COLOMBIA LftRARIl '■ HfAnH'.i.il'; > III! III! HX00025887 Cheyne-Sto^ Respiration, 6. A. Gibson, M.D., /),6'<". In Q^\^.\ Columbia ?inibers>itj>\ in tfje Citp of i^eto ^orb College of ^|)j)gicianB; anb ^urgeong l^eference Hihvavp /^i/^ .M*^ a.^^^/^C^^'-^^ ^^^ CHEYXE-STORES RESPIRATION. CHEYNE-8T0KES RESPIRATION. GEORGE ALEXANDER GIBSON, M.D., D.Sc, F.R.C.P.E, F.R.S.E., ASSISTANT PHYSICIAN TO THE ROYAL INFIRMAKY OF EDINPCROH ; LECTUKER ON TUE PUINCII'LKS AND PRACTICE OF MEDICINE AT MINTO HOUSE ; EXAMINEE ON MEDICINE AND CLINICAL MEDICINE IN TUE UNIVEUSITY OF GLASGOW. EDINBURGH: OLIVER AND BOYD. 1 8 y 2. Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/cheynestokesrespOOgibs Sir DOUGLAS MACLAGAN, Kt. M.D., LL.D., F.R.C.P.E., PnOFESSOR OF MEDICAL JUUISPKUDEKCE IN THE rxS'IVERSITT, CONSULTING I'lIYSICIAN TO THE ROYAL INFIRMARY, PBESIDENT OF THE ROYAL SOCIETY OF EDINBURGH, THIS LITTLE WORK IS DEDICATED IN TOKEN OF ADMIRATION AND AFFECTION. PREFACE. — «♦ Tfie contents of tlie following pages have appeared from time to time during the last three years in the pages of the Ediahurfjh Medical Journal under the title of " An Examination of the Phenomena in Cheyne-Stokes Respiration.' The somewhat lengthy period over which the publication of these papers has extended has not, perhaps, been altogether a disadvantage, as it has allowed full opportunities for considering the many questions involved in the explanation of a symptom so complex as that with which tiiis work is concerned. It is a duty as agreeable to, as it is incumbent upon, me to express my warm thanks to those who have rendered me assistance in ascertaining the views which have previously been advanced by others on the subject. I desire gratefully to acknowledge my obliga- tions in this respect to Drs Berry, Edinburgh; Billings, Wasliington ; Bull, Christiania; Cowan, Dordrecht ; Edes, Washington; Grawitz, Greifswald ; Langendorff, Konigsberg ; Pepper, Philadelphia ; and Schepelern, Copenhagen. I wish further to express my thanks for copies of the Transactions of their re.spective societies, which could not be obtained except througli their kindness, to the Secretaries of the h. Ic. Gesellscha/t (hr Atrzte zu Wiev, Societc dc Mcdccine el de Pliarmacie de VIsere, SocUU mcdicalc dc la Suisse romande, Uj^sala Ldharcforcnings Selskahj and Wisconsin Slate Medical Society. 17 Alva Street, Edinbdroh, 26th September 1892. CH 1'^ Y N ]>STO K l« RKSPI RATION . T?EW symptoms have within an equally brief space of time ■^ excited so much discussion as that peculiar modification of the respiratory rhythm which in every language bears the names of Cheyne and Stokes, and, as so much has already been written on tlie subject, there cannot fail to be some hesitation before adding another to the many contributions towards its elucidation. In our own country, however, the symptoms which frequently accompany the type of breatluiig in question are but imperfectly known, while of the many explanations that liave been advanced to account for its appearance, very few have been seriously considered, and it therefore seems unnecessary to give any reasons for bringing the matter forward once more. During the last four years several excellent examples of this type of breathing have been under my observation, and these have led me to study the phenomena which are linked with it, as well as to criticise the theories that have been formed to explain its mode of origin. In the following pages the results of these investigations are fully embodied, and as they naturally fall into three classes, it will be of advantage to group them in three divisions: historical, clinical, and critical. IIlSTOUICAL. The type of biuathing which forms the subject of the present remarks has aroused a great amount of interest and produced a corresponding number of contributions to medical science. Occurring as it iloes in the course of many varieil conditions, the symptom is, as miglit be expected, referred to in works on many ditlV'reiit diseases. The literature of the subject has tluMvfdrt' assunieil large proportions. Many of tlie writings which lia\o been (.levitttnl to it are of bnt little value, ami yet they have served a useful purpose by throwing light upon some of its phases, A 2 CHEYNE-STOKES KESPIRATION. or by recording its presence in conditions where it had not been observed before. Others again are remarkable at once for their clinical acumen and critical insight. Many even of the most important are utterly unknown to the literature of this country, and it seems to be my duty, even at the risk of being here and there somewhat tedious, to mention, to an extent proportionate to their value, the different writings on the subject. Hippocrates, like many other writers of antiquity, has suffered at tlie hands of his admirers, and his works have so often been wrested to suit the individual views of subsequent authors, that his name is only mentioned here with a certain degree of reluctance. It seems almost beyond doubt, however, that in the First Book of the Epidemics he makes reference either to the type of breathing about to be considered or to some nearly allied form of respiration. In describing the case of Philiscus, who died of an acute disease of a somewhat indefinite kind, accompanied by an enlargement of the spleen, he remarks : ^ — " Tovrecp Trveu/uLa Sia TeXeog, wcrxef avaKoXovfjievw apaiov, jut-eya. In this case, the respiration until the end, like that of some one recollecting himself, was infrequent and deep;" or, as it has been rendered by Adams,^ "The respiration throughout, like that of a person recollecting himself, was rare and large." The last-named author remarks in a footnote, — " The modern reader will be struck with the description of the respiration, namely, that the patient seemed like a person who forgot for a time the besoin de respirer, and then, as it were, suddenly recollected him- self. Such is the meaning of the expression as explained by Galen in his Commentary, and in his work, On Difficulty of Breathing." In his learned address on Medicine, delivered before the Edin- burgh meeting of the British Medical Association, Warburton Begbie^ called attention to this observation of Hippocrates, and the matter is put so clearly that it will be well to quote his words : — " It is, however, in respect to the peculiar character of the breathing that the case of Philiscus acquires its chief interest, and it is in this particular that a resemblance is to be found between the ancient and the modern examples now quoted. The attention of Hippocrates had been arrested by the peculiar char- 1 (Euvres completes d' Hi2)pocrate, par E. Littre, tome ii. p. 684. Paris, 1840. 2 J%e Genuine Works of Hippocrates, vol. i. p. 371. London, 1849. 3 British Medical Journal, vol. ii. for 1875, p. 164. irrsTOKifAL 3 nctcr nl tlic lutMtliiiiL,' wliicli existccl throughout tlihen(inienon, after re- ferring to the .state of the pulse which was extremely irregular, in the following manner: — "Mais ce qui etait bien plus extraor- dinaire que cette irregularite, c'etait une suspension absolue, uue f^riation des mouvements du poumon pendant vingt-cinq ou trente secondes, a chaque trente-cinquieme ou trente-sixifeme respiration ; alors le jeu de I'organe se retablissait pen i\ pen, et ])ar uue gradation trfes sensible, il reprenait son energie oidiuaire, pour cesser de nouveau t\ pen prtis ;\ I'instant marqud." It will be ol)Served that the a.scending phase of C'heyne-Stokes respiration is accurately described in the quotation just given, although there is no mention of a period of descending respiratit^n, and it is impossible to avoid coming to the conclusion that ' Journal de In Svci^t^f de M^decine r( de PhcniiKtrie de PI.. 267, lfS84. 4 CHEYNE-STOKES RESPIRATION. Nicolas had before him a typical example of the breathing now under consideration. With the exception of the observations made by the Father of Medicine and by the learned physician at Grenoble, the peculiar form of breathing which we are about to consider remained unnoticed until Cheyne, who carried the torch of medical science from our own shores to those of the sister island, observed it anew. In reporting' a case of fatty degeneration of the heart, he thus describes tlie type of the respiration: — "The only peculiarity in the last period of his illness, which lasted only eight or nine days, was in the state of the respiration. For several days his breathing was irregular ; it would entirely cease for a quarter of a minute, then it would become perceptible, though very low, then by degrees it became heaving and quick, and then it would gradually cease again : this revolution in the state of his breathing occupied about a minute, during which there were about thirty acts of respiration." Tn the description of the dissection, it is noted that there were between three and four ounces of fluid in the ventricles of the brain. A very interesting observation, which has most frequently escaped the notice of subsequent writers, is contained in a footnote, where Cheyne remarks:^ — "The same description of breathing was observed by me in a relative of the subject of this case, who also died of a dis- ease of the heart, the exact nature of which, however, I am ignorant of, not having been permitted to examine the body after deatii." Berton^ mentions changes in respiratory rhythm as being a common symptom in cerebral inflammations, and quotes some remarks by Dance, in which breathing, not very unlike that under consideration, is described. Subsequent French writers on children's diseases follow in the same path. It has been stated that Flourens, in the course of his celebrated experiments, observed the occurrence of periodic breathing as the result of injury to the nerve centres. But in the first edition of his work* there is no reference to such a phenomenon, while in ^ Dublin Hospital Reports, vol. ii. p. 216, 1818. 2 Ibid., p. 222, 1818. 3 Traite des Maladies des Enfants, p. 67. Paris, 1837. * Recherches Exp&imentales sur les Prop'ie'te's et les Fondions du Systeme Nerveux, dans les Animaux Vertebre's, p. 168. Paris, 1824. HISTORICAL 5 the second edition tlie exact condition wliidi is nienlionc.l admits of considiTiible di)ul»t. In tlic second edition, wlien critici.sin;,' the observations of Marsliall Hall, and describing the results of some experiments on tlie medulla oblongata,* he says: — "Je repetai cette experience, sur un lapin. L'aniinal survecnt a Toperatinn pendant a pen prbs vingt-deux minutes: sa respiration netait plus, k la verite, continue ; mais elle se reproduisait de temps en temps, et surtout quand on irritait I'animal." Such arrests of the respiration, as will be seen later, are regarded by some authors as belonging to the same series as Cheyne-Stokes respiration ; they are looked upon as essentially different by others. West'^ briefly refers to irregularity of l)reatliing as frequently occurring in intlammations of the brain and meninges, and later authors in this country also do so. Stokes, whose name, as well as Cheyne's, is now indissohibly bound up with the peculiarity of breathing in question, made it pathognomonic of fatty degeneration of the heart, Speaking of the symptoms of this condition he says:^ — " Rut there is a symptom which appears to belong to a weakened state of the heart, and which, therefore, may be looked for in many cases of the fatty degeneration. I have never seen it except in examples of that disease. The symptom in question was observed by Dr Cheyne, although he did not connect it with the special lesion of the heart. It consists in the occurrence of a series of inspirations, increasing to a maximum, and then declining in force and length, until a state of apparent apncea is established. In this condition the patient may remain for such a length of time as to make his attendants believe that he is dead, when a low inspiration, followed by one more decided, marks the commencement of a new ascending and then descending series of inspirations. This symptom, as occurring in its highest degree, I have only seen during a few weeks previous to the death of the ])atient. I do not know any more characteristic phenomena than those presented in this condition, wiiether we view the long continued cessation of breathing, yet without any suffering on the part of the patient, or the maximum point of the • Rechtrchfs Kxj>f'riiiu'titahs sur Us l'roprii(e's tt Us Foiic(i'»i.g du Syateme Nerveux, dans Us Animanx Vertebre's, Douxi(iinc t-dition, p. 2(>(i, 1842. 2 Lectures on the IHstates of Infancy and ChiUlhood, p. 16. Lomloii, 1848. » The Diseases of the Heart and of the Aorta, p. 324. Dul.liii, 1854. 6 CHEYNE-STOKl<:S RESPIRATION. series of inspirations, when the head is thrown back, the shoulders raised, and every muscle of inspiration thrown into the most violent action ; yet all this without lale or any sign of mechanical obstruction. The vesicular murmur becomes gradually louder, and at the height of the paroxysm is intensely puerile. " The decline in the length and force of the respirations is as regular and remarkable as their progressive increase. The inspira- tions become each one less deep than the preceding, until they are all but imperceptible, and then the state of apparent apnoea occurs. This is at last broken by the faintest possible inspiration ; the next effort is a little stronger, until, so to speak, the paroxysm of breath- ing is at its height, again to subside by a descending scale." Hasse,^ writing a year later than Stokes, observes, in describing the symptoms of tubercular meningitis, that " long pauses occur now and then, as if the patients had for the time forgotten inspira- tion." This may, however, have been an allied type of intermittent respiration. Schweig,^ writing in ignorance of previous observations, brings forward periodic breathing as a new symptom, and it is clear from liis remarks that he had the true plienomenon of Clieyne and Stokes before him. He records several cases. In all there was a comatose tendency preceding or accompanying the onset of the symptom in question. After death, one was found to have thickening of the skull, several ounces of fluid in the left ventricle, a flabby, but otherwise healthy, heart, old tubercular masses in the pulmonary apices, and abdominal adhesions. No notice is taken of the state of the kidneys. The second, in which the author states there was no change in the pulse during the phases of the breathing, had thickening of the skull, dropsy of the ventricles, old tubercular lesions in the lungs, and atheroma with cardiac hyper- trophy. The state of the kidneys is not mentioned. The third was a case of renal disease with hypertrophy of the heart, dropsy of the pleurae, and oedema of the legs. Here again it is noted that neither phase of the respiration had any influence on the pulse. The head was not examined after death. In the fourth case there was atheroma of the vessels with fatty degeneration of the heart, ^ Handbuch der speciellen Pathologic und Therapie, redigirt von Rudolf Virctow, iv. Band, i. Abtheihmg, S. 473. Erlangen, 1855. ^ Aerztliche Mittheilungen mis Badev, xi. Jahrgang, S. 49, 1857. HISTORICAL. 7 thickening of the skull, and a considerable quantity of fluid in Out left ventricle of the brain. The kidneys receive no nnticn. lit; lays stress in all these cases on the comatose tendency, and in the three wiiose heads were e.\aniined ,', i.\. Tlu-il, i. Hainl, S. 324. Luhr, 1858-59. 8 CHEYNE-STOKES RESPIRATION. every pressure upon it, makes the breathing less frequent and more laboured. "h. If the haemorrhage be larger or the pressure greater, a peculiar symptom is observed in different mammals, the like of which I liave as yet sought in vain for in human pathology, and to which I may direct the attention of physicians. The respirations entirely cease for a quarter of a minute or half a minute, then begin gradually, increase their rate, and afterwards wane, until a new pause occurs. This appears to be caused by variations in the amount of the pressure, which is of necessity dependent on the power of the heart beat." From this it is evident that Schiffs attention had never been called to the observations of Cheyne, Stokes, or Schweig. Eeid,^ in reporting two cases of aneurism with this symptom, one of a man aged 60, the other that of a woman aged 59, notes that the pulse was periodically irregular, becoming less frequent during the respiratory distress, and more so when the distress was lessened. In another paper^ the same author describes a case of aortic and mitral disease, without any change in the texture of the muscular walls on dissection, and from a study of it he concludes " that the symptoms of respiratory distress must henceforth cease to be looked upon by me as pathognomonic of fatty degeneration of that organ." He observes that in this patient " the pulse became invariably slow %vhen the distress was greatest^ and as invariably quick when it was subsiding, or whilst the patient had ceased to breathe." He is inclined to think that this change in the pulse is not a mere coincidence, " but that it and the distress stand towards each other in the relation of cause and effect ; " he does not, however, venture upon any theory. Trousseau^ mentions, as characteristic of cerebral inflammations, a symptom, which, if not exactly the same as Cheyne-Stokes respiiation, has a great resemblance to some forms of that type of breathing, as it has not only the cessation of respiration, but also the ascending and descending phases. Eeferring to this subject in the third edition of his treatise, ^ The Dublin Hospital Gazette, vol. vi. p. 308, 1859. 2 Ibid., vol. vii. p. 133, 1860. 3 Clinique Medicate de I'Hdtel-Dieu de Paris, tome ii. p. 318. Paris, 1862. IIISTOIMCAL. y Walslie^ remarks: — "I cannot avoid infenini; that tlie i»roxiniate cause lies in a failure (»(' the special nervous excitant of the respiratory act — in auiesthesia either of the vagus or of the medulla oblongata itself." This opinion is simply adhered to in the last edition of the work.- Ill a lecture by Laycock, reported by Kopes,*'' there is a descrip- tion of the peculiar breathing, and it is stated that the most probable explanation of the phenomena " is that a sentient palsy of the respiratory centre occurs, or a paresis of reHex sensibility of the mucous membrane of the lung." In a research undertaken with a view to solve some physio- logical and pathological questions connected with the brain, Leydeu^ notes that when the pressure is abnormally raised in animals there are changes in the respiration. The breathing became irregular, long pauses separating periods, during which respirations rapidly succeeded each other, so that, as the author states, there was a similarity to Cheyne-Stokes respiration ; there was never such a regular periodicity of the events or transition from the breathing to the pause. It is of interest to observe that in this contribution, in addition to changes of sensibility, mobility, and intelligence, the author noted alterations in the pupils. Head ^ recorded a case wliich presented this symptom, and in which fatty degeneration of the diaphragm was found after death, with atheromatous degeneration and dilatation of the aorta, and aortic incompetence. In this paper is a full notice of the condition of the pulse during the two stages of apnc^a and dyspnoea; from tracings taken by Grimshaw it was observed that the pulse was as strong during the former as the latter phase, while tracings obtained from another case under the care of Little showed stronger pulsations during the cessation of respiration. This type of respiration is said by von Dusch" to occur in ^ ..-1 rmctical Treatise on the iJtseases of the Heart aiid Great Vuistls. Tliinl eiUtioii, p. .345. Loiulon, 1862. '■^ Iliid. Fourth edition, p. 407. London, 1873. 3 The McdUal Journal for 1864, \\ llG. * Archil' fiir p(ithy tlie cerebral lesion ; that this produced arrest of the resjiiratioii, that the centres aft(!r ft certain time re;^'ained their excilal)ility sulUcieutly to relh^t a motor impulse, thus re-establishing respiration, but that btiiug weak, the centres could not sustain tlie elTort and apurea again occurred, and so on. He therefore concludes that tliere must in every case be a diseased condition of the circulatory and of the nervous mechanism, a ddulile patliological condition, wliich he states as follows : — " 1. A certain diseased state of the heart, by reason of which, indirectly, the excito-motor impulse upon the nervous centres, conveyed tlirough the pulmonary branches of the pneumogastric, is diminished. " 2. A certain weakened state of those nervous centres, by reason of which the reflecto-motor impulse is diminished." This brings us to the period of the classical clinique, in which Traube expounded his theory, published by Frautzel,^ and re- printed in his collected works.^ Describing a case of aortic and mitral disease, with hypertrophy of the left and dilatation of the right ventricle, in which the phenomenon appeared after a sub- cutaneous dose of morphine, he takes the opportunity to mention the first case in which he had met with this symptom — one of cerebral haemorrhage — and refers to other instances of cerebral haemorrhage, as well as cerebral tumours, tubercular meningitis, and uroemic coma, M-hich presented it. He concludes, therefore, that the peculiar type of respiration may occur in two classes of patients: 1. Those M'ith healthy hearts, but diseased contents of the cranial cavity ; 2. Those with healthy contents of the cranial cavity, but diseased hearts. He further observes that the duration of the periods may be .so short, and the pauses so inappreciable, tiiat the phenomenon may escape notice ; that, towards the end of long pauses, muscular twitchings may occur closely resembling those seen when the artificial respiration is su.spended in slightly curarised animals ; and that sometimes during long pau.ses the tension of the arteries ri.ses, while the pulse-rate diminishes. He proceeds to point out that all the cases in which the pheno- ' Berliner kl ill hche Wochfmchrift, vi. .laliiuMii;,', S- -77, l^fiO. * Gesammelte Beitriige zur Patholoijii nnd I'Inj.'iiolojif, ii. Bainl, S. SS2. lUiliu, 1871. 12 - CHEYNE-STOKES RESPIHATION. menon is present have one characteristic — they have all a diminu- tion of the supply of arterialized blood to the medulla, where the respiratory centre is situated. There is thus a smaller supply of oxygen, of w^hicli v^e know that it, in a higher degree, influences the irritability of the cellular nervous elements. Through this lessened amount of oxygen the irritability of the nerve cells becomes so much lowered that a larger quantity of carbonic acid is required to cause an inspiration, and therefore the time within which the carbonic acid will accumulate in suflicient quantity is lengthened. This is similar to the effects of section of the vagi, in which long pauses occur in the respiration, attended by dyspnoea. The respiration may be excited in two ways : 1. By the pulmonary fibres of the vagus, whose peripheral terminations are probably washed by the blood, and whose central ends are connected with the respiratory centre ; and 2. By the afferent nerves coming from all parts of the body, which are able to send a sufficient stimulus to the medulla, as in the case of dashing cold water on the skin, and the well-known effect of the gastric portion of the vagus on the respiration. The difference between these two is this, that the pulmonary endings of the vagi are bathed in blood containing much carbonic acid, while the others have a supply of blood which contains but little. If both be equally irritable, then in health only the pulmonic vagi will be called into action. If the vagi be cut the respiratory centre can only be excited by the other nerves, and this can only happen when the blood circulating throughout the body is as rich in carbonic acid as that normally passing into the lungs. It must be borne in mind that the number of the vagus fibres is incomparably smaller than that of the other nerves ; when these latter act, therefore, the effect is correspondingly greater, and simple respiration becomes dyspnoea. Applying this reasoning to the phenomenon in question, we find that the lessened irritability of the respiratory centre, caused by the cerebral pressure, or ursemic blood, or deficient arterial supply, requires a larger amount of carbonic acid as a stimulus, and thus there is a long pause. When this gas has accumulated in sufficient quantity it first stimulates the pulmonary terminations of the vagi, but, as was shown long before by Traube, the strongest stimuli applied to the vagi never cause dyspnoea, and this only causes the shallow breathing which appears first after the pause. The amount of carbonic acid HISTORICAL. 1 ^ menntime increases sufficiently to cause stimulation of the nerves coming from the skin and otlier parts of the hody, ami hence the dyspnoea sets in. The (piantity of the gas is greatly diminished hy the forcible breathing, and the e.xcitement of the other nerves ceases, so with the action of the vagi alone shallow breathing again occurs, until there is not enough carbonic acid gas to excite the pulmonary endings of the vagi, and a pause sets in anew. Traube ends by calling attention to the fact that the morphine directly induced the peculiar respiratory rhythm by reducing the irritability of the respiratory centre in a case where it was already at a low ebb. Mader' describes five cases in which Cheyne-Stokes respiration was present ; an extravasation into the floor of the fourth ventricle ; a tumour between the medulla, pons, and cerebellum ; an extra- vasation reaching from the right optic thalamus to the medulla ; an enlargement of the vertebral artery compressing the medulla ; and, lastly, renal disease with a tumour of the pons. He main- tains that the cause of the phenomenon must be sought in anatomical changes in the medulla oblongata, and opposes the vie'.v of Traube that the respiratory change can take place, without any palpable changes in its structure, through alterations in the circulation. Hesky, - observed the occurrence of Cheyne-Stokes breathing during the course of a fatal case of enteric fever. The chief point of interest in his description is the fact that the pulse almost ceased during the long pauses; the pulsation, indeed, appeared to become less before the respiration began to diminish. The section gave evidence, in addition to the characteristic abdominal lesions, of congestion of the brain and medulla, particularly of the floor of the fourth ventricle, and more especially of the points of origin of the vagus and hypoglossus. The author is of opinion that the cause of the symptom is a smaller access of oxygenated blood to the centres, produced by the lessened activity of the circulation. Esenbeck^ describes the case of a man, aged G2, l)elonging to an apoplectic family, and subject to no affection beyond nervous palpita- * JViener mfdicinischc Jfochenscri'/t . xix. P>aiiscli<: lUgpiratioHJi-Phuiiviiieii. Urv.-'lau, 1S70. 16 CHEYKE-STOKES RESPIRATION. to be the presence of purulent exudation surrounding the medulla oblongata. No trace of this observation is to be found in litera- tare elsewhere, and Professor Erb informs me that he lias never written or spoken on the subject. Lutz' describes a case of scarlatina followed by suppuration of the ear and cerebral symptoms, during the presence of which the respiration assumed this peculiar rhythm, Bjornstrom^ says that the phenomenon is probably not so rare as might be imagined from the paucity of literature concerning it, and describes three cases which he had seen. The first, a child ihree months old, was ill with capillary bronchitis, and during the last four days of life manifested this phenomenon. The second patient, aged seventeen years, suffered from tubercular meningitis, but here the symptom was not typical, and was accompanied by divergent strabismus. The last case was that of a patient of the age of seventy years affected by fatty degeneration of the heart. The author regards Cheyne-Stokes respiration as lethal. He does not approve of Traube's theory, but declines to formulate another. He further objects to the name by which the symptom is known. In the discussion which followed the reading of this paper, Glas mentioned that he liad seen stoppages of breathing in a case under his care, and a description of the case is given further on^ in the same publication. The patient in this case, who was a man aged 70, suffering from traumatic gangrene, had pauses in the respiration, without any change in the state of the circulation. Heidenhain,^ in a most interesting • paper on Cyon's theory of the central innervation of the vaso-motor nerves, points out that he has observed the Cheyne-Stokes phenomenon in chloralized animals, and he gives a tracing showing the rhythm of the respiration, which perfectly corresponds with that which we obtain in cases of disease in man. He draws attention to the fact that during the respiratory period the blood-pressure rose slightly. ^ Deutsches Archiv fiir klinische Medicm, viii. Band, S. 123, 1870. 2 Upsala Lakarefdrenings Fdrhandlingar, vi. Band, S. 307, 1870-1871. 3 Ibid., vi. Band, S. 315. * Archiv fiir die gesamvite Physiologic des Menschen und der Thiere, iv. Jahrgang, S. 554, 1871. HISTORICAL. 17 liriukner' inaki's n liricf n-fcrrnci.' in IS71 t(j tin; fiict that lii.s ilcceased fatlier liad, twenty-two years before the date of his coniinuiiication.caHcd hi.s attention to the phenomenon of f.'lipyne- Stokes respiration, and given it the name of " penduhini-like breatliing," because the alternation of the breathing and the ]iaiises is as regular as tlie swinging of a pendulum. Tlie author mentions that ho has fretjuently watched the .syniptom, particu- larly in cases of tubercular meningitis. Rehn''^ dcscril)es two cases (»f pulmonary disease in children, which jiresented this symptom. One was a child of one year of age, suffering from inieumonia; the other an infant si.\ weeks old labouring under l)ronchitis. For the e.x'iilanation of the jilieno- menon he accepts the theory that there is a lessened access of arterialized blood. MerkeP records a case in which the patient, who suffered from renal disease with cardiac dilatation and pulmonary emphysema, was attacked by apoplexy a year before his death. During the cerebral symptoms, Cheyne-Stokes respiration made its appearance, and during the pause, narrowing of the pupils and absence of reaction to light were observed, along with dulness of the mind. The autlior mentions that when a question was asked at the end of a ])eriod of breathing, it was answered at the beginning of the next period after the termination of tlie intervening respiratory pause. The patient recovered from this seizure, and on his death, about a year later, it was found tliat in addition to granular kidneys, emphysematous lungs, and a dilated and hypertrophied heart, with cyanotic atrophy of the liver and spleen, there was destructive disease in the corpus striatum, optic thalamus, and pons. In another ca.se narrated subsequently,'* the .same author found tiiis type of respiration in association with endocarditis and embolism of one of the posterior branches of the right artery of the Sylvian fossa. He found that even with total absence of reaction to light the pupils became di.stinctly smaller at the beginning of the pause. ' Archil' fiir yatholo{iische Anatomie nnd Physiologie und fiir klinische Median, lii. Band, S. inr), 1871. - Jahrhiirh fiir Kinderheilknnde nnd jdiysinchc Erziehung, lunv Ki'l;,'^, iv. JnliiKiin^', S. 432, 1871. 3 Deut.iches Archiv fiir klinijiche Mediciu, viii. I'aiul, S. 4-2\, 1>1\. * Ibid., X. Baiul, S. 201, 1872. C 18 CEIEYNE-STOKES EESPIUATION. Scliepelern^ describes several cases in which he met with this type of breathing, and adds to the rapidly advancing store of know- ledge in regard to the symptoms associated with it. The first patient was a man, aged 54. In this case the phenomenon appeared after a period of breathlessness and palpitation. The patient felt most comfortable at the beginning of the apnoea, and became unconscious towards the end of it, but could be awakened out of this state, and was able to talk during the pause. No con- vulsive or involuntary movements were present in the muscles or eyes. Ophthalmoscopic examination of the eyes showed nothing beyond a slight patch of haemorrhage near one papilla, and fulness of the veins. There was no variation in the size of the vessels of the fundus during the changing phases of respiration. The patient could be caused to breathe during the pause of respiration by constantly ordering him to do so, and this lessened the subsequent period of dyspnoea. Electric stimulation of the phrenic nerves during the pause produced no result. The relative duration of the apnoea and dyspnoea was not affected by sleep. The pulse remained small throughout the different phases of respiration, without apparent change in strength or tension, but the number of pulsations was less during the period of breathing, probably from intermission which was present. On section the heart was fatty, the aorta and arteries, especially the vertebral and basilar, atheromatous, the liver was fatty, and the kidneys cyanotic. The second case was that of a man, 75 years old, suffering from bronchitis with ascites and albutninuria. The Cheyne-Stokes respiration was well marked, but was not attended by muscular twitchings or pupillary variations. The patient could be made to speak during the pause, but could not be caused to breathe during that phase, and electric stimulation of the phrenic nerves pro- duced no result. There was no alteration in the rate or strength of the pulse during the changing respiratory phases. There was no examination after death. The third case was that of a man, aged 69, of gouty habit, suffering from aortic disease and cardiac hypertrophy with albu- minuria. There was no autopsy in this case. The fourth patient, a woman about 60 years old, was affected 1 Hospitals- Tidende, xv. Aargaiig, S. 77, 81, og 85, 1872. HISTOIIICAL. 19 l>y mitral disease. On section there was stenosis and incompetence of tlie mitral orifice and valve, with liypertrophy of tlie left and dilatation of tlie riglit ventricle, and a fatty heart. There was degeneration of the cerebral arteries and old tubercular disease of the apex of the right lung. Schepelern supports the theory of Tranbe.and believes the dulness of the mental faculties to be caused by the presence of an excess of carbonic acid in the blood. He does not approve of the view ad- vanced by Traube, tliat the mental obscurity is the result of cerebral anaemia. The dyspnoea he attributes to the action of the carbonic aciil oil the sensory nerves, and he compares this to the forced breatliiiig seen after section of the vagi, when the sensory nerves alone act as the respiratory stimulants. He states that he has never seen any deepening of the symptoms after the use of morphine or chloral. In conclusion, he describes another case, that of a man, aged 39, who, after paralysis of the left side with loss of speech, suddenly became uraimic, with delirium and sopor, and paralyzed on the other side. During the unconsciousness, which deepened into coma, the characteristic Cheyne-Stokes respiration appeared, and with it changes in the pupils were observed. They became larger during the period of respiration, even after the application of atropine, and the author regards the dilatation, therefore, as purely due to the influence of the sympathetic nerve. Nothing note- worthy could be seen on ophthalmoscopic examination of the eyes. On section, the kidneys were found to be granular, the heart degenerated, the arteries atheromatous ; there was also thrombosis of the cerebral vessels and patches of softening of the brain, but the pons and medulla were healthy. lioth places two cases on record,' — one, that of a child, aged 7 months, suffering frdin meningitis, the other, that of a girl, with ura-Miia and eclampsia, in which the typical respiration was present. Korber- describes the symptom as it occurred in a boy of 9 months, suffering from tubercular niLMiingitis, and notes that during the pause a certain stiffness of the paralyzed limbs cnme on, while during the period of breathing they were quite flexible. > Deutsches Archiv fiir kliuMie Malicin, x. IJiuul, S. 31n. 1S72. - Ibid., X. Band, S. C(K), 1872. 2D CHEYNE-STOKES KESPIRATION. A paper by Filehne^ deserves mention here, as in it be points out tbat after section of tbe vagi it is possible to cause apnoea, and carefully discriminates between true apnoea, or arrest of respiration from excessive oxidation of the blood, a;nd arrest of respiration caused by other conditions. Laycock^ enters very fully into the phenomenon of " Brief Eecurrent Apnoea," as he terms the Cheyne-Stokes respiration, in a very interesting lecture, but he cannot be regarded as adding anything of importance to the pathology of the condition. It is a singular, nay, even startling fact, that he makes no mention of Traube in his remarks, although in them he does full justice to most of those who had written on the subject in the vernacular. He refers to the case which has been already mentioned in connexion with his name. The same writer immediately afterwards contributed another paper on this subject to medical literature^ which is substantially the same as that to which reference has just been made. Two or three months after the publication of Laycock's remarks, Bernheim,^ who had the good fortune to be present at the historic clinique when Traube expounded his theory, gave an excellent review of much of the work that had been done on the Continent, along with an account of four cases which he had himself observed. These four cases were respectively — heart disease with emphysema; chronic alcoholism with nephritis ; pulmonary tuberculosis and dilated heart ; and the result of a fall from a great height. He points out that Cheyne-Stokes respiration is only the highest expression of a series of similar phenomena, in the less marked of which tliere is no pause, but alternations of deep and shallow breathing, and he gives the result of a careful study of the eye and pulse during the phases of the respiration. The pulse he describes as being sometimes altered, and at other times unchanged during the alternations of dyspnoea and apnoea. Like Leube he found that electricity would stop the pauses for a time. ^ Archiv fiir Anatomie, Physiologie, und ivissenschaftlichen Medicin, Jahrgang 1873, S. 361. 2 The Medical Times and Gazette, vol. i. for 1873, p. 433. 2 The Dublin Journal of Medical Science, vol. Ivi. p. 1, 1873. * Gazette Hebdomadaire de M^decine et de Chirurgie, Deuxieme Serie, tome x. p. 444 et p. 492, 1873. HISTORICAL. 21 Monti, ill an cxlianstive research inb) tin* jiliysical ('Xiiininiilitli:.i)U!sychischg€richtliche Medicin^ XXX. Baii.l, S. 419, 1874. •26 CHEYNE-STOKES RESMRATION. variation in tlie state of the pupil or pulse. It is interesting to notice that in two of these cases the periodic breathing was associated with epilepsy, and Zenker points out in this connexion that it is due to the proximity of the respiratory and convulsive centres. In regard to the causation of the phenomenon, Zenker says that there can be no doubt it is due to a disturbance of the respiratory centre, for the explanation of which it is necessary to clear up several physiological and pathological questions. Baas ' describes the phenomenon under the name of " inter- mittent respiration," which he prefers to the designation by which it is commonly known. In his contribution he records the case of a female child, not quite eight weeks old, who suffered from diar- rhoea and hydrocephalus; the patient, amongst other symptoms, such as coma with left-sided ptosis, and later, right-sided mydriasis, developed Cheyne-Stokes respiration, which continued for the last five hours of life until death took place. The author calls attention in this case to the early period of life at which the symptom occurred ; shows that it was caused by acute hydro- cephalus ; that it was associated with unconsciousness ; that in this, as in some other observations, the increase and decrease of the respiratory energy was less characteristic than the regular intervals of both phases of the breathing ; and points to the prob- ability that the condition was caused by one-sided pressure on the respiratory centre, as shown by the ptosis and dilatation of the left pupil in the early stage. Benson, whose previous observations on this subject have been already referred to, brought the matter before the Medical Society of the Irish College of Physicians,^ and in briefly detailing tlie facts of a recent case, took occasion to mention some of the theories which had been propounded, and to compare Traube's explanation with his own. He points out that in the case which he recorded, in which there was hemiplegia followed by cardiac failure, the peculiar type of respiration did not appear until the cardiac symptoms had added themselves to the cerebral, adding that in the previous case which he narrated the phenomenon only appeared after the cerebral symptoms had added themselves to the cardiac. 1 Deutsches Archiv fiir klinische Medkin, xiv. Band., S. 609, 1874, and Zur Percussion, Auscultation und Phonometrie, S. 264, Stuttgart, 1877. 2 The Dublin Journal of Medical Science, vol. Iviii. j). 519, 1874. IIISIOIMCAF,. 27 l''nl]n\\ iiiL: rxMi-^nii's iciiiaik^, Ilciiiy Ivriiiicilv iiiontioned^ that lu; liiid lii'fii It'll tn (lie (;()iiclu.si()ii lliaL llic; sy iiii>L(tlii was more nr less counseled with the iiervDUS system L^^eiieniliy ralJicr thaii wiili any jiarl icular di^mii comiecLcil wilh llio chust, wliicli vic^w was (j()iiliniic(l liy soiiK' coiiiiiion ]>li('n(jmi!iia, suuli as the altcralioii ftf" brtMiliiii^ in slcc]), sliowin^? tluit the breathing may vary in health ; the ciicliial liii Milling of Graves in fever; or the clianges of respiration in hydrocephahis. lie thouglit there was evidence enough to piovc that a temporarily modilied state of the nervous system might be capable of altering and modifying the breathing. ]Ie mentioned an interesting fact that, in j)atients showing this ty])e of respiration, the ascending and descending character dis- apiK-aicd when tliey were placed on their sides. A case of diphtheria in a boy 2^ years old afforded v. Hiitten- l)renner- the opportunity of studying Cheyne-Stokes breathing, whicii he attributes in this instance primarily to weakness of the heart from the diphtheritic poison. He n^fers to the Traube- lllehne controversy, but refrains from criticism. Ihill'* has placed three cases on record in which the peculiar breathing in question was noticed. The patients in whom it ap- ]iear(Ml siillrreil fiom chronic renal disease, with sclerosed arteries, hypcrtro})hicd heart, and cerebral Inemorrhage ; granular kidney, arterial atheroma, cardiac hypertrophy, and pericarditis ; and duo- denal cancer, in which, after the use of morphine for the agony caused by the disease, Cheyne-Stokes breathing appeared. In a letter which the author has kindly addressed to me, he states that he is not satisfied with any of the present theories. Hayden fully discusses the phenomenon in his work,'' and gives tlie following exj)lanation of it: — " I have already stated," he says, "that the only lesion of structure with which ihythmical irre- gularity of breathing lias been always found associated is athero- matous or calcareous change, with dilatation of tiie arch of the aorta, involving loss of elasticity in its walls. 1 lliiuk these changes sujiply the conditions of a rational theory ol' the pheno- ' Till- Dublin Joimial of Medical Scituce, vol. Iviii. p. 521. 2 Jahrburh fur Kinderhcilkumlc timl jihijuische Erzii/ivtuj, luui' I-'ul^'c. \iii, .ltibr;,'aii>,', S. 420, LsTf). 3 Norsk Mivinzin far Lmjcvideuskahfu, ill. Riu-kke, v. Bin. < The Disi'osni of the Hunt and uf (he Aorln, p. G32, UiiMiu, 1870. 28 CHEYNE-STOKES RESPIUATION, menon. During the period of greatest tranquillity of the heart's action, viz., in sleep or repose, the systemic capillary circulation fails, from want of the contributory aid rendered in health by the elastic reaction of the aorta. Hence arises a suspension of tissue- respiration, besoin de respirer, and accelerated or suspirious breath- ing, as shown by the experiments of Flint already referred to. Accelerated respiration must strengthen capillary circulation ; first, through the lungs, and then through the tissues of the body generally, by quickening the action of the heart and in- creasing its force. In proportion as the systemic capillary circulation becomes established, the lesoin de respirer is less urgent, and respiration gradually subsides, till a period of apnoea arrives. The descent of respiration below the normal standard would seem to arise from its previous excessive activity and the exhaustion of the patient. Now, again, comes a period of feeble action of the heart, and failure of capillary circulation, with its consequence of paroxysmal breathing. That imperfect circula- tion of arterial blood in the respiratory centre contributes in a special manner, and in a great degree, to the production of the respiratory derangement I have no doubt ; but the effect of this is not easily distinguished from that of a want of oxygen in the tissues of the body generally." Hayden also states that he has not observed marked alterations in the rate of the cardiac pulsa- tions with the different phases of the phenomenon ; only, " as in one or two cases, a slight acceleration during the period of dyspnoea, and a gradual decline in that of descent, till a minimum rate was reached on the accession of apnoea." Hazard^ records the case of a gouty lawyer, aged 54, who met with injuries in a railway accident at the age of 32 ; these caused paraplegia, from which there was only partial recovery. A blow on the head when 48 years of age impaired all his powers, and, in addition to some mental symptoms, there was after this date such evidence of a weak circulation as a frequent and irregular pulse, cyanosis, and dyspnoea. When seen he had weakness of both cardiac sounds without any symptom of valvular disease, and soon afterwards symmetrical gangrene of both feet set in, with absence of pulsation in any of the vessels of the lower extremities below ^ St Louis Clinical Record, vol. ii. p. 54, 1875. HISTOUICAL. 20 Scarpa's triangle. The patient had a great tendency to fall asleep, and when he do/ed Cheyne-Stokes res])iration apj)ear('(l. He dit-d from gradual extension of the gangrene u|)\vards, and uiiforlunaluly no post-ninitciii cxaiiiiiiat jnii was (ilii;iiiic(l. Tlic aulliur's diagnosis was fatty heart anil tlirombosis of the arteries of the lower ex- tremities. He enters into a long ])hysiol()gical argument without reaching very (ictinitc conclusions with regard to the causation of the res}>iratory rhylhni. Claus^ entered upon a criticism of I'ilchne's tiieory, based up(jn the observation of two cases under his care. The first part of iiis paper is historical, entering fully into the controversy between Traube and Filehne, and laying special stress on the statements made by the latter in regard to the oscillation of the blood-pressure seen when the vagi are intact, and absent when these have been divided. He then describes a case in which nitrite of amyl had no eflect on the periodicity of tlie respiration, which he tries to explain away by supposing that in Filehne's case the abnormal irritability of the vaso-motor centre was less pronounced than in his own. He will not allow that there is any evidence in favour of the view tiiat the cause of the phenomenon lies in any change of the quantity of blood supplied to the respiratory centre. From sphygmographic tracings, Claus concludes that there is an increase of blood-pressure at the end of the pause and beginning of the period of respiration, with a return to the normal pressure during the period of breathing and beginning of the pause, and that there is an increase of vascular contraction during the pause. He there- fore supports Filehne's theory as to the cause of the phenomenon. In a postscript to the paper the author narrates a second case, in which one inhalation entirely removed the periodic character of the breathing, while a second administration only partially modified its type. These results, however, he considers as being in favour of the theory to which he aiij)eai'S to have been predisj)n.seil. In an elderly jiatient, wliu dieil ajijiarenlly from caidiac failure, de Wette- watched the ]iheuomena of Cheyne-Stokes breathing tor thirteen day.^ and after a brief description of the case, he refers to Traube's theory. ' AUgei/ieine Zvitschrift fiir Puijclndtrit uud puijchuchjerkhtUclie Midicin, xxxii. Biuul, S. 437, 187.'>. - Con-espoiiden>BUtti fiir schiceker AcrJe, vi. .lalirgang, .S. 1-10, 187G. 30 CHEYNE-STOKES RESPIRATION. In a case of thoracic aneurism in an old man, described by de C^renville/ Cheyne- Stokes respiration was present for some days. No mention is made of the state of the pulse in the varying phases of the breathing, but the pupils are said to have remained in a condition of excessive contraction. The author takes the oppor- tunity of bringing forward an occurrence which seems to be unique — a case of intermittent respiration in a baby, one month old, caused by morphine taken by his mother. The mother had been suffering from neuralgia, for which she took a large dose of morphine, and next day the baby lost his appetite, became cyanotic, and fell into convulsions, attended by periodic breathing, during which the pupils varied in size, becoming larger with inspiration. Tlie infant recovered under appropriate treatment. In a case of cardiac dis- ease presenting Cheyne-Stokes respiration, de Cerenville found that morphine caused a diminution in the extent of the respiratory phenomenon, while neither digitalis nor bromide of potassium had any effect of the kind. Eoss^ describes the occurrence of Cheyne-Stokes breathing after the hypodermic administration of half a grain of morphine to an intemperate person of 40, who was found in convulsions almost entirely confined to the left side, with pupils of natural size. After the use of the morpliine the convulsions ceased and the pupils became contracted, while typical Cheyne-Stokes breathing made its appearance. The author notes that during the pause in the respiration the limbs became rigid, and relaxed again when the breathing began. This type of breathing made its appearance within four and a half hours of the time of the administration of the morphine, it remained for about six hours, and ceased five hours before death. The thoracic organs presented no abnormal symptom, and the urine was healthy. At the post-mortem examination the various organs of tlie body were found to be perfectly healthy. Biot^ carefully describes this type of breathing as it occurred in the case of a patient suffering from aortic and mitral disease, and for the first time publishes tracings of the pulse and respira- 1 Bulletin de la Socie'te medicate de la Suisse romande, dixieme annee, p. 152, 1876. 2 Canada Medical and Surgical Journal, vol. v. p. 544, 1876. 3 Contribution « Ve'tude du pMnomhie respiratoire de Cheyne-Stokes. Lyon, 1876. HISTORICAL. 31 tion. The pulse was rehiLively more frequent durijig tlie pause than duriufj the breathin<^, aiid llie tension fell durint; the former phase. He mentions several of the writing's which j)rece(kMl his work, ami criticises the rival theories of Traube and Filehne. He especially refers to the lessened arterial pressure during the apna'a, shown by his tracings, as being antagonistic to the theory of Filehne, which requires stimulation of the vaso-motor centre, and consc([uent contraction of the arteries duiing that jdiase. He mentions that the pupil was contracted during the pause, and states that chloral produced considerable benefit to the patient. In summing up he points out that the theory of Filehne is not applicable to all cases, but he declines, for the present, to formulate another. As a postscript he mentions the pauses of the respira- tion in meningitis, which he describes as being entirely irregular and sighing in character. He will not admit that such cerebral breathing belongs to the type of Cheyne-Stokes respiration, altlioufrh it is related to it. Pepper^ calls attention to the significance of Cheyne-Stokes re- spiration in cases of tubercular meningitis, and records two such instances in an interesting paper on the subject. In l)oth the cases which he describes there were variations in the condition of the circulation coincident with the changes in the state of the respira- tion, the pulse becoming less frequent during the cessation of the respiratory movements. The author regards the phenomenon as being caused by "a paresis or state of impaired sensibility and activity of the nervous centres of respiration," in which they cease to respond to the small quantity of carbonic acid in the blood when it has been oxygenated by active respiratory move- ments. It is worthy of note that Pepper refers to Begbie's mention of the case of Philiscus, described by Hippocrates, alluded to in the early part of this monograph, and it is permissible to (piote his words. " On reading the description of the case," he says, "which may pr(il)ably iiave been one of acute nephritis, with uriemia, in the original and in Dareml)erg's translation, however, I cannot see that anyLliing more is intended than the infrequent, deep breathing with long intervals, wliich is so often met with in states of partial or complete coma." ' l'hiladeli)hia Medical Times, vul. vi. \>. IIG, 187G. 32 CHEYNE-STOKES IlESPIEATION. Heiu* begins an elaborate contribution to the subject by stating that all arrests of respiration are not to be regarded as instances of Cheyne-Stokes respiration. He says that such irregular interferences with the usual rhythm are common in infants and children. He mentions that he has observed six cases of true Cheyne-Stokes breathing — two in patients suffering from Bright's disease, one of whom had a fatty heart, and the other oedema glottidis and pneumonia ; one in a patient who had induced fatty degeneration of the heart through alcoholism ; and three in patients dying of tubercular meningitis. He gives full details of a seventh case. The patient on this last occasion was an old lady, who had suffered for a long time from bedsores with profuse suppuration, in consequence of being confined to bed after a severe bruise to her left hip, and in whose case Hein diagnosed fatty degeneration of the heart. During the course of the illness Cheyne-Stokes breathing made its appearance, and, as it remained for five weeks, the author of this paper was able to make careful observations in regard to its phenomena. He calls attention particularly to the condition of the consciousness. He noticed, when she was sitting up, that during the respiratory pause, which took place with the thorax in the position of expiration, the head sunk forward as if in sleep, while with the commencing respira- tions she raised it again like one awaking from slumber. During the pause the eyes were shut as in sleep; she could be roused from this condition by loud speaking, showed her tongue when asked to do so, swallowed a mouthful of water, and could even speak a word or two, but the senses were dull ; with the first superficial respirations, however, the consciousness returned, she opened her eyes and spoke spontaneously, complaining particularly of her breathlessness. During the pause she could not be induced to breathe. At the end of the pause slight twitchings about the mouth were to be seen, but otherwise there were no involuntary muscular movements. No pupillary changes corresponding to the varying phases of the breathing could be determined, but this point was rendered difficult by the fact that there was a cataract in the left eye, while the lens and a piece of the iris had been removed from the right eye in a previous cataract operation. 1 Wiener medizinische Wochenschrift, xxvii. Jahrgang, S. 317 unci 341, 1877. HI.STOniCAL. 33 Hein points out that the fluctuations in the condition of the con- sciousness must be accounted fori)}' the same causes as those which give rise to the respiratory plumomena, and asserts that this j^ives a new position from which to consider the condition of tlie medulla oblongata. He allows that changes in the state of the consciousness have previously been noted in this condition, but shows that no one has called attention to the simultaneous return of the con- sciousness and the respiration, and holds that this fact is of such importance that he can only reject every theory that does not account for the return of the cerebral and medullary functions at the same time. He points out that the relation between the irrita- bility of the respiratory centre and the degree of respiratory stimu- lation must undergo a periodic change. Criticising the rival theories of Traube and Filelme, he remarks, in regard to the latter, that he has observed in a child, aged seven months, a fall of the blood-pressure in the great fontanelle at the time of the return of the breathing, and states, on the authority of Mayer and Friedrich, that amyl nitrite directly stimulates tlie respiratory centre and may thus cause regular breathing. He shows that the theory of Traube cannot account for the simul- taneous return of consciousness and respiration, while his own observation is in direct opposition to the hypothesis of Filelme, for it does not agree with his experience that in a patient suffering from cardiac weakness and its consequences, the dulness of the sensorium would be removed by means of a sudden contraction of the arteries and anaemia of the brain. Such an effect would sooner be produced by an arterial hypersemia through paralysis of the vessels, but such an explanation is negatived by the fact that the fulness of the vessels of the face and neck remained equal during both phases. He points out furtlier that the variations of the conscious- ness and respiration must have the same cause, and shows that in all his cases cyanosis was present, which, although arising from different conditions, has the same result. Just as is the case with tlie vitality in general, so in the medulla oblongata the irritability is le.s.sened, and hence interruptions in the breathing are caused ; it is open to question whether these breaks may not cause an influence on the circulation, so that what was a consequence may in other conditions be a cau.se. With a normal circulation such an effect he holds to be impossible, as Cheyne-Stokes respiration may be £ 34 CHEYNE-STOKKS RESPIRATION. imitated by the hour without any noticeable modification of the circulation. It is otherwise, however, when the blood-stream is retarded and oxygenation reduced, for if interruptions to the respiration take place, the functions are alternately increased and diminished, and such effects are shown in the medulla oblongata through variations in its irritability. The blood which has been arterialized during the respiratory period reaches the capillaries in greatest part at the beginning of the pause, at which time the circulation which had been quickened by the breathing becomes slower, while the tissue change is most active. The result is that the irritability of the medulla is again increased and the breathing begins. By means of the passage, during the breathing period, of the blood which has become venous during the pause, the tissue- change for the vitality necessary to the functional activity of the organ cannot be supported, the oxygen in the tissues is consumed without adequate compensation, and the irritability of the respiratory centre is lessened and suspended. It is again restored after arterialized blood has coursed through the vessels of the medulla and promoted internal respiration, as occurs at the end of the pause. That the irritability shows a stage of increase and a stage of decrease is due to the fact that the alternation in the conditions of the circulation and diffusion is gradual, not sudden. From the analogous conditions of the brain and medulla it is to be concluded that the respiratory nerve centre does not simply undergo a change in the degree of stimulation, but a periodic alteration of its own condition. Hein is of opinion that, although this theory of a periodic activity of the brain and medulla caused by variations in the amount of tlie tissue change is only hypothetical, it yet explains what he thinks cannot be otherwise accounted for. He holds that the frequent occurrence of the phenomenon in unconscious persons does not oppose his theory, for in such cases the periodic demand of tissue change may be so insignificant that, although it is in a position to affect the activity of the re- spiratory centre, it may not be able to influence the functions of the brain. Carrer' describes the case of a man, aged 60, who died of renal disease and cardiac failure. Cheyne- Stokes respiration appeared 1 Guzeta medica Italiana, Provincie Venete, tomo xx. p. 403, 1877. lIlSTOIMCAr.. 'Mj after tlie patient had iireseiited various head symptoms for some (lays, and remained h)n<^ enough to allow the author to mak(.' a number of interesting observations. He mentions that during the ]»i>riod (if breathing the pupils were dilated, while they were con- tracted in tiie ])ause. The ])ulse was less frequent during the former than during the latter phase; and spliygmographic tracings taken during these phases showed a difference in character, the jtulsalions being larger, but less regular, during tlie dyspno-a than (hiiing the apncea. It is of interest to note that the autiior f(juiid the a})n(ea could be interrupted by powerful stimuli : the aspersion of cold water, for e.\am{)le, caused a deep Ijreatli followed by dyspnoea. The peculiar riiythm of the respiration remained until the death of the patient — twenty-five days after its first appearance. At the post-mortem examination it was found that the ventricles of the brain and subarachnoid spaces were distended with fluid ; the pleural cavities contained each a litre of fluid ; the heart was hypertrophied ; the aorta dilated and atheromatous ; and the kidneys contracted. There was, in addition, a perforating nicer of the duodenum, Carrer, in conclusion, passes the opinions of other authors in review. Broad bent ^ describes the occurrence of Cheyne-Stokes breath- ing in a case of apoplexy witli right-sided hemiplegia. There was no alteration in the state of the pulse or heart during the varying phases of the symptom, but movements of the left leg were observed towards the end of the pause. He states that he has often watched it in uraemic coma, and on some occasions in sinking from exhaustion, as well as something very like it once in the case of an elderly gentleman in his usual health. He thinks that the effect of the phenomenon on the pulse varies, and remarks, " All the theories on the subject are unsatisfactory, and I have none of my own to of^er." Wharry - places on record four cases in which tlie symptom occurreil These were mitral disease with aortic dilatation, aortic and mitral disease, nephritis, and typhoid fever with pneumonia. Andrew ^ describes the phenomenon as occurring in a case of tyiihoid fever, which ended in recovery. 1 The Lancet, vi.l. i. for 1877, p. 3(>7. - Ibid., \\ 3G8. 3 iii,i^ J, 385, 36 CHEYNE-STOKES UESFIRATION. Treves ^ mentions the development of Cheyne-Stokes respiration after haemorrhage followed by operation, and notes that drawing the tongue forward diminished the pauses. On section the heart was found to be healthy. Frost gives some notes of a case of apoplexy ^ in which the symptom appeared, and where no variation could be perceived in the pulse during the different phases of the breathing. One of the most valuable contributions to the subject is a study of respiratory pauses by Frai)9ois-rranck.^ Having observed that the respiration which followed tracheotomy had a great resemblance to that with which we are concerned, and being inclined to explain this as the result of a free supply of oxygen, he investigated the conditions which influenced the phenomenon. He states that with a larger supply of oxygen the pause arrives sooner and lasts longer, while with a smaller supply the pause is later and shorter, and that the pause (or apnoea, in the sense of Filehne) can be stopped by compression of the carotids, which hinders the carriage of oxygen to the brain, just as in calm breathing compression of these vessels induces forced respiration. He attributes the pause following the suspension of artificial respiration in animals to ex- cessive oxygenation. Mentioning the pause in respiration which is observed after the cessation of cardiac inhibition caused by stimulation of the peripheral portion of the vagus, he explains it as being due to excessive oxygenation of the blood lying in the lungs during the cardiac inactivity, whic^h is thereafter supplied, on the recommencement of cardiac action, to the centres, as observed by Mayer. He describes experiments in which, after stimulation of the central portion of the vagus, there is complete arrest of respira- tion without any change in cardiac action. This pause, on the cessation of the stimulation, is succeeded by large and frequent respirations, which in turn are followed by a complete pause due to excessive oxygenation of the blood. He further calls attention to the pause which follows forced voluntary respirations in man — a pause accompanied by total absence of the besoin de respirer — as being caused in precisely the same manner. Turning now to the phe- 1 The Lancet, vol. i. for 1877, p. 481. 2 Ihid., vol. ii. for 1877, p. 238. ^ Journal de Vanatomie et de la physiologie normales et pathologiques de I'homme et des animaux, 1877, p. 545. IIISTOUICAL. 'M iiomona of Cljcyne-SLokes respiriition.lK* inentidiis a case of iimuiia in which this type of bieathin^ occurred. He points out that the form of arrest in it difVers completely from that of apna3a in the strict sense of that term, inasmuch as in Cheyne-Stokes respiration the pauses are gradual in their development and cessation, while in true apntea they are abrupt. In connexion with this case he men- tions some experiments performed by Cutter, along with himself and Jolyet. They injected ammonium carbonate into the veins of dogs, in accordance with one of the theories of anemia, and found that these injections were followed by arrests of respiration. These, liowever, were very similar to the stop[)ages in apncea, and had little resemblance to the pauses of Cheyne-Stokes respiration. He also describes another example of Cheyue-Stokes respiration observed in a case of mitral disease with cerebral embolism, in wliich also the pauses had no resemblance to ttie arrests of respira- tion in apncea. He mentions that in both the cases referred to there was an adynamic condition, and tliiuks that perhaps the suspension of the respiration may simply be due to the absence of voluntary participation in the acts performed. Sacchi ^ describes a case of aneurism of the ascending and trans- verse aorta in wliich Cheyne-Stokes respiration made its appear- ance. The pause of apncea could be broken by opening the closed eyelids or by speaking to the patient. Cold aflusion and iidiala- tion of amyl nitrite produced no effect, but the inlialation of oxygun prevented the return of the pauses for an hour and a half. The pupils contracted during the pause and dilated during the breath- ing, and when the apnoea was broken by means of speaking to or in any way rousing the patient, they also dilated. The pulse was very irregular, and sphygmographic curves showed no constiint relation between the circulation and respiration. The sensorium was clouded during the existence of the symptom. Tlie post- mortem examination showed that there was an aueurismal dilata- tion of the ascending portion and arch of the aorta with hyper- trophy of the heart. Both vagi were found to be compressed by means of inflamed lymphatic glands below the origin of the recurrent laryngeal nerves, a point of interest, inasmuch asTraube states that for the occurrence of this plienomenon both vagi must be intact. The brain was an;emic, and there was some etl'usion. ' liivista clinica di Buloyna, Secoiulo Seiio, tomo vii. p. 33, 1877. 38 CHEYNE-STOKKS KESPIEATION. The author will not give his adhesion either to the theory of Traube or to that of Filehne, and he holds that the result of the oxygen inhalations is enough to disprove the view that the apnoea is caused by too little carbonic acid in the blood. Mosso^ describes periodic breathing of the Cheyne-Stokes type as being a natural feature of the hibernation of the myoxus during winter, when the temperature did not exceed a certain limit. If the thermometer registers a heat of more than from 10°-16° C, however, the animal awakes from the hibernating condition Mosso further states that Cheyne-Stokes breathing is to be seen in the sleep of healthy men, and this paper contains several tracings of the respiratory movements taken in such conditions. Ottilie^ takes the opportunity, in describing a case of senile degeneration of the brain, in which this symptom occurred, of discussing the phenomena and causation of Cheyne-Stokes respira- tion. He holds that however varying the cases may be in which it appears, one condition is constant, an insufficient supply of arterial blood to the medulla. He further calls attention to the fact, that if the pulmonary portions of the vagus are rendered incapable of performing their functions, the sensory nerves from the rest of the body can induce inspiration when the blood contains the amount of carbonic acid gas which, under normal circumstances, is only found in the blood of the pulmonary artery, and that tliis gives rise to long pauses. Filatow^ describes two cases of Cheyne-Stokes respiration from which recovery took place. One of these was a child, aged three months, who suffered from dyspepsia and inanition ; the other was also a child, ten months old, labouring under whooping-cough accompanied by wasting. The observations of Cuffer * throw some light on certain aspects of the subject. These have already been referred to in mentioning the work of rran9ois-rranck. After stating that 1 Archivfiir Physiologie, Jahrgang 1878, S. 441, 1878. 2 Transactions of the Wisconsin State Medical Society, vol. xii. p. 66, 1878. 3 Gentralzeitung fiir KinderJcrankheiten, Baud ii. S. 35, 1878. * Recherches cliniqnes et exp&imentales sur les alterations du sang dans Pur^mie et sur la pathogenie des accidents ure'niiques — De la respiration de Cheyne-Stokes dans Vnremie, Paris, 1878. IIISTOIIICAL. 39 tlie authors who have written on the suhject of uneniia make no mention of the state of the hUnni curpwseles, or of the allinity for oxygen shown hy the blood in cases of Bright's disease, he describes a series of experiments performed to discover what changes are undergone by the blood in that disease, and what role is played by such changes. He shows that injections of urea have no eflect on the number of the blood corpuscles nor on the capacity of the blood for the absorption of oxygen, while injections of ammonium carbonate and of kreatin reduce the former and diminish the latter. Along with these effects the injection of these two substances causes the appearance of a respiratory rhythm similar to that of Cheyne-Stokes breathing. When the actions of these substances upon the iilood are tested in vitro it is found that urea has no eflect, but that carbonate of ammonium and kreatin destroy the blood corpuscles. In Jiright's disease the same effects are produced — lessened number of corpuscles and diminished quantity of oxygen. Cuffer thinks it logical to con- clude that in diseases accompanied by a diminution of urea there is generally a lessened number of blood corpuscles ; that the retention of urea, its possible transformation into ammonium carbonate, along with the retention of other w^aste substances such as kreatin and kreatinin, form the point of departure in that alteration of the blood ; and he regards these substances as causing the effects known under the term urremia by their action on the blood. In Bright's disease the corpuscles are fewer as well as more resistent; they do not undergo changes under the influence of reagents — they are, in short, paralyzed, and their capacity for absorbing oxygen is extremely diminished. Turning to dyspnoea, the author shows that the reason of the frequent occurrence of this symptom in Bright's disease is the reduced nunilier of corpuscles, and that the acceleration of the respiratory movements is in direct ratio to the dimiimtion of the number of the corpuscles, in connexion with which he mentions that in leukiemia, chlorosis, ami an;emia the same symptom depends on a similar cause. Car- bonate of ammonium is much more active in the ilestruction of the blood coriuLscles than kreaiin, and it is wurthy of note that the effects upon the respiration are much more profound after injec- tions of the former than is the case with injections of the lalli-r substance. In cases of Bright's disease the author notes a s[)asm 40 CHEYNE-STOKES RESPIRATION. of the arterial system, wliich he holds to be a powerful factor in determining the accession of the exacerbations of the respiratory disturbance. Entering next upon the consideration of Cheyne- Stokes respiration as seen in urseraia, he deals, firstly, with this as a clinical symptom, and, secondly, with the experimental produc- tion of similar phenomena by means of injections of ammonium carbonate and kreatin. He states that cases of Cheyne-Stokes breathing fall into two classes, in one of which there is marked dyspnoea, and in the other little more than a cessation of respira- tion. These two classes he holds to correspond to the effects pro- duced respectively by carbonate of ammonium and by kreatin. He briefly narrates seven cases of renal disease in which Cheyne- Stokes breathing was present, and which may be shortly sum- marized as follows : — Mitral disease with consecutive disease of the kidneys, in which no cerebral symptoms were to be seen ; mitral disease followed by renal affection ; lead poisoning resulting in interstitial nephritis with cardiac hypertrophy, where dilatation of the pupils and muscular agitation accompanied the dyspnoea ; chronic renal disease and cardiac hypertrophy ; interstitial neph- ritis, in which the respiratory pauses were not complete, but were represented by periods of shallow breathing ; chronic disease of the kidneys ; mitral and renal disease ; gout and chronic renal disease, in which Cheyne-Stokes breathing seemed to have per- sisted for years; and chronic inflammation of the kidneys, in which case the vascular spasm previously referred to was well marked. Turning to the experimental aspect of the subject, he describes his work in Marey's laboratory, where he had the assistance of Fran^ois-Franck. The first series of experiments was performed by injecting ammonium carbonate and kreatin into a vein, and the results may be briefly summed up. After injections of the former drug, the respirations assumed the character of Cheyne-Stokes breathing, with violent dyspnoea and muscular agitation, as well as dilatation of the pupils during apnoea. Injections of kreatin, on the other hand, simply produced Cheyne-Stokes respiration of a tranquil description. The employment of urea in similar experi- ments caused no respiratory symptoms. The second series of experiments was intended to elucidate the cause of apnoea. After performing tracheotomy on animals, which manifested symptoms of agitation during the experiment, apnoea IIISTOUKJAL. 41 appeared ; ami llie iiullior refers in Lliis connexion to the same syinptoMi a.s it occurs after openiii;; the trachea in children. ApiKi'a was induced by keepiui,' up artilicial respiration in animals alter (racheotomy ; and Cullfi-, hy means of several inj^eniou.s exi)eriments which cannot he described here, proved that this c(jn- dition was due to superoxygenation of the blood. He, therefore, regards the stage of apnoia in tlie type of respira- tion which we are considering as arising from excessive oxygena- tion of the blood, caused by dyspnoea ; the recommencement of the breathing and subsequent dyspncea as caused by the want of oxy- genation due to the arrest of respiration ; the superoxygenation of the blood and accompanying muscular fatigue determining in turn a new period of apncea. He regards the phases as caused by the action of the blood on the medulla as well as by the influence of a reflex action having its point of departure in the lung, the lung being the special regulator of the quantity of oxygen needed, and having its essential stimulus in the condition of the blood which it contains. The author, in concluding this most admirable investi- gation, finally directs attention once more to the arterial spasm at the beginning of the respiratory period, already mentioned as char- acteristic of ura3mia, and points out how it iutiuences the condition of the breathing. Further observations having l)eeu made by Biot, subsequent to the publication of his paper already reviewed, he embodied them in a work^ of much value. After quoting the clinical descriptions, given by Cheyne and Stokes, he lays stress on the differences exist- ing between such breathing as may be frequently seen in meningitis and that known as Cheyne-Stokes respiration, to emphasize which he (piotes from, or refers to, the writings of many authors who have described the former. He analyzes the cases narrated by Bernheim, anil asserts that, the type of respiration in some of these was not that of Cheyne-Stokes breathing, which he would like to keej) quite apart from all other varieties of respiratory rhythm. Passing from this subject he describes several cases, which may be briefly referred to. 1. Man, aged 74, with atheroma, aortic dilatation, cariliac hyper- trophy and degeneration, and pleurisy. L'. Man, aged 57, with ' Ktiidt' cliniijiie it t.rj)eriiii(.iilttle i)i ilc Cheijne-Sioktit. Tari.-', 1«78. F 42 CHEVNE-STOKES KKSPIRATION. atheroma, and aortic and mitral disease. Pulse less frequent in dyspnoea; pupil dilated during that phase. 3, (Eeported by Lupine.) Man, aged 47, with saturnine renal disease, cardiac hypertrophy, and hemiplegia. Pupils contracted during apnoea. 4. (Reported by Clement.) Man, aged 70, with mitral disease and cardiac hypertrophy. Pupils contracted in pause. 5. Man, aged 74, with cardiac hypertrophy and fatty degeneration. Pupils contracted during apnoea, and muscular spasms in that phase. 6. (Reported by Prost, and already mentioned.') Man, aged 63, suffering from apoplexy. 7. (Reported by Rocher.) Man, aged 46, with aortic stenosis and incompetence as well as hemiplegia. Pupils small during apnoea, but pulse less frequent instead of more so, as in most cases. 8. (Reported by Clement.) Man, aged 60, with cardiac faihire, pulmonary apoplexy, anasarca, and hydro- thorax. Pupils contracted during apnoea. 9. Man, aged 77, with mitral disease and cardiac hypertrophy. No pupillary changes. The author proceeds afterwards to analyze the symptoms presented by these cases. Taking up the apnoea, he speaks of its duration and frequency, and, as regards its causes, shows that it may be produced physiologically by superoxygenatiou, and pathologically by want of reaction of nerve centres. Turning to the dyspnoea, he speaks of its duration and frequency ; and attempting to account for its causation, he describes how he repeated Filehne's experi- ments on the blood supply of the brain without attaining similar results, which causes him to conclude that the theory of that observer cannot be supported, and that the views of Traube are correct. Taking up the state of the pulse, he finds the tension less and the rate greater during apnoea. With regard to the condition of the eyes, he usually observes contraction of the pupils and con- jugate deviation of the globes during apnoea. As to the intellect, it is usually clouded during apncea. Muscular spasms are often seen at the end of apnoea, due to vagus irritation. As a means of diagnosis, he holds the symptom to be a sign of a double affection — cerebral and cardiac. As regards prognosis, he considers it to be of very grave if not fatal significance. With reference to medicines, he points out the uselessness of all remedies tried, and lays stress on the hurtful influence of many drugs, such as ^ Vide antea, p. 36. IIlST'JlilCAI-. 43 liypiiolics, narcotics, and substances reducing retlcx action. In this connexion he narrates another case. 10. Woman, aged 53, with bronchitis and enii)hy.st'ina, alowj^ with tricu.spid dihitation. Ciieyne-Stokes breathing appeared, and after being pre.sent for some time disappeared. To reliev^e dyspnoea she liad 7 nig. of hydrocldorate of morphine, whicli caused tlie reappearance of the Cheyne-Stokes breathing, followed by death. He show.s, finally, l)y experiment that drugs wiiich induce or increa.se this type of respiration ilo so by lessening the amplitude and frequency of the respiratory movements, and by developing a pause at the end of each expiration. Filehne promptly replied' to the strictures of Biot, and pointed out that the latter had not repeated his experiments, which were per- foinied by stopping the current through the vertebrals as well as tlie carotids, while Biot had only compressed the carotids, and therefore left the blood supply to the medulla almost untouched. He further observes that the clinical arguments advanced by Biot are not more convincing, for the fact that the frequency of the pulse is greater during the pause than during the period is not against the theory of the author. The nuclei of the pneumogastric nerves may be excited at the end of tlie pause at the same time as the vaso-motor centre ; or, later than this, at the same time as the respiratory centre, so that the lessened frequency of the pulse may be found during the end of the pause or beginning of the ascending respira- tions. Filehne refers Biot to his own tracings, which he holds to be proof of this. He further expresses his opinion that the pheno- mena of the pupils may be explained in a similar way. He ends his paper by remarking that he is not called upon again to refute the theory of Traube which Biot wishes to resuscitate, and adds that in 1875 Traube addressed an oral communication to him, in which, recognising liow well founded were his objections to that theory, he accepted his views. Biot at once answered- the criticisms of Filehne by the pub- lication of an additional note on the subject. He regrets that, from an error in the medium from wliich he obtained his knowleilge of Kilehne's observations, he had been led to make a mistake in liis control experiments, and accepts Filehne's assertion that the pheno- ' Revue viensuelle de me'decine et de chiriirgif, iU'U.\icnie aniu-o, p. G68, 1878. » Ibid.y p. 935, 1878. 44 CHEYNP>STOKES RESPIRATION. meiia of Cheyne-Stokes may be produced by alternately allowing and preventing the afflux of blood to the brain. He again states the distinction between Cheyne-Stokes respiration and other, more or less irregular, modifications of respiration. He further reiterates his statement that the arterial tension is higher during the period of apnoea than during that of liyperpnoea, basing this upon tracings and the application of Marey's law. He brings forward an interest- ing fact, that when breathing is suspended the effect on the pulse- rate depends on the phase of respiration during which the stoppage takes place. When the breathing is stopped during the phase of inspiration, there is usually slowing of the heart's action; when, on the contrary, it ceases during expiration, tliere is always acceleration. He refers to his previous work, in which he states that the apncea in Cheyne-Stokes respiration begins in the phase of expiration ; and again mentions that during the pause the arterial tension falls, while the rate of pulsation rises. On the other hand, with the period of breathing the reverse occurs. He further criticises the work of Cuffer, in which he regrets the absence of tracings, and expresses his opinion that Cuffer attributes the dyspnoea of uraemia to a cerebral ansemia caused by a vascular spasm — a theory which he regards as cousin to that of Filehne. He concludes by maintaining his conclusions, that Cheyne- Stokes respiration has a double origin — cerebral and cardiac. Mickle^ has recorded three cases of insanity in which Cheyne- Stokes respiration made its appearance. The diseases with which the symptom was associated were in these three cases respectively, general atheromatous change with cardiac hypertrophy and chronic renal disease, pulmonary phthisis with dilated heart, and apoplexy with epilepsy. The author fully discusses the pathological con- ditions accompanied by the type of respiration in question, the state of the pulse during its phases, the duration of these phases, the disappearance of the symptom in some cases before death, and the arrest of the peculiar breathing by means of various stimuli. Zimmerman'^ describes the case of a drunken tailor, aged 55, who was seen in an epileptic attack caused by excess. He had been healthy up to within a few years of this attack, but latterly he had suffered from breathlessness, and he had also been affected by 1 British Medical Journal, vol. ii. for 1878, p. 308. 2 Canadian Journal of Medical Science, vol. iv. ji. 112, 1879. iiisiwKicAr,. 45 plilcrrnionous innanimatinn of Liu; lof;. After tlie epileptic seizure he Ix^canie a'deiiiatous, with a return of the iiillaniination of the Ici,' and severe dyspncca. TIk^ niinc cnniaiiKMl ncithrr alliuiiKMi nor tul»e- casts. Ahoiit a month after heiiiL; Hrst set'ii the lircathiiii,' as.snint.'d the Ciieynt!-Stokes character, and traces of albumen appeared in the urine, hut Nvithout casts. The patient dit'il in a comatose state, and it was found on post moitein examination that there was chronic renal disease witli cardiac hypertroidiy, arterial atheroma, and cerebral congestion. The author quotes Cuffer's cases and explanation, and refers to the work of Biot. He further states that since the paper was read he had met with Cheyne-Stokes respiration in an old man of 80, dying of chronic bronchitis and emphysema, and in a child 18 months old suffering from pneu- monia of the right lung. In this last case the patient had many symptoms pointing to tubercular meningitis, but recovered, and the Cheyne-Stokes breathing in this instance was not continuously present, but appeared and disappeared irregularly. Luciani^ prefaces one of the most valuable contributions ever made to this sul)ject by stating that he had, in the year 1873, com- menced a series of experiments under the superintendence of Ludwig at Leipzig, but that on account of various circumstances he had not been able at the time to complete his investigations. This paper begins with a brief retrospect of the work done by pre- vious observers, after which the author describes some of the results which he obtained by experiment. Finding, by means of operations on the heart of the frog, that its rhythmic contractions became periodic, the analogy between this phenomenon and the character of the rhythm of Cheyne-Stokes respiration led him to seek for their causes in a common condition. His experiments were conducted by fixing a ral)l)it in Czermak's apparatus ; liga- turing the carotid arteries to control hainorrhage during subsequent operations on the medulla; connecting the respiratory passage, by means of a canula, with a manometer, whose index recorded the respiratory movements on a revolving cylinder ; exposing the medulla oblongata ; and di\ iding it above the origin of the vagi. The resjjiratory movements after section of the medulla in this way fell into groups, but each group began with a deep • Lo Sperimcntalc. A mm xxxiii. Tmno xliii. y. 341 v \>. ■14!I, ISTi). 46 CHEYiNE-STOKES RESHHATION. inspiration and expiration, followed by a series of diminishing respirations. Luciani states tliat if he had published these ob- servations when they were conducted he would have deprived Filehne of some of the novelty of his work, but he would at the same time have been led to different conclusions. He was induced, however, by the hope of obtaining more precise information, to post- pone the publication of these results. He afterwards turned himself to the study of apncea caused by excess of artificial respiration. The method employed was to fix the dog or rabbit ; to inject laudanum into the veins of the dog, when such an animal was subjected to experiment, this proceeding not being resorted to in the case of the rabbit ; to perform tracheotomy and insert a canula into the trachea for the purpose of supporting artificial respiration and recording respiration ; to expose the vagi; to keep up artificial respiration until apncea was present ; to divide the vagi ; and in some cases to join the canula to a reservoir of air lead- ing by a tube to a Marey's tambour, by which means the result of gradual asphyxia could be recorded. He found that, after the pro- duction of apnoea by excessive artificial respiration, and without section of the vagi, the respiration did not at once begin as ordinary respiration, but in an ascending series; at the same stage, with previous section of the vagi, an ascending series of respirations was seen, but in this case the ascent was much more rapid ; after pro- found narcosis had been caused and apnoea induced, it was suc- ceeded by groups of ascending and descending respirations, separated by long pauses ; after section of one vagus, the breathing became deeper but less frequent, and after section of the other also it became laboured and very infrequent ; when the animal was allowed to breathe the air of the reservoir until death from asphyxia took place, it was found that section of the vagi caused but little effect, and the respiration became periodic when the animal was almost asphyxiated. Turning to the clinical aspect of the subject, Luciani remarks that Cheyne-Stokes respiration may occur in diseases of the brain, and of the heart and great vessels, in the coma produced by different intoxications, during the agony of certain affec- tions, and also in the sleep of healthy persons and the lethargy of hibernating animals. He refers to its appearance after the use of morphine in disease ; after the administration of morphine followed iiisioiJii.Ai,. 47 liy ether (»r clilDrofKrin ; after tlie injection of cliloral, kreatin, and anunoniuiii carbonate; after injury to the parts near the nieud vital ; after the employment of artificial respiration, subsequent to the injection of opium into tlie veins, so as to cause apnuia ; and during tiie last stage of aspliyxia. The respiratory phenomenon may appear in different forms. Tlie movements may increase or decrease in amplitude without change in frequency, or there may be more of the descending than ascending phase — in fact, the latter may be absent. The number of respirations during a period may vary from two to thirty, but the larger numljers are only found in the Cheyne-Stokes breathing of disease. The length of the pauses is very variable, and there may be a similarity in the duration of the successive pauses or a total want of equality. The author then enters upon a long and careful criticism of the theories of Traube, Filehne, and Hein, — into which it is, for obvious reasons, impossible to follow him, — after which he submits his own views on the subject. He is of opinion that it is impossible to solve the problem of Cheyne-Stokes respiration while resting upon the principle now generally admitted or sustained, that the capacity and functional activity of a nervous organ has always a direct and immediate dependence on the stimulant and nutritive conditions extrinsic to itself. That the life of an organ is intimately bound up with the surrounding conditions and influences cannot be denied without stilling science in the old vitalism ; but it does not follow from this that the organ does nothing in every case but to transform as much as it receives in a given time, both in the same measure and in the same rhythm with which it receives it. Drawing a clear line of distinction between reflex and automatic movements, Luciani points out that the determining cause of the former is extrinsic, while in the case of the latter it is intrinsic, and consists in oscillations of the internal nutritive movements, to which cor- respond as many oscillations of the excitability of the organ itself. He was led to this new conception of automatism by the dis- covery of the periodic grouping of the movements of the frog's heart, before referred to, for no one could doubt that when extrinsic conditions remained unchanged the cause of the alternate groups of pulsations and pauses in repose was intrinsic. 48 CHEYNE-STOKES KESPIRATION. Luciani therefore regards the diverse forms of respiratory rhythm as extrinsic expressions corresponding to the oscilla- tions of the nutritive changes taking place in the structure of the respiratory centre. If it be granted that the respiratory centre is automatic, it follows that the different forms of rhythm which con- stitute Cheyne-Stokes phenomenon may be regarded as effects of diverse kinds of automatic oscillations in the excitability of the centre itself. In a study of the action of morphine on the respiration, Filehne * again discusses the respiratory and circulatoryphenomenaof Cheyne- Stokes breathing, and somewhat modifies his original statements. He says : — " To my former theory of periodic breathing would I now make the addition that for its appearance it is quite sufficient that the arteries of the medulla oblongata be stimulated simul- taneously with the stimulation of tlie respiratory centre ; a previous contraction will strengthen the phenomenon, and may occur in the most pronounced cases ; it is, however, not indispensable, and per- haps not always present." He further says that the difference of opinion existing between his own and Biot's explanations of iden- tical observations is a purely verbal misunderstanding ; and he also replies to Hein by saying that the latter has concerned himself more with 'the how than the ivhy. To Rosenbach^ we owe a new explanation of the symptom in question. After pointing out that the different phenomena accom- panying Cheyne-Stokes respiration really constitute a complex of symptoms, he disputes Biot's statement that true Cheyne-Stokes respiration only occurs in cardiac diseases, and not in cerebral affections. He points out that the descending part of the phase of respiration is not so regular as the ascending, and agrees with most observers that the circulation is sometimes involved and at other times not. In some cases he mentions that there is a rise of the pressure and fall of the rate during the ascending respira- tion, while with the descending respiration the contrary takes place, and in other cases there is no increase of rate, only lessened frequency at the end of the pause. He shows that Filehue's ob- servation on the sinking of the fontanelles of the child's head 1 ArcJdv fill- experimentelle Pathologie und Pharmakologie, x. Band, S. 442, und xi. Band, S. 45, 1879. 2 Zeitschrift fiir Minische Medicin, i. Band, S. 583, 1879. IIISTOICICAL. 49 before the 1)oi;inniiiLj of the respiratory pliase i.s not eorrect f(jr all cases; the recession may occur aftt-r IIk; phase has be;4un or during' the heif^ht of the breathing,', from which he concludes that the sinking may be caused by an acceleration of the l)lood-flow from the brain by means of the respiration. lie recalls Leube's state- ment re^'arding stimulation of the phrenic nerves, and says that stimulation of the vagi, causing a change in the pulse rate, effects no change in the phenomena of Ciieyne-Stokes respiration, showing that ihey are independent of tlie supply of arterialized blood to tlic luaiii. lie lays stress on the contraction of the pupils during tlie pause and their dilatation during the period of breathing, as well as on the rolling of the eyeballs or conjugate deviation, and the general twitchings of the body occurring during the period of respiration. He further dwells on the changes in the sensorium, and on the iniluence of such drugs as morphine, chloral, and liromide of potassium, and recapitulates that there are changes in Cheyne-Stokes respiration connected with the cortical as well as with the basal centres, such as those of intellection, the muscular system, the vision, the circulation, and the respiration. Passing by Traube's first e.Kplanation, he states his second, which, though not entirely tenable, has yet some good points. He points out that it does not explain the ascending character of the respira- tion. He then enunciates Filehne's earlier theory, based on periodic changes of blood-supply, caused by a higher degree of e.xcitability of the vaso-motor centre, and without hesitation rejects it, inasmuch as in some cases the blood-pressure rises before tlie recommencement of breathing, and when this rise is present it attains its maximum at a point between the ascending and de- scending respirations. Filehne's later theory, that the stimulation (tf the respiratory centre and medullary vessels may occur simul- taneously is also rejected, liosenbach is of opinion that both ]ihenomena are co-effects, and he is strengthened in his views by the fact that other phenomena, such as the mental, visual, and muscular, are bound up with the respiratory, not with the circu- latory, symptoms. He emphasizes the dilferences between the circulatory and respiratory phenomena in this type of breathing, the great variability of the former and the monotonous similarity of the latter being noteworthy. He brings forward the fact, noted by Leuhe -dWil confirmed by himself, that artificial respiration during 50 CHEYNE-STOKES RESPIRATION. the pause (which prevents accumulation of carbonic acid in the blood) does not alter the next phase, as well as his own observation that stimulation of the vagi and slowing of the pulse during the descending period do not alter that phase, and holds that these facts prove that within wide limits the condition of the blood does not modify the type of respiration. He points out that the eye phenomena are not dependent on the state of the blood, as the widening of the pupils takes place along with the first inspiration, and therefore before any change can be effected in the state of the blood. In this connexion he refers to the work of Kiissinaul, Eahlmann and Witkowski, Sander, Plotke, and himself, on the relations of the eye and the central nervous system. He is there- fore led to conclude that the beginning and ending of breathing in Cheyne-Stokes respiration are independent of the blood-pressure and the amount of gas in the blood, and that the clianges of the pupils have no relation to the circulation or the blood, but to the excitability of centres not directly dependent on the condition of the blood. He points out that in health the vagus and vaso-motor centres are more excitable than the respiratory, but that in this phenomenon (with the highest pressure accompanying the deepest respirations) they are sunk to the level of the respiratory. He asserts that Filehne's theory postulates, in rhythmic contraction and dilata- tion of the arterial system, conditions without analogy in nature. He points out that at the end of the period of breathing there is no apnoea, for the pupils, eyeballs, and mental state speak of fatigue, not better arterialization, that amyl nitrite has often no influ- ence or very little, and that the drug is believed by some to act on the respiratory centre itself. He refers to Hein's explanation of the observation that unconsciousness is present during the pause and consciousness during the period as incompatible with Filehne's theory. Eosenbach seeks for an explanation of the phenomenon in the alternation of activity and repose characteristic of nature. In the respiration there is inspiration, expiration, and pause ; in the cir- culation, systole, diastole, and pause ; in the nervous system, wakinp and sleep ; while in curarized animals there are pei'iodic changes in the rate and tension of tlie circulation which are quite independent of the respiration. The origin of activity is in the cell, not the Mood, and it is illogical to seek a cause of respiratory and other IIISTOIMCAI,. 51 ]iliriii)iii('ii;i ill lilt' hluiid. I'rrii)(licity of activity of all nervous apparatus, tluTt'l'drc, (lc'])t'U(l.s on iniiuancnt pcciiliiiritirs of cltunciit- ary structures, and the Ulood is nut the dii-ect stimulus tor the cells, lull has its power in ,L;i\ iiisui' clinn-v. When the IiImhiI is altered there is necessarily a iuii(liiic;iti()ii in the alisor[)Liuu ut' oxygen and removal of tissue c]ianL,M' jirixhu'ts, and the mechanism will therefore be indirectly atlectetl ; the blood is thus only one link in the chain of apparatus needful for life. The regular alteriialion of activity and repose characteristic of lile is seen in the complex of pathological phenomena, of which periodic breathing is only one symptom, and Cheyne- Stokes res[)iration is therefore a condition in which the ex- haiisiibilily of the central apparatus, normally following its activity, is greatly increased. The resjiiratory centre has its irritaljility lowered, as the breathing is at first shallow, but the irritabiliiy } progressively increases, for in spite of better aeration dyspncea gradually develops. The irritability then diminishes and the descending phase begins. The supposition may be hazarded that the first descending respirations following the deepest have their origin in 1)etter arterialization of the blood, or in removal of waste ]iroducts from the centre, and that the fall in irritability begins with the first normal breathing. Rosenbach shortly summarizes his views in this way: — Throufrh certain disturbances of nutrition, the brain suOers from lessened How of blootl or altered quality of blood, and the processes of tissue change are modified in the entire central organs, or in particular ]iarts (if it, especially in the medulla oblongata, and here a>'ain more jiarticularl}' in the respiratory centre, so that the normal irritability of the parts is lowered more or less, and the normal jieriodic exhaustibility is increased even to complete paralysis. Uosenbach mention.s, as an appendix to his paper, a case in which a patient ill with tubercular meningitis suddenly ceased to breathe except once or twice per minute, the pulse continuin*' to beat. After artificial respiration had been employed the pheno- mena of (Jheyne-Stokes breathing a])peared. Purjesz^ describes a case whiidi he met with in the I'niversity * J'ester medkinisc/i-chirunjimfie I'rcsn, xv. liuinl, SS. 771, 7^7, u. >4C!, 1>7J. 52 CHEYNE-STOKES KESPIRATION. clinique of Wagner in Buda-Pestli. The patient, a man aged 57, was suffering from emphysema, renal cirrhosis, cardiac hyper- trophy, and general dropsy. During the last three days of his life typical Cheyne-Stokes breathing was present. No changes in the state of the pupils or alterations in the conditions of the brain cortex were to be seen. The author mentions another patient, in the same clinique, suffering from chronic renal cirrhosis, who had Cheyne-Stokes breathing. In this case an improvement in the patient's condition took place, and he left the hospital. Purjesz reviews at considerable length several of the theories which have been advanced to account for the phenomenon, but gives no opinion of his own. Edes^ has described five cases in which Cheyne-Stokes breathing made its appearance ; and it is a most interesting point to find that four of these instances belonged to the same family — a father, aged 80 ; his wife, whose age is not stated ; and two sons, aged respectively 50 and 45. The father was subject to attacks of un- consciousness, during which the pulse was completely lost and the periodic respiration appeared. The mother and the two sons were affected by chronic renal disease. The fifth case was that of an old woman with chronic renal disease, atheromatous arteries, and hypertrophy of the heart, in whom left hemiplegia occurred from plugging of the middle cerebral artery. Kronecker and Marckvvald,^ by a series of experiments on the rabbit, have shown some results of interest in this connexion. The medulla was severed between the respiratory centre and the brain, in such a way that the respiration was not much altered, and the lower part was stimulated by single opening induction shocks. At the right time such shocks strengthened the inspira- tion and expiration, and when given during the interval between the acts they induced others quite normal in character. When the animal was brought into the condition of apnoea by means of artificial respiration, the most powerful induction shocks failed to cause any inspirations. When long pauses in the respiration with intervening periods of dyspncea were produced by partial removal of the respiratory centre, every induction shock given during the 1 Boston Medical and Surgical Journal, vol. ci. p. 734, 1879. 2 ArcTiiv fiir Physiologie, Jahrgang 1879, S. 592. HISTORICAL. 53 pauses was foUowi-d ])y an ajiparently normal respiration. When (luriiii^ a respiratmy pause successive rliyllitnic induction shocks were t^'iven, phenomena were seen analogous to the chan;,'es in the ventricle of the frog's heart observed by Kronecker and Howditch (Rowd itch's stair). From the pen of lioseubach^ came an excellent article on the subject, based upon the views to which full reference has been made. In this article he again advances his opinions that the phenomena are not chiefly dependent on changes in the circula- tion, that they are independent of any periodicity in the blood- supply to the brain, and that they are co-ordinated by and joint effects of one and the same cause occurring periodically in the central organs, this cause being a periodic exhaustion of the centres. The whole Inain may be affected, when the entire com- plex of symptoms, to be termed Cheyne -Stokes phenomenon, is produced ; or only limited tracts may be implicated, giving simply Cheyne-Stokes breathing. He points out that, just as the respira- tory centre alone may be deranged, so the vaso-motor or vagus centre may be disturbed, as in tubercular meningitis, and cause changes in the tension or rate of the pulse. Kosenbach compares the periodic exhaustion with the normal pauses for rest shown by all rhythmically acting systems. The different phases resemble natural phenomena, but with longer intervals ; the period of breath- ing, for example, is to be compared with a respiration, and the period of apncea with the short pause following expiration. The vagus and vaso-motor centres show similar variations. The ex- haustion of the brain induces sleep, during which the pupils behave as in ordinary slumber. The centres are not only more easily exhausted, requiring longer rest, but their irritability is reduced, and dyspncea comes on in spite of better arterialization of the blood (which involves reduc- tion of stimulus). The meaning of this is that the centre is becoming more irritable although the stimulus is lessening. After a time the normal irritability is regained, which is accompanied by gentler breathing until the pause occurs. The author holds that this theory differs from all previous explanations in being based, not on periodic variations in the • Iieal-EnrijrJu}mlie ihr gesammten Heilkumli', Hi-musgcgeltun von Dr Albert Eulfiibei-y, iii. Band, S. 150. Wit-n luul Lt-ipzig, 1880. 54 CHEYNE-STOKES RESPIRATION. amount of stimuli, but on periodic changes in the irritability of the centre. Caizergues^ describes the case of a man, aged 64, suffering from mitral disease, in the course of which he laboured for some days under severe dyspnoea, which was replaced afterwards by Cheyne- Stokes respiration. During the pause the intelligence became very cloudy, but the patient could be awakened by a loud noise ; the eyelids drooped and the pupils contracted in this phase. When awakened by a loud noise the regular periodicity of the breathing was for a time arrested. Daring the period of breathing the eyes were opened, and the face bore a look of anxiety. The pulse, of which tracings are given, was more fre- quent during the pause than during the breathing, and during this latter phase it was extremely irregular. After death it was found that there was mitral incompetence with extensive arterial atheroma, more especially of the cerebral vessels, with congestion of the kidneys and other internal organs. BuU^ describes an interesting case in which the patient, belong- ing to a neurotic family, and herself the victim of many nervous symptoms, was seized, when 20 years old, with a hysterical affection of the breathing. This consisted in spasms of the thoracic muscles in the position of deep inspiration and deep expiration alternately, the former lasting as long as forty seconds, and the latter to thirty- five seconds. This condition cannot be compared with Cheyne- Stokes breathing, as the only point of resemblance lies in the pauses. Blaise and Brousse,^ in a joint communication on this subject, give a brief historical review of previous opinions as to the cause of the phenomenon, and then pass on to the description of a case in which it occurred. The patient in this case was a man, aged 88, suffering from bronchial and pulmonary inflammation associated with pleurisy, and accompanied by renal disease, as shown by albuminuria and ursemia. The authors watched the type of breathing under consideration for ten days ; it invariably ceased during sleep, and it disappeared finally two days before death, 1 Gazette hehdomadaire des Sciences m^dicales de Alontpellier, tome ii. p. 337, 1880, 2 Norsk Magazin for Lcegevidenskaben, 3 Raekke, v. Bind, S. 165, 1880. 3 Movtpellier mAHcal, tome xliv. p. 287, 1880. HISTORICAT,. 55 During tlie pauses the eyes closed, ami the pupils became small and reactionlcss ; two or three seconds before the return of the breathing the pupils dilated, and sometimes executed a series of oscillations during the dyspncwa; during the i)eri<>d of hnsithing they were sensible to liglit. There was considerable agitation at the height of tlie dyspntea, at which time consciousness was unim- l)aired, and there were no convulsions. By speaking to the patient during the ])eri()d of l)reathing tliis phase could be prolonged con- siderably. Sphygmograpliic tracings showed during the pause a fall of tension and an increase in rate ; during the respiratory period the reverse occurred along with irregularity of the pulse. There was never a rise of tension at the end of the pause, but, on the contrary, sometimes a fall. After an excellent description of this case, accompanied by ad- mirable tracings, the authors give a brief notice of another case, under the care of Caizergues, which appears to be that previously referred to. They then proceed to analyze the symptoms attending this phenomenon with great care, and subsequently criticise the views of previous observers, to which they, in the early jiart of their paper, had called attention. This brings them to consider the view of their teacher Grasset, which they fully expound. According to him, llie dyspnoea is the primordial fact, the apnoea being merely a consequence of it ; and the type of breathing is a symptom of excitement. The aniemia of the medulla, far from lowerin^^ increases the irritability of that organ. In anajmia of the nerve- centres such phenomena of excitement as convulsions are common. The diminution of the blood-current and consequent lessening of the nutrition reduce the vitality of the nerve-cells. This increases the irritability, but at the same time tends to produce weakness and liability to exhaustion of the nerve centres. In short, it leads to what the authors call, " that peculiar condition which the English have so happily termed irritable weakness." This gives the key to the causation of Cheyne-Stokes breathing: bulbar anivmia produces greater irritability of the centres which it con- tains; their usual excitant, carbonic acid, acts upon them with unaccustomed intensity ; the breathing assumes the character of dyspncea, which will be more marked if excitement of the vaso- motor centre causes constriction of the arterioles, thus increasing 56 CHEYNE-STOKES RESPIRATION. the bulbar anaemia. As the centres are easily fatigued, however, their excitement progressively diminishes, until it passes away entirely, whence the pause. After a time, the nervous elements repair their forces, and the cycle recommences. Franz,^ in the course of a paper on artificial respiration, takes occasion to refer to the observation of Leube, pressed by Rosenbach in opposition to Filehne's theory, that during tlie pause stimulation of the phrenic nerves has no influence on the respiration. He expresses his opinion that periodic breathing is not induced by a periodicity in the respiratory centre apart from the degree of arterialization of the blood, but that the origin of the periodic event is a certain degree of venosity of the blood. He states that in animals under the influence of morphine showing periodic breathing, faradization of the phrenic nerves, when the trachea is open, causes respiration, which he holds to show how little ground Eosenbach has for citing Leube's and his own observations in opposition to the theory of Filehne. Marckwald and Kronecker,^ as the result of further observa- tions on the respiratory movements, state that they have fully confirmed Traube's observations, that the occurrence of Cheyne- Stokes respiration is connected with the integrity of the vagi, for after cutting these nerves in the neck the phenomenon never appeared, and if present before section, it disappeared ; in fact, with division of the vagi, all regulation of the respiration was lost. Hein ^ asserts that neither the theory of Traube nor that of Filehne can account for what he had previously described, i.e., variations in the state of consciousness, and he believes that there must be the same cause for the cerebral and bulbar phenomena. He therefore again states his theory. He quite agrees with Biot that cerebral breathing is not the same thing as Cheyne-Stokes respiration. In the former there is periodic breathing of atypical form, often with long pauses, sometimes ascending and descending in character, and having no constant relation between the eye and breath symptoms ; but if the eye signs are present, the pupils are wide during the breathing and narrow in the pause. It occurs in many diseases, and the prognosis is not always unfavourable. 1 Archiv fiir Physiologie, Jahrgang 1880, S. 398. 2 Ihid., S. 441. ^ Deutsches Archiv fiir klinische Medicin., xxvii. Band, S. 569, 1880. IIISTOUICAL. 57 Penodic brealliing of llie Cheyiie-Stokes type lie ImMs to l»t', iis a rule, associatud with a state of iinconsciou.siies.s. Sonietinies consciousness returns durin;^ the period of breathing, but is absent in the pause, and if this is tlie case, tlie consciousness and the breatliinjT reappear simultaneously. If j)upillary variations are to be seen, the pupils are of middle size during respiration, become narrower during the descending phase, and are small and insensitive during the pause, gradually widening with the ascending respira- tions. If the vaso-motor nerves are affected, there is higher arterial tension during the respiratory period. This may pass from regular Cheyne-Stokes respiration into the atyi)ical form at times. The type of the respiration may be due to periodic varia- tions ill activity of the respiratory centre alone or associated with similar variations of other centres. Lowil,^ from a careful study of tracings obtained by means of the polygraph in a case of Cheyne-Stokes respiration, forms the opinion that this symptom is not to be regarded as identical with the periodic breathing produced experimentally by Filehne. He holds that Cheyne-Stokes breathing does not depend upon varia- tions in the condition of the circulation, but upon fluctuations in the activity of the nervous mechanism of the breathing, such as changes in the irritability of the respiratory centre from exhaustion and recovery. The irritability of the respiratoiy centre alters under conditions not yet perfectly known, but no doubt belonging to the processes of tissue change. He regards this as the cause of the symptom. Winternitz,- writing nf Cheyne-Stokes respiration in eliiMren, describes a case in which the patient, who was a highly hysterical girl, was thrown into a state of great nervous irritability after a painfid operation on the teeth, and in this condition developed the type of breathing in question. It was present during a period of thirty-six hours, and then disappeared. Another case described is that of a little boy suffering from catarrh of the nose and throat, with vomiting and diarrhtea, in whom the Cheyne-Stokes breath- ing was present for twelve hours, until the patient improved. During the pauses the pupils were contracteil. He is of eipinion that in such a case the determination of blood to the intestines, 1 Frwjer mcdici n iache irucluiu^chn/i, v. Haii.l, SS. 461, 473, 481. u. tiil), 1880. ' Archil' fiir Kimkriuilkundi, i. Vmu\, S. 142, 188i>. H 58, CHEYNE-STOKES RESPIRATION. acting on a delicate and nervous organism, caused anaemia of the medulla, and thus induced the Cheyne-Stokes breathing. He suggests mechanical compression of the abdomen in similar cases, but says he omitted it in his own. Solokow and Luchsinger, in giving the results of a careful series of experiments, contribute some interesting observations^ to this subject. They state that when frogs, which have been immersed for some hours in water, begin to recover from their stupor, they show the Cheyne-Stokes phenomenon ; that when frogs in winter are exposed to the action of heat, and the aorta is clamped, the same phenomenon occurs on the removal of the clamp and on its being again replaced ; that the periodic respiration is also seen on clamping the aorta, after cutting the cord in the neck and destroy- ing the spinal cord below that point, showing that it is quite independent of conditions of blood-pressure ; that its occurrence is not affected by any changes of pressure, or by the substitution of saline solutions in place of blood ; and that the vagi are not necessary for its appearance. They state that the conditions of periodicity are no other than such as are developed in every tissue, with growing asphyxia. Describing the administration of picro- toxin hypodermically during ether narcosis, they mention that tlie Cheyne-Stokes respiration and convulsions occurred synchron- ously, and that on the administration of more ether the convul- sions ceased while the periodic breathing went on. They compare the phenomenon with the periodicity of lymph hearts as seen by themselves ; with the periodicity of blood hearts described by Luciani ; with the periodicity of the heart observed by Rosenbach when a supply of defibrinated blood has been allowed to circulate too long and has lost its colour ; and with the occurrence of the contractions of exhausted Medusae in groups. They conclude that the observations of comparative physiology as well as the results of experimental analysis agree in showing the conditions of this grouping of movements. Increase of stimulus and decrease of elasticity show themselves to be the important factors. It may without hesitation be supposed that the cause of the periodicity is to be sought in the lessened elasticity and greater exhaustibility of the organ, and this view is supported by direct observation. 1 ArcMv fur die gesammte Physiologie des Menschen mid tier Thiere, xxiii. Band, S. 283, 1880. irisTonicAL. 59 Tn answer to Fileline's question/ why the exliaiistion doo.s not follow each respiration, instead of showing' itself after a series of respirations, they reply that the irritabiliiy of a nervous or<,'an will rise when after repose it is awakened to activity by stimuli, hut it will sink if the activity has lasted too hnv^. They refer to tiie obser- vations of Kronecker and Marckwald, already mentioned, as being entirely analogous to the phenomena of Cheyne-Stokes respiration. O'XeilF lays stress on the fact that the respiratory pause may be present without any ascending and descending phenomena, but is not prepared to say that arrests of this kind should be classed as Cheyne-Stokes resi)iration. He mentions the case of a lady suffering from chronic bronchitis and emphysema, with dilatation and hypertrophy of the heart, in whom arrests of respiration appeared, after an exacerbation of her pulmonary troubles, accom- panied by general anasarca. The arrests of breathing disappeared when the chest improved and the dropsy passed away. He describes a case in which there was difficulty of articulation and deglutition along with Cheyne-Stokes breathing, and he supposes there was an affection of the medulla as well as of other nervous centres. In this case the pauses appeared after the use of chloral. O'Xeill states that in two cases nitrite of amyl produced no effect, but that another patient suffering from renal disease, accompanied by Cheyne-Stokes respiration, felt much relief from this drug, ^vhich on several occasions "restored and reinvigorated the breath- ing when it was about to cease." Lereboullet gives an excellent summary of the various views held by several writers on the phenomena of Cheyne-Stokes respiration.^ He is evidently of opinion that Filehne's investiga- tions have tended to show that the primary cause of the symptom is an affection of the vaso-motor centre, while the respiratory centre is oidy concerned in its production in a secondary manner. Lere- boullet adds no original observations of his own to the subject with which he deals. liosenbach* gives another critical study of the phenomena of ■ Ueher des Ch^yne-St' ikes'. ■y llic gradually increasing recovery of the centre and hy progressive diminution of its excitability. G. The role attributed to spasm of the vessels in the causation of the symptom does not ajt[)ear to rest on suMiciently certain facts. 7. The fri'ipu'iicy with which the .symptom is associated with chronic renal disease depends less on tlic kidney aflection than on the va.scular degeneration with which it is associated. The urinary troubles only play a secondary part, by producing cardiac or ])uliiionary affections, ami by altering the state of the blood. The development of the phenomenon in these cases does not seem to have a direct relation to an intoxication by extractive matters or ammonium carbonate. 8. Occurring in very diverse conditions Cheyne-Stokes breathing has no precise diagnostic value. 9. The intermittent appearance of the phenomenon and its com- plete disappearance prove that it does not depend on a profound alteration in the structure of the respiratory centre. 10. Although most commonly the precursor of a speedy fatal i.ssuc, the symptom may be compatible with survival for a long period. 11. Without extolling narcotics it may be stated that in cases of Cheyne-Stokes respiration they may render good service, and that their dangers have been considerably exaggerated. Langer^ describes a case of tumour of the pons in a young woman, where Cheyne-Stokes respiration was present in its typical development. In an investigation into the periodic breathing of frogs, Langen- dorff and Siebert- note that after the blood-supply to the medulla has been cut off, frogs show a periodic rhythm of respiration, and that the result is the same, whether the blood-supplv is cut off by tying the aorta or bleeding the animal, while substitution of a physiological solution of common salt for the blood sometimes allows the ordinary type of respiration to continue, but often modifies it in various ways. Stimulation of the skin during the pauses between the periods of breathing causes the appearance of ' ^[ed^zinMle Jahrhiicher der k. k. Geselhchaft der Atntc in Jl'ten, S. 515, 1S81. - Archivfiir Phusinlinju; Jahrj^uni,' 1881, S. 241. 64 CHEYNE-STOKES RESPIRATION. a group of respirations. They regard periodic respiration as conditioned by disturbance of irritability induced by modifications of nutrition. The ascending character they attribute to the gradual disappearance of exhaustion — the descending phase is not so often seen. Langendorff^ has further observed periodic respiration in frogs after the administration of muscarine, which he regards as acting directly on the respiratory centre, causing a true disturbance of its nutrition. In the same paper he describes periodic respiration caused by digitalin, which he attributes to the influence of the drug on the heart, as the respiratory phenomena only appear when the heart is brought nearly into the condition of arrest. Sanson! 2 is of opinion " that the respiratory nerve centre is dhedly influenced — that it suffers a paralytic lesion, and so its irritability is impaired," but adds that "it may be doubted whether, in some cases, the symptom may not be initiated by disease of the heart-muscle itself." Davy^ describes the case of a man, aged 70, subject to attacks of cardiac asthma, who at times presented characteristic breathing of this type. Langer* commences an excellent contribution to the study of this subject by defining the symptom and describing the pheno- mena with which it is so often associated, after which he refers to modifications in its type, and states that his observations lead him to agree with Eosenbach that true Cheyne-Stokes respiration may occur in cerebral cases. He afterwards analyses the various phenomena, especially dwelling on those connected with the state of the consciousness, the muscular condition, the changes in the eyes, and the circulatory modifications. All of these he holds to be explicable by one of two possibilities — either that the excita- bility of the centres increases and diminishes, or that the stimuli vary while the excitability remains constant. This leads him to mention the rival theories of Filehne and Eosenbach. He then narrates the case of a mason, aged 29, suffering from ^ Archiv filr Fhysiologie, Jahrgang 1881, S. 331. 2 Manual of the Physical Diagnosis of Diseases of the Heart. Third edition, p. 38. London, 1881. 3 Cincinnati Lancet and Clinic. New series. Vol. viii. p. 492, 1882. * Wiener medizinische Presse, xxiii. Jahrgang, S. 1253 u. 1289, 1882. HI8T0HICAL. CJj climiiic, HriL^ht's disease. In this case Cheyne-Stokes breatliin^' was developed with chan<;es in the condition of tlie consciousnes.s and in the movements of the eyeballs, but witiiout any alteratif)n in the inipils corresponding; to the two phases of the breathint;. After this had cniitiiiued tnr twenty-four liours, periodic changes in the condition of the circulation showed themselves, the tension of the pulse risinj;, and its rate sinking' with the ascending' phase of the respiration, and the converse takin^j ])lace during; the descending phase and the subseciuent [)ause. After tiuise condi- tions had existeil for two days a change ensued, and on account of an alteration in the relation of the pulse and respiration, it often happened that the highest tension ami lowest rate of the former coincided with a pause of the latter. The author regards this observation as giving support to the theory of Kosenbach, to which, as well as to the work of Solokow and Luchsinger, and Hein, he refers in concluding his paper. De Witt' records a case in which the patient, an elderly man, fell down and probably struck the back of his head. He became unconscious, and developed long pauses in the breathing. It is open to question whether this case may be regarded as having any close connexion with the subject under discussion. Paterson- narrates the case of a middle-aged gentleman, suH'ering from Bright's disease, who presented the symptoms of Cheyne-Stokes respiration, which he is inclined to attribute to cardiac hypertrophy and pulmonary oedema, acting injuriously on the medulla oblongata. Knoll,^ in a contribution to the study of irregular and periodic breathing, distinguishes between spontaneous alterations in the state of the respiratory centre and changes which are produced retlexly. lie holds the latter class to be very much more extensive than the former, traces out the mode of origin in both, and gives examples of each. Amongst periodic breathing the author dwells on that of the " meningitic type" of Biot, which he holds to be dependent on a sinking of the irritability of the respiratory centre rather than on a stimulus caused by the blood, leaving it in doubt, however, whether other factors may not also be concerned in its production. ' Cincinnati Lancet and Clinic. New series. Vol. i.\. p. 2lK), 1882. 2 Lancet, vol. i. for 1883, \>. IJI. ^ Lotos, iieue Folj,'c, iii. ii. iv. liaii'l, S. 101), 1S83. I 66 CHEYNE- STOKES RESPIRATION. He also devotes some remarks to Cheyne-Stokes phenomenon, mentioning the various methods by means of which appearances more or less like it may be produced, and concluding that he would not be justified in regarding the symptom as a reflex phenomenon of deeply depressed irritability of the respiratory centre, in opposition to any theory of blood stimulus. FanOji in the course of some investigations on the red blood corpuscles, observed that after removing the heart from a tortoise the breathing persisted, not indeed with its previous regularity, but in a periodic manner, the respirations being grouped together and the different groups separated by long pauses. This observa- tion, which he repeated more than once with different forms of tortoise, and which he compares with the results of Solokow and Luchsinger, led him to consider the origin of Cheyne-Stokes respiration. Such experiments he holds to have entirely over- thrown the theory of Filehne, already refuted by Luciani. Fano proceeds to detail the methods which he adopted in his investiga- tions, and afterwards criticises the theories of Filehne, Traube, Solokow and Luchsinger, Langendorff and Siebert, and Luciani. This is followed by a description of his experiments with carbonic oxide and carbonic acid gases. He found that tortoises were able to live and breathe for many hours when in an atmo- sphere solely composed of either of these gases ; and he concludes this fact to be enough to show that there may be some doubt as to the production of respiratory movements by the state of the blood. Other experiments, performed with oxygen, hydrogen, and carbonic acid, confirmed his conclusions ; but at the same time, as he remarks, made some of the nervous functions involved even more mysterious and difficult of explanation. The occurrence of Cheyne-Stokes breathing in a case of apoplexy of the cerebellum, due to degeneration of the cerebellar arteries, has been placed on record by Hurd.^ In this case marked congestion of the whole medulla oblongata was found at the examination after death. In an exhaustive article on variola, Zuelzer^ says of that disease that the respiration in the early stages is usually hard and laboured, ' Lo Sperimentale, lomo li. p. 561, 1883. '^ Boston Medical and Surgical Journal, vol. cix. p. 195, 1883. ^ Beal-Encyclopadie der gesammten Heilkunde, xiv. Band, S. 393. Wien unci Leipzig, 1883. HISTOniCAL. 67 and not inficqnently sliows at a later stage tin; irre;:,'ularity of the Cheyne-Stokes respiration phenomenon, whicli continues more or less rpyularly and distinctly, until towards tlui end in fatal cases pneumonia or pleurisy appears. ruddicoiiilic' records a case ot" apoplexy occurriuL,^ in a man, n^fcd 04, ^vll() towards the end of the disease, in the last days of his life, ilevelo])ed Cheyne-Stokes respiration. This cliaracteristic form of lu'eailiiuL; niily appeared during sleep. The pauses could l>e interrupted hy strong stin)uli, but as soon as these ceased the patient again fell into the condition of apncea. Drugs which increased the tendency to sleep made the patient worse instead of better. The effect of nitrite of amyl is worthy of note. " Nitrite of amyl," says the author, " on being held to his nostrils, stopped the symptoms temporarily, but only by causing him to wake up, which he invariably did after it had been held to his nose for seven or eight seconds." Dunin- describes three cases in whicli Cheyne-Stokes respiration was present, two being in cerebral haemorrhage, and the third in enteric fever. He is of opinion that in the last-mentioned case, at any rate, the cause of the symptom was exhaustion of the nerve centres in the medulla. IMuri'i,^ after some historical remarks, considers the nature of the phenomenon and the type of breathing to be designated l)y tlie term Cheyne-Stokes respiration, wdiich leads him to mention the investigations which he had previously carried out. He holds that there is in this condition a regular increase and decrease of the activity of the respiratory centre caused by a mechanism as yet unknown. This definition is followed by a reference to some of the views advanced by previous observers, particularly Traube, Filehne, Luciani, Luchsinger and Solokow, IJosenlxich, Lowitt, Langer, Saloz, and Fano, and this is in turn succeeded by a descrip- tion of some of the more important work done by them, and a thorough criticism of their theories. Murri then turns to the influence of stimulants, and finds that variations in {]\c amount of carbonic acid in the blood, as well as » Tlie Lancd, vol. i. U>v 1883, ji. M(>. - . 7.57, 1^83 ; aiul Airltiies italienncs de Biologic, toiiit; v. \\ 1-13, 1884. 68 CHEYNE-STOKES KESPIBATION. sensory stimuli, the effects of coughing, or of changes in the brain circulation from pressure on the neck, together with the result of moral impressions and the exercise of the will, can modify the periodic breathing. He thinks that the respiratory centre has several zones of different degrees of excitability corresponding to different groups of muscles. In health the most sensitive zone responds promptly to stimuli, and is therefore sufficient for the function of respiration. If impaired, however, it needs stronger stimuli, and these rouse the other zones, causing dyspnoea, by means of which more oxygen is supplied to the blood, and there is a more rapid current in the medulla, leading to a slowing of re- spiration which ends in the pause, during which there is again an accumulation of carbonic acid and a repetition of the cycle. The decreasing or descending respirations are due to the continuance of activity after the interruption of the stimuli ; the dyspnoea is caused by the delay in the aeration of the medulla. It must be admitted, as postulated by Traube, that the irritability of the respiratory centre is impaired in order to have the necessary conditions for the development of Cheyne-Stokes respiration, but it is unnecessary that the pneumogastric nerves should be intact. Tizzoni^ describes the lesions which he observed in two cases under the care of Murri in which Cheyne-Stokes breathing was a prominent symptom. In one of these, where the primary disease was a cardiac lesion, there was chronic neuritis of the trunk of the vagus, with sclerosis and atrophy of the gray matter of the medulla. In the other case, where death was caused by renal disease and uremia, the vagi were healthy, but there were inflammatory changes in the internal or median nucleus of the vagus as well as in the posterior nucleus common to the vagus and spinal accessory nerves. Bramwell,^ in his admirable and exhaustive work on cardiac diseases, devotes considerable attention to Cheyne-Stokes respira- tion as one of the symptoms of circulatory affections. After describing its appearances and significance, he refers to the con- ditions which may lead to its development, and gives a brief sketch of the views of Traube, Sansom, and Filehne. This brings * Memorie delV Accademia delle Scienze di Bologna, serie qnarta, tomo v. p. 331, 1883 ; and Archives italiennes de Biologie, tome v. p. 226, 1884. 2 Diseases of the Tleart and Thoracic Aorta, p. 68. Edinburgh, 1884. HISTORICAL. 69 him to state the opini. 132, 1884. 2 British Medical Journal, vol. i. lor 1884, p. 220. 3 Lo Sperimentale, anno xxxviii., tonio liii. p. 233, 1884. * 0 zjawijiku odiUrlwive'm Heyne-Stokesa. MatUtkovuki Ksieya j>ami4stkoiPa Hoyerowi, S. 277, 1884. ^ Sur une noavelk TMoriedu PMnomine Respiratoiredi Chtyne-Stokes. Paris, 1884. 72 CHEYNE-STOKES RESPIRATION. presses his opinion that the various circulatory changes which accompany the symptom are of a compensatory nature. He does not allow that the forced breathing is true dyspnoea, and compares it with analogous symptoms seen in hysteria and other nervous affections. After criticising some of the most recent work done immediately before the appearance of liis thesis, he sums up his views, stating that there is in Cheyne-Stokes respiration a constant force whose intensity is invariable and subnormal, and whose source is in the condition of the tissue, not in the state of the blood ; that the tissue centre of respiration controls its subordinate, the automatic centre of respiration, and that this latter may be affected indirectly through disturbance of its superior centre or by means of influences acting directly upon itself. In an investigation into the action of sulphuretted hydrogen on the respiration, Smirnow^ found that when the air breathed con- tained from one-eighth to one-seventh per cent, of this substance, " a classical Cheyne-Stokes breathing," as he calls it, appeared, accompanied by variations in the diameter of the pupils, the sensibility of the conjunctiva, and the rate of the pulse. The condition was present as long as the animal breathed the mixture, and disappeared when ordinary air was allowed to replace it. The author mentions that on the periodicity and ascending and descending character of the respiratory movements section of the vagi and of both laryngeal nerves had no effect. He states that the blood-pressure fell during the cessation of respiration and rose when it recommenced, while the pulse became less frequent during the pause. On dividing the vagi the change in frequency did not appear, but the falling of blood-pressure remained. Smirnow was able, therefore, to produce almost all the features of the Cheyne- Stokes respiration phenomenon, and from his study of it he is of opinion that the periodicity of the breathing is only conditioned by weakness of the respiratory centre. He thinks that the appearances presented by the circulation, pupils, and other organs depend upon a synchronous affection of the other corresponding nerve centres, which is not connected with the type of the respira- tion. 1 Gentralhlatt fur die medicinischen Wissenschafien, xxii. Jahrgang, S. 641, 1884. HISTORICAL. 73 Kaufinaini^ contrihuto.s a paper on some artificially ])roilucetl phenomena in Choyiie-Stokes l)reatliin«,', which he observed in the case of a man, aged 54, snllering from general tnherculosi?, where it was developed after the use of chloral and morphine. The periodic breathing was accompanied by changes in the size of the pupils, in the movements of the eyeballs, and in the state of tlie intellect, but not, so far as could be made out by nutans of the finger, by any changes in the state of the circulation. Kaufmann found that during the pause of the breathing, respiration could be e.xcited by the application of cold, by striking the surface of the body, by tickling the sole of the foot, and by speaking loudly to tlie patient, and he gives tracings of the respiration showing tiiese effects. These results were usually accompanied by opening of the eyelids and widening of the pujiils. He is of opinion that such effects could not be produced if there were a total absence of irritability of the respiratory centre or a condition of true apnoea, and he also thinks theories based upon a conception of exhaustion of the centre require the additional hypothesis that the increase of irritability induced by external stimuli is so great as to prevent the exhaus- tion from giving expression to itself. He comes to the conclusion that much observation and experiment is required before we can arrive at a satisfactory solution of the phenomenon. Cantieri^ records a case of cardiac disease in a man aged 5*'. who presented the symptom of Cheyne-Stokes respiration during the course of the affection. After death it was found that there was great hypertrophy of the heart with pericarditis, myocarditis, and endocarditis — the latter especially affecting the left side and particularly the mitral valve — associated with atheroma of the aorta. Bordoni^ descril)es two cases presenting Cheyne-Stokes respira- tion, one being that recorded by Cantieri, which has just been referred to, and the other patient being a man aged 76, who died under the care of a colleague in consequence of pneumonia and cardiac degenerati«jn. In the former case the pulse increased in * Pru/jer medkini.^clu- iroch''iisr/iri/(, ix. Jalii-'^ani^, S. 344 u. ;};i4, 1884. -' BulMino ddla Socirtii tra i Cidtori dcllc Scienze iiudiche in Siaui, anno ii. p. 250, l,ss4. 2 //<(•3. 18-^4. K 74 CHEYNE-STOKES KESH RATION. rate and tension during the pause; the pupil contracted during that phase, and dilated during the period of breathing. In the latter case the rate and tension were greater during the period of breath- ing than during the pause, and there were no periodic changes in the size of the pupils. Bordoni mentions several of the writers who have concerned themselves with Cheyne-Stokes breathing, but restricts himself to facts, and abstains from making any- theoretical remarks. Oser^ describes the occurrence of this form of respiration in a woman aged 74, suffering from aortic and mitral disease. The symptom occurred during an attack of intestinal catarrh, and again a few days before death ; and it is noteworthy that it could at any time be produced when it was not present by compression of the two common carotid arteries. At the post-mortem examination, besides the cardiac lesions, nothing but the usual senile changes could be found, along with some discoloration of the medulla oblongata and upper part of the spinal cord. Howard,^ in a paper on some of the varieties of dyspnoea met with in kidney disease, after referring to the appearance of Cheyne- Stokes respiration in one of his puerperal cases, suffering from ursemic eclampsia, briefly describes its occurrence in a man, 52 years old, who was the subject of chronic renal disease. The chief interest of the case lies in the fact that the periodic breathing had persisted for two months before the author saw him in consultation with another medical man, and that there was no appearance of imminent danger when he was seen. Howard mentions another opportunity which he had of observing Cheyne-Stokes breathing in an aged man sinking apparently from senile decay. He is now inclined to think that failure of the renal functions may have been the immediate occasion of the symptom, and suggests that this is probably the underlying cause of the symptom in many cases. The author makes passing reference to the work of Cuffer, but shrinks from entering into any discussion of the numerous explanations that have been advanced. Mosso, in an exhaustive monograph,^ has materially contributed 1 Wiener vudizinische Blatter, vii. Band, S. 1480, 1884. 2 Canada Medical and Surgical Journal, vol. xiii. p. 193, 1884. ^ Atti delta Reale Accademia dei Lincei, anno cclxxxii., 1884-86, serie cjuarta, p. 457, 1885 ; and Archives italiennes de Biologic, tome vii. p. 48, 1886. JllsTOi{if:.\l,. 75 to the knowleil^i^'e we jxisscss of (liis syniidom. Ilr l)(!<^ins liy ])()iiiliii^ (»uL that the moveiueiits of respiration are not always uniform and reguKar. In the; profound repose and more especially the deep sleep of man and animals, the respirations are grouped in periods, and this pcriotlic hreathin^' is quite physiological. When this periodic respiration hecomes more intense, pauses appear from the remission or cessation of inspiration, and the author terms such breathing remittent when there is a slight respiratory movement during a pause, and intermittent when there is complete cessa- tion for a time. He mentions l»i-eaks in breathing, as if a respira- tion had aborted or failed, but points out that there is no conne.vion between such a break and the succeeding respirations. Inter- mittent respiration may be caused by injections of chloral, and this cannot be moditied by making the animal breathe pure oxygen through the tracheal canula, or by artitieial respiration from electric stimuli to the respiratory nerves, from which the author concludes that the internuttences cannot be altered by the intluence of oxygen. He states that there are periods of tonicity of the respiratory muscles independently of the rhythmic movements of breathing, and that the circulatory vessels take no part in the phenomena of periodic breathing, which disposes of the complicated and imaginary tiieories of Traube, Filehne, and others. Oscilla- tions in the tonicity of the respiratory muscles are closely united with the phenomena of periodic breathing. In general, when this tonicity is lessened there is a tendency on the part of the respira- tory centre to lessen the force of the movements of respiration, and a pause often ensues. It has been thought that the greater or less activity of the respiratory centre represents a greater or less need of provision Ity pulmonary ventilation for the chemical wants of the organism ; but the author is of opinion that he is not far from the truth in thinking that the respiratory movements modify themselves according to the states of sleeping or waking, of greater or less activity of the nervous system. He holds that the mechanical and chemical parts of respiration are distinct, that the mechanical is more representative of the vitality of the nerve centres than of the chemical wants of the organism ; that if the nervous excitability increases more air is inspired than is needed for chemical wants, while on the contrary during sleep the mechanical may lessen or become periodic without disturbance of 76 CHEYNI^-STOKES KESPIRATION. the chemical f miction of tissue respiration ; and further, that when the excitability of the centres is much lowered, it can be deter- mined that the accumulation of carbonic acid by asphyxia causes almost no effect on the respiratory movements. Mosso agrees with Fano in hesitating to accept the hypothesis of Luciani, but does not see how Fano's hypothesis can explain remittent respiration, for, if it were true, periodic breathing would always appear in animals whose nervous excitability gently died away, which it does not. He points out that the ascending part of the breathing is not due to arterialization of the blood, for it appears j ust as before after the diaphragm has been cut, so as to render the respiration useless. The periods of breathing appear during sleep without any consciousness. The pauses have no effect on the vaso-motor centre if they are not very long. If any influence is shown, it is opposite in effect to that of psychic phenomena ; during the intermittences there is a diminution in the tonicity of the bloodvessels, while under the influence of psychic activity there is an increase. Referring, again, to the hypothesis of Filehne, he says it is a mere supposition, and adds that his results are con- trary to his hypothesis. He has observed the fact described by Murri, that during the pause there is an increase in the bulk of the arm as tested by the plethysphygmograph, and is of opinion that it is caused by dilatation of vessels during profound slumber. Although periodic respiration is not in direct or immediate re- lation with vascular phenomena, alterations in the circulation of the nervous centres may cause periodic respiration ; in chloralized animals it appears on raising the head, and disappears when the head is again lowered. Mosso points out the intimate relations of periodic breathing with sleep, as shown by the variations of the iris and the intelli- gence. In discussing the phenomena of consciousness he points out that there is no distinction in kind, simply a variation in degree. He refers to a case under the care of his colleague, Bozzolo, where all the reflexes, even those of swallowing, were abolished during the pause. He does not believe that all cases are due to conditions resembling sleep ; he has seen it, for instance, under the influence of curara, where the arrest of the respiratory movements caused by the motor paralysis produced sufficient IIISTOHICM.. 77 excitemenl of llie iutvous activity to overcome the influence of tlu^ curaviv on the nerves. Davies^ gives an explanation by Foster of a case in which it was noted "that the heart and respiration alternated in rhythm, tiie heart being in full swing at the pause of the respiration, and being inhibited during the height of the respiratory period." This circumstance is explained by Foster as follows : — " Apparently coincident with changes in tlie medulla oblongata leading to Cheyne-Stokes respiration was a stimulation of the cardio- inhibitory centre in the medulla, occun'ing alternately with the former." Fazio- has described Cheyne-Stokes respiration as a symjitom occurring in the course of two cases of cholera. Langendorff ^ points out that a change from regular to periodic rhythm is not peculiar to the respiration, and as examples of similar change of rhythm mentions the frog's heart nourished by means of serum instead of blood ; the ventricle of the frog's heart separated from the auricle; and the heart of the embryo of the fowl. He then starts from the point of view that the commonest cause of the periodicity of rhythmic movement is asphyxia, and seeks to determine whether it can be produced ex- perimentally in this way. In mammals asphyxia is too rapid to induce periodic breathing, but in frogs, as he .showed before, he is able to do so. He calls attention to the increased motor activity during the period of breathing, which may even reach the stage of convulsions. Frogs poisoned by strychnine and then asphyxiated show convulsions during the breathing. Tlie movements appear even after the removal of the brain, and cannot tlierefore be voluntary. It has been observeil, further, that before the respira- tory period the heart and lymph-hearts cease for a time to beat. Langendorff interprets the various manifestations of activity asso- ciated together in an attack as being the co-ordinated effects of a periodic excitement of the gray substance of the brain and cord. lUit in order to explain this periodicity in the Cheyne-Stokes ]»henomenon it is necessary to admit some opposition to the normal ' Lancet, vol. i. for ISh"), p. 1183. * Rivutta Clinica e Ti'ra}>fn(ica, :mno vii. p. 4!)4, 1885. 3 linitlaiier iiiztlich'' Zeit.paratus within the vessels analogous to the lock and trap-door, there is an external force, viz., intracranial oedema, and he regards intracranial oedema as the principal, if not the only cause of Cheyne-Stokes respiration. He regards the phenomenon as the result of a struggle between the pressure of the blood within the vessels and the pressure of the adema outside of them, a struggle in which these forces are alternately supreme. He thereupon compares the appearances accompanying Cheyne- Stokes breathing with the symptoms which would naturally be expected to follow an alternate increase and decrease of pressure, and is strengthened in his views by the comparison. The author afterwards reviews a nnnibcr of liie tlieories which hav(> been advanced, and concludes that the series of symptoms cdu hardly be caused but by such a cause as he has suppo.sed. 80 CHhlYNE-STOKES RESPIRATION. Murri^ combats the opinion of Mosso that Cheyne-Stokes respiration presents a condition analogous to sleep. During sleep the respiratory movements may cease without any injury to the interchange of gases in the tissues and blood, because there is less need for oxygenation. Eemittent and intermittent respira- tion accordingly appear where a condition analogous to sleep is developed in the central nervous system. There is lowering of the irritability of the medulla oblongata, and Mosso differs from other observers in his opinion that in this lessened irritability there is a state analogous to sleep, whence intermittent breathing is a physiological appearance instead of a rare phenomenon. He therefore seeks to draw the conclusion that Cheyne-Stokes may iiave a twofold origin — physiological and pathological. Under ordinary circumstances the phenomenon is certainly associated with sleep, but just as certainly in pathological conditions this is not always the case. The origin of the symptom is often in such lesions as interfere with the harmonious successive and gradual working of the different parts of the respiratory centre. By means of such disturbances of particular phases of its activity, its functions are no longer continuous but periodic. Storch^ records intermittent respiration, perhaps not a typical instance of Cheyne-Stokes breathing, in a horse, 18 years old, which died from what is known in Germany and Austria as " Pferdetyphus," an affection characterized by general extravasation and exudation. In this case there was much extravasation into the mucous and serous membranes. The author discusses several of the well-known explanations of Cheyne-Stokes respiration, and states that he considers Eosenbach's theory as the most probable. Fano^ criticises Mosso's work, and points out that the views therein expressed on the automatism of the respiratory centre are essentially the same as those advanced by Luciani and himself He has some hesitation, however, in regard to Mosso's sleep hypothesis. Fenoglio,* to test the accuracy of Mosso's observation that in sleep the respiration may become periodic, watched the sleep of a 1 Revista clinica di Bologna, serie terza, tomo v. p. 161, 1885. 2 Revue fur Thierheiikunde und Thierzuchf, viii. Band, S. 145 ii. 165, 1885. 3 Lo Sperimentale, tomo Ivii. p. 1, 1886. * Ibid., tomo Ivii. p. 113, 1886. HISTORICAL. 81 hundred old men, whose aj,'es averaged 75 years, uiid an vi[\\:i\ number (if ol cineroie, the result of which was a cessation of respiration. Section below the upper level of the aire cinereaj was always followed by destruction of the respiration, which could not be restored by any means. The author has never seen an ascending and descending series of respirations produced artiticially, only a descending group, but he recalls the fact that in Cheyne-Stokes breathing the groups are sometimes also of this latter kind alone. He is of opinion that periodic breathing only takes place when at least a part of the higher brain tracts has ceased to act and has lost its influence upon the respiratory centre, which he believes to accord well with the mode of occurrence of Cheyne-Stokes breathing, as, for e.Kample, in sleep and hibernation ; after the use of certain drugs, which paralyze the upper nervous centres, or lessen the circulatory supply to the brain ; and from various experiments upon the nervous and circulatory systems. In this connexion Marckwald mentions a case of hemiplegia which he observed under the care of Lichtheim, where only the descending series of Cheyne-Stokes Ijreathing was present. The patient in this case was able to modify the breathing, but when left to herself it was always periodic. In this case one-sitled deficiency of the upper brain tracts was sufficient to produce Cheyne-Stokes breathing. Marckwald points out that after the production of periodic breathing experimentally, section of the vagi causes it at once to disappear, and he is therefore of opinion that for the appearance of periodic breathing it is necessary to have the peripheral branches of the vagi in connexion with the respiratory centre. As stimuli during the pause i)roduce respirations, he cannot admit that a diminished 86 CHEYNE-STOKES RESPIRATION. excitability of the respiratory centre is the cause of the pheno- menon. Descourtis^ describes a case of Cheyne-Stokes breathing in a man, aged 68, suffering from general paralysis. In this instance the pulse, as ascertained by the sphygmograph, remained constant in its characters throughout the varying phases of the respiration. In a short abstract by Smart^ of a paper read by him at the Medico-Chirurgical Society of Edinburgh, cerebral respiration and Cheyne-Stokes respiration are grouped together as " Multiple Com- plex Eespiratory Neuroses," but the author insists on their inde- pendence of each other. Stillman' has placed three cases on record in which Cheyne- Stokes breathing was present. These cases were : — A man, aged 47, who had received injuries in a fall, from which he recovered perfectly ; a woman, aged 76, dying of cerebral haemorrhage ; and a man, aged 27, who had received an injury to the skull, from which he died. The author is of opinion that " the starting point in the chain of causation is found in the equilibrium between the respiration and circulation being always disturbed by a relatively weak heart." A communication was recently made by me* with the view of showing that, whatever may be the nature of the condition under- lying the associated symptoms of Cheyne-Stokes respiration, it may produce the effects which depend on it by affecting the lower centres in the first place, and spreading upwards to the higher, or by acting upon the higher first, and afterwards invading the lower centres. This was illustrated by reference to the presence of Cheyne- Stokes breathing in a case of pneumonia, in which small doses of bromide of potassium had been administered, without any changes in the pulse, pupil, mind, or muscles ; to its appearance in a case of cardiac failure, in which it was accompanied by circulatory, pupillary, and mental symptoms ; and to its occur- rence in cases of urtemia in association with periodic alterations in the circulatory, visual, psychical, and muscular condition. These different classes of cases were regarded as presenting a 1 L'Encephale, vol. viii. p. 431, 1888. 2 The Edinburgh Medical Journal, vol. xxxiv. p. 529, 1888. 3 The Medical News, vol. liii. p. 555, 1888. * The Birminrjham Medical Review, vol. xxv. p. 30, 1889. IIISTOIJICAL. 87 roj,'ul;ir series of syiiiptonis, coiniuenciii<,' with those sliowiiig conse(|ueiices depeiulinj^' u|)()ii some iillectioii of the lespinitory centre ;Uone, and passing tliruugh otlier.s having a progressive tendency to involve dillerent centres. The paper next attempted to show that the periodic changes produced by alterations of the centres may commence in, and be limited to, those which are not concerned in vital phenomena. The case of a child sufTering from wliat clearly seemed to be tubercular meningitis, but which, owing to the recovery of the patient, may appear to have been possibly an error in diagnosis, was taken to illustrate my meaning. The patient was a little girl, aged three years, presenting all the symptoms of subacute tubercular meningitis. During the course of the disease, when watching her carefully one day, a periodic closure of the eyelids attracted my attention, and on fuitiier observation it was easy to determine that along with this closure of the lids there was a simultaneous contraction of the pupils, an«l a state of complete unconsciousness. This condition remained for several seconds, the eyelids were then raised, the pupils dilated, consciousness returned, and the child raised her head to look about. The conscious state was present for some time, how long it is not possible for me to say, as it did not occur to me to notice the interval, and was in its turn followed by the uncon- scious condition. In this case there was never, so far as my observation went, any tendency to a periodic change in the rhythm of the breathing. It seemed to me that such a phenomenon can only be regarded as analogous in every way to intermittent re- spiration, and, if this be granted, it follows that my contention is to be regarded as highly probable. This brings us to the end of the examination of the facts and views embodied in the different works on the subject. In addition to the authors who have been mentioned, reference might have been made to many others who incidentally touch upon the subject, but, in so far as my acquaintance with the literature is concerned, these authors neither add anything to the store of facts nor throw any light upon their explanation. It is, in consequence, unnecessary to devote time and space to them. Before leaving this division of the subject, a few remarks must be made upon three unpublished observations which have been communicated to me. 88 CHEYNE-STOKES KESPIRATION". Dr Muirhead, of Edinburgh, informs me of an elderly gentle- man, who for many years during his daily sleep after dinner breathed in the characteristic Cheyne-Stokes type. Dr Edes, of Washington, writes to me with regard to a lady whose breathing has for many years been periodic or cyclical, as he prefers to term it, during sleep. A most interesting fact is that this lady tells him the phenomenon had been observed by her mother in herself and her sister from childhood. Finally, Dr Tuke has placed the following interesting communi- cation in my hands : — " Balureen, "Edinburgh, 28th February 1889. *' Dear Gibson, — Knowing you are specially interested in ' Cheyne-Stokes breathing,' I send you a short report of a case which came under my observa- tion last Saturday. On that afternoon my two favourite Dandie l^inmonts were poisoned by strychnine, which had been laid down for rats in the stable ; the one fatally — dying in opisthotonus — the other recovering after fifteen hours of suffering. During all that time he was under my most careful observation. After five violent spasms (opisthotonus) I bolstered the dog in such a way that he could not move, as the slightest stimulus induced the attacks. By this means the general spasms were averted, and only occasional jerks were observed. But fifteen minutes after he was thus restrained well-marked Cheyne-Stokes breathing set in — the number of respirations was about 25, and the interval was somewhat longer than I have generally noticed in the human subject. The pupils were fully dilated during the breathing, the iris contracting slightly during the interval. So far as I could judge, the dog was conscious all the time, often trying to wag his tail. The rate of the heart was 120, and its action was regular, which is curious, as, under ordinary circum- stances, this dog's heart, like that of most dogs, is very irregular, and some- times intermitting. Its usual rate is 104. The femoral pulse was full and steady. When violent spasms showed themselves, the Cheyne-Stokes breathing ceased. I kept my hand slightly pressed on the ribs ; when doing so the breathing never reached dyspnoea, but when the pressure was removed the symptom tended to show itself. After thirteen hours all the symptoms disappeared — the Cheyne-Stokes breathing gradually growing less pronounced — except stiffness of the hind legs. — I am, yours sincerely, John Batty Tore." So far as my knowledge goes, Cheyne-Stokes respiration has not been observed as a consequence of the action of strychnine on mammals by any of the authors who have devoted attention to the subject. CLINICAL. 89 Clinical. Ill aiiproacliinp; the coii-sideration of Cheyne-Stokes respiration fmiii the clinical point of view, it will lie necessary to i^roiip the coiulitions, already mentioned in the historical sketch, in which it has been observed. IJefore doing .so, however, it must be stated that l)y the term om[)l()yed to designate the phenomenon is meant a periodic form of respiratory rhythm. It would be out of place to attempt, at this stage of the inquiry, any definition of the symptom, l)ut it will certainly tend to simplify the subject if it be distinctly understood that the term employed is limited in its application. It will not, in this paper, be held to include any irregular arrests of breathing, such as are frequently observed in diseases of the brain, and which are generally classed together under the term cerebral l)reathing. But in making this distinction there is no intention of drawing a luird and fast line between the regular periodicity of events seen in classical Cheyne-Stokes breathing and the altogether irregular stoppages of respiration characteristic of cerebral breathing. So many intermediate links are to be found between the two extremes, that the existence of an uninterrupted series of similar symptoms may safely be assumed. From the observations of some authors there can be no doubt that there is a hereditary tendency in certain families towards the conditions under which Cheyne-Stokes respiration arises, and in some cases an inherited liability to the symptom itself has been found. Amongst general diseases, Ciieyne-Stokes respiration has been observed in the course of enteric fever, small-pox, diphtheria, choli'ia, and w lioopiiig-cougli. The nervous disea.ses in which it has been described are: — meningitis, encephalitis, cerebral luemorrhage, cerebral embolism, cerebral thrombosis, insolation, insanity, liysteria, cerebellar luemorrhage, extravasation on the medulla oblongata, pressure of an aneurism on the medulla, and tumour of the medulla and pons. The symptom has been very fretiuently recorded as a cense- ([uence of general arterial degeneration, attemled in some cases by gangrene or degeneration. It has been obseived in hicmophilia, M 90 CHEYNE-STOKES EESPIRATION. as well as hsemorrhage following severe operation, and it has been seen in such more restricted diseases of the circulation as peri- carditis, myocarditis, fatty degeneration, valvular diseases, and aneurism. The respiratory affections in which Cheyne-Stokes respiration has been found are : — ^bronchitis, pneumonia, and phthisis, and it has been described as a sequel to tracheotomy. Amongst digestive disorders, the symptom has been placed on record as occurring in the course of severe catarrhal diarrhoea. Chronic renal disease is, without doubt, the most common cause of Cheyne-Stokes breathing, a large percentage of ursemic cases presenting the symptom in some part of their course. Before leaving this summary of the diseases in which Cheyne- Stokes respiration has been observed, reference must be made to two singular conditions in which it was present. Fatty degenera- tion of the diaphragm was in one case associated with this symptom, but disease of the aortic valves was also present. Narrowing of the foramen jugulare was found in several cases presenting this symptom, but in all of these there was also cardiac or renal disease. Cheyne-Stokes respiration has frequently been observed in the ordinary sleep of apparently healthy persons, and it has often made its appearance after the administration of bromide of potassium, chloral hydrate, and morphine. In one most interesting observa- tion the symptom was developed in an infant whose mother, while nursing, had taken some doses of the latter drug. In the lower animals, phenomena identical with Cheyne-Stokes respiration have been of frequent occurrence. Such appearances have been present during the deep sleep which has followed pro- longed exertion, and also during the condition of hibernation. Intermittent respiration has been produced by the administration of chloral, morphine followed by ether or chloroform, ether along with picrotoxin, muscarine, picrotoxin, digitalin, strychnine, sul- phuretted hydrogen, urea, kreatin, and ammonium carbonate. Periodic breathing has further been produced by considerable changes of external temperature, by prolonged immersion (in amphibians), by bleeding, by removal of the heart, by alternate compression and relaxation of the carotid and vertebral arteries, by section of the medulla oblongata, with or without section of the CLINICAL 91 vaj^n, by pressurt' t-ii the iiiciliilla, iind by various injuries to iIm" brain ami in('(hill;i, even after tbii aorta had been ticil. It is particularly worthy of notice, that section of the medulla at the h'Vi'l of the aUr. cincrecc, seems invariably to produce a periodicity of the respiration. "When the medulla is divided above that level, no ehani^fo in tlu' rhyllnn of the breathing' occurs, while section below iliat U'Vcl ]irtMlurcs an cntii'e cessation of respiration. Tuvnin^^f now from tlie cimsiilcration of the dillerent conditions in which Uheyne-Stokes brealhinif has been observed, the nature of the symptom in itself must be dwelt ui>on at somewhat greater len.^th. The ilescriptions given of thi.s phenomenon by Cheyne and Stokes, which have so often been quoted, have never been surpassed, and no attempt will be made here to describe a symptom which is now so well known. The purpose of this part of the paper is rather to analyze the different phenomena which make up the symptom. In Cheyne-Stokes breathing the normal rhythm is interrupted by distinct arrests of respiration ; there is an alternation of periods of resi)iratory activity, and periods of respiratory repose. Under ordinary conditions, the inspiration, the expiration, and the short pause which succeeds the latter phase, have a tlefinite relation in duration, and they are perfectly rhythmic in their recurrence. The arrests of respiration occur usually at definite intervals of time; they are therefore periodic, and it may be said that there is a secondary, superimposed upon the primary, rhythm. This, how- ever, is not all ; for an essential feature is that the period of activity consists of two distinct phases, termed by Cheyne ascending and descending. During the former phase there is a gradual increase, not only in the amplitude of the respiratory movements, but also in their rate ; while during the latter phase there is a gradual decrease, both in extent and rate, of these movements. The contrast between the period of repose and the period of activity is very striking. I taring the former phase there is an entire absence of all movement, and during the latter the patient often appears as if labouring under severe dyspntca, which is frequently accomi)anied Ity a lit of coughing at the height of the breathing. Such are the appearances in a simple instance of Cheyne-Stokes breathing. lUit Cheyne- Stokes breathing is frecpiently associated with other symptoms. 92 CHEYNE-STOKES KESPIKATION. and attention must be directed to changes in other systems besides the respiratory. There are in many cases alterations in the state of the circula- tion. These appear to have been first observed by Eeid, whose descriptions of the state of the pulse must be stated in passing to be extremely careless in the use of terms. Such circulatory altera- tions are at once inconstant and variable, presenting a marked contrast to the regularity of the respiratory phenomena. In many cases no change in the state of the circulation can be observed on the closest investigation, as in cases described by different writers. Sometimes the rate of the pulse is diminished during the pause in respiration, as in cases narrated by several observers. As lias been mentioned in the previous part of this paper, Hesky observed an entire arrest of the radial pulse during the period of repose. On the other hand, the rate of pulsation has been observed to be greater during the period of repose than during the period of breathing. Variations also in the volume and tension of the pulse have been met with. The pulse has been described as of larger volume and lower tension during the arrest of breathing than during the period of respiratory activity. In other instances no such changes could be detected, or the converse has been observed. Filehne observed a recession of the fontanelles of children before the arrest of resj)iration ; and, on the other hand, Eosenbach describes the recession as occurring late in the pause, or even during the period of respiratory activity. In this connexion reference must be made to the experiments of Heidenhain, who observed an increase in the blood-pressure during the period of activity. There are also certain appearances connected with the eyes which occur in association with Cheyne-Stokes breathing. In many cases the periodic rhythm of the respiration only takes place during sleep, when, as may readily be understood, no changes are observed in the eye. But in a large number of instances the symptom is present during the waking, as well as the sleeping hours. In a certain number of such cases Cheyne-Stokes breath- ing is unaccompanied by any eye-changes. In a certain number, hovfever, definite appearances make themselves manifest in con- CLINICAL. 9:i nexion with tlie visual apparatus, and tliesc must liave attention devoted to them. As was lirst noticed by Ixjube, the eye is open during the period of l)reathing, and closed durin^j the ces.sation of respiration. The eyes, furtlier, glance about while the patient is breathing, while, during the pau.se, on lifting up the eyelids, aeon- jugate tleviation of tlie eyeballs may be ob.served. A still more interesting fact is to be seen in some of the cases which present eye-symiitoms. During the breathing the pui)il is wiilely dilated, and tightly contracteil during the pause. As Leube pointed out, the dilatation begins along with the early superficial respirations, or the dilatation may even precede the active phase of the breathing cycle. Appearances exactly similar in character were observed by Leyden as the result of experiments on the medulla. This is, however, not all, for Finlayson, on close scrutiny of the pupil, found that it dilates a little with each inspiration, and con- tracts slightly M'ith each expiration, until the height of the respiratory phase is attained, and the pupil is widely dilated, after which the converse occurs, and the contraction with each expiration somewhat exceeds the dilatation accompanying each inspiration, until at the end of the active phase the pupil becomes fixed in the contracted condition. The contracted condition of the pupil during the cessation of respiration is evidently analogous to the appearances observed during sleep, and in this connexion it may be remarked that the pu[)il in some persons enjoying perfect health undergoes a considerable dilatation on deep inspiration and contracts to an equal degree on forced expiration. As Merkel first pointed out, the pupil reflex is absolutely abolished during the cessation of respiration, and no reaction to light can be elicited. It is a most important fact that no changes have been seen in the condition of the ves.sels of the retina during the varying phases of respiration. Both Schepelern and Ewald, who have devoted themselves to the investigation of this point, are perfectly confident in regard to the absence of any alterations in the calibre of the vessels. In many cases showing Ciieyne-Stokes respiration, the condition of the mental powers undergoes fluctuations. The most usual state of matters is, as Leube first showed, that the patient is con- scious during the period of breathing, while during the interval of repose he is bereft of perception and volition. This alternation of 94 CHEYNE-STOKIOS RESPIRATION. consciousness and unconsciousness is frequently, but not invariably, associated with the variations in the appearances of the eyes just referred to. The interesting observation of Merkel has occasionally been repeated since. He put a question to one of his patients to- wards the end of the descending phase of the period of breathing. The patient sunk into the state of absolute repose, but on the return of respiration he made a suitable reply to the question which had been put to him. This observation, to compare small with great matters, is somewhat similar to the classical account of the officer who was wounded in the head at the Battle of the Nile, when in the act of uttering a command to his men, and who, after tifteen months of unconsciousness, finished his order after the operation of trephin- ing. Such cases as these, in which patients are only in possession of their mental faculties during the phase of breathing, form a marked contrast to others in which the patients are conscious throughout, and often employ the pause in the breathing for the purpose of conversing with other people. Out of the many cases showing this symptom which have come under my observation, a few will now be narrated in illustration of the various appearances, and these will be arranged as far as possible in a definite series, in order to emphasize the difference which they present in the association of phenomena. Case I. — Lady, aged 73 ; seen for tlie first time 29th March 1888, about the ninth or tenth day of an attack of croupous pneu- monia affecting the lower lobe of the right lung. The rate of the . pulse and respiration and the height of the temperature may be seen on the accompanying cliart, Plate I., which is based upon the very excellent graphic clinical chart of my friend Dr Handford. There was free expectoration of rusty sputum, increased vocal fremitus over the base of the right lung, dulness on percussion over that region, and bronchial breathing, with increased vocal reson- ance in the same situation. The pulse was of moderate volume, low tension, and regular rhythm. The state of the heart was healthy. The urine contained no abnormal constituent. There was no delirium during either day or night. On the evening of 1st April, three days after the crisis took place, during the • administration of ten grains of bromide of potassium with ten minims of tincture of digitalis three times a day, Cheyne-Stokes Plate MARCH :-i!i 'U/ '// / •'. "> / / t'l M 7 P R T mIe ME M E ] m' e M E M E Ml E M E M E t -TOO h 1 i\ • .>T f\ ,^ 1 \ k — ^q| 1 l\ . \ 1 \ _ - „_ 1 >^^ '" 1 I , 1 \ \ ■iSv^ — 1 itrr . \ \ i\ \iti'\ ' 1 1 \ \ 11 \ j. . \ 1 \ 1 \ 1 \ -or \ 1 1 \i \ / \ ■4- 1 ' / ^, / tf / 1 120 30 104 \ ' ; 11 ^ / \ / 1 ' / \ t / V j > 29 \ A 9^ / \ 1 V X J i I I ' 28 1 \ f>i / ■] S \ 1 110 103 I J 1 ; ^ I 1 1 I f *. K / ^ A H y /> ? ^J ! ' 1 26 / / : •^J 1 S 1 ij 1 « '\ 100 25 102 ■M '. 1 N \ 124 • ^ 1 4 ^ ! A lA i 4 _ \ nr\ I \ A 1 t V CO r.rr i' •• .^*\ _- ■\ I '. 90 101 ri-j \ c f ' ''•^'' \ c y'*" '•- .;. U \ • V' ■'* , 1 ■••• 1 Zl 1 \ { 1 1 V 1 1 80 20 too 1 1 1 1 1 1 I ^ Ik A '• 1 la > l\ 1 1 \ / \ ' 1 ^ i A k. >v ! - A 10 ; ^w \ / ' V / S<^ 70 17 99 1 ' i >- - i 1 \/ ^ y A V \ Y \. i ^ \ NOINAL V \ v_y \ 16 LINE ^^ 1 V en nn yu 1 , "t*r ... |.. 1 ' ou y/ I<1 i 1 1 II 1 1 1 40 10 96 -J h>/s> Iir.';p/,-<'^'/ fi . /'//•' /v/-»r////'. CLINICAL. 05 hroiilliiiii,' uiiulc its iippoaraiice in typiial I'ashiuii. This symptom })ersisteil tlirouglioiil tliu ftill(»\viii;4 four days, diirin;,' waking as well as sleeping moments, and disappeared during the afternoon of 5th April, on the withdrawal of the bromide of potassium. The periodic changes in the res[)iration were accomi)anied by no corre- sponding alterations in the circulatory, visual, or mental processes. The patient's pulse beat with a steady uniformity during the waxing and waning phases of the breathing ; no modification in the rate or rhythm was jiresriit, and not the least alteration in volume or tension could be determiui'd in relation to the ascending and descending respiration. In the same way not the slightest ten- dency to closure of the eyelids during the arrest of respiration was at any ])eriod present, and it was therefore an easy matter to determine that the pupils underwent no modification in size, except when vision was accommodated to near or distant objects, or a change in the amount of light caused the usual retie.x altera- tion in size. Similarly, the state of the consciousness was abso- lutely independent of the pliases of the respiration. The patient had a tendency towards somnolence, but when waked had as much mental activity during the cessation of respiration as during the period of breathing ; in fact, as is often the case, she employed the pause by preference for the purpose of talking with those around her. This case forms an excellent example of the occurrence of Cheyne-Stokes breathing in a patient who, in spite of advanced years, showed no vascular degeneration, no cardiac allection, and no renal disease, and who, it may be added, made an entirely satisfactory recovery from the attack of acute pneumonia. It is to be regarded as a specimen of the simplest type of periodic respiration, in a patient entirely conscious of all her surroundings, unattended by any of the other symptoms often associated with it. Cask II. — Lady, aged 03, who showed the usual signs of chronic vascular degeneration without very obvitnis renal complications. On 7th February 1888 she was suddenly attacked by an ajjoplectiform seizure. When seen during the al'tcrnoon she was lying with a dusky Hush on her cheeks, and beads of perspiration on her lurehead, in a state of profound uncon.sciousness. The periodicity of breathing was very marked, nothing like the irregular 96 CHEYNE-STOKES EESPIEATION. arrests of respiration, commonly called cerebral breathing, being present, but the regular ascending and descending respiration, with pronounced stertor and flapping out and in of the lips and cheeks at the culmination of the ascending phase. The sensory and motor functions were entirely abolished. The eyes were closed, and on separating the eyelids the pupils were observed to be contracted to the size of a pin-point, and to undergo no varia- tions in diameter with the changing phases of respiration. The pulse was extremely frequent and of very high tension, but per- fectly regular, and manifesting uo alteration in tension, fulness, or rate corresponding to the respiratory phases. The Cheyne-Stokes type of breathing persisted until a few hours before the death of the patient, which occurred during the morning of the following day. On post-mortem examination the cause of death was found to be thrombosis of some of the branches of the middle cerebral arteries. The arterial system was somewhat degenerated throughout, the heart slightly hypertrophied, but otherwise healthy, and the kidneys showing to a certain extent, although not very markedly, granular clianges. This case is to be regarded as furnishing an example of Cheyne- Stokes respiration in a patient absolutely unconscious, which was not associated with any of the other symptoms often linked with it. Case III. — Farmer, aged 74, suffering from chronic arterial and renal degeneration. On 6th March 1888, in spite of every pre- caution, he showed symptoms of ursemia, and, notwithstanding the most energetic treatment, he sunk gradually into a comatose con- dition. During the last two days of his life he had, as one of his symptoms, Cheyne-Stokes respiration almost without intermission. Before the fully comatose stage of ursemia was reached, the patient was, during the arrest of respiration, in a state of unconsciousness, from which he could not be roused by any form of stimulation. But with the superficial respirations which ushered in the period of re- spiratory activity, the patient opened his eyes and looked around him, speaking, during this phase, to those who were with him. It was singular that the most rigid scrutiny of the eyes entirely failed to reveal the slightest difference in the size of the pupils during the opposite conditions of the respiration, and there never was the (LINICAI,. 97 loa.st tendency to conjui,'atc deviation of the eyeballs. The pulse was infrequent, of liit,di tension and al)Solute regularity, underj^oinj^ no changes in rate, volume, or tension throuf,djout the varyitig phases of the respiration. This case gives a good example of Cheyne-Stokes respiration attended by varying degrees of consciousness, but without any visual or circulatory jilienoniL'na accompanying the respiratory phases. Cask IV. — Housekeeper, aged (>0, suffering from chronic renal disease. Pnscnf condilio/i, Qlh November 1885. — The patient is of medium height and slender build, with a pallid complexion, tending towards an icteric tint, which is distinctly present in the conjunctivae. The expression is anxious and restless, with staring eyes and dilated pupils. The tongue is covered with a thick yellow fur. The temperature is 9S°*2 F. The pulse is 96 per minute, regular, tardy, and of extremely high tension. The radial artery, like the arteries throughout the body, is atheromatous. The impulse of the heart is somewhat diffuse, and the diastole is accompanied by a sinking inwards of the fourth, fifth, and sixth left intercostal spaces. The apex-beat has its point of maximum intensity in the fifth intercostal space, oh inches to the left of the mid-sternal line. The impulse is forcible, and is followed by a well- marked shock accompanying the second sound. No thrill is present. The first sound is dull and thumping in its character, and in the aortic area the second sound is much accentuated. No murmur is present, but a to-and-fro friction sound is to be heard very dis- tinctly over the base of the heart. There are no morbid symptoms connected with the lungs. The urine amounts to 25 ounces in twenty-four hours. It is of a pale yellow colour, with a specific gravity of 1013, and a highly acid reaction. It contains about one-fourth of albumin, and 75 grains of urea per ounce, or 187'5 grains per day. Microscopically, the urine contains broken granular tube-casts, and amorphous urates. J)i(tff)wsis. — Chronic granular kiilney, with some roughening of the pericardium as the result of an intercurrent pericarditis. The patient continued to grow worse in spite of free purgation N 98 CHEYNE-STOKES RESPIRATION, and other remedies employed. On the 12th November, after two nights of wandering delirium, Cheyne-Stokes respiration was first observed towards evening, and on the 13th it was fully developed. It was accompanied by most of the appearances usually associated with the symptom, but, as will be seen from the sequel, there were few variations in the state of the circulation. During the pauses in the breathing the patient lay perfectly motionless with the eyes closed ; immediately before the first shallow inspiration of the ascending series of respirations she opened her eyes, and the pupils dilated ; as the respiration deepened into dyspnoea her eyes began to roll about, her head was thrown from side to side, and her hands jerked violently in various direc- tions ; at the height of the breathing she attempted to rise up in bed and muttered to herself; with the descending series of respira- tions these phenomena passed away, and when the phase of arrest was reached she had resumed her motionless attitude. The pupils during the pause were found to be contracted. The pulse varied very slightly, if at all, in its rate throughout the cycle of events, never being less than 24 or more than 26 beats in a quarter of a minute. The tension, so far as could be estimated by the finger, varied still less. The following day, with the kind assistance of my friend Dr James, some tracings were obtained with the cardiograph and the stethograph, one of which is given in Fig. 1, Plate II. Tliis tracing, which, like the others, is to be read from left to right, shows the respiratory curve above and the cardiac curve below, with signals from a time-marker registering every fifth second. It shows that the number of respirations during the period of breathing was about 36 ; that the period occupied about 25 seconds, and the pause about 5 seconds ; and that the pulsations of the heart did not vary much in rate, although the tracing is naturally modified by the heaving of the chest during the period of dyspnoea. Unfortu- nately all attempts to obtain a tracing with the sphygmograph failed on account of tlie jerking which took place during the breathing. On the 15th the patient was in the same condition, and it was deemed advisable to have recourse to the use of nitrite of amyl. A few drops were administered by inhalation during a period of respiration. Tiie drug at once caused flushing of tlie face and ^'^AJ / h- ^ Plate !l. Frql Fiff4. Fiff. A 'V\/\/W^ /■I, 6. ci.iNiCAr,. 99 neck, liut (lid nut intcrft'io with tlie periodic pause in the respira- tion. Its ai'tion was tested by several inhalations, during sonic of whieli tracings were obtained from the chest. Fig. 2, Plate II. sliows the curve obtained while the drug was administered, and it proves how slight was the elVect of nitrite of amyl on the respira- tion. The lirst pause after the use of the drug appeared with its wonted regularity, and before the second pause a period of shallow breathing was found to intervene. By the IGth the urine had almost become suppressed, and as a last resource it was resolved to employ pilocarpine. One-quarter of a grain of the nitrate was administered subcutaneously, and in order to ascertain whetlier this substance had any effect on the conditions leading to Cheyne-Stokes respiration, tracings were taken with the stethograph. Fig. 3, Plate II., was taken immediately after the injection, and therefore before the drug could have caused any direct effects upon the central nervous system. It shows that three pauses were only present in the form of shallow breathing, but that the fourth pause was clearly marked. Fig. 4, Plate II., taken five minutes after the injection, has three complete pauses and one incomplete. Fig. 5, Plate II., taken ten minutes after administration, shows very irregular breathing, with pauses intervening between the periods. On the 16th the power of swallowing was lost, and the patient could not be roused ; on the 17th she sank steadily, and on the 18th she died. To the last the Cheyne-Stokes respiration was present. A post-mortem examination of the body was made, the day after death, by my fiiend Dr Eussell, to whose kindness I am indebted for the following description: — The body was fairly well nourished. There was a decided icteric tinge in the skin and conjunctiva?. liigidity and lividity were present. There was no anasarca. Tliorax. — There were 6 oz. of brownish-coloured lluid in the right pleural cavity, and 13 oz. of a similar iluid in the left. There were some old pleural adhesions on the right side. Both lungs were congested and oedematous, especially posteriorly. Otherwise they were normal. The pericardium contained no lluid. The heart was lirndy contracted. It was considerably enlarged. There was a large 100 CHEYNE-STOKES EESPIEATIOX. deposit of fat on its surface, more especially on the anterior aspect of the right ventricle. The coronary arteries were markedly atheromatous, segments of them being converted into rigid calcareous tubes. The anterior one contained a thrombus not far from its origin, which may have been formed during the process of dying. The muscle of the left ventricle was firm and of a good colour, it varied in thickness from | inch to I inch ; at the apex, however, it only measured I inch, and part of the muscle was replaced by fat. At this point a firm decolorized clot about the size of an almond, and not of very recent formation, had been moulded into a depression in the ventricular wall. The mitral cusps were somewhat thickened, and their free edges slightly retracted. At the junction of the posterior cusp with the cardiac wall there was a thick nodular crescent of calcareous matter over which the endocardium was intact. The chordce tendinece were also thickened. The aortic valve was competent, but its cusps presented a few small and hard calcareous nodules at their junction with the ventricular wall. The aorta immediately above the valves showed a consider- able tract of atheroma. The muscle of the right ventricle was deeply covered with fat, the muscle itself measuring \ inch in thickness. There was much tough blood-clot entangled in the meshes of the columnce carnece and musctili ijctpillares. The tricuspid and pulmonary valves were normal. Abdomen. — The abdomen contained 20 ozs. of brownish-stained serum. The surface of the organs was bile-stained. The intestines in places presented traces of recent peritonitis, their coils being agglutinated to one another by soft lymph. Both kidneys were very small, hard, and tough. On sec- tion the normal arrangement could be traced with difficulty and only at a few points. There were numerous cysts both on the surface and in the substance of the organs. The cortex was practically obliterated in places. The interlobular vessels were much thickened. The capsules were firmly adherent, and when torn off left a coarsely granular surface. The organs, in fact, presented the ordinary appearances of advanced atrophic cirrhosis. The liver had some old and firm adhesions at its posterior edge, and at this point there was a depressed cicatrix in the centre, on section of which there was found a calcareous mass CLINICAL. I'tl twice tlie size nf ;m alinoiiil. Its left edge extended f;ir into the left liypocliondriuin, and Wiis united to the upper border of the spleen by old adhesions. The organ itself was congested and fatty, with a slight increase of its connective tissue arranged in a polylobular fashion. The spleen was of normal size and somewhat linn consistence. An examination of the head was not permitted. The point which calls more especially for remark in a clinical res])ect, in addition to tlie persistence of the chief .symptom, is the fact that the pericardial serous membrane was quite healthy — there were no adhesions, and there was no roughening of the surface. The pericardial friction, therefore, was ap})arently caused by the irregular and projecting anterior coronary artery rubbing against the parietal layer of the pericardium. In this case nitrite of amyl caused no change in the type of the lireathing, although, as shown by the Hushing of the face and neck, it produced its usual effects on the circulation. The injection of pilocarpine caused a temporary disappearance of the periodic pauses in the respiration. In this case the periodic variations in the respiration were attended by associated changes in the mental, visual, and muscular functions, but in so far as could be ascertained by the most rigid scrutiny, there was not any synchronous moditicatiou of the condition of the circulation. Case V. — Gentleman, aged 63, with a history of chronic alcohol- ism, who had for four years suflered from paralysis of the right leg. For some weeks he had been confined to bed on account of general weakness, and when seen on the 7th June 18S9 he had general anasarca. The urine was increased in quantity, but markedly deficient in urea ; it contained albumin, but no tube-casts were present. The pulse was of high tension, showing, however, a tendency to failure of arterial pressure. The heart was dilated and hypertrophied ; the second sound in the aortic area was somewhat accentuated ; in the mitral and tricuspid areas there were soft systolic murmurs. The lungs, in the presence of crepi- tations at their bases posteriorly, gave evidence of pulmonary anlenui. The ca.se was obviou-sly an instance of chronic giiiuular kidney, with cardiac failure. 102 CHF.YNE-STOKES RESPIRATION. The last pliase of his malady was characterized by the occur- rence of uraemia, during the presence of which Cheyne-Stokes breathing was a prominent and persistent symptom. Fig. 6, Plate II., is a tracing of the respiratory movements of the thorax, obtained on the 13th June by means of Marey's stethograph with the kind assistance of my friend Dr Aitken, with whom the case was seen. During the pauses in the respiration the patient lay quietly in a state of unconsciousness, with the eyes shut, and it was difficult to rouse him even by powerful stimuli. On forcibly opening the eyes during this pause, the pupils were seen to be contracted to their smallest diameter. At this period the pulse was small, regular, and of high tension. After the lapse of from twenty to thirty seconds, the patient moved his head a little and partially opened his eyes. The pupils dilated to a slight extent, the pulse lost some of its tension, and these changes were followed by a superficial respiration. This respira- tion was succeeded by a slight and momentary contraction of the pupils, followed immediately by dilatation to a greater extent than at first, and succeeded by another respiration of greater depth than the first. This alternate dilatation and somewhat slighter contrac- tion of the pupil respectively preceded and followed each of the ascending respirations, until at the culminating point the pupil was widely dilated. The pulse during the phase of waxing respiration gradually became fuller in volume and less in tension. Fig. 7, Plate II., is the tracing obtained by means of Marey's sphygmograph during the period of repose ; Fig. 8, Plate II., during the phase of activity. They show that the pulse was smaller and more frequent during the arrest of respiration than during the period of breathing. The patient became more and more restless as the breathing deepened, until at the point of the most profound dyspnoea he showed considerable tendency to spasmodic jerkings of the arms and legs, and made efforts to converse with those near him. From this point the reverse series of phenomena began to be manifest. The respiratory movements became less in amplitude, the pupils after each breath contracted to an extent greater than the dilatation preceding it, the pulse-rate increased and its volume lessened, the eyes gradually closed, and the patient sank into the state of pro- found unconsciousness. In this case the entire complex of symptoms constituting the CLINK'AL 103 ClieyiieStokes iili('nniii(.'ii(ni uf tin; niDilciii (Iitimum S.Iioul funnfil ji strikiiiLf and coiiiplutu clinical idclurc. 'I'lii.s group ot" live cases presents an almost perfect series of j)liL'n<)niena, from the simplest form of Clieyiie-Stokes breathing, unaltendcd hy any other periotlic chan^^es, to the complex of symptoms— respiratory, circulatory, and nervous — known as the Cheyne-Stokes phenomenon. In the sequel an attempt will be made to analyze the conditions underlyini,' ihe diflurent appearances. Another case, somewhat anomalous in certain respects, and of much interest as throwing a strong side-light on the occurrence of the periodic respirations, must, in conclusion, be described. Case VI. — Gentleman, aged 65, seen 24th April 1886, suffering from arterial degeneration and cardiac failiu'e. Face somewhat cyanotic ; ankles slightly a3dematous. Pulse e.xtremely irregular in rhythm and variable in rate, of low tension in spite of some atheroma of tlie radial artery, as well as of the general arterial system. Heart considerably dilated, witli diffuse pulsation. No murmur couhl be detected, but the first sound was feeble, and the second sound in the pulmonary area considerably accentuated. The rhythm was extremely irregular. The lungs presented no abnormal phenomena. The urine contained no albumin. During calm waking moments and during sleep the breathing of the patient was perfectly regular, but whenever he was engaged in any mental effort the breathing fell into groups of ascending and descending respirations, and in conversation he found it necessary to employ the pauses for speaking. In this case the pulse showed no corresponding periodicity in any respect, and there was not the slightest approach to any changes in tiie opening of the eyelids or in the size of the pupil. It goes without saying, from what has just been described, that no alternations in the mental state attended the respiratory changes. This observation appears to me to be quite unique in the fact that e.xcitement produced the cyclical breathing, the converse of what has so often been previously observed. 104 CHEYNE-STOKES RESPIRATION, Critical. The most satisfactory method of entering on the consideration of the conditions underlying the complex of symptoms, already discussed from the clinical point of view, is obviously to be found in a survey of the ground traversed by previous observers. In the earlier pages of the present v^rork the gradual develop- ment of clinical knowledge in regard to the phenomena, and the continuous evolution of ^etiological doctrines with reference to their causation, have been dealt with in simple chronological order. But to have a thorough grasp of the entire subject it will be necessary, in weighing the different views which have been advanced, to arrange them in groups. Tiie discussion of these opinions will lead in due course to certain definite and substantive conclusions. The earlier observers advanced no theories in explanation of the periodicity of the respiration, for although Stokes regarded this as a consequence of fatty degeneration of the heart, and Schweig associated it with stenosis of the jugular foramen, causing pressure on the vagus, neitlier observer offered any opinion in regard to the possible means by which such lesions might produce the symptom. Somewhat analogous in its vagueness is the opinion of Broad- bent. In a work which made its appearance after the earlier portions of this work had passed through the press, and which will be more fully referred to in the sequel, he refers Cheyne-Stokes breathing to hish arterial tension, and cites some cases of this kind in which its presence was determined by the supervention of some complica- tion. From the consideration of these observations he is led to conclusions adverse to any hypothesis with regard to the respira- tory centre, whether of exalted or diminished sensibility, and he is of opinion that they point to a loss of the normal adjustment between the systemic and pulmonary circulations. He gives no explanation of the mode of operation of the loss of balance. It seems a sufficient answer to these views to recall the fact that periodic breathing occurs under very varied conditions. It is un- doubtedly true that Cheyne-Stokes breathing is more commonly found in cases presenting high arterial tension than in patients who have a low arterial pressure ; but it is necessary to take into CIMTFCAI.. 105 account cnses belon^ini,' to tlie latter class, and no hypothesis can be accepted as even plausible if it fails to do this. Broadbent's views, moreover, make no attempt to explain why the high arterial tension, whether with or without a disturbance of the normal adjustment lietwecn the systemic and pulmonary cir- culations, shdidd induce such a strikinn change in the rhythm of the respiratiiiii, and tiny dn iioi take iiitn consideration the various associated symptoms occurring with the periodic breatliing. For these reasons, as well as on accDunt of the I'act that Chcyne-Stokes respiration often occurs witliont liigli arliiial tension, his views cannot be entertained. The earnest attempts to explain the occurrence of the periodic phases of the breathing will now be considered according to the classes into which they naturally fall. There are, firstly, certain vague and indelinite views based upon the hypothesis of a persistent diminution of the functional activity of the respiratory nervous mechanism. "Walshe mentions "anaesthesia of the vagus or of the medulla (ibloiigata itself," a hypothesis wliich appears to be simply repeated in a transposed form l)y Laycock with his " sentient palsy of the respiratory centre," or " paresis of reliex sensibility of the mucous membrane of the lung," The conceptions of many other writers, such as San.som, are equally hazy. No hypothesis of this kind is adequate. Simple reduction of the excitability of the respiratory centre might cause infrequent and irregular respiration, but it most assuredly could not by any possibility lead to the regular periodicity of phenomena .seen in Cheyne-Stokes respiration. In the second place, many attempts have been made to explain the regular periodicity of the breatliing liy varying conditions of the stimuli which act upon the nervous mechanism controlling the muscular functions of the respiratory apparatus. Undoubtedly the earliest attempt of this kind is that of Little. He thinks that the cause is a loss of balance between the two sides of the heart, either when there is diminished force of the left ventricle, as in fatty degeneration, or when some abnormal burden has been imposed on the left ventricle, under which it is unable to get rid of blood as quickly as it is supplied to it, and the blood accumulates in the left auricle and the pulmonary veins and o 106 CHEYNE-STOKES RESPIRATION. capillaries. Being fully arterialized, tliis blood fails to excite the terminal filaments of the vagus, as venous blood does, and the respiration ceases. A few pulsations then displace this blood, and the venous blood streaming in excites the respiration anew. This explanation forms in some respects a transition towards the renowned hypothesis of Traube. It postulates an inter- mittent stimulation of the vagus-endings by alternating conditions of the blood contained in the lungs. It cannot be regarded as meeting the case, for many diseases produce Cheyne-Stokes breath- ing in which no disturbance of the circulation occurs. It fails, moreover, in not giving any adequate reason for the ascending and descending phases of the breathing ; and the assumed loss of equilibrium between the two sides of the heart is absolutely unproved. Traube begins his explanation, as we have already seen, by pointing out that all cases presenting Cheyne-Stokes breathing have one common feature — a lessened supply of arterial blood to the medulla, in which the respiratory centre is situated. Tiiere is in consequence less oxygen, which influences the irritability of the nervous elements. Through this lessened amount of oxygen the irritability of the nerve cells becomes lowered, and a larger quantity of carbonic acid is required to cause an inspiration ; the time, therefore, within which the carbonic acid will accumulate in sufli- cient quantity is lengthened. This is similar to the effects of section of the vagi, in which long pauses, attended by dyspnoea, occur in the respiration. The respiration may be excited in two ways : 1. By the pulmonary fibres of the vagus ; and 2. By the afferent nerves coming from all parts of the body. The difference between these two is this, that the pulmonary endings of the vagi are bathed in blood containing much carbonic acid, while the others have a supply of blood which contains but little. If both be equally irritable, then in health only the pulmonic vagi will be called into action. If the vagi be cut, the respiratory centre can only be ex- cited by the other nerves, and this can only happen when the blood circulating throughout the body is as rich in carbonic acid as that normally passing into the lungs. The number of tlie vagus fibres is incomparably smaller than that of the other nerves ; when these latter act, therefore, the effect is correspondingly greater. CRITICAL. 107 A]i|iI\iiiL;' lliis lensunin^- Lo llic iiliciioiiiciinii in (incstiuii, llie less- ened initiibiliLy of tlio respiratory centre, caused by cerebral pressure, or uneiiiic blood, or deficient arterial supi)ly, requires a larjrer amount of carbonic acid as a stimulus, ami thus tliere is a loni; pause. When this j,'as has accumulated in sufTicient fpiantity it lirst stimulates the pulmonary terminations of the vagi, but, as was shown long before by Traube, the strongest stimuli applied to the vagi never cause dyspncea, and this only causes the .shallow breathing which appears first after the pause. The amount of car- bonic acid meantime increases sufiiciently to cause stimulation of the nerves coming from the skin and other parts of the body, and hence the dyspncea .sets in. The Cjuantity of the gas is greatly diminislicd by the forcible breathing, and the excitement of the other nerves ceases, so with the action of tlie vagi alone shallow breathing again occurs, until there is not enough carbonic acid gas to excite tlic pulmonary endings of the vagi, and a pause sets in anew. This beautiful and ingenious explanation appears at first sight to fuliil all the requirements of a good working hypothesis. It is only on close inspection that it is found wanting. Tlie initial difficulty is that a simple and constant reduction of the functional activity of tlie respiratory centre could not by any possibility induce a change from regular rhythm to periodic rhythm of the respiratory movements, and that no real cause for the fluctuations in the blood-supply is advanced. Under the trenchant criticism of Filehne, indeed, the author found himself obliged to shift his ground, and in restating his theory, as we have previously seen, he fell back upon a tendency to rhythmic periodicity in the respira- tory centre, as well as upon exhaustion of that centre produced during the phase of breathing, and causing the subsequent pause. Even this addition, however, leaves the ascending or crescendo phase quite unaccounted for, and gives no valid cause for tiie beginning of the periodicity. It is hardly necessary to refer to the fact that Traube only deals with the res})iratory plienomenon, and leaves untouched the dif- ferent as.sociated .symptoms brought before the scientific world by the elinical arunieu of Lcubc. And it is equally needless to add that no theory can be complete tliat does not account for the occurrence of the entire complex of .synqitoms which may be I'resent. 108 CHEYNE-STOKES RESPIRATION. Hayden, reasoning from the fact that the only lesion with which rhythmical irregularity of the breathing has been, in his experience, found, is degeneration and dilatation of the aortic arch, involving a loss of elasticity in its walls, considers that during the period of greatest cjuiet of the heart's action, such as occurs in repose or sleep, the systemic capillary circulation fails, from want of the aid rendered in health by the elastic reaction of the aorta ; and there are a suspension of tissue-respiration, hzsoin de respirer, and acceler- ated or suspirious breathing. Increased respiration will aid capil- lary circulation, first, through the lungs, and then through the tissues of tlie body generally, by quickening the action of the heart and increasing its force. As the systemic capillary circulation is stimulated, the besoin de respirer is less urgent, and respiration gradually subsides, till a period of apncea arrives. The descent of respiration below the normal standard arises, he thinks, from its previous excessive activity and the exhaustion of the patient. A period of feeble action of the heart succeeds, with failure of capillary circulation, and paroxysmal breathing. Tliat imperfect circulation of arterial blood in the respiratory centre contributes in a special manner, and in a great degree, to the production of the respiratory derangement he has no doubt ; but he thinks that the effect of this is not easily distinguished from that of a want of oxygen in the tissues of the body generally. In this explanation the train of reasoning bears considerable resemblance to the arguments advanced by Traube in his second liypothesis. All the objections which have been, or may be, urged against the views of Traube may be, with equal cogency, brought forward in opposition to the views of Hayden ; and it is hardly necessary to add that in a considerable number of cases, exhibiting the Cheyne-Stokes phenomenon, there is no structural alteration of the aortic walls, or of any part of the circulatory apparatus. Hein, starting from the consideration that the fluctuating con- ditions of the cerebral and respiratory functions must have the same cause, considers that the irritability of the tissues in general, as well as of the medulla in particular, must be lessened by some underlying condition, which in his own experience was cyanosis. From the diminished excitability of the medulla pauses are pro- duced which may, he thinks, have an effect on the circulation, so that what was a consequence may in other circumstances be a CUITICAL. 100 cause. Willi a iinnnal (.irLulation .such an eflect is impos.sible, as Clieyiie-Stiikes ii'spiraiidn may be imitated by the hour without any notioeabU' modilicaliou of the circuhitiun. It i.s otherwise, however, whiii the blood-stream is slowed and oxygenation less- ened, fur if interruptions to the respiration take place, the functions are alternately increased and diminished, and such eHectsare shown in the medulla oblongata through variations in its irritability. The blood which has been arterialized during the respiratory period reaches the capillaries in greatest part at the beginning of the pause, at which time the circulation which had been quickened by the breathing becomes slower, while the tissue change is most active. The result is that the irritability of the medulla is again increased and the breathing begins. By means of the passage, during the breathing period, of the blood which has become venous during the pause, the tissue change necessary to the functional activity of the organ cannot be kept up, the oxygen in tlie tissues is consumed without adequate compensation, and the irritability of the respira- tory centre is suspended. It is again restored after arterialized blood has coursed through the vessels of the medulla and promoted internal respiration, as occurs at the end of the pause. That the irritability shows a stage of increase aud a stage of decrease is due to the fact that the alternation in the conditions of the circulation and diftusion is gradual, not sudden. From the analogous con- ditions of the brain and medulla it is to be concluded that the respiratory nerve centre does not simply undergo a change in the degree of stimulation, but a periodic alteration of its own con- dition. The explanation advanced by this author, so far as it is possible to understand his meaning, seems to rest upon the conception that alterations in the metabolic processes lead to an alternate increase and decrea.se of the functional activity of the centre for respira- tion. But in this theory there is absolutely no attempt to find a real cause for the initial phenomena of periodic alternation.s — in short, as was remarked by Filchne, it is solely concerned with the hoa\ and leaves the why untouched. At tlie conclusion of his argument, however, it must be noted, he makes mention of a periodic variation of the condition of the respiratory centre ; and, in his later contribution to the subject, he lays still more stress upon the [leriodic variations in the activity 110 CHEYNE-STOKES RESPIRATION. of the respiratory centre, with or without analogous fluctuations in the activity of other nerve-centres. He leaves us, notwithstanding, under the belief that tliis periodic variation of functional activity is produced by variations in the condition of the blood-supply, and offers no explanation of the original cause of this. Filehne allows that for the production of Cheyne-Stokes respira- tion there must be a lowering of the irritability of the respiratory centre, but he asserts that the irritability of this centre must be diminished to a greater dei2free than that of the vaso-motor centre. He holds that these centres remain at rest as long as they have a suffi- cient amount of oxygenated blood, and that they are excited when- ever the blood-supply is sufficiently arterialized, or when, although sufficiently arterialized, the supply is deficient in quantity. He asserts that in health venous blood excites in regular order, — 1st, the respiratory; 2nd, the vaso-motor; and 3rd, the convulsive centres. When the phenomenon is present, the blood during the pause gradually becomes more venous and develops the stimulus for the centres, but, from the lessened irritability of the respiratory centre, no respiration is caused, and the pause therefore continues until the point is reached when the vaso-motor centre is brought into action. This produces a diminution of the blood-supply, which causes the respiratory centre to act and originate the superficial breathing which is first observed. Some time, however, elapses before the blood arterialized by these respirations can reach the vaso-motor centre, and this is delayed by the contraction of the arterioles caused by its activity ; it also takes time before the vaso- motor apparatus can induce contraction of the arterioles, and time also before the contraction can pass away ; there is therefore a lengthening of the pause and deepening of the dyspnoea. Filehne states that when Cheyne-Stokes respiration is produced in animals by the administration of large doses of morphine, fol- lowed by tlie inhalation of ether or chloroform, there is a diminution of the pulse-rate during the pause, which sometimes goes the length of complete cessation of the pulsation ; while during the period of respiration there is a gradual acceleration until the normal rate is regained towards the end of this phase. In animals thus experi- mented on the blood -pressure rises during the pause and falls during the period of breathing. In a man dying froui a lethal dose of morphine and chloroform, who showed during the narcosis Cheyne- CKITICAt,. 1 1 ] Stokes respiration, (lie pulsr uiidrrwcuL tlie same cliaiij,'es as in the animals on which hf in'irormcd his ('.\]M'iimenls. J)iuiii,i,' his controversy with Trauhc, Fih'hnc refers, as previously mentioned, to the fact, observed by him, that the arteriiil tension rises befori' tiic be[,dnninj,M)f the jiha.se of respiratory activity; to the depression of the fontanelles in children, who present the symp- tom, before the adive phase ol' breathing ; to the disappearance of Cheyne-Stokes breathing on the administration of amyl nitrite ; to a rise of tension in some persons before inspiration ; and to the production of periodic breathing by alternate compression and relaxation of the carotid and vertebral arteries in the rabbit. In later contributions Filehne found himself driven to admit that the arterial changes may be synchronous with the periodic changes in the respiratory activity. This exceedingly complicated hypothesis rests, in the first place, on certain assumptions which have not been proved ; and. in the second place, on several observations whicli liave, without excep- tion, been proved to be, to say the least of them, inconstant. The statements in regard to the relative excitability of the centres in tlie medulla rest upon no basis of fact, and with refer- ence to an arterial spasm, upon a misconception. Filehne's observations on the alterations of pulse-rate and tension have been found \>y numerous writers to be altogether incorrect, inasmuch as the changes, when present at all. have been seen to be the converse of what he described, and to . G05, 1889. * Mimtrciil Mcdiral JiiHniaf, vol. .wiii., p. 21)4, 18SD-90. « The British Medical Jounuil, vol i. for 1890, \\ 427. 128 CHEYNE-STOKES RESPIRATION. changes in the bulb in connexion with Cheyne-Stokes respira- tion. West/ describing at the Pathological Society of London the long continuance of Cheyne-Stokes breathing in a case of granular kidney, mentions that the pauses at times disappeared, leaving respiration of an ascending and descending type. Mackenzie,^ in the discussion which followed West's remarks, asked if patients ever recovered after they had developed Cheyne- Stokes respiration ; and in answer to his question several cases are recorded. Kingston Fox^ narrates one of influenza with broncho- pneumonia, O'Neill* one of a febrile affection, Mallins^ one of cerebral hfemorrhage, Flux^ one of puerperal septiccemia, Adams'^ one of epilepsy and one of hydrocephalus, Aylward one of phthisis^ in which morphine produced the symptom, Lawford Knaggs^ one of renal disease, and Square ^"^ one of cerebral softening — all of wliich recovered. It is very interesting to note that Knaggs found a brother and a sister both suffering from renal disease and both showing periodic respiration. Pilkington^^ describes a case of cardiac disease with softening of the left cuneate lobe, third right temporal convolution, and right anterior pyramid of the bulb. Downs^^ has described a case of ursemia in which Cheyne-Stokes breathing occurred, and criticises some of the recent work on the subject, while Brush^^ records the case of an insane patient with chronic degenerative changes in the heart and bloodvessels who showed the same symptom. An important contribution to tlie subject is contained in Broadbent's recent work on tlie Pulse.^* He is of opinion that the symptom is mainly conditioned by a state of higli arterial tension. 'No doubt the . periodicity of the respiration is very frequently found in association with affections in which high arterial tension is a prominent symptom, as, for instance, granular 1 The Lancet, vol. i. for 1890, p. 545.^ 2 Ibid., loc. at. ^ Ibid., p. 571. •* Ibid., p. 260. 6 Ibid., loc. cit. " Ibid., loc. cit. "^ Ibid., p. 674. 8 Ibid., loc. cit. 9 Ibid., p. 744. lo Ibid., p. 776. 11 The British Medical Journal, vol. i. for 1890, p. 819. 12 Medical News, vol. Ivi. p. 589, 1890. ^Ubicl, vol. Ivi. p. 592, 1890. " The Pulse, p. 169, 1890. Al'l'KNDlX. 1-"J ilopjoncratiDii nl the kidney. I'm it lias to ho rcmenilMTo. M. lShall, .5. Ila.s.se, G. Ilauer, 127. Ilayden, 27, 108. Hazard, 28. 132 INDEX. Head, 9. Heidenhain, 16, 92. Hein, 32, 56, 108, 111, 114. Heitler, 24. Hesky, 13, 92. Hippocrates, 2. HoepfFner, 25. Howard, 74. Huber, 129. Hiird, 66. Hiittenbrenner, von, 27. Kaufmann, 73, 113. Kennedy, 27. Knaggs, 128. Knoll, 65. Korber, 19. Kronecker and Bowditch, 53. Kronecker and Marckwald, 52. Kussmaul, 15, 50. Langendorff, 64, 77. Langendorflf and Siebert, 63, 118, 124. Langer, 63, 64. Laycock, 20, 105. Lerebonllet, 59. Leiibe, 14, 93, 107. Leyden, 9, 93. Little, 10, 105. Lbwit, 57, 118. Luciani, 45, 114, 116, 117, 118, 124, 126. Lutz, 16. Macdonnell, 127. Mackenzie, 128. M'Vail, 84. Mader, 13. Mailing, 128. Mancini, 127. Mann, 127. Marckwald, 85, 123, 125, 127. Marckwald and Kronecker, 56. Mayer, 33, 36, 111. Merkel, 17, 93, 94. Mickle, 44. Monti, 21. Mosso, 38, 74, 117, 122, 124. Muirhead, 88, 122. Murri, 67, 80, 118, 119. Nicolas, 3. o'connell, 71. O'Neill, 59, 128. Oser, 74. Ottilie, 38. Paterson, 65. Pepper, 31. Piaggio, 71, 82, 113. Pilkington, 128. Plotke, 50. Poole, 81. Puddicombe, 67. Purjesz, 51. Rahlmann and Witkowski, 50. Rehn, 17. Reid, 8. Ricklin, 25. Robertson, 82. Rolirer, 21. Rosenbach, 48, 53, 59, 60, 92, 111, 115, 116, 117, 118, 126. Rosenthal, 69. Ross, 30. Roth, 19. Sacchi, 37. Saloz, 60, 118. Sander, 50. Sansom, 64, 105. Schepelern, 18, 93. Schiff, 7. Schweig, 6, 104. Smart, 86. Smimow, 72. Solokow and Luchsinger, 58, 118, 124. Sijuare, 128. Steiner, 124. Stillmann, 86. Stokes, 5, 91, 104. Storch, 80. TizzONi, 68, 127. Traube, 11, 23, 106, 114, 119. Treves, 36. INDKX. 133 TrousHcnii, 8. Tukc, 88. ViERORDT, 84. Vigonroiix, ITi. "Waller, 129. Waller ami lUi.l, 124. Walslu-, 1), Kir.. Wi'lli'iihcrKli, 78, 113. Wcrthciiiier, 129. West, 5, 128. Wptt^-, . Ziniiiu'ihans, 2.'>. ZiiiinuTiiiaiin, 44. Zuelzer, 66. TBINTED UV OUTBB AXD BOYD, EOlXatTBOB. COLUMBIA UNiVtfiSITY LIBRARY This book is due on tl] expiration of a definite p as provided by the rules rangement with the Libra] daf indicated below, or at the iod §ter the date of borrowing, Library or by special ar- charge. iL££DPEfi? C28(239)M100 sou n ^ .^^ ^ 4. ^ ^ O^ !!laS!i)!!!|!SiiS!li|)!liii!!ipfi'>ii!lt|l«l!^