The Third Danger

In the last few years a great many cases have been reported in which the patient, after apparently recovering from chloroform, would pass in a few hours or days into a condition of marked prostration, delirium, coma, and death. This condition has become known as delayed chloroform poisoning, and it has been the subject of much careful study.

The symptoms appear in from ten hours to six days after the anesthetization. The onset may be gradual or sudden. In the former the patient does not fully recover after the anesthesia, and gradually passes into a state of prostration with delirium, coma, and death. When the onset is sudden, the patient recovers from the anesthesia and is apparently doing well, and the first indications of anything wrong are marked cerebral disturbance, with the sudden appearance of periods of wild delirium, with shrieking and struggling, alternating with periods of stupor or coma. There may be vomiting of blood, cyanosis, jaundice, edema, intestinal or renal hemorrhage, and sweetish, acetone breath. The urine may contain albumin, casts, and blood, and in addition a high ammonia nitrogen and low urea nitrogen, and in some cases acetone, diacetic acid, and beta-oxybutyric acid. The delirium and .coma are followed by collapse, death taking place twelve to sixty hours after the first appearance of the symptoms.

Postmortem examination regularly reveals extensive fatty degeneration of the liver, with necrotic areas in the lobules and scattered hemorrhages, frequently some fatty degeneration in the kidney tubules with hemorrhagic areas, and sometimes fatty degeneration in the heart and arteries (Howland and Richards). Degeneration in the cardiac ganglia has also been reported. There may be hemorrhages in the stomach and intestines and in the serous membranes.

In experiments on dogs it has been found that in some instances even fifteen minutes' mild anesthetization from chloroform has been enough to produce areas of fatty degeneration in the liver. And it is believed that fatty degeneration of the liver of some degree must take place in every full chloroform anesthesia, though ordinarily this is rapidly recovered from. Muller (1905) and Offergeld in the same year demonstrated that in animals anesthetized twice within a few days the changes were more pronounced, and delayed chloroform poisoning more likely to follow. It has also been shown experimentally that a preliminary impairment of the kidneys or much hemorrhage favors the liver destruction.

In humans, delayed chloroform poisoning has occurred most commonly in children. It has rarely been recovered from. In animal experiments carbohydrates have been shown to be protective, and A. Weir reports one case of recovery following the administration of 15 gm. of glucose in 500 c.c. of water by stomach (tube through nares) every four hours, and 10 gm. of glucose in 100 c.c. of water by rectum. Graham attributes the toxemia to acids formed from the chloroform. He finds that he can produce similar effects by hydrochloric acid, and that sodium carbonate in hypertonic solution intravenously markedly inhibits the production of the lesions.

The conditions which favor the development of delayed chloroform poisoning are believed to be: Liver abscess, kidney disease, anemia, especially that due to hemorrhage, alcoholism, obesity, the lymphatic diathesis, childhood, previous chloroform anesthesia within two or three days, and prolonged anesthesia.

Several observers have reported acute liver atrophy following chloroform.

To repeat, then, the three dangers in chloroform anesthesia, which are slight or absent in ether anesthesia, are the following:

1. Sudden death before complete anesthesia is induced.

2. Small Margin Of Safety

The depression of heart and arteries and of the vasoconstrictor and respiratory center makes a small margin of safety between the stages of anesthesia and collapse, and difficulty in restoring the patient after signs of danger are manifest. This is especially true in persons with the lymphatic diathesis.

3. Delayed chloroform poisoning.

It is on account of these that the use of chloroform has been quite generally abandoned as a general anesthetic, except in a few special types of cases.

Possible preventive measures are:

1. To prevent vagus stoppage of heart - atropine, 1/60 grain (0.001 gm.) by hypodermatic, cocaine to throat, or well-diluted chloroform at the start.

2. To retard cardiac and central depression - oxygen, avoidance of too long a period of starvation before the operation, and the use of a minimum quantity of the anesthetic.

3. To lessen or check the fatty degenerations - oxygen, glycogen-forming food (glucose, sugar, etc.), alkalies, and avoidance of too long a period of starvation before the anesthesia. Hunter recommends that the patient be given a nutritious and easily digestible meal, well sweetened, two or three hours before the anesthetic.

Contraindications To Chloroform

Diabetes, sepsis, hemorrhage, eclampsia, conditions of much enfeeblement, fatty degeneration, and the lymphatic diathesis.

Acidosis In General Anesthesia

The development of acidosis following anesthesia, as shown by the appearance of acetone, diacetic acid, and beta-oxybutyric acid in the urine, is a matter of considerable importance.

According to Ewing, Becker found acetonuria in two-thirds of all anesthetized patients, the condition being most pronounced in children, and more marked in women than in men. It appeared in the first or second portion of urine passed, and persisted eight or nine days. Abram found acetone in 25 cases, and more frequently after chloroform than after ether. Wallace and Gillespie found it in 25 per cent. of cases before operation and in about 60 per cent. after operation. Waldvogel observed it in 75 per cent. of 50 cases, and in 13 of them noted diacetic and beta-oxybutyric acids.

These observations indicate the marked danger of general anesthesia in all conditions associated with acidosis, such as diabetes and the various toxemias, especially those associated with liver degeneration. Therefore general anesthesia, whether from chloroform or ether, requires special consideration in diabetes, eclampsia, vomiting of pregnancy, cyclic vomiting, acute yellow atrophy of the liver, general sepsis, uremia, and in those cases of intestinal obstruction with marked auto-intoxication. In all these types of cases the dangers of chloroform are greater than those of ether.

Of acetonuria, Wallace and Gillespie say that the vomiting after twelve hours is regularly related to the amount of acetone, and this can be lessened by lavage with sodium bicarbonate. But for administration as a prophylactic before the anesthesia glucose is to be preferred to sodium bicarbonate.

Effects On Infections And Immunity

Graham-Rubin (1907) showed that hypodermatics of alcohol, ether, or chloroform rendered rabbits more susceptible to systemic infection with streptococcus and pneumococcus; and Stewart (1907) showed that this was especially true of infections to which immunity was chiefly phagocytic. In other immunity studies also it has been shown of alcohol, which is of the same class, that after the injection of an antigen it retards the formation of the antibodies. The same is probably true of ether and chloroform.

Francois (1910) found that after chloroform or ether anesthesia the phagocytic activity of the leukocytes was lessened or abolished, and that this effect lasted for twenty-four hours. Graham (1910) also observed that the phagocytic power was not restored for many hours. He noted that while saline infusion did not hasten the restoration, olive oil by rectum, or lecithin, 0.1 gm. subcutaneously, shortened the period of phagocytic depression. But Mann, 1916, states that phagocytes that have been subjected for four to six hours to a concentration of ether capable of maintaining a dog under surgical anesthesia, do not exhibit any change in activity.

Some General Remarks About Administration

Before the administration the patient should be reassured and brought into a 20 calm state of mind, for the psychic factor is important. This is the idea in Crile's "anoci-association."

Skill in administering a general anesthetic involves not merely the prevention of death, but also the leaving of the patient in the best possible physical and mental condition after the operation. With both chloroform and ether the danger lies in over-concentration of the vapor or surcharging of the blood by too rapid administration, rather than in the total quantity of the drug employed in any given anesthesia.

It is wise to avoid anesthetizing beyond the point necessary, for if the patient becomes too deeply anesthetized, and then, by stoppage of the administration, is allowed to come back to the condition of surgical anesthesia, his centers are more depressed, and he is in a weaker and less resistant state than if he has been kept steadily at the proper degree of anesthesia throughout. To administer rapidly a large quantity of concentrated vapor, i. e., to "push" the ether or chloroform when the patient unexpectedly shows signs of recovery, adds to the depression of the respiratory and vasoconstrictor centers; and it is unjustifiable to try and cover up the faults of carelessness or inexperience by such a method. It is better to proceed carefully, even though the surgeon is kept waiting.