intI)fCttpo!lftt»gurk CoUese of ^fiv&imn& anti ^urseons; Hibrarp ANEMIA AND RESUSCITATION Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/anemiaresuscitatOOcril ANEMIA AND RESUSCITATION AN EXPERIMENTAL AND CLINICAL RESEARCH BY GEORGE W. CRILE PROFESSOR OF SURGERY, WESTERN RESERVE UNIVERSITY MEDICAL COLLEGE; SURGEON TO LAKESIDE HOSPITAL, CLEVELAND, OHIO. NEW YORK AND LONDON D. APPLETON AND COMPANY 1914 Copyright, 1914, by D. APPLETON AND COMPANY )u- If ' Printed in the United States of America TO HOWARD MELVILLE HANNA, ESQ. WHO IN HIS GENEROUS DEVOTION TO THE WELFARE OF HIS FELLOWMEN HAS FOSTERED MEDICAL RESEARCH BY WISE COUNCILS AND LARGE GIFTS IS DEDICATED ALL THAT IS OF VALUE IN THE RESEARCHES RECORDED IN THIS WORK PREFACE In presenting the material of this book for publication it gives me pleasure to express my many obligations to my associates. Although the problems originated in my clinic, and the experiments were planned by me, their accomplish- ment was made possible by the diligent labors of my asso- ciates. Part of the subject matter was presented before the College of Physicians, Philadelphia, in 1908 as the Mutter Lecture for that year under the title "Surgical Anemia and Resuscitation." To Dr. D. H. Dolley's untiring efforts, for which appre- ciation has already been expressed in "Hemorrhage and Trans- fusion," is due the large accumulation of data on cerebral anemia. In the research on anemia of the voluntary muscles I am indebted for the preliminary work to Dr. Lawrence Pomeroy, and for the later work to Dr. A. M. Tweedie. The research on anemia of the intestines was also in charge of Dr. Tweedie, Dr. H. G. Sloan conducting the experiments on certain phases of this important work. The neurocytologic work in this research, as well as some of the later work on cerebral anemia, was done by Dr. J. B. Austin. The drawings illustrating the changes in the brain cells in gangrene of the intestine were made by Miss Armenouhie H. Tashjian. vii viii PREFACE To Dr. Charles S. White, of Washington, D. C, are due my thanks for permission to use the three illustrations showing the relationship of the thoracic viscera, and also to "Surgery, Gynecology, and Obstetrics" for the blocks for the same. To Dr. F. W. Hitchings I wish to express my especial ap- preciation for his tireless labor and enthusiasm in the arduous task of compiling the various tables, abstracting the literature, arranging the experimental data, and assembling all of the material into book form. The final revision of the text was made by my editor, Miss Amy Rowland. G. W. C. CONTENTS PAGE INTRODUCTION 3 CHAPTER I ANEMIA OF THE CENTRAL NERVOUS SYSTEM. EXPERI- MENTAL OBSERVATIONS 5-54 Introductiox 5 The Blood Supply of the Brain : General Considera- tions 6 The General Effects of Complete Anemia of the Cen- tral Nervous System as Seen in Dogs Resuscitated after Relative Death 8 Technique of Experiments lo Recovery Results 13 Special Phenomena following Resuscitation . . 20 Comparison of the Author's Results with the Results of Others 28 Summary 30 Protocols of Ten Selected Experiments ... 31 Table I — Time of the Respiratory and Circulatory Changes 50 Table II — Ten Cases in Which the Total xA.nemia Lasted Seven and One-Half or More Minutes . ■ 51 Table III — The Course of the Blood-Pressure after Resuscitation 52 Table IV — The Time of Return of the Reflexes after Restoration of the Circulation 53 Conclusions 53 ix CONTENTS CHAPTER II PAGE ANEMIA OF THE CENTRAL NERVOUS SYSTEM: CLINICAL OBSERVATIONS. CEREBRAL ANEMIA THROUGH LIGATION OF THE COMMON CAROTID ARTERIES . 55-72 General Considerations 55 Analysis from the Literature of Five Hundred Cases OF Ligation of the Common Carotid Artery . . 57 The Author's Cases of Temporary Simultaneous Closure of Both Common Carotid Arteries . . 64 Technique of Ligation of the Common Carotid Artery AND Its Branches 65 Summary 72 CHAPTER III ANEMIA OF VOLUNTARY MUSCLES: EXPERIMENTAL OBSERVATIONS— ANEMIA OF THE POSTERIOR EX- TREMITY OF DOGS 73-107 Protocols of Forty-Three Experiments .... 75 Conclusions 105 Table — The Results Obtained by Causing Anemia of the Hind Legs of Dogs for Varied Durations of Time 106 CHAPTER IV ANEMIA OF VOLUNTARY MUSCLES : CLINICAL OBSERVA- TIONS—OCCLUSION OF THE ABDOMINAL AORTA IN MAN 108-122 CHAPTER V ANEMIA OF VOLUNTARY MUSCLES : CLINICAL OBSERVA- TIONS—ANEMIA OF THE LOWER EXTREMITIES IN MAN THROUGH LIGATION OF THE MAIN ARTERIAL TRUNKS . 123-13^ Ligation of the Common Iliac Artery 125 Ligation of the External Iliac Artery .... 126 CONTENTS XI PAGE Ligation of the Common Femoral Artery .... 127 Ligation of the External Femoral Artery . . . 130 General Recapitulation 132 CHAPTER VI ANEMIA OF VOLUNTARY MUSCLES : CLINICAL OBSERVA- TIONS— ISCHEMIC PARALYSIS 133-143 Case in Which Pressure on the Muscles Apparently Played an Important Part I33 Case in Which Embolism of the Brachial Artery Was the Only Etiologic Factor I35 Case in Which Marked Muscular Contracture Fol- lowed Contusion of the Leg; Spontaneous Re- covery 130 Case of Ischemic Contracture in Which Pressure Was Probably an Important Etiologic Factor but in Which Marked Relief Followed Freeing of Nerve Trunks from Pressure by Cicatricial Tissue . . 140 Case in Which Bandaging for Uncomplicated Pott's Fracture Was Followed by Gangrene, Necessitat- ing Amputation 141 - Case in Which Beginning Gangrene of the Hand Followed Prolonged Application of a Tight Sleeve 142 Conclusions ^42 CHAPTER VII CERTAIN CLINICAL APPLICATIONS FROM THE FOUR PREVIOUS CHAPTERS. LOCAL GANGRENE FROM ANEMIA OF THE EXTERNAL SOFT PARTS OF THE BODY . 144-149 Anemia in Lesions of the Spinal Cord .... 140 Saline Infusions ; . . . . 148 Flap Tension and Suture Tension I49 xii CONTENTS CHAPTER VIII PAGE ANEMIA OF THE SMALL INTESTINE: EXPERIMENTAL OBSERVATIONS. INTERFERENCE WITH THE CIR- CULATION OF LOOPS OF SMALL INTESTINE OF DOGS FOR DIFFERENT LENGTHS OF TIME UNDER DIFFERENT CONDITIONS i5o-i94 Experiments in Which a Loop of Small Intestine ■with Its Blood Vessels Was Ligated en Masse with Tape, the Tape being Removed Before the Abdo- men Was Closed 152 Experiments in Which a Loop of Small Intestine Was Ligated, a Lateral Anastomosis Having Been Previously ^vlade to Isolate the Loop, and the Tape Removed Before Closing the Abdomen . . . 162 Experiments in Which a Lateral Anastomosis Was Made, a Loop of Intestine Ligated, and the Tape Left in Place After the Abdomen Was Closed . 164 Experiments in Which a Lateral Anastomosis Was Made, a Loop of Intestine Ligated, and the Loop Excised at the End of the Period of Anemia Be- fore Closing the Abdomen 166 Experiments in Which a Lateral Anastomosis Was Made, a Loop of Intestine Ligated, a Drainage Tube Inserted Into the Loop, and the Abdomen Closed 168 Experiments in Which a Lateral Anastomosis Was Made, a Loop of Intestine Ligated, and the Loop Allowed to Project Through the Abdominal Wound -. . 172 Experiments in Which There Was Partial Occlusion of the Blood-Supply of a Loop of Intestine by Ligation of the Corresponding Arteries and Veins, in the ^Mesentery 174 Control Experiment 176 Tabulation of the Experiments on Intestinal Anemia 177 Summary of Experiments on Intestinal Anemia . . 178 CONTENTS Xiii PAGE The Injection into the Intestinal Tract and Perito- • NEAL Cavity of Dogs of Juice from Loops of Small Intestine Previously Rendered Ischemic for Vary- ing Periods of Time 179 Injection into the Peritoneal Cavity .... 180 Injection into the Lumen of the Intestine . . . 183 Injection Intravenously 186 Injection Intraperitoneally of Intestinal Juice from a Dead Dog 188 Injection of Sterilized Intestinal Extract (i) Intra- venously and (2) Intraperitoneally .... 189 Injection into Dogs of Intestinal Extract from Gan- grenous Intestine of Dogs, or of Extract from In- testine of Dead Dogs 190 Conclusions 193 CHAPTER IX ANEMIA OF THE KIDNEYS AND SPLEEN . . 195-219 Anemia of the Kidneys 195 Experiments in Which the Renal Artery Alone Was Clamped 199 Experiments in Which Both the Renal Artery and Renal Vein Were Clamped 207 Anemia of the Kidney of Dogs from Which One Kidney Had Previously Been Removed . . .211 Summary of All Experiments 212 Conclusions 214 Anemia of the Spleen 214 CHAPTER X RESUSCITATION OF THE BODY AS A WHOLE . . 220-240 General Considerations 220 Resuscitation of the Respiratory Apparatus . . . 221 Artificial Respiration 221 Schafer's Table Showing the Relative Efficiency of Methods of Giving Artificial Respiration . . . 223 Resuscitation of the Circulatory Apparatus . . . 226 Methods Commonly in Use 226 XIV CONTENTS CHAPTER XI PAGE RESUSCITATION OF THE BODY AS A WHOLE (Con- tinued) 241-249 The Author's Method of Resuscitation .... 244 CHAPTER XII GENERAL RECAPITULATION . . . . . . 250-251 Local Anemia 250 Resuscitation 251 BIBLIOGRAPHY ..... 253 APPENDIX 258 INDEX 299 LIST OF ILLUSTRATIONS FIG. PAGE I. Normal Small Intestine of a Dog (high magnifica- tion) 151 II. Normal Small Intestine of a Dog (low magnifica- tion) 151. III. Anemia of the Intestine. Duration of anemia four hours (high magnification) 157 IV. Anemia of the Intestine. Duration of anemia four hours (low magnification) 157 V. Anemia of the Intestine. Duration of anemia six hours (high magnification) 160 VI. Anemia of the Intestine. Duration of anemia six hours (low magnification) 160 VII. Cortex from Normal Dog. Brain cell changes pro- duced by toxemia due to anemia of the small intes- tines of a dog. Facing page 190 VIII. Cortex from Toxemic Dog. Brain cell changes pro- duced by toxemia due to anemia of the small intes- tines of a dog. Facing page 190 IX. Cerebellum from Normal Dog. Brain cell changes produced by toxemia due to anemia of the small in- testines of a dog. Facing page .... . 192 X. Cerebellum From Toxemic Dog, Brain cell changes produced by toxemia due to anemia of the small in- testines of a dog. Facing page 192 XI. Anemia of the Kidney. Duration of anemia seven hours (low magnification) 206 XII. Anemia of the Kidney. Duration of anemia eight hours (low magnification) . . -. . . . 206 XV xvi LIST OF ILLUSTRATIONS FIG. PAGE XIII. Longitudinal Frozen Section^ Showing Relation of THE Heart to the Diaphragm 235 XIV. The Thoracic Viscera as Seen from the Front^ the Ribs and the Sternum Intact ..... 236 XV. The Thoracic Viscera as Seen from the Front^ the Viscera Being Exposed by Removal of the Ribs and Sternum 237 XVI, Method of Giving Adrenalin by Injecting it Di- rectly INTO A Stream of Normal Saline Solution 244 SURGICAL ANEMIA AND RESUSCITATION INTRODUCTION The following studies of anemia as it affects the body as a whole or its component parts have been made in an endeavor to solve practical clinical problems which both the surgeon and the internist often confront. In regard to the resuscitation of the body as a whole, the fact has not been sufficiently appreciated that the greatest and most essential difficulty is to overcome the anemia of the brain. In apparent death from drowning, from gas poison- ing, from electric shock, or from any of the many other causes of suspended animation, the organ which most quickly suc- cumbs beyond the power of reanimation is the brain rather than the heart. Since continued normal action of the heart and lungs is dependent on the activity of the brain, the pres- ence or absence, as well as the degree and duration of anemia of the latter organ, decides the possibility of resuscitation. The field for the study of local anemia is very large. Among the commonest examples of causes of local anemia may be mentioned embolism and thrombosis, the too tight application of bandages and other apparatus, localized pressure from the weight of the body in unconscious patients, twisted pedicles of tumors and organs, too tight packing of wounds, and incarcerations and strangulations of intestines. New problems in local anemia have been presented in the last few years, largely through the work of Carrel in transplanting organs or even extremities from one individual to another. Successful organ transplantation presupposes knowledge of 3 4 INTRODUCTION the power of any given organ to resist anemia while the opera- tion is being performed. KuHabko's brilliant work in making the heart continue to beat after its removal from the body, supplemented by the work of Hill, Batelli, d'Halluin, and others abroad, and of Stewart and his associates in this country, paved the way to further study of the automaticity of action of that organ. Attempts to resuscitate the body as a whole by massage of the heart, by artificial respiration, or by the injection of saline or other solutions into the circulation were the natural sequence of their results. The experiments from the author's laboratory which are presented in this book are a continuation of those on surgical shock, in which it was shown for the first time that the blood pressure of a decapitated dog could be maintained for hours by means of the slow, continuous infusion of normal saline solution and adrenalin. This again led naturally to the use of the adrenalin-saline intravascular infusion combined with rhythmic pressure on the chest as a means of resuscitation, a method which, so far as is known, was first demonstrated by the author before the Cleveland Medical Society at Western Reserve University Medical College. In this monograph, as in some of those already published, it has seemed best to publish the experiments in considerable detail. The labor and expense of producing them have been great, and their publication may save other workers unneces- sary repetition. CHAPTER I ANEMIA OF THE CENTRAL NERVOUS SYSTEM. EXPERIMENTAL OBSERVATIONS. INTRODUCTION For a number of eminently practical as well as scientific reasons it is important to know the effects of total or par- tial anemia of the brain. For example, in the course of operation or as the result of injury the surgeon may be com- pelled to choose between ligating the common carotid artery or taking other hazards. It would assist him in making an intelligent decision if he knew the effect of anemia of the brain. In operating on the brain he may be obliged to retract a portion of it, thus causing localized anemia. How long will the brain safely endure such anemia? What will be the im- mediate and final results if he resorts to these measures? Will intermittent retraction be safe, when continuous retrac- tion would be certain to cause injury from local anemia? In cases of cerebral compression from fracture of the skull, from tumors, from abscesses, from edema of the brain, from hem- orrhage, anemia is in many instances the most important factor. It would be of considerable practical value to know whether or not all parts of the brain and spinal cord endure anemia equally well. Do differences exist between the resistance of the lower and higher centers, and if there are differences, are they because the one has been established earlier in the course 5 6 SURGICAL ANEMIA AND RESUSCITATION of evolution than the other, and has become, as some one has expressed it, hardened by longer use, or is it because some por- tions of the brain are more delicately poised ? Which will en- dure anemia longer, the sight or the auditory mechanism, an eye reflex or a tendon reflex, the emotional or the motor mechanism? Will a given amount of anemia abolish the memory and yet leave the motor mechanism intact? Among the medullary centers is the respiratory or the vasomotor, the cardio-accelerator or the cardio-inhibitory the more resistant to anemia? In the following pages an attempt has been made to throw light on these various questions. The importance and the difficulty of the subject must be the excuse for presenting so large a mass of data in detail as well as in summary. THE BLOOD SUPPLY OF THE BRAIN: GENERAL CONSIDERATIONS In the course of evolution, the brain, more than any other organ in the body, has been evolved in such a way as to have a constant supply of blood under even pressure. The brain can expand but the skull cannot expand under the influence of increased blood-pressure. Consequently, unless there were a protective mechanism which would afford a constant margin of safety against over-expansion, cerebral anemia due to pres- sure of the brain against the skull would be produced. Such a mechanism is provided by the water-bed of cerebral fluid on which the brain rests, and by the large venous sinuses. When the brain expands or when it shrinks in volume the cerebral fluid, which connects directly with the spinal fluid, ebbs and flows. At the same time the blood in the large venous sinuses is forced out or in. Under ordinary conditions this prevents undue pressure on the brain, but, as a protection against cerebral anemia, another mechanism has been evolved, ANEMIA OF THE CENTRAL NERVOUS SYSTEM 7 viz., the elevation of the arterial blood-pressure through stim- ulation of the vasomotor mechanism by anemia. Aside from the volume factor of safety, the importance of the brain being abundantly supplied with blood is empha- sized by the provision of a large artery, the common carotid, on each side of the neck. Moreover, each artery is well pro- tected by being deeply buried under strong muscles and fasciae, and is so placed as to be easily defended in case of attack on the individual. In addition to the great carotids there are also the vertebral arteries, which could scarcely be torn except by such an injury as would sever the head from the body. A still further addition to this quadruple supply is the small amount which passes through the arteries of the spinal cord. Besides such adequate protection against cerebral ane- mia, provision for equalization of intracerebral pressure is necessary. This is secured by that wonderful adaptive arrange- ment at the base of the brain, the circle of Willis, by means of which blood is simultaneously received and delivered from the above-mentioned sources. Under normal circumstances the distribution is under even pressure although the halves of the brain may not receive exactly the same amounts of blood. Under certain other circumstances, however, such as fighting, in unusual exertion of one part of the body, in certain posi- tions of the neck and head, and when one side of the neck is subjected to direct pressure, there may be inequality of pres- sure in the supplying arteries, but, subject to the laws of physics, the inequality must be largely eliminated in the circle of Willis and hence in the brain. The fact that cerebral ar- teries are straight and numerous and do not anastomose freely has an important and direct bearing. Closure of an artery between the heart and the circle of Willis is a very different matter from closure of one between the circle of Willis and the cerebral tissue. 8 SURGICAL ANEMIA AND RESUSCITATION To summarize the anatomical points which have a direct bearing on cerebral anemia : ( i ) Provision is made for cere- bral expansion and contraction within the skull; (2) there is a blood-pressure-raising mechanism with which to combat anemia; (3) the four major arteries are placed in the most favorable positions for both active and passive protection against injury; (4) these arteries empty into a circular receiv- ing vessel at the base of the brain which equalizes the pressure and from which an even start is made for the passage of the blood through the straight non-anastomosing arterial trees to every part of the cerebral tissue. THE GENERAL EFFECTS OF COMPLETE ANEMIA OF THE CENTRAL NERVOUS SYSTEM AS SEEN IN DOGS RESUSCITATED AFTER RELATIVE DEATH The method employed by the majority of investigators has been that of occlusion, either of the cerebral vessels or of the aorta at various levels. The objection to this method, which is frankly acknowledged, is that the factor of collateral circulation cannot be entirely eliminated, even in the most favorable animal, the cat. Further, the brain and the spinal cord have been investigated separately, a procedure which must make a vast difference, not in determining the relative viability of the various centers, but in fixing the limit of anemia, admitting of a complete recovery of the animal. Stewart says : "Division of the cord in the upper dorsal region (III to VI dorsal vertebrae), if done before fairly complete recovery of the cerebral centers, is followed by collapse, dila- tation of the pupil, cessation of respiration, cardiac failure, and death. The integrity of the spinal centers is necessary for the resuscitation of the cerebral centers." Other methods of investigation employed, such as artifi- ANEMIA OF THE CENTRAL NERVOUS SYSTEM 9 cial circulation through the decapitated head, and the introduc- tion of emboH, preclude the possibility of recovery studies. Within the last decade, with the more or less successful at- tempts at resuscitation of the heart, contributions to the sub- ject of anemia of the whole central nervous system have been made by several observers, notably Prus and Batelli. The author's study of brain anemia was the sequence of work on the resuscitation of animals killed by anesthetics and asphyxia, which may be briefly summarized as follows : By means of a centripetal infusion of salt solution into an artery together with the simultaneous injection into the stream of one or two cubic centimeters of 1-1,000 adrenalin chlorid, the simultaneous employment of vigorous artificial respiration and rhythmic pressure on the thorax over the heart, the animal may, within certain limits, be resuscitated. For as long as five minutes after total cessation of function resusci- tation is usually successful; for as long as from five to ten minutes there are more failures; while after ten minutes the chances of success are progressively less. As will be seen later, this method is uniformly successful within the limits which are compatible with viability of the central nervous sys- tem. The method is necessarily self-limited, for, in the case of a heart which is losing its irritability owing to lapse of time, dilatation may occur from the infusion before the beat is inaugurated. Even in dogs with rigid chest walls compres- sion of the chest has proved satisfactory. In periods under five minutes but little compression is necessary. Direct cardiac massage is, therefore, not essential. The primary purpose being to determine the period of anemia which the central nervous system can endure with subsequent recovery, the method offers the advantage that no operative procedure is necessary except the small incision for inserting the infusion cannula. The author's results are lo SURGICAL ANEMIA AND RESUSCITATION based, first, on a series of thirty unselected dogs, resuscitated after the lapse of various periods of time, in all but five of which the subsequent course of events was not disturbed. These five were killed after different times for the purpose of histologic examination. Secondly, the series of sixty experi- ments on dogs, previously reported in the paper on resuscita- tion, was drawn upon for data pertaining to this work. In the latter experiments blood-pressure and respiratory tracings were made. Technique For the recovery experiments, with one exception, the dogs were killed with chloroform. While open to objection on account of the paralyzing effect on the nervous system, and non-elimination of the chloroform until after the resuscita- tion, this method was adopted in imitation of the condition most likely to afford opportunity for resuscitative measures in failure of the heart in the course of surgical operations. All procedures were done with the customary aseptic precautions. The infusion cannula was inserted into the axillary artery. In order to estimate in some measure the effect of the anesthesia on the subsequent recovery of the dogs, two experi- ments were done in which the dog was anesthetized in the usual way to the point of respiratory failure and was then resuscitated by artificial respiration without cessation of the circulation being permitted. The first dog showed full return to intelligence in sixteen minutes. The second one took ether like an alcoholic patient, it being forced for ten minutes before struggling ceased. However, in twenty minutes after recur- rence of the respiration, the animal walked about and showed return of function, though extremely "groggy." The period of total anemia was estimated to start from the moment when the first heart sound ceased to be audible ANEMIA OF THE CENTRAL NERVOUS SYSTEM II with the stethoscope, this sound sometimes persisting for sev- eral minutes after the failure of blood-pressure as recorded upon the drum and the disappearance of the carotid or femoral pulse and the second sound. While this is only the statement of a well-known fact, attention is called to it, because very possibly in some experiments it made the stated period of anemia shorter than it actually was, the circulation being too feeble to reach the brain, although the first heart sound was still audible. In some cases on account of the heart sounds becoming fainter, it was impossible to record the actual mo- ment of failure. In these a leeway of at least one-half minute was allowed from the last distinct sound to the recorded cessa- tion. From the time of starting the chloroform to respiratory failure there was an average of two and three-fourths min- utes, with a minimum of fifty seconds and a maximum of seven and five-twelfths minutes. (See Table I, page 50.) The cessation of respiration and the final failure of the heart were synchronous in five cases; from which the inter- vening time varied up to six and three-fourths minutes, with an average of one minute and fifty-seven seconds. From a study of the tracings of the first series it was found that the blood-pressure was at the base line during a longer average time than the latter half of this period. It is probable, there- fore, that during this period the cerebral circulation was re- duced nearly to the vanishing point, and while a small amount of blood goes a long way in the brain, Leonard Hill saying, "It is obvious that the cortex can be kept from death for hours by the merest dribble of blood," this marked anemia of several minutes' duration had an effect which was apparent in that the cases with prolonged partial anemia did not recover as readily as did the average dog subjected to total anemia of equal duration. It is worthy of note that in the dog showing the maximum recovery period, which was one and one-third 12 SURGICAL ANEMIA AND RESUSCITATION minutes above the time of the second best result, only twenty- two seconds intervened between respiratory and cardiac failure. In five out of the twenty-nine animals killed by chloroform there was a brief spontaneous recurrence of the heart sounds, occurring from twenty seconds to one and one-half minutes after they had entirely ceased, and accompanied in two in- stances by two or three faint respiratory efforts. In only one instance was the carotid pulse palpable. As the total duration of anemia cannot be exactly classified, both the absolute and practical duration will be given. The time spent in resuscita- tion is included in the period of total anemia. While it seems reasonable to suppose that centripetal arte- rial infusion of salt solution aided by indirect massage of the heart would hardly reach the brain to any extent during a period of administration of from one to three minutes, and, further, as if it did there would be very little blood in the salt solution, the question was put to the test of experiment. In a dog which had been dead for twelve minutes a solution of methylene blue was infused into the axillary artery, and the usual procedures, with the exception of adrenalin injection, were carried out for double the average time. No indication of its having reached even the bulbar centers was found. This is in contradistinction to direct massage, which, according to d'Halluin, effects a veritable artificial circulation, which is sufficient to reanimate and maintain bulbar activity. Study of the tables of Prus shows that as a result of direct massage respiration returned in twenty-nine out of thirty-five experi- ments in one series, though there was no return of effective heart beat, and, in seven cases, reflexes and muscular move- ments reappeared. The definition of the end of the period of total cessation of the circulation was, however, sharp, the resumption of func- ANEMIA OF THE CENTRAL NERVOUS SYSTEM 13 tion on the part of the heart being abrupt and visible as well as palpable. After a few initial heart sounds blood-pressure rose rapidly, often within ten seconds, to as much as 200 mm. of mercury or over, this rise being due to the adrenalin. Recovery Results (Tables I and II, pages 50 and 51.) Permanent and complete recovery was obtained after five minutes, six minutes,^ six minutes and ten seconds, six min- utes and fifteen seconds,^ and seven minutes and thirty sec-' onds of total cessation of the circulation. That is, one dog out of twelve with total cessation of circulation between the periods of seven minutes and eight and one-half minutes re- covered, whereas only one out of seven between the periods of five minutes and six and one-half minutes died apparently as a direct result of the anemia. Complete recovery was pre- sumptive in another dog after cessation of circulation for seven minutes and thirty seconds. One dog of the second series, after cessation for five minutes and thirty seconds, was killed after twenty-four hours for the purpose of histological examination. As compared with the others of the same degree his condition assured a probable recovery. The asphyxiated dog, after cessation for five minutes and forty-five seconds, was killed on the fourth day. A second animal of the first series, after seven minutes' cessation, was killed on the third day. Our experience showed no intermediate condition uncom- plicated by accidental organic lesion ; in other words, no slow decline to death. The demarcation between recovery and death was sharp. In practically all the experiments the crisis was reached in from twelve to twenty-four hours. Then ^ Recurrence of heart sounds interjected for thirty seconds ; practical time, six minutes and thirty seconds. ^ Recurrence of heart sounds for one minute and twenty seconds ; practical time, six minutes and thirty-five seconds. 14 SURGICAL ANEMIA AND RESUSCITATION death ensued quickly, or else distinct improvements of nervous functions began shortly, continuing more or less rapidly until complete restoration, though the convalescent period lasted in two dogs four and six weeks respectively. From his studies on the effect of different degrees of anemia produced by occlusions, Leonard Hill says : "The degree of anemia required to produce dementia is separated by the narrowest line from that which produces coma and death of the respiratory center. There are either no symp- toms or death in a few hours." Our results accord with this statement. Up to a certain point, not to be exactly limited, but, roughly, six minutes, the after-effects are not marked, and the second, third, or fourth day brings complete recovery. For example, one dog (Experirnent lo), after four minutes and ten seconds' cessation of circulation in less than one hour showed entire return of intelligence, which was evinced partly in well-defined efforts to escape from the laboratory; while another, after six minutes and ten seconds (Experiment 29), showed general return of function within twenty-four hours. Beyond the six-minute limit, however, there is a great deal of after-effect, which increases disproportionately with the in- crease in the duration of the period of anemia, in some in- stances reaching a state in which the animal is little more than a cardio-respiratory mechanism. Beyond this limit recovery is altogether uncertain, but our experiments indicate that the stage of depression is tided over, and that recovery will be complete eventuall}^ though the nar- rowness of the escape is shown by the degeneration of a cer- tain number of neurons in the recovered dogs, whose brains were studied by the Marchi method. This does not exclude the possibility of a partial recovery with a permanent localized after-effect, such as the paralysis of one foreleg, a result de- scribed by Stewart in two animals which, however, were under ANEMIA OF THE CENTRAL NERVOUS SYSTEM 15 observation only seven and nine days, respectively. In our dog, which recovered after anemia of the maximum duration, the degeneration predominated in the pyramidal fasciculus. The distinction here has reference to the ability of the whole organism to maintain any life. The viability of the vital cen- ters, as well as of other centers, is considerably above that of the brain as a whole, as the recovery-results prove, and the im- mediate outcome must depend on the maintenance of the inter- relation and association of all brain centers, cortical and sub- cortical. Stewart says that, when exposed to adverse influ- ences, the synapse proves the weak link in the nervous chain. In general the following sequence of return of the various functions and reflexes was exhibited : respiration, vasomotor control, corneal reflex, and knee-jerk (tendon reflexes in gen- eral), winking, cutaneous reflexes, partial or complete con- traction of pupils, and light reflex. This order was subject to considerable variation, which will be considered under the special discussion of functions and reflexes. Hypertonicity of the voluntary musculature immediately succeeded the recovery of a normal tone, and was manifested by exaggeration of the knee-jerk, if not by a more or less widespread spastic condi- tion. This hypertonicity always immediately followed the reappearance of the knee-jerk. Reflex muscular movements, the result of skin or tendon stimulation, always preceded those of spontaneous origin. Spontaneous incoordinate movements appeared sometimes be- fore, sometimes after, the light reflex, but their later appear- ance occurred only when the light reflex returned relatively early. Succeeding the coordinate movements appeared what may be classed as purposeful movements, attempts to turn over, to arise, or to crawl forward — movements involving all the muscles of locomotion. Usually after the appearance of coordinate movements, auditory and visual reactions reap- 1 6 SURGICAL ANEMIA AND RESUSCITATION peared, the former being always the more definite, and usually- returning first. In many of the dogs that succumbed after some hours there was more than a mere revival of the re- flexes; some of the higher faculties reviving also. The course of events after resuscitation may be summar- ized as follows : A state of hyperexcitability follows reani- mation, reaching its maximum in from one to three hours, when retrogression begins. This second stage is characterized by uncontrolled muscular movements, either coordinate or convulsive, lasts a longer time, and passes gradually into the third stage of depression and paralysis, in which the reflexes are more or less impaired. The dogs which recovered never exhibited as much mentality nor such active reflexes on the second day as they did immediately after resuscitation. The average picture toward the end of the first stage in a recovery dog is of an animal in a condition of stupor, lying quietly for the most part, with an accelerated pulse and quick- ened respiration, expiration being prolonged and labored; with normal conjunctival reflexes; with cutaneous reflexes constantly present in the limbs; with exaggerated tendon re- flexes; and with pupil reflexes uneven and tardy if expressed at all. There is a general spastic condition of the muscles, the legs being commonly held in extension. After loud sounds in close proximity the head may be raised, the eyelids opened with dilating pupils, and the ears pricked up, the attitude being simply one of attention without localization or any indication of ideation. As a result of a flash of light the head may be withdrawn, but usually there is only a lid reflex. When dis- turbed, and sometimes without apparent cause, the animal rouses, barks, looks around, and exhibits coordinate and even purposeful and propulsive movements of the legs and body, attempts to rise or to crawl, usually unsuccessfully, but at times succeeds in standing or in making short progression for ANEMIA OF THE CENTRAL NERVOUS SYSTEM 17 a few seconds, depending on the extent of the paralysis, and then again falls into stupor. The second stage, retrogression, was a constant phenom- enon in all the dogs, but was much less marked after the shorter periods of anemia. The animal becomes progressively more comatose; the spastic condition, which had largely dis- appeared with the reanimation, returns; visual and auditory reaction disappear; and the skin reflexes become inconstant. Muscular movements, however, are kept up, but are less coor- dinate and less spasmodic, their character apparently depend- ing on the duration of the anemia, as convulsive movements are slight after the shorter anemias, while, on the other hand, the dog which recovered after anemia of the maximum dura- tion had definite tono-clonic convulsions. When such convul- sive movements are well marked, the animal later passes into a deep coma, with a general condition from which recovery hardly seems possible. This coma lasts from 6 to 12 hours, but on the second morning a distinct improvement is apparent. Up to this point the course of events in the animals which succumbed was similar to that in the dogs which eventually recovered. In the fatal cases a few did not attain a light reflex, and the majority recovered as far as to exhibit coor- dinate movements and auditory reaction; in but two, how- ever, was there apparently dim consciousness. Reanimation of the higher faculties was much more transient, if present at all, and the animal passed quickly into coma, from which it was impossible to arouse it. There were sometimes periods of violent convulsive movements alternating with periods of quiet and stupor. While these muscular movements were partly clonic and tono-clonic in character, they were distinctly propulsive and progressive, though violent and uncontrolled. Of the coordinate movements, the running motion of the legs, such as is frequently seen in the early stages of anes- 1 8 SURGICAL ANEMIA AND RESUSCITATION thesia, was the best example, and was performed with extreme rapidity, the dog lying partly on its back with its legs waving rhythmically in the air. Sometimes only the forelegs were involved, but usually the movement was general. If the dog was not too much paralyzed, this resulted in a crab-like pro- gression about the room. The strictly convulsive movements were very complex, clonic and tonic types being mingled, with a resultant violent thrashing about. In several instances there was some opisthotonos. The slightest disturbance provoked movements characteristic of the animal. The quiet periods in the early stages were of short dura- tion, but the intervals between them were distinct. In the later stages the intermediate periods of rest became more and more prolonged. Finally, as if worn out, quiet would ensue, the animal being perfectly limp ; tendon and skin reflexes dis- appearing first, next the eye reflexes, until only the cardio- respiratory functions were left complete, with respiratory fail- ure near. To show the slow return of faculties and the paralyzing effect of the maximum period of anemia from which recovery was made (seven minutes and thirty seconds in Experiment 2.y), the subsequent course of the animal in this experiment will be given in some detail. On the second day she was awake but paid no attention to her surroundings. To loud sounds there was only an occasional response, and blindness appeared absolute. The hind legs were entirely paralyzed, but when the hind quarters were supported she was able to walk on the forelegs, though the progression was cross-legged or sprawl- ing. Sensation was much more deficient than motion, no attention being made to the prolonged immersion of any foot in cold water. A strong bulldog clamp on a hind paw pro- voked restlessness only, though on a forepaw it was vaguely localized, but only to the extent of a reflex from the leg itself, ANEMIA OF THE CENTRAL NERVOUS SYSTEM 19 there being no coordinate attempt at removal. Food was not recognized when placed in the mouth, and was held there pas- sively. No notice was taken of tobacco smoke or ether vapor. On the third day she walked about, though unsteadily, and with a decided stringhalt gait of the hindlegs. She recognized water after standing in it for several minutes. The legs gave way when she jumped off a chair. Hearing was very acute, but vision appeared to go no farther than the mere perception of light. That localization of sensation was improved was shown by the clamp test, as she bit rather aimlessly and very incoordinately at the foot affected, very frecjuently attacking the wrong leg. It was not until the seventh day that the clamp was recognized, grasped and pulled off. On the third day the feet were withdrawn from cold water, but the sense of posi- tion was not evident until the fourth day, this being tested by resting the feet on boards at different levels. Only maximum differences of levels were recognized. While the animal ap- peared hungry, constantly licking her chops, food was not recognized until the fifth day. Tobacco smoke and ether vapor were not noticed until a week after resuscitation. While within a week the return of all the faculties with the excep- tion of vision was indicated to a greater or less degree, the animal was by no means normal, but exhibited great hebetude in all Vespects. She was very lethargic, would not run nor play, and response to any stimulus was delayed and feeble. How much of this lethargy was due to the blindness it was impossible to say, but certainly not all. For two weeks there was hardly any perceptible improvement in vision. She paid no attention to the attempts to test her vision, and she moved about slowly, feeling her way, though at about the end of the second week she noticed moving objects if within the range of a foot or two, especially when they were held above the level of her eyes. From this time on improvement continued stead- 20 SURGICAL ANEMIA AND RESUSCITATION ily, and, at the end of the fourth week, recovery of vision was complete. With the recovery of vision the condition of de- mentia entirely disappeared, and then for the first time the psychical faculties of fear, pleasure, and memory became nor- mally evident. In the case of the dogs which succumbed the following observations were made: Among seven dogs subjected to anemia lasting from five to seven minutes, one died after twenty-four hours. Of those which died after anemia from five to seven minutes in extent, two revived enough to exhibit spontaneous coordinate muscular movements, without visual or auditory reactions or return to consciousness. Of five which succumbed after eight-minute to nine-minute periods of anemia, one did not recover sufficiently to show even the light reflex, and did not come out of coma; two recovered to the extent of muscular motion; a fourth recovered auditory re- action; while in only one was there a suggestion of a return to consciousness. Among three subjected to from nine- to ten-minute periods of anemia one recovered so far as to ex- hibit apparent consciousness, one failed to recover the power of vision, and in the third the light reflex returned. One dog after anemia, lasting for twelve minutes and ten seconds, showed only a revival of the reflexes, and in the dog which recovered after the longest period of anemia only coordinate muscle movements appeared in addition to the reflexes. Special Phenomena Following Resuscitation Respiration. — (See Table III, page 52.) Respiration has recurred in every animal in which the circulation was restored and maintained for a sufficient period. The maximum case, thirty-two minutes of total anemia, twenty-one minutes after the circulation was established, showed return of respiration to the extent of three faint gasps, but cardiac failure imme- ANEMIA OF THE CENTRAL NERVOUS SYSTEM 21 diately ensued. Comparison of the time of restoration of respiration in our experiments shows a much more rapid re- covery than that recorded by several other observers. In our experiments the average time for the restoration of animals subjected to anemia for periods of from three to eight minutes was three minutes and fourteen seconds. The average recov- ery time in Stewart's cats and dogs after occlusion of vessels for the same periods was seven minutes and forty-one sec- onds; for Prus's chloroform series with periods from three to five and one-half minutes was seven minutes and nineteen sec- onds (with frequent return of respiration before efficient heart beats). Batelli's successful chloroform cases with the same periods are too few for comparison, but, in general, both these and the electrocuted dogs gave data in concordance with the above results. Hill says that a certain arterial pressure is necessary to invoke respiration. This explains the increased effectiveness of the higher blood-pressure due to the adrenalin used in the author's experiments. The first respiratory gasps were distinct and fairly strong. In the majority of the animals after a few gasps, inspiration exhibited a triple character, with the inspiratory-expira- tory ratio of three to one, such as occurs in sobbing. This lasted for several minutes. Gradually the rate increased and the rhythm became regular. A sudden resumption of the nor- mal type of breathing sometimes happened in the dogs sub- jected to short duration of anemia, and was always associated with the simultaneous recovery of the eye reflexes. A rapid increase of rate was the rule in all cases, as much as loo per minute being recorded, but usually the high rate did not long continue. For example, it was 72 per minute sixteen minutes after resuscitation in the dog which recovered after anemia of seven and one-half minutes and fell to 36 in about twenty minutes. Later it was subject to frequent changes, and in 22 SURGICAL ANEMIA AND RESUSCITATION some cases a normal rate was not established until the third day. As the rate slowed, a prolonged and labored expiration was characteristic. The changes of rate in the initial respira- tions will be best illustrated by reference to the protocols of two experiments. EXPERIMENT 27 Hound puppy, about eight months old. Seven and one-half min- utes total cessation of the circulation. 11.45.30. — Return of pulse was first noticed. 11.47.30. — First respiration. The first four respirations occurred at thirty-second intervals, and then, :':or about three minutes respira- tions occurred at seven-second intervals, each inspiratory act com- prising three distinct efforts. Fibrillary contractions of the tongue occurred after beginning of respiration. 11.55.00. — Lacrimal secretion began. The right pupil was dis- tinctly contracted. 11.58.00. — Respirations rather suddenly assumed normal char- acter and rhythm, with rate of 24. 12.00.00. — Respiratory rate jumped to 48. EXPERIMENT 30 One-year-old puppy. Twelve minutes and ten seconds total ces- sation of circulation. 1 1.30. 15. — The heart began to beat, recording from first observa- tion of the pulse in the axillary cannula. Though the infusion tube was partly clamped by the finger, pressure was sufficient to drive the blood into the infusion bottle at a height of five feet. 11.32.25. — First respiration occurred. This movement and those following for several minutes were deep and gasping. For four min- utes the rate was very irregular, at intervals varying from five sec- onds to one minute. Artificial respiration was kept up continuously during this time, but was stopped as soon as spontaneous respirations became more regular. 11.37.00. — Respirations now occurred at three to five-second in- tervals. 11.38.00. — Respiratory rhythm was more steady (20 per minute), and movements were more shallow. 11.44.22. — Respirations, 28 per minute. 12.00.00. — Respirations, 32 per minute, were somewhat more ir- regular and spasmodic. Expiration was distinctly labored. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 23 12.13.00. — Respirations, 40. 12.40.00. — Respirations, 32. The dog was evidently failing, and about one hour later was found dead. Blood Pressure. — (See Table III, page 52.) — The use of adrenalin complicated the study of the blood-pressure changes. In a successful resuscitation, as already noted, the blood pres- sure rose rapidly, often within ten seconds, usually to a height of 200 mm. of Hg, and in one case to 250 mm. This level was maintained from two to five minutes in all but the dog with 250 mm. of pressure, and then it began to fall as the effect of the adrenalin wore off. From ten to forty minutes elapsed be- fore the lowest level was reached. Depending on the extent of the vasomotor reactivation, either a tendency to rise was im- mediately exhibited or the low level persisted for from ten to twenty minutes, in the latter case with a subsequent rise. In two animals, after total anemic periods of seven minutes and thirty seconds and eight minutes and thirty seconds, one of which at least may be credited with presumptive recovery, this second level was maintained until the animals were killed — in twenty-four hours and in five and two-thirds hours respec- tively — but in the others, all with anemia of longer duration, it was only a temporary reanimation and, along with the re- flexes, steadily declined until death. On account of the adrenalin effect in overlapping the re- turn of normal vasomotor activity, particularly after the shorter periods of anemia, the relative time of the reactivation of the vasomotor center could not be absolutely determined. Stimulation of the sciatic nerve did not cause the usual rise of pressure until the secondary rise had begun, and respirations were well established (see Table IV, page 53). With one exception respiration in all experiments returned well before the end of the first fall in blood pressure. In one experiment of the second series as little adrenalin as possible 24 SURGICAL ANEMIA AND RESUSCITATION was used : the anemia lasted five and one-half minutes and respiration began in two minutes after restoration, while reac- tion to sciatic stimulation was not obtained for four minutes. Synchronously with the pressure reaction, respiration rather suddenly assumed a more normal type. It appears, therefore, that the return of activity in the vasomotor center is nearly synchronous with the return of respiration after the shorter periods of anemia, but is more delayed after the longer periods. In the puppy subjected to thirty-five minutes of anemia there was apparently no vasomotor reactivation. Reflexes. — (See Table IV, page 53.) While varying considerably in the time of their recurrence, after equal periods of anemia, the corneal reflex and spontaneous winking returned in all but the three experiments which were not suffi- ciently protracted. The light reflex reappeared constantly after eight minutes of anemia, though it was the least uniform in time of its return and in its degree of activity. In periods of anemia of more than eight minutes the recovery of the light reflex was inconstant. The maximum anemia period after which the corneal reflex reappeared was twenty-four minutes (maximum resuscitation in adult dogs), and for the light reflex the maximum time was fourteen and one-half minutes. The knee-jerk varied the least in its recovery periods. It was also noted in the resuscitation after the maximum anemia period. Not infrequently there was a difference in the time of recurrence of the bilateral reflexes, in two cases one corneal reflex reappearing three minutes before the other, though for the knee-jerks no difference of over one-half minute was noted. As to the relative time of the reappearance of reflexes, the knee-jerk usually appeared before the corneal reflex, though they were synchronous four times. The corneal reflex always ANEMIA OF THE CENTRAL NERVOUS SYSTEM 25 preceded spontaneous winking, while in every case the cutane- ous reflexes returned before the light reflex. Temperature. — While not recorded as a matter of routine, sufficient data have been obtained to indicate that the tempera- ture continues to fall for several hours following resuscita- tion. The lowest rectal temperature was 32.9° C, four hours after anemia of nine and one- fourth minutes (Experi- ment i), and 33.8° C. was reached in sixteen minutes after thirteen and one-third minutes of anemia (Experiment 5). From this point the temperature gradually rose to a state of hyperpyrexia, which was more marked in the animals which succumbed. In the dog which recovered after the maximum period of anemia the maintained level was reached the second day. Phonation. — Nine and one-quarter minutes of anemia (Experiment i) was the maximum period after which this faculty returned. Actual barking, indeed, occurred in but one other case of over seven and one-half minutes of anemia (Ex- periment 14), though there was whining or imperfect attempts at vocalization in three cases. Phonation usually appeared synchronously with or shortly after the exhibition of spon- taneous muscular movements, that is, one-half to one hour after resuscitations following anemia of about seven minutes. Micturition and Defecation. — Micturition or defecation oc- curred in the majority of animals during the period of hyper- excitability. Auditory, Visual, and Olfactory Senses. — As already indi- cated, the reaction to auditory stimuli was definite and unmis- takable during the period of hyperexcitability in the recov- ered dogs, while to various visual stimuli during the same period the only response was a lid or pupil reflex, but out of fifteen animals subjected to anemia for seven minutes or more, only six gave even a temporary recovery of hearing. 26 SURGICAL ANEMIA AND RESUSCITATION Further, in the animals which recovered the later effects on vision were much more marked, in general increasing as the limit of possible recovery was approached. For example, in the dog with recovery after the maximum anemia period, hearing was reasonably acute on the third day, though vision was not fully restored for three weeks, while in the animal with anemia of six and one-sixth minutes (Experiment 29), the best example of early visual recovery, hearing was normal on the second day, though a day more was required before the animal ran about without colliding with obstacles. The maxi- mum duration of anemia after which hearing was observed was nine and three-fourths minutes (Experiment 15). The sense of smell came back at a point between hearing and vision, though the test was never definite unless irritating fumes were employed. The first reaction to these was on the third and seventh days, respectively, in dogs with anemia of six and of seven and one-half minutes (Experiments 2 and 27). Phenomena Referable to the Cortex. — IMost of the animals which recovered passed through a final stage comparable in many respects to the condition of Goltz's decerebrates. Such a period was characterized by dementia and loss of intelli- gence, the lack of any psychic response to stimuli, and the in-: ability to recognize food and drink. Response to stimulation was purely reflex, or was absent if memory of past experiences was involved. For example, meat placed in the mouth was held there passively or in one case forcibly spat out, a flash of light was answered by a lid reflex, and there was indifference to the relative position of the fore legs. Power to localize stimuli was of gradual acquirement. Restlessness, however, was generally not observed. That the temporary paralysis was of cortical origin was indicated by the associated exaggeration of the knee-jerks. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 27 The motor function did not suffer as much as the sensory, for the paralysis disappeared before the return of intelhgent and normal response to stimulation. The clinical observation that the cortex suffered the most and was the last to recover is supported by the fact that the histological alterations were more marked in the cortex than in the lower centers. The other dog which recovered also gave a picture of de- generation, but of a different character. While the actual number of nerve fibers involved was greater, not only was there no localization but there was an early stage of degenera- tion with droplets of varying size, scattered in longitudinally cut spinal nerves at intervals along the course of the fibers affected. This animal, which was killed in six days, was, at the time of death, partially blind and deaf and, though it could stand, it was too paralyzed to maintain the upright posture or to walk. The question arises as to whether it would have eventually recovered. Judging from the other animals which, with final recovery, passed somewhat more rapidly through a sirpilar condition, and from the fact that there was a notice- able improvement from day to day in the animal just men- tioned, general recovery, with a complete destruction of a few neurons, is probable. An early degeneration similar to that mentioned occurred in the fatal cases, though the number of fibers involved was considerably less. None of these animals had lived over thirty-six hours at the outside. On account of the shortness of the time which had elapsed, this appearance was unexpected and will be further investigated. However, it corresponds with the organic changes in the cell-bodies which occurred during the same time. 28 SURGICAL ANEMIA AND RESUSCITATION Comparison of the Authors' Results with the Results of Others Mayer concludes that from ten to fifteen minutes of anemia is the maximum period admitting of general resusci- tation, though respiration and the vasoconstrictor activity may recover after that time. Stewart, with complete recoveries after occlusion of cerebral vessels for five, six, eight, nine and four-fifths, and sixteen and one-half minutes, agrees with Mayer's conclusion. Hayem says that, in general, brain func- tions are not recovered after from ten to eleven minutes. The conclusions of Batelli and of Prus are the only ones drawn from observation of animals resuscitated from ap- parent death. None of Batelli's dogs survived, and he ascribes this fact to the severity of the operation on the thorax neces- sary for his resuscitative measures of electrical stimulation and heart massage. He states that its condition being aggra- vated by the violent respiratory efforts, the animal passes into coma and dies. However, from the extent of reanimatjon exhibited, he concludes that the functions of the central nerv- ous system may be reestablished after ten minutes of total anemia, but not constantly after fifteen, and that the maximum limit is twenty minutes. Prus does not fix a definite limit. Stewart suggests that, in such prolonged periods of one and two hours as those of Prus, the auricles must have kept up a slow, but in some degree efficient, movement of the blood through the brain. On account of the injury from opening the thorax, Prus attempted recovery in only thirteen out of fifty-two reanimated dogs, the others being killed after a short time. Two of these survived. One was killed by as- phyxiation, after a period of total anemia of six minutes, estimating from the stoppage of the heart to the beginning of direct massage, as considered under "Technique." From the ANEMIA OF THE CENTRAL NERVOUS SYSTEM 29 data given, the subsequent course of this animal corresponds closely to the author's six-minute anemia cases. The other of Prus's recovery dogs after an anemia period of four minutes v^as killed by chloroform. The dogs that survived from three to five days were all subjected to anemia of short dura- tion, and of the two cases subjected to ten minutes of total anemia, one died in six and one-half and the other in twenty-four hours, all the deaths being ascribed to infection. From the author's experience, it seems justifiable to say that the observation of an animal resuscitated from a state of completely suspended animation is very misleading unless car- ried far enough, and that such observation does not permit of conclusions regarding the limit of anemia admitting of recov- ery. The reason is that there quickly ensues a condition of hyperexcitability of reflexes associated with voluntary move- ments and with greater or less return of the special senses, even with an apparent return to consciousness; consciousness may be transient, but appears in animals which succumb as well as in those which eventually recover. This phenomenon was exhibited in dogs subjected to nearly twice the duration of anemia from which recovery was made, and in several in- stances the appearance of reanimation was so decided as to make the prognosis very hopeful. But after a few hours, more or less, the special senses failed, the dog became progressively stuporous, convulsions ensued, then loss of reflexes, and, finally, respiratory failure. The decline to death indicated definitely a nervous origin ; and autopsies on all the cases fatal immediately after the resuscitation showed in only one case any organic lesion to which death could be attributed. This was a dog which had been subjected to anemia of eight and one-half minutes (Experiment 14) and which died between thirty and forty hours later, with an early and irregularly dis- 30 suRGic.\L axe:mia axd resuscitation seminated bronchopneumonia. As long a survival as this was exceptional. By the occlusion method, the general conclusion appears to be that ten to fifteen minutes of anemia is the maximum period after which resuscitation is practicable. This conclu- sion is not unassailable for two reasons; first, because of the impossibility of absolutely eliminating the factor of collateral circulation, and, second, because the brain and cord have been investigated separately. In the latter connection, apart from the interrelationship of the two, the possible percolation up- ward of the cerebrospinal fluid, with the circulation of the cord unimpeded, is worthy of consideration. As a result of the authors' experiments with an undoubt- edly total anemia and little opportunity for infectious acci- dents — conditions the most favorable for investigation of the possibility of recovery — the opinion is that the limit should be reduced one-half. For dogs killed by chloroform the average duration of anemia from which recovery may be made is be- tween six and seven minutes. The extreme limit appears to the author to be under ten minutes, and any recovery after more than seven and one-half minutes would be exceptional. The accurate fixation of the limit beyond which recovery is impossible is of great practical importance. Summary To determine the limits of recovery after a total anemia of the central nervous system, thirty dogs were killed by chloroform and resuscitated after the lapse of varying times of from three to fourteen minutes. If resuscitated in less than five minutes the recovery of function was rapid and was strikingly free from the after-effects which characterized longer periods. Of seven animals anemic from five to six and one-half minutes, only one died apparently as a direct result of ANEMIA OF THE CENTRAL NERVOUS SYSTEM 31 the anemia, but of twelve subjected to anemia from seven min- utes to eight and one-half minutes, only one recovered after seven and one-half minutes of anemia. The remaining dogs all died. Further corroborative data are drawn from the pre- viously published paper on the technicjue of resuscitation. Histological examination both of presumptive recoveries and of fatal cases was made by ordinary methods and by those of Nissl and Marchi. The neurocytes of the fatal cases uni- formly presented the greatest change, being not merely chrom- olytic but here and there definitely indicative of cell death. Marchi's method further supports these findings by proving the existence of fiber degeneration. Finally, showing the nar- rowness of the escape, in the animal showing the best recov- ery-result after seven and one-half minutes of anemia, which at the end of four weeks had apparently entirely returned to a normal state, histological examination by the Marchi method showed the degeneration of a number of fibers in the pyram- idal fasciculi, which were traced from the cord to the cortex, and in Flechsig's fasciculus, while a more sparsely scat- tered degeneration of both ascending and descending fibers was evident elsewhere. In recent works (1911) all changes due to cerebral anemia have been much more extensively studied. Protocols of Ten Selected Experiments -^ EXPERIMENT i Death from Chloroform; Resuscitation Begun 5 Minutes After Cessation of Circulation ; Total Duration of Anemia, 9j4 Minutes July, 1906. Small mongrel dog; fairly nourished, but with a general vesicular and pustular eruption. A cannula was inserted into the axillary artery, and connected by means of rubber tubing with the saline in- ^ The numbers of these experiments do not , correspond with those given in the foregoing pages, the former referring to the tables. 32 SURGICAL ANEMIA AND RESUSCITATION fusion bottle, at a height of five feet above the operating table. Ether was given at first, and then chloroform in lethal dose. After cardiac failure a tracheal intubation tube v^^as inserted, so that artificial respi- ration could be given with bellows. 10.20.30 A. M. — Respiration ceased. 10.21.30. — Respiration began again. More chloroform was given. 10.22. — Respiration ceased. 10.27.15. — Heart sounds ceased, and pulse was no longer palpable (5 minutes and 15 seconds after final cessation of respira- tion). 10.32.15. — Began to resuscitate; 5 minutes after cessation of circula- tion normal saline solution was given through the axil- lary cannula, 2 c. c. of 1-1,000 solution adrenalin chlorid solution were injected through the rubber tubing, just above the cannula, into the saline stream, by means of a hypodermic syringe, and artificial respiration was begun with the bellows. 10.36.30. — The heart began to beat, making the total duration of ces- sation of circulation 9 minutes and 15 seconds. 10.40. — Spontaneous respiration began, 4 minutes 15 seconds after return of circulation. 10.50. — The heart sounds were distinct, but slow and somewhat ir- regular, improving from this time on. The respiration was regular and normal. 10.55. — The respiration suddenly became irregular. Artificial res- piration was begun, with rapid improvement of the res- piration following. 11.37. — Conjunctival reflexes were first obtained, i hour ij^ min- utes after return of the circulation. The heart was apparently acting in an entirely normal manner. The blood-pressure, which had been very low, was about " 100 mm. of mercury, in so far as it could be judged from the pulse. 11.43, — Knee-jerks were obtained in the left hind leg, i hour 7^^ minutes after return of the circulation. They were then obtained in the right hind leg, but more feebly. 11.45. — Respiration was normal. The intubation tube was re- moved. There was some slight resistance to flexion and extension of the hind legs, but the fore legs were com- pletely relaxed. 11.47. — The knee-jerks were slightly stronger. The pupils were widely dilated and with no reaction to light. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 33 12.15. — The pupils were becoming narrow, and were just begin- ning to react to light, i hour 38^/^ minutes after return of circulation. The general muscular tone was better, but the fore legs were still relaxed, except at the shoulders. Moving the neck, especially flexing it, was resisted. The spinal muscles resisted when the back was bent. 12.50. — The hind legs were somewhat spastic, flexed at the thigh and extended at the knee. The fore legs were still more so. The muscles of the back were not spastic on flexion, but were somewhat so on extension. The reaction of the pupils to light was active. The right pupil was much more active than the left. The respiration and blood-pressure were normal. Spontaneous defecation occurred, 4 hours y/2 minutes after return of the circu- lation. The temperature by rectum wis 32.9° C. The skin was very cold. 1.50. — Temperature 33.3° C. The condition of the muscles was the same. On being moved the dog seemed to utter purposeful moans, and showed some apparently purpose- ful movements of the fore legs, as if trying to get up. The pupils were of normal size, the left being slightly more dilated than the right. When not disturbed im- mediate general relaxation, followed by sleep, took place. 2,00, — At about this time and shortly after, several spontaneous periods of awakening from the stupor occurred, the eyes being widely opened, while purposeful but futile attempts were made to turn over and stand up. After several of these attempts had been made at irregular in- tervals one was induced by pounding on an adjacent table. The dog evidently heard the noise, as he opened his eyes and tried to rise. When quiet ensued he re- lapsed again into stupor. When the hand was passed rapidly in front of his eyes he blinked. 4.00. — The dog was sleeping, with grunting respirations. On be- ing disturbed, he rose to his feet, but relaxed at once into a stupor, and fell down. Also when left alone he relaxed into stupor. Apparently he was able to see, for, when aroused, he looked fixedly but vacantly. A mov- ing object did not cause winking until the eyelids were touched. 5,30. — The spastic condition had passed off. The knee-jerks were 34 SURGIC-\L ANEMIA AXD RESUSCITATION active, but there -was no clonus. A comatose condition was present. Loud noises did not disturb. Under stimu- lation spontaneous attempts at forward locomotion oc- curred, the movements of the fore legs being coordi- nated. Relapse immediately followed the efforts. 9.00. — Temperature not taken, but dog in high fever. He lay stretched out in a spastic condition, with labored, ster- torous, rapid breathing, which soon became rapidly irregu- lar and gasping, although the pulse was still good. The knee-jerks had almost disappeared. Death was evi- dently near at hand. 9.15. — Respiration ceased. The heart continued to beat rhythmi- cally for about three minutes more. Autopsy was per- formed before the heart action had entirely ceased. Autopsy : The heart was empty and apparently normal. Xo clots were present. The lungs showed nothing of importance except slight congestion at the base. In two places the liver had been slightly injured by the mas- sage. Both liver and spleen showed a chronic inflam- matory change of no interest in the present connection. The other organs appeared, to be normal. EXPERIMENT 2 Death from Chloroform; Resuscitation Begun 3 Minutes After Cessation of Circulation; Total Duration of Anemia, 6^ Minutes July 25, 1906. Black mongrel bitch ; weight, about 7.0 kilos. Experiment con- ducted as in Experiment i, using ether at first and then the lethal dose of chloroform. 11.52.30. A. M. — Respiration ceased. 11.53.30. — Heart action no longer perceptible. 11.54.30. — Heart beats appeared again, but the pulse was barely per- ceptible. 11.55. — Heart beats ceased. Pulse no longer palpable. The cir- culation practically ceased at 11.52.30. 11.58, — Began to resuscitate in the usual way, 3 minutes after final cessation of circulation. 12.00. — Heart beats appeared, making the duration of complete cessation of circulation 6^^ minutes. 12.01. — Spontaneous respiration began 45 seconds after return of the circulation. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 35 12.09. — Knee-jerk appeared in the left hind leg, 8 minutes 45 sec- onds after return of the circulation, and Yz minute later in the right hind leg, 9 minutes 15 seconds after return of the circulation. ■12. II. — Conjunctival reflex appeared on stimulation, 10 minutes 45 seconds after return of the circulation. 12.13. — The fore legs began to stiffen, and incoordinate muscular movements occurred. In connection with the latter and in conjunction with the respiratory efforts movements of the head first appeared. The muscles of the hind legs became tonic, but were not stiff. 12.15. — Spontaneous winking occurred. 12.18. — General slight spasmodic muscular contractions occurred, while the muscular movements became more coordi- nated and purposeful. The pupils were still dilated. 12.20. — The respirations were still labored. The pulse was of good quality. The pupils began to narrow, and the gen- eral muscular movements continued. 12.25. — I'^ response to touching the skin the leg was drawn away, showing that the cutaneous reflex had returned, 25 min- utes after return of the circulation. 12.27. — O^ lifting the dog from the table to her box she raised her head and looked toward the bearer. The breathing had just become fairly quiet and normal. 12.32. — A spontaneous attempt to get up was made. 12.35. — The dog barked. The head was held in marked extension. 12.40. — It was shown by slight movements of the eyes or head that attention was paid to loud sounds made by ham- mering on a box. To loud whistling there was but slight response. The pupils were still dilated greatly, but showed faint reaction to light, 40 minutes after re- turn of the circulation. 12.45. — Notice seemed to be taken of the surroundings. The ani- mal's general appearance might be described as being stupid. Water was not drunk, even when the nose was placed in it. 5.00. — The dog was apparently brighter, languidly following movements in her immediate vicinity, but spent the time in quietly sleeping, if not disturbed. The spastic condi- tion had almost disappeared. 9.30. — She was found ten feet away from her box, egress having been barred by a side six inches high, over which she 36 SURGICAL ANEMIA AND RESUSCITATION had climbed. She was unconscious, barely arousing when returned to the box, when she immediately re- lapsed into deep stupor. Loud sounds only called forth subdued groans. Defecation occurred. Temperature, 40.1° C. Respirations were quiet and easy. The pulse was of high tension and somewhat thready. Constant shivering was present. The knee-jerks were again ex- aggerated, but most of the spasticity of the legs was lost. On being pinched the general spastic condition returned. Various muscular movements occurred, and occasionally they seemed to be in response to loud sounds. July 26, 1906. 9.00 A. M. — The dog was found quietly sleeping. The pulse was normal in character, the respiration easy, the tempera- ture 39.5° by rectum. The knee-jerks were still exag- gerated, but the legs had lost most of their spasticity. For the first time an exaggerated scratch reflex was obtained. When annoyed by flies she tried to wipe them away with her paws, and threw her head toward the point of irritation, but without trying to bite at them. On loud whistling the eyes were barely opened. On suddenly striking a match in front of her eyes only a delayed conjunctival reflex was caused. Attempts to disturb her merely roused her slightly from her stupor. Petting apparently did not arouse any cere- bral ideation. The general appearance was that of mod- erate morphin anesthesia. The same condition was maintained all day, the dog sleeping quietly when undis- turbed. Twice milk was given her by means of a . stomach tube — 300 c. c. at noon and 500 c. c. at night. July 27, 1906. 9.00 A. M. — The dog was lying outside her box. When put on her feet, she walked aimlessly, being rather shaky and ataxic, and did not see obstacles in her path in time to avoid them. Striking a match suddenly before her face caused opening and blinking of her eyes, but she was perfectly indifferent to a light moved slowly in front of her eyes. Only once did loud sounds cause her to move away into a corner. After that time she paid no atten- tion to whistling, or to stamping, even immediately in front of her head, regarding such actions with a vacant ANEMIA OF THE CENTRAL NERVOUS SYSTEM 37 stare. The odor of an old pipe had no effect. Chloro- form and tobacco smoke caused her to draw her head away, but this was considered to be a reflex action. Patting and petting brought forth only a scratch reflex. Water was refused, even when put into the mouth. She very quickly became tired, and lay down to sleep. She was given 500 c. c. of milk, as before. 12.00. — She licked the orderly's hand, and when her nose was put into some milk she drank abundantly, and continued to be fed in this way. Later in the day it was noted that when she was disturbed she observed things around her, but, if left alone, she slept. July 28, 1906. 9.00 A. M. — This morning she appeared more lethargic. The wound in the axilla, where the cannula had been inserted, was discharging freely. Temperature, 39.1° C. The scratch reflex was not satisfactory, only a head reaction being obtained. At times the dog seemed to be conscious of petting, but very vaguely so. In some instances threat- ening motions apparently caused slight cowering, but usually they were regarded with complete indifference. When left alone she slept all the time. She was very sensitive to pain. Sometimes she reacted to the odor of the old pipe. Sounds attracted attention only when made close to her. She still regarded with indifference a lighted match in front of her eyes. She drank milk only when it was put into her mouth. After being examined she sank into a deep stupor. July 29, 1906. 9.00 A. M. — When a door near her was opened she raised her head. She appreciated the proximity of milk, drinking spon- taneously when it was set near her head. She gave a slight scratch reflex. Whistling and calling caused her to raise her head, but otherwise she paid no attention. For the first time a lighted match 'near her head caused her to withdraw it. Threatening motions produced cow- ering and trembling. Petting produced nothing defi- nite except a head reflex, as though she were going to catch a fly. July 31, 1906. 9.00 A.M. — Since the last note the dog was practically in a uniform state of hebetude, although her physical condition was 38 SURGICAL ANEMIA AND RESUSCITATION almost normal. She walked with very little un- sseadiness when examined on the above date. Her sense of sight was very feeble, as she had no perception of objects so close to her nose that she could not turn aside quickly enough to avoid bumping into them with force. She would walk across the laboratory floor in a straight line until she hit whatever happened to be in her line of progress. Then she would have her direction changed, only to repeat the performance over and over again. To loud whistling she made only a delayed, indifferent, ideationless turning of her head. At times she seemed to appreciate being petted, while at others she was abso- lutely indifferent, only a scratch reflex being brought forth. On one occasion she rubbed against the ob- server's leg, as if petting gave her pleasure. For several weeks longer improvement of the mental state was so slow as to be almost imperceptible. The dog was utterly listless, sleeping, or at least lying down most of the time, occasionally walk- ing about in a very constricted area, or standing still with the head lowered. How much this was dependent on her almost total blind- ness it was impossible to say, but, with the return of vision, at least a vision sufficient for her purposes, ideation began to be apparent, and later appeared what might be called, for lack of a better phrase, a conscious initiative, an acting for herself. Inside of six weeks, to all appearances, her mental and physical functions were as before her period of relative death. EXPERIMENT 3 Death from Chloroform; Resuscitation Begun 3 Minutes After Cessation of Circulation; Total Duration of Anemia, 5 Minutes July 27, 1906. Mongrel dog; weight, about 7.0 kilos. Experiment conducted as in Experiment i. Total duration of anesthesia, 15 minutes. 10. 16.15 A. M. — Respiration ceased. 10.20. — The heart began to fail rapidly. 10.20.15. — Circulation ceased. 10.23.15. — Began to resuscitate in the usual way, 3 minutes after ces- sation of circulation. 10.25. — The heart began to beat again, making the total duration of cessation of circulation 5 minutes. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 39 10.25.40. — Spontaneous respiration began, 40 seconds after return of the circulation. 10.27. — Conjunctival reflexes were first noted, 2 minutes after re- turn of the circulation. The knee-jerks returned a little later, but were not uniform for some time, although the dog rapidly became rather spastic, with clonic muscular spasms and continuous barking. 10.40. — The pupils were contracted. On account of the struggles of the animal the pupillary reflexes were not satisfac- torily obtained. 10.42, — On being disturbed there was an ataxic effort to get up on his feet. 10.45. — -^^ unsuccessful, spontaneous effort to get up occurred. The pupils did not react to light. There was no scratch reflex. 10.50. — On being disturbed the dog struggled and tried to get away. The breathing, which had previously been very rapid and labored, was now quiet. 10.55. — The spasticity had diminished. When placed on the floor loud whistling caused the dog to stand on his feet and move away. The motion, however, was of a semi-crawl- ing character, there being very little control of the front legs. A lighted match held in front of the eyes caused the head to be jerked away. 2.00. — There was no scratch reflex. The knee-jerks were again somewhat exaggerated. The dog was in a somnolent state, paying no attention to loud sounds. A lighted match before the eyes produced only a conjunctival re- flex. Warming the paw to the point of slight discom- fort only caused it to be moved away, and there was apparently no evidence of pain being caused. Warming the ear caused only a muscle reflex. July 28, 1906. 9.00 A. M. — Earlier in the morning a feeding through the stomach tube was vomited, only a little of the milk being re- tained. The dog was found out of his box, suffering severely from snuffles, and with a respiratory defect, as shown by the slow and labored respiration. The heart action and blood-pressure were of good quality. The temperature was 39.1° C. On account of the lethargic condition little was brought out by the examination. He was indifferent to a lisfhted match held in front of 40 SURGIC-\L ANEMIA AND RESUSCITATION the eyes, hardly more than a conjunctival reflex being called forth. On loud sounds being made, he reacted but slightly, with coordinated muscular movements. To loud whistling at any distance he was indifferent. The smell test with the old tobacco pipe was negative. There was no scratch reflex. Apparently he was not conscious of pain. It was impossible to make him an- gry. He walked normally. On holding him he pulled away, and when let alone he at once went to a corner and lay down. To threatening motions with a broom he was absolutely indifferent. July 29, 1906. 9.00 A. M. — When the observer came into the room the dog re- garded his entrance with ordinary intelligence. Hear- ing and vision were apparently good. An error of judgment was made on the part of the observer in making threatening motions before conducting the rest of the examination. As a result the dog cowered and walked into a distant corner under a table, and the subsequent examination was not satisfactory, on account of his fear. Attempting to pull him out of the corner made him snarl, but he did not attempt to attack the observer. After prolonged petting, he finally wagged his tail, but he still seemed cowed. He would not drink milk when it was put into his mouth. He reacted poorly to the smell of the tobacco pipe. There was no scratch reflex. July 30, 1906. 9.00 A. M. — The dog refused milk, but ate an abundance of meat. He responded normally to petting and threatening. All his muscular movements seemed normal. In some un- known way he escaped from the laboratory to the street, and was chased by the orderly for half a mile before he was caught. While escaping he showed all evidences of normal canine intelligence in eluding capture. In about two hours he escaped a second time, probably through an open first floor window, and reached the street by a very devious route. He was seen no more, but there is no doubt but that he was well able to take care of himself. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 41 EXPERIMENT 4 Death from Chloroform; Resuscitation Begun 6 Minutes After Cessation of Circulation; Total Duration of Anemia, 83^ Minutes July, 1906. Young fox terrier ; weight, 7.3 kilos ; condition, good. Experi- ment conducted as in Experiment i. Total duration of anesthesia, 15 minutes. 9.57 A. M. — Respiration ceased. 9.58. — Circulation ceased. 9.59.30. — Several weak respiratory movements occurred, and the heart beat feebly again for about 10 seconds. The ac- tion was too weak to produce a palpable pulse in the carotids. 10.04. — Began to resuscitate, 6 minutes after cessation of circu- lation. 10.06.30. — The heart began to beat again, making the total duration of cessation of circulation 8^ minutes. 10.09. — Spontaneous respiration began, 2^ minutes after return of the circulation. 10.20. — The respiration was regular. 10.23. — The conjunctival reflex was first obtained and normal spontaneous winking noted, 163/2 minutes after return of the circulation. The fore leg reflex was first ob- tained 3^ minute later, and was more marked in the right leg. (Note. — This was the first experiment in which the leg reflex was obtained in a fore leg before being obtained in a hind leg.) The knee-jerks ap- peared somewhat later, and first in the right leg. 11.26. — The right knee-jerk was strong, the left weak. The dog began to utter an inarticulate cry. Rectal temperature, 36.1° C. 11.32. — The fore legs began to stiffen. The hind legs were still relaxed. 11.45. — The hind legs were considerably more spastic. There was no definite pupillary reflex. Temperature, 36.6°. 2.30, — Temperature, 36.1°. The dog was still unconscious, with no indication of even incoordinated muscular movements. The hind legs were very spastic, while the fore legs had become flaccid. The knee-jerks were exaggerated. There v/as no scratch reflex. The pupils were con- 42 SURGia\L AXEML\ AXD RESUSCITATION tracted, but the light reflex could not be obtained with certainty. The dog both vomited and defecated. 4.30. — A condition of complete coma was present. Xo muscular movement had been made, and the spastic condition had disappeared. Vomiting occurred again. The morning of the succeeding day the dog was found dead, and had evidently died early in the preceding evening, as the body was much distended with gas from an infection with Bacillus aero genes capsnlatus. Autopsy. — The heart had stopped in systole. There was no evidence of any injury of the thorax or its contents. In the heart a post-mortem clot was found in the light side, while in the left a small, firm, ante-mortem clot was entangled in the auriculoventricular valve. It was not large enough, however, to interfere with the circu- lation. The lungs were moderately congested — on the left side hypostatically so. Otherwise the viscera were negative. EXPERIMENT 5 Death from Chloroform; Resuscitation Begun 9 Minutes After Cessation of Circulation ; Total Duration of July, 1906. Anemia, 14 Minutes. Mongrel dog; weight, about 5 kilos. Experiment conducted as in Experiment i. Total duration of anesthesia, about 20 minutes. 11.28.30. A. M. — Respiration ceased. 11.28.40. — Circulation ceased. 11.37.40. — Began to resuscitate, 9 minutes after cessation of circula- tion. Ringer's solution was substituted for normal saline solution, and only 0.5 c. c. of adrenalin chlorid solution was used. 11.42. — The heart began to beat again, making the total duration of cessation of circulation 14 minutes. 11.46. — Spontaneous respiration began, 4 minutes after return of the circulation. 11.52. — Stopped giving artificial respiration. 11.56. — The knee-jerk was obtained in the left hind leg, 14 min- utes after return of the circulation. 11.56.30. — The knee-jerk was obtained in the right hind leg, and was faintly present in the fore legs. 11.58, — On touching the left eye the conjunctival reflex was ob- tained, 16 minutes after return of the circulation, and ANEMIA OF THE CENTRAL NERVOUS SYSTEM 43 in the right eye a little later. If the nose were pinched the right fore leg was moved. The pupils had become very much contracted. Temperature, 36.1° C. by rectum. 1.45 p. M. — Temperature, 36.1°. The dog was generally more spastic. The pupillary reaction to light was distinct, although slight and delayed, less than 2 hours after return of the circulation. Respirations were somewhat groaning in character. Voluntary movements of the legs, such as occur in the early stages of ether anesthesia, were made, and at times the head was raised, as if in an attempt to rise. Warming the paw to a moderate degree only caused withdrawal of the limb, and there was apparently no consciousness of pain. Temperature, 37.8°. 5.30. — Temperature, 39.0°. The condition was about the same. 10.00. — The dog was found out of his box on the floor. He made unconscious propulsive movements of the legs, and at times raised his forelegs, as if trying to get up. The latter movements did not seem to be purposeful. There was a general spastic condition of the muscles, and the knee-jerks were exaggerated. The pupils reacted, al- though slowly. There was no evidence of perception of pain, and the dog neither saw nor heard. Disturbing by touching evoked only reflex movements. The next morn- ing the dog was found on the floor in deep stupor, with thready pulse, quiet respiration, and temperature of 39.0°. He started when touched at any point, although the knee-jerks were not so exaggerated, and the spastic condition had disappeared. He was oblivious of stimu- lation through any of the special senses. There was no scratch reflex. Death occurred at about 11.30 A. M. Du- ration of recovered animation, 24 hours. EXPERIMENT 6 Death from Chloroform; Resuscitation Begun sV^ Minutes After Cessation of Circulation; Total Duration of Anemia, 7^ Minutes July,, 1906. Mongrel dog; weight, about 8 kilos. Experiment conducted as in Experiment i. lo.ii A. M. — Respiration ceased. 10,12. — The heart almost stopped, and then beat more strongly. The pulse was barely perceptible. 44 SURGICAL ANEMLA. AND RESUSCITATION 10.14. — The heart sounds ceased, and the pulse was no longer per- ceptible. 10.19.30. — Began to resuscitate, 5^ minutes after cessation of the cir- culation. 10.21.30. — The heart began to beat again, making the total duration of cessation of circulation 7I/2 minutes. 10.30. — Rectal temperature, 37.0° C. 10.35.30. — Spontaneous respiration began, 14 minutes after return of the circulation. 10.38. — Stopped giving artificial respiration. 10.50. — The knee-jerks were obtained, most marked in the right leg, 283^ minutes after return of the circulation. 10.51. — A faint conjunctival reflex was obtained on touching the eyes, 29^ minutes after return of the circulation. The pupils were contracted. 10.55. — Both pupils reacted to light, 33^^ minutes after return of the circulation, but there was no winking. 10.57.30. — Faint spontaneous winking appeared, 36 minutes after re- turn of the circulation. The knee-jerks had become very much exaggerated. There was a general return of muscle tone. 11.22. — Inarticulate barking sounds were made. 11.40. — The muscles were generally spastic. 12.00. — Movements of the leg, such as occur in the early stages of anesthesia, were begun. 3.35. —Temperature, 37.7° C. 5.00. — Temperature, 38.0° C. Periods of restlessness, with mov- ing about in the box, and respiratory cries alternating with periods of quiet. There was no response to a light moved in front of the eyes, nor to loud sounds. If touched the dog usually moved. There was no evidence of pain being felt. Even with frequent attempts the scratch reflex could not be obtained. 10.30. — The condition was the same, except that there was more restlessness and more spasticity. The next morning the dog was found dead and stiff. The autopsy revealed no gross lesions. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 45 EXPERIMENT 7 Death from Asphyxiation; Resuscitation Begun 4^ Minutes After Cessation of Circulation; Total Duration of Anemia, 5^ Minutes July, 1906. Mongrel collie dog; weight, about 9.2 kilos. Ether was used for carrying out the operative technique in the usual way. The trachea was exposed by a small incision and clamped to produce asphyxia. 10.42.40 — The heart almost stopped beating, only to start again with a distinct pulse perceptible. 10.45. — Respiration ceased. 10.45.15. — Circulation finally ceased. 10.49.30. — Began to resuscitate, 4^ minutes after cessation of cir- culation. 10.51. — The heart began to beat again, making the total cessation of circulation 5^ minutes. 11.00. — Stopped the artificial respiration. 11.03.30. — On touching the right eye the conjunctival reflex was ob- tained, 12^ minutes after cessation of the circulation, and Yi minute later it was obtained in the left eye. 11.05. — I^ the right eye the light reflex was good, but in the left it was faint, I4>4 minutes after cessation of the circula- tion. The right pupil was contracted, while the left was dilated. The hind legs were drawn up, but there were no knee-jerks. 1 1. 15. — The knee-jerks were obtained, 24^^ minutes after cessa- tion of the circulation. 11. 16. — An inarticulate crying began. 11.45. — For the first time spontaneous muscular movements were noted. There was no scratch reflex, and no conscious- ness of light or sound. Temperature, 37.9° C. by rectum. i.oo. — Temperature, 38.5°. 4.30. — Temperature, 39.6°. 5.00. — The dog was lying quietly in an extremely stupid condi- tion, but not sleeping. The striking of a match in front of his eyes caused him to raise his head and cock an ear just a little, but the pupils did not change. He seemed to be just a little conscious of pain. There was no scratch reflex. The hind legs were rather spastic. 5.30. — Temperature, 40.1°. 46 . SURGICAL ANEMIA AND RESUSCITATION 10.30 p. M. — The dog was entirely unconscious. His eyeballs were turned down and half covered by the conjunctivae. The pupils were dilated and gave but a faint light reflex. The knee-jerks were active. Only the hind legs were slightly spastic. On pinching the paw the leg was with- drawn. On warming the ear both the head and the body were moved slightly. The special senses were ab- sent. Temperature, 39.2°. On inserting the thermome- ter in the rectum the legs were moved. On the second day the dog was still in a deep stupor, and evi- dently very ill. No satisfactory results were obtained in making the usual examination. On the third day it was found that the dog was infected, and he was killed with chloroform. EXPERIMENT 8 Death from Chloroform; Resuscitation Begun 3^^ Minutes After Cessation of .Circulation; Total Duration of Anemia, 5 Minutes July, 1906. Male mongrel collie puppy; weight, 3.6 kilos. Experiment con- ducted as in Experiment i. Total duration of anesthesia, up to cessa- tion of respiration, about 15 minutes. 11.05.45 A.M. — Respiration ceased. 11.09. — Circulation ceased. 1 1. 12.30. — Began to resuscitate, 3}4 minutes after cessation of cir- culation. 1 1. 16. — The heart began to beat, making the total cessation of circulation 5 minutes. 11. 17. — Spontaneous respiration began. 11.26. — Stopped giving artificial respiration. From the first the blood-pressure continued to be good, and the spontane- ous respiration was well maintained. After stopping artificial respiration the latter was normal for 20 min- utes, then began gradually to fail. Artificial respi- ration was resumed for a while, but without effect. Up to this time none of the reflexes had reappeared (knee- jerks, muscle, or eye), and the muscles were entirely flaccid. At about 11.50 respiration failed altogether. On rapidly opening the chest the heart was found to be still beating, and continued to beat rhythmically for 15 minutes, even after both ventricles had been incised. ANEMIA OF THE CENTRAL NERVOUS SYSTEM 47 The lungs appeared to be normal. The abdomen con- tained a sHght excess of fluid. Portions of the brain were placed in alcohol about 15 minutes after opening the thorax, while there was still some circulation. EXPERIMENT 9 Death from Chloroform; Resuscitation Begun 35^ Minutes After Cessation of Circulation; Total Duration of Anemia, 53^ Minutes December 22, 1906. Mongrel dog; weight, about 8.0 kilos. Besides the usual arrange- ments a cannula was inserted in a femoral artery and connected with a mercury manometer, so that the blood-pressure could be recorded on a smoked drum. 12.10 p. M. — Control on drum. 12.13. — Vasomotor action elicited. Control. 12.17. — Forced the chloroform. 12.19.30. — Respiration ceased. 12.20. — The heart stopped beating, but after a few seconds began to beat again. 12.22. — Circulation ceased. ■ 12.25.30. — Began to resuscitate, 3}^ minutes after cessation of circu- lation. Only two thirds of a cubic centimeter of adrena- lin chlorid solution was injected. 12.27.30. — The heart began to beat again, making the total duration of cessation of circulation 5^^ minutes. 12.29.30. — A single respiratory gasp occurred. There was no vaso- motor reaction on stimulation. 12.30.30. — There were several respiratory gasps, but no vasomotor reaction. 12.31.30. — Respiration began steadily, and immediately after a distinct vasomotor reaction was obtained. 12.38. — Control. 12.40. — There was a feeble conjunctival reaction to touching the eyeball. The knee-jerks were first obtained, and were somewhat exaggerated. 12.43. — There was faint, spontaneous winking. 12.45. — There was a faint pupillary reaction to strong light. 12.50. — There was a general spastic condition of the muscles. The respiratory movements were labored. 12.55. — Slight spontaneous movements of the hind legs occurred. 48 SURGICAL ANEMIA AND RESUSCITATION 12.59. — On disturbing the dog he made purposeful muscular movements, and the head was raised, as if he wanted to rise. On warming the ear he showed definite signs of consciousness. I.OO. — There was a faint response to auditory stimuli, respiration stopped for a moment, the eyes opened, and the ears pricked up. To stimulation with light only winking was obtained. 1.30. — The dog tried to rise and move forward. The spasticity was distinctly less. There was no indication of con- scious vision. 1.42. — The dog tried to walk, but was too ataxic to succeed. - 2.00. — Condition about the same. 4.36. — There was the same degree of purely reflex visual action and also auditory reaction, which, as before, had the appearance of consciousness merely rather than of seeing or hearing. More spasticity was present. When first seen the appearance was more stupid than at 2.00, but, while being observed, there suddenly started a vio- lent dyspnea, in place of the normal respiration, and several unsuccessful attempts were made to crawl for- ward. This lasted for about 7 minutes, gradually sub- sided to quiet breathing for about a minute, and then began again. The second period of dyspnea lasted for about 3 minutes, to be followed by a short period of almost complete apnea, another minute of dyspnea, half a minute of apnea, and two or three more times the forward propulsive efforts were made. This arrhyth- mic, Cheyne-Stokes type of respiration continued as long as this period of observation lasted, about 40 minutes. When the dog was returned to his bed he became somewhat quieter. December 23, 1906. 10.00 A.M. — On approaching the dog he raised his head toward the observer with some appearance of intelligence, but he immediately relapsed into his stupid state. It is a ques- tion if any ideation was conveyed. The flash of a match repeated in front of his eyes evoked only a faint con- junctival reflex. The signs of more conscious reaction were apparent, although not more markedly so than on the preceding day. The pupils were very much di- lated, reacting to light both directly and indirectly, i.e., ANEMIA OF THE CENTRAL NERVOUS SYSTEM 49 stimulation of one eye only would cause the other to re- act also. Appreciation of pain was very doubtful. The knee-jerks were exaggerated, although there was less plasticity than on the preceding day. When placed on his feet, he was able to stand, although on walking he was very ataxic, largely because of paralysis of the right hind leg, the result of the operative procedures. There was no patellar reflex, even after repeated tests. Petting was submitted to without any appearance of ideation, while there was absolute indifference to threat- ening. Water was refused when placed in his mouth. He was etherized, and a portion of the brain at once transferred to 96 per cent, alcohol. EXPERIMENT 10 Death from Chloroform; Resuscitation Begun 5 Minutes After Cessation of Circulation ; Total Duration of Anemia, 10 Minutes December, 1906. Dog; weight not noted. Experiment conducted as in Experi- ment I. 9.55 A. M. — Began to anesthetize with ether. 10.10. — Changed to lethal dose of chloroform. 10.12. — Respiration ceased. 10.14.40. — Circulation ceased. 10.19.30. — Began to resuscitate, 5 minutes after cessation of circula- lation. Rather violent massage was employed, and three doses of adrenalin of two cubic centimeters each were given. 10.24.20. — The heart began to beat, making the total cessation of cir- culation 10 minutes. 10.29.30. — First indications of returning respiration were noted. 10.32.20. — Faint spontaneous respiration began. 10.40. — Stopped giving artificial respiration. ' 10.45. — Knee-jerks were obtained in the right hind leg. 10.50. — An occasional conjunctival reflex could be obtained in the right eye. The knee-jerks were exaggerated. 10.53. — The conjunctival reflex was obtained in the left eye. 11.00. — There were partially spontaneous conjunctival reflexes. 11.07. — The pupils had been contracting slowly, and were about one-half normal size. There was no pupillary reflex to so SURGICAL ANEMIA AND RESUSCITATION TABLE I— SERIES I The Time of the Respiratory and Circulatory Changes Duration of Time from Recurrence of Beginning of Time from Inefficient No. OF Administra- Respiratory Heart Beats Duration Experi- tion of Chloro- to Cardiac After Appar- of Total Results ment form to Res- piratory Failure Failure ently Com- plete Failure 1 Anemia 12 4f 3^ 3 Killed after i hour. lo 4^ i3^ 4^ Killed after i hour. 17 3 4M Died, 53 minutes. 3 iJ4 4 5 Recovery. 22 2 3 IM 5^(6-/2) Recovery. 8 2j^ K 2 5K(7H) Killed, 24 hours. 26 2 M sM Killed on 4th day; sec- ondary infection. 13 2 6 2 6(8) Killed after i hour. 2 2^ . I ^ 6(61^) Recovery. 23 2% iM 6A Died, 24 hours. 29 5. 6 3 6M Recovery. 25 I^ 4^ 7 Died after 30-40 hours. 7 3^ 7 Died, 34 minutes. II 7A ^ 73^ Died, 15-20 hours. 6 3 3 7^ Died, 12-20 hours. 27 2-i'2 22 7K Recovery. 20 2M iM 8 Died, 10-20 hours. 28 3^ iK 8^ Died, 12-20 hours. 18 2 8M Died, 63 minutes. 4 4 I M 83^ (8K) Died, about 12 hours. 19 2M If 8A Died, about 20 hours. 14 2 I 8>^ Died, 30-40 hours; dis- seminated broncho- pneumonia. 24 4^ 3 8J^ Died, 23 hours. I 6M 9K Died, II hours. 9 2 2% 9% Killed, I hour. IS 3^ y^ 9M Died, about 18 hours. 16 10 Died, 10-18 hours. 30 11^2 3 123^ Died, about 23^ hours. S M 13M Died, 24 hours. 21 2 3 14 Died, 40 minutes. ^This column refers to the spontaneous recurrence of the heart sounds in five cases from one-third to one and a half minutes after they had entirely ceased. As the extent of the circulatory recovery could not be exactly estimated, though usually it was not sufficient to produce a palpable pulse, in the next column the duration of the total period without any evidence of cardiac activity is given first, while the figures in parentheses include the partial recovery. 2 Asphyxiated dog. ' Synchronous. Note. — Time is expressed in minutes, and blood-pressure in millimeters of mercury. ANEMIA OF THE CENTRAL NERVOUS SYSTEM SI light. The knee-jerks were very much exaggerated. There was only moderate resistance to passive motion of the legs — to flexion more than to extension. 1 1. 12. — The fore and hind legs were held in rigid extension, with occasional tremors occurring. II. 15. — The right pupil was more contracted than the left, and gave no reflex. 11.40. — There was still no pupillary reaction to light, although the pupils were of equal size by this time. The respiration was normal, and the heai't action and pulse were of good character. The cerebral cortex was exposed and stimulated by an induced current in various places around the motor area. No muscular contractions re- sulted. Before the heart stopped beating the brain was transferred to alcohol. TABLE II— SERIES I Ten Cases in Which the Total Anemia Lasted Seven and One-Half or More Minutes Number of Experiment Mode of Death Total Duration of Anemia ' Results 28 19 Ether Asphyxia 73^ minutes 83^ minutes Presumptive recovery; killed after 24 hours. Killed after 6 hours. 3^ Chloroform 93^ minutes Died after 20 hours. 37 Chloroform g}/^ minutes Died after 20 hours. 48 Asphyxia 1 2 minutes Died after sH hours. 39 Chloroform 133/2 minutes Died after 15 hours. 41 Chloroform 15 minutes Died after 15 hours. 30 Ether 163^ minutes Died after 33^^ hours. 43 Chloroform 24 minutes Died after 4^^ hours. 49 Chloroform 32 minutes Died after 27 minutes. ^ The figures in this column include the time spent in resuscitating. 52 SURGICAL ANEMIA AND RESUSCITATION B< I ^ !-1h CXh RQ ■w C c "U .£f Sri xa! o g s-J n! C ■J; S 'ta o ?, ^« _ J, g a, Id > E-- g i^ ^ 5^ „ <^ c^ ^ 3' U O fN UO CO ^O O MO o o o o ■^ O l-l CO IN moo ^ H M CSOiClCNl-IMM M o z w « a 3 04 H W B ''' g o t3 c3" t^ d 13—1 — lu d r^ U3 +J d -tJ O) -; rf - S2 >> *- 13 tn -5 g^ g ^1. I— I h- 1 I— 1 Ph h- 1 O ANEMIA OF THE CENTRAL NERVOUS SYSTEM S3 TABLE IV— SERIES I The Time of Return of the Reflexes After Restoration of the Circulation No. OF Duration Respira- Corneal Light Cutaneous Experiment of Anemia tion Reflex Winking Reflex Knee-Jerlj Reflex (First) 12 3 2 A% 5 38 16 _ lO 4K 1% 10 lo3^ i83^ 10 13M 17 A% 2H 20 25 3 S % 2 1 io3€ 2 — 22 S>€ iM 1 ^sVi 128 17 23 8 5^ 2 13^ 16M i8>^ 12 26 S^/i — 12K — 14^ 243^ — 13 6 7A 1 19 2 35 39 2 6 M loM 13 40 m 25 23 6^ 2 10^ 193^ 3 313^ 32^ 29 6K M sK 7H 94 iiK 17^ 7 7 I 25 7 2,V 1 Under i 29 Under 15 Under 15 II 7^ 4M 17 23 34 17 34 6 73^ 14 293^ 36 333^ 28^ — 27 7^ 2 123^ 20^i 533^ 143^ 24H 20 8 3 21 1 21 66 28 8^ iH i7t 34 68 1 42 18 8M 2% 20 25 4 8M 23^ 1 18K 233^ iZV2 19 Sr? I IS 35 62 17 60 14 83^ i34 1 i83^ 17 — 24 m iH 14^2 38 3 1 S3 I qH 43i 6x3^ 1 983-^ 74^ 9 9% 8 2S 35 2 20% — IS 9^ i3^ 16 34 14 49 16 10 6 28 38 3 28 — 30 12^ 2M I2i.i 23/4 32 25M 28M 5 I3H 4 16 16 60 + 14 16 21 14 3 ^ Recurred; exact time not noted. ^ Insufficient time. ^ Did not return under observation. Note. — Time is expressed in minutes. CONCLUSIONS I. In dogs lightly anesthetized by ether and then killed quickly by chloroform the average limit of total cerebral ane- mia, estimated from cessation of the heart sounds to return of circulation, which admits of recovery, is between six and seven minutes. The ulterior limit appears to be under ten minutes, 54 SURGICAL ANEMIA AND RESUSCITATION hitherto stated as the most conservative figure, and any recov- ery after more than seven and one-half minutes of anemia would be exceptional. 2. Further experience with the resuscitation of animals killed by anesthesia and by asphyxia, embracing numerous un- recorded experiments, as well as those forming the basis of this chapter, establishes the former conclusion of the authors, viz., that the procedures detailed afford a reliable method of resuscitation within its limitations, and one uniformly success- ful within the limits compatible with the recovery of the cen- tral nervous system. CHAPTER II ANEMIA OF THE CENTRAL NERVOUS SYSTEM : CLINICAL OBSER- VATIONS. CEREBRAL ANEMIA THROUGH LIGATION OF THE COMMON CAROTID ARTERIES GENERAL CONSIDERATIONS Although the blood supply of the brain is better safe- guarded than is that of any other part of the body, experience in ligating the common carotid arteries in man has shown that harmful cerebral anemia may result. The brain of man, being a mesial and symmetrical organ, has two sets of arteries from which its blood supply is de- rived, each set consisting of (i) the common carotid, (2) the vertebral, (3) the profunda cervicis, and (4) the inferior thyroid. The common carotid and the vertebral artery of either side of the head furnish the main blood supply and con- nect with the arteries of the opposite side through the circle of Willis. The profunda cervicis arises actually from the superior intercostal, but so close to the origin of the latter that it may practically be said to arise from the subclavian, distal to the origin of the vertebral; it connects with the princeps cervicis, and through it with the occipital, the last-named being a branch of the external carotid. The inferior thyroid arises from the thyroid axis on the subclavian (also distal to the origin of the vertebral), connects with the superior thyroid, and the latter with the external carotid at its point of origin 55 56 SURGICAL ANEMIA AND RESUSCITATION with the common carotid. However, as it also connects with the inferior thyroid of the opposite side, it would be less effi- cient than the profunda cervicis as a path of collateral circula- tion on account of its stream being divided. From the anatomic relationships it necessarily follows that ligation of the innominate artery would shut off entirely direct circulation from the right side of the brain. Likewise ligation of the common carotid and of the subclavian proximal to the origin of the vertebral from the subclavian would completely shut off direct cerebral circulation on the side on which the ligation was done. If the common carotids and the vertebral arteries of both sides are ligated the remainder of the collateral vessels must take up the burden, a burden which, for practical purposes, is beyond their capacity. It is almost incredible that an indi- vidual could live for any length of time after such ligation, but, in the "Science and Art of Surgery," Erichsen mentions a case of Davy's in which life was maintained for "a consider- able time." In ligating either common carotid artery success may de- pend on the patency of the circle of Willis. While its absence must be extremely rare, Derby describes a case in which hemi- plegia followed ligation, and at the autopsy the circle of Willis was found actually to be absent. Granting that the circulation through the four major ar- teries is alone efficient to maintain the life of the brain, and that ligation of one common carotid leaves the three other ves- sels open, still it by no means follows that only one-fourth of the blood supply is cut off, since the common carotids are much larger than the vertebrals. Consequently it is not strange that this interference may cause harm. LIGATION OF THE COMMON CAROTID ARTERIES 57 ANALYSIS FROM THE LITERATURE OF FIVE HUNDRED CASES OF LIGATION OF THE COMMON CAROTID ARTERY -In order to ascertain with reasonable accuracy how fre- quently injury of the brain due to anemia has followed liga- tion of the common carotid artery, five hundred cases were chosen at random from reliable sources in the literature of the subject. Many cases were omitted in which serious injury to the head might have complicated the results. Among the 500 cases were 51, or 10.2 per cent, in which serious or fatal cerebral injury occurred as a result of the anemia. In securing these figures the conditions for which ligation was done were disregarded — the operation of ligation per se being considered alone. It is of interest to compare this result with the figures given by Keller in the table below : Author Number of Ligations Number of Cases with Cerebral Symptoms Number of Deaths Le Fort Pilz (i), Pilz (2) , Sattler. Keller.. 370 520 139 63 47 100 or ly .oYo 165 "32.0% 32 "23.0% 4 " 6.3% 4" 8.5% 71 or 21 .0% 91 " 17-5% 20 " 14.0% 3 " 4-5% 4 " 8.5% From this table it is readily seen that there is a consider- able variation in the number of cases in which cerebral symp- toms occurred. The later the cases occurred chronologically the better the results, i. e., up to a certain extent. This is doubtless due to the general improvement in surgical methods, particularly as regards asepsis. In analyzing the above 51 fatal cases it was found that they could be classified as follows : 58 SURGIC-\L ANEML\ AND RESUSCITATION 1. Number of cases with hemiplegia of the oppo- site side from that on which the ligation was made (including 4 cases with cerebral abscess) 42 = 8.4% (of 500) 2. Number with hemiplegia of the same side.. = 0.0% 3. Number with "paralysis" and inflammation of dura mater i = 0.4% 4. Number without paralysis but with other or not clearly stated fatal injuries of cerebral origin 8 ^ 1.6% Among the 42 cases with hemiplegia (see No. i above) there were: 1. Fatal cases, death occurring within a com- paratively short time 34 = 6.8% (of 500) 2. Recoveries with permanent paralysis (so far as could be determined) 6 = 1.2% 3. Recoveries with stated transient paralysis. . . . 2 = 0.4% Not included under recoveries with transient paralysis (see No. 3 above) were certain cases in which symptoms occurred which probably could be attributed, at least in part, to cerebral anemia; such symptoms as "peculiar sensation in arm of opposite side" ; "weakness in opposite arm" ; opposite arm and leg somewhat weaker, with hair of head turned from black to gray and the hair of the opposite side from the hga- tion thought to be grayer than that of the same side, and with temporary pallor of the same side of the head; headache, un- pleasant fullness in the head for three years, when the patient died; stupor for 48 hours; serous apoplexy (in a case of pulsating tumor of the orbit) ; convulsions immediately after tightening the ligature; pallor, cold sweat, and strabismus — all on the side on which the ligation was done. In the fatal hemiplegia cases which came to autopsy the cerebral lesion was found invariably on the same side as that on which the ligation was done, while the opposite side of the body had been paralyzed while life lasted. In only one LIGATION OF THE COMMON CAROTID ARTERIES 59 case in the entire series was embolism reported to have been found, one of Siegrist's cases, and in that the middle cerebral artery was not affected. The patient was a man, 47 years of age, who had carcinoma of the tongue and secondary hemor- rhage. The right common and internal carotids were tied. At the moment when the ligature was tightened the patient be- came pale and cyanotic, the pulse and respiration ceased, the sensoria were lost immediately (the operation was done under cocain), both pupils were dilated, the right almost completely, the left to a lesser degree, but all these symptoms ceased after about two minutes. Later in the day he complained that he could not see with his right eye, and the typical signs of em- bolism of the central artery of the retina appeared. This was confirmed at the autopsy. In addition a thrombus was found in the internal carotid artery which continued into the middle cerebral artery, the artery of the corpus callosum, and the posterior communicating artery. The mere fact that the above case was the only one of embolism found in the series strengthens the view that cere- bral injury following ligation of the common carotid is due to ligation rather than to embolism, just as in ordinary cases of apoplexy the lesions are caused by anemia, and it matters litt-le where the obstruction is as long as the blood supply is shut off. That anemia may not always be due to ligation directly is suggested by the autopsy reports of certain cases, notably Sie- grist's (see above), in which, as stated already, a thrombus was found to extend from the point of ligation for quite a dis- tance into the common carotid, with prolongations into some of its branches, no embolism being detected. In a case of fatal hemiplegia reported by Zimmerman, in which both the com- mon and internal carotids were ligated, there was found as- cending thrombosis in the internal carotid, which extended into the middle cerebral, the anterior communicating, and the 6o SURGICAL ANEMIA AND RESUSCITATION artery of the corpus callosum. Hemiplegia had not developed until evening of the day of the operation, death taking place on the third day. In a second case of Zimmerman's the com- mon, internal, and external carotids were tied. At the autopsy ascending thrombosis was found in the internal carotid with extension into the middle cerebral artery, the artery of the cor- pus callosum, the internal capsule, the corona radiata, and the temporal lobe. Acute meningitis and a double inspiration pneumonia were present, the attack of hemiplegia having come on on the day after the operation, with death occurring on the fourth day. In regard to the local conditions in the brain itself, it may be said that the autopsy reports stated almost invariably that "cerebral softening" was present on the side on which the ligation was done. In one case of hemiplegia it was re- ported that the consistency of the brain was unaltered, but that there was light stippling (Punktirung) of the white matter. In most of the cases the softening seemed to be throughout the hemisphere, although in a few cases it was localized, e.g., in one it was in the temporo-occipital and parie- tal region, in another in the corpus striatum, and in a third around the margins of the fissure of Sylvius. In a case of Dubreuil's the under half of the frontal lobe showed extrava- sation of blood from two-thirds of its substance with one-half of this area apparently softened. In one case only, in which other factors were not present to account for it, was edema stated to have been present. In considering the etiology of cerebral injury after ligation of the common carotid it may be stated at the outset that the dangers accompanying surgical interference with the circula- tor v system of the aged are in direct ratio to the age of the patient. In the 500 cases studied the age of the patient was stated 349 times. Of the 349 patients there were 301 in whom LIGATION OF THE COMMON CAROTID ARTERIES 6 1 cerebral symptoms were stated to have been absent, or not stated to have been present. The average age of the 301 pa- tients w^as 33.6 years. In the 48 cases of cerebral injury in which the age was stated the average age was 41.5 years. Therefore, in so far as such a rough comparison may have weight, the older the person the greater the likelihood of cere- bral injury. Conditions for which the common carotid artery have been ligated are varied, and some of them are now of historic in- terest only. The following table shows the distribution in the 500 cases : 1. Hemorrhag'e (including- traumatic aneurysms).... 206 = 41.2% 2. Tumors (almost all malignant) 100 = 20.0% 3. Traumatic pulsating exophthalmos, spontaneous pul- sating exophthalmos, and aneurysms of orbit.... 91 = 18.2% 4. Spontaneous aneurysms other than of the orbit 76^15.2% 5. Trifacial neuralgia 11= 2.2% 6. Preliminary ligations for hemostasis 8= 1.6% 7. Epilepsy 3 = 0.6% 8. Miscellaneous and unclassified 5= 1.0% 500 Among the tumor cases it was stated in only one instance that ligation was done to starve the tumor. In fact, in most of these cases control of hemorrhage was the object sought. Con- sequently a truer figure to represent the hemorrhage cases would be 61.0 per cent. No attempt has been made to arrive at the conclusions as to the bearing of the general mortality in these cases on liga- tion. In the first place, particularly among the traumatic cases, the injuries for which ligation was done were so severe that they overshadowed the possible effects of the ligation itself. The high mortality attributed by certain authors to 62 SURGICAL ANEMIA AND RESUSCITATION ligation should probably be attributed in great part to shock, hemorrhage, and infection. It would be manifestly illogical to classify a death in a case of traumatic pulsating exophthal- mos, the result of fracture of the base of -the skull, as due to cerebral injury resulting from ligation alone. The same would be true of a death the result of a head wound from a rifle ball or fragment of a shell. It is equally illogical to pre- sent cases of pulsating exophthalmos as affording evidence that the eyes may be injured by ligation of the common carotid artery. The usual cause of pulsating exophthalmos is rupture of the internal carotid in the cavernous sinus, and in cases which are not treated at all vision is frequently lost on the affected side. There is evidence of but few cases of serious injury to any of the organs of the special senses, due to ligation alone. The pupil of the same side may be narrowed temporarily, although not in all cases; but in practically all, if not in all cases, this is followed by permanent dilatation. Various observers have noted temporary disturbances of the circulation of the eye, such as pallor of the papilla, a weakened circulation in the arterial branches, and a diminished fulness of the veins. After ligation of both common carotids Jacobi and Ehrmann ob- served dimming of the eyesight. As to cerebral injury, it has been found that the time of occurrence of cerebral symptoms in relation to the time of ligation varied considerably. Some authors claim that cere- bral symptoms are not manifested immediately. In this con- nection the case reported by Quenu is of interest in spite of the fact that no autopsy was held. The age of the patient is not stated. He had had an operation for epithelioma of the neck with severe hemorrhage from the carotid. Preparations were made to ligate the common carotid without the use of a general anesthetic. Just before the ligature was tightened LIGATION OF THE COMMON CAROTID ARTERIES 63 the patient replied in a normal way to a remark made to him, and, although anemic, had previously seemed to be normal mentally. To quote Ouenu's own words (translation) : *T tightened the ligature, and at the instant the patient passed into coma : the entire left side was struck by flaccid paralysis. The patient died in the evening or the next morning without having regained consciousness." Whether or not an autopsy was held for confirmation of the cause of death the whole occurrence was perfectly consistent with what well might- happen, especially with a brain in a previously anemic condi- tion through general loss of blood and with the consequent physical impairment of the brain cells. In two other instances among the cases studied paralysis was said to have occurred immediately after the ligature was tightened. The first, a case of Verneuil's, was a man 30 years of age who had received a shot wound of the cheek. Hemi- plegia and coma resulted immediately with death 42 hours later. At the autopsy the cerebral hemisphere on the side of the ligation was found to be profoundly altered. The second, a case of Hopmann's, was a man, 23 years of age, who also had received a shot wound in the cheek. Immediately after ligation partial paralysis of the entire opposite side of the body occurred. It was a pus case, and eventually the eyeball had to be enucleated. The patient recovered. The table on page 64 shows the time in which cerebral symptoms were manifested in 51 cases in which they oc- curred. Further studies showed also that in general the older the patient the earlier the cerebral symptoms occurred. In the study of these 500 cases it was found that the in- ternal jugular vein of the same side as that on which the common carotid artery was ligated was occasionally either ligated also or rendered functionless through injury. This 64 SURGICAL ANEMIA AND RESUSCITATION Number of Cases 2 I I I I I 2 I I 3 I 6 5 I I 3 2 Total 51 Time of Appearance of Cerebral Symptoms 34 days. 31 26 21 19 II 10 7 6 5 4 3 2 I day. 20 hours. 12 "immediately after". Indefinitely stated or not stated at all. In the 33 cases in which the time was stated it is found that in 24, or y2.y per cent., the symptoms were manifested in less than a week. occurred in 16 cases, or 3.2 per cent. Among the 16 cases were 4 in which cerebral complications occurred — hemiplegia in each case. Whether ligation of the internal jugular had anything to do with the causation of cerebral symptoms is impossible to state. Owing to the richness of the venous anas- tomoses of the head it seems hardly probable that it did. In any case, if there were not free anastomosis then stoppage of a large venous trunk would tend to produce hyperemia rather than anemia. LIGATION OF THE COMMON CAROTID ARTERIES 65 The Author's Cases of Temporary Simultaneous Closure of Both Common Carotid Arteries ^ Case No. Sex Age M. F. ' 'm.' ' 46 21 48 58 7 mos. Nature of Operation Fibrosarcoma of mouth Congenital tumor of neck Epithelioma of mouth Epithelioma of mouth Epithelioma of lower jaw Angiosarcoma of cheek, and neck, of rapid growth Carcinoma of nasal septum Carcinoma of tongue Ligation Clamps Clamps Clamps Clamps Clamps Clamps Clamps Clamps Cerebral Symptoms None None None None None None None None Result Recovery Recovery Recovery Recovery Recovery Recovery Recovery Recovery 1 From " Problems Relating to Surgical Operations," Crile. TECHNIQUE OF LIGATION OF THE COMMON CAROTID ARTERY AND ITS BRANCHES Formerly ligation of the common carotid artery was some- times done when the comparatively modern procedure of tem- porarily closing the vessel would have better served the inter- ests of the patient. The author has repeatedly demonstrated that, when properly done, an artery may be closed temporarily without injury for as long a time as is ever required for an operation. Consequently certain operations on the head, for example, in which hemorrhage is troublesome, can be done with much greater ease and safety by temporary closure of the common carotid. By this procedure the local field is in better condition for the careful dissection which is so often necessary, and the danger of harmful cerebral anemia is al- most completely avoided. Moreover, as a preliminary step to permanent ligation temporary closure should be done when possible. This point the author wishes to emphasize strongly. There are very few cases in which it cannot be done, and the occurrence of harmful immediate symptoms can be taken as a warning against making a permanent ligation. The following observations constitute a brief resume of the author's experimental work to determine the effect of a 66 SURGICAL AXEML\ AXD RESUSCITATIOX temporary closure of the carotid : The immediate effect on the circulation of the temporary closing of one carotid artery was to increase the blood pressure, but usually a compensation followed, and the pressure returned to its normal level. Xo effect upon the respiration was observed. The simultaneous closure of both carotid arteries produced a greater rise in the blood-pressure, which also by physiologic compensation usually soon returned to the normal level. In many of the latter experiments there was a decrease in the respiratory action, although the eft'ect was very slight. In no instances were any striking results noted. In the recovery experiments no effect upon the animal was observed beyond that attribut- able to the anesthesia and the operation in the cases in which the clamps were alloAved to remain on the arteries. The ani- mals seemed playful and strong. Even after 24 hours of com- plete closure there was but little microscopic evidence of in- jury to the vessel wall. Circulation through the clamped por- tion was readily reestablished. However, in cases in which the animal had suft'ered infective inflammation of the wound during the application of clamps for a considerable length of time, say for two days, the damage to the vessel walls was marked, and in some cases the lumen was occluded. As to the after-effects, in no case was there any clotting; the aseptic cases made good recoveries; the circulation was reestablished; and no impairment of consequence occurred. The cerebral vessels were carefully observed at autopsy, and in no case were either emboli or thrombi found, nor was there noted any gross eft'ect on the brain. In the course of clinical operations the author has tem- porarily closed the common carotid artery 136 times. The ages of the patients ranged from 7 months to 69 years. In every instance the circulation was resumed as soon as the clamps were removed. There were no appreciable late effects LIGATION OF THE COMMON CAROTID ARTERIES 67 on the vessel wall at the point of clamping, and none on the circulation in the closed arteries and their branches. Less anesthetic was necessary in those cases in which both common carotids were closed. The respiration might be embarrassed, but was relieved by partially releasing the pressure on one cr both vessels. The operation time was much diminished as a result of the freedom from blood of the field of operation, and the amount of blood lost was much lessened, as was the difficulty of keeping blood out of the respiratory tract. In the closure of the common carotid artery, a valuable clinical procedure is to transfer the clamp to the external caro- tid just as soon as the latter vessel is reached, as, for example, in a block dissection of the neck. In elderly subjects, espe- cially those with atheromatous arteries, distinct cerebral im- pairment, amounting even to mild delirium, may appear after temporary closure of the common carotid artery and last for several days, but apparently no permanent damage is done to the brain. Since the adoption of this method of closing the external carotid artery from the beginning of the operation, or transferring the clamp in the course of the operation, no functional impairment of the brain has been observed. In the author's experience closure of the common carotid artery does not arrest hemorrhage as completely as does closure of the external carotid. The reason is that when the common carotid is closed and the external is open there is a back flow of blood via the anastomoses in the circle of Willis. This explains why rather free hemorrhage may be seen when the common alone is closed. The best control of all is secured by closing both external carotids. In his own series of cases the author has observed no in- stances of embolism or thrombosis as a secondary result of the temporary closure of either common or external carotids. As a general principle it stands to reason that, other fac- 68 SURGICAL ANEMIA AND RESUSCITATION tors not interfering, the ligation of a large artery should not be done when a small branch of the same vessel can be reached, the closure of which will control the bleeding. In regard to the carotids no one has emphasized this more strongly than Wyeth. In his classical "Essays in Surgical Anatomy," pub- lished in 1878, he says: "I cannot conclude the surgical anatomy of these arteries without protesting with all the earn- estness I may possess against the operation of tying the com- mon carotid for lesions of the external carotid or its branches when this last vessel may be ligated." While a discussion of the surgical anatomy of the vascular system of the head and neck is rather outside of the province of this book it has a direct enough bearing to make the fol- lowing extracts from Wyeth pertinent : "i. In all intracranial lesions involving alone the inter- nal carotid or its branches this vessel should be tied. If this procedure is not successful then the external carotid should be secured at the crossing of the digastric. If the facial be given off below this point it should be secured by a separate ligature. . . . For lesions of the internal carotid in the neck (excepting aneurysm) it should be tied above and below the lesion in all cases. The operation on the cardiac side alone, be the common or internal trunk the seat of the ligature, is not justifiable, death having occurred in many instances through the descending current from the circle of Willis. In aneurysm of this artery the single ligature on the cardiac side will suffice. "2. When the lesion (excepting aneurysm) exists within one-half inch of the bifurcation of the common carotid, in- volving this vessel, or the external or internal, or both, the common trunk must be tied on the cardiac side, and the other two arteries on the distal side of the lesion. The superior thyroid and any other branches of the external carotid be- LIGATION OF THE COMMON CAROTID ARTERIES 69 tween the ligature upon this vessel and the bifurcation should also be secured. "In case of aneurysm in either of these points the single ligature on the cardiac side will usually suffice. "3. In erectile or pulsating tumors of the orbit (intra- orbital aneurysm) ligature of the common carotid is to be advised. . . . Since the anastomoses between the termi- nal branches of the external and internal carotids, through the orbit, are more or less exaggerated in intraorbital aneur- ysm ... I am of the opinion that the ligature of the common carotid is the surest and safest operation . "4. Wounds of the superior thyroid artery too near its origin to permit a ligature on the cardiac side of the lesion require deligation of the common, external, and internal caro- tids and torsion of the distal end of the wounded vessel. "5. In incised, punctured, lacerated, and gunshot wounds of the external carotid or its branches where it is deemed in- expedient to secure the vessel at the seat of injury the external carotid of one or both sides should be secured below the origin of the lingual ... If the lingual or any other branch is in immediate contact with the ligature it (or they) should be also secured, "The common trunk should never be tied under such cir- cumstances except as a last resort. "6. Hemorrhage of the tonsils and pharynx, if not ar- rested by ligature of the external carotids as advised, will require either the separate ligature of the pharyngeal ascendens or of the common and internal carotids. "7. It must be assumed that when the ligature of the external carotid below the origin of the lingual does not arrest hemorrhage from the pharynx the bleeding is from the ascending pharyngeal, and that this branch originates from the bifurcation of the internal carotid. . . . (The history 70 SURGICAL ANEMIA AND RESUSCITATION gives one or two deaths from hemorrhage from the tonsils after hgature of the common trunk alone.) "8. Aneurysm of the external carotid or its branches (excepting the superior thyroid) demands deligation of the external carotid alone when a sufficient space exists between the tumor and the bifurcation to admit the hgature with safety. "9. Aneurysm of the internal carotid should be treated by ligature of this vessel alone when there is sound artery enough between the tumor and the bifurcation to admit the ligature with safety. "10. Aneurysm of the common carotid (if digital com- pression shall have been abandoned) should be treated by ligature of this vessel as far from the tumor (on cardiac side) as possible. "11. Ligature of the common carotid for aneurysm of the arch of the aorta is of doubtful propriety. "12. Ligature of the common carotid alone for the cure of innominate aneurysm is an exceedingly dangerous pro- cedure; 12 of 17 cases proved fatal from the operation; only 2 were cured. . . "16. In epilepsy, while the danger of death as a result of the operation is comparatively slight (5 per cent.), the pro- portion of cures or improved cases is not great enough to commend this procedure to the profession. . . "17. In persistent and exhaustive neuralgia of the fifth nerve when all other methods have proved ineffectual liga- tion of the common carotid should be practiced. "The external carotid of one or both sides should first be tied below the lingual (the point of election). If this fails the common trunk upon the affected side may be secured. "The operation is contraindicated when pressure upon the common carotid of the affected side does not arrest the pain. LIGATION OF THE COMMON CAROTID ARTERIES 71 "18. In hemiplegia or headache the ligature of the com- mon carotid is not justifiable. , . ." Facts like the foregoing furnish an invaluable basis for the control of hemorrhage — one of the most important parts of the surgery of the head and neck. Their value in pre- venting surgical anemia as far as possible lies in the light they throw on how best to avoid unnecessary closure of arterial trunks — a secondary but important matter. In addition to what has already been presented a few words may well be said in regard to ligation of the external carotid. While the weight of evidence is overwhelmingly against the probability that ligation of the external carotid may cause harmful or, in fact, any cerebral anemia that can be manifested clmically, nevertheless it may not always be a harmless surgical procedure, as is shown by the following case of Scudder. The patient was a woman, 50 years of age, with sarcoma of the superior maxilla. The left external carotid artery was ligated just below the origin of the facial artery, the patient being in the sitting posture. Then the jaw was completely excised. On the next day a right hemiplegia developed. Death occurred six days later, the patient being partially un- conscious during that time. The left middle cerebral artery was found at the autopsy to be occluded a short distance from its point of origin by a firm, gray-red, thrombus-like mass, which was apparently prolonged into some of the branches of the artery as a blackish red, somewhat softer material. At the site of the basal ganglia on the left side there was a pale, in places grayish-red, disorganized, more or less dis- integrated soft mass of brain tissue, which extended from the posterior portion of the left frontal lobe back as far as the posterior portion of the thalamus laterally, to the left of and involving a good part of the striate body and downward 72 SURGICAL ANEMIA AND RESUSCITATION into the temporal lobe. In the left temporal lobe the con- dition extended over quite an area, and reached as far as the cortical portion. In this situation the brain tissue was pale, disintegrated, and mushy. Elsewhere the brain tissue was not remarkable. There was no evidence of arteriosclerosis of the circle of Willis, SUMMARY The histologic evidence that^ even in so-called "recovered" animals, some or even many nerve cells are permanently lost and that all are temporarily damaged explains the great tem- porary and lesser permanent loss of power following any grave anemia of the brain. It argues against the practice of permitting the blood pressure to fall extremely low in cases of hemorrhage before resorting to transfusion. It warns the surgeon to be cautious in ligating or temporarily closing the common carotid artery in aged subjects. It warns him not to press on the brain with retractors and packings unless the pressure is made strictly intermittent, never exceeding five minutes at a stretch. It explains the reason why in all types of brain pressure the early depression of the higher functions, such as associative memory, occurs before the depression of the lower functions, such as respiration and circulation. It emphasizes the signifi- cance of the gradual onset of dulness and stupor in increased intracranial pressure. It fixes an absolute limit to the possi- bility of resuscitation in cases of drowning, and therefore makes one doubt the authenticity of many reported cases of resuscitation after apparently long intervals of suspended ani- mation. CHAPTER III ANEMIA OF VOLUNTARY MUSCLES I EXPERIMENTAL OBSERVA- TIONS. ANEMIA OF THE POSTERIOR EXTREMITY OF DOGS In collaboration zvith Dr. Lawrence Pomeroy and Dr. A. M. Tweedie How long can an extremity endure total anemia and sur- vive without consequent loss of function? Even in dogs this has not been an easy matter to determine, on account of the variety of factors which enter into the problem. One thing is very evident and that is, that while a dog's thigh may have a tourniquet applied to it so as to shut off all circulation for even as long a time as ten hours, and so that twenty-four hours later there is complete loss of function with disturbance in the electrical reactions (except the reaction of degenera- tion), yet no microscopical changes of a structural nature can be detected at this time. The same dog if allowed to live will show paralysis of a permanent nature, with or with- out the subsequent development of the reaction of degenera- tion, and hence the irreparable damage is done at the end of the twenty-four hours even if nothing but edema and inter- stitial hemorrhages be present. What will eventually become irreparable loss of function is not indicated by early struc- tural changes. In a rough way it may be said that permanent paralysis usually follows anemia of a dog's thigh of seven hours' dura- 73 74 SURGICAL ANEMIA AND RESUSCITATION tion. Recovery to the extent of apparently complete restora- tion of function has occurred after a longer time, but in a useful leg even grave microscopic changes may be found when the animal is killed, so that to a certain extent appearances may be very misleading. In regard to loss of knee-jerk the findings are quite con- stant. The knee-jerk was always lost after the 6-hour or longer durations of anemia. The fact that it was always lost after 6 hours of anemia did not mean necessarily that it rnight not return and become entirely normal again. The shortest period of anemia after which it was lost was 3 hours, and in this particular case (Exp. 7) it returned after 12 days. The same may be said in regard to the foot-drop — in fact, the time of appearance of the foot-drop was almost identical with the disappearance of the knee-jerk. The muscles con- trolling the foot-drop were always the first to become affected and the last to become normal. The occurrence of sensory paralysis was the most variable of the factors accompanying muscular anemia. It was less apt to be complete than was the motor paralysis, and usually disappeared within the first few days after the experiment. The reaction of degeneration was variable. It was ob- served earliest in Experiment 26, a 7-hour experiment, but in two other 7-hour experiments it was absent. In the experi- ments of still longer duration it was not invariably present. Possibly this was due to the variation of pressure with which the tourniquet was applied. For example, one might use much more than sufficient pressure to shut off the circulation, as no pressure gauge was connected with the tourniquet employed in the experiments. The microscopic changes showed rather definite progres- sion of degeneration. In all of the following experiments, unless otherwise spe- ANEMIA OF VOLUNTARY MUSCLES 75 cifically noted in detail, anemia of an extremity was obtained by the application of an Esmarch bandage which was tight- ened until arterial pulsation ceased, the dog being under mor- phia and light ether anesthesia throughout the time of appli- cation. Protocols of Forty-three Selected Experiments EXPERIMENT i November 10, 1908. Mongrel dog; condition, good. Ether; morphia, gr. ^. Tourni- quet applied to upper third of left thigh for / hour. After the appli- cation no pulsation could be detected in the femoral artery. At the close of the experiment the dog was in good condition. November 12. The dog limped a little, but the muscular strength of the leg seemed to be normal. The knee-jerk was normal. November 18. Leg apparently normal. December i. Leg apparently normal. All reflexes normal. Reaction to gal- vanic and faradic currents normal. EXPERIMENT 2 November 15, 1908. Small mongrel dog; condition, good. Ether; morphia, gr. ^. Tourniquet applied to upper third of left thigh for 2 hours. At the close of the experiment the condition of the dog was good. November 16. Some impairment of motion of the affected leg was present, and, while the reflexes were normal, the muscular power was slightly diminished. Reaction to galvanic and faradic currents normal. November 17. There was marked improvement. November 19. The leg seemed to be normal in every way. Reflexes and electri- cal reactions normal. EXPERIMENT 3 November 23, 1908. Mongrel dog; condition, good. Ether; morphia, gr. ^. Tourni- quet applied to upper third of left thigh for 2]/^ hours. At the end of the experiment the dog was in good condition. 76 SURGICAL ANEMIA AND RESUSCITATION November 24. There was "some impairment of the muscular power and activity. The knee-jerk was present, and sensation seemed to be normal. November 25. The leg was normal in every way. EXPERIMENT 4 November 24, 1908. Mongrel dog; condition, good. Ether; morphia, gr. Yz. Tourni- quet applied to upper third of left thigh for 2Y2. hours. At the close of the experiment the condition of the dog was good. November 25. The dog limped somewhat, but the leg was not paralyzed. The reflexes were normal. The dog was observed for several days more, but no changes could be made out, the anemia apparently not being sufficient to damage the muscle fibers. EXPERIMENT 5 December i, 1908. Mongrel dog ; condition, good. Ether ; morphia, q. s. Tourniquet applied to right thigh for ^^ hours. At the end of the experiment the condition of the dog was good. December 2. There was marked impairment of function in the leg, but not complete paralysis. The flexor muscles of the foot were more affected than other groups. There was occasional foot-drop. December 3. The impairment had disappeared, and the muscular power seemed to be normal. EXPERIMENT 6 November 25, 1908. Mongrel dog; condition, good. Ether; morphia, gr. ^<. Tourni- quet applied to upper third of left thigh for 2^ hours. At the close of the experiment the dog was in good condition. November 26. There was slight paralysis of the flexors of the foot. The other muscles seemed to be normal. December 6. The leg seemed to be normal to electrical stimulation. The re- flexes were normal. The dog was killed, and sections taken. ANEMIA OF VOLUNTARY MUSCLES 77 Microscopical Examination. — As a whole the muscle cells showed reduced stainability. The cross-striations of the cells were much reduced, and entirely absent at the periphery of the bundles. Throughout the sections there was marked fragmentation. Certain areas showed regeneration actively going on, while in others there were marked hyaline changes. The walls of the blood vessels were thickened. There was no hemorrhage into the tissues. There was but a small degree of inflammatory infiltration. EXPERIMENT 7 November 18, 1908. Black and tan bitch ; condition, good. Ether ; morphia, q. s. A tourniquet was applied to the upper third of the left thigh for j hours. At the close of the experiment the bitch was in good condition. November 19. There was partial paralysis of all the muscles below the tourni- quet, and the flexors of the foot were completely paralyzed, with con- sequent complete foot-drop. The reflexes were absent. Sensation to pain seemed to be delayed, but the electrical reactions were normal. November 25. The condition of the leg was about the same. December i. There was slight improvement. At times the bitch flexed her foot, and there was more motion in the other partly paralyzed muscles. The reflexes could not be elicited. Sensation to pain was more acute, and the electrical reactions were still normal. December 15. Slow improvement had continued, with partial return of muscu- lar power. The electrical reactions continued to be normal. December 30. The leg seemed to be normal in every way, including the reflexes. January 7, 1909. The bitch was killed with chloroform, and pieces of muscle taken lor sectioning. Microscopical Examination. — On the whole the sections pre- sented a normal appearance. In certain areas the cross-striations were a little less distinct than normal, but this may have been due to the way the sections were cut. The nuclei stained perfectly every- where, and showed no signs of degeneration, and there was no round cell infiltration. The sarcolemma was slightly thicker than normal. 78 SURGICAL ANEMIA AND RESUSCITATION EXPERIMENT 8 November 27, 1908. Mongrel dog; condition, good. Ether; morphia, gr. 5^. A tourni- quet was applied to the right thigh at the junction of the upper and middle thirds for 5 hours. At the close of the experiment the dog was in good condition. November 28. There was but slight impairment of the function of the muscles below the tourniquet. The reflexes were normal. December i. The return to normal seemed to be complete in every way. - EXPERIMENT 9 November 30, 1908. Bulldog bitch ; condition, good. Ether ; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 5 hours. At the close of the operation the dog was in good condition. December i. There was almost complete paralysis of the muscles of the leg below the tourniquet with foot-drop. The knee-jerk was not lost. December 2. The condition was markedly better. December 28. The leg was in apparently normal condition. EXPERIMENT 10 October 9, 1909. Mongrel dog; condition, good. Ether; morphia, gr. 5/2. A tour- niquet was applied to the upper third of the left thigh for j hours. At the close of the experiment the dog was in good condition. October 10. There was a pronounced toe-drop, but the other muscles were not paralyzed, and the electrical reactions were normal. The leg was very sensitive to pain, and the dog howled whenever the leg was touched. The temperature and pulse rate were normal. October 14. As far as could be determined the muscles were in normal condi- tion, except that, after exertion, the dog still showed a slight toe-drop ANEMIA OF VOLUNTARY MUSCLES 79 on the affected side. The electrical reactions were normal, and there was no difference in the reactions to pain between the two legs. October 19. The muscles seemed to be normal in every way. November 12. The dog was anesthetized, and the adductor magnus muscle re- moved and a portion of the sciatic nerve. No gross changes were ap- parent in either. The histologic examinations also showed no changes. EXPERIMENT 11 November 19, 1908. Mongrel dog; condition, good. Ether; morphia, gr. ^^. A tour- niquet was applied to the upper third of the left thigh for 4 hours. At the close of the experiment the dog was in good condition. November 20. The affected leg showed complete foot-drop, and the peroneal muscles were completely paralyzed. The other muscles still retained some power, but it was much below normal. The dog used the leg, but walked on the dorsum of the foot instead of the plantar surface. The knee-jerk was absent. To the faradic current there was delayed reaction, but to the galvanic the reaction was normal. November 30. The condition of the leg was the same. December i. There seemed to be slight improvement, and the flexors of the foot showed signs of regaining their power. The reflexes could not be obtained. December 5. The improvement was marked. The foot dropped occasionally. The knee-jerk had returned. No change could be made out in the electrical reactions. January 4, 1909. There was no paralysis of the flexor muscles. The dog was killed, and pieces of tissue removed for examination. Microscopical Examination. — In the muscle cells there was a general change involving all of the cytoplasm. The cross-striations were less plain, and, to a slight degree, fragmentation had taken place. Except for a slight increase of the granules about the nucleolus the nuclei were apparently normal. There was no inflammatory infiltra- 8o SURGICAL ANEMIA AND RESUSCITATION tion. The blood vessels showed no changes. Throughout the sections there was a general increase of connective tissue. In certain areas there was cloudy swelling, which seemed to be the result of a previ- ous edema. When compared with fields of normal muscle it was found that there was an increase in the number of nuclei, showing that cell division had been progressing faster than normal. The sarcolemma was not thickened. No nerve endings were made out in the preparations. EXPERIMENT 12 October 10, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 4 hours. At the close of the experiment the dog was in good condition, no change in the respiratory rate having been noticed. October ii. Marked toe-drop was present, and the leg seemed to be numb. The reflexes were absent, but the electrical reactions were normal. The leg was dragged, and voluntary movement was apparently lost below the tourniquet. October 16. The symptoms of disturbance had practically all disappeared. The toe-drop was shown only when the dog was fatigued, and then but slightly. The electrical reactions were normal. November 12. The dog was anesthetized, and the adductor magnus muscle and part of the sciatic nerve removed. No gross or miscroscopic changes could be detected. EXPERIMENT 13 December 31, 1908. Mongrel dog ; condition, good. Ether ; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 5 hours. January i, 1909. Marked impairment of muscular power was present, but not com- plete paralysis. There was marked paralysis of the flexors of the foot, with resulting foot-drop. January 8. The paralysis was somewhat less. The foot-drop was still pres- ent, and the knee-jerk was diminished. ANEMIA OF VOLUNTARY MUSCLES 8 1 January 14. Death occurred during the night from unknown cause, the autopsy- revealing no change to which death could be attributed. Blocks of tissue were taken for examination. Microscopical Examination. — The sections showed considerable change. Under low power magnification infiltration of leukocytes between the muscle fibers could be seen. The fibers themselves were poorly stained, and the striae were almost obliterated. In many areas the fibrillse did not show at all, the entire fibers showing hyaline changes. There was a great difference in the size of the fibers, many showing an increase in the number of muscle nuclei. These nuclei were round or oval in shape, and about three times as large as nor- mal nuclei. Marked fragmentation had occurred in all parts of the sections. The sarcolemma was greatly thickened. EXPERIMENT 14 January 4, 1909. Mongrel dog; condition, good. Ether; morphia, gr. Y^. A tour- niquet was applied to the upper third of the right thigh for 5 hours. At the close of the experiment the dog was in good condition. January 5. There was partial paralysis of the muscles below the point of con- striction, and partial toe-drop. January 8. The condition was about the same. January 12. Muscular power was more nearly normal. The foot dropped less. The electrical reactions were negative. January 17. Marked improvement had occurred, but there was still some im- pairment of the muscular power of the foot. January 18. The dog was killed in the course of a resuscitation experiment. Blocks of tissue were removed for examination. Microscopical Examination. — Extensive degeneration had oc- curred. In some areas the muscle fibers could not be distinguished as such at all, on account of proliferation of the nuclei and infiltration of leukocytes. In an occasional area cross-striation could be seen imme- diately adjoining fibers completely destroyed and undergoing absorp- 82 SURGICAL ANEMIA AND RESUSCITATION tion. Fragmentation was marked, and the sarcolemma was thick- ened. EXPERIMENT 15 January 23, 1909. Mongrel dog; condition, good. Ether; morphia, gr. y^. A tour- niquet was applied to the upper third of the right thigh for 5 hours. January 24. The dog died during the night. The microscopical examination showed only normal muscle. EXPERIMENT 16 October 14, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 5 hours. At the close of the experiment the condition of the dog was good. October 15. There was complete paralysis of all the muscles below the point of constriction. Foot-drop was pronounced. On stimulating with the faradic current the muscles seemed to be more irritable than normal. The latent period was increased, but it required less stimulus to produce a maximal contraction than in the other leg. The period of contraction seemed to be shortened, but, as compared with that of the other leg, the relaxation phase was increased. Frequent con- tractions soon threw the muscles into tetanus. No reaction of degen- eration could be made out. Sensitiveness to pain seemed to be dimin- ished. October 18. The paralysis had become only partial, and, with the exception of the muscles of the foot, the dog had considerable use of the leg. The foot-drop was as marked as at the time of the last observation. Sen- sitiveness to pain seemed to be increased. The reaction to galvanic stimulation seemed to be nearly normal. The length of the latent period was still increased, but a greater stimulus was required to produce a maximal contraction than was needed before. There was still no reaction of degeneration. The reflexes were still abolished. The foot was still somewhat edematous. The general condition of the dog was good. October 24. Except for some foot-drop the paralysis had disappeared, and the dog walked with scarcely any limp. The electrical reactions showed ANEMIA OF VOLUNTARY MUSCLES 83 no degeneration, and still greater stimulation was necessary to pro- duce a maximal contraction. The reflexes had not returned, but the sensitiveness to pain seemed to be normal. October 29. The foot-drop had disappeared. A slight knee-jerk could be ob- tained. The leg was used without any difficulty. November 12. No trace of the previously altered functions could be detected. The dog could leap and play as well as ever. Under ether anesthesia the adductor magnus and part of the sciatic nerve were removed. No gross changes could be detected. Microscopical Examination. — Evidences of an old hemorrhage into the muscle tissue were found. About the upper part of the muscle some edema was present, and in this region there was slight necrosis. About the blood vessels were areas of round cell infiltra- tion. In many places the sarcolemma had separated from the muscle fiber, apparently as a result of previous edema. No definite signs of regeneration could be made out, and there did not seem to have been any marked destruction of muscle fibers. EXPERIMENT 17 December 5, 1908. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 6 hours. The dog died about 2 hours after the close of the experiment. The autopsy was negative. No. changes in the muscles were detected. EXPERIMENT 18 December 7, 1908. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 6 hours. At the close of the experiment the dog was in good condition. December 8. There was complete paralysis of all the muscles below the point of constriction. The reflexes could not be obtained, and sensitiveness to pain seemed to be abolished. To the faradic current there was a delayed reaction, but no reaction of degeneration could be made out. December 15. The conditions were about the same. The dog was accidentally killed. No sections were taken. 84 SURGICAL ANEMIA AND RESUSCITATION EXPERIMENT 19 January 5, 1909. Mongrel dog; condition, good. Ether; morphia, gr. Yz. A tour- niquet was applied to the upper third of the thigh for 6 hours. At the close of the experiment the dog was in poor condition. January 6. The dog died during the night. The autopsy revealed no gross changes to which death might have been attributed. Blocks of tissue were removed for microscopical examination. Microscopical Examination. — The sections showed the presence of edema, but there were no structural changes present. EXPERIMENT 20 January 18, 1909. Mongrel bitch; condition, good. Ether; morphia, gr. j^. A tour- niquet was applied to the upper third of the right thigh for 6 hours. At the close of the experiment the bitch was in good condition. January 19. The general condition was good. Below the site of application of the tourniquet there was almost complete paralysis. The flexors of the foot were most involved, and the foot-drop was marked. The knee-jerk was absent. January 20. Death occurred during the night. Blocks of tissue were taken for examination. Microscopical Examination. — Edema alone was present. EXPERIMENT 21 January 20, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 6 hours. The dog died before the tourniquet was removed. At the autopsy the cause of death was undetermined. Sections of the anemic muscles did not reveal any changes. EXPERIMENT 22 October 14, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 6 hours. At the close of the experiment the dog was in good condition. ANEMIA OF VOLUNTARY MUSCLES 85 October 15. There was complete paralysis of all the muscles below the point of application of the tourniquet. Foot-drop was pronounced. The reaction to the galvanic current did not seem to be much altered, although the latent period was increased and the relaxation phase somewhat prolonged. Sensitiveness to pain seemed to be much diminished. October 18. The condition seemed to be about the same. The foot-drop was complete, but the sensitiveness to pain was increased. On stimulating with the galvanic current the period of shortening was greatly pro- longed, and the period of relaxation irregular. The muscles soon be- came fatigued, and after being stimulated for several minutes would not respond at all. No reaction of degeneration could be made out. On walking the leg was dragged, and it was evident that voluntary control was completely lost. The general condition was excellent October 24. There had been marked improvement since the previous note was made. A certain amount of voluntary muscular control had re- turned. The knee-jerk was still absent, and the toe-drop was as pro- nounced as before. The period of shortening on galvanic stimulation was prolonged, but not as much as before. It took about twice as long to cause the muscle to become tetanic. There was no reaction of degeneration. October 29. Improvement had beeni steady, and the dog was found to have good control over most of the muscles. The foot-drop was present only when the dog was tired. The electrical reactions were about the same, with the exception that the periods of both relaxation and shortening had become lessened. The latent period was still pro- longed, and the reflexes decreased. There was no reaction of de- generation. November ii. All traces of paralysis had disappeared, with the exception that the knee-jerk was greatly diminished. The electrical reactions were normal. The foot-drop had disappeared. November 27. Normal responses were made to every test, the knee-jerks now being as active as in the other leg. Still no reaction of degeneration was obtained. Under ether anesthesia the dog was killed, and the 86 SURGICAL ANEMIA AND RESUSCITATION adductor magnus muscle and a portion of the sciatic nerve removed. The muscle seemed to be firmer than normal, and to contain more fibrous elements. Microscopical Examination. — There was no doubt but that an increase in the fibrous elements had occurred. In many areas evi- dence of old hemorrhages vi^as present. The sarcolemma w^as thick- ened, and, in many places, separated from the fibers. The number of nuclei was increased, and their arrangement was irregular. There were fewer areas of necrosis in this experiment than in the last of the five-hour ones. The sciatic nerve showed no changes. EXPERIMENT 23 December 12, 1908. Mongrel bitch ; condition, good. Ether ; morphia, q. s. A tour- niquet was applied to the upper third of the left thigh for 7 hours. While the bitch was apparently in good condition at the end of the experiment, she was found dead the next morning. Blocks of tissue were removed for examination. Microscopical Examination. — Marked edema, with extensive interstitial hemorrhage, was found. There did not seem to be any specific change in nuclei or cytoplasm. EXPERIMENT 24 December 15, 1908. Mongrel dog ; condition, good. Ether ; morphia, q. s. A tour- niquet was applied to the upper third of the left hind leg for 7 hours. During the latter part of the experiment the respirations became very rapid, but decreased in rate on giving more ether. At the end of the experiment the dog was apparently in good condition. December 16. There was complete paralysis of the muscles below the point of application of the tourniquet, with complete foot-drop. The dog was unable to walk at all. December 18. The electrical reactions were normal, but there was no improve- ment in the paralysis, and the knee-jerk could not be obtained. December 28. Some improvement 'had appeared; the dog could walk with marked foot-drop. The knee-jerk could not be obtained. ANEMIA OF VOLUNTARY MUSCLES 87 December 30. There was voluntary movement in all of the muscles, although less in the flexors of the foot than in the others. January 7, 1909. Improvement was marked. The knee-jerk was obtained. The dog was killed in a resuscitation experiment. Microscopical Examination. — The sections stained poorly. In most areas the cross-striations had disappeared, and, where present, they showed very faintly. In many of the fibers KoUiker's columns showed. In some of the fibers hyaline degeneration was complete. In many places active regeneration was shown by the great increase in the number of nuclei. EXPERIMENT 25 December 16, 1908. Mongrel dog; condition, good. Ether; morphia, gr. 3^. A tour- niquet was applied to the upper third of the right thigh for 7 hours. At the close of the experiment the dog was in poor condition, and died during the night. Microscopical Examination. — Very few changes were found. The cross-striation was not prominent, but could be seen in most places. The muscle fiber and sarcolemma nuclei were well stained. No evidence of degenerative processes was found. EXPERIMENT 26 October 18, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 7 hours. During the last hour of the experiment the respirations rose to 70 per minute, and were not afifected by increasing the amount of ether. Tliis rapid rate was maintained for three hours after the experiment, or four hours in all. Otherwise the condition of the dog at the end of the experiment was good. October 19. All of the muscles below the site of application of the tourniquet were paralyzed. The knee-jerk was abolished, and there was com- plete insensitiveness to pain. Under electrical stimulation the muscles contracted, but the latent period was greatly prolonged. In the afifected 'leg the period of shortening was also much longer than in the other leg. There was not the great variation in the period of relaxation that there was in the period of shortening; the muscles 88 SURGICAL ANEMIA AND RESUSCITATION were soon in tetany, so that little could be determined. There was no reaction of degeneration, and the manipulations did not seem to cause pain. October 24. On this date there was some improvement. "While motor paraly- sis seemed to be complete, sensitiveness to pain was present. The entire foot was very edematous, and was dragged on walking. There was still no knee-jerk. The electrical reactions were the same. There was no reaction of degeneration. October 2y. There was some control of the leg, but the foot-drop was still absent. Stimulation with the galvanic current showed that the period of relaxation had decreased since the 24th, but that it was still pro- longed, and that there was the same disturbance of the phases of shortening and relaxation. Three minutes of repeated stimulation threw the muscles into tetany, from which they did not recover for several minutes. November 5. While the foot-drop was still marked the general condition of the leg had improved. The periods of shortening and relaxation were the same in both legs, but the latent period was much increased in the affected leg, even more so than at any previous time. The knee- jerk was still absent. Sensitiveness to pain seemed to be about nor- mal. The reaction of degeneration was shown for the first time, 18 days after constricting the leg. November 9. There was no apparent improvement in the involved muscles, and motor control seemed to be completely lost. The knee-jerk was ab- sent. The reaction of degeneration was still more marked. Edema was still present. Sensitiveness to pain was still present, although there was no evidence of any suffering from pain when the dog was not being tested. November 15. The condition of the muscles was unchanged as far as the reac- tions were concerned. If anything the edema was worse than before. The knee-jerk was still absent. November 17. The dog seemed to be suffering from pain. The edema was less. The other conditions were the same. ANEMIA OF VOLUNTARY MUSCLES 89 November 25. The edema had about disappeared, and there seemed to be other slight improvement. November 30. Considerable use of the leg had returned. On pricking it with a pin the leg was drawn away. The greatest improvement was in the electrical reactions, there being no disturbance of the periods of shortening or relaxation, although the length of the latter was still increased over the normal. December 8. The foot-drop was but slightly improved, but the control of the other groups of muscles was good. The knee-jerk was still absent, and the reaction of degeneration still persisted. The other electrical reactions were about normal. The dog whined a great deal, as if he were in pain, but this may have been due to a running sore (of trophic origin?) on the dorsum of the foot. December 14. Voluntary control was diminished again. The other conditions were as before, except that the muscles were more easily thrown into tetany. December 27. In general the condition was stationary, except that voluntary control was lessened still further. The reaction of degeneration was present, and the knee-jerks absent. February 24. At this date, more than 2 months after the constriction, the paralysis of the muscles below the point of application of the tourni- quet was complete. The reaction of degeneration was present, and the knee-jerk had not returned. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. The muscle was paler, firmer, and smaller than normal. The nerve was congested, but otherwise seemed to be normal. Microscopical Examination. — A great increase in the amount of fibrous tissue had occurred, with fragmentation of the individual fibers. For the most part the cross-striations were absent. In many areas pigmentation had occurred, and about these areas there was marked necrosis. Scattered through the sections were areas of round- cell infiltration and hemorrhage into the tissues. In certain areas the normal muscle fibers seemed to have been entirely replaced by con- nective tissue. The sarcolemma was everywhere thickened, and it was often separated from the fibrils, apparently by the previously oc- 90 SURGICAL ANEMIA AND RESUSCITATION curring edema. Everywhere there was a great increase of the mul- tinucleated cells, and these were arranged irregularly in reference to the long axes of the muscle fibers. To a large extent the condition was that of progressive muscular atrophy, which had undoubtedly passed beyond the stage where entire repair could have taken place. EXPERIMENT 27 December 26, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 7 hours. At the close of the experiment the dog was in good condition. - December 27. Partial paralysis. of all of the muscles below the point of applica- tion of the tourniquet was present. Foot-drop was present, and the knee-jerk was absent. The electrical reactions showed prolongation of the latent period, but otherwise they were normal. The general condition was good. December 29. The condition of the affected muscles was markedly better. The knee-jerk and foot-drop were as before, but considerable voluntary control was present. The latent period had become about normal. January 8, 1910. Slight foot-drop was still present. The knee-jerk had returned. January 15. The foot-drop had disappeared. The leg seemed to be normal in every way. Under ether anesthesia the adductor magnus muscle and a portion of the sciatic nerve were removed for examination. Microscopical Examination. — But few changes could be made out. The cross-striation was less apparent. The muscle nuclei had increased in number. In some areas there was slight fragmentation and pigment deposition. The sarcolemma was separated from the fibrillse, and thickened. The nerve seemed to be normal. EXPERIMENT 28 January 14, 1910. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 7 hours. At the close of the experiment the dog was in good condition. ANEMIA OF VOLUNTARY MUSCLES 91 January 15. Complete paralysis was present, with marked foot-drop and loss of the knee-jerk. The latent period was prolonged, and the phases of shortening and relaxation were very irregular. The leg was very edematous. The sensitiveness to pain was greatly diminished and delayed. There was no reaction of degeneration. January 26. Marked improvement had occurred since the last observation, eleven days previously. The edema had all disappeared. The knee- jerk was present, but diminished. The electrical reactions showed improvement, the latent period being the same for both legs. The muscles could still readily be thrown into tetany by repeated shocks, it not being impossible to do this with the sound leg. There was no reaction of degeneration present. The voluntary control was good. January 30. There was still slight foot-drop, but the improvement was even greater. The electrical reactions were normal, and the knee-jerk active. The edema had returned during the previous two days. The voluntary control was good. February 16. The foot-drop had disappeared, and the leg seemed to be normal. March 4. The leg seemed to be perfectly normal in every way. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. Microscopical Examination. — The muscle fibers stained well, but the number of cross-striations was reduced. In some areas the latter were faint, in others absent, and in still others present and normal in appearance. The nuclei were increased, both in size and in number, being distributed in varied relations to the long axes of the fibers. In certain areas there was hemorrhage into the tissues and round-cell infiltration. There had been a certain amount of regenera- tion of the muscular elements, but the increase of the connective tissue elements was not marked. In some areas the sarcolemma was thickened, and separated from the fibrillae by the previously present edema. In fact, a certain amount of edema had persisted, but it was confined to an area near the point of application of the tourniquet. The nerve was edematous in places, and, on cross section, the indi- vidual fibers were somewhat shrunken. 92 SURGICAL ANEMIA AND RESUSCITATION EXPERIMENT 29 January 7, 1909. Black and tan bitch ; condition, good. Ether, morphia, q. s. A tourniquet was applied to the upper part of the right thigh for 7^ hours. At the end of this time death occurred. Autopsy. — Microscopical examination of sections showed only normal muscle as far as structural changes were concerned. EXPERIMENT 30 January 6, 1909. Mongrel dog; condition, good. Ether; morphia, gr. y^. A tour- niquet was applied to the upper third of the right thigh for 8 hours. The dog died during the night, probably from the effects of the long anesthesia, as the autopsy revealed no explanation. Sections were made from the muscles, but no structural changes were made out. Evidently the blood had not circulated through the leg again after removing the tourniquet, as the tissues were pale and the blood vessels empty. EXPERIMENT 31 October 24, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 8 hours. At no time was there any variation in the respiratory rate, and the dog was in good condition at the end of the experiment. October 25. The muscles were completely paralyzed. The knee-jerk was lost, and the entire leg seemed to be numb. Marked edema was present. As regards the electrical reactions the latent period was prolonged, and the shortening phase was both prolonged and incomplete. The relaxation phase was also much prolonged, and the muscles were easily thrown into tetany. No reaction of degeneration could be detected. The general condition was good. October 27. The general condition of the muscles was the same, but the edema had increased. Apparently there was no pain. November 5. Some improvement had occurred, as there was partial voluntary control of most of the muscles, the foot-drop still being complete. The knee-jerk was absent, and the edema still present. There was no reaction of degeneration. The latent period was still prolonged, but the periods of shortening and relaxation were nearly normal. ANEMIA OF VOLUNTARY MUSCLES 93 November 9. . Steady improvement had occurred.. November 15. The knee-jerk was present for the first time. The foot-drop was present for the first time, but only when the dog was made tired by walking or running. The edema had practically disappeared. November 25. So far as could be determined the leg was normal in every way. December 25. The condition was still normal, the use of the leg being perfect. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. While the tissues were vascular the muscle was much smaller than the corresponding one in the , sound leg. No gross changes could be made out in the nerve, and there were no adhesions. Microscopical Examination. — Many areas were present in the muscle, which took the stain faintly, and in these the cross-striations had disappeared ; there was much fragmentation, and the connective tissue was much increased. The sarcolemma was thickened and sep- arated in many places by the generalized edema which had previously occurred. Everywhere there was a great increase in the number of nuclei, and they were often arranged irregularly and at an angle with the long axes of the fibers. The new nuclei were irregular and often vacuolated. In some places the muscle fibers were granular, and in others round-cell infiltration and interstitial hemorrhages had occurred. Everywhere evidences of cell proliferation and regenera- tion were present. The nerve fibers showed less marked changes, although in cross section they seemed shrunken, and the connective tissue seemed to be increased in the nerve sheaths. As a whole the changes produced in this experiment were much milder than those caused in Experiment 28, a seven-hour experiment. EXPERIMENT 32 February 14, 19 10. Mongrel bitch ; condition, good. Ether ; morphia, q. s. A tour- niquet was applied to the upper third of the left thigh for 8 hours. Before the close of the experiment the dorsalis pedis artery was opened in the foot, and it was proved by the absence of circulation that the blood was shut off from the entire leg. On removing the tourniquet the blood began slowly to flow. The artery was then 94 SURGICAL ANEMIA AND RESUSCITATION ligated, and the experiment terminated. The bitch was in good con- dition. February 15. Complete paralysis was present with foot-drop and loss of knee- jerk. The latent period was prolonged, and the phases of shortening and relaxation were irregular. There was no reaction of degenera- tion. Edema was very marked, and the leg seemed to be numb. Very few electrical impulses sufificed to throw the leg into tetany. The strength of current that would produce a maximal contraction in the sound leg failed to produce any contraction whatsoever of the affected leg. In the latter the reaction to the faradic was better than to the galvanic current. February 18. Very slight improvement had occurred, the condition being prac- tically the same as before. February 23. The general condition was the same. For the first time the reaction of degeneration was obtained. The latent period was shorter, and the periods of shortening and relaxation were more normal. Edema was still very marked. The knee-jerk had not returned. February 27. Except that the reaction of degeneration was more marked the condition was about the same. March 14. The reaction of degeneration was still more marked. Voluntary control was about the same, but sensation seemed to be returning. A strength of current sufficient to cause a maximal contraction in the sound leg caused the same in the affected leg. The edema was less. March ^y. There had been some improvement in the voluntary control, but the foot-drop was as marked as ever. The reaction of degeneration was still present, the other reactions now being normal. April 7. The improvement, if any, had been slight, and the voluntary con- trol was poor. The reaction of degeneration had persisted, as well as the foot-drop, and absence of knee-jerk ANEMIA OF VOLUNTARY MUSCLES 95 May 14. At this date, three months after the application of the tourni- quet, there was still but little change in the muscles of the affected leg. The reaction of degeneration had been present since its first appearance. The practically complete loss of voluntary control was the same, the foot-drop still being present and the knee-jerk absent. The amount of edema had varied from time to time, and the tem- porarily lost sensibility had returned, at least in part. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. The gross appearance of the muscle was strikingly altered, as it was only about one-third of the size of the normal adductor magnus muscle of the sound leg. It was also much darker in color than normal, from marked interstitial hemorrhage, and was more fibrous. The nerve was injected and thickened. Microscopical Examination. — The muscle was profoundly changed. The cross-striations could not be made out at all, and, in fact, in many areas it was impossible to recognize any muscle tissue; what had been muscle tissue had become a broken-down mass. Ex- tensive hemorrhages were everywhere, as was also edema. The tis- sues, as a whole, stained faintly. Many irregular, indefinitely ar- ranged nuclei were present. The sarcolemma was everywhere thick- ened, and separated by the still-present edema. Round-cell infiltra- tion was marked, and generally present. The condition seemed to be one of atrophy rather than of attempted regeneration. The sciatic nerve showed marked thickening of the neurilemma, with some hemorrhage into the sheath. Inside of the sheath many vacant spaces were present, which seemed to indicate absorption of por- tions of the fibers. EXPERIMENT 33 January 2.2, 1909. Mongrel bitch; condition, good. Ether; morphia, gr. Y^. A tour- niquet was applied to the upper third of the left thigh for 5^ hours. The bitch died during the night, probably from the effects of the long anesthesia. The autopsy was negative. Microscopically no structural changes were found. EXPERIMENT 34 January 22, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 8^ hours. The dog died during the night, probably from the effects of the ether, 96 SURGICAL ANEMIA AND RESUSCITATION as the autopsy revealed no explanation. The sections showed no structural changes, only anemia. EXPERIMENT 35 January 9, 1909. Mongrel dog; condition, good. Ether; morphia, gr. Yz. A tour- niquet was applied to the upper third of the right thigh for p hours. At the end of that time the dog was in good condition. January id. The muscles below the point of application of the tourniquet were completely paralyzed. The knee jerk was absent, foot-drop was pres- ent in marked degree, and the sensitiveness to pain was delayed as well as diminished. The electrical reactions were normal, although there was less response to the faradic current on the paralyzed than on the normal side. January ii. The dog died during the night from undetermined cause. The sections failed to reveal any structural microscopic changes beyond edema and interstitial hemorrhages. EXPERIMENT 36 November 5, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for p hours. During the last part of the experiment the respiratory rate rose to 60 per minute, but at the end the dog was in good condition. That there was no circulation in the leg was proved by opening the dorsalis pedis artery. November 6. Complete paralysis and universal edema were present. Foot- drop was complete, the knee-jerk was lost, and sensitiveness to pain was greatly diminished, if not entirely absent. The response to a galvanic current was very slow, and was still slower to a faradic current. A much greater impulse was required to produce a maximal contraction in the affected than in the sound leg. The latent period of contraction was much prolonged, the phase of shortening was both prolonged and incomplete, and the phase of relaxation pro- longed and irregular. Tetany was quickly caused by a few rapidly repeated impulses. No reaction of degeneration was present. ANEMIA OF VOLUNTARY MUSCLES 97 November 9. Except that sensitiveness to pain had returned the condition was practically the same as it was three days previous. November 15. There had been some improvement. While the foot-drop was as marked as before there was some power in the other voluntary muscles. The knee-jerk was absent, and the edema less. The reac- tion of degeneration was present. November 17. The reaction of degeneration was more marked. The knee-jerk was absent. Sensitiveness to pain was increased. The voluntary control was better. November 26. As a whole the condition had been about stationary. The reac- tion of degeneration was very marked, but the other electrical reac- tions were nearly normal. The knee-jerk had not returned. December 5. There had been no appreciable change, except, perhaps, less vol- untary control than before. Sensitiveness to pain was about normal. January 14, 19 10. The condition was about the same, being clearly one of pro- gressive muscular atrophy. The leg was paralyzed. The knee-jerk was absent, and the reaction of degeneration marked. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. The muscular tissue seemed to be very fibrous and harder than normal. The nerve showed no gross changes. Microscopical Examination. — The fibrous tissue was greatly increased in all parts of the sections. Fragmentation of the muscle fibers was marked, the cross-striations, to a large extent, being absent, and, when present, being very indistinct. The sarcolemma was thick- ened and separated from the fibrillse in many places by edema. In various areas hemorrhage into the tissues had occurred, particularly along the course of the blood vessels themselves. The blood vessels were much altered. The nerve trunk showed marked breaking-up of the bundles and shrinkage of the fibers. Vacuolated areas were numerous. EXPERIMENT 37 April 24, 1910. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for p hours. 98 SURGICAL ANEMIA AND RESUSCITATION At the close of the experiment the dorsalis pedis artery was exposed and opened. A slight continuous flow of blood resulted, which showed that the circulation had not been entirely shut off. At this time the dog was in good condition. April 25. All of the muscles of the affected leg were completely paralyzed, with foot-drop and loss of knee-jerk. The leg was very edematous and very numb. The electrical reactions showed marked prolonga- tion of the latent period, and delayed and irregular phases of shorten- ing and relaxation. There was no reaction of degeneration. April 29. The extensor muscles were completely paralyzed, but the volun- tary control of the others was present to a certain extent. Consider- able tenderness was present, as the dog snapped at anybody who tried to touch him. The knee-jerk was absent. It was impossible to determine the electrical reactions, on account of the pain that the attempt caused. May 12. Paralysis was almost entirely absent, the foot-drop showing only after the dog was fatigued by running around the room. The knee- jerk was still absent, no reaction of degeneration could be obtained. The latent period was the same in both legs. Much of the edema had disappeared. May 17. The leg was normal in every way. May 26. The leg was still completely normal as far as function was con- cerned. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. The muscle was somewhat smaller than normal, and firmer. Microscopical Examination. — The muscle bundles stained rath- er faintly with less prominence of the cross-striations than normal. In one small area there was marked fragmentation, while interstitial hemorrhages were numerous. In some places there was round-cell infiltration. The blood vessels had much thickened walls. About some of them amyloid changes had taken place. No areas suggesting infarction were found. On the whole the changes were irregularly distributed, in marked contrast to those found in some of the pre- ceding experiments. This was probably because the circulation had ANEMIA OF VOLUNTARY MUSCLES 99 not been entirely cut off. On account of the microscopic changes it was difficult to account for the rapid return of voluntary control of the leg. EXPERIMENT 38 April 2, 1909. Mongrel dog; condition, good. Ether; morphia, gr. y^. A tour- niquet was applied to the upper third of the right hind leg for IQ hours. At the close of the experiment the condition of the dog was good. April 3. The muscles below the point of application of the tourniquet were completely paralyzed. Sensitiveness to pain was both diminished and delayed. The reflexes were abolished. Reaction to the faradic cur- rent was somewhat sluggish, but was normal to the galvanic current. April 8. Slight improvement of function had occurred. Sensation was more acute. The response to the faradic current was more active. April 16. There had been slight continued improvement, the flexor muscles of the paw showing the least. Sensation was acute. May 7. The condition was apparently unchanged. May 16. Little or no improvement had occurred during the previous nine days. While voluntary movement was present in all of the involved muscles it was much less than in the normal leg. The electrical re- actions were normal. The knee-jerk was present but diminished. Under ether anesthesia the dog was killed, and the adductor magnus muscle and part of the sciatic nerve were removed. Microscopical Examination. — Everywhere through the sec- tions there was marked atrophy of the muscle fibers, with evidence of formation of new muscle cells. In the old fibers the cross-stria- tions were very indistinct, while in the new they were very distinct. In certain areas numerous, large, irregularly shaped, more or less vesiculated and granular nuclei were present. General fragmenta- tion was absent, such as there was being confined to a few small areas. The muscle cell proliferation seemed to have been most active around the larger blood vessels. The sarcolemma was everywhere much thickened. In some areas extensive hemorrhage and pigmen- tation had occurred. lOO SURGICAL ANEMIA AND RESUSCITATION ESPERIMENT 39 November 5, 1909. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was appHed to the upper third of the left thigh for 10 hours. During the latter part of the experiment the respiratory rate was greatly increased up to 76 per minute, and remained at this rate for three hours afterward. Otherwise the condition was good. Just be- fore the tourniquet was removed, opening the dorsalis pedis artery showed that the cessation of circulation had been complete. Ten minutes after removing the tourniquet the circulation seemed to be as vigorous as ever. November 6. All of the muscles below the point of application of the tourni- quet were completely paralyzed. The leg was edematous, with marked swelling, and numb. The latent period of contraction was greatly prolonged, while the periods of shortening and relaxation were irreg- ular. Fatigue soon followed the stimulation. November 7. The dog was found dead this morning, having been dead for several hours. The autopsy showed the presence of pneumonia. The muscles were very edematous, and there had been interstitial hemor- rhages. The sciatic nerve was also edematous, and hemorrhages had occurred along its course. EXPERIMENT 40 April 24, 1910. Mongrel dog; condition, good. Ether; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 10 hours. At the close of the experiment opening the dorsalis pedis artery showed that there was no circulation present. Toward the latter part of the time the respiratory rate rose from 33 to 95 per minute. The respiration was very labored, and neither rate nor character seemed to be dependent on the depth of anesthesia. This condition persisted for about four hours after the experiment. April 25. As usual there was complete paralysis, with marked foot-drop and loss of knee-jerk. The leg was very edematous, and sensitiveness to pain seemed to have been completely lost. The electrical reactions showed a marked increase in the latent period of contraction, as well as irregular and delayed phases of shortening and relaxation. No ANEMIA OF VOLUNTARY MUSCLES loi reaction of degeneration was present. The muscles were soon fa- tigued and then thrown into tetany by continued stimulation. April 28. The conditions were the same except for an increase in the amount of edema. May 2. There had been a slight return of voluntary control. The edema was less. The foot-drop was still complete, and the knee-jerk absent. There was no reaction of degeneration. A much greater stimulus was required to produce the minimal contraction on the affected side than the maximal contraction on the sound side. No reaction of degeneration was present. May 8. The reaction of degeneration was present. May 14. The condition seemed to be stationary in regard to voluntary muscular control. The reaction of degeneration was much more marked. The edema had almost disappeared., and sensitiveness to pain was very acute. May 27. The reaction of degeneration was still more marked. The knee- jerk had not returned. June 15. The leg had become much smaller in size. On making a urinary examination glucose was found to be present, but how long it had been present was not known, as this was the first time that the test had been made. June 16. By the polariscope 0.4 per cent, of sugar was present in the urine. June 18. Condition the same locally, with the dog in very poor general condition. June 24. The dog died during the night. The autopsy failed to show any suggestive lesions. The glycosuria had been present continually since it was first detected, the percentage of sugar varying much from day to day. The last examination of the muscles was made on the 2ist inst., and there was then no apparent change. The reaction of I02 SURGICAL ANEMIA AND RESUSCITATION degeneration was very marked, the knee-jerk had not returned, the size was reduced two-thirds, there had been extensive interstitial hemorrhage, and the muscles were hard. The sciatic nerve was hemorrhagically injected. Microscopical Examination. — Many profound changes had oc- curred, and in places it was difficult to tell that the tissue had ever been muscle. The cross-striations were often completely obliterated, and were nowhere distinct. Fragmentation was almost universally present. The nuclei were greatly increased in size and number, and bore no definite relation to the axes of the fibers. The sarcolemma was greatly thickened and very edematous. Round-cell infiltration was everywhere present. The hemorrhages in evidence macroscopi- cally were still more so microscopically. The nerve showed fibrous degeneration. The neurilemma was much thickened and edematous. On cross-section the individual fibers were seen to be atrophied, and often entirely absent, as shown by the vacant space which they had previously occupied. EXPERIMENT 41 April 27, 1910. Mongrel dog; condition, good. Ether, morphia, q. s. A tourni- quet was applied to the upper third of the right thigh for 10 hours. Absence of circulation was proved by opening the dorsalis pedis artery. At the close of the experiment the condition of the dog was good. April 28. The dog died during the night from aspiration pneumonia. In the gross the muscles showed edema without interstitial hemorrhage, but the microscopical examination showed no structural changes. EXPERIMENT 42 April 25, 1910. Mongrel dog ; condition, good. Ether ; morphia, q. s. A tourni- quet was applied to the upper third of the left thigh for 10 hours. Absence of circulation was proved by opening the dorsalis pedis artery. At the close of the experiment the dog was in good condition. April 26. Complete paralysis was present, with foot-drop and loss of knee- jerk. The leg was very edematous and numb. The latent period of contraction was increased, and the phases of shortening and relaxa- tion were irregular. The muscles were easily fatigued, and soon passed into tetany. No reaction of degeneration could be made out. ANEMIA OF VOLUNTARY MUSCLES 103 April 28. Sensitiveness to pain had returned. May 2. Some improvement had occurred. The dog could walk without much trouble. The foot-drop was still present and the knee-jerk absent. There was no reaction of degeneration. May 25. As far as could be determined no trace of the effects of the anemia was left. The electrical reactions were normal. May 27. Condition the same. Under ether anesthesia the adductor magnus muscle and part of the sciatic nerve were removed. The gross examination failed to show any changes. Microscopical Examination. — There was considerable intersti- tial hemorrhage and round-cell infiltration. In places the cross- striations did not show plainly, while in others they were distinct. Variable degrees of fragmentation were present. There was a great increase in the number of nuclei, and thei.- position was without rela- tion to the long axes of the fibers. The blood vessels were greatly thickened, and some of them were almost occluded. No infarcts were found. The sciatic nerve had a thickened neurilemma. The indi- vidual fibers were less distinct than normal. As a whole the condi- tion was that of recovery from a degree of anemia which had not been severe enough to cause permanent changes. Why this should be so, when such marked, changes followed lesser intervals of anemia, is difficult to explain. EXPERIMENT 43 April 25, 1909. Mongrel dog; condition, good. Ether; morphia, gr. y^. A tour- niquet was applied to the upper third of the right thigh for 16 hours. At the end of this time the dog was in good condition. April 26. All of the muscles below the point of application of the tourni- quet were paralyzed. The reflexes could not be obtained, sensitive- ness to pain was delayed, if not entirely absent, and the reaction to the faradic current was less than in the normal leg. The reaction to the galvanic current was nominal. April 27. The condition was about the same in the leg. The general con- dition was excellent. I04 SURGICAL ANEMIA AND RESUSCITATION May 3. There was slight improvement. The response to the faradic current was greater, as well as sensitiveness to pain. May 5. Slight voluntary muscular movement was present. The knee- jerk could not be elicited. May 8. Voluntary control had continued to return, the flexors of the paw showing the least improvement. May 15. The knee-jerk had partially returned. The electrical reactions were normal. On walking the dog dragged the limb. May 25. Since the last note there had not been much improvement in the paralysis, the condition seeming to be at a standstill. June i. Very slight improvement had occurred. June id. There was still marked paralysis present. The knee jerk was present, but it was very sluggish. The electrical reactions were nor- mal. The dog was chloroformed, and the adductor magnus muscle and part of the sciatic nerve removed. Microscopical Examination. — The muscles were generally atrophied with almost complete loss of the cross-striation. Frag- mentation was extreme, and the fibrillse were all but destroyed. Throughout the section there were many cells containing large granu- lar nuclei. The latter were indefinitely arranged. In many places the infiltration of leukocytes had been very great, and in some areas there was pigmentation, resulting from interstitial hemorrhages. In other areas numerous infarcts were found, with necrosis surrounding them. There did not seem to be the proliferation of the fixed cells that would be expected. The sarcolemma was everywhere thickened, and, in some areas, so much so that the muscle fibers were practically obliterated. As a whole the sections seemed to show that regenera- tion had not had time to start, and that general atrophy alone had taken place. "3 i-1 Recovery Recovery Recovery Recovery Recovery , . Recovery Recovery Recovery Recovery Recovery Recovery Recovery Death after 2 weeks from un- known cause Nearly well after 2 weeks, then killed Died during night — no micro- scopic changes Recovery Died during night — no micro- scopic changes Condition same after 8 days, dog killed Died during night; edema alone present Death on 2nd day. Edema only change Death before tourniquet was removed. No microscopic changes Recovery of function Died during night— no micro- scopic changes Almost complete recovery, 22 days, dog then killed Died during night — no micro- scopic changes "3 t-i a Ph o a 5 000000. SPooooS ^ ^ ^ ^ ^ ^ K ^ ^ Iz; ^ ^ 55 tn 13 o 11 0000000000000 O o o 1 1 a 0 >0 lO lO^O MO MO O MO MOt^ t~ t^ 1 H M r<0 Tj- lO^O t^OO O O M M O aj S -■ 2-^ r-j 1-1 o .^ fci ^ 5ct; «^\^ §-^ tn 1-1 en w c ►H rt -5- 3^ o >^ °° ^2 ° ■^^ .2 c-a _ _ _ _ rt o ri >\ &■ tn ,tj *^ ._H y (J tn ra ._- G, > tn >-. r5 CI.43 S1^ :2;.2 _^ . tn ft S « Ri >: -?, t^ O o P bj:i (J S > O ^- c3 " cd u a fv^ Pil P Q p^ ■^ bi "5 S fli tn ti3 c ' 3 ID =n CD PmQ q ? a o H >H PL|>H U >H Z Iz; ^ ^ emia : fou tion Dn). C "" rt -^ d -^a St5 fe ui « l- ^ c c 3 OJ 6 -^ 1- OJ be ;? -s ^ . a^ 3 ■-a g 2 > J^ ■'-' • 'C PIH m ° o .sec .° ^ Ji ■« "o .c > - c „ ■— 1) .s ^ (U P Vh ^ hours after the injection. l88 SURGICAL ANEMIA AND RESUSCITATION Group IV Injection Intraperit one ally of Intestinal Juice from a Dead Dog EXPERIMENT 25 November 19, 1909. Mongrel dog; weight, 7.2 kilos; condition, good. At 9:00 a.m. the temperature was 38.5° C, the pulse 114, and the respiration 24. Ten c. c. of intestinal extract, made from the small intestine of a dog that had been dead for 6^ hours, was injected intra- peritoneally. At 4:00 p.m. the dog was very sick and cold. No knee-jerks or reflexes from a lighted match held near the eyes could be obtained. The muscles were rigid. Temperature, 39.5° C. ; pulse, 84; respiration, 22. At 10:59 the temperature was 38.4° C. ; the pulse, 84; and the respiration, 18. There were still absolutely no reflexes to be obtained, and the condition of collapse was profound. Death oc- curred at 7:30 A.M., 22^ hours after the injection. The autopsy showed peritonitis to be present. EXPERIMENT 26 November 18, 1909. Mongrel dog; condition, good. Temperature, 37.2° C. ; pulse, 84; respiration, 32. At this time 10 c. c. of intestinal extract from the intestines of dogs dead for 16 hours were injected intraperitoneally. The dog became weak and sick, and soon began to suffer from diar- rhea. At 12:15 p. M. the temperature was 34.4° C, the pulse 96, and the respiration 24. Neither knee-jerks nor eye reflexes could be obtained. At 3 :oo p. m. the dog was having convulsions, his tempera- ture was still subnormal, and he felt cold to the touch. Reflexes were still absent. At 3:45 the dog was, dying. He seemed to be suffering from great pain, for which morphia, q. s., was given. Death occurred shortly after this observation, 8 hours after the injection. Autopsy. — There was much free fluid in the abdomen, but no peritonitis. The intestines were not dark in color, as they were in the dogs receiving intestinal extract from gangrenous intestine. ANEMIA OF THE SMALL INTESTINE 189 Group V Injection of Sterilized Intestinal Extract ( i) Intravenously and (2) Intraperitoneally EXPERIMENT 27 December 22, 1910. Mongrel dog; condition, good. Intestinal extract was heated for one hour to 56° C. on two successive days. On injecting 5.c. c. into the external jugular vein the respiration immediately increased from 20 to 60, and the pulse got very weak and rapid. In 5 minutes the respiration fell to 30, but the pulse continued weak and rapid, rate of 160. The next day the dog was not sick at all, and a com- plete recovery was made. EXPERIMENT 28 January 7, 191 1. Mongrel dog ; weight, 9 kilos ; condition, good. Five c. c. of the sterilized toxin used in the last experiment were injected into the external jugular vein at 9:00 a. m. At 7:00 p. m. the pulse was too rapid to count, the temperature was 39.2° C, and the respiration 56. The dog was sick, refused food, drank water, had incoordinated movements, and had bloody diarrhea. January 8. General condition, good. Temperature, 38.0° C. ; pulse, 60; respi- ration, 20. After this recovery soon followed and was complete. EXPERIMENT 29 January 7, 191 1. Mongrel bitch ; weight, 8 kilos ; condition, good. Five c. c. of the same sterilized extract that was used in the other two experi- ments in this group were given intraperitoneally. The effect was very slight, if present at all at any time, and the bitch made an unin- terrupted recovery. 190 SURGICAL ANEMIA AND RESUSCITATION Injection into Dogs of Intestinal Extract from Gangrenous Intestine of Dogs, or of Extract from Intestine of Dead Dogs Experiment Number Weight of Dog Amount of Ex- tract Injected Where Injected Results Group I: 13 14 Group II: IS 16 17 18 Group III: 22 23 24 Group IV: 2 25 26 Group V; 3 27 28 29 4.9 kilos 4.2 kilos ii.o kilos g.o kilos 14.0 kilos 7 . o kilos 7 . 5 kilos 6 . o kilos 10. o kilos g.S kilos 15.3 kilos II .0 kilos 8.5 kilos 12.5 kilos 7.2 kilos 10 c. c. 10 c. c. 10 c. c. 8 c. c. 10 c. c. 20 c. c. 10 c. c. 20 c. c. 10 c. c. 10 c. c. 10 c. c. 10 c. c. 10 c. c. 17 c. c. 60 c. c. in divided doses 20 c. c. at one time 30 c. c. 10 c. c. 300 c. c. at one time 20 c. c. 10 c. c. 5 c .c. 10 c. c. 10 c. c. 9.0 kilos 8 . o kilos 10 c. c. 10 c. c. 5 c. c. 5 c. c. Peritoneal Peritoneal Peritoneal Peritoneal Peritoneal Peritoneal Peritoneal Peritoneal Peritoneal cavity cavity cavity cavity cavity cavity cavity cavity cavity Peritoneal cavity Peritoneal cavity Peritoneal cavity Peritoneal cavity Peritoneal cavity Jejunum Duodenum Jejunum Jejunum Jejunum Duodenum Duodenum External jugular vein External jugular vein External jugular vein Intraperitoneally Intraperitoneally Ext. jugular vein Ext. jugular vein Intraperitoneally Death after 6 hours Death after 83^ hours Death after 12 hours Death after 16}^ hours Recovery Recovery Death after 15 hours Recovery Death after about 18 H hours Recovery Death after about 14 hours Recovery Death after 21 hours Death after about 15 hours Recovery, but dog verj' ill Death after 4 hours Death after about 18 hours Recovery, some prostra- tion Recovery, but very ill Recovery, but very ill Recovery, but very ill Recovery, very ill ' Death after 11 hours Death after 63^ hours Death, 22}^ hours Death after 8 hours Recovery after temporary disturbance Recovery, ill Recovery, no effect > This dog had probably previously acquired immunity — see experimental details. 2 Extract made from intestines of dead dogs. 3 The extract ordinarily used, but sterilized by heating. \ ?;5;'/'- .-^N- . 1 * *»! --■ ^G- 'f'y '/l~ • ; , ■'• 4:.- J' 9 '%' - j'..J,' a 0* ^ssiife*- ■■-'C^' P/- Fig. VII. — Cortex from Normal Dog. Fig. VIII. — Cortex from Toxemic Dog. Brain Cell Changes Produced by Toxemia Due to Anemia of the Small Intestines of a Dog. ANEMIA OF THE SMALL INTESTINE 191 Summary of Experiments on the Injection info Dogs of Intes- tinal Extract from Gangrenous Intestine of Dogs or of Extract from Intestines of Dead Dogs Group I. — Injection into the peritoneal cavity. Number of experiments 14 Recoveries 5 Deaths 9 (64.2%) Group II. — Injection into the lumen of the intestine. Number of experiments 7 Recoveries 5 Deaths 2 (28.5%) Group III. — Injection intravenously. Number of experiments ■ 3 Recoveries i ^ Deaths 2 (66.2/3%) Group IV. — Injection intraperitoneally of extract from intestines of dead dogs. Number of experiments 2 Recoveries o Deaths 2 (100%) Group V. — Injection of sterilized intestinal extract, such as was used unsterilized in Groups I-III, inc. Number of experiments ^ 3 Recoveries 3 Deaths o (0%) * This dog may have been rendered immune by a previous experiment. 2 Two intravenously, one intraperitoneally. From both of the series of experiments just presented one fact stood out with striking clearness, and this was the very poisonous nature of the substances absorbed into the circula- tion from the gangrenous gut, or injected into the circulation in the form of extract. The symptoms of collapse were prac- tically always severe, and were followed (or accompanied) by either a rise or fall of temperature. The change of tempera- ture in either direction might amount to several degrees. 192 SURGICAL ANEMIA AND RESUSCITATION When the gut was obstructed the symptoms were neces- sarily those of intestinal obstruction. When the gut was not obstructed, or when extract was injected, the symptoms were identical, showing that in clinical cases of intestinal obstruc- tion the mere fact of obstruction is of importance at least in part because it causes damming of the intestinal contents with increased toxin formation from increased bacterial activity, and subsequent increased absorption of the toxins. As long as there is gangrenous bacteria-laden gut present, even if only detached in the abdominal cavity, poisoning will result from the toxins which get into the circulation by way of the peri- toneal lymphatics. In Experiments 27, 28, and 29 of the second series steril- ized intestinal extract was injected intravenously twice and intraperitoneally once, and all three dogs lived. Apparently, therefore, the living bacteria present in either gangrenous, gut or extract made from it play an important part in the poison- ing. That the poisons are present when the bacteria are dead is indicated in Experiments 2^ and 28, in which the symptoms which followed the intravenous injection of sterile extract were identical with those caused by the non-sterile extract. Probably products formed during tissue decomposition act together with the toxins from bacteria. In Experiment 29 no symptoms occurred, but the dose of 5 c. c. was but half that ordinarily given intraperitoneally. In regard to toxemia from gangrenous gut, the amount of gut involved was a minor detail. Gangrene of 10 centimeters of intestine caused just as severe symptoms as did gangrene of 30 centimeters. A much more important factor was the length of time to which the dog was exposed to the toxemia. In the ligation experiments it was shown that the small intestine of a dog will not endure complete anemia for a longer period than 6 hours without becoming gangrenous. More- <^ . ^ '€ fe --_ '^ ; > ^ 5 T^-l^, ■\ ■^ f' -^ e ^ A ^ .. us Wrf C^'"^-, -^^/f±t TTUT? V'2 ,-^ > b CO ^ O Ul •O < 3 O -2 s s 0? < > fe 3 to 'S E S ANEMIA OF THE KIDNEYS 207 Group II Experiments in Which Both the Renal Artery and Renal Vein Were Clamped EXPERIMENT i January 15, 1910. Mongrel dog; condition, good. Ether anesthesia. The right kidney was exposed, and both vein and artery clamped for jo minutes. The incision was then closed. The operative recovery was good. January 25. The dog was in excellent condition. He was again anesthetized, the kidney exposed as before, and found to be secreting urine in which no casts or albumin were present. While there were a few surround- ing adhesions the kidney seemed in every way to be normal. The kidney was removed and sections made. Microscopical Examination. — While there was some desquama- tion of the tubular epithelium it was not so marked as in the 30-minute experiment in which the artery alone was clamped. The cells showed a dropsical condition similar to that of the other experiment, but the round-cell infiltration was not so marked nor was there hemorrhage into the renal substance. A few of the tubular epithelial cells showed diffusion of the nuclear chromatin, but this also was less marked than when the artery alone was clamped for the same length of time. No casts were found in the tubules. No evidence of connective tissue proliferation was found, and, in almost every respect, the kidney ap- peared to be normal. The capsule was somewhat thickened, but there had not been any formation of new capillaries. EXPERIMENT 2 January 16, 1910. Mongrel bitch ; condition, good. Ether anesthesia. The right kidney was exposed, and both artery and vein clamped for 4^ minutes. At the end of this time no gross changes were noted after the blood had again entered the organ. The incision was closed, and the bitch returned to the kennel in good condition. January 17. A specimen of urine was obtained by pressing over the bladder. No blood cells were found in sediment obtained by centrifugalization, but the benzidin test was positive. Albumin was present constantly 2o8 SURGICAL ANEMIA AND RESUSCITATION until the end of the experiment, while the benzidin test was positive only for four days. January 26. The bitch was again anesthetized, and the right kidney exposed. The ureter was divided. For twenty minutes urine flowed from it. The kidney, as a whole, was swollen and surrounded by adhesions. It was removed and split. The capsule was much thickened, very adherent, and, on stripping it, portions of the cortex came away with it. The entire organ seemed to be edematous, but no evidence of hemorrhage was found. Microscopical Examination. — Marked epithelial desquamation and round-cell infiltration had occurred. The cortex was very ede- matous, and did not stain well. The glomeruli appeared as homo- geneous masses, devoid of any structure whatsoever. Around them there was considerable hemorrhage. The most marked changes were in the tubular epithelium, which, in some places, was completely desquamated. Cells which had not desquamated had either a swollen nucleus or dififusion of the nuclear chromatin into the cytoplasm. These cells were very indefinite in structure. The condition in this kidney was worse than in the 45-minute experiment, in which the artery alone was clamped. EXPERIMENT 3 January 19, 1910. Black and tan dog; condition, good. Ether anesthesia. The right kidney was exposed, and the artery and vein clamped for a period of / hour. The operative recovery was good. Blood was present in the urine for four days after the operation and albumin in large amount throughout the experiment. January 29. The dog was anesthetized again, and the kidney exposed as be- fore. On dividing the ureter six drops of urine flowed in 20 minutes. The kidney was very edematous and bound down by dense adhesions to the peritoneum and intestines. The adhesions were so dense that it was impossible to remove the kidney without injuring the in- testines. Microscopical Examination. — Very extensive hemorrhage and epithelial desquamation were present. In some places the glomeruli were destroyed, with only a mass of blood detritus marking where they had been. In other areas remains of glomeruli were present, but no normal ones were found in any part of the kidney. The ANEMIA OF THE KIDNEYS 209 tubules contained numerous epithelial and hyaline casts. In some areas they had been obliterated by connective tissue formation. The desquamation of the epithelial cells was irregular, being complete in some areas and incomplete in others. In but few places could marked diffusion of chromatin be made out. From the extent of the connective tissue proliferation it seemed that the kidney must have been affected, at least to a certain extent, before the experiment, and that the marked extent of the changed after the experiment was due in part to the previous condition. More will be said later about the increased susceptibility to anemia of previously damaged kidneys. EXPERIMENT 4 March 9, 1910. Mongrel dog; condition, good. Ether anesthesia. The right kid- ney was exposed, and both artery and vein clamped for / hour. The next morning the urine gave a positive benzidin reaction, but nega- tive reactions were obtained on each of the following six days. March 19. The dog was again anesthetized, and the ureter divided. No urine flowed from the ureter while observed for a considerable time. The perirenal adhesions were very dense and firm. The kidney was very edematous and much larger than the other kidney. The capsule was thickened and adherent. Microscopical Examination. — The tubular epithelium pre- sented ragged borders, and, in many places, had desquamated. The glomeruli presented an appearance like that in the other experiments. ■While round-cell infiltration was present around the glomeruli it was not present around the tubules. In many cells diffusion of nuclear chromatin had occurred, and, where these cells were most numerous, desquamation was most extensive. The entire organ was edematous, but there was not much hemorrhage. As a whole, the condition was better than in the one-hour experiments in which the artery alone was clamped, but the changes seemed to be limited more to the parenchyma. EXPERIMENT 5 February 6, 191 o. Mongrel dog; condition, good. Ether anesthesia. The right kidney was exposed, and the artery and vein clamped for 7^4 hours. A few seconds after removing the clamp there was slight oozing from the capsule, and the color of the kidney changed from purple to bright red. The oozing continued until the end of the operation. 2IO SURGICAL ANEMIA AND RESUSCITATION The operative recovery was good. The next morning albumin was present in the urine, and a positive benzidin reaction was obtained. February i6. The dog was again anesthetized, and the kidney exposed as be- fore. No urine flowed when the ureter was divided, although the observation extended over a period of an hour. The kidney was firmly adherent, and could be removed only with difificulty. On sec- tion it was found to be very edematous, the line of demarcation be- tween cortex and medulla was not at all distinct, and interstitial hemorrhages were present. Microscopical Examination. — Extensive desquamation was present in all parts of the kidney. The glomeruli were hemorrhagic, and generally disintegrated, and, with the tubules, were surrounded with round-cell infiltration. In many places the connective tissue had been so freely proliferated that the tubules were occluded in whole or in part. In the patent tubules were many epithelial casts, the adherent cells having largely lost their structure. Nuclear chromatin was frequently diffused into the cytoplasm. The tissues were everywhere very edematous and stained poorly. Newly formed blood vessels had extended from the thickened capsule into the kidney substance. In short the anemia had been of long enough duration to destroy most of the renal parenchyma and produce interstitial pro- liferation. EXPERIMENTS 6, 7, AND 8 In these three experiments, the details of which will not be given, the anemia was for longer periods than in the preceding experiments in this series. The changes were in extent rather than in quality. In the three and four-hour experiments renal abscesses were caused. Summary The only differences found between the results obtained by clamping the renal artery alone or both the renal artery and vein seemed to consist in the production of greater changes in the latter case and also in greater damage to the parenchyma. In both series of experiments anemia of over 30 minutes caused permanent parenchymatous degeneration. When the time was increased to one hour the kidney ceased to secrete urine and its functions were lost. Hemorrhage into the renal ANEMIA OF THE KIDNEYS 21 1 substance seemed to depend more on the amount the kidney had to be handled in carrying out the technique than on whether artery alone or both vein and artery were ligated. It was a phenomenon of irregular occurrence at all times. Hemorrhage into the glomeruli was constant after anemia of 30 minutes. Group III. Anemia of the Kidney of Dogs from Which One Kidney Had Previously Been Removed EXPERIMENT i February 15, 1910. Ether anesthesia. The dog used in this experiment had previ- ously had his right kidney removed in Experiment 3, Group I. He was in good condition in every way before operation, and made a good immediate recovery after having his left kidney exposed and both the renal artery and vein clamped for 50 minutes. February 16. The dog seemed to be in good condition early in the morning, but during the afternoon he was found dead in his kennel. The autopsy revealed a double lobar pneumonia. The kidney was very edematous and had interstitial hemorrhages. There was no urine in the bladder. The renal pelvis was filled with blood. The micro- scopical examination showed the renal cells to be very edematous and the tubules to be filled with blood corpuscles and detritus. EXPERIMENT 3 February, 19 id. Ether anesthesia. The dog used in this experiment had previ- ously had his right kidney removed in Experiment i, Group I. He was in good condition before the operation, and made a good im- mediate recovery after having the remaining kidney exposed and the artery alone clamped for jo minutes. On the next morning pressure over the dog's bladder brought out a small amount of bloody urine, but no more urine could be obtained after that one time. The animal's condition seemed to be good for three days. He then became stupid, refused food, and was found dead on the morning of the fourth day after the operation. The autopsy revealed an acute parenchymatous nephritis of the remaining kidney, 212 SURGICAL ANEMIA AND RESUSCITATION with extensive hemorrhage into the renal substance. The condition, as a whole, resembled that found in the kidney after anemia of one hour in Group I. EXPERIMENT 3 February, 1910. Under ether anesthesia the remaining kidney of a dog from which one kidney had previously been removed was exposed, and the renal artery clamped for jo minutes. The dog died four days later from total suppression of urine. The histological examination re- vealed' changes identical with those found in the other two experi- ments in this group. In addition to these three 30-minute experiments three other dogs, which had recovered after removal of one kidney, had their remaining kidney rendered anemic for periods of 20 minutes each. All three died with suppression of urine, the histological changes being the same, only of less degree. Summary From these six experiments it was evident that a kidney that is doing an unusual amount of work cannot endure anemia so well as a kidney which is working under a normal load. It might be argued that suppression of urine in these last experiments was due to the operative technique alone, but this argument does not hold, because, when done carefully under proper conditions, almost all dogs survive having one kidney removed. The anemia must, therefore, have been the harmful factor in causing the fatal results. Moreover, dogs in which one out of a pair of kidneys was rendered anemic did not have that kidney permanently injured in the same length of time. Summary of All Experiments From all of the experiments in the three groups, as well as from evidence not reported here, the sequence of the changes ANEMIA OF THE KIDNEYS 213 following interference with the arterial blood supply to the point of complete occlusion is roughly as follows, it being recognized that the chronological variation is not exact on account of individual differences and other factors not clearly understood : 1. Edema of (a) parenchyma and (b) of interstitial sub- stance. 2. Exhaustion of the cytoplasm of the epithelial cells, and, later, liberation of the nuclear chromatin and its distribution through the cytoplasm. 3. Simultaneously with the exhaustion of the cytoplasm, hemorrhage from the glomeruli and round-cell infiltration around the glomeruli and tubules. 4. Death and desquamation of the epithelial cells. 5. Changes in the structure of the glomeruli. 6. Diminution in and final cessation of the renal func- tions. 7. Proliferation of connective tissue, beginning in the portions of the -kidney less richly supplied with blood. This proliferation is more or less independent of all of the other changes as regards time of onset. It seems to be an effort toward repair. 8. Occlusion of both tubules and glomeruli followed by epithelial regeneration in which the new cells bear little re- semblance to the old. 9. Beginning independently of the other changes and continuing after the functional death of the kidney, is the in- growth of capillaries from the capsule to the cortex, and even into the medulla when the renal artery has been completely oc- cluded. 10. Thickening and adherence of the capsule with peri- capsular adhesions. These changes may begin early, but, as a rule, the longer the anemia the more they are marked. 214 SURGICAL ANEMIA AND RESUSCITATION Conclusions From the foregoing facts it is evident that the following conclusions may be drawn regarding the changes caused by complete obstruction of the arterial supply of the kidney: 1. The gravity of the lesions produced is in direct pro- portion to the duration of the anemia. 2. The changes which occur after prolonged anemia vary in intensity rather than in variety. 3. More severe changes are produced by occluding the venous circulation as well as the arterial circulation. 4. Whether artery alone or artery and vein are occluded, anemia of over 30 minutes causes permanent changes in the renal structure. 5. Anemia of one hour causes almost total loss of renal function, while anemia of three hours (or less) totally de- stroys it. 6. After anemia of between 30 minutes and one hour enough functional power may persist to make the organ useful. 7. Anemia of less than 30 minutes causes no histological changes of consequence. Hence, while the human kidney may be more resistant than that of the dog, it would seem that one- half hour should be the maximum time for the occlusion of circulation in the human kidney. 8. Before interfering with the circulation in one human kidney it is as important to ascertain the functional activity of the other kidney as it is when one kidney is to be removed. n. ANEMIA OF THE SPLEEN In the following experiments the spleens of dogs were made anemic by occluding the arterial circulation by means of rubber-protected clamps for periods of time varying from thirty minutes to four hours. ANEMIA OF THE SPLEEN 21$ EXPERIMENT i February 7, 1910. Mongrel dog; condition, good. Ether anesthesia. Under careful asepsis the abdomen was opened, and the splenic artery clamped for 50 minutes. The dog was in good condition at the end of the opera- tion. The spleen showed no gross evidence of change. February 8. No ill effects from operation were visible, the dog eating and drinking heartily and playing around the kennel. February 21. The dog was again anesthetized, and the spleen exposed. A few adhesions were found where the clamp had been applied, but other- wise the spleen appeared to be normal. The artery and vein were ligated and the spleen removed. It was not enlarged. No macro- scopical changes could be made out from the cut surface. The dog was allowed to recover, and, after living for a week in good condi- tion, was used in a resuscitation experiment, and died. Microscopical Examination. — The tunica albuginea was thicker than normal, and the blood vessels running through it had thickened walls. The thickening was continued into the trabeculae. The muscle fibers were apparently undisturbed. In no place was hemor- rhage or round-cell infiltration found. The splenic pulp showed more breaking down than was to have been expected. In the Malpighian corpuscles evidences of proliferation were present. On the whole, but little change of consequence had taken place, and, in fact, no more than might have been consistent with healthy variation from the normal. EXPERIMENT 2 February 8, 1910. Mongrel bitch ; condition, good. Ether anesthesia. Under asep- tic precautions the abdomen was opened, and the splenic artery clamped for ^5 minutes. The pulse rate had risen from 87 to 132 beats, and the blood pressure fallen from 120 to 80 mm. of mercury at the end of the operation. The general condition was good. February 9. Condition, good. Pulse, no; blood-pressure, no mm. February ii. Condition, good. Pulse, no; blood-pressure, no mm. February 15. Condition, good. Pulse, no; blood-pressure, no mm. 21 6 SURGICAL ANEMIA AND RESUSCITATION February 21, The bitch was again anesthetized and the spleen exposed. The spleen was larger and softer than when clamped. There were numer- ous adhesions about the blood vessels and the upper pole. No hemor- rhage had occurred externally. The vessels were ligated, the spleen removed, and the bitch allowed to recover. She showed no after- effects. The blood-pressure became normal in three days. Microscopical Examination. — The thickening of the tunica al- buginea, noted in the previous experiment, was still more marked in this one. There was considerable hyperplasia of the muscle fibers, both in the tunica and the trabeculae. As the sections had not been stained to show the elastic tissue it is impossible to say whether it was affected or not. The blood vessels had thickened walls. In some places there had been hemorrhages into the trabeculae, as well as round-cell infiltration. The proliferation of the connective tissue elements along the trabeculae was apparent, and most markedly so near the hilum. The areas of pulp had been reduced in size, owing to this proliferation. The pulp contained many newly formed cells, which were larger than the others, and stained more intensely. The leukocytes showed all degrees of degeneration, and many of them did not stain at all. In ^he Malpighian corpuscles hemorrhages were present, which, in many areas, obliterated all traces of structure. The principal changes, therefore, consisted in increase in the connective tissue elements, a corresponding decrease in the pulp, round-cell infiltration, and intercorpuscular hemorrhages. Conse- quently anemia of 40 minutes was sufficient to cause the formation of permanent lesions. EXPERIMENT 3 February 15, 1910. Mongrel dog; condition, good. Ether anesthesia. Under aseptic precautions the abdomen was opened, the spleen exposed, and the splenic artery clamped for / hour. The blood-pressure fell from 115 to 85 mm. during the operation. The operative recovery was good March 9. The dog's condition had been excellent. He was again anes- thetized and the spleen exposed. It was found to be so densely ad- herent that it was impossible to remove it without killing the dog. Microscopical Examination. — The tunica albuginea was very much thickened. The muscle fibers were markedly hypertrophied. Throughout the connective tissue framework there had been exten- sive hemorrhage and round-cell infiltration. The connective tissue ANEMIA OF THE SPLEEN 217 around all of the blood vessels was very much thickened, so that the pulp had been so encroached upon as to be entirely obliterated in places. Around certain blood vessels the round-cell infiltration had been so extreme as to obliterate the trabeculae. The Malpighian cor- puscles varied. In some there had been extensive hemorrhage, while in others the proliferation of the lymphoid tissue had been so extreme as to efface all else. The number of large, deeply staining cells with large vesicular nuclei was greater than in the preced- ing experiment, and in some areas these cells predominated. Few or none of these cells can be found in a normal specimen. EXPERIMENT 4 March 16, 1910. Mongrel dog; condition, good. Ether anesthesia. Under aseptic precautions the abdomen was opened, the spleen exposed, and the splenic pedicle clamped for /^ hours. The operative recovery was good. Microscopical Examination. — The tunica albuginea was greatly thickened and edematous. The blood-vessel walls were also thickened, and there had been considerable hemorrhage into the tis- sues. The amount of connective tissue throughout was very great, so that the individual areas of splenic pulp had been obliterated. With this there was a correspondingly marked round-cell infiltration. The Malpighian corpuscles appeared as masses of red cells, their structure being entirely obliterated. Everywhere there were large vesicular cells with irregularly stained nuclei, many of them broken down with the chromatin diffused through the cytoplasm. Some areas showed nothing but connective tissue and round-cell infiltra- tion. The entire tissue was very edematous, and was filled with broken down masses of leukocytes. EXPERIMENT 5 March 17, 1910. Mongrel dog; condition, good. Ether anesthesia. The splenic artery was clamped for 2 hours in the usual way. The dog was in good condition at the end of the operation, but the color did not return to the spleen so rapidly as it did during the other experiments, and there was considerable oozing around the place of application of the clamp. 2l8 SURGICAL ANEMIA AND RESUSCITATION March i8. The dog was found dead. At the autopsy the abdomen was found to be filled with blood, the spleen having ruptured near the place of application of the clamp. Sections were not examined. EXPERIMENT 6 March i8, 1910. Black and tan bitch; condition, good. Ether anesthesia. Under aseptic precautions the spleen was exposed, and the splenic artery clamped for 2 hours. When the clamp was removed there was some oozing from the place of application. This soon stopped, and the bitch was returned to the kennel in good condition. April 8. The bitch had remained in good condition. She was again anes- thetized and such a dense mass of adhesions found around the spleen that it could be removed only with great difficulty. The organ, as a whole, was much smaller and firmer than normal, and felt like a mass of fibrous tissue. The artery was occluded with a thrombus. Microscopical Examination. — No normal splenic tissue was present. From the tunica albuginea dense adhesions extended into the surrounding tissue, and in these adhesions were many capillaries, but the blood vessels in the trabeculae were occluded. The oblitera- tion of the pulp was complete. In one area there was a large in- farct which had not stained at all. This experiment can hardly be considered as one which shows the effect of anemia for two hours, on account of the formation of the thrombus in the splenic artery. Most of the blood supply came from the capillaries in the adhesions. The experiment is of value, however, as showing that thrombosis may readily occur if too long or too great pressure be applied to a temporarily compressed artery. EXPERIMENT 7 March 18, 1910. Bulldog; condition, good. Ether anesthesia. Under aseptic pre- cautions the spleen was exposed, and the splenic vessels clamped for syz hours. The dog was in good condition at the end of the opera- tion, but was found dead the next morning with extensive hemor- rhage from rupture of the spleen. The spleen was much enlarged. EXPERIMENTS 8, 9, AND 10 In these experiments the splenic artery was clamped for periods ANEMIA OF THE SPLEEN 219 of 3, 4, and 5 hours. In each instance the animals went through the operation well, but were found dead twenty- four hours later from hemorrhage from rupture of the spleen. No changes were found in the organ except marked edema, as there had not been time for tis- sue degeneration to develop. Summary The chief changes caused by anemia of the spleen were marked proliferation of all of the connective tissue elements in the tunica albuginea, around the blood vessels, and in the trabeculse, and a gradual compensating reduction of the splenic pulp, w^ith its final obliteration. In the experiments in which the anemia was of short duration there was some hyper- trophy of the muscle fibers and formation of large cells, which tended to break down and to discharge their nuclear chromatin into the cytoplasm. The chief changes in the Malpighian cor- puscles consisted of hemorrhage and proliferation of the lym- phoid tissue. The only constant post-operative clinical change noted was a fall in the blood-pressure which persisted for several days. This fall averaged 30 millimeters of mercury. In experiments in which the clamp was applied for more than two hours rup- ture of the spleen always occurred. Whether this might have been obviated by permitting a gradual return of the cir- culation is not known. No changes were noted in the his- tological structure when the anemia was of less duration than forty-five minutes, but in longer periods permanent damage was done. CHAPTER X RESUSCITATION OF THE BODY AS A WHOLE GENERAL CONSIDERATIONS The popular conception of death does not permit of its being regarded as anything but absolute in character. This is really the only accurate conception. For scientific purposes, however, it is convenient, if not essential, to divide the process of dying into three stages. It should be recognized that each stage merges into the others — hard and fast lines between them cannot be drawn. In the opinion of the author these stages cannot be designated better than by the terms first em- ployed, so far as is known, by d'Halluin, i. e., apparent death, relative death, and absolute death. In apparent death, as the term implies, to all outward appearances the vital functions have ceased. Respiration is present, but at such a low ebb that special methods of exam- ination are needed to detect it. It is sufficient to maintain life, and life may persist for long periods of time. The heart beats feebly ; possibly so feebly that its action can be detected only with the stethoscope. Motor activity is inhibited. The skin is pale and cold. The eyes may be either closed or open, but are unseeing and motionless. Seldom is there sufficient relax- ation of the sphincters to cause incontinence. Unconscious- ness may be either present or absent. Relative death may be defined as the condition of the body during the few minutes between entire cessation of cardiac and respiratory activity and absolute death. In the early stages 220 RESUSCITATION OF THE RESPIRATORY APPARATUS 221 of relative death complete resuscitation is possible. In the later stages resuscitation is possible, but there is permanent loss of certain higher functions. In still later stages auto- maticity of cardiac and even respiratory action may be re- sumed, but consciousness may never be regained. At first thought, it would seem that immediately after cessation of the heart action the stagnant blood would be of little use to the surrounding cells. The probability is, how- ever, that stagnant blood contains enough absorbable oxygen to permit the tissues to undergo the stage of relative death. It is hardly credible that interchange of oxygen and carbonic oxid should cease the instant the blood stops flowing past the cells in the delicate-walled capillaries, and while the inter- change goes on the individual cells must benefit by it, even if in rapidly diminishing degree. There is every reason to be- lieve that the stage of relative death depends almost wholly on this interchange, at least for the central nervous system. Absolute death is that condition in which resuscitation of the body as a whole is impossible. The phrase "as a whole" is used advisedly, as different parts of the body, as has been shown elsewhere in this book, may be resuscitated hours or even weeks after absolute death. The determination of absolute death is unimportant, since in cases of apparently suspended animation time is so valuable that even a second should not be used in any but resuscitative measures. For this reason it is well to proceed at once to a discussion of various methods of resuscitation. fRESUSCITATION OF THE RESPIRATORY APPARATUS Artificial Respiration Any method of artificial respiration should aim to repro- duce normal respiration as nearly as possible. Careful ex- 222 SURGICAL ANEMIA AND RESUSCITATION perimentation has shown that what must be considered nor- mal respiration varies within wide Hmits in different indi- viduals. As determined by Vierordt, a normal average rate of exchange of air per minute is about 5,300 cubic centi- meters. This exchange, often called the flow of the tidal air, must not only be sufficient per given respiration, but the num- ber of respirations per given unit of time must be sufficient. Also a test of the efficiency of any method of artificial res- piration must show not only that amount and rate can be maintained, but also that about 5,300 cubic centimeters at least can be made to enter the lungs per minute. \ It is beyond the province of this book to discuss the his- torical side of artificial respiration, but it seems to have been first used largely to resuscitate the apparently drowned. In his recent Hunterian Lectures Keith gives a most interesting historical review of the subject. He mentions the facts that in Amsterdam in 1767 a society was founded for the resusci- tation of the drowned or apparently dead, while in 1774 the Royal Humane Society of England was founded with the same objects as part of its purpose. As far as can be ascer- tained, however, it was not recognized until within recent years that artificial respiration is really the most important of the different measures advocated. Of the best known methods for producing artificial respi- ration those of Silvester (with patient in supine posture), of Howard (with patient in prone posture), of Marshall Hall (with patient alternately in prone and lateral posture), Brosch's modification of the Silvester method (the modifica- tion consisting essentially in a further modification of the movement of the arms backward over the head with over- extension of the upper part of the spine), and the method of Schafer (with patient in prone posture), need no further comment with the exception of the Brosch-Silvester and RESUSCITATION OF THE RESPIRATORY APPARATUS 223 Schafer's methods. Keith states that in 1908 Meyer and Loewy tested the Brosch-Silvester method by Schafer's plan and found that they could get a respiratory exchange of from 7,000 to 16,000 c. c. per minute, as against 5,850 by Schafer's method. This claim makes the respiratory ex- change greater than that obtainable by any other method. Schafer compared his own method with the other methods just mentioned, with the exception of the Brosch-Silvester, and found that of these it gave the greatest air exchange. His findings are expressed in the table. No one of these methods, however, can be said to be preeminently the best, because no one method is applicable to all situations under which artificial respiration has to be given, j Schafer's Table Showing the Relative EIHciency of Methods of Giving Artificial Respiration Mode of Respiration Number per Minute Air Exctiange Per Respiration Air Exchange Per Minute Natural 13 13 13 13 13 450 C. C. I7S c. C. 310 c. C. 254 c. c. 520 c. c. 5,850 C. C. 2,280 c. c. Silvester Howard 4,030 c. c. 3,300 c. c. 6,760 c. c. Marshall Hall Schafer Statistics. — Age of subjects, 23. Height, S ft. 7^^ in. Chest at mammary line, 38 in. Weight, 10 st. i^ lbs. Vital capacity, 6,760 c.c. Pressure exerted in performing respiration, 60 lbs. ' In 1908 the Fifth Resuscitation Committee appointed by the Royal Society of Medicine recommended that the Schafer method of giying artificial respiration be adopted as prefer- able to that of either Marshall Hall or Silvester. It does not follow necessarily that this method is the most efficacious or that perfection has been reached, but, on account of the sim- 224 SURGICAL ANEMIA AND RESUSCITATION plicity and ease of application of the technique, the greater exchange of air than by any other method except the Brosch- Silvester, the postural drainage, and the prevention of the tongue from falling back in drowning cases, it is, at the pres- ent time, the method of choice. Keith, who was a member of this committee, does not regard it as being as efficient as the Silvester method when the latter is properly carried out, but he would advise its use unless the proper execution of the Silvester method could be guaranteed^ , Schafer's description of his method is as follows : "The subject, whether a drowned person or not, is al- lowed to lie prone, i. e., face downward, no preliminary manipulation of the tongue being required. The operator kneels or squats either across or on one side of the subject, facing the head, and places his hands close together flat upon the back of the subject over the loins, the fingers extending over the lowest ribs. By now.leaning forward upon the hands, keeping the elbows extended, the weight of the operator's body is brought to bear upon the subject, and this not only compresses the lower part of the.thorax, but also the abdomen against the. ground, the pressure being fairly equally dis- tributed. The result of this is that not only is the thorax diminished in extent from before back, but, owing to the pressure which is communicated to the abdomen, the viscera are compressed and tend to force the diaphragm up, so that the thorax is diminished in capacity from above .down. This is, no doubt, the reason why the pressure method when ap- plied in the prone position is more effective than when applied, as by Howard, in the supine position. The pressure is applied not violently, but gradually, during about three seconds, and is then released by the operator swinging his body back, but without removing his hands. The elasticity of the chest and RESUSCITATION OF THE RESPIRATORY APPARATUS 225 abdomen causes these to resume their original dimensions and air passes in through the trachea. After two seconds the process is again commenced, and is continued in the same way, the operator swinging his body forward and backward once every five seconds, or about twelve times a minute, without any violent effort and with the least possible exertion. This last condition, viz., the absence of muscular exertion, other than that Involved in swinging forward and backward, renders it possible to continue the process without fatigue for an indefinite time. It can further be carried out unaided by a woman almost as well as a man, by children upon children; it hardly requires to be taught — a simple demonstration suf- ficiently teaches it to a large audience. Its advantages in drowning cases over any other method which involves the supine .position are sufficiently obvious — for with it there is no risk of obstruction by water or mucus or the contents of the stomach which cannot accumulate in the throat but must come away by the mouth; and the tongue, in place of falling back, as in the supine position, falls forward, and is unable to produce obstruction." Resuscitation of the respiratory apparatus Is essentially a matter of keeping the respiratory centers from becoming ane- mic or of restoring to them a normal blood supply if they are already anemic. "Artificial Respiration" Without Movement of the Thorax. — In 1905, under the title "Concerning Artificial Respiration Through Ventilation of the Trachea," H. Hirsch, in his inau- gural dissertation, describes a method of keeping an animal alive by supplying oxygen to the lungs under pressure without going through the ordinary means of giving artificial respira- tion. He demonstrated that a dog could be kept alive for hours by this means, all voluntary muscular effort being inhib- 226 SURGICAL ANEMIA AND RESUSCITATION ited by means of curare. He also demonstrated that .atmos- pheric air similarly supplied would not keep an animal alive. Hirsch's method was to use a Volhard tracheal tube, in- troducing it into the trachea, inflating the little rubber bag with which the tube is surrounded (thus making an airtight connection between the tube and the trachea), and then mea- suring the pressure with which the oxygen was introduced. The Volhard tube consists of one glass, hard rubber, or cel- luloid tube within another, the outer mantle, or efferent tube, being perforated on its sides for a short distance up from the bottom, and the inner, or afferent, tube being open at the end, the stream of oxygen can enter the trachea through the inner tube, while the oxidized air passes out through the outer one. Ten centimeters from the lower end of the outer tube a small rubber bag is placed which can be inflated through a small rubber tube. The pressure which the efferent stream exerts can be measured by connecting the outer tube with a ma- nometer, and counterpressure to prevent too rapid exhalation is thus obtained. For the afferent stream Hirsch used a pressure of 60 centimeters of water. The principle of this method has been recently elaborated by Meltzer and Auer in the Rocke- feller Institute and has been used clinically with notable suc- cess by Elsberg. f RESUSCITATION OF THE CIRCULATORY APPARATUS Methods Commonly in Use ' General Considerations. — Kuliabko, d'Halluin, Stewart, Sollman, and many others have demonstrated repeatedly that the isolated heart may be made to beat for hours by perfusing it with different solutions, notably Locke's. Moreover, they have shown also that hearts from animals which have been killed may be removed from the body and made to beat again RESUSCITATION OF THE CIRCULATORY APPARATUS 227 after as long a time of inactivity as 12 hours, 24 hours, 3 days, and even 5 days (Kuhabko). In experimenting with the hearts of children dying from pneumonia Kuliabko succeeded in reanimating at least certain parts of the heart twenty and thirty hours after death. These facts demonstrate that, up to a certain extent, the heart is an organ whose action is in- dependent of the central nervous system. When an animal is asphyxiated the respiratory action almost always stops first, then the cardiac, and, finally, the cerebral. However, if arti- ficial respiration be supplied the heart will beat for a long time, even when the nervous functions are not resumed. The author has seen the heart continue to beat rhythmically for 12 hours in a decapitated overtrans fused dog. The continued heart action is more dependent on the presence of calcium salts in whatever fluid is passing through it than it is on stim- ulation from the nervous systeixL J Reanimation of the heart after a long interval has elapsed since its removal from the body does not mean necessarily that it will contract in a coordinated manner as it does during life — there may be contraction of the auricles without con- traction of the ventricles. In over one hundred cases tab- ulated by d'Halluin from his experiments, mostly on the hearts of dogs, there is no instance recorded in which the reverse of this statement was true, i. e., that the ventricles ever con- tracted without the auricles doing likewise. In 4 instances he obtained rhythmic beating of both auricles and ventricles be- tween 16 and 17 hours after death. The longest time he re- cords after which he obtained rhythmic auricular action, but no ventricular action, was 42 hours. In one case he records "tremulations" of the auricles, in 16 of the ventricles, and in one case fibrillary tremors of the ventricles. To these cases might be added many similar observations by the author. When death occurs, how long will the heart continue to 228 SURGICAL ANEMIA AND RESUSCITATION beat after respiration ceases? In dogs killed by clamping the trachea, by illuminating gas poisoning, by chloroform, or by ether, the author has made repeated observations in which the heart has continued to beat from one to three or even four minutes, both respiration and carotid pulse being recorded on the same drum. In pure asphyxia he has seen the heart beat for 6 minutes with sufficient strength to make the blood circu- late, while contractions have continued for a much longer timej According to d'Halluin, Vulpian observed fibrillary con- traction of the right auricle of a dog 93 hours after death, while Sailer and Reid observed heart beats, also in a dog, for 72 minutes. D'Halluin himself observed rhythmic contrac- tions in the auricles and right ventricle of a cat for more than an hour "even though the heart had been withdrawn from the chest and placed on an extemporaneously constructed cardiograph." In a recent observation made by Dr. F. W. Hitchings in the case of a patient with uremic convulsions, the heart at one time stopped beating effectively, as was determined by the absence of heart sounds (stethoscope) and by the cessation of all radial pulsation, for three and one-half minutes after the complete cessation of respiration. At the end of that time it began to beat again, at first very feebly, and respiration soon recommenced without the use of any measures to restore it. This observation was made near the end of the series of con- vulsions, and just after the last severe convulsion, death occur- ring six hours later. The rhythmic contraction of part of the heart cannot be regarded as sufficient to furnish efficient circulation, and it is doubtful if efficient contraction persists on the average longer than for from three to five minutes. In all cases duration of time between the final cessation of the heart beat and its restoration should be taken as the criterion of temporary sus- RESUSCITATION OF THE CIRCULATORY APPARATUS 229 pension of animation, rather than the duration of time from the cessation of respiration. Without doubt in many cases of accident the heart has beat feebly, to be sure, but with sufficient force to supply the brain with enough blood to sus- tain its functions, when, in the hurry and excitement, the ob- servers could not detect any action and have believed that it was absent. It is in such cases as these that artificial res- piration after apparently long intervals of suspended anima- tion has saved life. In experimenting on dogs the author has found that reani- mation of the heart does not always follow artificial respira- tion and the intraarterial injection of normal saline solution and adrenalin, or transfusion of blood. In some of the cases in which these procedures are begun, even within a couple of minutes of cessation of the heart beat, the heart cannot be made to beat again. The question at once arises as to why this should be. Probably the most frequent cause of failure Hes in technical obstacles, such as blood-clot, direct injury, and, above all, because the coronary pressure was not sufficiently raised. Fibrillary tremulation is perhaps the next most fre- quent cause. Moreover, if infusion be given too rapidly intra- venously the right heart may be paralyzed in diastole. The technique, rather than the latent powers of reaction of the animal, is therefore accountable sometimes. ' As to the practical application of different methods by which the heart may be made to beat again, it is found that they may be divided into two groups — -the indirect, in which the heart itself is not made accessible, through an open- ing in the chest wall or abdomen, and the direct, in which it is made accessible or is directly interfered with, as in tapping. Under indirect methods will be considered in this or the next chapter (i) compression of the chest" wall; (2) electrical ap- plications through the chest wall and massage of the heart 2SO SURGICAL ANEMIA AND RESUSCITATION itself; and (3) the use of infusions, i In discussing all of these methods it is to be understood that the heart has actually- stopped beating before beginning treatment, and that artificial respiration is being carried on simultaneously with the treat- ment. Before taking up each method in detail delirium cordis will be considered briefly. Delirium Cordis. — Aside from the sensitiveness of the cen- tral nervous system to anemia the most serious obstacle in the way of resuscitation is delirium cordis, or fibrillary tremu- lation. Up to the present time no satisfactory method of overcoming it has been found. When such a method is discovered, one that can be readily applied clinically, a great advance will have been made toward solving the problem of cardiac and, hence, general resuscitation. In performing experiments on the heart all physiologists have noticed the phenomenon of delirium cordis. Frequent allusions have already been made in these pages to vari- ous causes of this condition. Any sufficiently severe stimulus and many stimuli which would not ordinarily be called severe may cause it to appear. The stimulus may be either physical or chemical in nature, and is usually most efficacious when ap- plied directly to the heart. A heart which has ceased beating and has then been made to beat again, whether in situ or iso- lated, may show delirium instead of the normal rhythmic con- tractions. Faradic currents of even weak intensity may cause it. Direct currents of low voltage, up to 120 volts, are par- ticularly likely to cause it. Various ways of overcoming delirium cordis have been used, and a few with some success, at least in the laboratory. D'Halluin considered intravenous injections of chlorid of po- tassium to be the most efficacious treatment. He says : "The heart, after having been poisoned by a massive dose of this drug, may beat again rhythmically under the influence of the RESUSCITATION OF THE CIRCULATORY APPARATUS 231 massage in spite of the previous tremulations." Then he goes on to say that this poison when diluted in the entire blood mass does not seem to have any more action on the heart than on the rest of the organism. Of all the many things which he tried this was the least toxic and most easy to use. Among inefficacious substances used for this purpose d'Halluin mentions copper sulphate, corrosive sublimate, zinc lactate, aluminum sulphate, barium, strontium, strophanthin, digitalin, chloral, atropin, nicotin, magnesium sulphate, sa- ponin, fluorescin, curare, and magnesium citrate. The ox- alates, the fluorids, cocain, and stovain were hardly utilizable by reason of the injury which they did to the organism in dosage large enough to stop the tremulations. Only the salts of ammonia could compare with chlorid of potassium, and then action was feeble. Among inefficacious methods d'Halluin found that electric discharges, faradization of the pneumogastric nerves, local cooling, and bandaging with dressings wet with a solution of cocain were equally useless. D'Halluin's experience, larger than that of any other one investigator, coincides with the experiences of everyone else, except possibly Prevost and Batelli, who state that a very powerful and rapidly alternating current of electricity will arrest tremulation. Prevost and Batelli's method might be useful in industrial plants in which such currents could be commanded at an instant's notice, special arrangement being made for treating accidents due to electrical shock. Otherwise this method would be entirely impracticable on account of the lack of proper facilities. f Kesuscitation of the Heart by Rhythmic Pressure on the Thorax.) -In dogs the forcible rhythmic compression of the thorax over the heart by compressing the heart itself and the great vascular trunks, raises the blood-pressure to a certain 232 SURGICAL ANEMIA AND RESUSCITATION extent and thus aids its action. The mere stimulation of the first few compressions has a tendency to make the heart re- sume automatic action, and a feeble circulation may be main- tained by the continuation of the rhythmic pressure upon the chest. If the capacity of the medullary centers be early in- creased by the subsequent diminution in their relative anemia, the resumption of heart activity is much more apt to be per- manent. Success will be in inverse ratio to the feebleness of the heart beat, if present, and to the duration of its inactivity, if absent. / In adults, and especially in children, something can doubt- less be accomplished by forcibly activating the elastic chest wall. With the child flat on its back, pressure should be applied at the rate of about 30 to 40 times a minute. This will also afford efficient expiration, as in the Schafer method the elasticity of the thorax will take the place of inspiratory efforts. Care should be taken not to use too much force, al- though the action should be firm and vigorous. The applica- tions should continue for at least twenty minutes, or for as much longer if a stethoscope is not at hand so that the lack of heart action can be determined with accuracy. If no action can be detected with the stethoscope at the end of twenty minutes, there is little or no hope that it will be established, and, in all probability, the higher cerebral centers will long have been past hope of recovery, 1 Resuscitation of the Heart by Electrical Stimulation through the Chest "Wall. — In the opinion of the author the advisability of using electric currents for the purpose of inaugurating the heart beat is doubtful. With a current of fixed character and strength uniform results doubtless might be obtained, but the technical side presents what may Ije insurmount- able difficulties, and positive and irreparable harm may be done. The great danger is that of causing fibrillary con- RESUSCITATION OF THE CIRCULATORY APPARATUS 233 tractions of the heart muscle, with the result that the heart as a whole becomes an inefficient trembling mass of tissue. In cases of electric shock the effect on the heart may be summarized as follows : ^ 1. Low tension currents (up to 120 volts) cause fibrillary contractions and hence are the most dangerous. 2. Currents of medium tension are apt to have the same effect but are more likely to cause general inhibition. 3. High tension currents cause general inhibition through the central nervous system. These effects vary with the point and magnitude of the contact, the length of exposure, and the direction of the flow of the current. In his excellent monograph, "Resurrection du Cceur," d'Halluin says (page 172) : "The fibrillary tremors of the heart are the principal obstacle which is opposed to the re- sumption of the rhythmic function of the myocardium. There- fore, one will carefully azmd every measure which is capable of provoking them, and one zuill not run a risk by attempting the direct electrical stimulation of the heart . . ." What applies to the direct stimulation of the heart applies with equal force to stimulation through the chest wall. '""Direct Methods of Resuscitating the Heart. — Three so-called direct methods of massaging the heart have been employed, i. e., methods in which the heart is manipulated after opening the thorax or the abdomen. These are : ( i ) The intrathoracic, in which the thorax is opened and the heart massaged through the opened pericardium; (2) the transdiaphragmatic; and (3) the subdiaphragmatic. In the second method the heart is massaged from the abdomen through an opening near the ensi- form cartilage, the diaphragm being cut through as well as * From a research made in collaboration with Dr. J. J. Macleod. See reference No. (& in Bibliography. 234 SURGICAL ANEMIA AND RESUSCITATION the pericardium. In the third method the heart is massaged by way of an abdominal incision without opening the diaphra^nj Intrathoracic Method. — In a total of 50 cases of clini- cal massage of the heart White found 2 successful, 8 partially successful, and 18 unsuccessful cases in which this method was used. The advantages of this method are that the heart is directly under the hand of the operator, and he can actually see what he is doing. In cases in which wounds of the heart have to be dealt with there is no doubt but that this should be the method of choice. The thorax has to be opened- any- way and opening the abdomen would only increase the surgi- cal risk. The great disadvantages of this method are the time it takes to make the exposure, the danger of opening the pleura, the increased danger of causing shock, and the general disadvantage that it is unnecessary for many cases. The Transdiaphragmatic Method. — In the 50 cases referred to above White found only 3 (those of Mauclaire, Mauclaire and Coqueret, and Green) in which transdia- phragmatic massage of the heart was employed. One of these was partly successful, while the other two were failures. To the mind of the author this method has little to commend itself — if the abdomen is to be opened it is unnecessary, except possibly in very exceptional cases in which adhesions might interfere with getting a good grasp of the heart. The Subdiaphragmatic Method. — This is by all means the method of choice, with, as already stated, the exception of cases in which the heart or thoracic contents have to be ex- posed on account of traumatism. That the heart can be read- ily reached through the diaphragm may easily be demonstrated and is well shown in the frozen longitudinal section made by White (see Figs. XIII, XIV and XV). White gives in his table 8 successful, 5 partially successful, and 6 unsuccessful cases of the application of this method. The superiority of fe j:3 U J < u Iz; Q a M-l t:> o H ^ o Iz; 1> o h-1 3 1 O 1 U hH 1 — 1 Xi d t-H fe 236 SURGICAL ANEMIA AND RESUSCITATION this method is indicated by the fact that in only 19 cases, as against 28 in which the direct method was used, there were 8 Fig. XIV. — The Thoracic Viscera as Seen from the Front, the Ribs AND THE Sternum Intact. (Courtesy of Dr. Charles S. White, and "Surgery, Gynecology, and Obstetrics.") recoveries, or four times as many as in the larger group of cases — 42.1 per cent, as against 7.1 per cent. As the majority of major operations are on the abdominal viscera, the incision already made can be used, or enlarged if necessary. RESUSCITATION OF THE CIRCULATORY APPARATUS 237 In considering the subject of cardiac massage as a whole it is impossible to refrain from calling attention to the fact Fig. XV.— Same as Fig. XIV, the Viscera Being Exposed by Removal OF THE Ribs and Sternum. (Courtesy of Dr. Charles S. White, and "Surgery, Gynecology, and Obstetrics.") that in 35 out of 50 operative cases, or in 70 per cent., chloro- form was the anesthetic used, and caused, at least in part, the cardiac collapse. In another case chloroform and ether were given, and in still another the "A. C. E." mixture was used. 238 SURGICAL ANEMIA AND RESUSCITATION This fact alone should point the way to the prevention of many accidents which necessitate the use of cardiac massage. Some day the real and constantly present dangers of chloro- form will be universally recognized. As long as this anesthetic is used there will be cases of collapse in which desperate measures will have to be taken to save life. Experiments show that when the heart and the respiration have stopped the brain is paralyzed and can do nothing. And also, that when the heart has stopped it cannot be started by any nerve stimulus. It is now known that the way to start the heart is to raise the pressure in the coronary arteries and to supply oxy- gen to the lungs and hence to the blood, but that the way to keep it heating is to supply oxygen to the brain. This is the key to the entire problem. When the heart acts, then, and only then, can the circulation be reestablished. Confronted with a collapsed patient, in whom suspended animation implies a quiescent heart, how can the blood pressure in the coronary arteries be quickly raised to 40 mm. or more, and oxygen be supplied ? One might answer that cardiac massage should be suffi- cient to reestablish circulation, but experience has shown that this method gives inefficient coronary pressure, because, ist, but little blood reaches the heart and hence but little is thrown out, and, 2d, the vascular system is collapsed, so that the small amount of blood which is expelled by the pressure of the hand finds collapsed blood vessels, and therefore the aortic pressure is not raised materially. It might then be supposed that saline infusion forced into an artery toward the heart would so raise the coronary pressure as to activate the heart, but experiments have shown that this cannot be done effectively. The saline solution is taken up in large quantity by the relaxed blood vessels, but it RESUSCITATION OF THE CIRCULATORY APPARATUS 239 escapes from the blood vessels as rapidly as it enters, and col- lects largely in the abdominal viscera; saline solutions there^ fore cannot produce the needed rise of pressure in the cor- onary vessels. Could not an extreme head-down position of the patient combined with bandaging the extremities and the abdomen throw such a volume of blood into the thorax and into the heart that, by the further assistance of either direct rhythmic compression of the heart or by rhythmic compression of the thorax as a whole, the required coronary pressure would be supplied? Here again experiments have given a negative an- swer. The relaxed vascular trunks again cause defeat. Failure of this last measure means that the peripheral re- sistance must be so raised that the stream of blood which is thrown out of the heart by rhythmical compression may react against it and so raise the aortic and hence the coronary pres- sure. Can this increased resistance be supplied by electric stimulation of the vasomotor mechanism? All such efforts in the author's hands ha\e failed. It is obvious that the cor- onary pressure can be raised to 40 mm. or more only by the aid of a drug that will produce a vigorous contraction of the arteries against which the blood thrown out by rhythmic com- pression of the heart may react. Fortunately in adrenalin there is such a drug, but adrenalin must be brought into direct contact with the walls of the blood vessels. This can be done by infusing it into the circulation with saline solution. Arterial injection should be employed rather than venous, because the blood-pressure is dependent on the resistance offered by the muscles of the arteries. If injected into a vein the adrenalin must pass through the right auricle, right ventricle, pulmonary circulation, and thence to the left auricle and left ventricle before it comes in contact with the walls of the arteries when, for the first time, 240 SURGICAL ANEMIA AND RESUSCITATION it can be of assistance in raising the aortic and hence the cor- onary pressure. Not only is this a circuitous route, entailing loss of time, but the adrenalin itself must be somewhat dissi- pated. It wholly lacks the directness of effect secured by in- jecting it toward the heart through an artery. Saline-adren- alin arterial infusion toward the heart, combined with rhyth- mic pressure upon the thorax has proved most efficient in animals. CHAPTER XI RESUSCITATION OF THE BODY AS A WHOLE — CONTINUED The means employed for resuscitation in suspended anima- tion from drowning, from anesthetic accidents, from collapse in operations, from injury, or whatever the cause may be are roughly divided into three classes: ist, the artificial respiration and stimulant method; 2nd, direct massage of the heart added to artificial respiration and stimulation; 3rd, the adrenalin- saline infusion — rhythmic thoracic-pressure method devised by the author. It is quite obvious that all of the methods have their indications and their limitations. In the first method, the use of artificial respiration has the great advantage of requiring no special apparatus and being of ready application. The best method for producing artifi- cial respiration has already been considered. Artificial respira- tion alone cannot inaugurate the heart beat, but when there is still a feeble circulation or when there is no circulation if there is a rhythmic contraction of even the auricles this method may succeed. Simple artificial respiration is the only hope in drowning and other accidents occurring when professional help is not at hand. Experiments upon animals have abun- dantly shown that as far as asphyxia is concerned a very little air sustains the spark of life for a surprisingly long time. The advantages and the shortcomings of the second method, viz., that of direct or indirect massage of the heart 241 242 SURGICAL ANEMIA AND RESUSCITATION added to artificial respiration, are as follows : In the first place, it is wholly inapplicable in the hands of the layman. Even in professional hands the large wound made in opening the thorax or the abdomen and inserting the hand is likely to become infected, on account of the want of precaution that haste demands. This constitutes in itself a grave danger. Then, too, aside from the danger of such a wound, the effect of direct massage on the heart itself is most serious. It may cause fibrillary contraction, which is certain to defeat resusci- tation, or clotting of the blood in the chambers of the heart may result from the physical injury. The author has fre- quently seen the latter occur. There is one point of advantage in direct massage of the heart, viz., in the course of abdom- inal operations there may be sudden collapse. If this happens, with one hand in the abdomen and the other on the chest the heart may be rhythmically compressed. This may be done with little loss of time, while preparations are being made for the application of a better technique to be described later. The author's experimental researches and the work done by others may now be summed up in such a way as to enable decision, ist, as to the type of method to be used in any given case, and, 2nd, the most practical technique of performing each method. This summary is as follows : The various organs and tissues of the body endure anemia in vastly different degrees. The part that endures anemia least well is the brain. The cortex is killed beyond resuscita- tion in about seven minutes. In order to save the brain reanimation of the body as a whole must begin with reanima- tion of the heart. Even while the heart is inactive the blood may be artifi- cially circulated through the brain by rhythmic compression of the thorax and the abdomen. This pressure is doubly benefi- RESUSCITATION OF THE BODY AS A WHOLE 243 cent ; it simultaneously produces artificial respiration and arti- ficial circulation. It serves to supply to the brain enough oxy- gen to keep the slender thread of life from breaking. In artificial respiration, by the Schafer method especially, an artificial circulation of no mean value is simultaneously pro- duced. / It must be borne in mind that when any part of the body, but especially the chest and the abdomen, is subjected to pres- sure, the valves of the heart and of the veins inevitably cause the blood of the veins to flow toward the heart and the blood in the arteries to flow toward the periphery. Now this is pre- cisely what the heart does. If, instead of a single local pres- sure, a series of rhythmic pressures upon the thorax and abdo- men are made the entire blood stream may be energized and moved, that is to say, the person who makes the rhythmic pressure furnishes an external pseudocardiac action. The au- thor has personally been able to effect a complete circulation in a recently dead subject, producing a radial pulse and bleed- ing of peripheral vessels, and even to make a blood-pressure of measurable tension (registered by a sphygmomanometer) by the combined effect of a tightly inflated rubber suit cover- ing the lower extremities and the abdomen and strong rhyth- mic pressure from the broadly extended hands applied upon each side of the chest. Indeed, the face could be made to flush and fade appreciably at will. Undoubtedly such an excellent method as Schafer's for producing artificial respiration owes its effectiveness as much to the factor of artificial circulation as to artificial respiration. This point seems to have been missed. Schafer's method should be used in all cases in the absence of medical assistance or outside of a hospital, and even in a hospital in the absence of immediate surgical aid. 244 SURGICAL ANEMIA AND RESUSCITATION THE AUTHOR'S METHOD OF RESUSCITATION The author's method is appHcable only in a hospital service in which the staff is trained for prompt action, and the simple apparatus for infusion and a bottle of adrenalin are ever in readiness. A staff may be so drilled that the adrenalin may be introduced in two minutes. In the author's method the ^^P ^ \ V W \ \ / h v>U- :^ -Xt^ ^ V—" — "^ ^ " \ ^^^ ^ -ssaLi \ "■ J. -- ^-^^^_____^ V __— — Fig. XVI. — Method of Giving Adrenalin by Injecting It Directly into A Stream of Normal Saline Solution. The needle of the syringe is thrust through the wall of the rubber tube, and the adrenalin then injected with rapidity and certainty into the circulation, by way of the flowing saline infusion. patient is kept in a supine position. Rhythmic pressure is made on the thorax and upper abdomen for the double purpose of producing artificial respiration and artificial circulation. Any artery, but preferably the brachial, is laid bare with rapid strokes of a scalpel, picked up, and an elliptical hole snipped into it with scissors, leakage being controlled by digital pres- sure or clamps. Into this hole, directed toward the heart, a small cannula of an ordinary "funnel, tube, and cannula appa- ratus" filled with normal saline solution is inserted and tied. The stream is allowed to flow at once and immediately half the contents of a hypodermic syringe filled with adrenalin chlorid, i-i,ooo, is injected into the inflowing saline stream as RESUSCITATION OF THE BODY AS A WHOLE 24$ near the artery as possible by piercing the rubber tube, or is injected directly into the artery, now distended with salt solu- tion (see Fig. XVI). The instant this is done the rhythmic pressure is rather vigorously applied, so that the adrenalin will be distributed as widely as possible. As soon as the coronary pressure is raised high enough with oxygenated blood the heart will begin to beat with a strong thump. Care must be taken not to cause acute dilatation of the heart, and the flow should be stopped the instant blood begins to be forced back into the tube by the sudden rise in blood-pressure. If resuscitation is successful the artery may then be resected and an end-to-end anastomosis made. J The author's associates, Dr. Lower, Dr. Dolley, and Dr. Sloan, have made a number of attempts at resuscitation, some of which were made before Dr. Dolley and the author ascer- tained the period during which various parts of the brain can endure anemia. These experiences, amounting to ten in all, may be briefly summarized as follows : The cases of electro- cution resisted every attempt at reanimating the heart. Later, in the before-mentioned research with Prof. MacLeod on the attempted resuscitation of electrocuted dogs, it was found that there was fibrillary contraction of the heart, which prevented resuscitation. This gives an almost hopeless aspect to cases of suspended animation from electric shock. ^ In other cases in which the patients were drowned and also in the case of seriously injured persons who died on enter- ing the hospital, it was usually possible to resuscitate the heart and the respiration but impossible to resuscitate the cerebrum. ^ In order to prevent such accidents an apparatus was devised made of wire netting which fitted snugly around each Hmb and around the neck, the upper and lower parts communicating with each other by means of insulated wires. In this manner the electric currents received by the head, neck, and extremities were shunted around the vulnerable heart and the apparatus served as a sort of lightning rod. 246 SURGICAL ANEMIA AND RESUSCITATION In one case success might have been attained had there not been a fatal lesion of the brain. In this case the entire occipital skull was crushed deeply into the brain. Even then the resuscitation succeeded beyond all expectations. The heart quickly began beating and a blood pressure of 80 mm. was secured and sustained. The author proceeded to elevate the depressed fractures, the patient moving about during the cut- ting, but as the fragments were raised blood gushed out from lacerated sinuses. The wounds were packed but the patient soon died. In another case a patient with a crushed skull who died on arrival at the accident room was reanimated partially, but the reanimation was brief. In this case, also, there was a mortal wound of the brain. As previously stated, the fact, that the cortex, the associative memory part of the brain, was so extremely susceptible to anemia, was not then known. In three instances, among over thirteen thousand personal operations, the author has seen patients succumb on the operat- ing table under circumstances which permitted an attempt at resuscitation. In the very first case, resuscitation was success- ful. The patient presented a serious risk, a case of delirious Graves' disease, in which, in the course of operation for ex- cision of the lobe of the thyroid, collapse occurred without warning. The lobe had just been removed and the wound was ready to be closed. The assistant was at once directed to make rhythmic compression on the chest while the jugular vein was opened and adrenalin and saline solution introduced; the pa- tient meanwhile seemed to be dead. The heart began to beat immediately and respiration was soon resumed. This patient survived the immediate effects of the operation and resuscita- tion, but died later with symptoms of exhaustion and of the disease. Another case was that of sudden collapse while an at- RESUSCITATION OF THE BODY AS A WHOLE 247 tempt was being made to remove a tumor of the brain in a child of eight. The tumor was situated at the cerebellar-pon- tine angle. The patient was in a very emaciated, weakened state, and a poor risk for any operation. In the course of the deep dissection, while trying to dislodge the tumor, the heart and the respiration suddenly stopped, and the child was apparently dead. An assistant kept up rhythmic pressure on the thorax while the author hastily laid bare the axillary ar- tery, picked it up, snipped an oblong opening in it and inserted the cannula of a saline apparatus into it. The solution at once flowed into the axillary artery toward the heart, and 15 minims of adrenalin chlorid solution, 1-1,000, were injected into the rubber tubing near the cannula. In about one minute the heart began to beat strongly, and the saline apparatus was at once closed by a clamp. After a time a sudden strong spontaneous inspiration occurred and eventually respiration was resumed. The wound was packed with iodoform gauze, a dressing was applied, and the patient sent to her room. In several hours absolute death followed without her having regained con- sciousness. The last case was that of a middle-aged woman who had a growing tumor of the uterus, operation upon whom had been deferred because of a serious lesion of the heart. At times there had been swelling of the feet and nephritis. Finally the tumor had grown so large and caused so much distress that, despite the risk, operation was undertaken. The patient went through the operation well enough until the wound was nearly sutured and the anesthetic had been removed, when, without warning, the heart stopped. Rhythmic pressure on the chest was at once made, the axillary artery was opened, and adrenalin in saline solution was given as before. There was some delay in securing a response from the heart, but when it came it was energetic. The respiration did not appear 248 SURGICAL ANEMIA AND RESUSCITATION spontaneously for nearly an hour, but meanwhile there was good circulation. The first intimation of inspiration was a sudden, long, deep breath. Following this the respirations were slow, deep, and of a sighing type. In time the respiratory rate increased and the artificial respiration that had still been maintained as a precautionary measure was discontinued. The patient was taken to her bed and Professor G. N. Stewart, the consulting physiologist to Lakeside Hospital, was asked to see her. There were no reflexes, either deep or super- ficial; no response to painful stimuli; no conjunctival, nksal, laryngeal or pharyngeal reflex ; the pupils were contracted and did not respond; and the intraocular tension was markedly increased. The heart beat was regular and ranged from 90 to 100 per minute. The respiration ranged from 12 to 16 per minute. These two functions persisted for about 6 hours, when both gradually failed. ' The interpretation of the failure is that the time before inauguration of the heart beat in the course of the resuscita- tion was unusually long, so that from the moment of collapse and relative death to the moment of reestablishment of circula- tion was about 9 minutes. It is quite certain that this was a clear case of cerebral death before death of the respiratory and circulatory centers. On the other hand, it is equally certain that had the heart become reanimated as quickly as in former cases the patient would have been resuscitated as a whole. From the other experiments on the resistance of other tis- sues than the brain which have been reported in other chapters of this volume it is quite certain that all of the body was alive during the six hours following the resuscitation excepting that part of the brain in which associative memory and other higher functions lie. Assuming, then, that the cortex died on the table and the balance of the brain and all of the remainder of the body lived six hours longer, when did the patient die? RESUSCITATION OF THE BODY AS A WHOLE 249 / The author and his associates have resuscitated fully one hundred dogs in the course of the original research on resus- citation and in the numerous demonstrations of the technique to those interested. In comparing the results with the resus- citation of patients he is convinced that the human heart is as readily resuscitated as is the heart of the dog. I CHAPTER XII GENERAL RECAPITULATION LOCAL ANEMIA Experimental and clinical observations of total anemia of various organs and tissues of the body have been presented in the foregoing pages. From them the lesson is learned that some organs or tissues, such as the skin, bone, and connective tissue at one extreme endure anemia for many hours, while at the other the brain endures anemia for only a few minutes. Moreover, the component parts of organs endure anemia un- equally; the connective tissue framework is more resistant by far than the parenchymal cells, and there is strong evidence that the power to endure anemia is in proportion to the del- icacy of the function of an organ or tissue. The results of local anemia may not be confined to the immediate organ affected, but may produce constitutional dis- turbances. For example, anemia of a muscle may result in atrophy and functional death of the muscle while the remain- der of the body is virtually uninjured. On the other hand the death of a coil of intestine not only destroys the coil but also results in the formation of a powerful life-destroying toxin which acts by injuring the brain cells chemically. Whether aseptic necrosis of intestine would alone furnish this toxin is of little moment, but doubtless tissue necrosis per se assists the toxins of the invading bacteria. Again, aseptic death of a kidney or spleen might cause no general disturbance, while septic death would be sure to do so. 250 GENERAL RECAPITULATION 251 From the fact that there is a pretty sharply defined time limit beyond which organs cannot survive anemia, many im- portant lessons are to be learned. A common example is shown in the application of bandages, too tight applications resulting either in death of a limb as a whole, or death of only certain parts, e. g., of the muscle fibers, and of the skin and connective tissue, the bone alone surviving. Another important underlying principle which has been strongly proved is that in partly or wholly anemic organs the susceptibility to infection is increased. This is notably true of the intestine as is shown by the ready invasion of bac- teria into the intestinal wall, which is not anemic enough to die of anemia alone, and which would not be invaded at all if it were not anemic. This recalls the fact that previously injured or overworked kidneys are more susceptible to anemia than are normal kidneys. It also suggests the necessity of avoiding unnecessarily long pressure of clamps on the intes- tines and the renal pedicle, not only so as not to cause harm through anemia, but also to avoid lowering the resistance to infection. Finally, these studies also show that unconscious or paralyzed patients should be protected against both anemia and infection by being turned in bed at regular intervals, such individuals having lost the protecting warning of beginning injury which pain would otherwise give. RESUSCITATION Whatever the method of resuscitation, the one primary and essential object is to supply the brain with an oxygenated circulation. Artificial respiration can be maintained indefi- nitely with ease ; the heart is rather readily started, but unless cerebral anemia be overcome in less than seven minutes the patient passes into the death that knows no awakening. BIBLIOGRAPHY Chapter I 1. Crile and Dolley. An Experimental Research into the Resus- citation of Dogs Killed by Anesthetics and Asphyxia. J. Ex- per. M., 1906, VIII, 713-715. 2. Hayem et Barrier. Effets de I'Anemie Totale dc I'Encephale et de ses Diverses Parties, Studies a I'Aide de la Decapitation suivie des Transfusions de Sang. Arch, de physiol. norm, et path., Paris, 1887, 3 s., X, 1-45. 3. Hill, Leonard. Phil. Tr. Roy. Soc, 1900, CXCIII, 121. 4. Batelli, F. Restaurations des Fonctions du Coeur apres I'Anemie Complete. Compt. rend. I'Acad. de sc, Par., 1900, CXXX, 800-803. 5. . Influence des Differents Composants du Sang sur la Nu- trition des Centres Nerveux. Jour, de physiol. et de path, gen., 1900, II, 443. 6. Prus. Ueber die Wiederbelebung in Todesfallen in Folge von Erstickung, Chloroformvergiftung, und electrischem Schlage. Wien. klin. Wchnschr., 1900, XIII, 451-458; 482- 487. 7. d'Halluin^ M. Tremulations Fibrillaires dans le Massage du Cceur. Compt. rend. Soc. de biol.. Par., 1904, LVII, 1 18-120. 8. . Le Massage du Coeur. Presse med., Par., 1904, I, 345-349. 9. . Diagnostic Immediat de la Mort. i. Critique de I'fipreuve de la Phlyctene Explosible. 2. Expose d'un Procede Nouveau. Lille, 1906, These. 10. Stewart, Guthrie, Burns, and Pike. The Resuscitation of the Central Nervous System of Mammals. J. Exper. M., 1906, VIII, 289-321. 11. Guthrie^ Pike^ and Stewart. The Maintenance of Cerebral Activity in Mammals by Artificial Circulation. Am. J. Physiol., 1906-07, XVII, 344-349. 12. Stewart and Pike. Resuscitation of the Respiratory and Other Bulbar Nervous Mechanisms with Special Reference to the Question of Their Automaticity, Am. J. Physiol., 1907, XIX, 328-359. 253 254 BIBLIOGRAPHY 13. Pike, Guthrie, and Stewart. Studies in Resuscitation. — 11. The Reflex Excitability of the Brain and Spinal Cord after Cerebral Anemia. Ibid., 1908, XXI, 359-371. 14. Pike^ Guthrie^ and Stewart. Studies in Resuscitation. — I. The General Conditions Affecting Resuscitation and the Re- suscitation of the Blood and of the Heart. J. Exper. M., 1908, X, 371-418. 15. Stewart and Pike. Loc. cit., No. 12. 16. Hill, Leonard. The Physiology and Pathology of the Cerebral Circulation. London, 1896, 132. 17. Mayer, Med. Centralbl., 1878, XVI, 579; 594. 18. Hayem, G. De la Mort par Hemorrhagic. Arch, de physiol. norm, et path., Par., 1888, 4s., I, 103-136. Chapter II 19. Derby, G. S. Ligation of the Common Carotid Artery for Ma- lignant Recurrent Hemorrhage of the Vitreous. J. Am. M. Ass., Chicago, 1907, XLIX, 107-10. 20. Keller, E. Beitrag zur Kasuistik des Exophthalmus pulsans. Zurich, 1898, In. Diss., 207. 21. Siegrist, a. Die Gefahren der Ligatur der grossen Hals-schlag- adern fiir das Auge und das Leben des Menschen. v. Graefe's Arch. f. Ophth., 1900, L. 511-646. 22. Quenu. a Propos de la Ligature de la Carotide Primitive. Bull, et mem. Soc. de chir. de Par., 1904, n. s., XXX, 686- 694. 23. Verneuil. Gaz. des hop., Par., 1871, 442. 24. HoPMANN. From Siegrist, loc. cit., No. 21. 25. Wyeth, J. A. Essays in Surgical Anatomy and Surgery. New York, 1879. 26. ScuDDER, C. L. Cerebral Embolism following Ligation of the External Carotid Artery. Boston M. and S. J., 1906, CLIV, 317. Chapter IV 27. Keen, W. W. A Case of Ligature of the Abdominal Aorta, etc. Am. J. M. Sc, Phila., 1900, CXX, 251-77. 28. Bristowe, J. S. Three Cases of Sudden Obstruction of the Abdominal Aorta by Aneurysm. Lancet, Lond., 1881, I, 131; 166. 29. Pozzi, M. S. Hernie Mesenterique Ancienne, etc. Bull, et mem, Soc. anat. de Par., 1872, XLVII, 14-18. BIBLIOGRAPHY 255 30. Meynard. L'Obliteration de I'Aorte Abdominale par Embolic ou par Thrombose. Paris, 1883, These. 31. TuTSCHEK. Ein Fall von vollstandiger Verstopfung der Aorta abdominalis an der Theilungsstelle in Folgen wahrer Herz- thrombose nach abgelaufenem Erysipelas faciei. Aerztl. Int.- Bl., Miinchen, 1873, XX, 257-263. 32. Barie and du Castel. £tude Clinique sur les Embolics de I'Aorte ct Rccherches Experimcntalcs sur la Production dcs Souffles Cardiaques. Arch. gen. de med., Par., 1881, CXLVII, 29-52. 33. Lauenstein, C. Ein Fall von Embolic der Aorta. Dcutschcs Arch. f. klin. Med., Leipz., 1876, XVII, 491-496. 34. MoNTEiRO, C. B. Observation dc Ligature dc I'Aorte Abdomi- nale, Pratique en 1842. Rev. med.-chir. de Par., 1852, XI, 147-155- 35. TiLLAUX. Anevrisme Diffus Consecutif de I'Artere Iliaque Ex- terne; Ligature de I'Aorte. Mort au Trentc-Ncuviemc Jour. Bull, et mem. Soc. de chir. de Par., 1900, XXVI, 473-475. 36. Gull, W. Paraplegia from Obstruction of the Abdominal Aorta. Guy's Hosp. Rep., Lond., 1857, III, 311-313. Chapter V 37. Dreist, K. Ueber Ligatur und Kompression der Arteria iliaca communis. Deutsche Ztschr. f. Chir., Leipz., 1903-4, LXXI, 5-34- 38. Gillette, W. J. Ligation of the Left Common Iliac Artery. Ann. Surg., 1908, XLVIII, 22-24. 39. MoscHOWiTZ, A. V. Simultaneous Ligation of Both External Iliac Arteries for Secondary Hemorrhage following Bilateral Ureterolithotomy. Ann. Surg., 1908, XLVIII, 872-875. 40. Rabe, L. Zur Unterbindung der grossen Gefassstamme in der Continuitat bei Erkrankungen und Verletzungen der unteren Extremitaten. Deutsche Ztschr. f. Chir. Leipz., 1875, V, 140- 280. Chapter VI 41. Barnard, H. L. Two Cases of Contracture of the Flexors of the Forearm Treated by Lengthening. Lancet, Lond., 1901, I, 1 138. 42. Langer, a. Ein Fall von ischamischer Lahmung durch Embolic einer Armatcrie bewirkt. Jahrb. d.- Wien. k. k. Krank.- Anstalt., 1897, IV, 375-82. 256 BIBLIOGRAPHY 43. Barbier. Deux Cas de Contracture Traumatique. Bull. Soc. clin. de Par., 1884, VIII, 151-158. 44. Freeman, L. The Desirability of Early Operations upon the Nerves in Ischemic Paralysis. Tr. Am. Surg. Ass., Phila., 1907, XXV, 284-92. 45. Nevitt. Gangrene of the Hand Induced by a Tight Sleeve, Recovery. Canad. Pract., Toronto, 1890, XV, 97-99. Chapter IX 46. Karsner and Austin. Studies in Infarction. Experimental Bland Infarction. J. Am. M. Ass., Chicago, 191 1, LVII, 951-958. 47. LiTTEN. Untersuchungen iiber die hamorrhagischen Infarct und iiber die Einwirkung arterieller Anamie auf das lebende Gewebe. Ztschr. f. klin. Med., Bed., 1880, I, 131-227. 48. Carrel^ A. Transplantation in Mass of the Kidneys. J. Exper. M., 1908, X, 98-140. 49. . Remote Results of the Replantation of the Kidney and the Spleen. J. Exper. M., 1910, XII, 146-150. 50. EiSENDRATH and Strauss. The Effect on the Kidney of the' Temporary Compression of Its Vessels. J. Am. M. Ass., Chi- cago, 1 9 10, LV, 2286-2290. 51. Guthrie. The Effect on the Kidney of Temporary Anemia Alone and Accompanied by Perfusion. Arch. Int. Med., Chicago, 1 910, V, 232-45. 52. Carrel, A. Cultivation of Adult Tissues and Organs Outside of the Body. J. Am. M. Ass., Chicago, 1910, LV, 1379-1381. 53. MacNider, W. de B. The Pathological Changes Which De- velop in the Kidney as a Result of Occlusion by Ligation of One Branch of the Renal Artery. J. Med. Research, 1910, XXII, 91-3. Chapter X 54. IcARD. La Mort Reelle et la Mort Apparente. Nouveaux Pro- cedes de Diagnostic et Traitement de la Mort Apparente. Paris, 1897. 55. D'Halluin, M. Contribution a I'fitude des Signes de la Mort; Rubefaction provoquee au Diagnostic de la Persistance de la Circulation dans le Cas d'Absence des Bruits du Cceur. Bull, med., Par., 1906, XX, 832. 56. ViERORDT. Physiologic des Athmens, Karlsruhe, 1845., BIBLIOGRAPHY 257 57. Keith. Three Hunterian Lectures on the Mechanism underly- ing the Various Methods of Artificial Respiration, etc. Lan- cet, Lond., 1909, I, 745 ; 825 ; 895. 58. ScHAFER^ E. A. Artificial Respiration in Man. Harvey Lec- tures, Phila., 1907-8, 223-243. 59. HiRSCH, H. Ueber kiinstliche Atmung durch Ventilation der Trachea. Giessen, 1905, In. Diss. 60. KuLiABKO. Studien ueber die Wiederbelebung des Herzens. Arch. f. d. ges. Physiol., Bonn, 1902, XC, 461-474. 61. . Neue Versuche ueber die Wiederbelebung des menschli- chen Herzens. Centralbl. f. Physiol., Leipz. u. Wien, 1902, XVI, 330. 62. . Versuche am isolirten Vogelherzen. Ibid., 588-90. 63. . Weitere Studien ueber die Wiederbelebung des Herzens Arch. f. d. ges. Physiol., Bonn, 1903, XCVII, 539-566. 64. D'Halluin, M. Resurrection du Coeur. La Vie du Coeur Isole. Le Massage du Cceur. Paris, 1904. 65. . Les fitapes de la Mort. Compt. rend. Soc. de biol.. Par., 1905, LIX, 370. 66. . Contribution a I'fitude du Massage du Coeur (suite). Les Tremulations Fibrillaires. Paris, 1905. 6y. Prevost and Batelli. Quelques Effets des Decharges filec- triques sur le Coeur des Mammiferes. J. de physiol. et de path, gen., Par., 1900, II, 40-52. 68. Crile and McLeod. Some Observations on the Effect of Alter- nating Currents of Moderate Frequency on Dogs. Am. J. M. Sc, Phila., 1905, CXXIX, 4^7-424- APPENDIX Through the courtesy of the following Commissions, rep- resenting The American Medical Association, The National Electric Light Association, The American Institute of Electri- cal Engineers, and the Bureau of Mines, their reports and rules are reprinted here on account of their important prac- tical bearing upon the subject of this monograph. REPORT OF THE COMMISSION ON RESUSCITA- TION FROM ELECTRIC SHOCK The electric current may kill either by temporarily paralyz- ing the nervous control of the muscles of respiration, or by stopping the regular beat of the heart. When the heart is seriously affected it ceased to contract as a whole, but continues to contract in parts here and there, so that it appears to quiver. It is then said to ''fibrillate." In this condition the heart fails to keep the blood circulating, and death quickly results. At present no practical procedure has been discovered which will restore the regular beat of the heart in man after it begins fibrillating. Hope of resuscitation is now restricted to proper treatment of the cases of paralyzed respiration; and, since deprivation of oxygen for about ten minutes injures irreme- diably some of the nerve centers of the brain, it is particularly important that measures for resuscitation be applied imme- diately and continued until natural breathing returns. In some instances, however, the heart may be merely weakened without being made to fibrillate ; in such cases artificial respira- tion may be of vital importance, because a greatly weakened 258 APPENDIX 259 heart leads to impairment or total stoppage of respiration, which in turn destroys the last vestige of the heart-beat. In all cases, therefore, an attempt should be made to restore natu- ral breathing. Fortunately, artificial respiration can be ap- plied by laymen without immediate need of complicated appa- ratus. The older rules for artificial respiration, which were widely posted in this country, described the Silvester method, a method which directs that the victim of the accident be laid on his back, and his chest expanded and compressed by draw- ing his arms forward and then pushing them back against his ribs. After these rules were published, however, a new method of artificial respiration was devised by Sir E. A. Schafer, of Edinburgh, called by him the "prone pressure method." It consists in laying the victim on his belly and applying pressure rhythmically on the loins and lowest ribs. Since there was some difference of opinion regarding the relative merits of these two methods of artificial respiration, and since the time seemed ripe for a revision of the old rules and for a possible standardization of new rules for resuscita- tion. President Gilchrist, of the National Electric Light Asso- ciation, requested that the American Medical Association and the American Institute of Electrical Engineers cooperate with his own Association in this undertaking. Through the ap- pointment of representatives of these Associations a Commis- sion on Resuscitation from Electric Shock was organized in the autumn of 1911, with the following membership: For the American Medical Association, Dr. W. B. Can- non (chairman), Professor of Physiology, Harvard Univer- sity; Dr. George W. Crile, Professor of Surgery, Western Re- serve University ; Dr. Yandell Henderson, Professor of Physi- ology, Yale University; and Dr. S. J. Meltzer, head of the de- 26o APPENDIX partment of Physiology and Pharmacology in the Rockefeller Institute for Medical Research. For the National Electric Light Association, Dr. E. A. Spitzka, Director and Professor of General Anatomy, Daniel Baugh Institute of Anatomy, Jef- ferson Medical College, and Mr. Wm. C. L. Eglin, Past Presi- dent of the National Electric Light Association. For the American Institute of Electrical Engineers, Dr. A. E. Ken- nelly, Professor of Electrical Engineering, Harvard Univer- sity, and Dr. Elihu Thomson, Electrician, General Electric Company. Mr. W. D. Weaver, editor of the Electrical Worlds was elected Secretary of the Commission. The Commission was confronted with three problems : (i) The determination of the best manual method of artificial respiration that can be instantly applied by laymen, and the clear description of that method; (2) a consideration of spe- cial mechanical appliances for continuing artificial respiration, and the possible invention of a simple and effective arrange- ment, the action of which might be quickly and easily learned; (3) an investigation of the possibilities of restoring the fibril- lating heart to its natural pulsation. The third of these prob- lems has not been solved, and possibly, because of the sensi- tiveness of important nerve cells of the brain to lack of blood supply, a sensitiveness which results in abolition of their func- tions when deprived of blood for about ten minutes, the solu- tion of the problem in a manner permitting the life of the indi- vidual to continue may be impracticable. The Manual Method of Artificial Respiration The advantages claimed for the Schafer method over the Silvester method are : ( i ) Greater simplicity and ease of per- formance; (2) absence of trouble from the tongue falling back and blocking the air passages; (3) little danger of injuring the liver or breaking the ribs if pressure is gradually and not APPENDIX 261 violently applied; and (4) larger ventilation of the lungs. There is no question regarding the first three of these claims. The claims for larger ventilation Professor Schafer supported by experimenting on conscious human subjects. He compared the volumes of air taken into and expelled from the lungs by the prone pressure method and by the other manual pro- cedures of artificial respiration. His results showed a to-and- fro tide of air sufficient to maintain life indefinitely when the prone pressure method was used, but a volume considerably less than normal when the Silvester and other methods were employed. Professor Schafer's claim for larger ventilation with his method was examined by Drs. Henderson and Cannon mainly on conscious healthy men and by Dr. Meltzer on animals. When, in a conscious person placed in the prone position, arti- ficial respiration is substituted for normal breathing, the re- sult indeed is a taking in and giving forth of air in practically the usual amounts, as can be shown by a gasometer. Conse- quently when the operator ceases the rhythmic pressure the subject at once takes up his natural breathing again. He does not breathe more rapidly, as he would if the artificial respira- tion had been insufTficient, nor does he cease breathing for a moment, as he probably would if the artificial respiration had been excessive. Our experiments showed that the pressure applied in the Schafer method is quite sufficient to expel the air from the lungs to a degree not surpassed by vigorous efforts at expira- tion. Not only is the chest diameter lessened from front to back, but further, because the pressure on the abdominal vis- cera tends to force the diaphragm upward, the chest is also lessened in extent from above downward. Schafer declared that the natural elasticity of the chest and abdomen causes a resumption of their original positions as soon as pressure is 262 APPENDIX removed, and that consequently air passes into the lungs as in inspiration. The fundamental question, however, is whether the taking in of air because of the elasticity of the parts will be the same in an unconscious as in a conscious person. If the muscles con- tinue to exert their moderate contraction or tone, as in a con- scious person, the parts disturbed by pressure will evidently be restored to their former positions more completely than if the muscles are toneless. Besides this tonic contraction of the muscles as an aid to inspiration, it is highly probable that quite involuntarily the conscious subject permits the normal nerv- ous and muscular mechanism, which naturally acts without in- volving volition, to expand the chest and thus take in the air. The fact that natural breathing is resumed after a period of artificial ventilation of the lungs, without any indication of too little respiration or too much, rouses the suspicion that the ventilation is, in fact, being regulated by the subject involun- tarily. Consequently a testing of the methods of artificial respiration under conditions as near as possible to those in the breathless, toneless subject is desirable. A critical examination of the Schafer and other methods of artificial respiration was undertaken, early in 1912, by Dr. Henderson on students who, after over-ventilating their lungs by two or three minutes of voluntary forced respiration, showed a lack of desire to breathe (apnea), lasting from 40 to 80 seconds. Schafer had, indeed, produced in his tests some degree of apnea, but his subjects took only "several deep respirations," and the apnea seems to have lasted only a brief period during the first part of the artificial respiration. In subjects in true apnea the tone of the muscles would be re- tained, but the tendency to inspiration after the breath was pressed from the chest would probably be reduced to a mini- mum. The following figures, obtained by Dr. Henderson, APPENDIX 263 show the amount (in cubic centimeters) of the exchange of air, as measured by a gasometer connected with the subject's mouth, in men in true apnea, and again without this condi- tion, by different methods of artificial respiration : Silvester method Schafer method (arms flexed at the sides) Schafer method (arms stretched forward) Natural breathing (at the same rate as the artificial) Subject normal . . . , 500-600 500-600 500-600 500-600 Subject in apnea . 150-200 125-200 200-300 It is interesting to note that as the period of apnea came to an end the movements of the chest were increased involun- tarily to approximately the normal extent. In some cases the artificial movements (on non-apneic subjects) were of some- what greater amplitude than the natural ; but the rate was cor- respondingly slower, so that they got (or rather, quite involun- tarily, they took) exactly the amount of air that they needed — no more and no less. According to the results obtained with the subjects in apnea, the Silvester method is somewhat more effective than the Schafer, when the subject's arms are at his sides. The latter is, however, the better when the prone pres- sure procedure is reinforced by the inspiratory position of the chest, which drawing the arms forward tends to induce. In both the exchange of air is considerably less than the usual tidal volume (about 450 c. c). These results have recently been confirmed by Liljestrand, Wollin and Nilsson (Skandinavisches Archiv fur Physiologic, 19 1 3, xxix, 198), who found that the amount of air moved by artificial respiration when the conscious subject was in apnea was much less than in experiments when the same sub- ject was not in apnea. These Swedish observers report an insignificantly greater tide of air (about o.oi liter) with the Silvester method than with the Schafer method. They paid no attention to the position of the subject's arms, however, 264 APPENDIX which we may assume not to have been drawn forward. In fact, so far as we are aware, the advantage of having the sub- ject's arms extended beside his head so as to pull the ribs out- ward into a more nearly inspiratory position than is otherwise afforded has not previously been referred to by any writer, although it has been reported that the position has been used by English coast guards. The experiments above reported fully demonstrate its importance. The observations of Liljestrand, Wollin, and Nilsson (in part upon cadavers) likewise indicate that on a toneless body the exchange of air induced by artificial respiration would probably be considerably less than on a man who was merely in apnea. The following observation by Dr. Henderson points to the same conclusion, but suggests that the tone (or elasticity) of the muscles wears off gradually, and is not en- tirely lost until after a period beyond which resuscitation is in any case impossible. The windpipe of a cat under chloroform was connected with a small gasometer and the volume of the natural breaths recorded. The chloroform was then adminis- tered in such amount that respiration failed. Artificial respira- tion by the Silvester method was given. It afforded a move- ment of the gasometer at first only about a quarter as large as the natural, then about a third, then about a half, and then spontaneous breathing returned. Chloroform was again ad- ministered until both breathing and heart action had ceased. Artificial respiration now gave only 15 per cent of the normal volume. Five minutes later, i. e., six minutes after death, it was only 8 per cent, and after another five minutes only 5 per cent. A modification of the Silvester method has been suggested by Brosch, in that the arms after being drawn past the head are pressed downward so that the chest is raised away from contact with the body's support. A large ventilation, even as great as from i to 3 , APPENDIX 265 liters for each respiration, has been reported as occurring in this procedure. But the violent and painful character of the manipula- tion must lead to as great participation as possible by the subject in order to minimize the degree of dislocation of the parts, and the volumes of air breathed in and out do not therefore represent solely the mechanical effects of the procedure. The Brosch modification of the Silvester method has not commended itself as a means of artificial respiration. Dr. Meltzer examined the efficacy of the two methods on dogs after completely abolishing, by means of curare, all possi- bility of muscular participation by the animal and also all mus- cular tone. Twelve minutes was the longest time during which respiration was sufficient to keep the heart beating when the Silvester method was used, while with the Schafer method the shortest time was eighteen minutes and the longest thirty-one. The foregoing observations indicate that, so far as the amount of ventilation of the lungs is concerned, the Schafer method, reinforced by the extension of the arms forward, is decidedly better than that suggested by Silvester. And this advantage, taken in conjunction with its greater simplicity and safety, caused the Commission to vote unanimously in favor of the prone pressure method of artificial respiration as an effec- tive means of giving immediate aid. After a careful consideration of the conditions under which accidents occur, and of the" need for clear and brief statements of the proper procedures, the Commission prepared a description of facts and procedures, which has been issued as a booklet. Since the manual procedure is not well learned merely by reading about it, superintendents, foremen and others having charge of men are advised in the booklet to give practical instructions and demonstrations on the use of the rules to all employees. Besides the booklet the Commission has prepared a slight abbreviation of Sections i, 2, and 3 of 266 APPENDIX the Instructions, which has been issued as a chart to be posted in central stations where accidents are likely to occur. Mechanical Devices for Artificial Respiration The Need for Mechanical Devices In experimental attempts to cause death of animals by ether, chloroform, illuminating gas, drowning, etc., respira- tion sometimes returns spontaneously after a complete suspen- sion for two minutes and longer. For this reason it is often difficult to decide whether the restoration of respiration has really been brought about by any manipulation which has been applied. Only when such manipulation, applied to a living ani- mal unable to breathe, keeps up a sufficient exchange of res- piratory gases to maintain the circulation for a considerable period, and when discontinued no spontaneous respiration sets in, is the conclusion strictly justified that the manipulation is efficient for artificial respiration. The keeping alive of com- pletely curarized animals by artificial respiration is therefore the most rigorous proof for the efficiency of any method. The methods applied to human beings have not been tested in this rigid manner. The air exchange effected by the various methods has been determined on healthy conscious individuals, not on the relaxed victims of drowning and shock, and the re- covery of the victims by one method or another is cited as evi- dence of the value of the method. Keith has examined the an- nual reports of the Royal Humane Society for the past 140 years, and in hundreds of instances recovery of the apparently drowned has been reported when, at different times, the chief means employed were fumigation (rectal), or warmth, or in- flation (mouth to mouth), or friction, or artificial respiration by manual methods, or combinations of these (see Lancet, 1909, p. 897). APPENDIX 267 Since a certain percentage of cases recover spontaneously, each one of these methods has been credited with causing re- covery, and yet an examination shows that some of them, as fumigation, friction, and warmth, have no direct effect on breathing. Although the manual methods of artificial respira- tion provide an exchange of air, the amount of which in the toneless victim has not been accurately determined, they prob- ably afford a sufficient exchange of air until dangers from tem- porary causes are averted. Thus, in mild cases of respiratory failure, in which reflex irritability of the breathing mechanism is retained, and therefore a tendency to recovery exists, these methods may be of the utmost value in reestablishing the nor- mal movements. Certainly, in all cases when breathing is sus- pended and no better means are at hand to supply air to the lungs, manual methods should be used, and of these the most commendable is the prone pressure method with arms ex- tended forward. Even a relatively poor method of artificial respiration, if begun immediately, may maintain life and per- mit ultimate recovery in cases in which an ideal method with all the resources of laboratory and hospital would be ineffec- tive after a delay of a few minutes. If, owing to delay, certain cells of the brain have been deprived of their supply of oxygen for more than the critical period (rarely more than ten min- utes), it is utterly impossible for any later treatment to restore them to their normal condition. Because the amount of ventilation supplied by this modified prone pressure method in apneic subjects may be close to a dangerous minimum, mechanical devices assuring more effi- cient respiration than can be assured by manual methods are desirable. In order to test the action of devices now being ad- vocated, a subcommittee, with Dr. Meltzer as chairman, was appointed. The apparatus examined was used according to 268 APPENDIX directions, and the effects were demonstrated before the mem- bers of the Committee. Commercial Mechanical Devices At least four machines for performing artificial respiration are now in the market — the Pulmotor, the Dr. Brat Apparatus, the Lungmotor, and the Salvator. The last two devices have not been examined. The first two machines are alike in pro- viding for inspiration by oxygen pressure and for expiration by suction. In the pulmotor the inspiratory air contains only 60 per cent oxygen, while in the Dr. Brat apparatus it is all pure oxygen. In the latter apparatias the respiratory changes are made by hand, while in the pulmotor they are made auto- matically by the mechanism of the instrument. The apparatus of Dr. Brat was used by some surgeons in experimental intra- thoracic work while its inventor was alive, but it seems never to have become a successful commercial article. The pul- motor, on the other hand, although it has lacked scientific, sur- gical, and medical sponsors, has received wide publicity through the daily press. The Pulmotor The pulmotor is manufactured by the Draeger Works in Liibeck, Germany, manufacturers of various rescue apparatus. The firm has a very active agency for its goods in Pittsburgh. Although several years have passed since the pulmotor was introduced in Germany, the medical literature of that country has only one publication on this machine, a short article by Dr. Roth (Berliner klinische Wochcnschrift, Sept. 18, 191 1), known for the Roth-Draeger inhalation apparatus. In this article Dr. Roth states that he had made experiments on ani- mals and human cadavers with the machine several years be- fore. He found that air is liable to be driven into the stomach. APPENDIX 269 but that this can be prevented by pressure on the trachea. Al- though years passed by after the introduction of this appara- tus and although Germany has many active life-saving socie- ties, no medical report of its use in a single case has appeared in the very prolific medical literature of that country. Jelineck {Wiener medezinische Wochenschrift, 1912, No. 25) men- tions the efficiency of the pulmotor, but his knowledge of the machine is derived from the brief article of Dr. Roth and from a report sent to him by the Pittsburgh agency, that Dr. Sherman, in Pittsburgh, saved two lives with this machine. In the medical literature of this country the following no- tices have been found : The Journal of the American Medical Association for Au- gust 31, 191 2, contains an answer to a question regarding the pulmotor, with a reference to Dr. Roth's article and to the re- ports in Chicago newspapers. McCombes, of Philadelphia, in an article on illuminating gas poisoning in the American Journal of Medical Sciences, Oct., 1912, says of the pulmotor: "It maintains artificial res- piration perfectly. Reports from all over the country relative to its efficiency have been received. Whenever possible it should be used." He does not say from whom and by whom the reports were received. From a study of the wording of this writer it is highly probable that he had neither personal experience with cases nor any medical literature at his dis- posal. In volume VI of Keens Surgery is an article by W. L. Estes (Director, Physician, and Surgeon-in-Chief of South Bethlehem, Pa.), in which there is a picture of the pulmotor used in the act of resuscitation. Quoting the Survey, he states that the Red Cross First Aid car is equipped with "the pul- motor for restoring respiration to asphyxiated persons." Not a single report of personal knowledge has been found in a 27© APPENDIX standard medical journal. And only when an observer pub- lishes his experience in detail, gathered in a number of cases, can we judge whether his observations are unbiased, his state- ments truthful and his conclusions justifiable. By the kindness of the head physician to the New York Edison Co., opportunity was obtained to examine 21 records of gas poisoning in which the pulmotor was reported as having been used with success. Most of the reports were written by chauffeurs and a few only by physicians. In most of the re- ports no distinction was made between unconsciousness and absence of respiration. In a few cases only was there reason to suppose that respiration might have been suspended. Let- ters sent to the various physicians mentioned brought either an unsatisfactory answer or none at all. Of two additional cases which were reported no machine was used in one, and in the other, a case of opium poisoning, an entirely different method (intratracheal insufflation) was employed. A series of reports made by miners to the Bureau of Mines and another series made by several physicians were ex- amined. The miners' reports comprise few cases. In one case, according to the daily press, the man was revived by the pulmotor, while the report does not even mention the pulmotor, and the physician in attendance expressed the belief that suc- cess was due to hypodermic treatment. Of the remaining nine cases four were revived by the administration of oxygen, and two by the Silvester method of artificial respiration in com- bination with oxygen. In the seventh case (Webb) the Silves- ter method had been applied for three minutes and was fol- lowed immediately by the pulmotor for six minutes. In the eighth case (Burgess) the pulmotor was first applied thirty minutes after the victim had been removed from the gas at- mosphere. No statement was made as to what was done for him in the interim. In the ninth case (Enzian) Dr. McGuire, APPENDIX 271 of Wilkes-Barre, "endeavored for two hours to revive her by artificial respiration. Failing in this, a pulmotor was brought a distance of eight miles, and under the manipulation of Mr. G. T. Holdaman the patient was revived in two or three hours." Cases eight and nine, in which the victims lived a long time before the application of the pulmotor (half an hour and two hours), do not present convincing evidence. In case seven the pulmotor did at least as much as the Silvester method; but that does not show it did more, since the same result might have been attained if the pulmotor had been used first and the Silvester method later. These reports are in no manner satisfactory documents for demonstrating the supe- riority of the pulmotor as a device for artificial respiration. The second series consists of statements of physicians transmitted by Dr. Wm. O'Neil Sherman, chief surgeon of the Carnegie Steel Co. in Pittsburgh. It comprises reports of seven cases in which the pulmotor was used successfully. Dr. Sherman himself reports two cases. In the first (June 20, 1912) a collapse occurred during an amputation, "breathing ceased, pupils dilated and did not react to light, with a very small, thin pulse." "The pulmotor was brought into use, and as a result the patient soon began breathing normally (italics ours here and elsewhere), recovering from the collapse in ten minutes." In the second case (Dec. 20, 1912) nitrous-oxid- oxygen anesthesia was being given, "when respiration sud- denly ceased, eye reflexes absent, pupils fixed, cyanosis gradu- ally increasing, pulse weak and slow. Artificial respiration (Silvester method) — tongue drawn out, cyanosis becoming greater. Artificial respiration was continued with no sign of returning respiration for two and a half minutes. Pulmotor was then used; respiration returned in one to one and a half minutes; cyanosis soon cleared up, and the operation continued under ether." 272 APPENDIX Dr. Urmson, Newcastle, Pa., reports (Dec. 23, 1912) the case of a man overcome by gas . . . "it was impossi- ble to detect any sign of respiration. Mask was applied and pulmotor started ; in a short time patient showed marked signs of improvement." This patient recovered. Dr. Botkin, Duquesne, Pa., reports (April 20, 19 12) the case of a strangulated man, his clothes having been caught in the drill of the press. Respiration stertorous, 10 or 12 per minute. "We immediately cleared his mouth and throat of mucus and gave oxygen by use of pulmotor." "It did splen- did work, inflating his lungs fully and regularly, and estab- lished normal respiration." (Natural respiration had not stopped in this case.) Dr. Evans, Union Mills, Youngstown, Ohio, reports (Dec. 17, 1912) the case of a man overcome by gas, "unconscious, scarcely if any respiration, pulse weak. Pulmotor applied, kept going for five minutes, respiration returned, pulse became stronger and consciousness returned." Dr. Rossiter, company surgeon, Swissdale, Pa., reports two cases of "gassing." In one case (Nov. 21, 1912) "the patient was unconscious, not breathing, no pulse, and I was not \^sic'\ able to detect only faint flutter of the heart. The pulmotor was used, and in the course of about ten minutes the man showed signs of life, and after keeping it on for about twenty minutes he was almost completely revived." In the second case of "gassing" (Dec. 28, 1912) "the patient was un- conscious, had no pulse, no signs of respiration, very feeble heart, loss of all reflexes. Before I arrived the hospital at- tendant performed artificial respiration in connection with the inhaling device of the pulmotor. I continued this treatment after my arrival for about one-half hour, at the end of which time there was very little change in the patient. I then switched over the pulmotor and adjusted it without pulling APPENDIX 273 out the tongue or pressing on the larynx. In the course of a few minutes the patient began to move his head, and in ten to fifteen minutes he started to fight and wanted to sit up." (In this case manual artificial respiration combined with oxy- gen was capable of keeping up the respiratory function for longer than half an hour.) In five of these cases the pulmotor was used only a few minutes, and furtherrnore respiration was restored so soon after it had ceased that the conclusion that the pulmotor was essential is not justified. The evidence is similar to that in the cases of the apparently drowned, previously cited, who were restored by fumigation or friction. In another case spontaneous breathing was not absent, and therefore the credit of restoration does not belong to the instrument. The last two cases are the most favorable to efficiency of the pulmotor, and in one of these the support of life by manual respira- tion for more than half an hour is rather in favor of that method. Although the cases reported above do not furnish convin- cing proof of the necessity or the exceptional value of the pul- motor, that instrument is probably capable of creditable per- formance, and doubtless has, in some instances, favored the restoration of normal breathing. Its present vogue, however, is not supported by a critical examination of the principles in- volved in its mechanism or of its effects when used for long periods. As stated above, no well-considered testimony to its action is to be found in medical literature, and in this country at least its loudest sponsors are the newspapers, which have spread the impression that the pulmotor is a perfect and most reliable resource when respiration is suspended. A high official of one of the important electric companies in the country testified to a member of the Committee : "We have to buy these machines, even if they are no good, as an 274 APPENDIX evidence of our good faith and our desire to do everything possible to safeguard the public and employees." Experiments with Commercial Devices for Artificial Respira- tion The effects of the Dr. Brat apparatus and the pulmotor were studied by the subcommittee in experiments on anes- thetized and curarized animals. The animals were thus doubly prevented from making any response to the action of the ap- paratus, and were, therefore, in a condition analogous to ex- treme prostration. The Dr. Brat apparatus, obtained by cour- tesy of the Westphalia Engineering Co., was used in a few ex- periments only, but the results were in essential points similar to those secured with the pulmotor. One pulmotor used was loaned by the Pittsburgh station of the Government Bureau of Mines. On returning the machine, Mr. Paul, the mining engineer in charge of the station, stated that the machine was in the same good working condition when returned as it was when sent. Another pulmotor, loaned by the New Haven Gas Co., was also tested, and gave confirmatory results. Experi- ments were performed on dogs, cats, and rabbits. The oxy- gen was applied through specially constructed masks adapted to the individual animals. The efficiency of these masks was tested by other respiratory apparatus at hand in the laboratory. The tongue was kept well pulled out. In several experiments the trachea was connected by means of a lateral cannula with a water manometer. In some cases also the intrapleural pres- sure was measured, and in others the thorax was opened and the behavior and appearance of the lungs observed. Of eleven dogs only one small animal (under 4 kilos), com- pletely curarized, could be kept alive by means of the auto- matically working pulmotor for as long as one hour. The animal remained in fairly good condition, had about thirty APPENDIX 275 respirations per minute, and no air entered the stomach. In another dog the usual laboratory method of artificial respira- tion (inflation of the lungs) had to be substituted for two to three minutes every eight or ten minutes in order to keep the animal alive. The respiratory movements would go on with the pulmotor regularly for a while, and then they would begin to change from a slow to a rapid rhythm, and the pulse would gradually become dangerously slow. In two other animals the pulmonary respiration would continue regularly at one position of the head, but stop at the slightest change from that position. On other occasions changes in the respiration would occur without any visible cause. In the majority of the ani- mals respiration could not be kept up even for five minutes when left to the automatic activity of the apparatus. The re- sult was evidently better when the respiratory alternations of the machines were guided by hand, so as to have sixteen to twenty respiratory cycles per minute. But even under these circumstances the circulation could rarely be kept up in a nor- mal state for longer than twelve or fifteen minutes. When the thorax was opened the lungs were seen becom- ing gradually smaller and smaller. In a young dog and in a cat the unopened thorax was also observed getting smaller as soon as respiration was started by the pulmotor. An equili- brium was soon reached, and the respiratory changes in the size of the thorax apparently took place then within the normal expiratory diameters. The respiratory changes in the tracheal manometer would often be only from a more to a less nega- tive pressure, never positive. The changes in the tracheal pressure amounted often only to 30 or 40 millimeters of water. When the thorax was opened, after the pulmotor had been used for a while, the lungs often presented an uneven appear- ance, small collapsed areas alternating with much dilated areas. After connecting with the ordinary laboratory respiratory ap- 276 APPENDIX paratus this unevenness soon disappeared. When the pulmotor was connected directly with a tracheal tube respiration was kept up in a more reliable way, especially in cats and rabbits. \\'hen regulating the respiration by hand air often entered the stomach. Pressure upon the trachea or larynx rather pre- vented the entrance of air into the lungs and increased its en- trance into the stomach. These observations on animals indicate that there are two factors which interfere with the efficiency of the pulmotor as a reliable device for artificial respiration. The first is its auto- matic activity and the ease with which inspiration is turned into expiration. Inflation and deflation of a bag — the method used by agents to demonstrate the action of the pulmotor — is deceptive, because the bag, unlike the air passages of the body, offers no resistance until full. As soon as the inspiratory blast meets an obstacle in the air passages it is automatically cut off and turned into expiration, and thus frequently no efficient inspirations are performed. In lower animals, certainly, the blast often meets obstacles while passing from the pharynx into the alveoli, and the inspiratory pressure of the automati- cally working pulmotor is in many cases insufficient to over- come them. AA^hen guided by hand the inspiratory pressure is permitted to increase; hence the greater efficiency under these circumstances. The second harmful factor brought out by these experi- ments is the performance of expiration by suction. In normal respiration expiration is accomplished by a power which does not suck, but drives the air out by the elasticity of the dis- tended or compressed tissues, aided, sometimes, by muscular contraction. The finer bronchioles have no cartilages; when air is sucked out from the trachea and larger bronchi, the bronchioles are liable to close before the suction reaches the alveoli. Furthermore, when the air is actively sucked out the APPENDIX 277 walls of many of the bronchioles and alveoli are liable to col- lapse and stick together, so that the next inspiratory pressure, which is barely sufficient to overcome the elasticity of the lung, is not strong enough to overcome the resistance offered by the adherent surfaces. The successive additional respiratory changes may therefore take place largely in the bronchial tree and not sufficiently in the alveoli; that is, there may be a les- sened exchange of gases while the movements of the thorax still simulate normal respiration. Hence failure of the circu- lation ensues with diminution of the size of the lungs and the thorax. This obstacle, however, need not remain permanent. After several attempts an inspiration may finally succeed in driving air into all the isolated alveoli or into many groups of them; hence the occurrence of changes in the respiratory rhythm of some animals, and the uneven appearance of the surface of the lungs in others. On the other hand, in some one or other individual animal the passage into the larynx, the organization of the bronchial tree, etc., appear to be well adapted to the rhythm of the pulmotor, which therefore may be capable of keeping up the respiration of such an animal even when it is completely curarized. Finally observation shows that the entrance of air into and escape of air from the stomach may cause movements of the thorax which simulate respiration while actually no air enters or leaves the bronchial tree. Upon the basis of these observations the conclusion was reached that the automatic mechanism of the pulmotor, while being an ingenious technical contrivance, instead of assuring artificial respiration, may interfere greatly with its efficiency, because it is liable to cut off inspiration prematurely. The management of the changes in the phases bf respiration when the pulmotor is worked by hand is more reliable. But when handled in this manner no practical difference exists between 278 APPEXDIX the pulmotor and the Dr. Brat apparatus, at least so far as the mechanism is concerned. In both machines, howe^-er, the ex- piration is accompHshed by suction, which is again a serious defect. The sucking action of these devices might prove even dangerous if they were used continuously to keep up respira- tion for a long time. In connection with the experiments on animals, which in most instances could be continued a rela- tively short time only, it is pertinent to recall the fact that the successes reported by the physicians connected with the Car- negie Steel Corporation were obtained in cases in which- the pulmotor was used for a short period only. That both machines are heavy, expensive, and waste a great deal of oxygen, with which they are not sufficiently pro- vided, are minor points in their disfavor. The absence of careful analysis of the action of the pulmotor in clinical cases, the ease with which it may fail to cause inflation of the lungs, the bad effects which occur if its sucking action in expiration is permitted to continue for a long period, are all important considerations which should be taken into account in judging the instrument. A\'hen they are taken into account the high credit given the machine in popular opinion seems not to have a substantial foundation. In view of the facts obtained by a study of the Dr. Brat apparatus and the pulmotor the members of the subcommittee agreed upon the following suggestions : In cases without any respiration the pulmotor should be used only when guided by hand and then not faster than twelve to fifteen complete res- pirations per minute; when left to run automatically it is liable to be inefiicient and dangerously deceptive. Because of suction on the lungs neither the pulmotor nor the Dr. Brat apparatus should be used longer than for a few minutes (five to six) at a time, and, if there be no better contrivance, should be alter- nated with the Schafer method combined with oxygen inhala- APPENDIX 279 tion. In cases of slow and stertorous breathing, however, both machines can probably be used for a longer time with benefit and without danger. Dr. Meltzer's Mechanical Method of ArtiUcial Respiration About a year ago Dr. Meltzer published a brief communi- cation on pharyngeal insufflation as a method of artificial respiration. It was based upon the following considerations : When air is insufflated into the pharynx it may escape from there through the nose, the mouth, into the stomach, and into the lungs. In order to have it enter the lungs the facilities for escape through the other exits must be prevented or greatly reduced. The escape through the nose was practically pre- vented by the elastic tube in the pharynx which raised the soft palate and thus shut off the exit into the nasopharynx. The escape through the mouth was sufiffciently restricted by apply- ing pressure under the chin. The evil effects of the entrance of air into the stomach were met by two methods : In one a tube was introduced into the stomach; this tube restricted on the one hand the entrance of air into the esophagus, and on the other hand readily re- moved the surplus air from the stomach. In the other method a heavy weight was placed upon the abdomen, which effec- tively restricted the entrance of air into the stomach and pre- vented its passage into the intestines. The inspirations were thus provided for by rhythmical insufflations through a cathe- ter, the inner end of which was placed in the pharynx, while the outer end was connected with hand bellows or a respiratory apparatus. The expirations took place during the pauses be- tween the insufflations by the elastic recoil of the extended ribs and of the compressed abdominal viscera. The expired air escaped through the mouth alongside the tube. Experi- ments on curarized animals (dogs, cats, rabbits, and monkeys) 28o APPENDIX have shown definitely that pharyngeal insufflation as described above is capable of keeping up efficient artificial respiration for many hours. When Dr. Meltzer later attempted to apply this method on human beings he found that it failed to work ; here the insuf- flated air escaped so readily through nose and mouth that the remaining pressure was insufficient to produce an inspiration. Furthermore, pharyngeal insufflation in its original form did not sufficiently provide for getting rid of the expired air. Dur- ing the past year the method has been improved, and as a re- sult the following simple and effective devices are suggested (see Journal of the American Medical Association, 19 13, Ix, p. 1407) : Two methods may be used to convey the air to the respira- tory passages — the pharyngeal and the mask methods. In the pharyngeal method insufflation takes place through a metal pharyngeal tube which has been made to fit the human anat- omy. The tube (see Fig. i) measures about four centimeters transversely and three centimeters vertically; the lower (tongue) side is flat, while the upper (palate) side is round. The upper side is longer than the lower. When the tube is in- serted the end of the upper side should touch the posterior wall of the pharynx, while the lower side terminates at about the root of the tongue. The entrance to the nasopharynx is thus closed, while air enters freely into the lower pharynx. The size of the tube almost completely prevents the escape of *air through the mouth. The outer end of the tube carries a neck for connection with the respiratory apparatus, and has a hole through which a well-fitting tube can be introduced into the stomach. When not used this hole is kept closed by a movable plate. The neck of the pharyngeal tube is connected by means of a short piece of strong rubber tubing with the proximal end APPENDIX 281 of the "respiratory valve" (see Fig. i). This Httle device is a metal cylinder containing a valve which is readily moved by a ring outside. When the ring is moved to the right, air or oxy- gen passes through the cylinder in the direction of the pharynx, thus causing an inspiration. When the ring is moved to the left, the cylinder is closed for the inspiratory air or oxy- gen, and instead an opening is made above the valve through Fig. I. — Arrangement of the Meltzer Apparatus rbR Artificial Res- piration. P. T., pharyngeal tube. R. V., respiratory valve. The ring turns the valve; turning to the right (facing the pharyngeal tube) brings an inspiration and to the left brings an expiration. B, foot- bellows. S. v., safety-valve. The bottle of the safety-valve should be shorter and have a wider diameter than the one in the figure ; it is less likely to turn over. S. T., stomach-tube introduced through the opening in the pharyngeal tube. which the expiratory air can readily escape. The cylinder can be conveniently held in the hand and the ring moved to right and left by the thumb. The distal end of the respiratory valve is connected either with foot bellows, which give practically a continuous air current, or with an oxygen tank. A safety valve is interpolated between the source of pressure and the respiratory valve; some heavy weight and a strong belt to compress the abdomen complete the outfit. 282 APPENDIX The procedure is as follows: (see Fig. 2) (i) Heavy weights should be placed upon the abdomen, (The pressure may be reinforced by a belt. A broad belt alone is insuffi- cient.) (2) The tongue should be pulled out by means of proper tongue forceps, and the pharyngeal tube inserted as far as it may go. For the sake of being in readiness, the respira- tory valve should be kept attached to the pharyngeal tube. ^ V li t N Fig. 2. — Meltzer Apparatus in Use. M., mask. Infl., tube for inflating the rubber ring around the rim of the mask. R. V., respiratory valve. S. v., safety-valve. An oxygen cylinder provides here the insufflation pressure. The figure shows also the weight on the abdomen and the belt around it. The connecting tube should be strong and short (the latter in order to have the expiratory dead space as short as possible. (3) The distal end of the respiratory valve should be con- nected with the apparatus supplying the pressure, i. e., bellows or oxygen tank plus safety valve. The respiratory valve should now be turned for two to three seconds to the right and as long to the left. Respiration should not be repeated more frequently than twelve to fifteen times per minute. In case of necessity the same man may work with his hand the respiratory valve and APPENDIX 283 with his foot the bellows ; and if there are no weights at hand he may rest part of his own weight upon the abdomen of the victim. In case of collapse and suspension of respiration dur- ing an abdominal operation, when no weights can be placed upon the abdomen, a large stomach tube (33, French size) should be pushed through the opening in the pharyngeal tube ; it will slip down readily into the stomach and render the neces- sary service. It would probably be better to do this in every case, but untrained laymen, who in most cases may have to render the first aid, might hesitate to insert the stomach tube. The pressure upon the abdomen may likewise render good service to a failing circulation. Experiments on lower animals show that in failing circulation strong pressure upon the ab- domen raises the blood pressure effectively and fills the heart, and thus also, of course, may benefit the medulla. When a suitable pharyngeal tube is not at hand, artificial respiration may be executed with the aid of a well-fitting face mask provided with a tube for connection with the respiratory valve. All other parts needed for artificial respiration are the same as with the pharyngeal tube, except that no stomach tube can be introduced. No time should be lost in fastening the mask; it should be pressed to the face with one hand, while the other hand is working the respiratory valve, until more help is obtained. Both methods have been tried on numerous animals and have been demonstrated, keeping animals alive for many hours while under the exacting conditions of curare and ether and of opened thorax. The methods have also been proved effi- cient in causing inflation of the lungs in cadavers in rigor or after hours on ice. Even when rigidity of the walls obscured external movements auscultation demonstrated clearly the en- trance of air into the lungs. Especially in cases dying with pulmonary edema, the rhythmical crackling which could be 284 APPENDIX readily heard was very convincing. The pharyngeal tube seemed to work somewhat more efficiently than the mask method. The apparatus which Dr. ]\Ieltzer has devised has the fol- lowing commendable features : ( i ) Its positive action is de- termined by the operator, and not left to a mechanism which may fail to operate. (2) It is free from the sucking action during expiration. Expiration results from the natural recoil of the disturbed parts. (3) It is light. (4) It is relatively inexpensive. (5) It is simple. (6) It embodies in a form which can be used by laymen a method of artificial respiration which has been employed for many years in scores of labora- tories and on thousands of animals, and is known to be effec- tive and free from danger. These are virtues which stand out prominently at points where present commercial devices are in fact most defective. The Commission therefore recommends this apparatus as a satisfactory means of continuing artificial respiration and sug- gests that in cases of suspended breathing the modified prone pressure method be supplemented as soon as possible by the use of the IMeltzer apparatus. 'Drs. W. B. Cannox, Chairman George W. Crile Yaxdell Henderson S. J. AIeltzer Edward Antony Spitzka A. E. Kennelly Elihu Thomson \Y. C. L. Eglin W. D. AA'eaver, Secretary Members of the Commission APPENDIX 285 REPORT OF THE COMMISSION ON RESUSCITA- TION FROM MINE GASES The Committee on Resuscitation from Mine Gases, which was appointed in June, 19 12, has visited mines in the soft and hard-coal regions in Pennsylvania, has met and had discus- sions with men engaged in first-aid work, has witnessed dem- onstrations of methods of giving artificial respiration, has ex- amined critically these methods, has studied old and new de- vices to maintain breathing, and as a result herewith offers a review of its findings, and some suggestions which, the Com- mittee believes, will increase the chances of reviving victims of mine accidents. Two classes of accidents requiring methods of resuscita- tion occur in mines : ( i ) shocks from the electric current, and (2) poisoning or suffocation by mine gases. Although the present Committee was not asked to consider means of resuscitating victims of electric shock, most of its members have also been members of a Commission on Resuscitation from Electric Shock and have had to deal with both problems. And in some respects the matters of primary importance in both conditions are the same. Thus in electric shock respira- tion may be suspended or the heart may become ineffective from weakness or fibrillary contraction, and in consequence the body is not supplied with oxygen. Lack of oxygen in the tissues is also the fundamental difficulty in persons overcome by mine gases. Deprivation of oxygen for about ten minutes may injure irremediably some of the most essential nerve cells of the brain. In both conditions, therefore, the prime neces- sity for promoting survival is the prompt supply of oxy- genated blood. From this it follows that, when spontaneous breathing has stopped, methods of artificial respiration are the most valuable means of bringing back a normal condi- 286 APPENDIX tion of the body. And yet not all methods are equally useful for this purpose, even though they may cause an equal ventila- tion of the lungs. The reasons for this statement will become clear if we consider the various conditions of accident which bring about a serious diminution of oxygen in the tissues. Simple Asphyxiation. — If in electric shock the nervous con- trol of the muscles of respiration is temporarily paralyzed, the heart continues for a few minutes to pump blood through the body, but because the blood is not supplied with oxygen the heart soon stops beating effectively and the victim dies of asphyxia. The same result follows in drowning, and likewise in sufifocation when carbon dioxid or excess of nitrogen has largely replaced the oxygen of the atmosphere. In such cases artificial respiration, in which the lungs are at once adequately supplied with ordinary air, is a sufficient treatment. Carbon Monoxid Poisoning. — If the victim has been over- come by carbon monoxid (CO), the principal poisonous sub- stance in illuminating gas and in the gases after mine explo- sions, the case is somewhat different. The poisonous charac- ter of this substance depends primarily upon its strong chem- ical affinity for the hemoglobin of the blood — the substance which normally transports from the lungs through the body the oxygen used by the tissues. The affinity of CO for hemo- globin is between two and three hundred times as great as that of oxygen for hemoglobin. Carbon monoxid, however, does not form a permanent combination with hemoglobin any more than does oxygen, but unites with it or separates from it according to the law of mass action in amounts determined by the partial pressure of oxygen and CO in the atmosphere breathed. A\'hen a miner after a dust explosion, or a person in a room into which gas is escaping, breathes for a number of hours an atmosphere containing a small amount of CO, a con- dition of partial saturation of the hemoglobin is attained. APPENDIX 287 Thus, if air containing only o.i per cent, of CO is breathed continuously, it will, because of its great affinity, unite with about half of the hemoglobin of the blood. The hemoglobin combined with CO cannot transport oxygen, and the subject is thus brought into a condition of partial suffocation. Since the demands of the tissues for oxygen vary with their activity the first effect is a lessened ability to work. Walking becomes difficult, then impossible; after a time consciousness is lost; and ultimately, unless the subject is removed from the at- mosphere, death from asphyxiation ensues. If before death the subject is brought into an atmosphere free from CO, the combination between this gas and hemo- globin immediately begins to break up. The separation is more rapid if pure oxygen is breathed. Even if merely air is breathed the hemoglobin may thus after ten or fifteen minutes be freed to a degree sufficient to transport the necessary amount of oxygen, i. e.j, the percentage saturation of hemo- globin with CO may be reduced below the danger point. Usu- ally within six or eight hours practically all the CO is elimi- nated, and the hemoglobin is then just as efficient for the trans- portation of oxygen as if the subject had never been poisoned. In spite of the elimination of CO, however, in a large per- centage of cases the subject does not recover. He may die during the next few days, or weeks, or may continue to live with impaired sight or disturbed mentality. These effects, however, according to available evidence, are in the main not due to direct poisonous action of CO, but to deprivation of oxygen. Men employed in gas works and constantly breathing amounts of CO insufficient to interfere with oxygen transpor- tation by the blood do not show cumulative ill effects, and in animals which have no hemoglobin CO is an entirely inert gas. Thus insects in an atmosphere containing even a high per- centage of the gas are quite unaffected so long as there is a 288 APPENDIX percentage of oxygen present reasonably equivalent to that in the air. Furthermore, as Haldane has shown, a mouse just overcome by CO recovers quickly and will even run about, if exposed to two atmospheres of oxygen in a pressure chamber, so that a quantity sufficient to supply bodily needs can be car- ried by the blood in simple solution. Such a mouse removed to air may suffer a recurrence of symptoms if it has not breathed the oxygen long enough to set free from CO a sufficient amount of its hemoglobin. In persons dying as the result of CO poisoning the blood, if they have survived more than twelve hours, usually contains no noteworthy amount of this gas. What, then, is the cause of death? At autopsy such cases exhibit distinct areas of cell de- generation in the brain. From this and other evidence, it is clear that the fatalities are the result of an insufficient oxygen supply during the time the subject was breathing the at- mosphere containing CO. If the pathological changes are well started no amount of oxygen, nor any other treatment, can restore the damaged nerve cells. If they have not been much damaged, recovery may follow even without therapeutic as- sistance. There is, perhaps, no class of cases of disease, or any form of poisoning, in which it is so difficult for even an expert to decide with any degree of accuracy whether such treatment as was given played any considerable part in the re- covery of the patient. A large number of cases of illuminat- ing gas poisoning which happen in all American cities in which a high percentage of water gas is used recover spontaneously. The subject is found in the morning in a room smelling strongly of gas, unconscious, breathing stertorously, with eyes half closed and rolling, and with teeth frequently clenched. The person making the discovery turns off the gas, opens the windows, and telephones for the doctor and for the ambu- lance. By the time such assistance arrives the mere breathing APPENDIX 289 of fresh air has already reduced the amount of CO in the blood so that the hemoglobin set free is sufficient to transport the oxygen that the patient needs. If the degenerative process in the brain cells has not been started before the patient was dis- covered, recovery ensues. If, on the other hand, the amount of hemoglobin combined with CO exceeded a figure between 60 and 70 per cent., so that only 30 or 40 per cent, of the hemo- globin was available for the transport of oxygen, and if the patient has been in this condition for half an hour or more, degenerative processes and death or serious nervous or mental impairment will certainly follow. At the time when the pa- tient is discovered, or even for an hour or more thereafter, it is quite impossible for anyone to state whether the degree of poisoning has passed the danger point. The subject may be profoundly unconscious, and not only apparently, but actually, at the point of death, and yet, if the length of time during which the deficient oxygenation of the brain cells has contin- ued has not been too great, a half hour in the fresh air will be enough to effect an apparently remarkable recovery. It is a natural mistake for the attending family or ambulance physi- cian to regard the recovery as due to his efforts, when, as a matter of fact, it might have occurred if he had done nothing whatever. It is altogether probable that many of the brilliant recoveries, claimed in the newspapers as due to this or that de- vice, occurred in the victim's breathing spontaneously, and therefore not requiring artificial respiration. As in simple asphyxia, however, so also in carbon monoxid poisoning, there is a critical period beyond which recovery is out of the question. It is of the utmost importance in every case, therefore, to supply the cells with oxygen as soon as pos- sible, on the chance that the critical period has not been reached. And because the surrender of carbon monoxid by hemoglobin proceeds more rapidly when pure oxygen is 290 APPENDIX breathed, and, further, because breathing pure oxygen increases the supply to the tissues by increasing the amount dissolved in the blood, the proper treatment for CO poisoning is the breathing of oxygen. If the victim, though unconscious, is breathing in nearly the normal manner, he may be allowed to inspire the oxygen himself. If the breathing is slow and ir- regular, or if it has stopped entirely, as may be the case in sud- den exposure to concentrated CO, artificial respiration should be performed, but with the administration of oxygen. In both simple asphyxia and in asphyxia from CO2 and CO, therefore, artificial respiration may be essential to recov- ery of the victim. A consideration of the efficiency of dif- ferent means of artificial respiration is obviously important. Two general methods of producing artificial respiration are advocated : ( i ) the manual method, which can be utilized wherever the air is good by any intelligent adult, and (2) the mechanical method, by which the lungs are inflated by pump- ing air or oxygen into them. These two general methods will be considered in turn. (Note. — The description of these methods has already been given in the Report of the Commission on Resuscitation from Electric Shock.) Members of the Commission Drs. W. B. Cannon, Chairman George W. Chile Joseph Erlanger Yandell Henderson S. J. Meltzer ' APPENDIX 291 RULES FOR RESUSCITATION FROM ELECTRIC SHOCK RECOMMENDED BY COMMISSION ON RESUSCITATION FROM ELECTRIC SHOCK ' Dr. W. B. Cannon, Chairman Professor of Physiology, Harvard University Dr. George W. Crile Professor of Surgery, Western Reserve University Dr. Yandell Henderson Professor of Physiology, Yale University Dr. S. J. Meltzer Head of Department of Physiology and Pharmacology, Rockefeller Institute for Medical Research Dr. Edw. Anthony Spitzka Director and Professor of General Anatomy, Daniel Baugh Institute of Anatomy, Jefferson Medical College Mr. W. C. L. Eglin Past-President, National Electric Light Association Dr. a. E. Kennelly Professor of Electrical Engineering, Harvard University Dr. Elihu Thomson Electrician, General Electric Company Mr. W. D. Weaver, Secretary Editor, Electrical World Copyright, 19 12 National Electric Light Association Permission to reprint will he granted on application 1 Reprinted by permission. 292 APPENDIX Superintendents, foremen, and others having charge of men are advised to give practical instruc- tions and demonstrations on the use of these rules to all old and new employees. Physicians who may be called upon in cases of shock should be given copies of these instructions and, where practicable, placed in communication with the physician of the electrical company. The prone-pressiire method of artificial respiration de- scribed in these rules {Section III) is equally applicable, after clearing the mouth and throat of froth, to resuscitation of the apparently drozmied, and also to cases of suspended respira- tion due to inhalation of gas or to other causes. Treatment for Electric Shock An accidental electric shock usually does not kill at once, but may only stun the victim and for a while stop his breath- ing. The shock is not likely to be immediately fatal, because : (a) The conductors may make only a brief and imper- fect contact with the body. (b) The skin, unless it is wet, offers high resistance to the current. Hope of restoring the victim lies in prompt and continued use of artificial respiration. The reasons for this statement are : (a) The body continuously depends on an exchange of air, as shown by the fact that we must breathe in and out about fifteen' times a minute. (b) If the body is not thus repeatedly supplied with air, suffocation occurs. APPENDIX 293 (c) Persons whose breathing has been stopped by electric shock have been reported restored after artificial respiration has been continued for approximately two hours. The Schafer, or "prone pressure" method of artificial res- piration, slightly modified, is illustrated and described in the following resuscitation rules. The advantages of this method are: (a) Easy performance; little muscular exertion is re- quired. (b) Larger ventilation of the lungs than by the supine method. (c) Simplicity; the operator makes no complex motions and readily learns the method on first trial. (d) No trouble from the tongue falling back into the air passage. (e) No risk of injury to the liver or ribs if the method is executed with proper care. Aid can be rendered best by one who has studied the rides and has learned them by practice on a volunteer subject. Instructions for Resuscitation Follow these Instructions Even if Victim Appears Dead I. — Break the Circuit Immediately I. With a single quick motion separate the victim from the live conductor. In so doing avoid receiving a shock your- self. Many have, by their carelessness, received injury in try- ing to disconnect victims of shock from live conductors. Observe the Following Precautions (a) Use a dry coat, a dry rope, a dry stick or board, or any other dry nonconductor to move either the victim or the wire, so as to break the electrical contact. Beware of using 294 APPENDIX metal or any moist material. The victim's loose clothing, if dry, may be used to pull him away ; do not touch the soles or heels of his shoes while he remains in contact — the nails are dangerous. (b) If the body must be touched by your hands, be sure to cover them with rubber gloves, mackintosh, rubber sheeting, or dry cloth; or stand on a dry board or on some other dry insulating surface. If possible, use only one hand. If the victim is conducting the current to ground, and is convulsively clutching the live conductor, it may be easier to shut off the current by lifting him than by leaving him on the ground and trying to break his grasp. 2. Open the nearest switch, if that is the quickest way to break the circuit. 3. If necessary to cut a live wire, vise an ax or a hatchet with a dry wooden handle, or properly insulated pliers. II. — Send for the Nearest Doctor This should be done without a moment's delay, as soon as the accident occurs, and while the victim is being removed from the conductor. The doctors entered on the opposite page are recom- mended : Name ^ Address Telephone Call Name Address Telephone Call APPENDIX 295 Name . Address Telephone Call Name . Address Telephone Call III. — Attend Instantly to Victim's Breathing (i) As soon as the victim is clear of the live conductor, quickly feel with your finger in his mouth and throat and re- move any foreign body (tobacco, false teeth, etc.). Then be- gin artificial respiration at once. Do not stop to loosen the pa- tient's clothing; every moment of delay is serious. (2) Lay the subject on his belly, with arms extended as straight forward as possible, and with face to one side, so that the nose and mouth are free for breathing (see Figure i). Let an assistant draw forward the subject's tongue. If possible, avoid so laying the subject that any burned places are pressed upon. Do not permit bystanders to crowd about and shut ofif fresh air. (3) Kneel straddling the subject's thighs and facing his head; put the palms of your hands on the loins (on the mus- cles of the small of the back), with thumbs nearly touching each other, and with fingers spread over the lowest ribs (see Figure i). (4) With arms held straight, swing forward slowly so that the weight of your body is gradually brought to bear 296 APPENDIX FIG. 1— -INSPIRATION; PRESSURE OFF. upon the subject (see Figure 2) . This operation, which should take from two to three seconds, in list not be violent — internal organs may be injured. The lower part of the chest and also the abdomen are thus compressed, and air is forced out of the lungs. (5) Xow immediately swing backward so as to remove the pressure, but leave your hands in place, thus returning to the position shown in Figure i. Through their elasticity the APPENDIX 297 chest walls expand and the lungs are thus supplied with fresh air. (6) After two seconds swing forward again. Thus repeat deliberately twelve to fifteen times a minute the double move- ment of compression and release — a complete respiration in four or five seconds. If a watch or a clock is not visible, fol- low the natural rate of your own deep breathing — swinging forward with each expiration, and backward with each in- spiration. While this is being done, an assistant should loosen any tight clothing about the subject's neck, chest, or waist. (7) Continue artificial respiration (if necessary, two hours or longer), without interruption, until natural breathing is restored, or until a physician arrives. Even after natural breathing begins, carefully watch that it continues. If it stops, start artificial respiration again. During the period of operation, keep the subject warm by applying a proper covering and by laying beside his body bot- tles or rubber bags filled with warm (not hot) water. The at- tention to keeping the subject warm should be given by an assistant or assistants. (8) Do not give any liquids whatever by mouth until the subject is fully conscious. First Care of Burns When natural respiration has been restored, burns, if seri- ous, should be attended to until a doctor comes. A raw or blistered surface should be protected from the air. If clothing sticks, do not peel it off — cut around it. The adherent cloth, or a dressing of cotton or other soft material applied to the burned surface, should be saturated with picrjc acid (0.5 per cent.). If this is not at hand, use a solution of baking soda (one teaspoonful to a pint of water), or the 298 APPENDIX wound may be coated with a paste of flour and water. Or it may be protected with a heavy oil, such as machine oil, trans- former oil, vaselin, linseed, carron, or olive oil. Cover the dressing with cotton, gauze, lint, clean waste, clean handker- chiefs, or other soft cloth, held lightly in place by a bandage. The same coverings should be lightly bandaged over a dry, charred burn, but without wetting the burned region or apply- ing oil to it. Do not open blisters. INDEX Abdominal aorta, embolism of, Anemia, cerebral, ligation of ex cardinal symptoms of, 112 cause of, 109 followed by ischemic paraly- sis, 133 occlusion of, 108, no diagnosis of, 117 establishment of collateral circulation after, 108, 117 followed by gangrene, 114, "5 of endovascular origin, no prognosis of, 117 treatment of, 121, 122 thrombosis of, symptoms of, "3 Adrenalin, coronary pressure raised by, 239 methods of using, to raise cor- onary pressure, 239, 244 resuscitation by means of, 4 Alcohol, prevention of bed-sores with, 147 Anatomy, surgical, of vascular system of head and neck, 68 Anemia, cerebral, 3, 5, 55, 65, 72, 242, 251 anatomical protection against, 8 ligation of common carotid arteries as a- cause of, 55, 57 ternal carotid artery, effect of, 71 limit of possible duration of life with total, 30, 53 protection against, 6 temporary closure of com- mon carotid, effect of, 65 changes due to, which just fall short of gangrene, 123 changes due to, of the kidney, 210, 214 complete, with complete recov- ery, 143 death of tissue due to, 145 degrees of, produced by vascu- lar occlusion, 14 effect of total, on kidneys, 198 from too tightly tied stitches, 149 fundamental law of, 114 gangrene caused by, 115, 144, 193 infection after, 251 in spinal cord lesions, 146 intestinal, 150, 178, 179 tabulation of experiments on, 177 ischemic contracture due to, 133. 142 local, 250 muscular, accompanied by paralysis, 74 299 300 INDEX Anemia, muscular contracture due to, 134, 136, 137, 138, 143 of central nervous system, 5, 8, 55 of extremities of dogs, 73, 75, 106 of kidney, 195, 196, 210, 212, 214 hemorrhage in, 211 of lower extremities in man, 123 of skin, 147, 149, 250 of spinal cord, 113, 146 of spleen, 214, 219 of voluntary muscles, j'i^, 100, 123, 133 paralysis due to, 73, 74, 133 partial, with complete recov- ery, 143 pressure as a cause of, 142, 144, 149 prevention of local death from, 146 recovery results after varying periods of, 13 required to produce dementia, 14 resistance to, 145 restoration of the higher fac- ulties after, 17, 18 results from, 105, 210, 250 surgical, 71, 133 total, 145, 147, 148 Anesthesia, effect of, on recovery after complete cerebral anemia, 10 resuscitation of animals killed by, 54 Arterial injection of adrenalin, resuscitation by means of, 239 Arteriosclerosis, 72, 124 . Artificial respiration, indications and limitations of, 241 methods for producing, 222 relative efficiency of methods of, 223 resuscitation by means of, 9, 221, 222, 229, 241, 243 Schafer's method of, 22^^, 224, 243 without movement of the thorax, 225 Auditory senses after resuscita- tion, 17, 25 Author's method of resuscitation, 244 Bed-sores, alcohol for the pre- vention of, 147 cause of, 146, 147 low blood-pressure in the for- mation of, 147 mechanism of formation of, 147 prevention of, by alcohol, 146, 147 Blood-pressure, 23, 72, 122, 148, 219, 231, 238 after anemia of the spleen, 219 after resuscitation, 23, 52 effect of simultaneous closure of both carotid arteries on, effect of temporary closure of common carotid on, 65 fall of,_ from anemia, 146, 147 from shock, 146 INDEX 301 Blood-pressure, increase of, in coronary artery as means of resuscitation, 238 by rhythmic pressure on the thorax as means of resus- citation, 231 intracerebral, equalization of, 7 Blood-supply, of brain, 6, 55 occlusion of, by ligation of arteries, 56 of kidneys, changes due to oc- clusion of, 213, 214 Brain, anemia of, 72 blood-supply of, 6, 55, 56 Cardinal symptoms of occlusion of abdominal aorta, 112 Cerebral anemia, 3, 5, 55, 58, 65, 72, 242, 251 anatomical protection against, 8 effect of temporary closure of common carotid artery on, 65 ligation of common carotid as a cause of, 55, 57, 59 limit of possible duration of life with, 53, 242 protection against, 6 Cerebral circulation, effect of ligation of innominate artery on, 56 of common carotid on, 56 Cerebral injury, from intestinal gangrene, 193 from ligation of the carotid arteries, 57, 58, 59, 60, 62 from temporary closure 'of the common carotid, ^y Chloroform, danger in the use of, 238 Circle of Willis, 7, 55, 56, (ij, 68, 7^ Circulation, cerebral, effect of ligation of common carotid artery on, 56 effect of ligation of innomi- nate artery on, 56 collateral, establishment of, after occlusion of abdomi- nal aorta, 108, 117 in kidneys after ligation of the renal artery, 197 effect of temporary closure of the carotid artery on, d^i in kidneys, 195 changes due to occlusion of, 196 Common carotid artery, effects of closure of, 65, 6(i, 67, 72 ligation of, 55, 56, 57, 59, 65, 69, 70 Common femoral artery, ligation of, 123, 124, 127, 128 Common iliac artery, ligation of, 123, 125 Coronary pressure, means of raising, 238, 239 Degeneration, of muscle fibers due to anemia, 73, 105 of nerve fibers, ascending and descending, 31 in pyramidal fasciculi, 31 Degrees of anemia produced by vascular occlusions, 14 Delirium cordis, 230 Dementia, anemia as a cause of, 14 302 INDEX Diag'nosis of occlusion of ab- dominal aorta, 117 Edema due to occlusion of ab- dominal aorta, 116 Embolism, causing muscular con- tracture, 135, 137 from ligation of the common carotid, 59 from temporary closure of the common carotid artery, 67 of the abdominal aorta, 112 cause of, 109 of the brachial artery, 135 Esmarch bandage, 75 External carotid artery, ligation of, 71 temporary closure of, (ij External femoral artery, ligation of, 130 Faculties, slow return of, after complete anemia, 17, 18 Flechsig's fasciculus, 31 Fractures, treatment of, 144, 145 Fundamental law of anemia, 114 Gangrene after occlusion of the abdominal aorta, 114 cerebral symptoms in death from, 193 from anemia, 144, 193 from ligation of common iliac artery, 125 of external iliac artery, 126 of the femoral artery, 128, 130 from saline infusions, 148 intestinal, principle in opera- tions for, 193 occurrence of, 132, 134, 141, 142 Heart, direct massage of, 4, 12, 241, 242 effect of electric shock on, 233 reanimation of, 227, 229, 242 resuscitation of, 233 Hemorrhage, control of, by liga- tion of arteries, 70 from anemia of the spleen, 219 in kidney anemia, 211 ligation of iliac artery after, 124, 127 of the tonsils and pharynx, ligation .of arteries for, 69 Hemiplegia, vascular ligations followed by, 56, 58, 59, 60, 70 _ Hyperemia, 65, 113 Hyperexcitability, following re- suscitation, 16, 29 Hypertonicity of the voluntary musculature, 15 Iliac artery, ligation of, 123, 125, 126, 127 Intestinal anemia, 150, 178, 179 tabulation of experiments on, 177 Intestinal gangrene, principle in operations for, 193 Intestinal obstructions, 192 Intracerebral pressure, equaliza- tion of, 7 Ischemic contracture, cause of, 140, 141, 142 Ischemic paralysis, 133, 141 caused by anemia, 133 Kidney, anemia of, 195, 196, 210, 212 effect of total anemia on, 19S reimplantation of, 195, 196 INDEX 303 Ligation, of common carotid ar- tery, 55, 56, 57. 59. 65, 70 cerebral anemia after, 55, 57, 59 cerebral injury after, 57, 59, 60, 62 embolism after, 59 injury to the eyes after, 62 mortality in cases of, 61 technique of, 65 of common femoral artery, 123, 124, 127, 128 of common iliac artery, 123, 125 of external carotid artery, 71 of external femoral artery, 130 of external iliac artery, 126, 127 of external iliac arteries simul- taneously, 127 of innominate artery, effect of, on cerebral circulation, 56 of main arterial trunks as a cause of anemia, 123 of main artery of the limb as a cause of gangrene, 134 of posterior branch of renal artery, 197 Limit, of resuscitation in cases of drowning, ^2 of total cerebral anemia, 53 Methods of resuscitation, au- thor's, 244 of heart, 234 direct, 23 intrathoracic, 234 subdiaphragmatic, 234 transdiaphragmatic, 234 Schafer's, 223, 224, 243 Micturition and defecation after resuscitation, 25 Muscular anemia, accompanied by sensory paralysis, 74 functional recovery after, 74, 105, 123 paralysis due to, 105 Muscular contracture, from an- emia, 134, 136, 137, 138, 143 from nerve injury, 140, 143 from pressure, 138, 140, 143 Muscular movements, during re- suscitation from anemia, 17 reflex, return of, after recov- ery from anemia, 15 spontaneous incoordinate, after recovery from anemia, 15 Necrosis, aseptic, 147, 250 of cortex from ligation of posterior branch of renal artery, 197 Occlusion, degrees of anemia produced by vascular, 14 of abdominal aorta in man, 108 Olfactory sense after resuscita- tion, 25 Paralysis, from anemia, y% 74, 105, 133 ischemic, following embolism of abdominal aorta, 133 resulting from ligations, 63 Paresthesia, 113, 114, 135 Phonation, return of, after re- suscitation, 25 Pott's fracture, 141 304 INDEX Pyramidal fasciculi, fiber degen- eration in, due to anemia, 31 Raynaud's disease, 117 Reanimation of the heart, meth- ods of, 229, 242 Recovery, complete, after partial anemia, 143 after total anemia, 143 effect of anesthesia on, 10 functional, after muscular anemia, 74, 105, 123 Recovery experiments, technique of, 10 Recovery results after complete anemia for varying peri- ods, 13 Reflex muscular movements, 15 Reflexes, return of, after resus- citation, 24 after restoration of the cir- culation, 53 sequence of return of, after anemia, 15 Respiration, following resuscita- tion, 20 return of, as result of direct massage of the heart, 12 Resuscitation, 251 adrenalin-saline infusion for, 241 arterial injection of adrenalin, as means of, 239 artificial respiration as means of, 4, 9, 221, 241 author's method of, 244 blood-pressure after, 52 by adrenalin in saline intra- vascular infusion, 4, 244 Resuscitation by direct massage of the heart, 4, 239, 242, 244 by injection of saline solution, 4 by rhythmic pressure on the chest, 4 over the heart, 9 course of events after, 16 from complete anemia, 17 muscular movements in, 17 from death on the operating table, 245 from drowning, ^2, 245 ' in relative death, 221 of animals killed by anesthesia and asphyxia, 9, 54 of a body as a whole, 4, 220, 241 methods of, 241 of circulatory apparatus, 226 of dogs after relative death, 8, 227 of heart, by direct methods, 233 intrathoracic, 234 subdiaphragmatic, 234 transdiaphragmatic, 234 by electrical stimulation, 232 of electrocuted dogs, 245 of respiratory apparatus, 221, 225 raising coronary blood-pres- sure as means of, 238 respiration following, 20 Schafer's method of, 223, 224, 243 special phenomena following, 20 Resuscitation Committee, Fifth, 223 INDEX 305 Saline infusions, sequence of events after use of, 148 Saline intravascular infusion as means of resuscitation, 4 Schafer's method for giving arti- ficial respiration, 22^, 224, 243 Sensory paralysis accompanying muscular anemia, 74 Shock, blood-pressure in, 146 Skin, anemia of, 147, 149, 250 Spastic condition after resuscita- tion from complete ane- mia, 17 Spinal cord, anemia of, 113, 146 Spleen, anemia of, 214, 219 Temperature following resusci- tation from anemia, 25 Thrombus, after ligation of carotid arteries, 59, 60 cause of, in occlusion of ab- dominal aorta, 113 Toxemia from gangrenous intes- tine, 191, 192 Traumatism, ligation of common femoral artery after, 127, 128 Vascular system of head and neck, surgical anatomy of, 68 Viability of vital centers, 15 Visual reaction in resuscitation from complete anemia, 17, 25 Volhard tube, for artificial res- piration, 226 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