In the production of anesthesia by chloroform there are four stages, as in ether anesthesia, and the symptoms are the same in nature. But chloroform, properly diluted with air, is not unpleasant to the patient, is scarcely irritating to nose and throat, and is more prompt in producing anesthesia, hence the first and second stages are comparatively short and not so disagreeable, and the stage of intoxication is seldom troublesome. With chloroform a patient may be anesthetized in from two to five minutes; with ether it may take ten or fifteen minutes. The recovery is correspondingly rapid. Again, the amount of ether required is much greater, it being reckoned in ounces, while that of chloroform is reckoned in drams. In chloroform anesthesia the face is usually pale rather than flushed, and the breathing is quiet; in fact, so different is this from the ether effect that it sometimes worries the anesthetist or surgeon who has been regularly employing ether.

Chloroform would therefore have some decided advantages over ether were it not for the fact that it is less safe. The advantages are: (1) Smaller dose. (2) Simplicity of administration - a small container and small mask, a good thing in field work; or a few drops on a handkerchief. (3) Easier and pleasanter for patient. (4) Less marked stage of intoxication. (5) Anesthesia more quickly produced. (6) Anesthesia more quickly recovered from. (7) No bronchial or lung irritation. (8) Respiratory mucus and saliva not excessive. (9) Nausea and vomiting less common after-effects. (10) Chloroform is not inflammable, and its vapor does not make an explosive mixture with air.

These are decided advantages in the administration of an anesthetic, yet in spite of them ether is preferred because chloroform is more dangerous.

The special dangers of chloroform anesthesia are - (1) Early heart failure; (2) the cardiac depression with limited margin of safety; (3) delayed chloroform poisoning.

The First Danger

This may come from too concentrated vapor at the start, or from ventricular fibrillation, the result of too weak vapor (see Pharmacologic Action). In the laboratory it is not uncommon that when a dog is made to inhale concentrated chloroform its heart will be promptly slowed, and in some cases will stop and not beat again. Death from concentrated vapor takes place before enough chloroform has been absorbed to cause death by systemic action. But if, before the inhalation, a dog is given a hypodermatic of a large dose of atropine, or if his vagus nerves are cut, even very concentrated chloroform does not cause a stoppage of the heart at all. The cessation of the heart-beat must, therefore, be due to excessive vagus activity. But this stoppage of the heart is also prevented if the laryngeal nerves are cut or if the throat is anesthetized with cocaine; therefore the effect is a reflex one, and the stimulation of the vagus is the result of the irritant action of the chloroform upon the throat.

It has been surmised that many of the chloroform casualties have taken place in this way, for they have occurred in the first few moments of the administration, before the surgeon had begun to operate and before the stage of full anesthesia had been reached (90 per cent of casualties take place in the first fifteen minutes - Gwathmey). This possibility of excessive reflex inhibition, therefore, becomes a serious matter.

Ordinarily, it is impossible to kill an animal by excessive vagus stimulation, for after a brief period the heart will go on beating again in spite of the vagus. But in the administration of a gas by the lungs the area of absorption is large; and the pulmonary blood, charged heavily with vapor, passes instantly to the left heart and poisons its muscles.

Cases are not reported of excessive vagus inhibition from the use of ether as an anesthetic, but Muehlberg and Kramer have shown that an injection into the carotid artery of as little as 2 minims of ether or chloroform can cause almost instant death in a rabbit. They also show that even if vagus inhibition is prevented the heart is weakened. The conclusion is that when death takes place during the early stages of chloroform administration there is probably either ventricular fibrillation, or a combination of three conditions, viz.: (1) Weakening of the heart due to direct action of the poison. This, absorbed by the extensive lung surface, makes a concentrated solution in the pulmonary blood which passes at once into the left heart and to the coronaries; (2) reflex vagus stimulation, and (3) reflex vasoconstrictor stimulation. The combination of these three effects, viz., inhibition, muscle poisoning, and increased peripheral resistance, results in heart failure.

Levy says that enough chloroform to weaken the ventricles will prevent their fibrillation. On the other hand, if the chloroform is given to a dog in sufficient dilution with air to avoid the local irritation of the throat, both the vagus center and the throat soon become less sensitive, and then it is impossible to produce this vagus inhibition with any strength of chloroform. Hence the excessive reflex activity of the vagus may be prevented by avoiding too great concentration of the vapor at the outset, or by a preliminary injection of a large dose of atropine, or by thorough cocainization of the pharynx and larynx.

The Second Danger

We have already learned that chloroform is much more depressing to the muscles of the heart and arteries and to the medullary centers than is ether. This depressing effect is seen almost from the start, while with ether such a depression is not noted except in prolonged anesthesia or from overwhelming doses of concentrated vapor. In addition, the chloroform has a special affinity for the heart muscle, so that it is less readily discharged from it than ether. Hence resuscitation is difficult.

These factors make the margin of safety for chloroform a narrow one, the stage of complete anesthesia being much nearer the stage of collapse than with ether. Furthermore, when collapse comes on from ether, the patient may often be restored with comparative ease, while when the signs of collapse appear from chloroform the chances of recovery are small.