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STUDIES ON ETHER AND CHLOROFORM, FROM PROF. SCHIFF'S PHYSIOLOGICAL LABORATORY.
BY T. G. HAKE, M.D., F.C.S., M.R.C.P.
DURING a prolonged stay at Florence, I have enjoyed frequent opportunities of witnessing Professor Schiff's methods of experimenting on living animals in a state of complete anesthesia, and have been so deeply interested in his researches, especially those on the comparative merits of ether and chloroform as anæsthetic agents, that with his sanction I propose to describe to you certain important results which I have myself witnessed. Much curiosity has been awakened here of late by some illadvised parties having commenced proceedings in the law courts against the Laboratory of Physiology, but the process has been withdrawn, the accusation of cruelty to animals made against the eminent Professor having proved utterly futile and based only on ignorant rumours, as has since been admitted in writing by the principal complainant.
Whatever may have been the object of his researches, Professor Schiff during the period of twenty-five years has never lost sight of the laws of anesthetic action, and his observations on this subject, as far as regards practical usefulness, rank among his most valuable results, those on the physiological
effects of ether and chloroform having a direct and most important bearing on human interests, while those on the curara poison invite further inquiry as to whether this agent is anything more than a paralyser of muscular movements. I may here add that he is at the present time earnestly occupied in seeking a substantial remedy for paralysis of the circulation occasioned by the use of chloroform, a fatality for which no reliable means of treatment has hitherto been found; galvanism, owing to its exciting very irregular contraction of the muscular fibres, which fails to exert any mechanical effect, having signally failed; and transfusion, which is more promising, being not at all times practicable. Further, that he has cause for hope of yet bringing this search to a successful issue.
That the heart is in a vital state favourable to its renewed action when paralysed by the influence of chloroform on the vaso-motor nerves, is demonstrated by Professor Schiff's practice of artificial circulation. He lays open the thoracic cavity, and, compressing the passive heart with his fingers, imitates in it the periodic movements of that organ. The circulation is restored, the nerves of the heart recover their force, and the organ finally resumes its spontaneous action. Before long, signs of returning sensibility become apparent, the reflex action of the eyelid returns, and the animal is now capable of being brought back to cerebral consciousness; it would, however, be both cruel and useless to extend the experiment so far.
In all his experiments the preliminary condition with Professor Schiff is that the animal employed should be in a complete state of insensibility, a rule which he never deviates from, it being a fixed principle with him never to inflict suffering. Consequently, doubts having arisen in his mind as to whether the curara poison acts as an anesthetic, or only paralyses movement, and so prevents the outward expression of pain, an anxious question has been opened to him, this agent being much used in physiological experiments on living animals under the notion that it destroys sensation. In the new edition of his work, "Sopra il metodo seguito negli esperimenti sugli animali viventi," expressing these doubts, he says: "We have at the present time made fresh experiments on frogs, and have found that curara given in large doses really destroys sensibility: but
it does not act as an anesthetic until a considerable time after having destroyed all voluntary movements and automatic respiration. In the mammalia it is impossible to make such experiments as indicate with precision how soon sensation ceases after the commencement of poisoning. But it is certain that in these also sensibility still exists after all voluntary movements have ceased, and we have no right to consider that a mammal poisoned with curara is insensible because it is unable to manifest its sensibility by means of ordinary movements and cries. Under these circumstances we are bound to admit the possibility of consciousness and pain persisting during the whole period after poisoning, while an animal responds still to any strong impression with manifest contraction in the vascular or in other unstriped and involuntary muscles--contractions which we are not able to recognise in a direct manner, but which are manifested by the complicated means afforded us by science. It is possible, I admit, that sensation may have already ceased, but one cannot prove it, the proof being wanting which other anæsthetics afford us in man. As a friend observed to me, 'In experiments for measuring the pressure of the blood, made with the exclusive use of curara, and in which the pressure was found at the normal height, the curara has acted only as a tranquillising agent which in impeding movement conceals the pain from the bystanders. It is no other than hypocrisy wishing to convince oneself and others that the animal under curara never feels pain.""
While curara acts as a paralyser of all movements, voluntary, reflex, and irritative, the temptation of using it as a supposed anæsthetic is very great, its effects leaving intact the influence of the irritation of a sensitive nerve on the automatic movements of the circulation and respiration, to those who would. make this an object of study. Professor Schiff only contends that until more than theoretical evidence of its anæsthetic properties can be adduced, the use of curara is unjustifiable; and he urges this view the more strongly on the ground that we have no right to inflict pain for the purposes of research.
Professor Schiff's observations on ether and chloroform have a direct bearing on surgical practice, though not pursued with that view, but solely for the advancement of physiological science
by means of the most perfect methods. "We adopt ether and not chloroform," he says, in the work already cited, “because a very extensive experience has shown that etherisation pushed to the very last stage of insensibility is never dangerous to life so long as one maintains the act of respiration. And even if one presses the inhalation of ether yet further, so that the respiratory movements cease, or, in other words, the appearance of death is complete, life is never menaced, if only at the moment of the paralysis of the thoracic walls inhalation is interrupted and a species of artificial respiration is immediately commenced by means of periodic compression of the thoracic parietes themselves. "Chloroform has been preferred to ether because it acts more quickly, and its use is more agreeable to the patient, who dislikes the odour of ether. But chloroform has a paralysing action much greater than that of ether, and in like manner, at least in man and the mammalia generally, has a special influence on the nerves of the heart and of the vessels. If chloroform is pushed so as to produce a considerable weakening of the respiratory movements, the interruption of the inhalation may, in a majority of cases, lead to the re-establishment of respira tion and afterwards of sensation; but sometimes, a short time. after the commencement of inhalation, the force of the circulation is so enfeebled that it no longer renews, fast enough, the blood in the lungs. The blood of the body no longer comes into necessary contact with the atmospheric air introduced by respiration into the lungs.
"Death is sometimes sudden, but it may be preceded more or less by signs of sinking of the pressure of the blood in the vessels. The cases in which paralysis of the circulation shows itself while respiration continues are comparatively rare, but the annals of human surgery record many examples, and we have ourselves observed some in animals. If the action of chloroform is prolonged until respiration ceases, we are not even sure of being able to revive the individual after having re-established the respiratory movements, for these often again cease owing to the disturbance of the circulation, while these same movements, if restored after the inhalation of ether, become always more frequent in the individual when left to himself.
"We are able to say that in the present state of science the medical man is responsible for every case of death occasioned by the application of ether, because a careful watching of the respiration is capable of preventing death, whilst the lethal effect of chloroform depends in part on individual predisposition which the physician is unable to recognise."
To explain this latter statement, it should be understood that both ether and chloroform, pushed to the last stage of their action, give rise to paralysis of the respiration, vessels, heart and motor nerves, but that ether invariably produces its effects in the order of sequence now given (life of course being sustained in all cases by artificial respiration when automatic breathing has ceased); while chloroform sometimes produces paralysis of the vessels in the first instance, then of respiration, and finally of the heart. The result of the action of chloroform is thus variable; it frequently happens that its effects manifest themselves in the same order of sequence as those of ether, only much more rapidly; and it also happens that they follow each other in an inverse order as respects the first two phenomena, paralysis of the respiration and of the vessels. It is this variable action of chloroform which the physician is unable to foresee and to provide against in individual cases, and to which the danger to life is traceable. Very often at the beginning of the inhalation of chloroform by the trachea the vessels become at once paralysed, the pulse is insensible, and death follows rapidly with a deep inspiration. All this Professor Schiff has frequently verified by experiments on dogs and rabbits, in which during inhalation the manometer has been constantly in connection with the carotid artery.
That the heart is the last of these three factors of life which dies, the Professor clearly demonstrates in the following way. When by the action of chloroform the pressure has gone down nearly to zero, and there is no pulsation visible, compression of the thoracic aorta between the crura of the diaphragm, or the mere compression of the abdomen, restores to the pulse its strength and frequency, and causes the pressure in the manometer to rise to a considerable height, very often to 100 or 120 millimeters. This fact proves that the heart, notwithstanding its apparent paralysis, is still able to maintain the almost normal