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Introduction

Contents

The Physiologic Effects of Wounds


Introduction

A report is spread that there is, in some country or other, a giant as big as a mountain; and men presently fall to hot disputing concerning the precise length of his nose, the breadth of his thumb, and other particulars, and anathematize each other for heterodoxy of belief concerning them. In the midst of all, if some bold sceptic ventures to hint a doubt as to the existence of this giant, all are ready to join against him, and tear him to pieces.--Attributed to Voltaire

Shock-the Background

Although warriors have died of their wounds from the beginning of time, the first scientific approach to an analysis of how and why they die was made during World War I. In that war the wound surgeon lifted his eyes from the shattered limb to inquire with some degree of precision about the nature of the processes that a wound may initiate in the body as a whole. Because, even if the limb were amputated and every organ of the body was sound, death was likely to occur as the terminal event of a profound disturbance known as wound shock.

World War I revealed wound shock as a complex problem. Its nature was not solved nor were sufficient observational data accumulated to permit clear identification and subsequent analysis. Certain pre-existing hypotheses (vasomotor exhaustion, acapnia, adrenal exhaustion) were discredited, but other concepts inadequately supported by facts (traumatic toxemia, the distinction between shock and hemorrhage) were substituted. These concepts centered on wound shock as an entity not accounted for by hemorrhage, infection, brain injury, blast, asphyxia of cardiorespiratory origin, fat embolism, or any other clearly demonstrable lethal effect of trauma. World War I thus recognized a problem of shock but left it wrapped in mystery.

At the end of World War I the so-called shock problem was transferred to the experimental laboratories of medical science. Attempts were made to resolve it by physiologic and chemical techniques under a wide variety of experimentally induced circumstances. As the methods of initiating experimental shock were multiplied, the term itself became broadened, so that it


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included a number of processes that appeared to have one feature in common--a reduced effective volume flow of blood with inadequacy of the peripheral circulation and resulting tissue asphyxia. In the clinic as well as the laboratory, shock became separated from wounds, and "medical shock," "obstetrical shock," "burn shock," "shock due to infection," and other types were described as entities. So-called shock became synonymous with the process of dying from almost any cause unless death was practically instantaneous or, as Henderson1 stated, "unless one is burned alive." The phrase, "the problems of shocks," was used by Mann2 to describe this confusion of definition.

In the welter of animal experimentation during and after World War I there were certain findings pertinent to the original problem. Bayliss and Cannon3 had imitated wound shock by crushing and lacerating the thigh muscles of anesthetized animals. This was supposed to produce a destruction of tissue but not a very great extravasation of blood. Failure to measure the factor of blood and fluid loss in the local area of trauma (and, as shown later, failure to recognize the superimposed clostridial infection) enabled Cannon4 and other experimenters to propose that toxic products of tissue disintegration were absorbed into the general circulation, causing what was termed traumatic toxemia. Parsons,5 Parsons and Phemister,6 and Blalock7 measured the local blood and fluid loss in traumatized legs by precise methods and showed that it was far greater than had been suspected and quite sufficient to account for the reduction in blood volume observed.

It was thus made clear that estimation of the amount of hemorrhage in an injured man must include the blood extravasated into the tissues as well as that poured on the ground or caught by the dressings. It was also found necessary to consider the blood volume that remained in circulation

    1HENDERSON, Y.: Fundamentals of asphyxia. J.A.M.A. 101: 261-266, July 22, 1933.
    2MANN, F. C.: In Bulletin on Shock, minutes of third meeting of Subcommittee on Shock, Division of Medical Sciences, National Research Council, 18 May 1942, p. 117.
    3BAYLISS, W. M., and CANNON, W. B.: Sections IV, V, and VI in Report VIII, Traumatic Toxaemia as a Factor in Shock, Special Report Series, No. 26, Medical Research Committee. London, H. M. Stationery Office, 1919.
    4CANNON, W. B.: Traumatic Shock. New York, D. Appleton and Co., 1923.
    5PARSONS, E.: Experimental shock and hemorrhage. Tr. A. Resid. & ex-Resid. Physicians, Mayo Clin. (1929) 10: 106-108, 1930.
    6PARSONS, E., and PHEMISTER, D. B.: Haemorrhage and "shock" in traumatized limbs; experimental study. Surg., Gynec. & Obst. 51: 196-207, Aug. 1930.
    7BLALOCK, A.: Experimental shock; the cause of the low blood pressure produced by muscle injury. Arch. Surg. 20: 959-996, June 1930.


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in terms of plasma and red cells, for the proportionate loss of these elements varied under different circumstances. The phenomena of hemoconcentration and hemodilution were thus made understandable. Nevertheless certain investigators insisted on using the physical state of the blood to define shock as an entity, and confusion was introduced by proponents of the thesis that shock could not exist unless hemoconcentration was present.

In a critical review of the shock problem in 1942,Wiggers8 commented that contributions to the literature on shock appeared to be directed toward the support of one or another favored theory. Experimental conditions, he stated, had not been carefully evaluated and conclusions, rather than facts, were emphasized. "Beneficial effects," Wiggers said, "are claimed for various forms of therapy in instances in which it was never shown that the subjects were in a state of shock which would have proved fatal without treatment."

Obvious loss of blood (hemorrhage), or plasma (burns), or water and electrolytes (dehydration), or all elements (trauma) were generally accepted as clearly recognized initiating factors in shock. Beyond these, however, experimenters continued to search for other mechanisms by which the volume of blood returned to the heart might be reduced. Belief in a generalized increase in capillary permeability, a concept introduced with "traumatic toxemia," held sway for years, and many investigators insisted that this, and only this, accounted for the "true" shock that had been witnessed in World War I.

Analysis of the course of events in progressive circulatory failure was pressed in the attempt to identify and define a phase-line that ushered in what was called an "irreversible" state. It had been claimed in World War I that the seriously wounded could be resuscitated by appropriate measures if their condition was attributable to hemorrhage alone, but that if profound shock had been superimposed on hemorrhage or had appeared independently of hemorrhage, all measures, including blood transfusion, were futile. The term "irreversible" was used by some with specific reference to the function of tissues or the closely linked processes of intermediary metabolism. It was used in this sense by the Subcommittee on Shock9 of the National Research

    8WIGGERS, C. J.: The present status of the shock problem. Physiol. Rev. 22: 74-123, Jan. 1942.
    9SUBCOMMITTEE ON SHOCK, Committee on Surgery, Division of Medical Sciences, National Research Council: Shock, p. xxi (Preface). In NATIONAL RESEARCH COUNCIL, DIVISION OF MEDICAL SCIENCES. Burns, Shock, Wound Healing and Vascular Injuries. Military Surgical Manuals, vol. V. Philadelphia, W. B. Saunders, 1943.


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Council: " . . . the process of shock brings about certain changes in the function of the tissues which, after a time, become irreversible."

By others the term "irreversible" was applied to the dynamics of the circulatory system itself. It was held that at some point in the deterioration of the organism in shock the circulatory failure became irreversible and the subject displayed this change by becoming nonreactive to transfusion. "Apparently," as Wiggers10 wrote, "at a certain stage an adequate circulation cannot be restored by merely filling the system as one does an automobile radiator." The same writer expressed his surprise at "how well tissues or organs withstand a very low rate of blood flow before they cease to function or are unable to revive."

Thus the assumption was made that at one moment restoration of blood volume could stay the progress of death, but in the next moment it would be unable to do so. It seemed reasonable to believe that if this phase-line could be identified by experiment and an analysis be made of the physiologic processes then in motion, corrective measures might suggest themselves. But even under precisely controlled laboratory experimentation, minor variations in conditions may determine whether the animal lives or dies. Subtle differences in environmental temperature, anesthetic agents, age, and previous nutritional state of the subject, as well as other conditioning factors make it difficult to halt the cinema of life at a particular frame where one may say: Up to this point continuing life is possible--beyond this, death is inevitable. If difficult in precise experimentation, identification of the onset of irreversible shock becomes impossible when one is confronted by the results of the random trauma sustained by soldiers under combat conditions. Although the diagnosis of "irreversible shock" appeared with some frequency on the clinical records in World War II, it was merely a pretentious way of indicating that the man had died of a lethal wound.

This, then, was the background of our knowledge of wound shock when World War II began. It was entered with the concept that (1) plasma to restore the bulk of the blood in the intravascular space and (2) sodium chloride solution for dehydration and electrolyte depletion of the interstitial space were therapeutic measures adequate to the purpose of adjusting homeostasis in a wounded man. As the war progressed, this concept changed. It soon became clear that much precise information about the physiologic state of a wounded

    10See footnote 8.


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man was wanting, and efforts toward this end culminated in establishment of the Board for the Study of the Severely Wounded in the Mediterranean Theater of Operations. The chronology of events leading to a better understanding of the disturbed physiology of the severely wounded and their management in World War II may be traced through several phases, beginning with the preliminary one of planning for the treatment of shock.

Management of Severely Wounded in World War II

PRELIMINARY PLANNING FOR TREATMENT OF SHOCK

The first problem encountered in the combat area was the need for whole blood transfusion, for while plasma was in plentiful supply, it proved inadequate for the purposes envisioned. An extract from a "Report on the Activities of the Surgical Section of the 77th Evacuation Hospital," dated 10 December 1942, provides a baseline for a review of the planning for the treatment of shock in World War II. This unit shipped from England with Torch Forces and entered on the landing at Oran.

The W.I.A. [wounded in action] had for the most part either succumbed to or recovered from any existing shock before we saw them. However, later traumatic cases came to us in shock and some of the early cases were found to be in need of whole blood transfusions. There was plenty of reconstituted blood plasma available. However, some cases, particularly those with large blood loss, were in dire need of whole blood. We had no transfusion sets, although such are readily available in the United States, no sodium citrate, no sterile distilled water, and no blood donors. Transfusion bottles were borrowed from the British, sodium citrate was purchased from a French pharmacy, a water still appeared from some unexplained source, our enlisted men who had been working long hours volunteered as donors, and whole blood transfusions were given. It would seem that there is grave need of provision for whole blood at the locality and time of definitive treatment.

The initial decision to rely on plasma rather than blood transfusion for the resuscitation of the wounded appears to have been based in part on the view held in the Office of The Surgeon General of the Army, and in part on the opinion of the eminent civilian investigators summoned by the National Research Council to act as advisers to the Armed Forces. The Committee on Transfusions first met on 31 May 1940. The Army representative made the following statement: "If the theaters of operations are mostly outside the United States...the Army would likely discourage the use of


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blood banks. If war should come closer they might want to use blood that could be transported by airplane or specially devised refrigeration. In more distant places where blood could not be collected locally, plasma, either plain or dried, would have to be used." The representative of the Navy also favored "dried blood" (plasma).

The following is quoted from a report of the meeting submitted to the Chairman of the Committee on Surgery, National Research Council, under date of 24 July 1940:

The greater part of the day was devoted to a consideration of whole blood and blood plasma and blood serum transfusions. The consensus of opinion was that the greatest emphasis should be placed on the use of blood plasma for the following reasons: (1) Most instances of shock are associated with hemoconcentration and a given quantity of plasma is more effective than an equal quantity of whole blood in treatment; (2) blood plasma is approximately as effective in the treatment of hemorrhage as is whole blood; (3) the difficulties of preservability and transportability of plasma are considerably less than those of whole blood; and (4) matching and typing are not necessary when pooled plasma (suppression of iso-agglutinins) is used.

The last two reasons given may have been concessions to the position taken by the representatives of the Army and Navy; the first two, however, appear to reflect the prevailing concept of wound shock held by experts at that time. The efficacy of blood in the treatment of hemorrhage had been established in World War I. In small quantities it had been preserved and transported considerable distances, even up to regimental aid posts. It had been recorded that "in cases of profound shock accompanied by loss of blood, excellent results are obtained from direct blood transfusion."11 Robertson12 had cast doubt on the efficacy of various fluids used as "substitutes" for blood in World War I (gum acacia, gelatin) and called attention to the fact that their beneficial effects were often slight. "The only means available of increasing the oxygen-carrying power of the blood is the addition of new red blood cells," he had said. "This constitutes the unique value of blood transfusion." Whole blood transfusion also had become universally employed in surgery in civil life.

It is of real interest, therefore, to inquire into the process of reasoning

    11FRASER, J., and COWELL, E. M.: A clinical study of the blood pressure in wound conditions. Report II, sec. I, Special Report Series, No. 25, Medical Research Committee. London, H. M. Stationery Office, 1919, p. 49-71.
    12ROBERTSON, O. H.: Memorandum on blood transfusion. Report IV, Special Report Series, No. 25, Medical Research Committee. London, H. M. Stationery Office, 1919, p. 143-180.


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that led the Committee on Transfusions of the National Research Council to take the position that "most instances of shock are associated with hemoconcentration and a given quantity of plasma is more effective than an equal quantity of whole blood in treatment." This concept can be traced back to observations on the wounded made in World War I by Cannon, Fraser, and Hooper13 who reported that counts of red cells in blood taken from the capillary bed were high, particularly when compared with those of venous blood. This also was a keystone in the establishment of shock as an entity distinct from hemorrhage and led to the widely accepted hypothesis of a generalized increase in capillary permeability. "Hemoconcentration was found to furnish a practical means for differentiating shock from hemorrhage, but the enormous potential value of this sign was not comprehended by the members of the Special Committee on Wound Shock nor has it been sensed by physicians during the 20 years since that time," wrote Moon14 in 1938. The manual on shock15 (1943), prepared under the auspices of the Committee on Surgery of the Division of Medical Sciences of the National Research Council, also set forth this erroneous concept.

The other statement of the Committee on Transfusions, namely, that "blood plasma is approximately as effective in the treatment of hemorrhage as is whole blood," appears to have found origin in conclusions drawn from laboratory experiments that were purposely designed so that the number of variables could be rigidly limited. Transference of these conclusions to a situation that introduced a number of additional variables was an error of human reasoning. An example may be found in the widely quoted experiments of Rous and Wilson16 (1918). These authors made a precise determination of the limits within which plasma may replace the loss of whole blood in acute hemorrhage induced in rabbits. In summarizing the results of their experiments these authors stated that "however desirable transfusion may be, it is not essential to recovery from even the severest acute hemorrhage, if

    13CANNON, W. B.; FRASER, J., and HOOPER, A. N.: Some alterations in the distribution and character of the blood. Report II, sec. 2, Special Report Series, No. 25, Medical Research Committee. London, H. M. Stationery Office, 1919, p. 72-84.
    14MOON, V. H.: Shock and Related Capillary Phenomena. New York, Oxford University Press, 1938.
    15NATIONAL RESEARCH COUNCIL, DIVISION OF MEDICAL SCIENCES. Burns, Shock, Wound Healing and Vascular Injuries, prepared under the auspices of the Committee on Surgery of the Division of Medical Sciences of the National Research Council. Military Surgical Manuals, vol. V. Philadelphia, W. B. Saunders Co., 1943.
    16ROUS, P., and WILSON, G. W.: Fluid substitutes for transfusion after hemorrhage. J.A.M.A. 70: 219-222, Jan. 26, 1918.


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only the blood bulk can be restored in other ways." The conclusion drawn from this and subsequent observations by others17 led to formulation of the statement by the Committee on Transfusions. The brief description of a rabbit in which up to three-fourths of the blood volume, as measured by the hemoglobin depletion, had been withdrawn and replaced by plasma contains one phrase that is significant: "The least exertion would cause the animal to pant heavily."

Presumably the rabbit had no semblance of a wound other than the needle puncture. Substitute for the rabbit housed quietly in its cage a wounded soldier picked up by litter bearers and transported by ambulance, who has in addition an extensive and painful wound with continuing extravasation of blood and plasma into adjacent tissues. Then add sedation, roentgenographic examination, anesthesia, and surgical operation with a further loss of blood. It is obvious that the introduction of these and other variables, purposely and of necessity excluded from the original experiments, may completely negate the conclusion. Both errors, the association of wound shock with hemoconcentration and the estimation regarding the effectiveness of blood plasma, are understandable in view of the paucity of observations made in World War I concerning the disturbed physiology of wounded men.

Restoration of the blood bulk in the intravascular space by infusion of a colloid solution that might be expected to stay within the confines of the semi-permeable membrane of the capillary walls was envisioned during World War I. This was a projection of the Starling18 concept elaborated by Scott19 in 1916. Tests were made of the properties of soluble starch, dextrin, gelatin, and gum arabic, and preparations of the latter were given extensive field tests, particularly by the British, guided by the basic experiments of Bayliss.20

The advent of human plasma, as a result of the development of methods that enabled it to be preserved and packaged in desiccated form, appeared to provide a final answer to the problem of the restoration of blood bulk by infusion. The treatment of shock and hemorrhage was thus reduced to the simple terms of the exchange of fluid between the intravascular space and

    17BAYLISS, (see footnote 20) for example, had shown that "more than one-half of the blood in the cat can be replaced by gum solutions with satisfactory results."
    18STARLING, E. H.: On the absorption of fluids from the connective tissue spaces. J. Physiol. 19: 312-326, May 1896.
    19SCOTT, F. H.: The mechanism of fluid absorption from tissue spaces. J. Physiol. 50: 157-167, Feb. 1916.
    20BAYLISS, W. M.: Intravenous injections to replace blood. Report I, Special Report Series, No. 25, Medical Research Committee. London, H. M. Stationery Office, 1919, p. 11-41.


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the interstitial space under clearly defined physicochemical laws. Extension of this same reasoning led to the proposal that because the serum albumin fraction of the blood as prepared by Cohn21 packaged a high proportion of the total colloid osmotic activity of the serum in small liquid volume, it was peculiarly appropriate to military needs. It was postulated that the interstitial fluid compartment would provide the necessary diluent unless the patient were badly dehydrated.

This oversimplified physicochemical approach, which was an extension of the World War I quest of Bayliss aided by the availability of refined and human-derived preparations, not only failed to take into account the variables described, but also placed undue emphasis on a single physicochemical property of the blood; namely, the osmotic activity of the plasma proteins. Not only was the important function of the red cells as oxygen carriers ignored, but also their contribution to the total blood mass under abnormal circumstances. Both the magnitude of the initial loss of whole blood occasioned by wounding and the significance of a continuing seepage of blood and its fluid components into the tissue spaces were underestimated. And finally, an effort to restore and maintain blood bulk based on colloid preparations, either derived from human proteins or otherwise, presupposes a space bounded by a semipermeable membrane--not one in which large areas of the membrane may have been rendered freely permeable by the direct effects of trauma.

EVOLUTION OF KNOWLEDGE DURING WORLD WAR II

The evolution of the management of the seriously wounded during World War II may be divided into three phases for purposes of description, although it is apparent that as phases they are not pencilled with the clarity observed in phase-lines on a tactical map. A first phase may be recognized in which efforts to identify the gross nature of the problems and devise immediate solutions predominate. Cobwebs of theory and hypothesis were swept away by simple observations and precise definitions. This was followed by a phase during which all efforts centered on the development and perfection of the practical art of resuscitation. In the final phase systematic and precise meas-

    21COHN, EDWIN J.: Memorandum on the preparation of normal human serum albumin. Report No. 1, Subcommittee on Blood Substitutes, Division of Medical Sciences, National Research Council (acting for Committee on Medical Research, Office of Scientific Research and Development), 11 February 1942.


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urements were made that for the first time described the actual physiologic state of the wounded man as it was observed on the field of battle.

A search among the records of World War II for novel and challenging hypotheses regarding the nature of shock is likely to prove disappointing. The very abundance of facts and experience discouraged "hot disputing" and debate. And yet from this experience emerged certain concepts that, when fully grasped, will be found no less significant because they appear simple and direct.

First Phase: Identification of the Problem

Although in retrospect the North African Campaign was but a brief curtain raiser for the sustained action that was to come later, it stands historically as a period in which the major problems of the management of the wounded were clearly identified. The campaign was over before many needs of the military organization could be met, but the foundation for future action was secured.

The Surgical Consultant, North African Theater of Operations (U. S. A.), reported for duty in Algiers on 7 March 1943. His first official report, submitted under date of 24 March 1943, following a period of temporary duty in II Corps on the southern Tunisian front, was a Memorandum on whole blood transfusion. Further data were collected and a formal report on whole blood transfusion was made to the Theater Surgeon, NATOUSA, on 16 April 1943. The following conclusions and recommendations were made.

Conclusions

a. There is a need for whole blood transfusion in the treatment of a significant proportion of the wounded. Plasma is not an adequate substitute in these cases.

b. Adequate and conventional safeguards that govern blood transfusion are difficult or impossible to attain in forward echelons.

c. The British Base Transfusion Unit has demonstrated the feasibility of supplying large amounts of whole blood to the combat area.

Recommendation

That a central laboratory be established in NATOUSA to provide whole blood, intravenous solutions, distilled water, and plasma.

The Italian Campaign had progressed to the establishment of the Anzio Beachhead before the distribution of preserved blood from a central laboratory


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was realized. In the meantime, however, the evacuation hospitals and later the field hospitals employed for forward emergency surgery were encouraged to establish their own blood banks with supplies requisitioned for that purpose.

Following this decision on therapy, the next important question that faced the Surgical Consultant in southern Tunisia in March and April 1943 was whether casualties were dying of irreversible shock--in fact, whether wound shock, unassociated with hemorrhage and other clear results of trauma, existed as an important problem in World War II. It was obvious that a precise definition was necessary if this question was to be answered, for, as was noted in the Report of the Surgical Consultant dated 2 July 1943:

In Field Medical Records, Case Reports, and Death Reports, as well as in verbal discussions among Medical Officers, the term "shock" is used with vague definition or quite commonly with no definition whatsoever. In the case reports of battle casualties dying in the forward area, "shock" or "irreversible shock" is almost invariably recorded as a secondary cause of death. This is true whether the wounded man had a lethal craniocerebral wound, an overwhelming peritonitis, fulminating gas gangrene infection, or simply died of uncontrollable hemorrhage.

Circulatory failures from peritonitis, bacterial infection, intrathoracic injury, burns, and injury to the central nervous system were placed in separate categories. All other forms of circulatory failure which arise within a few hours as a result of wounding were considered as "wound shock."22 A study was undertaken that covered the course of the evacuation of some 1,263 casualties from the battalion areas through the evacuation hospitals. No record could be found of a death from wound shock under terms of the restricted definition, in which hemorrhage could be excluded as the important factor. The conclusions drawn from this study as well as from direct observation of large numbers of wounded were expressed as follows:23

Under conditions that prevailed in the management of battle casualties between 20 and 25 March in the sampling area of II Corps, wound shock was not a cause of death.

This does not imply that wound shock did not occur among the survivors, but if so it appears that remedial treatment was adequate.

    22The Battle of El Alamein (October and November 1942) was one of the first occasions on which blood and blood substitutes were used on a large scale for the resuscitation of battle casualties in forward medical units. Report No. 1, Medical Research Section, GHQ, MEF, by Lt. Col. W. C. Wilson, RAMC, described the condition of the wounded with special reference to wound shock and its treatment. The necessity for the restricted definition of wound shock was presented with great clarity.
    23Report of Surgical Consultant, Office of the Surgeon, Headquarters, North African Theater of Operations, U.S.A., 2 July 1943. (Appendix B, 1; Par. B, 2.)


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"Irreversible" wound shock does not appear to be a problem of pressing significance.

The problem of shock as observed in the Tunisian Campaign centered in the application of accepted means of treatment, rather than in the need for additional methods of management.

Second Phase: Development of Resuscitation

The second phase in the advancement of understanding of the management of the seriously wounded was development and perfection of the practical art of resuscitation. The many experienced surgeons of the Theater contributed to and shared the responsibilities of a Theater-wide educational program. Special acknowledgment is made of the contributions of Colonel Howard Snyder, Surgical Consultant to II Corps and subsequently to Fifth Army, and of Lt. Colonel Henry K. Beecher, assigned to AFHQ as Consultant in Resuscitation and Anesthesia and working on temporary duty in the forward installations. Simple and direct observations made while actually caring for battle casualties confirmed the conclusions of the Tunisian Campaign and led to the complete discard of the confused theories of traumatic shock that had been elaborated from the experience of World War I.

A highly significant product of the development of the art of resuscitation was merging of consideration of shock with consideration of the implications of the wound. Historically, wound surgery has been linked with the prevention and treatment of infection, and, as a matter of fact, in the less seriously wounded this function of surgery still is predominant. In World War II this concept was modified, as it was not applicable to the many desperately wounded casualties that came under surgical management. It was no longer valid to hold that a seriously wounded man could be resuscitated solely by measures directed toward restoring blood volume, and that when this was accomplished wound surgery could be undertaken, depending only on the time necessary for prevention of infection. Wound surgery under these circumstances assumed the new position of being in itself the climax of resuscitation. General recognition of the principle that procedures commonly grouped as "resuscitative" are but integral steps in the management of a situation that must be viewed as a whole, and that wound surgery may in itself be the most potent act of resuscitation, stands as a basic achievement of military surgery in World War II.

This concept was glimpsed in the Tunisian Campaign and led to the


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following comment in the official report of the Surgical Consultant dated 2 July 1943:

Resuscitation comes to be regarded as a sub-specialty of military surgery and as such becomes a goal in itself. One central fact must be kept in mind and, although it appears obvious, it is often overlooked both in theory and practice. A wounded man is resuscitated not only to save life but to prepare him for necessary surgery.

This divorce of surgeon from shock is a disquieting outgrowth of the war that cannot be too strongly condemned. Resuscitation in every case being prepared for operation is an integral part of the surgical management of trauma and must remain so if optimal results are to be achieved.

The concept was more fully developed during the Italian Campaign by Lt. Colonel Henry K. Beecher24 who presented the following broad definition of resuscitation that includes operation as an essential component:

The enemy has produced the worst wound he could, and its consequences are cumulative--dehydration increased by unusual fluid loss in sweat and vomitus, continuing hemorrhage or plasma loss, pain making rest impossible, increasing emotional exhaustion, developing infection--these and other factors are set in operation by the initial wound. Their progress in the seriously wounded is to be checked in most cases only by surgery or by death. Resuscitative measures give a temporary stay and make successful surgery possible in the severely wounded; but in most cases true release from the consequences of the wound is effected only by surgery. Surgery is not only the goal but is itself a part of resuscitation in the broad sense. Any other view is likely to lead to unfortunate separation between the activities of the "shock team" and those of the surgical team. Care of the wounded man must be continuous and supervision uninterrupted.

This concept now appears obvious, and in fact is a principle soon grasped by the practical worker in the field. It is likely to be overlooked when conclusions are drawn from laboratory experiments purposely designed to isolate and test the efficacy of single therapeutic measures.

The establishment of wound surgery as inseparable from the management of wound shock had many practical applications. It was a strong consideration in the placement of the surgical hospital for treatment of the severely wounded alongside the divisional clearing station, as was determined in Sicily. A short litter carry placed the casualty in the hands of a competent surgical team equipped not only for resuscitation in the conventional sense but for the major procedures of surgery. It led to the close observation of a wounded man's response to blood replacement therapy. If the response was transient

    24BEECHER, H. K.: Preparation of battle casualties for surgery. Ann. Surg. 121: 769-797, June 1945.


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or unsatisfactory, it was not judged that his shock was "irreversible" or that he displayed a "negative reaction" because of widespread capillary damage, or that it was futile to try "to repair the damage done by prolonged oxygen want." It was assumed that either continuing hemorrhage or spreading infection was present, or that a dead limb required amputation or dead tissue called for excision; operation was immediately undertaken with continuing transfusions to support the patient's condition.

Another practical result was that resuscitative measures carried out in the field, forward of a surgical hospital, came to be regarded as temporary and designed only to preserve life during transportation. They thus became both qualitatively and quantitatively different from those combined with surgery. It was necessary to rely on plasma as the chief measure to support the patient during transport, but plasma was used in minimal amounts without intent to restore the blood volume flow to a normal level. The dangers of the overuse of plasma became apparent. Resuscitation within the hospital included use of additional plasma, whole blood, ancillary measures, such as bronchoscopy, oxygen therapy, and nerve block to relieve pain or to restore respiratory effectiveness if crippled by the wound, and initial wound surgery.

Third Phase: Documentation by Scientific Evidence

By the summer of 1944 it was evident that although nearly two years of experience had enabled the Theater to develop the procedures of resuscitation to a high peak of effectiveness, this was largely an accomplishment of the practical art and remained to a considerable extent undocumented by scientific evidence. If left in this status at the end of World War II, it would tend to be forgotten, as are many other practical lessons that emerge from the experience of war. Even the validity of the experience would be open to question. Bayliss,25 toward the end of World War I, had written: "On the whole it is remarkable that so little positive evidence is forthcoming as to the superiority of blood transfusions. Statements are made on the basis of general impressions, rather than on convincing proof. In the nature of the case, such proof would be difficult to provide." The question was often asked whether the experience in Italy was really accepted at face value and whether the precepts that had been formulated would be transferred to the conflict in the Pacific and to civilian needs.

    25See footnote 20.


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EARLY STUDIES

Some data of a precise nature had been obtained, but they were of a fragmentary nature. Lt. Colonel John D. Stewart, a member of the Consulting Surgical Staff of the Surgeon, NATOUSA, while on temporary duty with the Fifth Army in December 1943, made arrangements with the Commanding Officer of the 2d Medical Laboratory, with the concurrence and support of the Surgeon, Fifth Army, to conduct a clinical study of the freshly wounded. A small mobile laboratory was set up at the 3d Platoon of the 11th Field Hospital on 20 January 1944. This platoon was situated near the 36th Divisional Clearing Station, northeast of Mignano, about seven miles behind the front. The objective was to study by formal biochemic methods certain aspects of shock, hemorrhage, and dehydration.

A preliminary report was submitted under date of 17 March 1944. Observations had been made on some 35 badly wounded patients immediately after admission, usually within 12 hours after wounding. A final report of this study, extended to include 100 desperately wounded observed during the first 6 months of 1944, was submitted on 2 January 1945.26 The data indicated (1) absence of hemoconcentration in shock, (2) reduction of blood volume in shock, (3) greater reduction of red-cell concentration than of plasma protein concentration early after wounding, (4) lowering of both red-cell and plasma protein concentration later, and (5) frequency of later dehydration.

During approximately the same period (11 February through 4 June 1944) the Consultant in Anesthesia and Resuscitation, NATOUSA, and Captain Charles H. Burnett carried out an extensive study27 on the wounded at the 94th Evacuation Hospital, observing 557 cases on the Cassino Front (Mignano) and 2,296 cases on the Anzio Beachhead. In the latter site the position of the evacuation hospital bore the same relation to the front as a field hospital. While the greatest significance of this contribution lay in formulating procedure for the clinical management of resuscitation in the seriously wounded, in 37 of the most severely wounded fairly extensive laboratory observations were made. These confirmed the absence of hemoconcentration.

Starting in March 1944 in a field hospital platoon, Captain Joseph J. Lalich,

    26STEWART, J. D.: Observations on the severely wounded in forward field hospitals of the Fifth Army, with special reference to wound shock. Report to the Surgeon, Mediterranean Theater of Operations, U.S.A., 2 Jan. 1945. Also, J.A.M.A. 133: 216-219, Jan. 25, 1947.
    27BEECHER, H. K., and BURNETT, C. H.: Field experience in use of blood and blood substitutes (plasma, albumin) in seriously wounded men. M. Bull. North African Theat. Op. (no. 1) 2: 2-7, July 1944.


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2d Auxiliary Surgical Group, carried out a series of hematocrit and plasma protein determinations by the copper sulfate method. His findings, like those of the other workers, were quickly made available to forward surgeons and were submitted as a formal report on 12 November 1944. Attention was called to the low hematocrit readings obtained from 3 to 5 days after initial surgery despite the very liberal use of blood transfusions in resuscitation. This was a phenomenon that was exciting interest in the general hospitals in Peninsular Base Section. For the success of the vigorous program of reparative wound surgery that was being formulated, it was found necessary to provide for the liberal use of whole blood transfusion at the base.

There was need, however, for a far more comprehensive study. In the opinion of the Medical Research Committee of the Theater there was little doubt that the impetus of the tremendous program undertaken to provide so-called "substitutes" for blood in World War II would be projected into the postwar period. It might be revived with any threat of a future war. It was essential, therefore, that the so-called impressions derived from experience be documented by hard, cold facts about the condition of a freshly wounded man. To this end, everything about a seriously wounded soldier that could be observed and recorded by precise measurement should be ascertained and recorded. The collection of data needed to be extended to a sufficient number of casualties to make the findings conclusive.

ESTABLISHMENT OF BOARD FOR THE STUDY OF THE SEVERELY WOUNDED

The summer of 1944 in Italy was a period of readjustment to meet the over-all strategy of the war in Europe. Between mid-June and the end of July more than a division a week was withdrawn from the forces to train and stage for Operation Anvil, the attack in southern France executed on 15 August. Pursuit of the enemy to the north had brought the Allied armies up against the "Gothic Line," an elaborate defense system in the northern Apennines. Then on 10 September a general offensive was launched to break through into the Po Valley. As it became apparent that the Medical Service was to face a renewed heavy flow of casualties, the Medical Research Committee sponsored certain fact-finding tasks that required concentrated and carefully organized effort for accomplishment. One of these was further analysis of the state of the seriously wounded.

More information was urgently needed regarding the problem of anuria.


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Kidney damage associated with crushing injuries sustained in air raids had been described as a component of the "crush syndrome" by Bywaters et al.28 early in the war. Identification of damaged kidney function as a component of injury in the soldier seriously wounded by flying missiles on the battlefield came slowly, but experience had already suggested that it either was being overlooked or was subject to misinterpretation. Identification was slow because first of all it requires the coordinated effort of a wide variety of expert skills in the forward area to rescue desperately wounded soldiers and keep them alive until such time as suppression of kidney function manifests itself. This involves the activity of the entire medical department from the company aid-man in the field to the surgical team and nursing staff in a mobile hospital. When a gravely wounded man dies within 48 hours of being hit, the chances are that any suppression of kidney function will pass unrecognized.

In the N. R. C. Conference on Shock held on 1 December 1943, Dr. Donald D. Van Slyke had presented a communication on the "Effect of Shock on the Kidney." The concept was developed that the peripheral vascular constriction that compensated for a deficit in the volume of circulating blood in shock may practically stop the blood flow through the kidneys. Urinary excretion stops, and prolonged ischemia may be followed by permanent suppression of renal function. Although presented as a hypothesis, this concept brought a fresh point of view to a clinical problem that was beginning to be identified in the field. Under date of 16 February 1944, a letter, from which the following extract is quoted, was addressed to Dr. Van Slyke by the Surgical Consultant.

By excellent forward surgery and the liberal use of whole blood transfusion as well as plasma, we are saving lives but also keeping certain men alive temporarily only to display the type of kidney damage you describe. This has been either complete anuria with death, or in one case a fall of urinary output to 200 cc. with ultimate recovery of kidney function. As you suggest, this phenomenon is not unique to the "crush" syndrome but may occur in any wounded man who experiences a long period of greatly reduced volume flow.

Delay in the identification of the problem of anuria in battle casualties was not solely a matter of organization or preoccupation with more pressing problems. Recognition of anuria depended on a close check of fluid intake and output, items that are difficult to secure even in well-run civilian hospitals.

    28BYWATERS, E. G. L.; DELORY, G. E.; RIMINGTON, C., and SMILES, J.: Myohaemoglobin in urine of air raid casualties with crushing injury. Biochem. J. 35: 1164-1168, 1941.


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Chemical tests for azotemia were not available in the mobile hospitals. The terminal event of pulmonary edema from forcing fluids in order to correct supposed dehydration was subject to misinterpretation as a manifestation of blast injury or other result of direct trauma to the lungs.

Even when suppression of urinary excretion was recognized, other causes than the specific effects of the injury required exclusion. In the earlier phases of the war medical officers were alerted to the effects of sulfonamide administration on the kidney. Early in 1944 the widespread usage of sulfonamides was still making it difficult to clarify the problem of posttraumatic anuria. This was referred to in the Annual Report of the Surgical Consultant (1943) as follows: "Kidney damage is probably the most frequent and easily overlooked sequel of shock and is manifested by anuria or reduced urinary output. Information relative to renal damage produced by decreased volume flow of blood is particularly desired because of a close linkage with policies on sulfonamide therapy."

Even more important, however, was the use of blood transfusion in resuscitation. The question arose again and again how often blood transfusion itself might be responsible for kidney damage. To interpret posttraumatic anuria, blood given in transfusion must meet rigid specifications. It must be compatible both in type and iso-agglutinin titer. It must be collected and stored in a closed system to avoid contamination. When supplied in bulk in military operation, frequent checks must be made for free hemoglobin content both at the bank, in the forward hospital, and by examination of the recipients' plasma after transfusion.

With the increased use of transfusion in the forward area and the distribution of preserved whole blood from the central laboratory in Naples, the identification of posttraumatic anuria became tangled with that of "transfusion kidney." Informal requests came from Anzio Beachhead for distribution of Type A blood for massive transfusions in this type of recipient. The policy of issuing only Type O blood in which the iso-agglutinins had been titered was adhered to. Blood with titer 1:64 or above was labeled "for O-Type recipients only"; that with weaker iso-agglutinin titer was considered suitable for universal use. The problems of poorly preserved or contaminated blood encountered elsewhere in the field during World War II were not encountered in the U. S. Army, Mediterranean Theater.


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The basic conditions outlined above had been established in Italy by late summer in 1944. The medical department personnel were expert from long experience; penicillin had replaced sulfonamides in the treatment of the seriously wounded; the Theater blood bank was issuing a liberal supply of whole blood that met the required specifications. The total situation, both military and medical, was thus favorable for an intensive study of the seriously wounded soldier. To this end, the Theater Surgeon recommended on 1 September 1944 that a Board to Study the Treatment of the Severely Wounded be appointed by the Commanding General, NATOUSA. Such a board was established on 3 September 1944 and it is the report of this Board which is presented in this volume. In retrospect, it is doubtful that this particular effort would have been feasible at an earlier date; even if undertaken it probably would not have been as productive, for reasons that have been presented.

Selection of the personnel of this Board was a matter of vital importance, and the recommendations of his Medical Research Committee were generously accepted by the Theater Surgeon. It was essential that medical officers be selected who were skilled in the techniques of clinical investigation that can be utilized without harm or discomfort to seriously injured patients. Different phases of the study required precise and critical observations in the laboratory, in the ward tents, and in the operating tent. It was essential that the members of the Board be familiar with the subjects to be studied--seriously wounded soldiers. Those finally selected had long experience in identification of the complex sequelae of wounds, and those in charge of the clinical aspects were experts in the practical art of resuscitation. Further, and most important, all had become expert in the art of overcoming, rather than being frustrated by, the retarding element of "friction" ever present in a huge military undertaking.

It is of more than passing interest to note that the minutes of the first meeting of the Committee on Transfusions of the National Research Council, already referred to, contain the suggestion "that a group of men be allowed to work in the Army, freed from any of the obligations of Army officers, who would study cases of shock as investigators. This would give opportunity to observe shock on a big scale, an opportunity to get an insight into the nature of shock." This was on 31 May 1940. In May 1945, as the Germans in northern Italy capitulated and brought the task of the Board to a conclusion, this objective had been accomplished--not precisely as visualized, but effectively. The


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members of the Board were in no way "freed from any of the obligations of Army officers," but were, on the contrary, selected because they were competent to assume the highest privilege accorded officers--the freedom of individual judgment and action. They were not a group that merely worked "in the Army"; they were of the Army.

                    EDWARD D. CHURCHILL, M.D.
                    (Formerly Colonel, MC, A.U.S., Surgical Consultant, North African-Mediterranean Theater of Operations)
                     

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