THE search for the ideal anesthetic has become intense. When the anesthetists of this country and Canada organized some twenty years ago to form the International Anesthesia Research Society, the interest of physiologic and pharmacologic research workers was at once aroused. Since that day these men of the laboratory, in collaboration with our outstanding anesthetists, have brought about marked advances in methods of anesthesia.
Luckhardt produced ethylene; Gwathmey perfected colonic ether-oil analgesia for obstetrics; Waters of the University of Wisconsin gave us a real advance in gas anesthesia with his closed-circuit, carbon-dioxide absorption technic; pre-medication with the barbiturates synergizing morphine has been a boon to the operative patiently and the introduction in Germany of overtone as a basal anesthetic soon became international in extent. With the discovery of “Spinocain” by Pitkin, spinal anesthesia was popularized and its technic so perfected that it is safe in the hands of the expert.
During the past year, from the work of two pharmacologists, Henderson of the University of Toronto, and and Leake of California, came the announcement of cyclopropane and divinyl oxide or vinyl ether. Leake, noting the close chemical relationship better the formulae of ethyl ether, ethylene, and divinyl oxide investigated the latter in 1930, and demonstrated that it possessed anesthetic properties. With other workers, experimenting on mice and dogs, he found that anesthesia could be much more easily produced using vinyl ether than by using ethyl ether. with less struggling and excitement and less mucous secretion; that recovery was rapid, with nausea and vomiting less marked, leaving no significant pathologic effects on the various organs. It was preferable to either chloroform or ethyl ether.
Extensive physiologic, pathologic and clinical studies have since been made on the dig, the monkey and man. It has been shown that the anesthetic potency of vinyl ether is seven times that of ethyl ether and 1.3 greater than that of chloroform. At the same time there is a wider “margin of safety” between the anesthetic and lethal concentrations of vinyl ether in the blood as compared with those of the other two drugs. These longed divinyl ether anesthesia, but no liver necrosis ether to 500 patients of all ages and conditions and for operations of a very varied nature,. In these they encountered no untoward effects on respiration, circulation, liver or kidneys.
Believing that a very good estimate of the general effects of a drug may be made its action on the liver, Wesley Bourne, anesthetist and research worker of McGill University, has contributed some very interesting results from his studies. Vinyl ether was administered to normal dogs, to dogs with damaged livers, and to partially starved dogs, and the liver function eleven normal dogs show that vinyl ether administered for periods of one hour or more on three successive days does not alter the live function appreciably. In those cases where cyanosis was a feature of the anesthesia, moderate impairment of liver function occurred, but this was not directly due to the drug, but to the associated anoxemia.
For a study, measured degrees of liver impairment were produced by chloroform administration. At various times during the recovery period from chloroform poisoning, vinyl ether was given to determine whether additional liver damage occurred. It had been shown in the laboratory that chloroform always causes marked impairment of liver function. From seven experiments, Bourne found that vinyl ether does form poisoning, nor does it retard the progress of recovery. Furthermore,. repetition of vinyl ether on two successive days did not alter the period of recovery from chloroform poisoning at all.
With respect to starved dogs, since the glycogen reserve of the liver is lowered through starvation, four animals were place on half ration for three days, then given vinyl ether in order to observe its effect on glycogen-poor livers. It was found that there is no appreciable difference in the effects of vinyl ether in order to observe its effect on glycogen-poor livers.
It was found that there is no appreciable difference in the effect of vinyl ether upon normal and starved dogs-that is, upon normal and glycogen-poor livers. Three experiments performed to determine accurately whether death from this anesthetic is respiratory or circulatory in character, when after one hour of anesthesia, showed that respirations ceased before the the heart stopped. This corroborated the work of other investigators.
Bourne decided that this should be an ideal anesthetic in obstetrics, and thus far has reported on over 300 administrations at the Royal Victoria Montreal Maternity Hospital. The method used was to bubble oxygen through the dinyl ether in an apparatus using carbon dioxide absorption to preclude asphyxia and prevent waste. He found strikingly rapid induction, a few inhalations being sufficient, little excitement; and degree of muscular relaxation it compared favorably with ethyl ether. Post anesthetic nausea and vomiting were no more frequent than is usual in obstetrics. Tests of liver function showed practically no impairment. He concludes that vinyl ether is very suitable for employment in obstetrics, especially to replace chloroform.
Through the kindness of Dr. Beach, anesthetist of the Graduate Hospital of he University of Pennsylvania, who has been active in the clinical research work with this drug, I received a large supply for clinical trial from Merck & Co., the manufacturers. In the last several months we have administered vinyl ether, both by the drop method on the open mask; as an adjuvant to gas, replacing ethyl ether for muscular relaxation; and on the mask as an induction agent for ethyl ether, to some fifty patients. The operative procedures varied from incision of abscessed jaw, rib resection for empyema in several children, dilation and curettage in septic abortion with severe haemorrhage and consequent anemia, pelvic laparotomies, appendicectomies, breast amputation, and nephrectomies. It was given to children and adults.
In vinyl ether we have a highly volatile, clear, practically colorless liquid. It has a somewhat pungent odor, not at all unpleasant, that reminds one of ethyl chloride. It is inflammable with an explosiveness approximately the same as that of ethyl ether. It has a boiling point of 83 Fahrenheit.
We found that in using vinyl ether by the drop method on the open mask, rate of from sixty to eighty drops per minute, essentially the same as for chloroform, produced unconsciousness about as rapidly as does ethyl chloride. In most cases there was no excitement whatever, and if present at all, if was very slight. We noted an increase in salivation, particularly in cases in which there apparently was no irritation to the respiratory tract. Muscular relaxation was excellent, similar to throat obtained with ethyl ether. The recovery of consciousness was very rapid, and is comparable to that following nitrous oxide. Post-operative nausea or vomiting were practically nil.
When used in the gas apparatus as an adjuvant instead of ethyl ether, it was noted in several instances where administration was continued for some times that the systolic and diastolic pressure rose gradually, with a flushing of the skin which persisted for some time after the anesthesia was discontinued. In one case, a male, the systolic pressure advanced from 120 mm. to over 2 mm. Although vinyl ether has an advantage over ethyl ether as an adjuvant in that a much smaller quantity is needed, we believe that it is not advisable to use it for prolonged periods.
Its sphere of usefulness appears to be in minor surgery where a short period of anesthesia is sufficient; as an ideal replacement of chloroform in obstetrics; as the inducing agent for an ethyl-ether sequence when gas is not available. It permits of a very smooth change latter, overdosage striking at the respiratory system rather than the circulatory. This factor is prime importance in the chance of resuscitation.
Vinyl ether has certain rather serious disadvantages, among which are:.
(1) Its high degree of volatility which tends to waste fulness when used on the open mask.
(2) Its instability-undergoing chemical changes when exposed to light and air. The manufacturers state that it should not be used after the bottle has been opened twelve hours. A date limit is also stamped the label.
(3) Because of the low boiling point, and consequent increase of volatility in hot weather, its use in such periods would require constant watchfulness to prevent any of the reactions which may follow the use of a potent anesthetic.
(4) Because of its rapid action it will not allow of a too concentrated use-in other words-it cannot be “pushed”.
From our experience we may say that vinyl ether should have a very definite place among anesthetic agents. It is outstanding as a pleasant, rapid anesthetic with quick recovery and safety comparable to that of ethyl ether. This should appeal to the average physician when the expert anesthetist and his gas apparatus are not available.