes lowered, and the respiratory and cardiac movements are slower. Though he has not finally completed his researches, M. Calvet advances the opinion “that the above phenomena are the dyspnœa, dizziness, etc., sometimes seen during the operation of intravenous injection of milk.” A study of these cases[33] (milk injections) shows us that these phenomena rarely if ever present themselves until a large bulk of fluid (from two to six ounces) has been added to the blood, and that, therefore, the argument does not hold good.