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Chapter I

Contents

CHAPTER 1

Internal State of Severely Wounded Men on Entry to the Most Forward Hospital

The effects on the human body of the destructive forces of warfare have been described many times in terms of organic damage and tissue loss. Our concern was rather with the internal state of the severely wounded man. Gross tissue damage is obvious, or becomes obvious on surgical exploration, but our purpose during the first phase of this investigation was to describe the latent consequences of the wound as revealed in impairment of organic function and in abnormalities of the blood and the urine. These initial studies were made shortly after the patient entered the most forward field or evacuation hospital, before either vigorous resuscitative measures or operation had yet been undertaken. The physiologic studies were continued, whenever possible, throughout the patient's course. Other aspects of the investigation as a whole relate to diagnosis, treatment, and pathology of the severely wounded.

The very severely wounded ("nontransportable patients") were those selected for study. They were the most critically wounded or injured battle casualties to reach a forward hospital alive. With few exceptions, chiefly cases of injury,1 the casualties2 studied were from the "wounded in action"3 group. The cases are listed in Appendix D.

    1AR 40-1025, Sec V, par 79a, 12 Dec 44, sub: Definition [of injury]. "The term 'injury' is used here in its broad sense to include such conditions as fractures, wounds, sprains, strains, dislocations, concussions, and compressions, commonly thought of as 'accidents' . . ."
    2ASF Manual M 807, 25 Oct 44, Glossary. "Casualty (Personnel). A soldier who is rendered unavailable for service as a result of disease, injury, or enemy action . . ."
    3AR 40-1025, Sec II, par 26, 12 Dec 44, sub: [Definition of] WIA (wounded in action) cases. "The term will include wounds or injuries incurred as a direct result of a hostile act of a military enemy. It will not include injuries accidentally incurred while in combat, or those incurred on purely training flights or missions."


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TABLE 1.-TIME FROM WOUNDING TO SURGERY, MEDITERRANEAN THEATER OF OPERATIONS
In all, 186 casualties were examined in the most forward hospitals by members of the Board. From previous studies made in the Theater, it was estimated that of 10,073 battle casualties in the area to reach forward hospitals alive during the period of the study, between 201 and 252 were seriously wounded. Hence the 186 studied here may be considered an adequate sample of the severely wounded in the Theater. One hundred and eight of these 186 casualties were seen at the time of admission and were studied rather completely (including blood chemistry and urine analyses) at that time. Account was taken of the nature and type of the wound, and also of the evacuation time, including the distance to be covered and the character of the terrain, since delay along the evacuation trail, the reaction of the patient to his wound, and his response to subsequent management all influence the factors under study and increase the significance of the laboratory data.

In addition to the data obtained as background material, the initial studies included determination of blood loss, of plasma protein and hemoglobin levels, analysis of other biochemic changes encountered, initial kidney function studies, and a study of liver function in the newly wounded man.

It will be observed in the tables and charts of this and following chapters that different groups and varying numbers of patients have been drawn from the total for consideration in given instances. This has been done because it was often found in comparing two or more factors that records were incomplete for the specific comparison in question and had to be omitted. As a re-


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TABLE 1.-TIME FROM WOUNDING TO SURGERY, MEDITERRANEAN THEATER OF OPERATIONS-Continued
sult comparatively small numbers of cases are presented in some instances. No attempt has been made to keep the number of cases uniform in any of the various phases of the study; rather we have presented all the data that were complete for any one phase. This method was considered desirable because of the nature of the study and the exigencies under which it was carried out. In the tables throughout the study the standard error of the mean is shown whenever the data were sufficient to warrant this method of statistical treatment.

Initial Studies

Time from Wounding to Hospital
Entry and Surgery

Although some of the casualties were wounded near the forward hospitals, the majority had to be transported some distance, often over mountainous terrain, by litter carry or motor transport. Since the time required to transport a patient from the place of wounding to the most forward hospital may greatly influence his condition on arrival, some indication of the length of this period in the Mediterranean Theater of Operations is given in Table 1, which shows the average progress of three groups of casualties along the evacuation route. The first group consists of 100 men selected at random from those in our study


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FORWARD HOSPITAL in Italy after a rain (above). In evacuation by jeep, as shown below, plasma could be administered during the trip, even over rough roads, but the terrain in Italy often made all types of evacuation difficult and affected the condition of the patient on his arrival at a forward hospital.


25

who were wounded during a relatively quiet period in the fall, winter, and spring of 1944-45. The other two groups represent men who were severely wounded during offensives in the spring of 1945. In the third locale cited, it was contended by those concerned that, considering the circumstances, evacuation had been effected rapidly. The table also shows the average time from hospital admission to surgery and the total time from wounding to surgery in the three groups.

Type and Location of Wounds

For various correlations throughout the study wounds are grouped according to their type, or location, or both. Many patients incurred multiple wounds, some multiple major wounds. For certain purposes two broad classifications of type were utilized: peripheral and nonperipheral, and this terminology will be used whenever pertinent. Nonperipheral wounds were defined as those involving the major body cavities (the abdomen, the thorax, and the interior of the skull); all others were considered as peripheral. Crush cases are excluded in some of the correlations because they were studied separately.

In the following classification the severe wounds only are considered, since they were pertinent to the study. Thus in the patients with multiple severe wounds some wounds were listed as the principal major ones; no attempt was made to record minor wounds, such as fracture of a phalanx, for example. In general, the types of wounds found in our patients were as follows:

    Severe peripheral wounds were present in 116 patients, constituting a major injury in 81 instances. Nearly all were wounds of the extremities. Thirty-three patients had peripheral wounds without fracture, 16 of which were the patient's major wound. Fifty-three of 70 patients had major peripheral wounds with fracture, and 13 had traumatic amputation of an extremity. In 10 of these 66, a major wound was also listed in another category. Three patients among those with peripheral wounds had injury to the spinal cord.

    Of the severe nonperipheral wounds, 34 patients had thoracic wounds (a major wound in 30 instances) and 56 patients had intra-abdominal wounds, a major wound in 50 instances. An additional 21 patients had combined thoraco-abdominal wounds and 2 patients had separate wounds of the chest and abdomen. Of the total abdominal wounds, there were 25 wounds of the liver, 20 wounds of the kidney


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TABLE 2.-RELATIONSHIP OF PAIN TO MAJOR WOUND IN 215 PATIENTS
(Data Taken from Study on Pain in Men Wounded in Battle1)


27

    (treated by nephrectomy in 11 instances), and in 1 case it was not known whether a kidney or liver wound had been present. Wounds of the urinary tract involving the bladder or structures above it occurred in 9 patients. Ten patients with nonperipheral wounds had multiple major wounds.

    Crush injuries were found in nine patients, and there was only one case of head injury.

Clinical Condition of Patients on Arrival at the Most Forward Hospital

Pain

The frequency and severity of pain in different types of wounds had been extensively studied under similar conditions and on the same types of patients shortly before the Board was organized and the study was therefore not repeated on these 186 patients. Part of the data obtained in the early study4 is shown in Table 2. The incidence of severe pain was surprisingly low. The data showed that severe pain was not to be accounted for on the basis of the patients' having received less morphine or having received it earlier than patients who reported little or no pain. It was also pointed out that three factors are chiefly important in the distress of the wounded: pain, mental distress, and thirst. In the severely wounded patient in good general condition, the first two factors are important. In the man in shock, thirst is the main and often the only cause of evident distress, but it may be extreme.

Shock

Grading of Shock.-The view sometimes has been taken that shock is either present or absent in a given case and that to try to distinguish between degrees of shock is futile. In this study, however, it was found instructive to separate the patients arbitrarily into four categories; namely, those with "no shock," "slight shock," "moderate shock," and "severe shock." This was done on the basis of the criteria listed in Table 3 which in turn were based on preliminary observation of large numbers of battle casualties by members of the Board. A patient was assigned to a particular category if he exhibited the ma-

    4BEECHER, H. K.: Pain in men wounded in battle. Ann. Surg. 123: 96-105, January 1946; also Bull. U. S. Army M. Dept. 5: 445-454, April 1946.


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TABLE 3.-GRADING OF SHOCK*


29

jority of criteria for that category as opposed to another. These signs were inadequate, of course, for management of a case, for a comprehensive appraisal of the patient's condition must include not only an accurate concept of his present state but also a shrewd estimate of his probable course in the immediate future.

On the basis of this arbitrary classification the 186 patients under study were evaluated as to the degree of shock they had at the time of their admission to the hospital. In three of them the degree of shock could not be ascertained. Those 78 patients who were not seen on admission by any member of the Board were classified by the Board on the basis of the available clinical data and on discussion with medical officers who had seen them on admission. In the 108 patients who had been observed on admission by some member of the Board the degree of shock was probably more uniformly classified. Table 4 shows the clinical evaluation of shock and its distribution in these 108 patients as well as in the entire series. It is apparent that the distribution remained about the same when the 108 were separated from the entire group. Since the percentages were essentially unchanged when the magnitude of the cases was roughly doubled, it was assumed that the size of the sample 108 cases was adequate.

TABLE 4.-CLASSIFICATION AND DISTRIBUTION OF SHOCK
Relationship to Time from Wounding.-Examination of the records of 167 of the entire group of severely wounded men under study on whom these data


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TABLE 6.-WOUND COMPOSITION IN EACH SHOCK CATEGORY-121 PATIENTS


31

were complete failed to show any correlation between the time from wounding until examination (clinical appraisal and blood analysis) and the presence or severity of shock (Table 5). The time elapsed in each of the four groups was approximately the same. There was, however, a striking correlation between severity of shock and blood loss, as will be shown later.

TABLE 5.-RELATIONSHIP OF DEGREE OF SHOCK ON HOSPITAL ENTRY TO TIME FROM WOUNDING-167 CASES
Relationship to Wound.-Table 6 indicates the wound composition of 121 patients in each shock category. It merits some comment. If the two types of serious extremity wounds--traumatic amputation of extremities and compound fractures of long bones--are combined (the two are often very similar as to blood loss), it can readily be seen from Table 7 that the incidence of such wounds rose progressively in each category of increasing severity of shock. In the section on Blood Loss it will be shown that the greatest loss of hemoglobin occurred when the wound involved compound fracture of the long bones or

TABLE 7.-INCIDENCE OF COMBINED CASES OF SERIOUS EXTREMITY WOUNDS (MAJOR OR CONCOMITANT INJURY) IN EACH SHOCK CATEGORY


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A SEVERELY WOUNDED MAN receives treatment in the forward area.

traumatic amputation of an extremity. Since most patients having such wounds were in severe shock, one can generalize with probability of accuracy and say that it is the wounds that are associated with great hemorrhage that cause severe shock. Reasons for laboring this rather obvious point will be discussed later.

In contrast to the rising incidence of severe extremity wounds in progressive shock categories, the percentage of penetrated abdomens, although rather high, shows no such consistent rise. In the severe-shock group, abdominal wounds are definitely less often a cause of the poor condition of the patient than are the combined extremity wounds. (Incidentally, this evidence does not support the view that clostridial infection plays an important part in producing shock in general.)

The question might be raised as to whether the relative importance of ab-


33

dominal wounds as a cause of shock has heretofore been exaggerated. The poor prognosis often encountered in patients with abdominal wounds probably has a great deal to do with the apprehension felt in the presence of such lesions. The concealed hemorrhage or concealed contamination often present in these cases may lead to subsequent profound shock. So, while on the average abdominal wounds were not as often a cause of severe shock on hospital entry as were serious extremity wounds, the impossibility of accurate preoperative appraisal of the abdominal wound makes it difficult to exaggerate its potentialities.

Shock will be discussed in each of the following sections of this chapter and an attempt will be made to correlate degree of shock with the data under discussion whenever possible.

Cardiovascular System

Electrocardiographic Observations.-Prior to organization of the Board, 58 electrocardiographic records were made on 30 patients in severe shock and after recovery.5 Since the observations were made on the same type of patients as those studied by the Board and under similar circumstances, electrocardiograms were not made on the Board's cases. The results of that study are summarized here. In 10 patients (one-third of that series) the blood pressure could not be measured on hospital entry. In the other two-thirds the degree of circulatory collapse was somewhat less severe, but even so the systolic blood pressures ranged from 60 to 70 millimeters of mercury and the diastolic from 20 to 40 millimeters.

Definite abnormalities of the electrocardiograms were observed in 5 of the 30 patients. The most striking feature was the normal character of the findings in the remaining twenty-five. In 2 of the 5 patients with abnormal findings, the electrocardiograms showed striking but transient inversion of the T wave in lead 1. In a patient with an intrathoracic injury there was a shift from marked right-axis deviation back to normal following operation. The electrocardiogram in the fourth patient showed bizarre QRS complexes of low voltage, and in the fifth showed evidence of an unusual degree of temporary cardiac irritability with paroxysmal fibrillation and ventricular tachycardia.

    5BURNETT, C. H.; BLAND, E. F., and BEECHER, H. K.: Electrocardiograms in traumatic shock in man. J. Clin. Investigation 24: 687-690, September 1945.


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This electrocardiographic evidence of abnormality is of some interest but difficult to explain. In no instance were there clinical signs of cardiac weakness, such as abnormal accentuation of the pulmonary second sound, basal râles, gallop rhythm, or congestion of the cervical veins or of the liver. As stated, the majority of the electrocardiographic findings were within normal limits. Several patients in the series were in severe shock, having low blood pressure for a period of hours with no effect upon the electrocardiogram. It may be significant that in both patients with transient inversion of the T wave in lead 1, the wound involved the left side of the chest, although so far as could be determined by roentgenographic examination and clinical findings at the time of operation, the heart and pericardium escaped injury. Furthermore, the transient nature of the inversion was more in accord with a temporary functional disturbance (possible hypoxia) than with lasting tissue injury.

Pulse Rate.-The pulse rates of the patients in the present study were considered in relationship to shock and no significant difference was found between the four categories (Table 8). The pulse rates considered were those taken as close as possible to the time the condition of the patient was evaluated. When the pulse was imperceptible at the time of initial examination, the first recordable rate was used unless the record showed evidence that the patient was well on the way to resuscitation.

TABLE 8.-RELATIONSHIP OF DEGREE OF SHOCK TO PULSE RATE-106 CASES
The finding that the average as well as the minimum and maximum pulse rates were about the same in all degrees of shock was surprising. There are two possible explanations for this: 1. The tachycardia in the lesser degrees of shock may have been due in part to excitement. 2. In some cases the elevation of the pulse rate (and the vasoconstriction accompanying it) may have been adequate to ward off the signs of shock. It is interesting that even patients judged to be


35

in severe shock can have a pulse rate as low as 60 beats per minute. Of greater significance than the actual rate of the pulse is its volume, which often was decreased so much in severe shock that the pulse could no longer be felt.

Blood Pressure.-Blood pressures were analyzed in only those 70 cases out of the 186 in which they had been recorded at the time the patient's condition was evaluated. The volume of the circulating blood was also determined in these 70 patients. There was no significant fall in the average systolic blood pressure except in those in moderate or severe shock (Table 9). It will be shown that these patients with considerable shock had lost on the average 33.6 percent of their calculated normal blood volume and nearly 50 percent of the total circulating hemoglobin. In those with severe shock, the systolic blood pressure fell rapidly, the average being 49 millimeters of mercury. This group had lost approximately half the normal blood volume (see Table 22). There was, however, a progressive drop in the average diastolic blood pressure with increasing degrees of shock (Table 9). The average diastolic blood pressure of the patients in severe shock was half that of the patients in moderate shock. As severity of shock increased, there was a significant and progressive decline in the pulse pressure (Table 9). This confirmed the clinical observation that the volume of the pulse was closely correlated with the degree of shock.

TABLE 9.-RELATIONSHIP OF DEGREE OF SHOCK TO BLOOD PRESSURE-70 CASES
"Irreversible" Changes in the Cardiovascular System.-Everyone who has treated many patients for shock has encountered some who fail to respond to the transfusion of blood deemed adequate under ordinary circumstances, and this is often attributed to "irreversible" changes that have presumably taken place during prolonged hypotension, ischemia, and anoxia. This problem is


36

further discussed in the section on Blood Loss. In most instances, adequate explanation can be found for the failure of patients in shock to respond to blood transfusion; some common examples are concealed and continuing hemorrhage, hemothorax, irritant contamination of the peritoneum, peritonitis, clostridial myositis, and fat emboli. Four cases from our series are illustrative.

CASE REPORTS

Case 77.-A patient with a severe thoraco-abdominal wound was received at a forward hospital in severe shock 8¼ hours after he was wounded. Resuscitative measures were continued for nearly 9 hours. During that time he received only 1,500 cc. of whole blood. His condition failed to improve and he was operated upon but did not survive the operation.

Necropsy showed massive collapse of the right lung with a plug of mucus in the right main bronchus. The lower lobe of the left lung was collapsed and about one-third of the left upper lobe was atelectatic. There was gross dilatation of the right ventricle of the heart. On histologic examination minimal evidence of fat embolism in the pulmonary vessels was found but considered of no clinical significance.

Comment.-There was adequate cause for this patient's failure to respond to resuscitation. More aggressive measures should have been taken, including bronchoscopy and the use of more blood in less time. There should have been more concern when no improvement occurred during the first 3 hours after the patient's admission to the hospital.

Case 45.-A patient with a severe abdominal wound was admitted to a forward hospital in severe shock 8 hours after wounding. During the next 3 hours, 2 units (600 cc. total volume) of plasma and 1 liter of whole blood were transfused. The blood pressure during that time changed from imperceptible to 90 millimeters of mercury systolic and 70 diastolic. An additional unit of plasma was administered and an infusion of 500 cc. of 2-percent solution of sodium bicarbonate was given intravenously. Although this was the optimum time for surgery, operation was delayed and 5 hours later the blood pressure was again unmeasurable. It was restored to 86 millimeters of mercury systolic and 60 diastolic after transfusion of 1 liter of whole blood, and operation was performed which lasted 4 hours.

At operation the abdominal cavity was found to be "full of blood." The blood pressure and pulse rate were unmeasurable during much of the operation. The patient never regained consciousness and died 3¾ hours after the end of the operation. Necropsy showed perforation of the inferior vena cava. There was histologic evidence of minimal fat embolism in the pulmonary vessels, probably of no clinical significance.

Comment.-The recurrent hypotension in this patient was probably due to continued extraperitoneal and intraperitoneal hemorrhage. Operation should


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have been performed while he was responding well to resuscitative measures during the first 3 hours after admission to the hospital.

Case 100.-This patient had multiple wounds involving both arms, the left thigh, and the face. There were compound fractures of the left humerus, radius, and ulna, and of the right ulna. There was also a transection of the right femoral artery with vascular insufficiency in the leg. He was admitted in severe shock to a forward hospital 3½ hours after wounding, and within 90 minutes he received 300 cc. (total volume) of plasma and 2 liters of whole blood. He showed general improvement but his blood pressure was still only 80 millimeters of mercury systolic and 50 diastolic. His pulse rate was 144 beats per minute. Three hours after admission his blood pressure was 90 millimeters of mercury systolic and 58 diastolic. Operation was delayed for 3 additional hours. At no time during operation did the recorded blood pressure fall below 85 millimeters of mercury systolic. The patient had received a total of 4,500 cc. of whole blood before, during, and immediately after operation.

Ten hours after operation the patient's blood pressure was low and he looked pale and "anemic." A transfusion was started, but an hour later he suddenly died. Ten minutes earlier he had carried on an intelligent conversation. Pulmonary embolus was suspected but at necropsy no cause could be found for the sudden death. Microscopically, a moderately severe grade of fat embolism was found in the lungs.

Comment.-The question was raised whether the 5- or 6-hour period of hypotension in this patient could have caused irreversible changes in the cardiovascular system so that it simply "gave out" when it did. This cannot be answered with certainty. The fat embolism in retrospect appears to be the more important consideration.

Case 120.-This patient had a simple penetrating wound of the thigh caused by a shell fragment. The femoral artery below the origin of the profunda femoris was severed. During evacuation the patient had received 4 units (1,200 cc. total volume) of plasma and when he reached the evacuation hospital, about 9 hours after wounding, he must have appeared in good condition for no resuscitation was deemed necessary. At operation, performed 4½ hours after admission, the femoral artery, vein, and nerve were found to be completely transected. The vessels were ligated and the foreign body was removed.

At the conclusion of the operation, the systolic blood pressure was only 70 millimeters of mercury and remained between 70 and 60 throughout the day. Despite this the patient appeared to have good color and his skin was not cold. Transfusion of 1 liter of whole blood did not improve the blood pressure. The right leg looked as though it would not survive. Anuria developed and the patient died 48 hours after operation. Necropsy revealed nothing to account for the postoperative hypotension. There was no concealed hemorrhage and no evidence of clostridial myositis in the involved extremity. There was no histologic evidence of fat embolism.

Comment.-This patient probably had lost more blood than was realized.


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Resuscitation

Before admission of the patients in this study to a forward hospital, resuscitative efforts had been limited chiefly to control of pain and hemorrhage and to administration of blood plasma. Relatively little whole blood was given. The 108 patients seen by us on admission had received, on the average, 2 units6 of plasma before the first blood sample was taken. Plasma administration was distributed in this group as follows:

Number of Patients

Units of Plasma

32

None

25

1

17

2

13

3

12

4

3

5

1

6

1

7

2

8

1

9

1

11


Thus 69 percent (74) of these patients had received two units (6oo cc.) or less of blood plasma before or shortly after arrival at the most forward hospital. Twenty-seven of the 108 patients received transfusions of whole blood prior to withdrawal of the first blood specimen for laboratory analysis. Three of these, or 3 percent, had received whole blood in an aid station before admission to a forward hospital. The blood transfusions were distributed as follows:

Number of Patients

Units of Blood

13

1/5 to 1

10

1½ to 2

2

3

1

4

1

6


The following tabulation summarizes the average quantities of blood and of blood plasma used in resuscitating 157 of the very seriously wounded patients in our series (the 108 referred to above and 49 others on whom we had clinical notes):

Blood plasma preoperatively (average of 122 cases)

3.08 units

Blood plasma during operation (average of 10 cases)

1.68 units

Whole blood preoperatively (average of 127 cases)

1,450 cc.

Whole blood during operation (average of 95 cases)

1,160 cc.

    61 unit = 250 cc. of normal plasma diluted to 300 cubic centimeters.


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In round numbers, our average patient in this series had just over 3 units (total volume) of blood plasma and 5 blood transfusions (total of about 2,500 cc. of whole blood) to support him from the time of wounding until his operation was completed. It is interesting to observe that plasma was used during surgery in only 10 of these 157 patients.

The information concerning the cases referred to here was drawn from the shock tents of most of the hospitals of the Fifth Army and represents a broad sample of current practice in Italy over the last year of the European War. Essentially the same type of case had been studied by two of us earlier at Anzio.7 In that series the average patient received 1,537 cc. of whole blood (three transfusions) to prepare him for and carry him through surgery. These three transfusions contrast with the five referred to above. A notable difference between the Anzio study and Mediterranean Theater practice in general was in the time elapsed from hospital entry to start of surgery. In the Anzio study this averaged 2 hours, 21 minutes. Reference to an earlier part of this section on Time from Wounding to Hospital Entry and Surgery will show that over the Fifth Army Area as a whole, the average time from hospital entry to surgery varied from 5 hours to 8 hours. Two differing views as to the correct preparation of wounded men for surgery are represented in these figures: the extended, and the rapid. The extended required five transfusions of whole blood; the rapid, three. This has been discussed in a previous publication.8

Plasma Protein Concentration and Hematocrit Values On Admission to Forward Hospital

The concentration of protein in the plasma and the blood hematocrit value (both calculated from specific gravities measured by the copper sulfate method9) give a clue to the shifts that have taken place between the blood stream and the tissues as well as to blood loss from the body. When considered

    7BEECHER, 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.
    8BEECHER, H. K.: Preparation of battle casualties for surgery. Ann. Surg. 121: 769-792, June 1945.
    9PHILLIPS, R. A.; VAN SLYKE, D. D.; DOLE, V. P.; EMERSON, K., JR.; HAMILTON, P. B., and ARCHIBALD, R. M.: Copper sulfate method for measuring specific gravities of whole blood and plasma. BUMED News Letter, U. S. Navy, vol. 1, June 25, 1943.


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with quantitative measurements of whole-blood loss, a fairly accurate picture of one consequence of the wound can be obtained. The plasma protein and hematocrit levels were determined in our patients shortly after their admission to the most forward hospital, before resuscitation, anesthetization, or operation had been undertaken.

Relationship to Type of Wound

In Table 10 the relationship of the average plasma protein concentration and the average hematocrit value to the type of wound is shown for 50 patients who, prior to study, had received only 1 unit (300 cc.) of blood plasma or less than 1 unit (in some instances no plasma had been administered). The patients whose wounds were peripheral are grouped and compared with those having nonperipheral wounds; crush cases are not included.

From the table it may be seen that there is no decided difference between the plasma protein levels of patients with peripheral and those with nonperipheral wounds. On the other hand the hematocrit values were significantly higher in.the latter group which is consistent with the hemoconcentration sometimes found in such patients. There was also less loss of hemoglobin (as will be discussed in the section on Blood Loss) in those patients with intra-abdominal and thoraco-abdominal wounds than in those having severe wounds of the extremities. Maintenance of a more nearly normal blood volume in patients with such nonperipheral wounds doubtless reduces the need and tendency for blood dilution, although this factor alone would not account for the hemoconcentration when it is found in such cases.

TABLE 10.-RELATIONSHIP OF PLASMA PROTEIN CONCENTRATION AND HEMATOCRIT VALUE ON ADMISSION TO TYPE OF WOUND IN PATIENTS WHO HAD RECEIVED 1 UNIT OR LESS OF PLASMA


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Relationship to Blood Loss

When average plasma protein concentrations and average hematocrit values in patients with peripheral and nonperipheral wounds are compared with loss of blood volume (39 cases), it may be seen from Table 11 that the hematocrit values were significantly lower in all patients who had lost more than 30 percent of their calculated normal blood volume. The hematocrit level of 36 is 23.4 percent below the normal of 47 (Wintrobe method).

In the case of the plasma proteins, however, even when there was a loss of 30 percent or more of the normal blood volume, the average concentration was 6.1 Gm. per 100 cc. (only 6.1 percent below the normal of 6.5). In other words, the hematocrit level fell proportionately about four times as much as that of the plasma proteins. The blood appears to have been diluted by protein-rich fluid (6.1 Gm. per 100 cc. of blood). The evidence is too meager to justify much speculation here. However, as pointed out by Evans,10 the axial stream of corpuscles is surrounded by a plasma envelope. This varies in thickness and total volume, depending upon certain hydraulic principles. It might be possible that the alterations in the circulation caused by the loss of 30 percent or more of the normal volume of blood (slowing of the peripheral circulation, for example) resulted in dragging an appreciable volume of plasma with normal protein content into

TABLE 11.-RELATIONSHIP OF PLASMA PROTEIN CONCENTRATION, HEMATOCRIT VALUE, AND TYPE OF WOUND TO BLOOD LOSS IN PATIENTS WHO HAD RECEIVED 1 UNIT OR LESS OF PLASMA

    10EVANS, ROBLEY: Personal communication.


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the circulating blood. Or it might be possible that protein was brought into the circulation from the liver.

Influence of Plasma Therapy

The influence of previous administration of blood plasma upon the concentration of plasma protein and the hematocrit value was considered, and the findings in different types of wounds are shown in Table 12 and Charts 1 and 2. Only three of the patients had had blood transfusions; these will be ignored. It is clear from the table and charts that plasma therapy did not influence the plasma protein level, but it did have an important effect on the hematocrit level.

The plasma protein concentration and hematocrit value were also analyzed in regard to shock, the data being broken down into two categories in which "no shock" and "slight shock" were grouped together, as were "moderate shock" and "severe shock." No important differences were found between the two categories.

TABLE 12.-EFFECT OF PLASMA THERAPY ON AVERAGE PLASMA PROTEIN AND HEMATOCRIT ADMISSION LEVELS IN 89PATIENTS WITH VARIOUS TYPES OF WOUNDS


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CHART 1. Influence of plasma therapy on plasma protein and hematocrit levels in peripheral wounds

CHART 2. Influence of plasma therapy on plasma protein and hematocrit levels in abdominal wounds

Relationship to Shock

Plasma protein and hematocrit levels were also studied in relation to the clinical condition of about 100 badly wounded patients (crush cases excluded) on admission to the forward hospital. The fall in average plasma protein concentration is probably significant as the cases are grouped in Table 13 and Chart 3; the fall in hematocrit value is definitely significant. There was no evidence of hemoconcentration. When the patients were grouped according to

TABLE 13.-PLASMA PROTEIN AND HEMATOCRIT LEVELS ON ADMISSION IN RELATION TO SHOCK*


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TABLE 14.-PLASMA PROTEIN AND HEMATOCRIT LEVELS ON ADMISSION IN RELATION TO SHOCK IN PATIENTS WITH ABDOMINAL WOUNDS
 CHART 3. Plasma protein and hematocrit levels in relation to shock--all types of wounds

location of the major wound, there was no significant fall in the concentration of plasma protein in those with peripheral wounds in relation to the degree of shock. The findings in patients with abdominal wounds showed up differently (Table 14). In the group with minimal shock, the plasma protein concentration may possibly be accounted for by weeping of the irritated peritoneal surfaces, fluid being released which contained less protein than the plasma. As shock became moderate or severe, probably due to greater blood loss, the plasma protein concentration fell to a figure like that for extremity wounds, with hemodilution overcoming the effects of exudation. These data indicate that the plasma protein and hematocrit values can vary independently.


45

Blood Loss

Volume and Hemoglobin

The quantity of blood a wounded man can lose and yet recover has generally been underestimated. One indication that this is so was the fact, well shown in the prolonged campaigns of the Mediterranean Theater, that robust young soldiers tolerated surgery well, long before the blood volume or even the blood pressure had been restored to normal. Actually the concept of restoration of the patient in shock to normal prior to surgery is based upon a false premise. Full organic restoration probably requires days to achieve. A good response of a young wounded man to treatment is by no means admissible evidence that his circulatory system has been restored to normal; it is evidence of the existence of safety factors in human physiology. These points have been discussed elsewhere.11

In the belief that measurement of the blood loss that had been sustained by these severely wounded men by the time of their arrival at a forward hospital would clarify the matter of the importance of whole blood for the wounded, such a study was carried out. The direct relationship between quantity of blood lost and degree of shock had long been recognized, but further evidence of this relationship was desirable in view of the ever-recurring suggestions that the cause of shock is mysterious and to be explained by the presence of toxins in the body or by the breakdown of some vague but vital force.

The blood volume and the hemoglobin concentration were determined in 67 patients12 shortly after their arrival at the most forward hospital (which in most instances was a field hospital). The blood volume loss and the total hemoglobin loss, expressed as percentages of a calculated normal for each patient, were then determined on the basis of these findings. Normal blood volume was considered to be 8.5 percent of the body weight, after Gregersen. (See Appendix C for the method used.) Peters13 has commented on the loss of the dye T-1824 from the blood stream. Such loss of dye would of course

    11See footnote 8. Also see section on Resuscitation in volume on general surgery of the series: The Medical Department of the United States Army. To be published.
    12The blood studies were actually made in 71 cases (see Table 15), but one case was discarded because of a probable technical error and three others are excluded from the present discussion since they represent types not common to the group; namely, two crush injuries (Cases 93 and 124) and a head injury (Case A-7).
    13PETERS, J. P.: Role of sodium in production of edema. New England J. Med. 239: 353-362, Sept. 2, 1948.


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TABLE 15.-INITIAL BLOOD CHANGES IN 71 SEVERELY WOUNDED MEN


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TABLE 15.-INITIAL BLOOD CHANGES IN 71 SEVERELY WOUNDED MEN--
Continued


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TABLE 16.-BLOOD CHANGES IN 69 SEVERELY WOUNDED MEN CLASSIFIED ACCORDING TO DEGREE OF SHOCK
A. No Shock-12 Patients

give a falsely high value for blood volume. Our blood-loss values were estimated by difference, difference between an average normal blood volume (8.5 percent of body weight) and the value found. Therefore the losses we report are lower than the fact; they are minimal rather than maximal.

To compensate for the effect on his blood volume of the blood and plasma received by the patient, certain corrections were applied to our blood volume determinations. The majority of patients had received some plasma prior to hospital admission and a few had received whole blood. Although blood volume determinations were made as soon after hospital admission as possible, resuscitative procedures had likewise been initiated. Actually, in most cases, determinations and resuscitation proceeded concurrently. Two methods of correcting blood volume findings were therefore utilized: Correction A and Correction B.

    Correction A was the subtraction of the total quantity of blood and blood plasma received by the patient from the time of wounding until


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TABLE 16.-BLOOD CHANGES IN 69 SEVERELY WOUNDED MEN CLASSIFIED ACCORDING TO DEGREE OF SHOCK
B. Slight Shock-20 Patients

    completion of the test.

    Correction B was the subtraction of only the quantity of blood and plasma received from the time of the patient's hospital admission until completion of the test.

Correction A was applied for the purpose of correlating the patient's clinical condition on arrival at the hospital with the amount of blood (the percentage of his estimated normal blood volume) that he had actually lost due to his wounds, regardless of the amount that may have been replaced. Correction B was for correlation between the patient's clinical condition on arrival and the blood deficit existing at that time. The same corrections were applied in calculating the total hemoglobin loss. However, in the case of hemoglobin


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TABLE 16.-BLOOD CHANGES IN 69 SEVERELY WOUNDED MEN CLASSIFIED ACCORDING TO DEGREE OF SHOCK
C. Moderate Shock-21 Patients

there was essential agreement between calculation A and calculation B because, with rare exceptions, whole blood had not been administered before the patient reached the most forward hospital.

Tables 15 through 22 show blood and hemoglobin loss in relation to other findings for patients individually and by groups. The loss is given as the percentage difference between a calculated normal and the observed value, or between the calculated normal and the observed value modified by Corrections A and B. For blood all three determinations are shown. For hemoglobin only the estimated loss derived by Correction B is shown. It will be noted that a few entries (shown as plus values in the tables) seem to indicate that the blood volume was greater than normal despite loss of blood. Several factors, indi-


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TABLE 16.-BLOOD CHANGES IN 69 SEVERELY WOUNDED MEN CLASSIFIED ACCORDING TO DEGREE OF SHOCK
D. Severe Shock-16 Patients

vidually or collectively, might have brought about this apparent discrepancy: 1. In the case of uncorrected entries, blood and plasma administered may have been in excess of blood loss. 2. Entries are from calculations based upon an average normal which may have been too low for some patients. 3. There may have been errors in technique in blood volume determination.

Relationship of Blood Loss to Type of Wound

Fifty-nine of the patients listed in Tables 15 and 16 suffered primarily from a single major wound (abdominal, chest, or peripheral) and could therefore be more readily studied as to the relationship of blood loss to type of wound.


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CHART 4. BLOOD VOLUME LOSS IN RELATION TO LOCATION OF WOUND

The findings in these 59 patients, and in 6 others who had combined thoraco-abdominal wounds, are presented in Tables 17 and 18, and in Charts 4 and 5. The huge standard errors present in several instances indicate the wide variations in the results found. From the table it would appear that loss of blood volume was greatest in the patients with peripheral wounds (Table 17). However the number of cases was small, the variability in the data was wide, and the true state of affairs possibly was masked by dilution of the blood volume after wounding by movement of fluid from the tissues to the blood stream.

The data on hemoglobin loss are probably more revealing. There is a significantly greater loss of hemoglobin in men with peripheral wounds than in those with abdominal wounds (Table 18) and in this case the situation is not


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CHART 5. HEMOGLOBIN LOSS IN RELATION TO LOCATION OF WOUND

obscured by the factor of hemodilution. This difference is in agreement with the previous finding that more patients with compound fractures of long bones

TABLE 17.-RELATIONSHIP OF BLOOD VOLUME LOSS TO TYPE OF WOUND


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TABLE 18.-RELATIONSHIP OF HEMOGLOBIN LOSS TO TYPE OF WOUND
or traumatic amputations were in severe shock than were those with abdominal wounds (Tables 6 and 7). Data on the comparison of blood loss in the two types of serious extremity wounds are scanty but are presented for what they are worth, Table 19. The blood loss in patients with compound fractures was greater than it was in those with traumatic amputation, probably because of the greater tissue damage usually found in the former.

TABLE 19.-LOSS OF BLOOD VOLUME AND TOTAL HEMOGLOBIN IN 31 PATIENTS WITH SEVERE EXTREMITY WOUNDS
Table 20 shows the average blood volume and hemoglobin losses in 40 patients with all types of wounds who had received either none or small amounts of plasma but in no instance more than 1 unit before the determinations were made. The losses here are less than those shown in Tables 17 and 18 because the group includes fewer of the patients in severe shock. Again a greater average loss of hemoglobin than of blood volume is shown. This is explained by


55

hemodilution which normally takes place after blood loss. Red blood cells are not replaced appreciably during the interval from wounding to arrival at a forward hospital except by transfusion.

TABLE 20.-LOSS OF BLOOD VOLUME AND TOTAL HEMOGLOBIN IN 40 PATIENTS WHO HAD  
RECEIVED 1 UNIT OR LESS OF PLASMA

Relationship of Blood Loss to Time from Wounding

There was no important average increase in blood volume loss or in hemoglobin loss with increased time elapsing between wounding and hospital entry (Table 21). However, those men who were suffering from continuing blood loss were probably given priority of evacuation. Somewhat greater blood losses were usually found in those who arrived at the hospital soon after wounding than in those who were brought in later.

TABLE 21.-RELATIONSHIP OF BLOOD LOSS TO TIME FROM WOUNDING IN 67 CASES
(ALL TYPES OF WOUNDS)


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Relationship of Blood Loss to Degree of Shock

It is well known that individuals do not respond alike to a given blood loss; even previously healthy, normal young soldiers vary greatly in their response. This fact, together with the inexactness inherent in any clinical appraisal of the degree of shock plus the errors of the experimental method used, might have tended to obscure a real relationship between shock and blood loss. However this relationship was so striking that, even with the relatively small number of cases, the positive correlation of blood loss to the severity of shock was statistically significant (Table 22 and Chart 6).

TABLE 22.-RELATIONSHIP OF BLOOD LOSS TO DEGREE OF SHOCK IN 67 CASES
(ALL TYPES OF WOUNDS)

The degree of wound shock as we saw it in men injured in battle precisely paralleled the quantity of blood actually lost. Conversely, recovery from shock resulted promptly from administration of whole blood. Although we made intensive search at the bedside of thousands of wounded men throughout the shock tents in Italy, we never found a clear case of "irreversible shock," mentioned so frequently in the literature. It is true that there were wounded men in whom the loss of blood was so rapid and so great that it was impossible to transfuse them with blood fast enough to save their lives. (For example, we were unable, in the case of the soldier who had both thighs blown off by a shell burst just outside our door at Anzio to get blood into him fast enough to save his life; he died in a very few minutes.) Nor were we able to resuscitate patients who had had inadequate circulation in the central nervous system


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CHART 6. RELATIONSHIP OF BLOOD LOSS TO DEGREE OF SHOCK

so long that nearly all centers except the respiratory appeared to be dead; we were not able to overcome death of organs or of nervous tissue by resuscitative effort. But we believe that application of the term "irreversible shock" to either type of case is to use a definition that has no place at the bedside, however interesting it may be as a concept, and that may do real harm by providing an excuse for limiting resuscitative effort.

In short, if "irreversible shock" in the accepted sense was present, we missed it. If toxins caused any of the shock we saw, with the exception of that due to overwhelming and clinically apparent bacterial infections, we failed to recognize it. The shock we saw was caused by loss of blood (or of fractions of the blood). It was relieved by administration of whole blood.

From our data it may be said that, in general, when a third of the blood volume is lost, clinical shock of more than slight degree will result, and when half is lost, severe shock will result. It was also shown that in individual cases as much as 75 percent of the blood could be lost and the patient survive. Cases A-17, A-21, A-29, A-37, A-38, 127, and 139 are examples of severe blood loss and survival. The greatest blood volume losses found were 78.6 percent in Case 107 and 75.7 percent in Case 139 (Table 16, C and D). Both de-


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terminations were obtained by Correction A. Shock was moderate in the first case and severe in the second. The greatest loss of total hemoglobin found was 83.8 percent in Case A-21 (Table 16, D). This patient had serious extremity wounds and was in severe shock.

Our data also indicated that, on arrival at the hospital, generally the deficiency in total hemoglobin was greater than the deficiency in blood volume. This is understandable in view of the well-known mechanism for replenishing blood volume at the expense of tissue fluid. On the other hand, once the readily available reserves of hemoglobin have been called into action, no mechanism is available to replace them rapidly; consequently it would be expected that greater deficiencies would be found in the total hemoglobin.

There was no correlation between passage of time and the degree of shock encountered, in that the elapsed time was the same in each of the four categories of no shock, slight, moderate, and severe shock. This does not say that continuing hemorrhage, for example, is not related to degree of shock; certainly it is, but the important factor in the development of shock is the character of the wound, particularly as it indicates the quantity of blood lost, not the passage of time per se.

We have tried various ways of handling the data on shock. Some investigators have attempted to separate the effects of blood loss alone from the effects supposedly accounted for by "sympathico-adrenal activity." Practically, this is impossible. Moreover, the validity of any such separation even if possible must be questioned. For example there is the matter of increased glycogenolysis in shock. Following all the recent advances in knowledge of carbohydrate metabolism, it seems to be too great a simplification to hang the explanation on the rather shaky peg of "sympathico-adrenal activity," so we take refuge in our purpose of merely stating our findings, with little conjecture, and leaving to future study the search for their significance.

One great consequence of blood loss is the intense vasoconstriction, the shrinkage of the capacity of the vascular bed to accommodate the decreased blood volume. Contraction of the spleen probably plays a relatively small role in compensating for the blood lost in battle. Other body adjustments to blood loss do, however, take place, such as the entry of fluid into the blood vessels in an attempt at compensation. The greatest extravascular store of readily available fluid in the body is that in the extracellular space. Dehydration and oligemia may make quite early demands, not only on this extracellular but also on the intracellular supply.


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Biochemic Changes Encountered

The clinical appearance of the newly wounded man, as well as his subsequent course, offers abundant evidence that profound changes have occurred in his internal state by the time he is admitted to a hospital. To be reported here are chiefly the changes found in the blood although certain urinary findings also are recorded. These changes are significant not only because they reveal the problem at hand, but also because they offer some basis for reasonable therapy. Several factors influence the presence or extent of the abnormalities found. These are discussed in the following sections.

Blood Chemistry Findings

Relationship to Location of Wound.-No significant relationship was found between the location or type of the wound and the plasma nonprotein nitrogen, creatinine, uric acid, phosphorus, or magnesium (See Table 24, page 60). Average values for serum sodium, plasma chlorides, and plasma carbon-dioxide combining power also were determined and likewise failed to show any significant relationship to the type of wound.

Relationship to Delay in Hospital Arrival.-With increased passage of time following wounding, the average plasma nonprotein nitrogen level rose (Table 23). This upward swing of the nonprotein nitrogen offers a basis for some inter-

TABLE 23.-RELATIONSHIP OF PLASMA NONPROTEIN NITROGEN LEVEL TO TIME
FROM WOUNDING IN 92 PATIENTS WITH ALL TYPES OF WOUNDS


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TABLE 24.-BIOCHEMIC FINDINGS1 IN RELATION TO TYPE AND LOCATION OF WOUND


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esting speculation, out of place here, but one might ask in passing: Is this rise a reflection of decreased renal blood flow? Does this rise mean that renal impairment is initiated by the wound and continues, with accumulation of nonprotein nitrogenous waste products? Does this presumed malfunction set the stage for later trouble with the kidneys? The plasma creatinine level did not rise significantly with the passage of time preceding hospital entry, nor did that of uric acid, phosphorus, or magnesium (Table 25). Also no correlation was found between passage of time and levels of plasma chlorides, serum sodium, or plasma carbon-dioxide combining power.

TABLE 25.-RELATIONSHIP OF SEVERAL PLASMA CONSTITUENTS* TO TIME FROM WOUNDING
Relationship to Clinical Condition.-The interesting relationships of the plasma nonprotein nitrogen, creatinine, phosphorus, and magnesium to the degree of shock are shown in Table 26. Statistically significant rises occurred for nonprotein nitrogen, phosphorus, creatinine, and magnesium in progressive categories from "no shock" to "severe shock," with the chief difference occurring between the moderate- and severe-shock groups. The rise in uric acid was not statistically significant. When these substances were compared with blood loss, the same positive correlation was found for the nonprotein nitrogen, creatinine, phosphorus, and magnesium, as would be expected. Again the correlation in the case of uric acid was not significant. These comparisons are shown in Table 27; blood loss was divided into five categories from no loss to loss of more than 40 percent of the calculated normal blood volume.

Data relevant to acid-base balance are presented in Tables 28 and 29 and Chart 7. An acidosis was present in those patients with severe shock and is


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TABLE 26.-BIOCHEMIC FINDINGS* IN RELATION TO SHOCK
 TABLE 27.-BIOCHEMIC FINDINGS* IN RELATION TO BLOOD LOSS


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CHART 7. Plasma electrolytes (on hospital admission) in relation to shock

reflected in the carbon-dioxide combining power. A significant fall of carbon-dioxide combining power was correlated with shock (Table 28). Evidence that these low values are due to a metabolic acidosis will be presented in the discussion of azotemia in Chapter IV. Plasma chlorides were uniformly normal in all shock categories (Table 28); likewise, urinary chlorides were essentially normal although they showed wide variations in concentration (Table 29). There was, then, no evidence of salt deprivation on hospital entry. Phosphates, although significantly higher in terms of total anions in those in severe shock than in those with no clinical evidence of shock, could have had little effect on the acid-base balance. Plasma proteins are not included in Table 28, but they showed insufficient variation in terms of electrolyte concentration to have affected acid-base balance.

The plasma was examined for lactic acid in 5 patients shortly after they were wounded. The findings were compared with those in 7 normal, active


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TABLE 28.-PLASMA ELECTROLYTES ON ADMISSION IN RELATION TO SHOCK


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TABLE 29.-PREOPERATIVE URINARY FINDINGS IN RELATION TO SHOCK
soldiers and in 10 bed patients convalescing from severe wounds. The results are recorded in Table 30. They show a twofold increase in the concentration of lactic acid in the wounded when compared with normal, active soldiers and with convalescent bed patients.

TABLE 30.-CONCENTRATION OF LACTIC ACID IN PLASMA IN SEVERELY WOUNDED SUBJECTS AND CONTROLS


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TABLE 31.-AVERAGE PLASMA BILIRUBIN AND HEMOGLOBIN LEVELS IN PATIENTS WITH VARIOUS TYPES OF WOUNDS
 TABLE 32.-AVERAGE PLASMA BILIRUBIN AND HEMOGLOBIN LEVELS IN RELATION TO TIME FROM WOUNDING


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Plasma Bilirubin (van den Bergh Index)
and Plasma Hemoglobin Levels

Relationship to Type of Wound.-On comparison of the type of wound with the plasma bilirubin and hemoglobin, no impressive relationships were found (Table 31).

Relationship to Time from Wounding.-The van den Bergh index rose significantly with increases in time from wounding to examination (Table 32). This may have been due to the absorption of breakdown products from hematomas, and to impaired liver function (see Chapter II). The situation was simpler at this time (when most of these patients had not yet been transfused with blood) than it would be later when large volumes of blood had been given which might tend to elevate the bilirubin level. The plasma hemoglobin level appeared to rise with the passage of time, but this was not significant so far as the data at hand are concerned.

Relationship to Clinical Condition.-There was no clear relationship between degree of shock and the plasma bilirubin or hemoglobin levels (Table 33). However, when the bilirubin level was compared with the blood loss (Correction A), a significant relationship seemed to emerge, although the values were all at a rather low level (Table 34). Presumably the rise is to be accounted for by hemolysis of blood in damaged tissues, followed by absorption into the blood stream. There was no apparent correlation of blood loss with plasma hemoglobin levels.

TABLE 33.-AVERAGE PLASMA BILIRUBIN AND HEMOGLOBIN LEVELS IN RELATION TO DEGREE OF SHOCK*


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TABLE 34.-AVERAGE PLASMA BILIRUBIN AND HEMOGLOBIN LEVELS IN RELATION TO BLOOD LOSS*
 TABLE 35.-AVERAGE PLASMA GLUCOSE LEVELS IN SEVERELY WOUNDED MEN


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CHART 8. PLASMA GLUCOSE LEVELS
 
 Blood Sugar

The blood-sugar level was determined in 57 severely wounded men as they arrived at the forward hospital and was found to be above normal in all of them (Table 35 A and Chart 8). Normal by the method used was considered to be from 80 to 90 mg. per 100 cc. of plasma. Some of the men had received


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plasma but none had had a significant quantity of whole blood before the determination was made. The blood-sugar level appeared to rise significantly both with increased blood loss and with increased severity of shock (Table 35 A and B). The glucose level may fall with the passage of time following wounding, but our data were not extensive enough to demonstrate this (Table 35 C). Presumably the elevation in blood-sugar level was due to mobilization of liver glycogen following adrenal activity and probably reflected the emotional and physical stress the men had experienced.

TABLE 36.-URINE TESTS FOR CREATINE IN 32 PATIENTS


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Urinary Findings

Acid-Base Relationship.-Sodium in the urine was measured in too few cases for reliable averages. Most of the values found were within the normal range. Magnesium, like phosphates on the acid side, was increased but not sufficiently so to affect total acid-base equilibrium. Urinary pH and specific gravity indicate that these men had essentially normal renal function at the time they were wounded, in that they could make both an acid and a concentrated urine. The acid-base relationship will be discussed further in Chapter III.

Creatinuria.-The appearance of creatine in the urine of adult males is abnormal. On the assumption that there might be some abnormality in the metabolism of creatine and creatinine in shock, the urine was examined for creatine in 32 patients (Table 36). In all, 69 urine specimens were tested; the results are summarized in Table 37. Creatine was found in the urines of 26 of the 32 patients. It was present in 6 out of 15 of the patients examined preoperatively, and in 20 out of 29 patients whose urines were examined postoperatively. In 13 of the 32 patients urine tests yielded only positive results, in 11 patients only negative, and in the remaining 9, different specimens tested yielded both positive and negative results.

With one exception (Case 121) all patients who died showed creatinuria at one time or another. It was also present in approximately half the patients who survived. In relation to shock, 14 of 18 patients who had been in moderate or severe shock showed creatinuria. This tendency for creatine to be excreted in the urine in cases of moderate and severe shock and in fatal cases might indicate that it is the result of metabolic changes which accompany shock.

TABLE 37.-SUMMARY OF RESULTS IN 69 URINE SPECIMENS TESTED FOR CREATINE


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Liver Function in the Newly Wounded Man

As will be discussed in Chapter II, the only direct laboratory test of liver function carried out here was that of the bromsulfalein excretion. The van den Bergh index and uric acid levels have also been considered as being in part at least related to liver function.

Bromsulfalein Retention

On Arrival at the Most Forward Hospital.-In 59 severely wounded patients the average bromsulfalein retention on forward hospital arrival was 12.4±1.2 percent (standard error of the mean) 45 minutes after 5 mg. of dye per Kg. of body weight had been injected intravenously. This is well above the normal of 1.0±0.1 percent (as established in a control group of 45 subjects), and above our arbitrarily chosen upper limit of normal of 3 percent (see Chapter II).

Relationship to Time from Wounding.-There was no difference between the average bromsulfalein retention in 29 men examined within the first 6 hours after wounding (14.4±1.8 percent) and in 19 men examined after the first 6 hours (13.1±1.6 percent).

Relationship to Location of Wound.-In 22 patients with serious extremity wounds there was 13.3±2.3-percent average retention, and in 18 patients with abdominal wounds there was an average of 14.7±2.1-percent retention-no difference. In 11 men with penetrating chest wounds, however, the average retention was only 7.0±1.8 percent, which is significantly lower than that found in the other groups.

Relationship to Shock.-In 57 patients separated into the 4 shock categories (no shock, slight, moderate, and severe shock) no significant correlation with bromsulfalein excretion could be found; neither was there any correlation with blood volume or hemoglobin loss.

Relationship to Plasma Administration.-Curiously enough, there was a great increase in average bromsulfalein retention (14.0±2.0 percent) in 25 men who had had one or two units of plasma, over the average retention (8.0±2.0 percent) in 15 men who had had none. Three or more units of plasma did not increase the effect beyond that produced by one or two units. The effect was transient and disappeared between the first and second day following operation.


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Plasma Bilirubin and Uric Acid

The bilirubin and uric acid concentrations in the blood have been discussed earlier in this chapter in relation to other factors studied.

SUMMARY

In the past, battle wounds have been described chiefly in terms of organic damage or tissue loss. The purpose of this chapter has been to describe, shortly after the soldier arrived at the forward hospital, the latent consequences of his wounds as they influenced organic function and produced changes in blood volume and chemistry, and abnormalities in the urine. These matters were studied, before vigorous resuscitative efforts had yet been made, in 108 patients. Altogether, 186 patients were studied in the course of the work carried out by the Board for the Study of the Severely Wounded.

In considering patients who had received not more than one unit of plasma, or none at all, it was observed that the hematocrit level was higher in those with abdominal wounds than it was in those with peripheral wounds, but even in the patients with abdominal wounds the average hematocrit values were somewhat below normal. While severe hemoconcentration can occur in cases of burns, crush, and abdominal wounds, this was infrequent in our series and was by no means a general characteristic of shock as we saw it.

When the patients who had received little or no plasma or blood therapy at the time of first examination were divided into two groups, depending upon whether more or less than 30 percent of the blood volume had been lost, a puzzling situation was apparent: the average concentration of protein in the plasma in the more severely bled-out group was 6.1 grams per 100 cubic centimeters. This is 6.1 percent below normal. On the other hand, the average hematocrit value in this same group had fallen to 36 from the normal of 47, a reduction of 23.4 percent. The hematocrit level thus fell about four times as much as that of the plasma proteins. One implication of this is that the blood had been diluted with protein-rich fluid. Its possible source is discussed.

Evidence is presented that the plasma protein level was not influenced by plasma therapy, although the hematocrit level was. There was a sharp fall in hematocrit value with increasing severity of shock. Other examples of the independent variation of these two factors are given.

It is shown that men can lose about 75 percent of their blood and yet re-


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cover-more than had been generally supposed. Blood loss in various types of wounds is discussed. Data presented show that there was a quantitative relationship between loss of blood volume or hemoglobin and the degree of shock met clinically. This supports the view that the major cause of the shock we encountered was hemorrhage.

No important differences in blood volume or hemoglobin loss were encountered with the passage of time from wounding to examination. This was possibly to be accounted for by the high priority and consequent rapid evacuation given to patients with bleeding wounds.

The clinical condition of the newly wounded man offers abundant evidence that his internal state has been profoundly altered by the time he enters a forward hospital. In addition to the matters already mentioned, this was studied in terms of nitrogenous waste products, electrolytes, bilirubin, and blood sugar. In general, these substances were found not to be influenced by the location of the wound. The plasma nonprotein nitrogen level rose rather strikingly with delay following wounding. The full significance of this is not clear, but it offers grounds for some interesting speculation. Examination of the four shock categories in sequence from "no shock" to "severe shock" shows significant rises in nonprotein nitrogen, creatinine, phosphorus, and magnesium.

Acidosis was present in the patients in severe shock. They showed a considerable fall in carbon-dioxide combining power as compared with that of patients with no clinical evidence of shock. The acidosis appeared to be of the "metabolic" type.

No evidence of salt deprivation was found on hospital entry. Examination of the admission urine specimen with regard to hydrogen ion concentration and specific gravity indicated that the men studied had essentially normal renal function at the time they were wounded.

The van den Bergh index rose significantly with increasing time from wounding to examination. This is discussed briefly. No clear relationship of shock to bilirubin or plasma hemoglobin levels was found. The blood-sugar level was found to be above normal. It was particularly high in the patients with severe shock.

Definite depression of liver function, as measured by bromsulfalein retention, was found on hospital arrival. We found no correlation between liver function and the degree of shock. The administration of one or two units of plasma appeared to impair liver function still further. This was a transitory effect and was not increased by giving three or four units of plasma.

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