"On the pathological effects of atmospheres vitiated by carbonic acid gas, and by a diminution of the due proportion of oxygen"

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By John Snow, M.D., London

The greater part of the experiments contained in the following paper were related to the Westminster Medical Society on March 30, 1839, and a very brief report of them appeared in the Medical Gazette and the Lancet at the time; but, as the subject to which they relate is of great importance, I have thought it desirable that these experiments should be placed in detail before the profession, and accompanied with some explanations.

There are on record a great number of cases of gradual or slow [49/50] asphyxia from atmospheric air contaminated with carbonic acid gas, but the circumstances under which these accidents occur are always such as to preclude the possibility of analyzing the air producing them. The greatest difference of opinion has existed amongst authors, not only with respect to the amount of deterioration which is fatal or dangerous, but also as to whether carbonic acid is an active poison, or is merely injurious by displacing the atmospheric air; and although the experiments of Collard de Martigny show, in my opinion, the active nature of carbonic acid, they do not show the quantity necessary to produce injury or death; and I know of no experiments on animals, except those I am about to relate, which are calculated to point out the condition of an atmosphere which may or may not be fatal to persons breathing it.

When there is more carbonic acid in the air than the fraction naturally present, there will always be a diminution of the due proportion of oxygen; but this diminution will vary very much with the manner in which the carbonic acid has been produced: if it has been given off from a fermenting vat, or separated from lime or any body with which it was in combination, it becomes added to the air, mixing with it and displacing the nitrogen and oxygen alike. In this case the diminution of the oxygen is equal to twenty-one hundredths of the carbonic acid gas present, or about one-fifth. But if the carbonic acid is the result of the breathing of a number of persons in a limited portion of air, or of the combustion of charcoal or other matter in it, then the carbonic acid gas being formed by union of carbon with the oxygen of the air, the diminution of the oxygen in a given bulk will be always equal to, and in many cases somewhat greater than the amount of carbonic acid present. As an illustration of the above difference in the constitution of the air, I may here remark that a small wax taper is instantly extinguished in air which has been contaminated by respiration till it contains 4 per cent of carbonic acid, whereas 20 parts carbonic acid, or 25 parts nitrogen, require to be added to 100 parts of common air before it will extinguish the flame.

In order to investigate this subject properly, I sought to determine separately the effects of carbonic acid and of a diminished amount of oxygen; and the quantity of air used, in proportion to the size of the animals experimented on, was so great that the result could not be vitiated by the products of their respiration during the experiments.

FIRST DIVISION.--Experiments undertaken to determine the effects of diminishing the amount of oxygen.

First Experiment.-- Into a large glass vessel, containing 2000 cubic inches of atmospheric air, inverted over water, 70 cubic [50/51] inches of nitric oxide gas were passed, which, combining with part of the oxygen of the air, formed nitrous and nitric acid, which were absorbed by the water. After the entire absorption of these acids, and the volume of the air had been restored to 2000 cubic inches, the composition of this factitious atmosphere was found to be 18 ½ oxygen, 81 ½ nitrogen in every 100 parts, the oxygen being reduced 2 ½ per cent. Into this a white mouse was introduced, and the small quantity of carbonic acid given off from its lungs was absorbed by lime water. It seemed unaffected, and was taken out at the end of five hours.

Second Experiment.-- A sparrow was placed in a factitious atmosphere similar to the last, and at the end of five hours was breathing laboriously. Being left for the night, after seven hours longer, it was found dead.

Third Experiment.-- Into the same vessel 100 cubic inches of nitric acid gas were passed, and an atmosphere was thus formed, in which the oxygen was diminished 3 ½ per cent, being composed of 17 ½ per cent oxygen, and 82 ½ per cent nitrogen. In this a white mouse was placed for ten hours, but seemed unaffected, and was taken out at the end of that time uninjured, and remained well.

Fourth Experiment.-- A sparrow placed in an atmosphere similarly constituted was taken out at the end of half an hour unaffected, and it continued well.

Fifth Experiment.-- The last experiment was repeated with another sparrow, which was allowed to remain. After a time its breathing became laborious, and it died at the end of six hours. Its blood remained fluid after death, and that in the lungs was of a florid colour. In this, as in all this division of experiments, the small quantity of carbonic acid gas given off from the lungs of the animal was absorbed by lime water.

Sixth Experiment.-- In the same vessel and by the same method 6 per cent of the oxygen were removed, leaving 15 per cent oxygen and 95 per cent nitrogen. A sparrow put into this atmosphere opened its bill and became convulsed at the end of 35 minutes. It was now taken out, but never completely recovered. It died in the course of the following night, and its lungs were found to be soft and gorged with dark fluid blood.

Seventh Experiment.-- A white mouse was placed in a similar atmosphere, and at the end of five hours and three quarters it was insensible, breathing deeply, but very seldom. It was now taken out, and it soon recovered.

Eighth Experiment.-- A green linnet was placed in an atmosphere containing 1 per cent more oxygen than the last, viz. 16.5 per cent only having been abstracted; and it died in ten minutes. [51/52]

Ninth Experiment.-- Half of the oxygen having been removed, and the volume restored as before, an atmosphere was formed consisting of 10 ½ per cent oxygen and 89 ½ per cent nitrogen. A white mouse was introduced into this, and it became immediately distressed, breathing deeply and quickly. In five minutes it was nearly exhausted, being no longer able to stand, and evidently on the point of death. It was now taken out, and very soon recovered.

SECOND DIVISION.-- To show the effects of carbonic acid gas, the due amount of oxygen being preserved.

Tenth Experiment.-- Eighty cubic inches of carbonic acid gas and twenty cubic inches of oxygen were passed into the same large vessel, placed over a saturated solution of common salt, and it was filled up with atmospheric air. It then contained a factitious atmosphere constituted as follows,-

21 Oxygen

04 Carbonic acid

75 Nitrogen

100

A linnet was placed in this for eleven hours; it was dull and listless during the experiment, and its respiration was rather deeper than natural; otherwise it was unaffected, and it resumed its usual vivacity directly after the fresh air was admitted to its cage.

Eleventh Experiment.-- 240 cubic inches of carbonic acid, 60 of oxygen, and 1700 of atmospheric air being mixed, an atmosphere was formed containing

21 oxygen

20 carbonic acid

67 nitrogen

in every 100 parts.

A small bird was put in, and its respiration became quicker, deeper, and difficult in less than an hour, and it appeared very uneasy at the end of two hours and a half. When it was left for the night it was in the same state. In the morning it was dead; its limbs were rigid, and the blood in the heart and adjoining large vessels and in the lungs was fluid and dark coloured.

Twelfth Experiment.-- An atmosphere being formed of the following composition,

21 oxygen

20 carbonic acid

59 nitrogen

100

Two birds were put into it. They became greatly disturbed almost immediately, and were taken out at the end of a few minutes, but died shortly afterwards. [52/53] Their feathers, however, got wetted whilst they were being withdrawn, which would diminish their chance of recovery.

Thirteenth Experiment.-- A white mouse was placed in a similar atmosphere. Its respiration became hurried, it became feeble, and died at the end of an hour and a half.

THIRD DIVISION.-- In which there is carbonic acid, with a diminished amount of oxygen.

a. In which the oxygen is diminished only by about one-fifth the amount of the carbonic acid gas present, as in cases where the air is vitiated by a fermenting vat or by a lime kiln.

Fourteenth Experiment.-- Six per cent of carbonic acid were put into the same large vessel, the remaining 94 being atmospheric air; the oxygen was consequently diminished from 21 to very nearly 19 ¾ per cent. Two brown linnets were put into this atmosphere, and they immediately began to breathe deeply, and in ten minutes they opened their bills. They continued to breathe laboriously for four hours and a half, when one of them died. The other one was then taken out, and it commenced to breathe naturally directly afterwards, and remained well till employed in another experiment. The blood of the one that died was of a cherry red colour.

Fifteenth Experiment.-- A white mouse was put into the vessel whilst containing 10 per cent carbonic acid, and 90 common air; the oxygen being thus diminished by two per cent very nearly. The mouse was distressed and breathed deeply from the commencement, and at the end of three hours was removed in a very feeble state, but it recovered directly.

b. In which the diminution of oxygen equals or exceeds the amount of the carbonic acid gas present, as in cases in which the air is vitiated by respiration, by the combustion of charcoal, or artificial lights.

Sixteenth Experiment.-- A factitious atmosphere was formed, containing 1 ½ per cent of carbonic acid, and in which the oxygen was diminished by 2 per cent. It was consequently constituted as follows.

01.5 carbonic acid

19.0 oxygen

79.5 nitrogen

100

A linnet was placed in this and allowed to remain for twelve hours. It was not particularly affected during the experiment, and it remained in good health after its removal.

Seventeenth Experiment.-- A candle was allowed to burn in [53/54] the large glass filled with atmospheric air, till on the point of going out. It was removed before the evolution of those poisonous gases which arise from the slow combustion of the tallow in the wick after the flame is extinguished. Consequently, the products of combustion were some carbonic acid and vapour of water, and the composition of the vitiated atmosphere was found to be

03.00 carbonic acid

16.75 oxygen

80.25 nitrogen

100

The air had, therefore, lost 4 ¼ per cent of oxygen, and acquired 3 per cent of carbonic acid very nearly.

A brown linnet was put into this; it began to breathe deeper than natural, and died in 2 ½ hours.

Eighteenth Experiment.-- A wax taper having burnt till it went out for want of sufficient oxygen the remaining air was found to be composed as follows.

03 carbonic acid

16.5 oxygen

80.5 nitrogen

100

It had consequently lost 4 ½ per cent of oxygen, and acquired 3 per cent of carbonic acid. A white mouse, introduced into this atmosphere, was uneasy from the first, endeavoured to find its way out, breathed laboriously, and after four fours was lying on its side, exhausted and scarcely breathing. It was withdrawn, and recovered after a while.

In this class of birds, the respiratory function is in its highest perfection: the development of animal heat, and the necessity for a constant supply of fresh air are greater than in the rest of the animal kingdom. In the mouse, the respiratory function and the development of caloric are rather low. Contrary to the habit of the small song birds, who live always in the open air, it lives naturally in holes, where the air will necessarily be somewhat vitiated by its own respiration. Accordingly we find that the birds were uniformly sooner distressed and killed than the mice by corresponding atmospheres. The human being, as regards his respiratory function, is placed between the bird and the rodent, and we may therefore conclude that the fatal effects of vitiated atmospheres on him will likewise be intermediate. It must follow, then, that 5 or 6 per cent of carbonic acid cannot exist in the air without danger to life, and that less than half this amount will soon be fatal, when it is formed at the expense of the oxygen of the air, as it is in most cases of accident and suicide.

Whilst these experiments clearly establish the fatal effects of [54/55] carbonic acid, they disprove some of the arguments from which this gas has hitherto been concluded to be poisonous. It has been said that the illness following exposure to its effects, in cases where the patient was discovered before death, showed its poisonous nature; but in the sixth experiment we have illness and subsequent death after removal from an atmosphere deteriorated by removal of part of its oxygen, whilst no carbonic acid was present; and the chance of recovery after these experiments seemed to depend on the extent and duration of the previous suffering, rather than on the presence or absence of carbonic acid.

It has been argued, that the blood being found florid in the body, was a proof that there was sufficient oxygen in the air, and that, hence, death resulted solely from the carbonic acid. But, in the fifth experiment, the blood in the lungs was florid, when none of this gas was present, and death arose from an insufficiency of oxygen--an insufficiency to maintain life, yet enough to redden the blood.

Carbonic acid gas caused deep and laborious breathing, but in what way it was destructive to life, these experiments do not enable us to state. Its injurious effects seem to depend rather on its physical properties, viz. its density and solubility in the blood, than on any strictly poisonous qualities; and this view is supported by Nysten's experiments of injecting it into the blood-vessels. He sums up the result of his experiments as follows: "Le gas acide carbonique injecté dans le systéme veineux en quantité considérable, mais avec les précautions nécessaries pour ne pas occasionner la distension du cœur pulmonaire, ne donne lieu à d'autre phénomène consécutive notable qu'une foiblesse musculaire qui cesse au bout de quelques jours" [Recherches de Physiologie et de Chimie Pathologiques, p. 93].

The experiment of Collard de Martigny, in which he was immersed in the gas without breathing it, might seem opposed to this view; but it is to be observed, that he breathed through a long tube, which process, by obliging him to respire part of the same air over and over again, would sufficiently account for all the symptoms he experienced.

The appearance after death in the experiments recorded in this paper were somewhat various, and seemed to depend, rather on the slowness or quickness of dying, than on the constitution of the air causing death. There was no appreciable congestion or other morbid appearance in the brains of those animals which died. Apoplexy has occasionally occurred to human beings under similar circumstances; but the brain of man is a much more complex organ than that of the bird and rodent. Many of these birds sweat profusely during the experiments, breathing laboriously, and placed, as they were, in an atmosphere saturated with moisture. [55/56]

Naturalists tell us that birds do not perspire; the fact, however, is otherwise; but, under natural circumstances, the perspiration passes off insensibly in the form of vapour, on account of the high temperature of their bodies.

These experiments agree with some points which have been observed in accidents to human beings. For instance, a contaminated atmosphere has been known to prove fatal, though it produced no inconvenience at first. Now, in the majority of these experiments, the animals were apparently not affected till after a longer or shorter time. It has been observed, that air contaminated with carbonic acid may be dangerous, although a candle will continue to burn in it, and such was the state of the air in the fourteenth and fifteenth experiment.

Professor Graham suggested a plan, which has been published in the reports of the Royal Humane Society, of absorbing the carbonic acid gas remaining after the explosion of fire-damp in coal mines, by means of inhaling the air through a cushion filled with a mixture of slaked lime and pounded sulphate of soda. But we have seen that the carbonic acid is not the only cause of injury; and since, from the constitution of fire-damp, the loss of oxygen by its explosion will, in every instance, be at least twice as great as the carbonic acid which is added, this ingenious contrivance could remove but a small part of the vitiation, and, by giving a false idea of security, would be likely to increase, instead of diminishing accidents.

Professor Graham evidently partakes of an error, which, I believe, is pretty general in the profession, viz. that the whole, or nearly the whole, of the oxygen of the air is available for respiration. He says, "In many cases the oxygen of the air is not exhausted by the explosion, although, from the presence of 5 or 10 per cent of carbonic acid, it is rendered irrespirable." Now, if but 5 per cent of carbonic acid were present after the explosion, half the oxygen of the air would be gone, and the other half would not support life for five minutes; consequently, after the absorption of the carbonic acid, the residual air would be instantly fatal.

The amount of oxygen cannot be reduced by any notable amount without danger. I mean the amount in proportion to the nitrogen; for the amount in a given space may be greatly reduced, provided the nitrogen be reduced pari passu, since, on high mountains, persons suffer only a little inconvenience, when the quantity of oxygen in a given space is reduced below what would be quickly fatal, and what would admit of the combustion of no ordinary materials, if the full amount of nitrogen were present.

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