The State of the Yasomotobs in Acute Lobab Pneumonia, AND ITS BeABING ON TREAT- MENT. BY E. VAN SANTVOOED, M. D. IMPRINTED PROM THE Well) STorft J&eUtcal Sournal for October 8, 1898. Reprinted from the New York Medical Journal for October 8, 1898. THE YA«OMOTOES IN ACUTE LOBAE PNEUMONIA, AND ITS BEAEING ON TEEATMENT * E. VAN SANTYOOED, M. D. In the Berliner Jclinische Wochenschrift of 1895, Nos. 51 and 52, Romberg published a series of investi- gations undertaken to determine what parts respectively the state of the heart and that of the vasomotors take in the condition commonly regarded as weak heart in acute infectious diseases. He experimented upon rab- bits with the Bacillus pyocyaneus and with the pneumo- coccus of Prankel. In a second paper read before the Fourteenth German Congress for Internal Medicine, Pasler and Romberg presented a further communica- tion on the same subject, the Loeffler bacillus being on this occasion the organism experimented with. It was found that the effect of infection by any one of these agents was to increase markedly the amplitude of the pulse tracing and to lower arterial tension. The effect of abdominal massage, which mechanically emp- * Read before the New York Academy of Medicine, April 21, 1898. Copyright, 1898, bt D. Appleton and Company. 2 THE YASOMOTORS IN LOBAR PNEUMONIA. ties the abdominal vessels, was always to at once cause a marked increase of vascular tension up to a short time before the death of the animal, it being thus demon- strated that the circulatory failure was due to dilata- tion of the vessels, not to failing heart power. Irrita- tion of peripheral nerves (pinching of the nose of the animal experimented with) failed to cause the increased vascular tension which it does in a normal subject. As this reflex irritation has been demonstrated to act through the medullary vasomotor centres, this failure was regarded as proving that these centres were para- lyzed. Asphyxia, which acts upon both the spinal and medullary centres, caused a slight elevation of pressure, the relative intactness of the former being thus shown. Chloride of barium, which has been proved to act on the peripheral vasomotors, caused a marked elevation of pressure. The final conclusion arrived at from these experiments was that in eases of infection from the pneumococcus. Bacillus pyocyaneus, and the Loeffler bacillus the circulatory embarrassment heretofore attrib- uted to cardiac weakness produced by toxaemia and mal- nutrition is due mainly to vasomotor paralysis. This conclusion did not apply to the late circulatory disturb- ances in diphtheria, which have been demonstrated to be due to cardiac lesions, the circulation in the acute stage of the disease only being considered. During the past winter I have been studying cases of pneumonia as they presented themselves in hospital and private practice with these conclusions in mind, in order to determine if possible what applicability they have to pneumococcus infection in the human being. Sphyg- mographic tracings were taken in eighteen cases of the disease. As these records confirm the results of obser- THE VASOMOIORS IN LOBAR PNEUMONIA. 3 vations made by many other observers in like cases, they may safely be accepted as the basis for the following remarks. The tracings were almost invariably of great ampli- tude, the primary wave being generally sharply pointed, without any indication or only a faint indication of the tidal wave. The dicrotic wave was often very pronounced, sometimes not very strongly indicated. These charac- teristics were strongly developed in all cases in which constitutional symptoms were very marked until a few hours before death in fatal cases, when the pulse would become too feeble to give a good tracing, or convales- cence. They were also pronounced in some cases in which the disease ran an only moderately severe course, judged by the general condition of the patient. In a few mild cases the deviation from normal was not very great. The pulse, as a rule, was large, often bounding, but usually of less than average tension, as judged by the finger, in the severe cases very much below the average. These latter observations were confirmed in several instances by the use of the sphygmomanometer of von Baseh. This instrument measures the amount of pressure necessary to compress the pulse so that it can not be felt beyond the point of pressure. It is a measure, therefore, of the tension that exists at the period corre- sponding to the apex of the pulse tracing. The tracings demonstrate the fact that the arterial pressure falls with great rapidity after this primary wave, so that we have proof that the mean arterial tension is often low. It is the commonly accepted explanation of this form of tracing that it is due to dilatation of the peripheral vessels. We have the fact demonstrated, therefore, that in pneumonia, as it exists in the human subject, we have THE YASOMOTORS IN LOBAR PNEUMONIA. the same condition of low arterial tension due to relaxed peripheral vessels as was found to exist experimentally in animals infected by the same coccus. The one constant factor in the circulation of the blood is gravity. When the general arterial tension is lessened, either as a result of cardiac weakness or of excessive dilatation of the peripheral vessels, this factor increases in its relative importance and the blood tends to accumulate in dependent portions of the body at the expense of the more elevated. Owing to the greater ease experienced by dyspnoic individuals in a position with the head and shoulders raised, this is the attitude which a patient gravely ill with pneumonia assumes, and this position is obviously directly provocative of cere- bral anemia. Here we have a mechanical factor which is probably of considerable importance in causing the nervous manifestations of the disease and in determin- ing its final outcome. The condition of the peripheral vessels which makes the least demand upon the heart in order to secure an adequate capillary pressure throughout the body is one of medium contraction. When the peripheral arteries are strongly contracted, as in cases of renal cirrhosis, the ventricle is forced to hypertrophy in order to over- come the obstruction, and toward the last we have the striking combination of ringing heart sounds and tense arteries with the dyspnoea and swollen feet indicative of inadequate capillary circulation. On the other hand, when the peripheral vessels are greatly relaxed, the ca- pacity of the arterial system is largely increased. If the heart continues to inject into the aorta only the amount of blood in a unit of time that was adequate to maintain the tension at a safe level, under normal conditions, the THE YASOMOTORS IN LOBAR PNEUMONIA. 5 result must be slowing of the current, lessened friction, hence lessened tension, which decrease may be suffi- cient to dangerously impair the circulation in the organs at a higher level than the heart. This danger may be avoided by the injection by the heart into the aorta of a larger quantity of blood in a unit of time—i. e., by in- creased rapidity of contraction, or by the discharge of a larger amount of blood with each systole. When, finally, extreme dilatation takes place, this compensation becomes impossible. The heart is imperfectly supplied with blood, it falters and stops. This sequence of events Eomberg declares takes place as a matter of observation in his infected rabbits. At first, although the increased oscillation of the tracing showed a general relaxation of peripheral vessels (his measurements were taken in the carotid), the average tension did not fall. Later, when this did fall, the heart still responded when abdominal massage was employed, showing that the decline was due, not to failing heart power, but to increased relaxation of the vessels. Pinal- y this response ceased and the animal died. It is often stated in the books (Wagner’s Pathology, for instance) that the characteristic pulse of pneumonia is one of high tension. In the limited number of cases that I examined with this particular question in view this was certainly not the case, though the variation was very considerable in different cases, those of very low tension corresponding to great rapidity of heart action and grave constitutional conditions. The bound- ing character of the pulse due to the wide variations in tension during each cardiac cycle and its fullness give it a deceptive feeling of vigor which may readily be mistaken for high tension. The number of cases exam- 6 THE YASOMOTORS IN LOBAR PNEUMONIA. incd by me for the purpose was not sufficient to establish the rule, if there is a rule. There is, unfortunately, no exact method of determining clinically the exact tension of the arteries. From the foregoing, however, it is ob- vious that if in a given ease of pneumonia the tension approaches or exceeds the normal, it can be only by rea- son of increased exertion on the part of the heart. In extreme vascular relaxation, therefore, we have a me- chanical factor which renders necessary increased exer- tion on the part of the heart, in order to adequately sup- ply all the organs with blood, and the ability of the heart to respond to this demand may determine the outcome of Fig. I.—Alcoholic, aged fifty-one. Pulse 153. Two hours before death. Fig. 2 —Boy, aged sixteen. Never very ill. the given case. I present here two sphygmograms which are almost identical—one taken about twenty-four hours before death from a case of pneumonia with tremor and delirium and very low arterial tension in a middle-aged alcoholic, the other from a boy of sixteen, who not only recovered but never appeared to be gravely ill. The dif- ference in the outcome of the two cases was probably largely influenced by the difference in the ability of the hearts to respond to the increased demands upon them. The weak point in the transfer of the results of ex- periments upon rabbits with the pneumococcus to the human being is that in the former the infection produces only a septicaemia, without the pulmonary lesions which THE YASOMOTORS IN LOBAR PNEUMONIA. 7 form the prominent feature in the latter. Nevertheless, the animal experiments shed light, I think, not only on those cases in which the toxasmia is the prominent symp- tom, but also on the frequent eases in which the pul- monary infiltration plays a prominent part, of which the following is a type: A previously healthy and vig- orous man was admitted into the Harlem Hospital with an infiltration, which finally involved the whole right lung. Dyspnoea was marked, and became gradual- ly worse, until in three days he developed oedema of the left lung and died. Nervous symptoms were not marked. The sclera were yellow. The second sound over the pul- monary valves was louder than over the aortic. The tracing of his pulse, taken the day before his death, is here shown. Eig. 3.—Extensive pulmonaiy infil- tration. Marked dyspnoea. The autopsy disclosed the following conditions so often seen in death from pneumonia: The cavities of the right heart contained much yellow clot and fluid blood and were dilated. The left ventricle was relaxed, but contained little clot or fluid blood. The right lung was in a condition of red hepatization throughout; the left congested, cedematous, and coated externally with fibrinous exudate. The liver was congested. What causes this obvious blocking of the right heart? Direct observation shows that when a living tissue is irritated the effect is to cause, first, a dilatation of the vessels, with sometimes a temporary acceleration of the blood stream. Then occurs a slowing of the latter amounting, when the irritation is intense, to complete stasis. To trans- 8 THE VASOMOTORS IN LOBAR PNEUMONIA. late the words of Cohnheim, in speaking of this phe- nomenon : “As the driving force and the blood itself have undergone no change, the local retardation of the blood current can result only from local resistance; the lumen of the vessels, however, does not offer this in any locality; on the contrary, arteries, veins, and capillaries are universally relaxed—they are even dilated above the normal. Therefore there remains, so far as I can see, no other possibility than that the increased resistance is to be sought in the changed relations of friction and adhesion between the blood and the walls of the ves- sels.” This sort of resistance, therefore, doubtless is offered to the circulation of the blood in the hepatized lung, as is generally recognized; the pulmonary exudate, by interfering with the normal dilatability of the vessels, being an additional factor. How are we to explain the oedema of the unhepatized lung? The mere narrowing of the blood current by the more or less complete shut- ting out of the vessels of the solidified lung does not explain it, because we frequently see patients with one lung solidified who nevertheless exhibit no marked signs of respiratory or circulatory distress. Welch long ago demonstrated that the only way in which oedema of the lungs could be produced mechanically in the laboratory was by causing relative insufficiency of the left heart, so that the sufficient right heart keeps on pumping blood into the lungs which the deficient left is not able wholly to receive and forward, a mechanism which is exquisite- ly exemplified in many cases of chronic interstitial nephritis. Extensive ligation of pulmonary arteries never produced oedema in the portion of lung sup- plied by the unobstructed branches. The conditions here are exactly the reverse. We THE VASOMOTORS IN LOBAR PNEUMONIA. 9 have the left ventricle forcing blood through the abnor- mally relaxed greater circulation and the right ventricle forcing the blood through an abnormally contracted lesser circulation, so that in this instance the strain is upon the right ventricle, which, if it proves insuffi- cient, is not able to dispose of the blood brought to it by way of the greater circulation, with the result that con- gestive phenomena in the abdominal organs, most mark- edly in the liver, as in the above case, are to be noted. In the lungs we would look for nothing except possibly some hypostatic congestion in the portions not inflamed, as the narrow point past which the right heart must exert itself to force the blood is the pulmonary arterial system, not the wider capillaries and veins. Yet this increased strain upon the right heart is in part due to the greater amount of work thrown upon the organ as a whole by the necessity of maintaining the equi- librium of the circulation which is threatened by the paralysis of the vasomotors. Congestion, other than hypostatic, and cedema of the lungs occurring under these circumstances can not be due to any mechanical cause. It can only be inflammatory, and the inflamma- tory oedema of previously not involved portions of lung with distention of the right heart, which so often accom- panies the end of the disease, is to be regarded as an ex- tension of the pulmonary inflammation, and the final giving out of the right heart is owing to this added obstacle. That this is the explanation of the particu- lar case cited above by way of illustration is rendered still more probable by the existence of considerable fibrinous exudation on the surface of the congested and oedematous left lung. We turn now to the bearing of the above-enumerated 10 THE YASOMOTORS IN LOBAR PNEUMONIA. considerations on the treatment of the disease. It is hardly necessary to state that so conspicuous a phe- nomenon as the relaxed condition of the peripheral ves- sels has not escaped observation and consideration from a practical point of view on the part of other authors. Romberg’s especial point is that this factor is the domi- nant one in certain acute infectious diseases in causing embarrassment of the circulation, and I have endeavored to present the reasons for accepting his conclusions from a clinical standpoint, so far as the grave symptoms of the disease under discussion depend upon general tox- aemia and not upon local lesions. The most obvious method of combating extreme dilatation of the peripheral vessels is to administer drugs which cause their contraction. With this object in view, I have employed the chloride of barium in doses of four grains every four hours. In one case, after two days, the previously very much relaxed arteries contracted ma- terially, the pulse slowed, and the marked delirium and prostration of the patient disappeared, although the tem- perature and pulmonary lesion remained unchanged. In others, no apparent result followed the same treatment. Fluid extract of ergot in doses of half a drachm every three hours had apparently some good effect in a few cases. The number of eases on which these drugs were used was, however, entirely too small to warrant any conclusion as to their utility, and I mention them only by way of suggestion. It is, I think, significant that the sulphate of strych- nine, which is now so widely used, and upon which I have mainly relied of late years, not only has a tonic effect upon the heart but also causes contraction of the peripheral vessels, through its action upon the spinal THE YASOMOTORS IN LOBAR PNEUMONIA. vasomotor centres, which, according to Eomberg, are not affected by the pneumococcus. Although in Eomberg’s experiments the terminal cardiac failure was apparently secondary to the extreme dilatation of the peripheral vessels, yet it has been dem- onstrated that before the final failure occurred increased work was demanded of the heart. The outcome of any given case may depend upon the ability of the heart to respond to this demand. I have previously shown the almost identical tracing presented by a boy of sixteen, who recovered, and a middle-aged alcoholic, who died, the difference in result depending probably on the dif- ferent ability of the two hearts to meet the extra de- mands upon them. Owing to the number of cases in which antecedent cardiac lesions exist and to the difficulties imposed upon the right heart by the pulmonary lesion, the necessity of directly stimulating the heart is more often present in the disease as it occurs in man than as it is arti- ficially produced in rabbits. The remedy which theoretically and in the opinion of many practitioners practically best meets the require- ments of the situation is digitalis, because it contracts the peripheral vessels as well as stimulates the heart. The use of digitalis in pneumonia is an old and much- discussed question. Its most energetic supporter to-day is Professor Petresco, of Bucharest.* He stated, in 1891, that he and his pupils had treated 1,641 cases of pneumonia with a mortality of only 2.06 per cent. He gives the drug in an infusion of four grammes of the leaves to two hundred cubic centimetres of water, * Therapeutische Monatshefte, February, 1891. 12 THE YASOMOTORS IN LOBAR PNEUMONIA. to which are added forty cubic centimetres of syrup of orange peel, in doses of a tablespoonful every half hour to begin with, and in quantities representing four, six, eight, or twelve grammes of the leaves daily, according to the indications of the individual case, and continues these doses for from three to four days. He claims to have found it well borne by the digestive or- gans, and never to have seen a case of poisoning, al- though the pulse will sometimes drop to 24 to the minute. So far as lam acquainted with the literature of the subject, there are few who have the courage to imitate his example; yet it may well he that in the vasomotor paralysis which we have been discussing we have both the explanation of the tolerance of such enor- mous doses and the indication for their employment. In delirium tremens it is acknowledged that the toler- ance for digitalis is enormously increased. It is quite oossible that in pneumonia a similar tolerance exists and that most of us have been too conservative in the use of this drug because we have based our expectations of the effect to be looked for on results obtained in non-febrile maladies, and that the condemnation of the use of the drug in large doses in pneumonia in particular by high authority has been influenced by experience derived under conditions of the circulation which are vastly dif- ferent from those obtaining in this disease. It is not to be forgotten that the preparation used by Petresco— viz., the infusion—does not represent the full potency of the leaves, as one of the most powerful alkaloids, digitoxine, is not soluble in water. The U. S. P. infu- sion contains alcohol, and is therefore a more powerful preparation than Petresco’s. With regard to the treatment of those eases in THE VASOMOTORS IN LOBAR PNEUMONIA. 13 which right-heart embarrassment occurs, I desire to call attention especially to nitroglycerin, the use of which is Fig. 4.—Pneumonia. Fig. 5.—Convalescence advocated by Dr. A. H. Smith. I here show the tracing taken from a patient during an attack of pneumonia of considerable severity, one taken during conva- lescence, and one a few moments after the latter, when the circulation was under the influence of a very large dose of nitro- glycerin. The similarity of the first and the last is apparent. Fig. 6.—Nitroglycerin. It seems a little like carrying coals to Newcastle to administer nitroglycerin in such a state of the periph- eral vessels; yet, nevertheless, a still greater relaxation of the vascular system than that already existing may be a source of relief to the embarrassed right heart by lessening temporarily the amount of blood which it is called upon to force through the obstructed lungs. Its action is exactly analogous to bleeding. Its use should, however, be reserved for this specific indication. In the cases in which the vasomotor paralysis is a source of danger, this danger would be obviously increased by its employment. As we all are only too painfully conscious, the treat- 14 THE VASOMOTORS IN LOBAR PNEUMONIA. ment of acute lobar pneumonia is not as satisfactory as we could wish. I offer these suggestions in the belief that the conditions of the vasomotors is a factor in the pathology of the disease which has not received the con- sideration which its importance demands, and that in- telligent effort on the lines above indicated would save lives which would otherwise be sacrificed by trying to stimulate the heart under the idea that the circulatory failure present is due solely to insufficiency, from what- ever cause, of the heart muscle, and neglecting to lessen its labors by toning up the peripheral circulation. 106 West One Hundked and Twenty-second Street. TRAUMATIC INJURIES OF THE BRAIN AND ITS MEMBRANES. With a Special Study of Pistol-Shot Wounds of the Head in their Medico-Legal and Surgical Relations. Bt CHARLES PHELPS, M. D., Surgeon to Bellevue and St. Vincent’s Hospitals. Bvo. 582 pages. With 49 Illustrations. Cloth, $5.00. SOLD ORLY BY SUBSCRIPTION. “ This work is a concise and systematic treatise on that division of brain surgery arising from injuries of the brain through external violence, and has been based almost exclusively on the observation of five hundred consecutive cases of recent occurrence. Although the cases were so numerous, it seems they were incomplete only in the illustration of secondary pyogenic infection, which is naturally a trib- ute to the skill of the surgeons in charge of the cases, inasmuch as they were kept from infection. This clinical deficiency has been supplied by excerpts from Mac- ewen’s work on Inflammations of the Membranes of the Brain and Spinal Cord, with the permission of that gentleman. We have no hesitation in saying that it is the most complete work on this division of brain surgery which has yet ap- peared in America.”—Journal of the American Medical Association. “ This book will prove of great service to both physician and surgeon’; and to those interested in medical jurisprudence it will be of incalculable value. The author is not embarrassed by his great wealth of material ; he studies it exhaust- ively, and arranges it clearly, concisely, and with great care and discrimination. The chapters on Pistol-Shot Injuries are particularly instructive, and the series of experiments on cadavers replete with interest. One of the strongest features of the book is the large number of photographic representations of cranial in- jury.”—National Medical Review. “ We have here a new work highly creditable to American authorship and add- ing a material contribution to our present literature upon brain surgery. The first part of the work is devoted to the consideration of traumatic lesions of the cranium and its contents, embracing their pathology, symptomatology, diagnosis, prognosis, and treatment. Part II is an exceedingly interesting and original dis- cussion of medico-legal and surgical relatione and treatment of pistol-shot wounds of the head. Part 111 contains a condensed history of three hundred cases of intracranial traumatism verified by necropsy. A most interesting feature of the work is the introduction of a large number of full-page photographic illustrations of the effects of pistol-shot wounds produced by those of different calibers and at different distances. The work will at once be appreciated as one of original investigation, and especially by those who are particularly interested in brain sur- gery.”—North American Practitioner. D. APPLETON AND COMPANY, NEWYORK.