<\ STrm* OF THE Influence of Chloroform UPON THE RESPIRATION AND CIRCULATION. A CONTRIBUTION FROM THE LABORATORY OF EXPERIMEN- TAL THERAPEUTICS OF THE JEFFERSON MEDICAL COLLEGE OF PHILADELPHIA. being a Report to surgeon lieutenant-colonel edward lawrie and to THE GOVERNMENT OF HIS HIGHNESS THE NIZAM OF HYDERABAD. BY H. A. HARE, M.D., » PROFESSOR OF THERAPEUTICS AND MATERIA MEDICA IN THE JEFFERSON MEDICAL COLLEGE, AND E. Q. THORNTON, M.D., DEMONSTRATOR OF THERAPEUTICS, JEFFERSON MEDICAL COLLEGE. DETROIT, MICH.: GEORGE S. DAVIS, PUBLISHER. 1893. Reprinted from The Therapeutic Gazette, October 16, 1893. A STUDY OF THE Influence of Chloroform UPON THE RESPIRATION AND CIRCULATION. A STUDY OF THE INFLUENCE OF CHLOROFORM UPON THE RESPIRATION AND CIRCULATION. TO any one who endeavors to view the sub- ject of chloroform anaesthesia in an en- tirely impartial light two objects raise them- selves so high above all others that they form the peaks about which the smaller .questions must cluster. The first object on which the judicial eye rests is the firm belief of many clinicians that chloroform may cause sudden cardiac death; the second object to be seen is the statement of the Hyderabad Chloroform Commission that death from chloroform is never due to cardiac failure. In the support of the first belief we have not only wide clini- cal observation, but also the experimental evi- dences of a number of investigators. In sup- port of the second statement we have an array of experimental study not equalled by any other research extant, associated with an enor- mous number of negative observations on man. Negative observations because Lawrie alone in twenty-five thousand cases has never had a car- diac death. The controversy concerning the action of chloroform upon the animal organism has been waged so incessantly for many years, and has led to such extraordinary efforts for its elucidation and final decision, that any one who attempts to take part finds himself almost swamped by the number of statements and opinions which he is forced to regard. We have therefore approached this research feeling it was no or- dinary task, and that a path already so well travelled must be gone over with the utmost care if anything new or of value was to be discovered. In March, 1892, Surgeon Lieutenant-Colonel Lawrie, whose interest in this subject is recog- nized by the medical profession the world over, wrote to one of us (Hare), asking that another chloroform research be instituted, for which the government of His Highness the Nizam of Hy- derabad would pay. The express object of the research was the reconciliation of at least some of the contradictory conclusions reached by va- rious experimenters during the past few years. From the immense number of observations, in regard to the action of chloroform, in the laboratory and in the operating-room it is evi- dent that sufficient data are at hand to give us material to reach positive conclusions, and that the contradictory results hitherto obtained must have been reached by misinterpretation and error in experimental method, tinctured perhaps by opinions formed previous to the completion of a line of study. There are cer- tain facts in regard to chloroform which few will deny, the chief of which are that it has the advantage of rapid action without disagreeable preliminary or subsequent symptoms, its bulk is small, and its odor agreeable; but, more important than all, it is much more dangerous than ether. Though the Hyderabad Commission in their preliminary conclusions (page 30, paragraph 43) assert that ether is as dangerous as chloroform if given sufficiently to produce true anaesthesia, we believe that the safety of ether is so univer- sally recognized that this conclusion of the Commission can only be excused by the re- membrance that ether has probably been used as little by those who wrote this paragraph as chloroform is used in many parts of America. This possibility is made a probability when we read that "if surgeons choose to be content with a condition of semi-anaesthesia, it can no doubt be produced with perfect safety, though with discomfort to the patient, by ether held rather closely over the mouth. Such a condi- tion of imperfect anaesthesia would never be accepted by any surgeon accustomed to operate under chloroform. ' ' That this statement shows, to put it mildly, that the writer knows not whereof he speaks is proved by the universal employment of ether by hundreds of the best surgeons the world over in preference to chlo- roform. Further than this, medical literature contains so many statistical papers showing the small percentage of deaths from ether as com- pared with chloroform that this point need not be debated. There are certain other points in regard to the action of chloroform which may be put aside as settled, and therefore not needing fur- ther study, being generally received as beyond A Study of the Influence of Chloroform upon the Respiration and Circulation. 3 criticism, and we have made no experiments looking to their reproduction, but have devoted our efforts solely to the questions over which discussion still proceeds. Thus, all investiga- tors concur in the statement that chloroform, even in ordinary therapeutic quantity, acts as a powerful and constant depressant to arterial pressure. This conclusion has been reached by Bowditch and Minot and Coats, H. C. Wood and H. A. Hare, Gaskell and Shore, the Hyderabad Chloroform Commission Nos. 1 and 2, and by every experiment in the re- search now carried out which forms this re- port. There is no evidence to the contrary, and practically it has never been denied. Gas- kell and Shore state, however, that chloroform may cause anaesthesia without lowering blood- pressure, and that chloroform causes primarily a rise of pressure. They also believe that the chief cause of the fall of arterial pressure is car- diac and not vaso-motor depression. The rise we have never seen except from struggles, and we have never been able to produce anaesthesia without lowering the blood-pressure, even when the drug was used in the smallest quantity capa- ble of causing anaesthesia and given as slowly as possible. We agree with the statement of the Hyderabad Commission that a fall of blood-pressure always occurs when chloroform anaesthesia is produced. We are also forced, as the result of our studies, to differ entirely with Gaskell and Shore in their statement that the fall of arterial pressure is due primarily to a weakening of the heart's action and not to paralysis (depression ?) of the vaso-motor centre. We believe that both factors cause the fall, but that the dominant factor is vaso-motor depression, because, as will be seen in several of bur tracings, the pulse-waves were quite strong, though the blood-pressure, through vaso-motor relaxation, was absolutely to the abscissa line, and we agree with Lawrie that no conclusions as to the action of chloroform when inhaled can be drawn from the injection experiments of Gas- kell and Shore into the arteries. One of our reasons for this belief is the entire difference in method necessary and the corresponding differ- ence in result. Another reason is that any pow- erful drug injected into the brain will cause a rise of blood-pressure. Even nitrite of amyl, the prince of vaso-motor paralyzants, will do this. (See Gaskell and Shore, page 17, para- graph 68.) We also believe that results obtained by such interesting methods of experimentation as em- ployed by Gaskell and Shore are not capable of giving us positively reliable information, as the conditions are so utterly at variance with those in which chloroform is given to man ; and, further, that their methods are such as to give room for fallacious results, which cannot be excluded by the greatest caution on the part of experimenters, experienced as they are. Secondly, it is not denied by any one, that we know of, that chloroform exerts a powerful depressant, paralyzant action on the respira- tory centre. This is agreed to by clinicians and by every one who has experimentally studied the action of the drug on the lower animals. (See results of collective investi- gation.) Thirdly, it is universally conceded that chlo- roform is_a lethal agent of great power when brought in direct contact with highly-vitalized tissues. Aside from these facts, there are a number of others in which we find ourselves strictly in ac- cord with the conclusions of the Hyderabad Commission. In order to make clear those points in which we agree and differ, we print the conclusions reached by the Commission, and to be found on page 17 of their official report.* " 1. Chloroform, when given continuously by any means which insures its free dilution with air, causes a gradual fall in the mean blood-pressure, provided the animal's respira- tion is not impeded in any way, and it con- tinues to breathe quietly, without struggling or involuntary holding of the breath, as almost always happens when the chloroform is suffi- ciently diluted. [See our Experiments 1, 4, 13, 23, and 27 (Hare and Thornton).] f "As this fall continues the animal first be- comes insensible, then the respiration gradually ceases, and, lastly, the heart stops beating. [In every one of our experiments this course was followed as soon as struggles ceased (Hare and Thornton).] " If the chloroform is less diluted the fall is more rapid, but is always gradual, so long as other conditions are maintained ; and however concentrated the chloroform may be, it never causes sudden death from stoppage of the heart. The greater the degree of dilution the less rapid is the fall, until a degree of dilution is reached which rib longer appreciably lowers * These are not the final conclusions, published in the Lancet and elsewhere, which were drawn up for general readers, but from the more scientific and accurate deduc- tions of the research itself. j- It is unfortunate that space does not permit the re- production of every experiment made, or even every part of the ones given. As far as possible every valua- ble part has been included. A Study of the Influence of Chloroform upon the 4 again. The heart was in all these experiments very weak, but it recovered rapidly from its weakness, so we must conclude that the cardiac condition was one of weakness or depression and not paralysis or death. " 2. If the inhalation is interrupted at any stage, the fall of pressure still continues at a rate which depends altogether on the rapidity of the fall while the chloroform was being in- haled. This after-fall is probably due to ab- sorption of a portion of the residue of chloro- form in the air-passages after the stoppage of the inhalation. In this way it often happens, if chloroform is given rather freely, that though the respiration may be going on when the chlo- roform is discontinued, it afterwards stops. [Our results are identical with this conclu- sion.] "3. If the administration of the chloroform is stopped at an early stage the pressure very soon begins to rise again, and gradually be- comes normal. [See our Experiments 8, 13, 17, 23, and 27 (Hare and Thornton).] But if the chloroform is pushed further, there comes a time, not easy to define, when the blood- pressure and respiration will no longer be re- stored spontaneously, although the heart con- tinues to beat after the inhalation is stopped. [See our Experiments 1, 5, 10, 13, 16, 17, 18, and 23, all of which confirm this conclusion (Hare and Thornton).] "4. If the fall has been very gradual, it may occasionally happen that the respiration stops completely, and still the blood-pressure rises again, the respiration recommencing sponta- neously in the course of the rise. [See our Experiments 12, 13, 17, and 26 (Hare and Thornton).] In the same way, when the in- halation has been discontinued, the respira- tion may stop during the after-fall of the blood- pressure and begin again spontaneously. As a rule, if the respiration has stopped, or even be- comes slow and feeble at the time when the in- halation is discontinued and artificial respira- tion is not resorted to, the fall in blood-pressure will continue until death ensues. [See end of our Experiments 1,5, 10, 13, 17, 18 (Hare and Thornton).] "5. There are two conditions which fre- quently disturb the gradual fall of the blood- pressure,-viz., struggling and holding the breath,-and it is only by great care that they can be avoided in animals. [Our results are entirely in accord with this.] " 6. Struggling, independently of any change in the respiratory rhythm, appears generally to raise the blood-pressure. [See our Experi- ments 13, 15, 16, 27 (Hare and Thornton).] the blood-pressure or produces anaesthesia." (See below.) With this entire statement our results are practically in accord, but we would like to qualify the words " however concentrated the chloroform may be, it never causes sudden death from stoppage of the heart" by saying it never has caused sudden stoppage of the heart in any of our experiments unless respiration ceased primarily. We make this modification because, as we will point out later in this report, we be- lieve circumstances may exist in which the dis- eased heart may stop suddenly under chloro- form. On the other hand, we do not believe that it is possible in a lower animal (the dog) to cause cardiac death by the freest possible use of chloroform by inhalation without causing primary respiratory arrest, and respiratory ar- rest having taken place, the death which fol- lows is partly due to asphyxia and partly to direct cardiac failure and vaso-motor paralysis. In reaching this conclusion one of us (Hare) is well aware that his position is directly op- posed to his conclusions published in a joint paper by H. C. Wood and himself in the Medical News of February 22,, 1890. The tracings shown in that paper, to prove that chlo- roform was capable of causing primary arrest of the heart, are all (except No. 5) tracings of experiments in which chloroform was injected directly into the jugular vein, which is an en- tirely different thing from its absorption from the lungs into the blood well mixed with air. Even quinine injected into the jugular vein will cause cardiac arrest. Further than this, this research has shown us that in only one of the three tracings presented by Wood and Hare did death certainly occur from cardiac failure, even when the drug was given intravenously,- namely, in their tracing No. 4. Perhaps if ar- tificial respiration had been resorted to recovery would have occurred, as our experiments have proved is possible even after both heart and respiration have apparently stopped. (See Nos. 3, 13, 17, and 27, Hare and Thornton). The pulse-line in Tracing No. 3 (Wood and Hare) is more than reproduced by jugular injection in No. 14 in this research, and No. 5 (Wood and Hare) by inhalation in No. 23 (Part XV. and XVI.) of this research, and it will be noted that though the heart failed in these experiments to make a pulse-mark, for the time being, that it eventually recovered sufficiently to do so or was found beating when the chest-wall was opened or a needle was thrust into the heart. Again, in Experiment 13, in this research (Hare and Thornton), it will be seen that when the pen was practically at the abscissa it suddenly rose Respiration and Circulation. 5 In one case of a dog much weakened from phosphorus the pressure fell every time he struggled. [We agree with the first sentence, but believe that struggling and change in re- spiratory rhythm are inseparable. Of the facts in the second sentence we have no knowledge.] "7. When struggling is accompanied, as it often is, by acceleration of the respiration and pulse, especially if the respiration is deep and gasping, it leads to a more rapid inhalation of chloroform, and consequently to a more rapid fall of blood-pressure and a greater after-fall. [Compare our Experiments (Hare and Thorn- ton) 13, 16, and 27 with Experiment 23, in which there was no struggling and a gradual fall.] In order to keep the chloroform-cap or inhaler in its place during the animal's struggles, the administrator is obliged to hold it down more tightly over the nose and mouth, and this ma- terially assists in hastening the rapidity of the inhalation, and consequently of the fall in blood-pressure. [We agree with this state- ment.] " 8. The effect of involuntarily holding the breath, which, as anybody can prove by ex- perimenting upon himself, must happen when an inhaler saturated with chloroform is first applied to the face, is much more remarkable, the pressure often falling with great sudden- ness, while the heart's action is markedly slowed. [See Experiments 1 and 5 of Wood and Hare, No. 1 being reproduced in this paper.] As soon as the animal draws breath again the pressure rises as suddenly as it fell, but the gasping respiration which succeeds then causes very rapid inhalation of chloro- form with immediate insensibility and a rapid fall of blood-pressure which becomes danger- ous. [See our Experiment 13 (Parts IV., V., VI.), and Experiment 17. This fall is some- times dangerous and sometimes not. Cer- tainly not a dangerous fall in Tracing No. 16 under atropine. Taking the paragraph as a whole, we agree with its statements en- tirely, and believe that the first action named is solely due to reflex inhibition through vagal and trigeminal irritation (Hare and Thornton).] "9. The combination of struggling with al- ternate holding the breath and gasping, which results if chloroform is applied closely to the face without sufficient dilution with air, causes violent fluctuations and then a speedy fall of the blood-pressure, which very soon leads to a dangerous depression with deep in- sensibility and early stoppage of the respira- tion. [See our Experiments 13 and 27 (Hare and Thornton).] The after-fall under these circumstances is rapid and prolonged (Vr). [We also find it rapid.] It is this combina- tion of events which causes struggling animals to go under chloroform so quickly. "io. The effect of holding the breath may occasionally cause a temporary fall of blood - pressure after the chloroform inhalation has been stopped, or even when the animal is quite out of chloroform. This fall is recovered from directly the animal breathes again. [We con- cur in this.] " n. Slight, continuous asphyxia, such as is produced by pressure on the neck by straps, a badly-fitting muzzle, or hinderance of the chest- movements by the legs being too tightly bound down, gives rise to exaggerated and irregular oscillations of the blood-pressure and slowing and irregularity of the heart's action. If it leads to, or is accompanied by, deep gasping inspiration, it is apt, like anything else which causes this, to increase the intake of chloroform and bring about a rapid decline of blood- pressure. [We concur in this conclusion.] " 12. Complete, or almost complete, as- phyxia, as by forcibly closing the nose and mouth, or closing the tracheal tube after tracheotomy, has an effect similar to, but more marked than, that produced by holding the breath, and the character of the trace corre- sponds precisely to that produced by irritation of the peripheral end of the cut vagus. The pressure falls extremely rapidly, sometimes al- most to zero, and the heart's action becomes excessively slow or even stops for a few seconds. "13. This effect of asphyxia is the result of stimulation of the vagi. The proof of this is (<z) that the trace corresponds exactly, as stated above, to that produced by direct irritation of the vagus; (A) division of both vagi entirely abolishes it; and (c) the administration of atro- pine, which paralyzes the vagus, also abolishes it. [Tracing No. 15 Part I. (Hare and Thorn- ton). That vagal irritation does account for some of the circulatory disturbance is no doubt true, but in reality the changes are chiefly vaso- motor in character. We have not found that either vagal section or vagal paralysis with atro- pine prevented these phenomena, although it may modify them. See Tracing Nos. 10 and 17 (Hare and Thornton).] "14. In Trace 158 (Fick, No. 4), which was taken during asphyxia after a full dose of atro- pine, it will be seen that there is an alternately slow and rapid pulse, according to the phase of the respiratory movement, but no continued slowing of the heart, as in vagus irritation. But there was still a distinct fall of pressure after the atropine when the breath was held, 6 A Study of the Influence of Chloroform upon the and it was thought that the slowing of the pulse above noted in this condition might be due to the disturbance of the heart from ten- sion in the pulmonary vessels in the absence of respiratory movement rather than to irritation of the vagi. To test this point Experiment 184 was instituted. In this experiment the dog's chest was forcibly inflated with bellows con- nected by a tube with the trachea, and the effect of this proceeding was to cause a fall of pressure and slowing of the heart, exactly the same as in involuntary holding of the breath. The dog was then poisoned with atropine, after which inflation of the chest still caused a fall of but without slowing of the heart (vide Fick, Nos. 8 and 9). The fall of pressure must be in some degree independent of vagus irritation, which, however, usually accom- panies it. "15. It only remains to be considered whether the slow action or temporary stoppage of the heart, with great fall of pressure pro- duced by vagus irritation, is in itself an element of danger in chloroform administration, and if it is not, wherein the danger actually lies. [See note to paragraph 16 (Hare and Thornton).] " 16. The experiments in which deliberate irritation of the vagi was carried on during anaesthesia show unmistakably that irritation of these nerves diminishes rather than enhances the danger of anaesthetics. The effect upon the heart is never continuous, and as the vagus becomes exhausted, of when the irritation is taken off, the blood-pressure rises again, as it does when the same result is produced by asphyxia. The slowing of the heart and circu- lation which is produced by irritation of the vagus by any cause, such as holding the breath in chloroform administration, retards the ab- sorption and conveyance of chloroform to the nerve-centres, just as holding the breath, whether voluntary or involuntary, prevents chloroform from entering the lung; and of itself slowing or temporary stoppage of the heart in chloroform administration is not dan- gerous. [We shall point out later in this re- port how we differ from this conclusion, for we believe that true fatty heart, plus ventricular engorgement, plus vagal irritation, plus possible valvular disease, and, finally, plus extreme vaso-motor relaxation, may result in death in frightened persons. While this is not, scien- tifically speaking, a cardiac death from chloro- form, practically the chloroform is the last straw which upsets the cardiac balance. How- ever, Lawrie and his colleagues recognize this as well as ourselves (see paragraph 38, Hare and Thornton).] " i"j. To answer the second part of the last question in paragraph 15 is easy enough, if it is kept in mind that the effect of vagus irritation upon the heart is never continuous; and in chloroform administration, as the pressure rises again after the slowing of the heart and tempo- rary fall of pressure produced by any form of asphyxia, violent respiratory efforts with bound- ing heart's action lead, as in the case of strug- gling, to a rapid and dangerous inhalation of chloroform, and consequent rapid and danger- ous decline in blood-pressure. [We believe in the healthy animal or man that this is true.] It is, in fact, the temporary exhaustion of the vagi after stimulation that is to be feared, and not the actual stimulation as long as it is continued. "18. In accordance with this fact it will be found that in chloroform administration neither holding the breath, even if involuntary, or vagus inhibition can be kept up beyond a cer- tain time; and if the chloroform is not re- moved from the face, one or both of two things happen : (1) when the animal breathes again it takes deep and gasping inspirations, the lungs become filled with chloroform, and an overdose is taken in with extreme rapidity; or (2) when the restraining influence of the vagus is taken off the heart, through the irrita- tion ceasing or the nerve becoming exhausted, the heart bounds on again, and the circulation is accelerated in proportion. The blood then becomes quickly saturated with chloroform, and an overdose is at once conveyed to the nerve- centres. [We believe this is true of the healthy heart, but not of one engorged with blood which has undergone fatty degeneration. This is only an hypothesis, however, as we have no experimental basis for this belief (Hare and Thornton).] The theory which has hitherto been accepted is that the-danger in chloroform administration consists in the slowing or stop- page of the heart by vagus inhibition. This is now shown to be absolutely incorrect. There is no doubt whatever that the controlling in- fluence of the vagus on the heart is a safe- guard, and that it is the exhaustion of the nerve which is dangerous. [We believe that this conclusion is more theoretical than practi- cal (Hare and Thornton).] "19. It can be readily understood how a condition in which the pulse is rapid and bounding, with high blood-pressure, leads to more rapid absorption of chloroform from the lungs and a more rapid propulsion of the chlo- roformed blood to the medulla oblongata, and consequently to a more rapid paralysis of the respiratory and vaso-motor centres and pre- Respiration and Circulation. 7 cipitous fall in the blood-pressure. Such a condition is produced in some cases by ether or by division of both vagi, or by a full dose of atropine. Not only is the poisoned blood carried more swiftly to the vital centres in these cases, but added to this there is the fact that as*the heart is already doing its before the chloroform is given, it is unable to stave off by increased work the fall in pressure that occurs when, the vaso-motor centre is paralyzed. On the other hand, it seems clear from Experiment 92 that the direct action of chloroform upon the heart's substance is not the cause of the fall of pressure that occurs when it is inhaled. [That we (Hare and Thornton) agree in general with these conclusions (paragraphs 15, 16, 17, 18, and 19) is shown by the following extract from the research of Wood and Hare in the Medical News, February 22, 1889 : "The theory has from time to time found advocates that the vapors of chloroform may, by irritating the larynx and adjacent parts, cause arrest of the heart through a reflex in- hibition. To test the possibility of this, we have made a number of experiments. When the tracheal canula is tied tightly into the trachea some distance below the larynx, it is evident that the latter organ is isolated from the general respiratory tract, and that chloro- form injected into it will exert only a local in- fluence. In all the experiments which we have made in the way just indicated, the in- jection has been followed by an immediate and very pronounced primary fall of the pressure, followed, after a very brief interval, by a rise, which usually reaches decidedly above the norm. As an example of one of these experi- ments, we give the preceding tracing. [See Tracing 1, Wood and Hare, here appended.] "The primary fall of arterial pressure, which has just been spoken of, can scarcely be pro- duced except by reflex inhibition of the heart or of the vaso-motor centres, while the second- ary rise is probably the result of a reflex vaso- motor spasm. In order to throw light upon this question, we have made experiments by in- jecting chloroform into the Larynx after division of the pneumogastric nerves, the trachea being ligated so as to prevent the entrance of the anaesthetic into the lungs. [See Tracing 2, Wood and Hare, here appended.] " In making practical application of the ex- periments thus discussed, it must be noted that in no case have we succeeded in completely ar- resting the heart's action by injecting chloro- form into the larynx, and as the chloroform was injected in liquid form, it is plain that the irritation was more intense than could be pro- duced by the mere vapors of the anaesthetic, however concentrated; therefore, while it must be considered that it is possible for a re- flex inhibitory arrest of the heart to occur during the inhalation, such an accident is ex- tremely improbable, and we consider it prac- tically certain that a heart so arrested could, a few seconds later escaping from the inhibitory control, recommence its beat. [See our Ex- periment 15 (Hare and Thornton).] It cer- tainly has never been proved that chloroform can cause in the human subject permanent re- flex inhibitory cardiac arrest, and as our experi- ments upon the dog have failed to cause arrest, we consider it very improbable that reflex car- diac arrest is ever produced in man by chloro- form." To this we wish to add, unless the cardiac disease or condition is such as to be un- able to withstand any shock whatever (Hare and Thornton).] " 20. In Experiment 92 repeated injections of 20 minims of chloroform were made into the jugular vein, and its effect was not to paralyze- the heart, but to produce anaesthesia and a gradual fall of blood-pressure, exactly as if the chloroform had been inhaled. In Experi- ment 72, after a considerable amount of ether had been injected into the jugular vein and a bounding condition of pulse had been pro- duced, the effect of injecting chloroform into the jugulars was much greater and the fall of blood-pressure much more rapid and dangerous than is the case when chloroform alone was in- jected. Granting; then, the truth of Ringer's conclusions from experiments on the frog's heart (which have not been repeated and con- firmed by the Commission), that chloroform has a gradual paralyzing effect upon the heart's tis- sue, we must conclude that such an effect, in the degree in which alone it could occur in the practical inhalation of chloroform, would rather be a source of safety than of danger. [With these conclusions we have to entirely disagree, and we cannot understand how results so com- pletely at variance with our own and with those of Wood and Hare could have been arrived at. (See Tracings Nos. 19 and 20.) The tracings we present do not admit of wrong interpreta- tion. Perhaps the difference lies in the fact that in our studies enough water was added to the chloroform to carry it en masse to the heart, whereas in the East Indian studies the pure un- diluted drug was injected, and had not suffi- cient volume to reach the heart, and was grad- ually volatilized in the vein, and so produced •a gradual effect. (This is shown in Tracing No. 8, Hare and Thornton.) We find the in- 8 A Study of die Influence of Chloroform upon the jection of from 2 to 4 cubic centimetres of chlo- roform into the jugular vein causes arrest of respiration, rapidly followed by cardiac arrest, which is not secondary to the respiratory fail- ure, but to a primary action of the chloroform on the heart-muscle, which is found more re- sponsive to stimulation. We have made this experiment over one hundred times. It having been denied that chloroform, when injected into the jugular vein, causes cardiac depression, and the recent experiments of Leaf and his colleagues in Hyderabad having been cited to support this view, let us discuss the facts before us. In these researches they found when chloroform was given in excessive amount, that the pen fell to the abscissa line and failed to record a pulse-wave, but that a needle in the heart-muscle continued to beat for many seconds. While at first glance these results, which we have also obtained (see our Experi- ments 19 and 20), seem to prove that the cardiac arrest is only apparent and not real, in reality they have been given an importance far in excess of their value. We have proved again and again that the movement of the needle may be due, not to a true cardiac con- traction, but to inco-ordinated contraction of one of the ventricles, and to contractile move- ments of bands of the cardiac muscle, which movements are very often rhythmical enough to make the needle beat regularly. We have found this needle movement taking place even after an injection of chloroform had been sent directly into the heart through the chest-wall, and in a heart the muscle of which failed to respond to any strength of faradic irritation, except in those parts which had not come in contact with the poison. Further than this, if an animal be given very large doses of chloroform intravenously or by direct intracardiac injection, respira- tion invariably ceases if the amount be large enough, and if the chest be opened one con- dition will be constantly found-,-viz., the heart so widely dilated as to fill the pericardium al- most to bursting, and the cavities, particularly the ventricles, engorged with blood. Although they may still be feehjy contracting, the con- traction is abortive and fails to cause arterial flow. If the drug has been used intravenously, by the jugular, the blood in the right and left heart will be found red, provided death has come on rapidly. If not, it will be dark and venous. The lungs will be found of that peculiar pink hue due to altered blood. If the injection has been cardiac, it will be found that the ventricle with which the poison has come in direct con- tact has become paralyzed, while the other is making fairly good efforts to work. (See our Experiment 21, Hare and Thornton.) When the injection takes place into the right ventri- cle, so that the poison passes to the left cavity, both ventricles fail to act voluntarily or to faradism. (See our Experiment 25, Hare and Thornton.) Chloroform is capable, therefore, of causing death of the cardiac muscle when- ever it comes in contact with it, and that there is no possibility of this arrest being due to vagal irritation is proved by experiments in which vagal section preceded the use of the chloro- form. (See our Experiments 22, 24, and 25.) We doubt whether the last sentence of para- graph 20 is justified by our present knowledge.] "21. The committee discussed the advisa- bility of cutting the vagi some time previous to experimenting on the blood-pressure with chlo- roform. The effect of this procedure is to cause continuous rapid action and tendency to exhaustion of the heart, as well as to degenera- tion of the terminal branches of the nerves in the heart if the animal lives sufficiently long. Such experiments might be of some interest theoretically, and also have had a practical bearing upon the condition of the heart in cer- tain cases of chronic alcoholism ; but the com- mittee decided not to perform them, as they con- sidered the end to be gained did not justify the pain they would have inflicted. [We have not made this particular experiment, but we found that vagal section immediately before the drug was used did not materially alter the result.] "22. In Experiment 178, the case of a dog that had had morphine, remarkable slowing and even temporary cessation of the heart's action occurred again and again at the same moment as the respiration stopped, but the heart invariably recovered itself and began again to beat regularly before any steps were taken to restore the animal, and without any respiration occurring. We found in this case that it was possible to restore the animal even after unusually long intervals had been allowed to elapse between the cessation of natural and the commencement of artificial respiration. The failure of the heart, if such it can be called, instead of being a danger to the animal, proved to be a positive safeguard by preventing the absorption of the residual chloroform and its distribution through the system. [We have not made any experiments on this point.] " 23. The effect of artificial respiration after the natural respiration has ceased is to cause an alternate rise and fall of small amount in the blood-pressure, the trace thus formed upon the drum being a coarse imitation-altered some- what by the shaking of the table-of the nat- Respiration and Circulation. 9 ural respiratory curve. [We concur. (See our Experiments 3 and 27, Hare and Thornton.)] The difference consists chiefly in the fact that the artificial rise and fall is more abrupt than in normal breathing, and that the rise always coincides with expiration or compression of the chest. After artificial respiration has been con- tinued for a certain time the blood-pressure begins to rise again, and a little later natural respiration returns. [We concur in this re- sult.] "24. The effect of artificial respiration in restoring an animal after the respiration had stopped was always marked. [See our Ex- periments 3 and 27 (Hare and Thornton). We therefore concur, as qualified by the next paragraph.] In a few exceptional cases, such as No. 159, a phosphorus dog, and No. 142, a horse which had an enormous overdose, al- though the artificial respiration was commenced as soon as possible after the breathing was no- ticed to have stopped, it was not successful. "25. Complete stoppage of the respiration always means that an overdose has been ad- ministered, and the overdose may have been so great as to render restoration impossible. It is impossible to say whether, after chloroform has been pushed and then discontinued, the respiration will be restored spontaneously or not, and it is never in any case certain that arti- ficial respiration will restore the natural respira- tion and blood-pressure, no matter how soon it is commenced after the respiration stops. [See our Experiments 1 and 5 (Hare and Thorn- ton).] A great deal depends upon the amount of the after-fall: in some cases, even after the respiration has been restored, the pressure con- tinues to fall and respiration again ceases, and artificial respiration then fails. We thus find z respiration restored by artificial respiration while chloroform is still being absorbed, and this tends to show that artificial respiration does not merely pump the chloroform out of the blood, but exerts considerable influence in exerting the natural respiration. " 26. The time which elapses before artifi- cial respiration succeeds in restoring natural respiration varies very greatly. In one case (No. 116) it was continued for eleven minutes before the first natural gasps commenced. This period is undoubtedly prolonged in some cases by a condition of physiological apnoea which renders it unnecessary for the animal to breathe. Consequently, whenever the pressure rose considerably during artificial respiration, it was stopped, and the animal then generally breathed after a few seconds. [Whenever apnoea developed, the fall of pressure would persist and a rise not take place (Hare and Thornton).] "27. The time which may be allowed to pass with impunity before commencing artifi- cial respiration also seems to vary consider- ably. This point was not particularly attended to in the manometer experiments 162 and 178, which were instituted to test the truth of the opinion formed by the sub-committee, that morphine had some slight action in impairing the efficiency of artificial respiration. In these cases the commencement of artificial respira- tion was postponed for more than two minutes after respiration ceased, and was successful; but this is certainly far above the average in- terval that can be allowed with safety. The success of artificial respiration in restoring the blood-pressure is, in some cases, very remark- able. In Experiment 40 the heart had appar- ently ceased beating, and the dog was believed by every one present to be dead, and yet re- covered with artificial respiration. The success in this instance is due to the fact that concen- trated chloroform had been pushed for two minutes, regardless of the breathing, and the stoppage of the heart was due to stimulation of the vagus through asphyxia. The animal was therefore easily restored, as he was suffering more from asphyxia than from chloroform- poisoning. " 28. It corresponds to those cases, which are so often reported, in which dangerous fail- ure of the heart is said to have occurred some minutes after the administration of chloroform had been discontinued, and which are some- times restored, and sometimes not, by artificial respiration. There is nothing at all sudden about the failure of the heart in these cases, but the attention of the chloroformist, which has been wandering, is suddenly called to the fact that the patient is apparently dead. When the animal was really dead, it was found in some cases that artificial respiration still main- tained a small amount of mean pressure in the manometer. In others the pressure seemed to fall to the zero line between each compression of the chest. [We reach a similar conclu- sion.] "29. The dangers of too vigorous artificial respiration were illustrated in some of the acci- dental deaths. In one case the liver was badly ruptured, and in another the pleural cavity was full of blood. In three cases (Nos. 80, 92, and 103) rhythmical movements of the diaphragm were noticed after the heart had ceased beat- ing and after the chest had been opened. It is remarkable that in two of these cases the splanchnic nerve had been divided. The third 10 A Study of the Influence of Chloroform upon the was a case in which chloroform had been in- jected into the jugular, and in this case there was a synchronous movement of the jaw as well. In all, death and stoppage of the heart had occurred gradually, and in No. 103 the heart was still irritable. These movements cannot be called respiration, though the last gasp of a dying animal-that ineffective jerk of the diaphragm which is such a fatal symp- tom-is very likely in many cases a movement of the same character. Similar movements, which were continued much longer, occurred in Experiment 104, after the thorax was opened, while the heart was still beating. Still more remarkable convulsions of the mus- cles of the jaws, ears, and forefeet occurred in Experiment 167, in the case of a dog that had been poisoned with nicotine. These move- ments continued at regular intervals for more than ten minutes after death, and were suffi- ciently forcible to jerk the handles of a pressure forceps fixed on the end of the tongue off the table at each spasm. In a rabbit in Experi- ment 153 the auricles of the heart continued to beat rhythmically for three hours after it was supposed to be dead from chloroform and its thorax had been laid open. Irritability of the heart after death was noticed in many cases, but seemed to be most marked in cases where ether had been used. [We have made no studies in regard to this point.] " 30. Chloroform injected into the heart through the jugular vein did not cause clotting of the blood, as was the case when ether was injected. [Chloroform did cause clotting in our experiments (Hare and Thornton).] "31. In the course of the experiments of the committee various drugs were administered, in order to ascertain if they had any effect in modifying the action of chloroform. The re- sult showed that none of them had any effect in preventing the typical descent of the blood- pressure that occurs when chloroform is in- haled. Atropine, when given in a dose suffi- cient to paralyze the vagi, of course prevents the action of those nerves in asphyxia, and, by increasing the action of the heart, it appears to cause a more rapid descent in the blood- pressure when chloroform is inhaled, as has been already explained. [We cannot agree to this. (See our Experiments 10, 16, 17, and 18, Hare and Thornton.)] Morphine appeared in Experiment 162 to render the rise in blood- pressure that occurred when the chloroform was discontinued slower and less complete and to bring about a more or less permanent condi- tion of anaesthesia. It may be noted that the animal used in this experiment was a monkey, and in other experiments with monkeys, when no morphine had been given, it was remarked that the animal, after a few inhalations of chlo- roform, would often lie quite quiet, in a state of semi-sensibility, for a long time without further inhalations ; still, this condition was much more marked in Experiment 162 than in any of the others. No action of this kind was noticed in the dog (Experiment 178); but other experi- ments (Nos. 90 and 94) showed that pariah dogs are very indifferent to the action of mor- phine, and it is probable that the dose of mor- phine in this case was insufficient to bring about the condition noted in the monkey. The peculiar behavior of the heart in Experi- ment 178 was not the result of the previous ad- ministration of morphine, for a similar phenom- enon had occurred in other cases (49 and 60) in which no morphine had been given. Ex- periments 162 and 178 prove conclusively that morphine has no effect in shortening the period that may be allowed to elapse between the ces- sation of natural respiration and the commence- ment of artificial respiration. [We have al- ready shown in Nos. 10, 16, 17, and 18 of our experiments that atropine seems to produce a very gradual fall of pressure and to preserve the circulation. With the other drugs we have not experimented (Hare and Thornton).] "32. The other drugs used had no effect upon the action of chloroform, except when their own special action became the leading feature in the case, as, for instance, during the vomiting from apomorphine (Experiment 104, Fick, No. 9) or the convulsions produced by nicotine (Experiment 167). "33. In order to test the alleged danger from shock during chloroform administration, the committee performed a very large number of those operations which are reputed to be particularly dangerous in this connection,■'such as extractions of teeth, evulsion of nails, sec- tion of the muscles of the eye, snipping of the skin of the anus, etc. In many cases the opera- tion was performed when the animal was merely stupefied by the chloroform and not fully in- sensible. In such cases a slight variation in the blood-pressure would sometimes occur, such as one would expect from the irritation of a sensory nerve or from the struggling that en- sued, but in no case in any stage of anaesthesia was there anything even suggestive of syncope or failure of the heart's action. In thrusting a needle into the heart there was often a momen- tary but well-marked fall of blood-pressure, but even this was absent in all other injuries. If chloroform really has any power to increase the tendency to shock in operation, it is im- Respiration and Circulation. 11 possible to believe that it would not have been manifested to some degree at least in one or other of these numerous experiments. The Commission was, however, not content with this negative result, and determined to ascer- tain the effect of direct irritation of the vagi during continued chloroform administration. The result of such experiments (Nos. 65, 117, and others) proved that inhibition of the heart's action prevented rather than assisted the fatal effects of prolonged chloroform in- halation. An animal that was put into a con- dition of extreme danger (from which it could only be restored by means of artificial respira- tion) by inhalation of chloroform for one minute, recovered spontaneously and readily after five minutes of chloroform, together with inhibition of the heart, by electrical irritation of the vagus carried on simultaneously. In one of these experiments (No. 117) chloroform was pushed for seven minutes; and during con- tinued irritation of the vagus the animals re- peatedly came round without artificial respira- tion. The danger really begins when the irri- tation is discontinued or fails to inhibit the heart, and thus enables the chloroform in the lungs to be rapidly absorbed and thrown into the blood by means of artificial respiration ; for animals in which this was done, although they showed a tendency to recover when the chloro- form and irritation of the vagus were discon- tinued, afterwards died rapidly. " 34. On another occasion, during Experi- ment 117, the animal was very nearly killed by a comparatively short inhalation of chloroform, owing to the electrodes becoming accidentally short-circuited and failing to keep up the irri- tation of the vagus. Something similar oc- curred in Experiment 177, the effect of the irritation of the vagus passing off while the chloroform was still being pushed, and thus putting the animal into a condition of extreme and unexpected jeopardy. Nothing could be more striking than these near approaches to accidental death from failure to irritate the vagus efficiently. "35. Other experiments were made to test the truth of the statement that chloroform in- creases the action of electrical stimuli applied to the vagus, and showed conclusively that it has no such effect. In one instance only the inhibition seemed to be intensified as the chlo- roform was commenced and diminished when it was discontinued; but apart from the fact that the supposed effect ceased much too suddenly, a repetition of the experiment on the same and other animals showed that there was in reality no such effect. The increased inhibition in this instance was due to the chloroformist com- pelling the attendant who was holding the electrodes to change his position, and thus making him unconsciously apply them more efficiently. When the chloroformist withdrew thqy were restored to their former position. This affords an instance of the care that has to be taken in making experiments if one is not to be deceived. " 36. To test the effect of shock due to vaso- motor change rather than affection of the heart, Goltz's experiment on the frog was repeated on three dogs. In one there was slight lowering of pressure, which was not extensive, but in the others no effect was produced at all. Other operations which seemed likely to produce shock, such as violent blows upon the testicle, were singularly devoid of effect. Failing to lower the blood-pressure by any of these methods, recourse was had to section of the splanchnics, but the low condition of blood- pressure this produced appeared, like stoppage of the heart from vagus irritation, to be a source of safety rather than of danger during chloroform administration. In this connection Experiment in may be studied. There was not much external hemorrhage, but the splanch- nics were divided,-a proceeding which, as is often said, bleeds the animal into his own ves- sels. The pressure was after this extremely low, but chloroform was repeatedly given and various other actions taken, and then chloro- form had to be pushed on a saturated sponge inclosed in a cap for eleven minutes before respiration ceased. "37. The experiments on dogs that had been dosed with phosphorus for a few days pre- viously show that the fatty, and consequently feeble, condition of the heart and other organs so produced has no effect in modifying the ac- tion of chloroform. The ease with which vagus irritation and the Glasgow trace could be produced in these animals, by even slight degrees of asphyxia (vide Experiment 148), was very remarkable; but this was equally the case in dogs that had been given phosphorus only a few hours before the experiment, and whose organs were not yet fatty (vide. Experiment 156). Many of these cases were in the last stage of phosphorus-poisoning, and several of their companions died without any experiment having been performed on them, before or on the same day as they did (yide the low state of blood-pressure in Experiment 163). [We have no experience to offer (Hare and Thornton).] Numerous attempts were made in these animals to produce shock by operations in the re- cumbent and vertical positions, but with- 12 A Study of the Influence of Chloroform upon the out any result more than in those that were healthy. "38. The truth about the fatty heart appears to be that chloroform per se in no way endan- gers such a heart; but, on the contrary, by lowering the blood-pressure, lessens the work that the heart has to perform, which is a posi- tive advantage. But the mere inhalation of chloroform is only a part of the process of the administration in practice. A patient with an extremely fatty heart may die from the mere exertion of getting upon the oper- ating-table, just as he may die in mounting the steps in front of his own hall-door, or from fright at the mere idea of having chloroform or of undergoing an operation, orf during his in- voluntary struggles. Such patients must in- evitably die occasionally during chloroform administration, and would do so even were attar of roses or any other harmless vapor sub- stituted for chloroform." z [We agree entirely with this statement; but as chloroform has confessedly some cardiac action and a very positive vaso-motor and respiratory effect, the fatal result might be more direct.] SUMMARY. Having given the evidence we have accumu- lated, let us see what practical deductions may be drawn. From a careful study of the experiments so far reported, from studies made by one of us some two years ago with H. C. Wood, and, finally, from the careful series of experiments (the tracings of which we herewith append), we believe that the question can be settled by the acceptance of both views in a modified form, or, in other words, that there is no real antagonism in the beliefs that chloroform kills by depression of the heart or depression of the respiration. We very positively assert that chloroform practically always kills by failure of respiration when administered by inhalation, provided- and this provision is most important-that the heart of the anaesthetized is healthy and has not been rendered functionally incompetent by fright or violent struggles, or, again, by marked asphyxia. By a healthy heart we mean one which has not undergone true fatty degeneration, or has not so severe a valvular lesion as to make the slightest variation in the even tenor of the circulation fatal. As positively as we assert that chloroform kills primarily by respiratory failure, so do we also assert that in excessive dose by inhalation it has a depressant effect on the circulation, which is chiefly due to centric vaso-motor de- pression, with final depression of the cardiac muscle itself. Depression of the cardiac mus- cle alone is never great enough to cause death when the chloroform is given by inhalation, but we believe that gradual asphyxia, with the direct depression of the circulation, may do much towards producing a fatal result, for vaso-motor integrity is almost as necessary to life as an intact cardiac mechanism. This cir- culatory depression has been considered a safe- guard because it was supposed to prevent chlo- roform going to the vital centres ; but in reality it is no safeguard, because profound circulatory depression is as great an evil as respiratory nar- cosis. That the circulatory depression may be dangerous is not only evident, but it is stated to be so by the second Hyderabad Commission itself at the end of paragraph 8. This circulatory depression may be so profound that recovery is impossible even with the most thorough artifi- cial respiration, a fact stated by the second Hyderabad Commission in paragraph 25, which we quote in this paper. This empha- sizes the fact that we cannot afford to totally ignore the effect of chloroform on the circula- tion, and we cannot consider the patient in danger of circulatory failure only when the respiration ceases, but as soon as it becomes abnormal. On the other hand, we should re- member that, even if chloroform has been given properly, the arterial pressure may be so low as to give no pulse in the radial artery, and yet the circulatory system be ready to respond at once when the drug is removed. If, there- fore, the chloroform is properly administered, is there danger of its circulatory effect in man ? We think that it is just at this point that our research, and every other research on animals, fails, and necessarily fails, to produce a positive reply. The variation in the action of a drug on a diseased individual from its effect on the normal one is notorious, and we have no right to dogmatically assert that there is absolutely no danger of circulatory depression in man, even if we found no evidence of failure in dogs, because there may be many idiosyncrasies or variations, through disease in the human being, which may completely reverse the results of experiments on healthy animals. In other words, supposing that the amount of depression from very full doses of chloroform equals 25 units, this amounts to little in the normal heart; but if the heart be depressed 25 additional units by disease, the depression of 50 units may be fatal, particularly if to this 50 is added 25 units more of depression through fright and cardiac engorgement, through dis- ordered respiration or struggling. That true Respiration and Circulation. 13 depression of the heart-muscle may take place under chloroform seems to us most undoubted, and we think that the tracings in every research that we have seen support this view. There is always a decrease in cardiac power manifested by the decrease in the force of the individual pulse-beat, and this passes away only if chloro- form is removed early enough. We also agree with McWilliams that from the very first in- halation of chloroform there is a constant ten- dency to cardiac dilatation. We come, finally, to the all-important ques- tions : 1. Is chloroform a safe anaesthetic ? 2. Are we to watch the pulse or respiration during the use of the drug, and what are the signs in the respiratory function indicative of danger to the patient ? 3. What is the true cause of death from chloroform ? 4. Is death from chloroform possible when it is properly administered ? 5. Under what circumstances is the surgeon to use chloroform in preference to the less dan- gerous anaesthetic ether ? 6. What is the best way of administering chloroform ? To the first question the answer is, Yes, for the majority of cases, provided it is given by one who is skilled in its use, and not only knows how to give it, but to detect signs of danger. It is not so safe as ether at any time, other things being equal, and never so safe in the hands of a tyro. To the second question the answer is, Watch the respiration, because as soon as enough chlo- roform is used to endanger the circulation, the respiration will show some signs of abnormality, either in depth, shallowness, or irregularity. In other words, the very effect of the drug may be to cause such deep and rapid respirations that an excessive quantity of the drug is taken into the lungs and continues to be absorbed even after the inhaler is withdrawn. As there is always a fall in pressure under chloroform, it is difficult to feel the radial or temporal pulse, and the respiratory centre rec- ognizes the degree of arterial depression which its sister vaso-motor centre has permitted by finding that its blood-supply is insufficient. As respiration fails first, it should be watched first. Finally, it is only by watching the res- piration that we can tell how much chloroform the patient is getting. We do not watch this function for danger alone, but to tell us of fhe dose. The answer to Question 3 is that death is always due in the healthy animal to respiratory failure accompanied by circulatory depression, which latter may be severe enough to cause death, even if artificial respiration is used skil- fully. Death only occurs in the healthy ani- mal when chloroform is given in excessive quantities. Question 4 is impossible to answer for man from the basis of experimentation, as we can- not produce identical diseased states in animals with those developed under various conditions in man. The physician having a case of heart- disease should always advise the patient of the danger of any ansesthetic, and he should re- member, whether it is wise to tell the patient or not, that anaesthesia always means a step towards death, even in the healthiest of men. In the event of a death under chloroform, the physician is not to blame if he has taken proper preliminary precautions and given the chloro- form properly. Every one is agreed that the patient taking chloroform should have plenty of fresh air, and in India we understand that, to all intents and purposes, patients are operated on in the open air, at least as compared to the closed rooms necessary in America and Europe. This free supply of air is important, whether we believe death to be imminent from cardiac or respira- tory failure; but this supply of air matters little to the patient if he does not breathe freely, nor does the dose of chloroform amount to aught if it is not drawn into the chest. The dose of chloroform is not the amount on the inhaler, but the amount taken into the chest, and, finally, the amount absorbed by the blood- vessels. The rapidity and depth of respiratory movements is, therefore, as Lawrie asserts, the entire key to the situation. We watch a wind- mill over a well to see if it is pumping into a reservoir a given quantity of water. If the windmill works irregularly, so that we know its pumping action is deranged, we separate it from the pump until it works steadily. Simi- larly we withdraw chloroform, as Lawrie says, whenever respiration becomes disturbed in rhythm or when struggling disturbs it, because it is the first indication that the drug's action is uncertain, and because there is no telling the dose which is absorbed. While watching the respiration will not warn us of a sudden car- diac arrest in fatty heart plus chloroform de- pression, neither will the pulse give us such warning, and we are confident that the state- ment of the Hyderabad Commission, that the respiration should be watched, is correct, for we believe, from a long series of observations, that gradual cardiac failure never occurs with- out producing respiratory changes from the A Study of the Influence of Chloroform upon the 14 very first. In other words, we do not believe that in a healthy heart chloroform can cause serious disorder without, as a result of begin- ning disorder, disturbing respiration; and, second, that in a healthy heart a quantity of chloroform sufficient to disorder it will by its direct action disorder the respiration. If, as an extra precaution, one assistant watches the pulse while the other watches the respiration, very well, for though the respiration is the more important function to watch, the man watching the pulse might discover an irregu- larity which the ansesthetizer may not see re- produced in the respiratory action ; but as di- vided attention generally means a slighting of both objects in view, Lawrie is right in insist- ing on the pulse being let alone. In answer to Question 5 we have several points to offer: 1. Hot climates (where ether is inapplicable), where a free circulation of air increases the safety of the patient. 2. Chloroform may be used whenever a large number of persons are to be rapidly anaesthe- tized, so that the surgeon may pass on to others and save a majority of lives, even if the drug endangers a few, as on the battle-field, where only a small bulk of anaesthetics can be carried. 3. Its employment is indicated in cases of Bright's disease requiring the surgeon's atten- tion, owing to the fact that anaesthesia may be obtained with so little chloroform that the kid- neys are not irritated, whereas ether, because of the large quantity necessarily used, would ir- ritate these organs. Quantity for quantity, ether is, of course, the less irritant of the two. 4. In cases of aneurism, or great atheroma of the blood-vessels, where the shock of an opera- tion without anaesthesia would be a greater danger than the use of an anaesthetic, chloro- form is to be employed, since the greater struggles caused by ether and the stimulating effect which it has on the circulation and blood-pressure might cause vascular rupture. 5. In children or adults who already have bronchitis, or who are known to bear ether badly, or, in other words, have an idiosyncrasy to that drug, chloroform may be employed. 6. Persons who struggle violently, and who are robust and strong, are in greater danger from the use of chloroform than the sickly and weak, probably because the struggles strain the heart and tend to dilate its walls. The safest method of administration is by Lawrie's or inhaler, because these provide free circulation of air and do not dis- tract the attention of the ansesthetizer from the respiratory movement by complicated ap- paratus. Apparatus much like these, in allow- ing a free amount of air, are the Hyderabad chloroform inhaler or open-ended cone, with Krohne's and Seseman's respiration indicator attachment. The Junker inhaler, even with its modifica- tions, is too complicated and cumbersome, and while less chloroform is wasted in admin- istering the drug, it must all be thrown out of the bottle afterwards. If used at all, it should be used with the increased air-supply and respiration indicator of Krohne and Sese- man. We agree so heartily with Lawrie's personal conclusions that we print them below: 1. The chloroform should be given on ab- sorbent cotton, stitched in an open cone or cap. (A depression made through the open- ing in the inside flannel bag will answer as well.) 2. To insure regular breathing, the patient, lying down, with everything loose about the neck, heart, and abdomen, should be made to blow into the cone, held at a little dis- tance from the face. The right distance throughout the inhalation is the nearest which does not cause struggling or choking or hold- ing of the breath. Provided no choking or holding of the breath occurs, the cap should gradually be brought nearer to, and eventually may be held close over, the mouth and nose as insensibility deepens. 3. The administrator's sole object while pro- ducing anaesthesia is to keep the breathing regular. As long as the breathing is regular, and the patient is not compelled to gasp in chloroform at an abnormal rate, there is ab- solutely no danger whatever in pushing the anaesthetic till full anaesthesia is produced. 4. Irregularity of the breathing is generally caused by insufficient air, which makes the patient struggle or choke or hold his breath. There is little or no tendency to either of these untoward events if sufficient air is given with the chloroform. If they do occur, the cap must be removed, and the patient must be al- lowed to take a breath of fresh air before the administration is proceeded with. 5. Full anaesthesia is estimated by insensi-' tiveness of the cornea. It is also indicated by stertorous breathing or by complete relaxation of the muscles. Directly the cornea becomes insensitive or the breathing becomes stertorous, the inhalation should be stopped. The breathing may become stertorous while the cornea is still sensitive. The rule to stop the inhalation should, notwithstanding, be rigidly enforced, Respiration and Circulation. 15 and it will be found that the cornea always becomes insensitive within a few seconds after- wards. It is only necessary to add that the patient should be so dressed for an operation that his respiratory movements can be easily seen by the chloroformist. In the climate of India this is not difficult to manage, but it is rather more so in the climate of Europe; so that in this respect, and in this respect alone, the chloroformist in England is placed at a distinct disadvantage compared with the chloroformist in India. Note.-Since writing this report two impor- tant papers upon this subject have appeared in the London Lancet,-the one by Gaskell and Shore, in which they carried out a complete line of ingenious cross-circulation experiments, and from which they conclude that the fall in blood- pressure seen under chloroform is due to car- diac rather than vaso-motor depression; and another paper, published by Lawrie, in the London Lancet for February n, 1893, in which he refutes the statements made by Gas- kell and Shore, and details experiments which he believes combat those of the two investiga- tors just named. We cannot help believing that cross-circu- lation experiments in regard to the action of chloroform must be received with considera- ble doubt by the practising physician. Even if such work is carried out with the greatest skill, the opportunities for error are innumer- able ; and while results are obtained which, if in accord with other studies, might be ac- cepted as confirmatory, the fact that they differ makes their negative conclusion of little value. The object of the investigator of the action of chloroform is to perform experiments which, so far as possible, will be counterparts of the employment of the drug for human beings. To the physiologist it is important to study • a drug in order that certain results may be ob- tained, whether they have practical bearing or not; but the practising physician only wishes those points which should guide him in the administration of the remedy. The concluding paragraph of Lawrie's latest contribution to the subject states the facts so clearly, and is so in accord with what we have tried to set forth in our own report, that we cannot do better than quote the paragraph : "The Hyderabad Commission's work proves that, while Syme's principles are right, there is no such thing as a safe method of chloroform administration. It is no longer a question of the superiority of the London method or of the Edinburgh method; absolute safety can be at- tained neither by watchipg the respiration nor the pulse for signs of danger, which are in either case proof of improper administration or of overdosing. Moreover, overdosing may take place whether the anaesthetic is given on lint or on a towel or on a cap such as we use, or with Junker's or Skinner's or any other form of apparatus. The all-important point is that the breathing shall never be interfered with in any way. Safety under chloroform can unquestionably be insured, but it can only be so by attending to regular natural breathing; and whatever method is employed, no one can deny that it is the bounden duty of the chloro- formist to maintain natural breathing through- out the whole period of administration. To maintain natural breathing requires careful training and considerable experience; but if these conditions be fulfilled it is impossible to produce anything with chloroform but anaes- thesia, and the Hyderabad Commission has shown that anaesthesia alone is entirely free from risk."* In reply to a general request for reports of cases of accident under chloroform, we received the answers shown in the appended table, which may be summarized as follows : Number of respiratory failures 29 Number reported unable to feel pulse, while respiration continued 4 Number of simultaneous failures I Number not stated 1 Total number of accidents reported... 35 » Of the 29 respiratory failures there were 5 deaths, a percentage of Of the 4 cir- culatory failures there were 2 deaths, a per- centage of 50. The 1 case of arrest of respira- tion and circulation simultaneously resulted in death. This summary is particularly interesting in that the great majority of accidents were due to respiratory failure and not to the heart, and this failure was irrespective of age, sex, condi- tion, or magnitude of operation ; also that the accident may occur before, during, or after the operation; and, finally, that in some instances circulatory failure takes place while respiration continues. * Provided the patient is in ordinary health. We would prefer to make the last sentence read, " Anaes- thesia can be safely produced by chloroform." (Hare and Thornton.) 16 A Study of the Influence of Chloroform upon the Report of Accidents occurring during the Use of Name of reporter. Age. Sex. Operation. State of pa- tient at time of beginning anaesthetic. Kind of chlo- roform ad- ministered. Anaes- thetist. How ad- ministered. Rapidity of adminis- tration. Concen- tration of vapor. Length of time chloroform had been adminis- tered at time of accident. 21 yrs. Male. Oblique inguinal hernia. Patient calm. Squibb's C. P. chloro- Skilled. On towel. Few drops at a time. Plenty of air. 5 minutes. form. A. M. Haydem, Evansville, Ind. 67 yrs. Male. Epithelioma of upper lip. Patient calm. Chloroform. Not stated. Not stated. Not stated. Not stated. Not stated. H. S. Harrington, Bertrand, Neb. 8 mos. Male. Talipes varus. Not stated. U. S. P. chloroform. Skilled. Not stated. Not stated. Not stated. Not stated. T. F. Hallett, Rose, N. Y. 6 yrs. Male. Amputation of cut finger. Not stated. Quality of chloroform Skilled. Not stated. Not stated. Not stated. Not stated. not stated. W. H. Washburn, Milwaukee, Wis. 45 yrs. Male. Renal colic. Not stated. Squibb's C. P. chloro- Skilled. On hand- kerchief. Few drops at a time. Plenty of air. Not stated. form. M. P. Murin, Den- 9 yrs. Male. Tenotomy oftendo Not stated. Not stated. Unskilled Not stated. Pushed as Concen- Operation half ver, Col. Achillis and plan- tar fascia. intern. if it were ether. trated vapor of chloro- over; time not stated. form. M. P. Murin, Den- 22 yrs. Male. Tight stricture; Patient Pure chloro- Not stated. Not stated. Not stated. Not stated. Operation ver, Col. internal urethrot- calm. form. over; exact omy. time it had been admin- istered not M. P. Murin, Den- 45 yrs. Male. Stricture. Took drug Not stated. Not stated. Not stated. Not stated. Not stated. stated. Operation not ver, Col. badly. begun; time not stated. E. Lamphear, Kansas City. Not stated. Not stated. Cancer of pan- creas. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. A. W. Wilmarth, Norristown, Pa. 16 yrs. Female. Epileptic convul- sions. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. C. T. Southworth, Monroe, Mich. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not Stated. C. T. Southworth, Not Not Not stated. Not stated. Not stated. Skilled. Esmarch Few drops Plenty of air. Operation Monroe, Mich. stated. stated. inhaler. at a time. nearly over; exact time C. D. Wescott. Not stated. not stated. 16 yrs. Male. Sarcoma. JNot stated. Not stated. Not stated. Not stated. Not stated. Not stated. No. i. 3 yrs. Female. Harelip, cleft pal- ate. Not stated. J. H. Kellogg, Bat- tle Creek, Mich. 24 yrs. Male. Left inguinal her- nia. Quiet. Chloroform supposedly pure. Not stated. Junker in- haler. Given care- fully. Not stated. Late; opera- tion almost completed. L. Reynolds, Hor- ton, Kan. 28 yrs. Male. Enteralgia. Quiet. Squibb's C. P. chloro- form. Not stated. Handker- chief. Patient pulled drug over face Not stated. After a few moments. and mouth. 5 yrs. Male. Crushed finger. Not stated. Not stated. Unskilled. Not stated. Given care- Not stated. Early in ad- fully. ministration. H. Mallens Wat- son, Norfolk, S. D. 2 yrs. Male. Removal of can- cerous tentacle. Not stated. Not stated. Not stated. Not stated. Given care- fully. Not stated. 5 minutes. Robt. T. Morris, 4 yrs. Male. Club-foot. Took drug Not stated. Not stated. Not stated. Not stated. Not stated. Mew York. well up to time of full anaesthesia. Robt. T. Morris, 30 yrs. Female. Dilatation of cer- Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Before opera- New York. vix. tion; time not stated. Robt. Morris, New York. 35 yrs. Female. Straightening a flexed uterus. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. J. T. Webster, Emporia, Kan. 4 yrs. Male. Paraphimosis. Not stated. Not stated. Unskilled. On cloth. Not stated. Not stated. Not stated. J. T. Webster, Emporia. Kan. Not stated. Male. Amputation of the thumb. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. J. N. Coons, Pal- Young Male. Removal of ne- Very weak Not stated. Skilled. Not stated. Not stated. Well diluted Not stated. myra, Mo. adult. crosed seques- trum of tibia. and ex- hausted. with air. J. P. Hachenberg, Austin, Texas. 35 yrs. Female. Operation on foot. Not stated. Not stated. Skilled. Not stated. Not stated. Not stated. A few min- utes. G. W. Shidler, York, Neb. 38 yrs. Male. Fistula in ano. Not stated. Not stated. Skilled. Not stated. Not stated. Not stated. Not stated. Respiration and Circulation. 17 Chloroform to produce General Ancesthesia. Quan- tity ad- minis- tered up to this time. First symptoms. State of patient at time of acci- dent. Respiration ceased first. Heart stopped first. Time of accident. Remarks. Treatment. Result. 8 c.c. Patient suddenly Strug- Respiration ceased sev- Operation Inverted and ar- Death. of drug livid. gling. eral minutes before not begun. tificial respira- taken. heart stopped. tion. Not Suddenly respira- Not Both practically ceased Not stated. Has seen a number of non-fatal Inverted and ar- Death. stated. tion and pulse stated. at once. cases have respiratory failure, tificial respira- ceased. and resuscitated them. tion. Not Slight gasps given. Not Breathing stopped three Not stated. stated. stated. minutes; heart con- tinued to beat for this period after cessation of respiration. Not Patient stopped Not Breathing stopped; Not stated. Everything going well. Drug Inverted and ar- Recov- stated. breathing. stated. heart beating. withdrawn from 2 to 4 minutes tificial respira- ery. before accident occurred. tion. Not Respiration Not Respiration ceased, but No opera- After first recovery chloroform Artificial respi- Recov- stated. ceased. stated. pulse continued. tion. again given, and accident re- ration. ery. peated. Full Respiration Proba- Respiration ceased; Operation 54 grain sulphate of morphine Artificial respi- Recov- quanti- ceased. bly not heart beating. half over. was given before anaesthetic ration for 25 ery. ty;exact strug- was begun. minutes. amount not gling. stated. Not Face suddenly Quiet. Respiration ceased; Operation Respiration stopped, as bladder Artificial respi- Recov- stated. purple; eyes pulse strong. over. was distended with irrigation. ration, inver- ery. protruded. sion, nux vom- ica, belladon- na, whiskey. Not Spasm of muscles Strug- Respiration ceased; Operation All muscles of respiration very Inverted and ar- Recov- stated. of respiration; gling. pulse good. not begun. spastic. tificial respira- ery. Not respiration stopped. Respiration Not Respiration stopped; Operation Respiration stopped as finger tion. Artificial respi- Death. stated. stopped. stated. pulse good for 5 min- begun. touched diaphragm through an ration and utes. incision in belly. stimulation. Not Not stated. Not Respiration stopped be- Not stated. stated. stated. fore heart. Not Not stated. Not Respiration stopped be- Not stated. Operator and others noticed that Death. stated. stated. fore heart. pulse continued. Not Stopped breathing Quiet. Respiration stopped; Operation Operator and others noticed that Not stated. Death. stated. radial pulse good. over. pulse continued. Not Respiration Quiet. Respiration stopped, but Operation Artificial respi- Recov- stated, ceased. pulse full and strong. not yet ration and in- ery. but large begun. version. Artificial respi- Recov- ration and in- ery. version. Not Face assumed Not Heart Operation Particular attention paid to see Death. stated. livid color. stated. stopped; completed. which stopped first, heart or respiration continued * respiration. for a few moments. Not Respiration Not Respiration stopped; Artificial respi- Recov- stated. stopped. stated. heart strong. ration. ery. Not Pulse stopped; Not Pulse Operation Same occurrence three times in Artificial respi- Recov- stated. respiration la- stated. stopped; not com- same case before operation was ration and ery. bored. respiration pleted at completed. stimulation. labored. time of accident. Not Respiration Not Respiration ceased. Before op- The accident being repeated, no Artificial respi- Recov- stated. ceased. stated. eration. operation was done until next ration. ery. , day ; then under ether, without difficulty. t Not Stopped breathing Not Respiration ceased. Not stated. Not stated. Recov- stated stated ery. Not Cessation of res- Not Respiration ceased; Just before Not stated. Recov- stated piration. stated pulse good. I operation. ery. Not Stopped breathing Not Respiration ceased. Not stated. Not stated. Recov- stated stated Inverted and ar- ery. Not Stopped breathing Not Respiration ceased; Not stated. Recov- stated stated pulse continued good. tificial respira- ery. Not Stopped breathing Perfect Respiration ceased; During op- Inverted. Recov- stated lv limp. pulse full and regular. eration. Stimulated with ery. Not Pulse stopped for blot Pulse could Not stated. Thinks death would have re- Recov- stated at least r minute. stated not be felt. suited had he not closely ammonia, and ery. watched the pulse. fresh air ad- mitted to room Not Stopped breathing Deathly Respiration ceased. After opera- Attributes the accident to his al- Artificial respira Recov- stated pale. tion, and lowing patient to regain her tion and cold ery. patient feet too soon after operation. interrupted stood erect douche to chest. 3 or 4 Heart ceased to Not . Pulse conic Not stated. Patient had taken chloroform ten Artificial respi- Death. drachm beat. stated not be felt; years ago for extraction of ration. respiration continued tooth. for a min- ute longer. 18 A Study of the Influence of Chloroform upon the Report of Accidents occurring during the Use of Name of reporter. Age. Sex. Operation. State of pa- tient at time of beginning antesthetic. Kind of chlo- roform ad- ministered. Anes- thetist. How ad- ministered. Rapidity of adminis- tration. Concen- tration of vapor. Length of time chloroform had been adminis- tered at time of accident. Louis J. Pons, Roxbury, Conn. 25 yrs. Male. Not stated. Not stated. Not stated. Not stated. On napkin. Not stated. Not stated. Not stated. J. T. Baldwin, Columbus, 0. Elderly adult. Female. Removal of ure- thral caruncle. Not stated. Not stated. Young physician. Not stated. Not stated. Not stated. A few minutes. A. W. Wilmarth, Norristown, Pa. 16 yrs. Not stated. No operation; given to quiet epileptic convul- sions. Struggling. Not stated. Skilled. Not stated. Not stated. Not stated. A few minutes. T. Walter Todd, Redondo Beach Not stated. Female. Not stated. blot stated. Not stated. Skilled. Not stated. Not stated. Not stated. A few minutes. Cal. Louis J. Pons, 6 yrs. Male. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Not stated. Roxbury, Conn. Thos. R. Savage, New York. 3° yrs- Female. Operation upon rectum. As the pa- tient was in- sane, it is probable she was not calm. Not stated. Not stated. Esmarch inhaler. Not stated. Admixture of air. Not stated. Thos. R. Savage, New York. 24 yrs. Male. Removal of cathe- ter from bladder. Not stated. Not stated. .Not stated. Esmarch inhaler. Not stated. Admixture of air. Not stated. Thos. R. Savage, New York. 47 yrs. Female. Carcinoma of breast. Not stated. Not stated. Not stated. Esmarch inhaler. Not stated. Admixture of air. Before anaes- thesia was complete. Thos. R. Savage, New York. 7 days. Male. Spina bifida. Not stated. Not stated. Not stated. Esmarch inhaler. Not stated. Admixture of air. Not stated. Respiration and Circulation. 19 Chloroform to produce General Ancesthesia.-Continued. Quan- tity ad- minis- tered up to this time. First symptoms. State of patient at time of acci- dent. Respiration ceased first. Heart stopped first. Time of accident. Remarks. Treatment. Result. Not stated. Not stated. Not stated. Respiration ceased. Not stated. Artificial respi- ration ; hypo- dermic injec- Recov- ery. tion of ammo- Not stated. Respiration ceased and heart Not stated. Respiration; pulse good for some time. Not stated. nia. Artificial respi- ration. Death. feeble. Not stated. Respiration sud- denly stopped; pulse good. Not stated. Respiration ceased. Not stated. Artificial respi- ration. Recov- ery. Not stated. Respiration ceased. Not stated. Respiration ceased. Not stated. Same accident occurred twice in this operation. Artificial respi- ration. Recov- ery. Not stated. Not stated. Not stated. Respiration ceased. Not stated. Artificial- respi- ration ; hypo- dermic injection Recov- ery. Not Respiration Not Respiration ceased. Under full The same result was experienced ot ammonia. Artificial respi- ration and in- stated. ceased. stated. anaesthesia a month later in another opera- ery. during op- eration. tfon upon her. version. Not stated. Respiration ceased. Not stated. Respiration ceased. Under full anaesthesia Inversion and artificial respi- Recov- ery. during op- ration. Not Respiration Not Respiration ceased. eration. Before com- The accident reoccurred several Artificial respi- Recov- stated. ceased. stated. plete anaes- thesia. times, and as it was thought this was a case with idiosyn- crasy to chloroform, ether was ration. ery. substituted, with satisfactory result. Not Cyanosis and ar- Not Respiration ceased. During op- Inversion, and Recov- stated. rested respiratory movement. stated. eration. slaps upon back. ery. Experiment No. i. This tracing shows how the degression of pressure under chlorofcrm is only tempjrary and followed by a rise if chloroform is stopped for a moment. Slight rise seen in Part III. It also shows hew, if chloroform is pushed, respiration and circulation are hopelessly depressed, the respiration stopping first. Dog, weight twenty kilos. Chloroform given on towel closely applied to head. Twelve cubic centimetres of chloroform given in the two minutes preceding the beginning of this tracing. Struggling from first inhalation very slight. Tracing No. i-Continued. Part II. Without pause. Tracing No. i-Continued. Part III. No pause. Shows slight rise of pressure. Tracing No. i-Continued. Part IV. No pause. Tracing No. t-Continued. Part V. Ten seconds pause. Tracing No. i-Continued. Part VT No pause Tracing No. I (Wood and Hare) Tracing No. 2 (Wood and Hare). Tracing No. 3. Part I This tracing shows how artificial respiration causes a return of breathing and pressure. Respiration was stopped by ten cubic centimetres of ch'oroform, pushed rapidly. Dog, weight eight kilos. Tracing No. 3-Continued. Part II. Tracing No. 4. Part I. ■BKflKSSMh 9 Shows that with anaesthesia there always ensues a fall ot arterial pressure. There is also a gradual failure of heart- force, as seen particularly in Parts VII. and VIII. in this tracing. Tracing No. 4-Continued. Part II. BTZS9 ■ No pause. Tracing No. 4-Continued. Part III. PfriiSS No pause. Tracing No. 4-Continued. Part IV. No pause. Tracing No. 4- Continued. . Part V; No pause. Tracing No. 4- Continued. Part VI» No pause. Tracing No. 4- Continued* Part VII. No pause. Tracing No. 4-Continued. Part VIII. No pause. Tracing No. 5. Part I. Weight ten kilos. Chloroform given on Esmarch inhaler to the amount ot twenty cubic centimetres in preceding ten minutes. Artificial respiration instituted as soon as voluntary respiration ceased at first X markj failed to restore respiration and to preserve circulation. See Part II. of this tracing. Tracing No. 5-Continued. Part II. .■ ' Respiration stopped at first X mark. Tracing No. 5-Continued. Part III. Tracing No. 8. Part I. Tracing No. 8-Continued. Part IL No pause. Tracing No. 8-Continued. Part III. No pauset Tracing No. 8-Continued. Part IV. Two m'nutes finee Part III. Tracing No. 8-Continzied. Part V. No pause. Tracing No. io. Part I. This tracing shows how, if chloroform is pressed, the respiration finally ceases, and the circulation is persistently de- pressed ; also, that atropine prevents a rapid fall of pressure. H Tracing No. io-Continued. Part IT Tracing No. io-Continued. Part III. Tracing No. io-Continued, Part IV. Tracing No. io-Continued. Part V, A pause of one and one-half minutes between this part and Part IV. Tracing No. ic-Continued. Part VI. kiJM Tracing No. io- Continued. Part VII. Tracing No. io-Continued. Part VIII. ' ' SBrafir No pause. Tracing No. io-Continued. Part IX. No'pause. Tracing No. io-Continued. Part X. MEfjlMgJM- Two minutes' pause in changing drum. Tracing No. io-Continued. Part XI. No pause. Tracing No. io-Continued. Part XII. B/jmEH No pause. Tracing No. io-Continued. Part XTII. No pause. Tracing No. io-Continued. Part XIV. [BBWWpWw WKwWnwi No pause This tracing shows how the pulse and respiration may apparently cease finally, yet return after some moments, and then fail again, the respiration stopping first, the heart finally being in good condition. See Part V. Tracing No. 12. Part I. Br/HPwS F<1 Dog, weight ten kilos. Four cubic centimetres of chloroform given thirty seconds before this tracing begins Tracing No. 12-Continued. Part II. No pause. Tracing No. 12-Continued. Part ITT. No pause. Tracing No. 12-Continued. Part IV. No pause. Tracing No. 12-Continued. Part V. No pause. This tracing shows characteristic fall of blood-pressure under chloroform, the irregular pulse due to struggling, and the effect of primary irritation of the vagal and trigeminal nerves. It also shows how, when the arterial pressure and heart-action seem practically nil, recovery of both may occur, if the chloroform is not pushed. Also recovery of respiration voluntarily. (See Parts VI., VII., XL, and XIV. of this experiment.) Also shows how, when chloro- form is pushed, there comes a time when respiration ceases finally and pressure falls very low. (See Parts XV. and XVI.) As usual, respiration ceased before heart. Tracing No. 13. Part I. BBS -Dog, weight six kilos. Struggling began before chloroform was given, as marked on paper. Tracing No 13-Continued. Part IT. - '•? ':> Xs-'■ Tracing No. 13-Continued. Part III. No pause. Tracing No. 13-Continued. Part IV. No pause. Tracing No. vt,-Continued. Part V. No pause. Tracing No. 13-Continued. Part VI. ';v A pause of twenty seconds, owing to pen getting caught in thread. During this pause pen fell to point shown in very beginning of this tracing. Tracing No. 13-Continued. Part VII. Tracing No. 13-Continued. Part VIII. No pause. Tracing No. 13-Continued. Part IX. No pause. Tracing No. 13-Continued. Part X. Beginning of another paper on second drum. About forty seconds lost in removing first drum and placing second drum in place. Shows complete restoration of blood-pressure. Tracing No. 13-Continued. Part XI. No pause. Tracing No. 13-Continued. Part XII. No pause. Tracing No. 13-Continued. Part XIII. No pause. Tracing No. 13- Continued. Part XIV. No pause. Tracing No. 13-Continued. Part XV. No pause. Tracing No. 13-Continued. Part XVI. No pause. This tracing shows that an animal apparently dead from cardiac failure caused by chloroform has a temporary return of heart-action. Tracing No. 14. Part I. Dog, weight six kilos. Four cubic centimetres of chloroform injected into jugular. Tracing No. 14-Continued. Part II. No pause. Tracing No. 14-Continued. Part III. M ■JtWB Thirty seconds' pause. Tracing No. 15. Part I. - Chloroform in concentrated vapor from towel tightly around head. Tracing No. 15-Continued. Part II. tfjLWH No pause. Tracing No. 16. Part I. This tracing shows that chloroform, even when given very freely in four cubic centimetre doses, does not lower blood-pressure as rapidly when atropine is given as when it is not. It also shows how, when chloroform is pushed, the respiration finally ceases and the pressure falls lower and lower. See Parts X., XI., and XII. Tracing No. 16-Continued. Part II. No pause. Tracing No. 16-Continued. Part III. No pause. Tracing No. 16-Continued. Part IV. IrjBitMbl No pause. Tracing No. 16-Continued. Part V. No pause. Tracing No. 16-Continued. Part VI. No pause. Tracing No. 16-Continued. Part VII. No pause. Tracing No. 16-Continued. Part VIII. Tracing No. 16-Continued. Part IX. Tracing No. 16-Continued. Part X. '<<<c ? ;*■' . ■ ' ' ■ fcl No pause. Tracing No. 16-Continued. Part XI. No pause. Tracing No. 16-Continued. Part XII. No pause. The section of the vagi was made to see if any effect would result, and not because it was thought these nerves were stimulated. Tracing No. 17. Part I. This tracing shows how chloroform may so depress the circulation as to make one think the animal is dead, but the heart, if given time, regains its action. (See Parts IX., X., and XI.) It also shows how, if chloroform is pushed, the respiration stops and the pressure falls (see Parts XIII., XIV., XV., and XVI.), and that the respiration may begin spontaneously as the pressure rises. (See Parts X. and XIII.) Tracing No. 17-Continued. Part II. No pause. Tracing No. 17-Continued. Part III. No pause. Tracing No. 17-Continued. Part IV. No pause. Tracing No. 17-Continued. Part V. HEmH HMfSgmSM KhlS| Pause of twenty seconds. Tracing No. 17-Continued. Part VI. IWiJtagslSsSl JEa No pause. Tracing No. 17-Continued. Part VII. E3 No pause. Tracing No. 17-Continued. Part VIII. No pause. Tracing No. 17-Continued. Part IX. Tracing No. 17-Continued. Part X. Kh Four minutes lost in changing drum. During this time no chloroform was given. Tracing shows recovery of blood-pressure. Respiration returned during pause. Tracing No. 17-Continued. Part XI No pause. Tracing No. 17-Continued. Part XII. No pause. Tracing No. 17-Continued. Part XIII. No pause. Tracing No. 17-Continued. Part XIV. Tracing No. 17-Continued. Part XV. No pause. No pause. Tracing No. 17-Continued. Part XVI. ' X3M ■ No pause. This tracing shows very long circulatory maintenance when atropine is given. It also shows how, when chloroform is pushed, it finally causes arrest of respiration and fall of pressure. Tracing No. 18. Part I. wtwwi Dog, weight seven kilos. This is beginning of second drum. During first drum (ten minutes) he had received grain of atropine and two drachms (eight cubic centimetres) ,of chloroform eyery minute, or eighty cubic centi- metres. As this first drum-tracing is a counterpart of No. 17, it is not given. Tracing No. 18- Continued. Part II. MtJlEA No pause. Tracing No. 18-Continued. Part III. No pause. Tracing No. 18-Continued. Part IV. No pause. Tracing No. 18-Contintied. Part V No pause. Tracing No. 18-Contintied. Part VI. No pause. Tracing No. 18-Continued. Part VII. [Plate lost by maker of plates.-Showed no change except gradual fall of pressure.] No pause. Tracing No. 18-Continued. Part VIII. No pause. Tracing No. 18-Continued. Part IX. SMg S8jj No pause. Tracing No. 19. Part I. Dog, weight twelve kilos. This shows tracing before chloroform was used. Tracing No. 19-Continued. Part II. BBSS A pause of three minutes since last tracing to fix pen, which was out of order. Tracing No. 19-Continued. Part III. No pause. Tracing No. 20. Part I. WMKE1 Tracing No. 20-Continued Part II. No pause. Tracing No. 20-Continued. Part III. ■M^f* j • . •„ ' HrjKs No pause. Tracing No. 2c-Continued. Part IV. No pause. Tracing No. 20-Continued. Part V. No pause. Tracing No. 20-Continued. Part VI. No pause. Tracing No. 21. Part I. This tracing shows arrest of heart by injecting chloroform into the left ventricle, and that the right continues to beat though the left stops. (See Part VII.) BS0WS Dog, weight twelve and a half kilos. Tracing No. 21-Continued. Part IT. No pause. Tracing No. 21-Continued. Part III. No pause. Tracing No. 21-Continued. Part IV. No pause. Tracing No. 21-Continued. Part V. No pause. Tracing No. 21-Continued. Part VI. No pause. Tracing No. 21-Continued. Part VII. mrimliiii imiwMMliM'iOffiiiiiii i iBim : H^Tmir No pause. MM ffiHMMMMM Tracing No. 22-Continued. Part II. For explanation, read text and tracing, Part I. Vagi cut before chloroform was given. Tracing No. 22. Part I. ' No pause. QjHNgm H Qgggg H £1 Ejj grown 1 H Tracing No. 22-Continued. Part III. Tracing No. 22-Continued. Part IV. No pause. No pause. Tracing No. 23. Part I. This tracing shows how chloroform depresses the circulation, but that the pressure very soon rises as the animal frees itself from the drug. (See Part IX.) It also shows how, if chloroform is pushed, respiration ceases and the pressure falls. (See Parts XII., XIII., XIV., XV., and XVI.) See interesting rise of pressure in Parts XVII. and XVIII. Tracing No. 23-Continued. Part II. No pause Tracing No. 23-Continued. Part III No pause. Tracing No. 23-Continued. Part IV. No pause. Tracing No. 23-Continued. Part V. No pause. Tracing No. 23-Continued. Part VI. No pause. Tracing No. 23-Continued. Part VII. No pause. Tracing No. 23-Continued. Part VIII. - ... No pause. Tracing No. 23-Continued. Part IX. EEMEiMBESM No pause. Tracing No. 23-Continued. Part X. [Si i " riMBaamM Wr Jr - itS - - MyWjMBB " No pause. Tracing No. 23-Continued. Part XI. [Tracing lost by maker of plates.] Chloroform given. Two minutes lost in changing drum. Tracing No. 23-Continued. Part XII. No pause. Tracing No. 23-Continued. Part XIII. No pause. Tracing No. 23- Continued. Part XIV. No pause. Tracing No. 23-Continued. Part XV. No pause. Heart maintains same pressure in vessels, though very feeble and apparently stopped so far as pulse work is concerned. Tracing No. 23-Continued. Part XVI. No pause. This shows the same as Part XV. Tracing No. 23-Continued. Part XVII. Tracing No. 23-Continued. Part XVIII. No pause. No pause. This tracing shows how chloroform, when in contact with the heart, acts as a direct depressing poison. Tracing No. 24. Part I. Dog, weight six and a half kilos. Full-grown bitch. No chloroform until after vagal section. Tracing No. 24-Continued. Part II. MBHDRKvHBK&fl EmhSS No pause. Tracing No. 24-Continued. Part III. No pause. < Sv Tracing No. 24-Continued. Part IV. No pause. Tracing No. 24-Continued. Part V. fWKEQ "No pause. This tracing shows how chloroform paralyzes the heart-muscles when it comes in direct contact with it after injection into right ventricle. (See Part II.) Also, that the heart stops independently of any vagal action. ■ .. By S3 Dog, weight eight and a half kilos. Vagi cut before chloroform used. S3 Tracing No. 25-Continued. Part II. Tracing No. 25. Part I. No pause. LS Tracing No. 26. Part I. This tracing shows slight fall of pressure, stoppage of respiration, and spontaneous'jrenewal of respiration. Dog, weight twenty pounds. Four cubic centimetres of chloroform given on towel tightly applied to head. -Tracing No. 26-Continued. Part II No pause. This tracing shows how artificial respiration, resorted to at the proper time, may result in recovery of respiration'jand circulation. Tracing No. 27. Part I. Dog, weight twenty kilos. Chloroform on towel tightly about head. Shows fall of blood-pressure. Arrest of respiration at X mark on next section of tracing. Tracing No. 27-Continued. Part II. No pause. Respiration stopped at second X mark. Tracing No. 27-Continued. Part III. Ten seconds' pause. Tracing No. 27-Continued. Part IV. No pause. Tracing No. 27-Continued. Part V. Two minutes later.