Source:  Snow, John. Assoc. Med. Jour. 3 (April 6, 1855): 313-18.

The breathing and the pulse under the influence of chloroform

By John Snow, M.D., President of the Medical Society of London.

It seems physically impossible that the breathing should not be noticed during the administration of narcotic vapours, for it is by the breath that they are exhibited; and it is extremely improbable that the state of the respiration has ever been disregarded. Even a stranger to medicine could hardly go on giving chloroform after the breathing of the patient became stertorous and laboured, especially as a state of complete insensibility always accompanies this kind of breathing. In treating of sulphuric ether in 1847, I made the remark that, "if there is the least snoring, I always leave off the vapour entirely";*(*The Inhalation of Ether in Surgical Operations, p.38) and, in treating of chloroform, I have always stated that the inhalation should be suspended whenever the breathing becomes stertorous. In doing so, however, I never supposed that I was propounding anything new; I looked on the matter as one of those truisms that every one would at once assent to, but which could not with propriety be omitted in treating systematically of the subject.

I have always considered the pulse amongst the secondary symptoms in administering chloroform, not because any serious affection of the pulse would be a trifling matter, but because the vapour should be so given that it would be impossible for it to exert any serious effect on the pulse. After stating, in a paper written four or five years ago, that the most important point in giving chloroform is to take care that its vapour is systematically diluted with a sufficient quantity of air, I said that, the above precaution having been taken, "it is chiefly by attention to the respiration and the eye that danger is to be avoided"; and I [313/314] added, "The pulse may be felt as a physiological inquiry, or with reference to the operation, but gives no guiding information concerning the chloroform, for the following reasons: when the vapour is diluted to a safe extent, it might be continued till death, as I have ascertained in animals, and the pulse would still beat distinctly for many seconds after the respiration had ceased; and if, on the other hand, the vapour be of dangerous strength, the heart might suddenly cease to beat, and the first intimation of danger from the pulse would come only too late."* (*Medical Times, August 1850, p.228.) In several of the deaths from chloroform which have since occurred, the pulse, which was carefully noted, ceased suddenly, without giving previous warning of danger.

When the vapour of chloroform is so diluted that it does not constitute more than four or five per cent of the air that is breathed, its effects are produced very gradually: and I have ascertained, by very numerous experiments on animals, that when the vapour is continued of this strength till they are killed, the breathing ceases gradually, being first embarrassed and feeble; and in all cases the pulsations of the heart continue freely for one or two minutes, or even longer, after the breathing has ceased; the circulation being ultimately arrested in consequence of the absence of respiration, as in asphyxia. I have satisfied myself of this by keeping the stethoscope carefully applied to the chest of the animals whilst they were dying. During the interval that the heart is still beating after the respiration has ceased, the animal can easily be restored by artificial respiration. It moreover often happens that the animal takes one or two deep gasps just at the moment when the heart is ceasing to beat; and if the chloroform have been removed, so that fresh air is allowed to enter by these gasps, they usually have the effect of re-establishing the action of the heart, and recovery takes place.

The fact of chloroform not acting directly on the heart, when given in this way, does not arise from its want of power to do so, but from the circumstance that the functions of the medulla oblongata and nerves of respiration can be arrested by a smaller dose of the vapour than that which is required to arrest the functions of the ganglionic system of nerves, on which the contractions of the heart depend. This is the case with sulphuric ether, as well as with chloroform, as I pointed out in 1847.† (†Opus cit., p. 81.) The power of chloroform to arrest the contractions of the heart by its direct action can be proved by blowing some of the vapour on the surface of that organ, when the chest and pericardium have been opened whilst it is still beating, and also by continuing the chloroform by artificial respiration immediately after the natural breathing has ceased. Frogs go on absorbing the vapour of chloroform by the skin after the respiratory movements have ceased; and I took advantage of that circumstance to ascertain the exact amount which is required to arrest the action of the heart.‡ (‡See Medical Gazette, 1848, vol.xlii, p.415.)

It unfortunately happens, also, that, when the air is charged with vapour to the extent of about ten per cent, the motion of the heart may be arrested by the direct action of chloroform in the ordinary way of inhalation; and it is due to this circumstance that accidents have occurred; for it does not appear that any patient has died by the mistaken continuance of vapour so diluted that it caused death by acting only on the function of respiration. In several experiments on cats, rabbits, and other animals, with air containing ten per cent or upwards of chloroform, I always found that the action of the heart ceased as soon as the breathing, and in a few cases even before it.§ (§See Medical Gazette, 1848, vol.xlii; and London Journal of Medicine, April 1852.) In some of the experiments, the lungs and heart were exposed whilst the animals were under the influence of chloroform vapour of moderate strength, and artificial respiration was performed. On inflating the lungs with air containing ten per cent of the vapour, the right cavities of the heart, and in one instance the left also, became immediately distended from the loss of power of the heart, which in fact ceased to beat; the lungs not being congested, but, on the contrary turning paler.

A few simple facts and considerations will show how it is that chloroform may suddenly arrest the action of the heart. This agent, when inhaled, acts on the nervous system, by coming in contact with all parts of it, through the medium of the circulating blood. Without alluding to the facts and experiments which prove that all narcotics act in this way, it is only necessary to mention that, in some experiments in which I assisted Dr. Sibson, we found that chloroform and ether produced their effects after both pneumogastric nerves had been divided, exactly the same as before. I ascertained, by experiments which I performed very carefully in 1848*, that the blood, in a state of very complete insensibility from chloroform, contains one twenty-eight part as much as it will dissolve, or one part by measure of chloroform to rather more than eight thousand parts of blood. To arrest the respiratory movements, about one twenty-second part as much chloroform as the blood will dissolve is required; and to stop the action of the heart, one eighteenth part. If we take the estimate of Valentin, that the average quantity of blood in the human adult is thirty pounds, then the quantity of chloroform in the body, when the inhalation has been carried as far as it can be with safety, is twenty-four minims: the quantity that would be required to arrest the breathing, supposing the chloroform were equally distributed throughout the circulation, would be thirty minims and a half; and the quantity, in like circumstances, to stop the action of the heart, thirty-seven minims.

When the vapour of chloroform is largely diluted with air before it is inhaled, it enters the lungs gradually, and each portion of the blood is gradually impregnated with chloroform as it passes the pulmonary circulation; the whole circulating fluid being by degrees charged with chloroform to the requisite amount. The symptoms become developed one after another in a regular manner; the proper moment for leaving off the inhalation can be observed; and there is never any great amount of chloroform in the lungs at one time. As the blood in the lungs becomes charged with chloroform, it passes first to the left cavities of the heart, and thence into the aorta; and, as the first vessels given of from the aorta are the coronary arteries, the heart receives its dose of this agent a little before the other organs, and is always somewhat in advance of them as regards the amount of chloroform it receives throughout the process of inhalation. As the heart can bear more chloroform than the other organs, it is not much affected as long as the vapour is slowly and gradually introduced; but when it enters the lungs in a concentrated form, it is easy to perceive how the heart may be paralysed by a very small quantity. According to the experiments mentioned above, a little more than a minim of chloroform, entering any single pound of blood as it passes the lungs, would suffice to arrest the action of the heart; and patients have died suddenly, like Mdlle. Stock of Boulogne, in 1848, after a few inspirations of the vapour, without being brought under the influence of the agent.

Each minim of chloroform produces very little more than a cubic inch of vapour; in fact, twenty-five minims produce twenty-six cubic inches. The vapour of chloroform, it is true, cannot exist alone, under the ordinary pressure and temperature of the atmosphere; but the whole of a fatal dose of it may be contained in a very limited quantity of air. Eighteen minims is about the average amount that requires to be absorbed in the adult, in order to produce sufficient insensibility for a surgical operation. Twenty-four minims, as was stated above, will cause a very profound state of insensibility; and thirty minims, or rather more, being present in the system at one time, would have the effect of stopping the process of respiration. One hundred cubic inches of air, at 60º Fahr., will take up fourteen cubic inches of chloroform vapour; and at 70º they will take [314/315] up twenty-four cubic inches: it is quite possible, therefore, that the patient may breathe air containing ten per cent of vapour, if no means be taken to prevent such an occurrence. In this way, thirty minims of chloroform would be contained in three hundred and twelve cubic inches of air and vapour; but, since about one-half of the vapour which is taken in by inspiration is expired again without being absorbed,* six hundred and twenty-four cubic inches, containing a fluid drachm of chloroform, is the average quantity that an adult would require to inhale in order to get a fatal dose. (*See Medical Gazette, vol. xli.) As the whole of this might be taken into the lungs in a very few deep inspirations, it must be very evident that systematic means for ensuring the copious dilution of the chloroform vapour are absolutely necessary.

The quantity of air in the lungs of the adult, in ordinary breathing, is about two hundred cubic inches. Therefore, if air containing ten per cent of vapour were breathed in over so leisurely a manner, there would be twenty cubic inches of vapour in the lungs at the moment when the inhalation might be discontinued; or, at all events, this quantity minus what is being carried away by the blood in its passage through these organs. But twenty cubic inches of vapour contain rather more than nineteen minims of chloroform. About half of this would be expired again with being absorbed; but the remaining nine minims is a fearful quantity to be added to that already in the system. If the ordinary quantity of eighteen minims had been absorbed, the patient might be brought to the brink of death, or still more certainly if about twenty-four minims were already in the blood, even if the additional nine minims were distributed equally throughout the circulation; but, as they certainly would not be so distributed, the result would be what I have met with in experimenting with vapour of this strength on animals, viz., sudden death, with arrest of the action of the heart.

If the inhalation of chloroform be not left off very gradually, the symptoms may be observed to increase for about twenty seconds, in the adult, after the exhibition of it is discontinued; owing to the absorption and circulation of the vapour that remained in the lungs at the moment when the chloroform was removed. I had the honour of pointing out this, together with many of the above mentioned sources of danger, to the Westminster Medical Society, on January 8, 1848, before any accident had yet happened from this agent.† (†See Lancet, February 12th, 1848.) The danger from the accumulation of the effects of chloroform is of course in direct proportion to the strength of the vapour, and the quantity of it in the lungs at the moment when inhalation is suspended. A great number of the accidents from this agent have occurred just after the inhalation was left off, and have been caused by the vapour remaining in the lungs at the moment of its discontinuance. The fact of fatal accidents not having happened to children, is chiefly due to the circumstance that the effects of chloroform show themselves much more quickly after the vapour has been received into the lungs, than in the adult.

It must be quite evident, from the above considerations, that it is unsafe to cause insensibility very quickly. It was the occasional practice in some quarters to make the patient insensible in half a minute, when chloroform was first introduced; but, as two-thirds of this time are occupied in the absorption of the vapour from the lungs and the development of its effects, this period does not allow of the gradual production and proper noting of the symptoms. In fact, there are cases in which death has occurred within a minute after the beginning of inhalation; and it is probably owing to the circumstance that the irritability of the air-passages generally opposes the inhalation of strong vapour, in the first instance, that such accidents have not happened more frequently. I consider it decidedly unsafe to cause insensibility in less than two minutes. Four minutes is the most suitable period to occupy in this process in the adult; and in strong robust persons it is desirable to take rather more time than this. It is not enough to take sufficient time in giving the chloroform, but care must also be taken that it is given in such a manner that the air is never, even for a moment, too highly charged with the vapour; for accidents have happened after the patient had been inhaling more than five minutes; and in the fatal case which occurred in an out-patient of the Western Dispensary, in 1849, half an ounce of chloroform was used without making the patient insensible, and when a fresh supply was procured, two hours afterwards, the patient suddenly died.

The patients requiring most care in the administration of chloroform are strong, muscular, persons, accustomed to hard labour, or to athletic sports. Such patients are nearly always affected with muscular rigidity and involuntary struggling before they are quite insensible. These symptoms do not occur till three-quarters as much chloroform has been absorbed as can be present in the system with safety; and, as the patients often hold their breath whilst struggling, and take deep inspirations suddenly and at long intervals, the greatest care is required that the vapour be administered in a very diluted state. Several accidents have happened whilst the patients were struggling and excited. Dr. Black, in commenting on a fatal case of inhalation of chloroform which occurred in St. Bartholomew's Hospital, attributes the accidents, in the cases where the patients have struggled violently, to a supposed exhaustion caused by the struggling.* (*Medical Times and Gazette, 1853, vol. ii, p.562.) This, however, is contrary to everyday experience; for the patients who struggle violently are precisely those who bear chloroform the best, provided they do not get an overdose of it, and are certainly the least liable to the depression which sometimes follows its use. In speaking of an overdose of chloroform, I am making no allusion to the quantity used, but to the fact of the blood, or some part of it, being at some moment charged too highly with the vapour. Dr. Black admits in his communication that no attention had been paid at St. Bartholomew's Hospital to the percentage of vapour in the air breathed by the patients, though he thinks that the inhaler employed might be made to afford information of that kind.

There is an opinion which has often been expressed with regard to chloroform that cannot be too strongly combated, as it is of the most dangerous kind. The opinion to which I allude is, that chloroform vapour requires to be administered with plenty of air, merely for the purposes of respiration, just to prevent its suffocating a person, as hydrogen or nitrogen gas might do. Now, plenty of air is a good thing of itself; but, if it contain too much vapour, the more air the patient gets the greater the danger. The Academy of Medicine in Paris advocated the above opinion, in their report of the fatal case that occurred at Boulogne;† and M. Malgaigne, their reporter, even denied that chloroform could cause death by its direct action, and especially by poisoning. He supposed that we had in chloroform the strange anomaly of a powerful narcotic or soporific, which was incapable of causing death by its narcotic action. (†See London Journal of Medicine, April 1849.) That it can do so, and that its fatal effects are not due to the exclusion of air, the following, amongst other reasons, sufficiently prove. 1. The patients generally breathe more air during the inhalation of chloroform than at another time, because the respiratory movements are usually increased both in frequency and extent, and the vapour does not occupy more than about one-tenth of the volume of the air, even in cases where fatal accidents occur. 2. The vapour of ether may occupy a much larger volume in the air breathed by the patient, without his incurring any risk. 3. Another anæsthetic vapour, that of hydrocyanic acid, will cause death when present in the air in very much smaller amount than that of the chloroform which may be breathed with safety. 4. The blood is quite florid in colour, immediately after death, in the lungs and left cavities of the heart of animals that are killed by chloroform with great [315/316] rapidity. I have not time to enter in this place on the modus operandi of chloroform; but I have done so at some length in the concluding volume of the Medical Gazette for 1851.* (*See also Association Journal, 1853, p. 1114.)

In some of the cases where death from chloroform has been threatened, the medulla oblongata and nerves of respiration have been overpowered by the vapour, whilst the heart has been less seriously affected; but, in all the fatal cases in which the symptoms have been recorded, the heart has been directly paralysed by the chloroform, or so weakened by it as to be unable to carry on the circulation. In some of these cases the medulla oblongata, etc., have had their functions also suspended, at the same time, by the direct action of the chloroform; in other cases they have not, for the respiration has continued after the heart has ceased to beat.

As the fatal accidents from chloroform have been caused by its direct action on the heart, it seems a ready and natural conclusion to watch the pulse in order to prevent such accidents. Many medical men have inculcated this rule, and I may mention Mr. Stanley and Mr. Erichsen as having published their opinions to this effect; but, when we remember that the fatal symptoms have always occurred without any warning, and that sudden accidents may be entirely prevented by taking care that the vapour is so diluted that it shall never form more than five per cent of the air breathed by the patient, the fallacy of relying too much on the pulse is evident. I do not, of course, mean that there is any harm in attending to the pulse as closely as possible, for that need not divert the attention from other symptoms; but the placing too great reliance on the pulse is an evidence that the true source of danger, in giving chloroform, is not understood.

On the other hand, the mere fact of not attending to the pulse is not proof that the source of danger is rightly appreciated. We learn from a clinical lecture recently delivered by Mr. Syme, that the pulse is very much disregarded in Edinburgh, from a belief that danger always begins with the respiration. The medical profession in Edinburgh appear to be influenced very much by a paper of Mr. Bickersteth's, which appeared in the Monthly Journal for September 1853. Mr. Bickersteth performed some experiments on animals, and found that the breathing ceased before the pulse; and he concluded that this must be so in all instances, although out of four cases of suspended animation from chloroform, in operations which he witnessed and relates, there is distinct evidence that the action of the heart was nearly suspended by the direct effect of the chloroform in three of the instances; and this was probably the case in the fourth instance also, but the pulse is not mentioned. I ought to remark, in passing, that four cases of suspended animation from chloroform are a very large number to fall within the observation of one practitioner, however great his experience, and indicate, in my opinion, that the method of giving this agent in Edinburgh is not the right one. Mr. Bickersteth also mentions some cases in which the pulse became suspended for four or five seconds, just when the surgeon was making his first incision, but recovered itself immediately. He attributes this circumstance to the effect of the knife, notwithstanding the insensibility. It is a phenomenon I have not met with; and I am inclined to think it due to the chloroform. The moment when the surgeon is commencing his operation is usually that when the greatest effect of the vapour remaining in the lungs, at the time of leaving off the inhalation, would be produced.

Mr. Bickersteth relates two experiments, in which he introduced chloroform by artificial respiration, after the chest had been opened and the heart exposed. They are exactly the same as one I detailed more than a year previously,† with the single exception that, instead of employing air charged with ten per cent of vapour, he merely employed air strongly charged with vapour. (†London Journal of Medicine, April 1852.) If the sudden arrest of the circulation by the direct action of chloroform, at the same time as, or even before, the breathing ceases, were the ordinary mode of death in giving chloroform to animals, it might fairly be asked why accidents are not of everyday occurrence in the human subject, instead of happening only once in about a thousand times, even when no special case is taken to dilute the vapour. The truth is, that although I have been able to kill animals at will, in the above manner, ever since 1848, it requires a little care and contrivance to make the air take up eight or ten per cent of vapour in every instance. It is reasonable to suppose that, if the chloroform is given to animals merely as it is given to patients, one would have to wait a good while before meeting with the kind of sudden death that has happened now and then to patients. For it must always be remembered that the accidents have not happened through mistaking or disregarding the symptoms, and continuing the inhalation too long.

I still consider, as I have all along, that artificial respiration, promptly and efficiently applied, is the best means for affording the patient a chance of recovery from an overdose of chloroform; but I know from experiments that this will not answer if the heart is completely paralysed. The way in which artificial respiration acts is no doubt as follows. It first empties the lungs of any remaining vapour, which then frees the blood, present in the lungs, of some of the chloroform it has absorbed. By these means, and by the action of the air, the passage of the blood through the capillaries of the lungs is assisted; the right side of the heart becomes a little relieved of its over-distention; and if some of the blood in the lungs, which has been deprived of chloroform by artificial respiration, passes forward into the left cavities of the heart, and is thence thrown into the coronary arteries by any slight power remaining in the left ventricle there must be a fair prospect of recovery. From what I have observed in animals, I believe that taking a little blood from the jugular vein might be of service in some cases, by relieving the distention of the right cavities of the heart.

From the above facts and considerations, it must be very clear that the most important rule in giving chloroform is to take care that the vapour is diluted to a sufficient extent with air. In administering sulphuric ether, it was sufficient to watch the symptoms in order to prevent danger, although even then a knowledge of the strength of the vapour was a useful guide; but, with chloroform, the proper dilution of the vapour becomes more important even than the symptoms. However, when the quantity of chloroform that is required to make a patient insensible is diffused through as much air as was occupied by the dose of ether vapour, the one anæsthetic is as safe as the other. The most perfect way of diluting chloroform vapour is to mix it with air in a very large hydrogen balloon. I gave it in this way in several cases of tooth drawing, in St. George's Hospital, in 1848, the proportions being four per cent of vapour and ninety-six per cent of air; and the results were very uniform and satisfactory. In practice, however, it is often necessary to sacrifice perfection more or less to convenience. I have since the latter part of 1847 used an apparatus for the administration of chloroform, which allows me to regulate the proportion of vapour in the air with sufficient accuracy for practical purposes. It was described in one or two of the medical journals soon after its introduction, but after this lapse of time it may perhaps not be amiss to allude to it again; and the accompanying wood-cut, with the explanatory references, will make it sufficiently understood.* (*It is made by W. Matthews, 8, Portugal Street, Lincoln's Inn Fields.)

The receptacle for chloroform is surrounded by a bath of cold water, for the purposes of regulating the amount of vapour taken up by the air, and supplying the caloric, which is carried off by the evaporation of the chloroform. I have ascertained that air passing through the inhaler, in the way of ordinary respiration, takes up six per cent of vapour at the temperature of 60º Fah.; and by turning the expiratory valve a little on one side, the amount of vapour [316/317] can be reduced at pleasure. It is desirable to begin the inhalation with the vapour very much diluted, till the air passages get accustomed to the vapour, then to increase the strength to the requisite amount, by gradually closing the valve more or less. When the breathing is much deeper and more rapid than natural, it is desirable to have the valve a little more open, as also in hot weather, when the water is above 60º. The air passes over the surface of the bibulous paper during inhalation, and meets with no obstruction, provided too much chloroform is not poured in at once. About two drachms is the best quantity to introduce at a time; but it must be remembered that the amount of this which the patient may inhale is to be regulated by the observation of the symptoms.

Care should be taken that the bibulous paper is rightly arranged; and it should be dried from time to time, to free it from the minute quantity of water contained in all the chloroform at present in the market. This water remains in the paper after the chloroform is inhaled, and would ultimately accumulate, so as to stop the action of the inhaler.

The best criterion that an operation may begin, is the suspension of the sensibility of the conjunctiva. When the free edge of the eyelid can be touched without causing decided winking, the patient will hardly ever show signs of pain from the surgeon's knife. The chloroform, as I said before, must always be suspended if the breathing becomes stertorous; but it is seldom necessary to wait for this symptom.

During the removal of tumours of the jaw, and in other operations on the face, in which the inhaler cannot be applied after the surgeon begins, I apply chloroform on a hollow sponge, first diluting it with an equal quantity of rectified spirit, to limit the amount of vapour given off. Dr. Warren, of Boston, in America, long ago recommended what he called strong chloric ether, which consisted of one part of chloroform and two of spirit by measure. The patient inhales hardly any of the spirit, as the chloroform evaporates first, leaving nearly all the spirit behind. The process of inhalation is not uniform, owing to the varying strength of the solution as the chloroform evaporates; but this plan is well worthy the attention of those who wish to give this agent with no other appliance than a handkerchief or sponge. Either one or two parts of spirit have the effect of so limiting the quantity of vapour taken up by the air, that no sudden accident could happen.

The following circumstances show very clearly the influence of diluting chloroform with spirit. The so called strong chloric ether of Dr. Warren had been employed on a sponge in the Massachusetts General Hospital for three or four years without accident; when one day a new dispenser handed pure chloroform in mistake for that solution, and two accidents happened in two consecutive operations: one was fatal, but in the other case the patient was [317/318] resuscitated from a state of suspended animation.* (*New York Journal of Medicine, vol. x. New series, 1853.) The accidents were, no doubt, chiefly due to the circumstance that it had been the custom to use the diluted preparation more freely than pure chloroform would have been used; still they illustrate equally well the comparative safety of diluted and undiluted chloroform, when used on a sponge or handkerchief.

Dr. J. Mason Warren has informed me that, since these accidents, the governors of the hospital have prohibited the inhalation of any other agent than sulphuric ether, for preventing pain in surgical operations.

18, Sackville Street, March 1855.