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Chapter 12

Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV

Renal Changes in Patients Dying of War Wounds: Korea, 1950-1952

A Preliminary Report

    Captain Thorwald R. Anderson, MC, USAR
    Lieutenant Colonel Arthur Steer, MC, USA

Shortly after the onset of war in Korea there was concern lest the use of group "O" blood for all transfusions in the combat zone should cause serious reactions and a high incidence of acute renal failure.* When, after the first 6 months of combat, it became apparent that this fear was exaggerated, study of autopsy material was continued in an effort to learn more about the relation between fatal battle wounds and renal complications. The results of these studies were published in the annual reports of the 406th Medical General Laboratory1, 2, 3 and played a part in indicating the need for and justifying the establishment in 1952 of a renal failure center in Korea. Subsequently, publication of the study of the physiologic effects of wounds in the Mediterranean Theater in World War II4 showed that the experience in Korea was a confirmation of previous experience. It is probable that acute renal failure had always been an important complication of severe battle trauma, but had received little notice masked as it was by the direct effects of trauma and the attendant shock and infection. Of 324 autopsies performed on men who died after receiving wounds in battle in Korea, 111 showed the histologic changes of acute renal failure.

Materials and Methods

During the period 1 July 1950 to 1 January 1953, the protocols and tissues of autopsies on 324 battle casualties who died in military medical installations in the Far East were studied by the Pathology Department of the 406th Medical General Laboratory in Tokyo. Autopsies on patients who died of battle wounds were irregularly performed in the surgical hospitals in Korea and generally in 1950 and 1951 only 


*In this report acute renal failure, acute renal insufficiency, lower nephron nephrosis, hemoglobinuric nephrosis and acute tubular necrosis are considered synonymous in that they refer to a similar pathologic process.


236

when death was unexpected or unexplained. Autopsies were regularly performed on battle casualties who died in evacuation hospitals in Korea and in the hospitals in Japan. There was a considerable increase in the percentage of autopsies performed on men who died of wounds in hospitals in Korea as the battle situation became stabilized. In 1950 the ratio of autopsies to deaths from wounds was unknown but quite low; in 1951 it was approximately 3 per cent and in 1952 it was approximately 25 per cent. In 1950 and the first few months of 1951, a policy of rapid evacuation of patients to hospitals in Japan was in effect and much of the information obtained during this time came from these hospitals.

As the percentage of autopsies increased in the hospitals in Korea, protocols and clinical histories were given in greater detail and probably with greater accuracy. In part, this reflected the static battle situation which permitted more thorough study of patients and, in part, also reflected the influence of the various research teams in Korea which stimulated investigation along many lines.

Table 1. Regional Distribution of War Wounds in 324 Autopsies

Region

1950

1951

1952

Total

Head, neck, or spine

44

22

9

75

Thorax

4

6

11

21

Abdomen

19

10

13

42

Abdomen and thorax

12

8

11

31

Extremities

18

17

19

54

Abdomen and extremities

9

9

17

35

Multiple

19

18

*29

66

Total

125

90

109

324

*Including 6 with severe burns.

An attempt to determine whether the regional distribution of wounds (Table 1) was similar to that reported for other wars5 failed because the present autopsies, yielding more accurate information, frequently implicated multiple regions of injury while previous surveys, based on simple inspection and information giving only the presumed major wound of entrance, reported only a single region of injury.

Autopsy material from men who died of battle wounds was received from the 1st Medical Field Laboratory in Korea and from all hospitals in Korea and Japan. A special search was made in all cases for evidence of renal changes using paraffin sections stained with


237

hematoxylin and eosin. Selected cases were further studied using the following stains: fat, Schiff periodic acid, Feulgen, Heidenhain, LaPehne, Dunn-Okajima, and Wilder reticulum. The protocols of the 111 autopsies with histologic evidence of renal failure were studied to determine what part blood transfusion, shock, severity of injury, site of injury, and infection played in the pathogenesis of the renal lesions.

Clinical Course

The relation between severe trauma and acute renal failure was obscure and required cautious interpretation of clinical findings. The severely injured patient frequently showed clinical evidence of renal failure which was transient and disappeared with recovery from shock. Persistence of clinical findings was therefore required to establish the clinical diagnosis of acute renal failure. Consequently, diagnosis became difficult in patients so severely injured that death occurred within a few days after injury. Often in such patients there was little, if any, clinical evidence that death was hastened or made inevitable by superimposed renal failure although recognizable renal changes were found at autopsy. Further, evidence of nephropathy was found so frequently in patients who died of war wounds that, in some cases, it could be considered, like pulmonary edema and septic splenitis, a system or organ failure associated with the delayed death peculiar to trauma and the battle environment.

In the study on the physiologic effects of wounds in World War II4 it was concluded "that the clinical syndrome of renal insufficiency which follows shock is remarkable chiefly for the scarcity and mildness of its symptoms" and that "the symptom complex of oliguria, pigment excretion, azotemia and hypertension established the diagnosis." Search for such evidence is not always practical under battle conditions, and therefore, the pathologist's report of a renal complication sometimes surprised the clinician. Review of the protocols showed in retrospect that especially in 1950 the diagnosis might have been made more frequently (Tables 2 and 3) but not in all cases. Some of the patients died of their wounds before clinical evidence of renal failure developed, while in others the renal changes were probably a terminal event.

The severity of the azotemia varied considerably, and frequently was not sufficient of itself to establish a diagnosis of renal failure. Since rapid tissue breakdown and destruction could also produce azotemia, an ante-mortem diagnosis of acute renal failure usually was not made without other evidence. Similarly, oliguria was usually present


238

Table 2. Recorded Ante-mortem Evidence of Renal Failure in 111 Patients with Renal Changes at Autopsy

Ante-mortem Findings

1950

1951

1952

Total

Azotemia

0

2

1

3

Oliguria

4

6

6

16

Oliguria and azotemia

12

9

21

42

Oliguria and hypertension

1

0

0

1

Uremia

12

3

2

17

Oliguria, azotemia and hypertension

1

2

3

6

Total with ante-mortem findings

30

22

33

85

Total with renal changes at autopsy

43

35

33

111

Table 3. Clinical Diagnoses of Renal Failure in 111 Patients with Renal Changes at Autopsy

Clinical Diagnosis

1950

1951

1952

Total

Lower nephron nephrosis

12

15

27

54

Possible lower nephron nephrosis

1

2

0

3

Uremia

3

3

2

8

Total with diagnoses of renal failure

16

20

29

65

Total with renal changes at autopsy

43

35

33

111

during shock and in patients living only a few days this was not of great aid in establishing a diagnosis of acute renal failure.

A clinical diagnosis of acute renal failure was made more frequently in 1952. Many of these patients were treated at the Renal Failure Center but there was also a greater awareness among medical officers in other hospitals of the possibility of renal complications and a greater effort was made to treat this complication.6

Possible Etiologic Factors

Blood Transfusion. During the period of this report, more than 200,000 bottles of group "O" blood were sent to Korea, most of which was used for the treatment of the battle wounded. Blood labeled "Low Titer" could be given to all patients and blood labeled "High Titer"


239

was intended for group "O" patients only. It was neither practical nor possible to cross-match patients in forward hospitals or to determine the Rh type of the recipients. Very few reports were received of transfusion reactions. In only 4 of the 324 autopsy procotols was such a reaction reported and in only 2 of these was the reaction considered of sufficient severity to warrant naming transfusion reaction as a contributory cause of death. However, all four patients showed typical renal changes at autopsy.

Progressively larger amounts of blood were used in the treatment of battle casualties as the war continued. This was true also for the amount of blood given to the battle casualties who were found to have renal changes at autopsy (Table 4). These patients received more blood than the average of approximately 4.3 bottles of blood given to all battle casualties who were transfused,7 indicating that these patients were among the more seriously injured. The studies of the Surgical Research Team indicated that serious transfusion reactions due to the use of group "O" blood were rare.8

Table 4. Blood Transfusions to Patients Who Died of War Wounds and Had Histologic Evidence of Renal Changes-87 Autopsies

 

1950

1951

1952

Total

Number of patients

35

22

30

87

Total bottles of blood

203

198

360

761

Average-bottles per patient

5.8

9

12

8.7

Extremes-bottles per patient

1-52

2-28

2-40

 

Battle Trauma. Although it was desirable and perhaps theoretically possible to distinguish the renal effects of traumatic shock, tissue damage and infection, this could not be accomplished. Many variables influenced and determined the response to therapy and the occurrence of acute renal failure. These included the degree and duration of shock, the interval between injury and treatment, the site and severity of injury, the presence of infection, the climate and weather, the battle situation, the number of casualties requiring treatment at the same time, etc. Information concerning many of these factors was either fragmentary or unavailable.

Shock. Because of the large amount of blood given to the patients who died and showed renal changes at autopsy, it was assumed that most had suffered shock of a significant degree and duration. The protocols of 19 patients who died in 1952 stated that traumatic shock


240

had been present in all, with a duration of 11/2 to 20 hours and an average duration of slightly over 3 hours. The average interval between injury and surgery was 7 hours. For the other cases, only an estimate of the severity of shock could be made. This was based on the blood pressure when recorded, the pulse rate, the hematocrit, the type and severity of injury, the interval between injury and treatment, and the amount of blood transfused. Using such estimates, of 75 patients who could be evaluated, 58 had suffered severe shock probably for a considerable duration and 17 had suffered moderate shock.

Severity of Injury. The autopsy protocols of the 111 men showed renal changes were reviewed to determine the severity of their wounds. Twenty-five were judged to have wounds of moderate severity and 86 were classified as severely wounded. Those with wounds considered to be moderate would ordinarily have been expected to respond to modern forms of treatment if some other factor or combination of factors, such as prolonged shock, infection, gangrene, renal failure, secondary hemorrhage, had not complicated the course of recovery. Those judged to have severe battle wounds had a guarded or poor prognosis because of the amount and type of tissue damaged by the missile or because the wounds involved vital organs. A similar estimate of the patients who did not have renal changes at autopsy is not available.

Site of Injury. Study of the protocols of the 324 patients who died after receiving wounds in battle indicated that there was a relation between the site of injury and the ocurrence of renal failure (Table 5). Two groups were compared in an attempt to explain this. The first group consisted of all patients who died of wounds of the head,

Table 5. Regional Distribution of Fatal Wounds and Incidence of Autopsy Evidence of Acute Renal Failure

Region Wounded

Number Wounded

Number with Renal Changes

Per Cent with Renal Changes

1950

1951

1952

Average

Head, neck or spine

75

4

5

9

0

5

Thorax

21

0

0

0

0

0

Abdomen

42

26

63

50

69

62

Abdomen and thorax

31

12

57

25

27

39

Extremities

54

28

61

65

32

52

Abdomen and extremities

35

13

44

56

24

37

Multiple

66

28

37

56

38

42

Total

324

111

34

39

30

34


241

neck, spine or thorax. Few of these patients had histologic changes of acute renal failure at autopsy although many were exposed to the various factors accepted as possible causes of acute renal failure. Patients with head wounds usually suffered little shock and often did not receive blood transfusions but patients with thoracic wounds did suffer shock and were transfused. Infection occurred in all types of wounds. The second group consisted of all patients who died of wounds of the abdomen or extremities. This group had a high incidence of acute renal failure. Abdominal wounds generally had a relatively high mortality rate while extremity wounds, as a group, had a low mortality rate. Both severe extremity wounds and abdominal wounds were associated with shock, large blood transfusions and infections. It was not apparent why a majority of patients who died after receiving wounds of the abdomen or extremities showed autopsy evidence of acute renal failure while such evidence could not be found in any patient who had a fatal wound involving the thorax alone.

Infection. Infection present at the time of autopsy was difficult to evaluate as a factor in the pathogenesis of the renal changes. It appeared that infection frequently progressed because of lowered resistance in part due to renal failure but one could not be certain that infection had played a role in causing the renal failure or in making the renal changes more severe. A common clinical observation at the Renal Failure Center6 was that the blood nonprotein nitrogen level frequently rose more rapidly after dialysis than would be anticipated and that often this unexpected rise was an indication of the presence of unrecognized infection. Study of 24 patients who were treated at the Center and who had renal changes at autopsy (Table 6) indicated that patients with infections tended to have a high blood nonprotein nitrogen level.

Table 6. Relation Between Azotemia and Infection

 

Highest Recorded Blood Nonprotein Nitrogen Level

Finding at autopsy

35-100

100-200

200-300

300-400

400-500

Infection present

2

4

3

9

1

Infection absent

0

3

1

0

1

Severe infection was frequently present and often involved more than one region (Table 7). Peritonitis and cellulitis were the most frequent findings. The incidence and severity of infections found at autopsy of patients who did not have renal lesions are not available.


242

Table 7.-Presence of Infection at Autopsy

 

1950

1951

1952

Total

No. of patients with renal lesions

43

35

33

111

No. of patients with infections

?

27

23

?

Peritonitis

28

14

15

56

Cellulitis

12

8

10

30

Pleuritis

11

2

5

18

Pericarditis

2

0

0

2

Brain abscess

0

2

0

2

Meningitis

0

1

0

1

Pyelonephritis

0

0

4

4

Pathology

Although certain features of interest were observed in the study of these cases, little was added to our knowledge of the pathogenesis of or the actual site of injury in this condition variously known as lower nephron nephrosis,9 hemoglobinuric nephrosis,10 acute tubular necrosis,11 acute renal failure,12 etc. All of the cases met the requirements for histologic diagnosis although there was considerable variation in the severity of the lesions.

Weight of Kidneys. In most instances the kidneys were heavier than normal and in the few patients who had one kidney removed surgically, the remaining kidney showed hypertrophy. The weight of both kidneys, and of single remaining kidneys, after nephrectomy ranged from 200 to 725 grams with a median weight of 450 grams. The kidneys of patients who lived more than 13 days after wounding usually weighed more than 600 grams and those of patients who lived less than 10 days after wounding usually weighed less than 400 grams.

Histologic Observations. Necrosis of the epithelial cells of the tubules was a constant finding but no consistent relation could be recognized between the amount of tubular necrosis and the severity of injury, duration of life after injury, severity of renal failure, number of pigmented casts, or number and size of foci of inflammation.

Pigmented casts were also frequently present but no relation could be found between the number of casts in the cortex or the medulla and the duration of life after wounding in 31 of the patients who died in 1952. Casts were found in larger number in the medulla than in the cortex.

Foci of interstitial inflammation in the kidney were absent to minimal in patients who died within 5 days after injury, were numerous


243

and extensive in patients who lived from 6 days to 2 weeks after being wounded and tended to be fewer but larger in patients living more than 2 weeks after injury (Table 8). The infiltrates were found predominantly in the region of the cortico-medullary junction but when renal failure was severe and of long duration they were also found in the cortex about necrotic distal convoluted tubules. Because of the epithelial degeneration and the cellular reaction, involvement of the proximal portion of the nephron could not be recognized with certainty.

Table 8. Severity of Interstitial Infiltration and Interval Between Injury and Death

Interval Between Injury and Death (days)

Number of Patients

Severity of Interstitial Infiltration

Minimal

Mild

Moderate

Severe

3-5

10

8

1

1

0

6-10

8

3

2

2

1

11-15

8

1

2

2

3

16-19

5

1

2

1

1

Mallory4 reported significant fat droplet alterations in the epithelial cells of renal tubules in men dying 18 to 96 hours after injury and traumatic shock. He interpreted these changes as being morphologic evidence of parenchymatous injury and functional impairment. A search was made for similar changes in the kidneys of 23 of the patients who died in 1952 and showed renal changes at autopsy. Only one of these men died in the critical 18- to 96-hour interval after injury. Fat droplets measuring one to several micra in diameter were observed in many of the kidneys. They were found most frequently in the ascending tubules and less frequently in distal convoluted and collecting tubules. They were most prominent in sections from three patients who lived less than 6 days after injury but on the other hand were minimal in sections from three other patients who lived less than 6 days after injury. Control sections from patients who died a few hours after injury contained more fat droplets than this last group of three patients.

Tissues from the 23 patients studied for fat droplet changes were also studied for the presence of iron in the tubules. Controls for this study were provided by producing athrocytosis in rats13 by the injection of human hemoglobin. Within 2 days after such injections, gran-


244

ules appeared in the epithelial cells of the proximal portion of the nephron which had the same affinity as erythrocytes for the LaPehne and Dunn-Okajima stains. In none of the 23 human patients was there similar evidence of demonstrable iron or hemoglobin in the epithelial cells of the tubules. However, in sections from patients who had a short interval between injury and death, the pigmented casts in the proximal portion of the nephron showed some affinity for the stain. Similar casts in the distal portion of the nephron took the stain less intensely and those in the collecting tubules generally did not react at all. The pigment in the casts was not unequivocally identified as hemoglobin.

Discussion

It has been shown that the changes of acute renal failure are frequently found at autopsy in patients dying after being wounded in battle and that this is related, at least in part, to the degree and duration of shock, the region wounded and the severity of the wound. In addition to saving many lives, modern treatment of battle wounds delayed the death of the severely wounded and permitted the development and recognition of complications such as acute renal failure. In a certain number the renal changes were probably an indication of the failure of one system during the process of slow death after trauma. It was difficult to evaluate the effect of the renal changes in some of these cases because death occurred before clinical signs and symptoms could be recognized, and because in others the process was probably so mild that recovery from renal failure could have occurred were it not for the injuries and infection. However, the majority of patients did succumb to the combination of trauma, infection and acute renal failure. This combination occurs more frequently under military situations than in civilian life because the factors associated with the development of renal failure occur more frequently under battle conditions.

The diagnosis of acute renal failure was not always evident but when clinicians became aware of the frequency of occurrence of this complication they were much more successful in recognizing its presence. In 1950, 37 per cent of the cases were diagnosed and in 1952, 88 per cent were recognized. With increasing accuracy of diagnosis, more patients were treated more vigorously for renal failure with a saving of some lives. In war the severely wounded will continue to develop acute renal failure and it is likely that successful methods of prevention and treatment offer an opportunity for further reduction in the mortality rate from war wounds.


245

Conclusions

1. Approximately a third of men dying from war wounds in medical installations show histologic evidence of the changes associated with acute renal failure.

2. Predisposing factors for the development of these changes include site and severity of injured and duration and severity of shock.

3. The use of group "O" blood for all transfusions did not appear to be an important factor in causing acute renal failure.

4. Wounds of the abdomen and extremities were associated with a high incidence of renal changes and wounds of the head, neck, spine or thorax with a low incidence of renal changes.

5. Progressive and severe infection was frequently present in patients who showed renal changes at autopsy.

6. Diagnosis of acute renal failure required a high index of clinical suspicion.

References

1. Annual Historical Report, 406 Medical General Laboratory, 1950. APO 500, c/o P.M., San Francisco, California.

2. Ibid., 1951.

3. Ibid., 1952.

4. Board for the Study of the Severely Wounded, North African-Mediterranean Theater of Operations: Surgery in World War II. Med. Dept., U. S. Army, Washington, D. C., 1952, U. S. Government Printing Office.

5. Beebe, G. W., and DeBakey, M. E.: Battle Casualties, Incidence, Mortality and Logistic Considerations. Charles C. Thomas, Springfield, Illinois, 1952.

6. Meroney, W. H., and Herndon, R. F.: The Management of Acute Renal Insufficiency. J.A.M.A. 155 (10): 877, 1954.

7. Steer, A., and Hullinghorst, R.: The Blood Program in the Korean War.

8. Crosby, W. H., and Akeroyd, J. H.: Some Immunohematologic Results of Large Transfusions of Group O Blood in Recipients of Other Blood Groups; a Study of Battle Casualties in Korea. J. Hematology 9: 103, 1954.

9. Lucké, B.: Lower Nephron Nephrosis (renal lesions of the crush syndrome, of burns, transfusions and other conditions affecting lower segment of nephrons). Mil. Surgeon 99: 371, 1946.

10. Mallory, T. B.: Hemoglobinuric Nephrosis in Traumatic Shock. Am. J. Clin. Path. 17: 427, 1947.

11. Oliver, J.: Correlations of Structure and Function and Mechanisms of Recovery in Acute Tubular Necrosis. Am. J. Med. 15: 535, 1953.

12. Smith, H.: The Kidney; Structure and Function in Health and Disease. Oxford University Press, New York, 1951.

13. Rather, L. J.: Renal Athrocytosis and Intracellular Digestion of Intraperitoneally Injected Hemoglobin in Rats. J. Exper. Med. 87: 163, 1948.