In 1899 Meltzer noted paralysis in a rabbit from the intracerebral injection of magnesium sulphate, and in 1905 was joined by Auer in an investigation of this action. They found that a 25 per cent. solution applied to a nerve-trunk completely blocked both sensory and motor impulses; that on subcutaneous injection there was complete anesthesia with muscular relaxation lasting for two or three hours and without any cathartic effect, and that the injection into the spinal canal was followed by sensory and motor paralysis and profound narcosis. The paralysis began in the hind legs and spread upward until it involved the anterior extremities. With lethal doses the blood-pressure was but little affected, and death was due to respiratory paralysis.

In one experiment on a monkey a lethal dose was given in-traspinally. Respiration failed, but as the heart continued beating, artificial respiration was instituted. After seven hours the artificial respiration was stopped, and the animal was found to be still incapable of spontaneous respiration. After seven hours more the artificial respiration was again stopped, and then the animal continued to breathe without aid. During all the period of respiratory paralysis the heart's action continued good, and there was evidently no cardiac or vasoconstrictor depression.

Meltzer and Lucus found that after its subcutaneous injection the drug was eliminated by the kidneys, and that when the kidneys were impaired, it was twice as poisonous, and might have a cumulative action. According to Meltzer the dominant action of magnesium salts, no matter what the mode of administration, is depression or inhibition. Intramuscularly and intravenously the action is rapid and of short duration. Intraspinally the effect lasts twenty-four hours. There may be slight irritation of the kidneys, retention of urine, or glycosuria with hyperglycemia. Canestro (1910) found that the addition of a small amount of epinephrine made it less toxic to the respiratory center. That it is a central anesthetic as well as peripheral has been fully established by Meltzer and his associates. Hyndman and Mitch-ener (1910) found it no more depressing to the motor area of the brain than ether, as tested by electric stimulation. Cloetta showed that the salts do not penetrate the cells of the brain and do not act like the volatile anesthetics of the alcohol series.

Meltzer's Theory To Explain The Anesthetic Action And Its Neutralization By Calcium

Magnesium readily enters the "synaptic membrane" (Sherrington) between the neurons, and interrupts the passage of afferent nervous impulses. The synaptic membrane between motor nerves and muscle are more resistant to magnesium, so efferent nervous impulses are less readily affected. Calcium enters the synaptic membrane readily and displaces or neutralizes there the obstructing or inhibiting magnesium. When, however, magnesium by its long presence in the lymph manages to enter the inside of the nerve-cell, the calcium is incapable of readily dislodging or neutralizing it.

Following these experiments the drug has been used for the production of anesthesia and the treatment of tetanus and other spasmodic affections.

Anesthesia

J. A. Blake and many others used the intraspinal method, and concluded that the action was too uncertain and likely to be too prolonged, though even with the most profound anesthetic effects the heart's action remained regular, and the blood-pressure was not lowered. But Peck and Meltzer (1916) have reported cases of its intravenous use, employing about 8 c.c. per minute of a 6 per cent. solution. Sensation, consciousness, and muscular tone were more or less abolished, and recovery took place within a few minutes of the cessation of the administration. They found the dose very variable. Auer and Meltzer (1916) were able to obtain in dogs a stage of analgesia with relaxed abdominal muscles while the respiration remained normal and the lid reflex was fair or even normal. They advise against its use if there is cardiac insufficiency or acute nephritis.

Dawbarn, and also Wainwright, in using spinal analgesia to block afferent impulses in traumatic shock, found that when the effect of a rapidly acting local anesthetic wears off, the shock may reappear and the patient die, death being merely postponed an hour or two. In two cases Dawbarn employed a solution of magnesium sulphate with tropacocaine, and found that in both the nerve-blocking began quickly and continued for from twenty-four to forty-eight hours, i. e., the tropacocaine began the anesthesia early, and the magnesium sulphate continued it. Injected along the course of the nerves it also anesthetizes.

Tetanus

The most striking effects are the relief from pain and the cessation of the spasms so that swallowing of food becomes possible. The dose is renewed when there is a feeling of tightness about the chest or inability to swallow. Meltzer gives the following plan of treatment, with the precautions: In mild cases inject subcutaneously 1.2 c.c. of 25 per cent. solution three or four times a day. In severe cases administer intraspinally 1 c.c. of 25 per cent. solution for each 20 pounds (10 kg.) of body weight, or for children 0.5 c.c. for each 20 pounds. If the symptoms are alarming, as in spasm of pharynx, larynx, or diaphragm, give 2 to 3 c.c. per minute of a 6 per cent. solution intravenously till the dangerous symptoms subside or the respiration becomes shallow or too slow. If from the intravenous solution the respiration becomes depressed a small amount of 2.5 per cent. calcium chloride intravenously may restore it almost immediately and this may be supplemented by 1/65 grain (1 mg.) of physostig-mine. Never continue the calcium salt beyond the restoration of respiration or the whole magnesium action will be annulled and the tetanic symptoms recur. If there is suspended respiration, intrapharyngeal insufflation or some other method of artificial respiration should be instituted, and if necessary continued for hours. For respiratory paralysis from intraspinal administration calcium and physostigmine are useless, and the spinal canal should be washed out several times with Ringer's solution.

Owing to its prolonged action magnesium sulphate, used intraspinally, would seem to be particularly valuable and safe in the convulsions of tetanus, strychnine poisoning, and eclampsia, and in preventing shock from severe traumatism. Used intraspinally or injected into the nerve, it has been suggested as a possible measure of relief in refractory sciatica.

Besides these uses the drug has been employed intraspinally in delirium tremens, intravenously in puerperal streptococcemia (Huggins and Harrar report good results), and intravenously or subcutaneously in chorea and spasmophilia. Bryant reports the cure of a purulent cerebrospinal meningitis from copious draughts of a dilute solution, and Wyatt-Smith cures of non-amebic dysentery from colon irrigations. It is to be remembered that Auer and Meltzer (1914) found that it might be absorbed from the small intestine with fatal effects.

Locally, a, saturated solution of magnesium sulphate (it is soluble in 0.85 part of water) has been much employed in the form of a wet compress as a local application to reduce the pain in neuralgia, neuritis, dermatitis, and burns. Tucker (1911) reports good results in epididymitis, arthritis, cellulitis, and erysipelas. (See also Saline Cathartics.)