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Chapter 2

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

Post-traumatic Renal Insufficiency in Military Casualties

I. Clinical Characteristics*

    Major Paul E. Teschan, MC, USA, Captain Robert S. Post, MC, USAR, Captain Lloyd H. Smith, Jr., MC, USAR, First Lieutenant Robert S. Abernathy, MC, USAR, Captain John H. Davis, MC, USAR, Major Dell M. Gray, MC, USA, Captain John M. Howard, MC, USAR, Captain Kenneth E. Johnson, MC, USAR, Captain Edward Klopp, MC, USAR, Captain Roy L. Mundy, MSC, USA, First Lieutenant Maurice P. O'Meara, MC, USAR, and First Lieutenant Ben F. Rush, Jr., MC, USAR

I. Introduction

Post-traumatic renal insufficiency is a major problem in military medicine. In World War II, 40 per cent of one group of severely wounded patients developed acute post-traumatic renal insufficiency with a case fatality rate of 90 per cent among the severely oliguric.1 Renal lesions were found in 18.6 per cent of 427 unselected battle casualties who died in Army hospitals.2 Among 165 autopsied Korean battle casualties pathological evidence of renal damage occurred in 39 per cent and clinical uremia was severe enough to account for death in 14 per cent of the cases.3

The renal lesion in acute renal failure of traumatic and other origin has been studied by several investigators,2, 4-6 and the underlying similarity in the lesions has been emphasized by Lucke.4 The definitive description and concept of pathogenesis has been further clarified by the work of Oliver.7 A unified concept of acute renal failure as a clinical and biochemical sequel of several diseases has been documented by Swan and Merrill.8

The type of injury to the kidney and the subsequent clinical and biochemical changes in the renal insufficiency of military casualties are not qualitatively different from those seen in civilian medicine; but special consideration of the former seems warranted because-(1) development of clinical uremia and potassium intoxication is accelerated in this group of patients, with a resulting excessively high case


*Previously published in American Journal of Medicine 18: 172, 1955.


8

fatality rate; (2) this rapid course presents special therapeutic problems in which use of the artificial kidney requires evaluations; (3) occasional civilian patients injured in accidents, or after extensive surgery, develop renal failure with these characteristics;9 (4) there is a clear possibility, in the event of war, of widespread civilian casualties who may be expected to follow a similar course and to present similar problems.

The experience presented here includes all patients, 51 in number, who developed post-traumatic renal insufficiency and were admitted to a Renal Insufficiency Center* in Korea during 1952. This represents most of the combat casualties who developed oliguria, as defined below, and who survived the first 48 hours of resuscitation and surgery; patients who developed overt transfusion reactions were excluded from this group. The Center was equipped with a trained staff, an adequate supporting laboratory and a Brigham-Kolff-type artificial kidney. Ten additional patients were treated in a detailed, preliminary survey by members of the staff before the artificial kidney was available or a permanent location for the Center established. This experience presented here constituted a unique opportunity to evaluate the usefulness of a center for the treatment of this group of patients in the forward chain of casualty evacuation.

II. Definitions and Methods

By post-traumatic renal insufficiency is meant impairment in renal function secondary to diffuse parenchymal renal damage7 following trauma to the patient. Manifestations of post-traumatic renal insufficiency include the characteristic urinary, chemical and clinical findings in patients with acute renal failure of any origin. These findings are superimposed upon the expected sequelae of the antecedent wound, from which they cannot always be clearly differentiated.

Oliguria is arbitrarily defined as a urine output of less than 500 ml. in 24 hours. This is based on the demonstration that 500 ml. approximates the lowest sufficient volume of urine to clear the plasma of a normal metabolite load at normal maximal renal concentrating ability.10 Of course, with impairment of concentrating ability high levels of azotemia may occur at much higher rates of urine formation.

Diuresis is defined as beginning when a 24-hour urine volume equals or exceeds 1 liter after a preceding period of oliguria. During the


*Operated jointly by the Surgical Research Team, AMSGS, Washington, D. C., and personnel of the Eighth Army, Korea.


9

recovery phase the level of azotemia is seldom lowered by a urine volume of less than 1 liter.*

The 24-hour urine collections were taken by constant drainage from an inlying Foley catheter. Blood for chemical determinations was drawn with minimal stasis into previously heparinized syringes, centrifuged promptly and the plasma analyzed (by the following methods) for nonprotein nitrogen,11 carbon dioxide combining power12 and chloride.13 Sodium and potassium were measured in diluted, heparinized plasma by means of a Baird-Associates flame photometer using an internal lithium standard.

Electrocardiograms were taken with a direct-writing Sanborn electrocardiograph using standard and unipolar limb leads and precordial leads V1 through V6.

III. Diagnosis and Incidence

The incidence of post-traumatic renal insufficiency as defined above could be determined only by the routine use of sensitive diagnostic renal function tests on a large random sample of wounded men. Unfortunately, such a study has not been carried out. The diagnostic criterion used at the forward hospitals as a basis for referring patients to the Renal Insufficiency Center was that of oliguria (less than 500 ml./24 hours) without hypotension on the second or third post-wound day. The presence of uncomplicated dehydration as a cause of oliguria was excluded by a urinary specific gravity of less than 1.030 (it was usually below 1.020). Diagnosis was occasionally substantiated by lack of a diuresis in response to a water-load test, such as the infusion of 1,000 ml. of 5 per cent dextrose in water intravenously in 1 hour. These simple criteria indicated the patients' need for specialized therapy and doubtless excluded many cases of milder renal damage.† Because potassium intoxication and clinical uremia developed rapidly in the oliguric patients, they were evacuated to the Center as soon as the diagnosis was made.

During the last 6 months of 1952 there is reason to believe that almost all combat casualties who developed oliguria and who survived 48 hours after surgery were referred to the Renal Insufficiency Cen- 


*In contrast to the finding of Swan and Merrill,8 24-hour urine volumes in these patients did not usually increase at noticeably different rates below and above a 400 ml. daily output level; however, typical diuresis uniformly followed daily urinary outputs of 750 to 1,000 ml.
†As will be emphasized below, it is possible that renal insufficiency without oliguria might represent more of a therapeutic problem in an older casualty population, but this was rarely the case in these military casualties whose average age was 22.7 years.


10

ter. During this period 42 patients were referred to the Center from among approximately 8,000 wounded or injured-in-action patients admitted to medical treatment facilities.14 This represents an incidence of about 0.5 per cent or 1 oliguric patient per 200 surviving casualties. In a group of 4,000 consecutive acutely wounded patients treated at one forward hospital (1952-53), 19 patients developed oliguria, an incidence also approximating 0.5 per cent.

Post-traumatic renal insufficiency therefore is a statistically minor complication of wounding. This is not a cogent indication of its importance in military medicine, however. Approximately 20 per cent of soldiers hit in action in Korea were killed instantly or died before they reached forward hospitals.14 Of the casualties who reached the forward hospitals alive, approximately 97 to 98 per cent survived their wounds. Most of these had relatively minor wounds with uncomplicated convalescence. It is in the smaller number of severely wounded that renal failure constitutes an important cause of death during the postoperative period. In Italy during World War II at least 40 per cent of a group of very severely wounded casualties* studied at one forward hospital developed acute renal failure. Uremia was thought to be the major cause of death, accounting for 54 per cent of all fatalities in this group and resulting in an over-all mortality among severely wounded of 19 per cent.1

In Korea prompt evacuation made possible the early treatment of casualties with massive injuries. Forty-three such casualties who lived 3 days or longer after receiving 15 or more pints of blood on the day of injury were studied by the Surgical Research Team. Twenty one per cent of this group developed oliguria and an additional 14 per cent developed azotemia and clinically evident uremia while maintaining a daily urinary output of more than 500 ml.15 It is this range of incidence which indicates the real importance of post traumatic renal insufficiency as a military medical problem.

If may be anticipated that the incidence of post-traumatic renal insufficiency will vary in different military situations, depending on the availability of blood and the rapidity with which casualties are evacuated. Hence the data from Korea may represent a minimum 


*Non-transportable injured. In the subsequent discussion it is recognized that there is no completely satisfactory, objective definition of the term severely wounded as employed here. Because of improved technics of evacuation and medical care in the forward areas more extensive wounds became compatible with survival. In general, the "severely wounded" were those patients whose immediate survival, in the judgment of physicians in the forward areas, depended on prompt evacuation, resuscitation and surgery. In such patients, large volumes of injured tissue were regularly found and hypotension responded only to massive transfusions.


11

incidence with present methods of evacuation, resuscitation and surgery.

IV. Etiology

Extensive studies on the effects of shock1, l6-21 and of hemoglobin22-27 on renal function in man, and attempts to produce acute renal failure in experimental animals28-31 have not completely elucidated the relative roles of renal ischemia and of blood or tissue pigments in the pathogenesis of the renal tubular damage. Although it was realized that little could be added to the basic information about pathogenesis in such an uncontrolled, clinical study, an attempt was made to evaluate some of the antecedent and possibly etiological factors in this group of patients. It was hoped that a pattern might emerge by which the occurrence of post-traumatic renal insufficiency in an individual patient could be predicted.

1. Evacuation Time

As a general rule the acutely wounded patient is carried by litter from the point of wounding to the aid station supporting his battalion. Preliminary first aid treatment is given. Severely wounded patients are then evacuated to a forward surgical hospital by helicopter during the day and by ambulance at night. Less severely wounded patients travel by litter-jeep or ambulance through regimental collecting and division clearing stations and for definitive surgery if necessary at the forward surgical hospital. Albumin, dextran and whole blood are given as indicated along the route of casualty evacuation, and entries are made on the field medical record. Subsequent data have been obtained from these entries.

The time required for this evacuation sequence from time of wounding to forward hospital admission averaged 4.6 hours (range, 1 to 11 hours) in 51 patients whose records permitted this calculation. Approximately half of the patients reached a forward hospital within 3 hours of the time of wounding. The average time of evacuation in a control group of 41 severely wounded patients who did not develop renal insufficiency was 3.5 hours. It can be concluded that the delay in resuscitation necessitated by evacuation per se did not lead to the development of post-traumatic renal insufficiency.

2. Duration and Severity of Hypotension

(Systolic arterial blood pressure of less than 100 mm. Hg.)

In 50 patients from whose records estimates could be made, the duration of hypotension averaged 7.3 hours (range, 2 to 26 hours). Over half of the patients were hypotensive for 6 hours or less, but


12

no patient in this group was hypotensive for less than 2 hours. The mean duration of hypotension is considerably longer than the average evacuation time. This reflects the fact that persistent hypotension frequently prolonged preoperative resuscitative efforts, or recurred during or following operation.

Serial blood pressure readings were not available on any patient (and single readings only on 6) prior to admission to the forward surgical hospital, so that any estimate of the total duration of arterial hypotension is necessarily crude. These estimates include the evacuation time when the patient was hypotensive on hospital entry, unless normal blood pressures were previously recorded.

The estimated duration of hypotension in a control group of 41 severely wounded patients who did not develop oliguria was approximately 6 hours. It can be concluded that hypotension alone cannot be incriminated as a cause of renal failure. The amount of volume replacement therapy administered at the forward surgical hospital and during the prior evacuation period constitutes a further general measure of the degree of hypotension.

All 61 patients* received whole blood (and occasionally albumin, plasma or dextran) during the immediate post-wound period. Total volume therapy averaged 5.9 liters per patient (range, 0.5 to 15.5 liters). Whole blood accounted for 95.3 per cent of the total volume therapy given with the remainder divided among plasma 2.4 per cent, albumin 1.8 per cent and dextran 0.5 per cent. This approximated the relative use of these various oncotic agents in all the wounded at the time of this study. The resuscitative use of volume therapy was distributed in time as follows:
 

During evacuation to hospital

11%

Before surgery at hospital

30%

During surgery at hospital

40%

Postoperative period

12%

Unable to assign

6%

This distribution of volume replacement gives only a fair index of the presence and severity of hypotension, however, because (a) during evacuation blood was not always readily available and was difficult to administer, and (b) many of the most severely wounded patients were operated upon before their blood pressures were restored to normal.

In the group of 41 severely wounded patients who did not develop post-traumatic renal insufficiency, each received an average of 12 liters of volume therapy, largely as whole blood, during the total period of resuscitation (first 24 hours after wounding). It is possible 


*See Introduction, p. 8.


13

that the more liberal use of whole blood may have protected these patients against more severe renal damage.

3. Hemolysis and Plasma Hemoglobin

Type O whole blood was used exclusively in these patients. No overt transfusion reactions occurred. If increased, but subclinical, hemolysis of the recipients' erythrocytes by the hemagglutinins of the transfused blood contributed to the pathogenesis of the renal damage, it would be anticipated that fewer patients with type O blood would be found in this series than the relative incidence of type O in the population as a whole. Table 1 lists the blood types in the present series and a random sample of Occidental individuals; the differences are not statistically significant. This agrees with a similar study carried out by the Board for the Study of the Severely Wounded in World War II.1

Table 1. Incidence of Blood Types in Patients With Acute Post-traumatic Renal Insufficiency

Agglutinogen

No. of Patients

Per Cent

Per Cent of Normal Population*

O

23

55

41.8

A

12

29

37.7

B

5

12

13.9

AB

2

5

6.6

*From Sunderman and Boerner: Normal Values in Clinical Medicine, p. 74, W. B. Saunders Company, 1949.

Because of the long supply route from the United States, whole blood was used in the forward areas in Korea 7 to 28 days (average of about 2 weeks) after its withdrawal from the donor. Figure 1 illustrates the relationship between the age of blood and its plasma hemoglobin level.32, 33 Thus a patient receiving 6 liters of 2-week-old blood receives an infusion of about 2 gm. of hemoglobin at a time when there is probably marked renal vasoconstriction. In a study of renal function in casualties in Korea, however, Ladd could find no correlation between the plasma hemoglobin concentration and the degree of impairment of inulin and PAH clearances.16 He also found similar reduction in clearance in two patients resuscitated with dextran alone and in one patient resuscitated with fresh type-specific, compatible whole blood. The plasma hemoglobin concentrations and


14

FIGURE 1. Plasma hemoglobin (·) and potassium (0) of stored blood in relation to age. Values are means of at least 10 samples except for those on day 7 (5 samples) and day 9 (2 samples). Plasma was obtained from bottles later used for resuscitation at a forward surgical hospital.

total amount infused are low in comparison with amounts producing renal vasoconstriction in man.24, 25 Myoglobin may have been implicated in patients with massive tissue destruction or with severe, prolonged shock.1

4. Severity and Location of Wound

Post-traumatic renal insufficiency tended to occur as a complication in the most severely wounded, as might be anticipated from what is known of the pathogenesis of the condition and from the amount of volume replacement (5.9 liters per patient) needed for resuscitation. Ladd found that the renal blood flow and filtration rate were in general depressed in direct relation to the severity of the wound, as graded by an arbitrary point system for estimating the extent of the physiological impact including volume replacement required and amount of tissue damage.16

Table 2 lists the location of wounds encountered in the present series of patients compared with similar data obtained during World War


15

II1 and in previous combat experience.14, 34 Both perforating and penetrating wounds occurred in all groups.

Table 2. Number of Wounds of Selected Sites per 100 Casualties With Wounds of Any Site: General Casualty Population Compared With Patients With Post-traumatic Renal Insufficiency

Site of Wound

Korean Conflict1

Patients with Renal Failure

All Wounded in Action Admissions2

Patients Dying of Wounds2

Present Series 61 Patients

World War II 78 Patients3

Head, face, neck, extremities, with and without fracture

 145

 98

50

50

Abdomen4

13

33

59

35

Chest

13

17

 

22

Thoraco-abdominal

1

6

26

14

Liver

1

4

21

19

Kidney

1

3

23

17

Spinal Cord and vertebrae

2

4

2

1

Crush

5NA

5NA

5

6

1Based on preliminary unpublished data compiled from tabulations of individual medical records on all battle wound and battle injury admissions to medical treatment facilities in 1950-1952. Data obtained from Medical Statistics Division, Office of The Surgeon General, Department of the Army.
2Data for wounded in action admissions (WIA) include data for patients dying of wounds (DOW).
3Studied by Board for the Study of the Severely Wounded.1
4Includes pelvis and excludes liver and kidney.
5Not applicable (NA) to data for all WIA and DOW, all of which have been tabulated according to anatomical site, including those whose diagnosis was "crushing."

The higher incidence of thoraco-abdominal and abdominal wounds in patients developing renal failure compared with the general casualty population or with the group dying after initial hospital care is striking. Duration of hypotension and volume of whole blood given were also generally greater in patients with wounds of the trunk. Of interest also is the high incidence of wounds of the kidney usually resulting in nephrectomy. None of the patients sustained bilateral renal trauma, however.

In summary, prolonged periods of hypotension, infusion of necessarily large volumes of relatively old whole blood, and the severity


16

of the initiating wounds are possible factors in the etiology of post-traumatic renal insufficiency, implicated by their uniform occurrence in the oliguric patients referred to the Renal Insufficiency Center. There were a number of casualties, however, who failed to develop oliguria despite apparently identical histories and similarly severe wounds and prolonged periods of hypotension.

Likewise the occurrence of acute post-traumatic renal insufficiency could not be predicted on the basis of the foregoing data. However, such prediction with an accuracy of about 33 per cent15 was possible by observing the response of low postoperative blood pressures to whole blood transfusion. Many of the patients might well have died in shock without energetic and sustained resuscitative care in the postoperative interval. Patients who did not develop oliguria usually experienced a prompt blood pressure response to small transfusions. This experience indicated that acute renal failure impended in the postoperative period when an excessively large volume of blood was required to correct hypotension in the absence of continuing hemorrhage.

V. Renal Insufficiency Without Oliguria

Table 3 presents eight patients studied at the Renal Insufficiency Center who had marked impairment of renal function but who were never, or only transiently, oliguric. Renal insufficiency without oliguria probably occurred much more frequently than indicated here, but with absent or undiscovered oliguria and without obvious clinical uremia, such patients passed through the regular chain of evacuation. Potassium intoxication was usually not a serious problem in this group of patients.*

Clearance studies of renal function indicate that there is probably some measurable damage to the kidneys in almost all casualties who are severely wounded and undergo a period of hypotension.1, 16 It is not clear whether such patients develop the same type or severity of morphologic renal lesion as that seen in the oliguric patients. The smooth frequency distribution of the duration of oliguria in surviving patients suggests that at least the functional renal lesion in oliguric patients differs only in degree of severity rather than qualitatively from that in non-oliguric patients (Fig. 2). The characteristic peak


*Patient 17 had severe hyponatremia (serum Na, 117 mEq./L.) on admission to the Renal Insufficiency Center. A concurrent potassium level of 7.3 mEq./L. was associated with marked ECG findings of potassium intoxication. Dialysis was performed at once. Further inquiry revealed renal disease in the past in which his physician recommended his taking added salt. Persistent hyponatremia required such therapy during the diuretic phase.


17

Table 3. Patients With Evidence of Renal Failure Without Oliguria

Pt. No.†

Type of Wound

Evacuation Time

Duration of Hypotension

Volume of Colloid Therapy

Maximum NPN (BUN) Concentration

Minimum Urine Volume

PWD of Diuresis

hrs.

hrs.

liters

mg. % on PWD*

ml. on PWD

17

Bilateral blast amputation of legs with extensive infection; superficial wounds; laceration of femoral vein

3.0

5.0

14.3

219---------8

1050-----2

 

24

Lacerations, inf. vena cava; 2 perforations of duodenum

3.5

4.0

12.0

235**---------6

915-----3

 

31

Perforations, hepatic and splenic flexures of colon; laceration of inf. vena cava; bruise of duodenum

2.5

3.0

8.7

109***---------2

500-----1

2

52

Perforations, rt. and lt. lobes of liver, ascending colon, duodenum and stomach

?

?

3.5

321---------6

1000-----1

 

A

Bilateral traumatic amputation of legs at mid-calf, with many metal and bone fragments

2

8

9.5

(130)---------5

1100-----1

 

B

Perforated colon

8

8

1.0

100---------4

800-----4

 

C

Extensive lacerations of scalp, face, arms, left leg and back; multiple perforations of small bowel; fractures of both humeri

3

4

13.3

85---------4

1200-----1

 

D

Perforations of kidney, spleen, lumbar spinal canal with lower-extremity diplegia

4

?

4.3

210---------5

750-----1

 

†Patients 17, 24, 31, 52 from the series reported here. Patients A-D selected from experience at a forward surgical hospital.(15)
*Post-wound day.
**On PWD 3: CIn 2 mil./min.; CPAH 10 ml./min. On PWD 7: urine volume was 3600 ml., CIn 22 ml./min.; CPAH 131 ml./min.;
TmPAH 27.6 mg./min.
***On PWD 3: urine volume was 1540 ml., CIn 41; CPAH 208 ml./min.; TmPAH 30 mg./min.


18

FIGURE 2. Post-wound day on which urine volume exceeded 1,000 ml./24 hours in 29 surviving patients with post-traumatic renal insufficiency.

expected on days 9 to 11 is not seen although it might have been found had a larger number of patients survived long enough for diuresis to begin.

The occurrence of (1) renal damage demonstrated by relatively sensitive clearance technics, (2) marked azotemia and occasionally clinical uremia without oliguria or with very transient oliguria, and (3) overt oliguria of varying duration among severely wounded casualties who have sustained a period of hypotension suggests that there is a regular gradation of renal damage following wounding. Attention has been largely directed toward the most marked degree of renal damage manifested by oliguria because it alone appears to require specialized treatment.

VI. Potassium Intoxication

The frequency and rapidity of potassium intoxication constitute the most important difference between the post-traumatic renal insufficiency of combat casualties and the acute renal failure usually seen in civilian practice.

Myocardial potassium intoxication occurs in the presence of hyperkalemia but its severity is not strictly correlated with the plasma potassium concentration. Potentiated by concurrent hyponatremia, hypocalcemia, and possibly other factors, its actual myocardial effect and the imminence or remoteness of fatal cardiac arrest are accurately reflected in the electrocardiogram.35-41

Figure 3 compares the first recorded plasma potassium concentration, corresponding to the day of admission to the Renal Insufficiency Center, with the theoretically expected value in the non-traumatized "normal" as calculated by Strauss.42 Nine plasma potassium values fell within normal or expected limits; the low value in one of these patients may be explained by severe metabolic alkalosis due to unreplaced gastrointestinal fluid losses. Elevated initial plasma potassium concentrations were recorded in all but 6 of 51 oliguric patients and in 6 of 8 "non-oliguric" patients. In one patient a plasma potassium value of 7.5 mEq./L. was noted on the first post-wound day, and


19

FIGURE 3. Plasma potassium concentrations on admission to Renal Insufficiency Center. Average and range of values given for the number of patients indicated in each group. Diagonal represents theoretical accumulation of 0.3 mEq./L./24 hours.42

concentrations exceeding 7.0 mEq./L. occurred in one-third of the patients within the first 4 days of wounding. Death from cardiac arrest secondary to potassium intoxication occurred not infrequently as early as the fourth day after injury prior to the use of the artificial kidney. All patients demonstrated electrocardiographic evidence of myocardial intoxication sometime during the course of oliguria persisting longer than 5 days.

In 20 patients with adequate records, the mean increment of plasma potassium concentration following the initial value (obtained on admission) was 0.7 mEq./L. per 24 hours, over twice the theoretical rate.42 The average patient may therefore accumulate lethal concentrations of plasma potassium (9.0 mEq./L. or above) within 6 days of wounding, well before significant diuresis may be expected. Because of frequent hemodialyses, supervening diuresis, use of cation exchange resins for potassium removal and gastrointestinal losses of potassium, increments in plasma potassium concentrations following the initial values rarely reflect the true rate of catabolic potassium liberation, but rather afford a minimum estimate of it.

Case 1 was studied before the artificial kidney was available in Korea and illustrates the practical clinical problem:

A 20-year-old infantryman received multiple shell fragment wounds of his left arm with a severed brachial artery and damage to his median and ulnar nerves. Débridement and direct anastomosis of the brachial artery were performed 4.5 hours later at a forward surgical


20

hospital. Although admission blood pressure at the surgical hospital was 140/80 and pulse was 104, systolic blood pressure soon dropped below 100 mm. Hg where it remained for 12 hours before, during and after surgery despite infusion of 8 liters of whole blood. Postoperatively the patient's skin remained warm, dry and vasodilated. Thirty-seven hours later, blood pressure reached 110/70 where it remained. The left arm appeared non-viable. On the fourth post-wound day, clinical uremia appeared with stertorous breathing and stupor, the patient bled from nose and gums, mild cyanosis appeared and he died quietly. Pertinent data are summarized in Table 4.

Table 4. Data in Case 1

Post-wound Day and Time

Urine Volume

Plasma

ECG

Treatment

NPN

K

hrs.

ml.

mg. %

mEq./L.

1 – – 0600

68

73.8

4.3

 

1000 ml. 5% D/W

2 – – 0600

79

158

7.5

Moderate K intoxication

1500 ml. 5% D/W

3 – – 0600

100

220

8.0

 

40 gm. cation exchange resin;* 1000 ml. 5% D/W

4 – – 0100

179

232

8.6

 

 

4 – – 0800

 

272

8.7

Severe K intoxication

40 gm. cation exchange resin

4 – – 1920

 

277

11.2

 

Oxygen

*All resin used was the carboxylic exchanger SKF No. 648, furnished by Smith, Kline and French Laboratories.

Death on the fourth post-wound day in cardiorespiratory failure is felt to have been due to potassium intoxication.

There are three general reasons why potassium intoxication may occur so frequently and progress so rapidly in this group of patients:

(1) The Breakdown of Infused Erythrocytes. Erythrocytes contain approximately 100 mEq. of potassium per liter of cells. Figure 1 illustrates the rise of potassium concentrations in the plasma of stored blood prior to infusion into casualties in Korea.32 The average patient in this series receiving 5.9 liters of 15-day-old blood during resuscitation received 50 mEq. of potassium in the infused plasma. Following transfusion about 10 per cent of infused red cells disappear from the circulation within the first few hours, with consequent liberation of about 30 mEq. of potassium. Destruction of infused red


21

cells is accelerated in the severely wounded for several days following wounding as evidenced by falling hematocrits, slight elevations of serum bilirubin and studies of red cell survival.33

However, an infusion of 80 to 100 mEq. of potassium may not be expected to raise plasma levels significantly since it is distributed in an exchangeable body pool of about 3,300 mEq. in a normal 70 kg. subject.43 The potassium of infused plasma and that derived from erythrocytes of diminished viability do not produce significant hyperkalemia. This is demonstrated by eight patients who received between 6.5 and 24 liters of whole blood during resuscitation.44 The mean plasma potassium on admission to a forward surgical hospital was 4.4 mEq./L. (range, 3.5 to 5.4); following resuscitation and surgery the mean level was 4.8 mEq./L. (range, 3.0 to 6.2).

(2) The Breakdown of Tissue Cells. Potassium is contained primarily in muscle cells in a concentration of nearly 160 mEq./L. of cell water. Potassium is released from this reservoir in the wounded man by destruction of tissue at the site of initial injury, in the course of secondary infection, and because of ischemia and necrosis secondary to injury of nutrient blood vessels. Tissue catabolism is accelerated by the stress of wounding and surgery, fever, starvation and the immobility imposed by bed rest, casts and painful wounds. The rate of potassium release apparently varies widely according to the nature of the wound and the amount of ischemia and infection. In a number of cases, progression of hyperkalemia seemed to be blunted by removal of a gangrenous extremity or a second débridement of a dirty wound.45

(3) Electrolyte Shifts. Especially in the presence of acidosis, movement of potassium ions from the intracellular to the extracellular fluid may further contribute to the rising plasma potassium concentration.8, 37

Despite the large excretory load of potassium in patients with varying degrees of post-traumatic renal insufficiency, usually only those patients who were actually oliguric developed dangerous hyperkalemia (see footnote, sec. V). This reflects the remarkable ability of the kidney to excrete potassium even when diseased.46

VII. Clinical Manifestations

The progressive clinical, biochemical and electrocardiographic abnormalities following acute urinary suppression and their prompt resolution with diuresis are now well recognized and will not be recounted here.8, 37, 42 In acute renal failure following wounding this basic pattern is altered in the following important respects: (1) rates of clinical and chemical change, (2) prominent malnutrition,


22

loss of body weight, rapid edema accumulation, (3) severe infection, (4) impaired wound healing, (5) bleeding tendency and anemia, and (6) the incidence of hypertension.

(1) Rates of Clinical and Chemical Change

(a) Clinical Uremia. Anorexia, nausea, vomiting, lethargy and drowsiness attributable to uremia appeared in two-thirds of these patients by the fifth post-wound day and, as evidenced by clinical improvement following hemodialysis, as early as the second day. In several patients without intervening dialysis or diuresis, lethargy soon progressed to disorientation and coma, and death usually occurred approximately 6 days following wounding.47

Many manifestations of clinical uremia could often be attributed rather to the expected effects of severe sepsis, extensive wounds, reparative surgery of the chest or gastrointestinal tract, and persistent or recurrent hypotension. However, uremic symptoms usually developed in patients without such severe intercurrent processes when NPN concentrations exceeded 200 to 250 mg. per 100 cc. in the absence of diuresis.* Since these levels usually occurred by the fifth post-wound day (see below) uremia was thought also to contribute to the clinical picture in most instances, in addition to the other factors.

The clinical behavior of these patients contrasts sharply with that in cases of acute renal failure of non-traumatic origin in which uremic symptoms may appear by the sixth or seventh day and remain mild throughout the entire course.8

(b) Azotemia. Figure 4 compares the first recorded plasma NPN concentrations, corresponding to the day of admission to the Renal Insufficiency Center, on each of 52 patients with the theoretically expected value.42 Initial values are uniformly higher than the theoretical figure. Following the initial value, the mean rate of plasma NPN accumulation in the entire series is 50 mg. per 100 cc. per 24 hours, four times the rate calculated by Strauss.42 This may occur despite the therapeutic regimen described in the companion paper.47

The accelerated accumulation of NPN is a measure of the accelerated catabolism which characterizes these patients and corresponds to rates of clinical progression and of developing hyperkalemia and potassium intoxication (see section VI).

(c) Hyperkalemia has been discussed in section VI. 


*Onset of diuresis was usually associated with marked clinical improvement although NPN levels continued to rise. One patient was clinically well with a massive diuresis (5 to 8 liters of urine per day) for six consecutive days during which NPN exceeded 300 mg. per 100 cc.


23

FIGURE 4. Plasma NPN concentrations on admission to Renal Insufficiency Center. Average and range of values given for the number of patients indicated in each group. Diagonal represents theoretical accumulation of 12 mg./100 cc./24 hours.42

(2) Malnutrition, Loss of Body Weight, Rapid Edema Accumulation

Marked wasting of both muscle and subcutaneous fat was noted in patients surviving longer than 7 to 10 days. Adequate body weight measurements not affected by changes of casts, interval amputations and large débridements are available in 16 patients. The mean body weight loss was 1 kg. per day (range, 0.5 to 1.6), clinical degree of hydration remaining approximately constant. Patients lost between 10 and 30 per cent of their admission weights during an average course of 11 days (range, 4 to 33 days). Marked fluid restriction had been enforced in these patients, and weight loss was not usually more rapid during diuresis.

Parenteral caloric intake varied between 100 and 1,000 calories per 24 hours. Oral or intragastric intake was only rarely possible but permitted 1,000 to 2,500 calories per 24 hours during the oliguric phase. All caloric intake was sharply curtailed by necessary volume restriction, ileus or direct injury to the gastrointestinal tract. Caloric intake was thought to be insufficient in all instances despite vigorous efforts to increase it.


24

Accelerated catabolism was demonstrated in several striking instances when peripheral edema developed in the presence of positive non-colloid fluid balances not exceeding 400 ml./day. It was thought that, relative to tissue mass, the body water pool gained volume at a rate exceeding the combined rates of insensible, sweat and other fluid losses. With restricted intake, such increments in volume could arise only from the preformed water and water of oxidation of the catabolized tissue, with a small contribution from the infused glucose. It is concluded that conventional replacement allowances (measured water losses plus 750 to 1,000 ml./day) are excessive for patients with post-traumatic renal insufficiency. In any event, fluid balance should be adjusted on clinical grounds, not made to approximate a fixed, empiric value.

(3) Severe Infection

Penicillin and streptomycin were routinely given beginning on the day of injury. Broad-spectrum antibiotics were usually substituted within 5 days in most patients. Despite liberal use of antibiotics in patients whose renal antibiotic excretion was undoubtedly impaired, fever, leukocytosis, pulmonary and/or wound infection regularly occurred as is shown in Table 5. Whether the blood or tissue antibiotic concentrations achieved exerted any harmful effects could not be evaluated in this group of patients.

Table 5. Incidence of Infection on Patients With Post-traumatic Renal Insufficiency

Data

No. Patients with Adequate Records

No. Patients Affected

Per Cent Patients Affected

1. Site of infection

      a. Wound, including peritonitis or empyema in missile tract

45

38

84

b. Pulmonary, including purulent tracheal secretions; lung and pleura not in missile tract

39

30

77

2. Fever

39

37

95

3. Leukocytosis*

38

 

 

a. 10-20 thousand/cu. mm.

15

 

 

b. 20-30 thousand/cu. mm.

16

 

 

c. Over 30 thousand/cu. mm.

7

 

 

*Highest recorded value during course.


25

Peritonitis and/or empyema (localized or generalized) were found in 16 or roughly one-third of patients with adequate records. An additional 10 patients had extensive infection of buttock or extremity wounds necessitating either reamputation or repeated débridement. Evidence of massive infection was the prominent finding at autopsy and was thought to be the main cause of death in the majority of fatal cases after the artificial kidney became available.47

(4) Impaired Wound Healing

Granulation tissue appeared in some open wounds between the fifth and tenth post-wound days, but never in areas of infection and necrosis. Failure to slough necrotic tissue and establish a clean, granulating surface by the tenth post-wound day was taken to indicate impairment in the reparative process. Dehiscence of incisions and of vascular and even intestinal anastomoses provided another index. Dehiscences were thought to be rare in the general casualty population.48

In this group of patients, absence of granulation and of healing of open wounds was noted beyond 10 days in 16 of 24 records with specific data. Dehiscence of one or another type occurred in 9 instances or 16 per cent of 55 adequate records. In the absence of histological studies, the true incidence of delayed capillary and fibroblastic proliferation in the healing wound sites cannot be stated, nor can the relation of these to infection, anemia, azotemia, electrolyte imbalance, edema and nutrition be established.

(5) Bleeding Tendency and Anemia

Bleeding from the gastrointestinal tract, ecchymoses in skin, mucous and serous membrances, or epistaxis unrelated to trauma or unhealed surgical lesions was recorded in 15 or 27 per cent of 55 patients. In two patients with serious bleeding, bleeding time, clotting time and platelet counts were normal; in two additional patients the prothrombin time was prolonged in one, normal in the other. The use of heparin during hemodialysis accelerated bleeding in only two instances. Bleeding occurred on days prior to hemodialysis and in patients not subjected to the procedure.

Low and falling hematocrits irrespective of bleeding occurred in all patients surviving for 7 days or longer. In four patients hematocrits failed to rise significantly after whole blood transfusions even in the absence of, or with minimal amounts of blood loss. Frequent blood transfusions in an attempt to support blood pressure, wound healing and nutrition rendered pertinent studies impractical.


26

(6) The Incidence of Hypertension

Blood pressures of 140/90 mm. Hg or above were recorded in 85 per cent of 42 patients with adequate records during the course of acute renal failure. In 70 per cent, hypertensive blood pressure levels were recorded within the first four post-wound days. Most of the remaining patients who did not develop hypertension harbored severe wound infections, empyema or peritonitis. The average maximum blood pressure on the sixth post-wound day was 160/99, although readings of 180-200/100-110 were not infrequent. The clinical course was not apparently affected by the occurrence or degree of hypertension. These findings confirm observations in World War II1, 4 in which hypertension was uniformly noted in patients with acute renal failure. Elevated levels of blood pressure were also recorded in two-thirds of the patients studied by Swan and Merrill.8

Case 2 illustrates several of the foregoing features. Daily urine output, NPN, potassium and hematocrit values are presented in Figure 5.

FIGURE 5. Data in Case 2.

A 27-year-old infantryman sustained traumatic amputation of his right leg at the knee with multiple penetrating wounds of both buttocks and right arm in a land mine explosion. Evacuation required 5 hours during which 100 ml. albumin was given. Blood pressure was unobtainable by auscultation on admission to the forward surgical hospital. At surgery, severed vessels were ligated, a traumatic rectovesical fistula was discovered and repaired, and a diverting colos-


27

tomy established. Hypotension persisted for 16 hours and 3.6 liters of whole blood was used. Oliguria persisted on the third post-wound day and evacuation to the Renal Insufficiency Center was accomplished on the fourth.

Diuresis occurred on the twenty-third post-wound day, the most prolonged oliguria of any surviving patient. Although potassium intoxication occurred only prior to dialysis I, it is doubtful whether this patient could have survived the recurrent clinical uremia without repeated hemodialyses. Response of appetite, mental awareness and ability to cough was dramatic after dialyses I and II, less so after dialysis III. Infection was evident: A persistent cough productive of purulent sputum and a deeply-lying abscess in the right popliteal fossa were noted on the fourth post-wound day. Both infection and impaired wound healing were apparent on the twentieth post-wound day when the left leg wound was found to have necrotic skin flaps; some granulation tissue was noted in uninfected areas. On the twenty-fourth day urine appeared in the buttock wound indicating probable dehiscence of the retrovesical repair site. Wounds seemed improved on the twenty-eighth day and were granulating well by the thirty-third day. Epistaxis on the tenth post-wound day and melena between the twentieth and twenty-fourth days suggested a bleeding tendency since the patient sustained no facial or gastrointestinal wounds proximal to the colostomy. The hematocrit remained low in spite of 8 liters of transfused whole blood between the ninth and thirty-first post-wound days. All transfusions were well tolerated. A weight loss of 17 kg. or 32 per cent of admission body weight occurred in 34 days, despite oral food intakes after dialyses and parenteral allowances exceeding 400 calories daily. Generalized peripheral edema is recorded on the nineteenth day; preceding average positive measured fluid balance did not exceed 500 ml. per day.

VIII. Summary

Post-traumatic renal insufficiency is important as a cause of illness and death in initially surviving combat casualties and may be seen in civilian medical practice after accidents or extensive surgery. Hypotension appears to be a primary etiological factor although delay in therapy, inadequate blood replacement, increase in plasma hemoglobin and other pigments, and the severity of the wound may contribute to the extent of renal damage and to the hypotension itself. Impairment of renal function following trauma may be reflected in different patients by sensitive clearance tests only, by azotemia and decreased urinary concentrating ability, by transient oliguria, or by marked oliguria of varying duration. This suggests a wide variabil-


28

ity in the extent of functional and parenchymal renal injury. With few exceptions, only the oliguric patients develop sufficient electrolyte abnormality or clinical uremia to require special care. In the latter instances rapidly progressive potassium intoxication necessitates prompt evacuation to a treatment center and, in the patients reported here, was the major cause of death prior to the use of hemodialysis. In addition to potassium intoxication, evidence that accelerated tissue catabolism characterizes post-traumatic renal insufficiency is found in (1) rapidly developing clinical uremia with corresponding rates of NPN accumulation, (2) early signs and marked degree of weight loss and emaciation, and (3) edema formation on less than conventional fluid intake allowances. The contrast with acute renal failure of non-traumatic origin has been repeatedly emphasized. Frequently occurring extensive and progressive infection, impaired wound healing and a marked bleeding tendency in some patients complicate the clinical course and intensify the therapeutic challenge.

Acknowledgments

In addition to those mentioned in the Introduction to this volume, the authors wish to acknowledge the vital contributions made to this study and the operation of the Renal Insufficiency Center by the Surgeons, USAFFE and Eighth Army, Korea; the Center laboratory staff, especially Cpl. Burton F. Pease and Pfc. John T. Mackemull; the nurses and medical technicians of the 11th Evacuation Hospital under Capt. Mary Wilborne, ANC, Capt. Alice Service, ANC, and Lt. Anna Smyth, ANC; the Hospital laboratory staff under Lt. Robert P. Gibb, MC; and by the many officers and men of the chain of casualty evacuation to whom the patients who survived also owe their lives.

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29

7. Oliver, J., MacDowell, M., and Tracy, A.: The Pathogenesis of Acute Renal Failure Associated with Traumatic and Toxic Injury. Renal Ischemia, Nephrotoxic Damage and the Ischemuric Episode. J. Clin. Investigation 30: 1305, 1951.

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19. Barnett, C. H., Shapiro, S. L., Simeone, F. A., Beecher, H. L., Mallory, T. B., and Sullivan, E. R.: Renal Function Studies in the Wounded. Surgery 22: 856, 1947.

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21. Van Slyke, D. D.: Effects of Hemorrhage on the Kidney. Ann. N. Y. Acad. Sci. 49: 593, 1948.

22. Yuile, C. L.: Hemoglobinuria. Physiol. Rev. 22: 19, 1942.

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25. Smith, H. W.: The Kidney. Oxford University Press, New York, 1951.

26. Brandt, J. L., Frank, N. R., and Lichtman, H. C.: The Effects of Hemoglobin Solutions on Renal Functions in Man. Blood 6: 1152, 1951.

27. Ross, J. F.: Hemoglobinuria and Hemoglobinurias. New England J. Med. 233: 691, 732, 766, 1945.

28. Flink, E. B.: Blood Transfusion Studies. III. The relationship of hemoglobinemia and of the pH of urine to renal damage produced by injection of hemoglobin solution into dogs. J. Lab. and Clin. Med. 32: 223, 1947.

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30. Phillips, R. A., Dole, V. P., Hamilton, P. B., Emerson, K. J., Archibald, R. M., and Van Slyke, D. D.: Effects of Acute Hemorrhagic and Traumatic Shock on Renal Function in Dogs. Am. J. Physiol. 145: 314, 1946.


30

31. Phillips, R. A., and Hamilton, P. B.: Effect of 20, 60 and 120 Minutes of Renal Ischemia on Glomerular and Tubular Function. Am. J. Physiol. 152: 523, 1948.

32. 406th Medical General Laboratory: Annual Historical Report, 1952, Tokyo, Japan.

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34. Holmes, R. H.: Wound Ballistics and Body Armor. J. A. M. A. 150: 73, 1952.

35. Keith, N. M., and Burchell, H. B.: Clinical Intoxication with Potassium: Its Occurrence in Severe Renal Insufficiency. Am. J. Med. Sci. 217: 1, 1949.

36. Marchand, J. F., and Finch, C. A.: Fatal Spontaneous Potassium Intoxication in Patients with Uremia. Arch. Int. Med. 73: 384, 1944.

37. Merrill, J. P., Levine, H. D., Somerville, W., and Smith, S., III: Clinical Recognition and Treatment of Acute Potassium Intoxication. Ann. Int. Med. 33: 797, 1950.

38. Levine, H. D., and Merrill, J. P.: Advanced Disturbances of the Cardiac Mechanism in Potassium Intoxication in Man. Circulation 3: 889, 1951.

39. Currens, J. H., and Crawford, J. D.: Electrocardiogram and Disturbance of Potassium Metabolism. New England J. Med. 243: 843, 1950.

40. Moore, N. S., and Stewart, H. J.: Disappearance of Intraventricular Heart Block Occurring in Uremia following Intravenous Injection of Hypertonic Glucose Solution. Am. Heart J. 5: 469, 1930.

41. Teschan, P. E., and McDowell, M. E.: Artificial Kidney. Armed Forces Med. J. 3: 391, 1952.

42. Strauss, M. B.: Acute Renal Insufficiency due to Lower Nephron Nephrosis. New England J. Med. 239: 693, 1948.

43. Moore, F. D.: The Metabolic Response to Surgery. Charles C. Thomas, Springfield, Illinois, 1952.

44. Frawley, J. P.: Personal communication.

45. Rush, B. F., Jr., Teschan, P. E., and Post, R. S.: The Metabolic Response in Patients with Acute Renal Failure Associated with Massive Tissue Destruction and Infection: Surgical Aspects of Treatment. In preparation.

46. Leaf, A., and Camara, A. A.: Renal Tubular Secretion of Potassium in Man. J. Clin. Invest. 28: 1526, 1949.

47. Smith, L. H., Jr., Post, R. S., Teschan, P. E., Abernathy, R. S., Davis, J. H., Gray, D. M., Howard, J. M., Johnson, K. E., Klopp, E., Mundy, R. L., O'Meara, M. P., and Rush, B. F., Jr.: Post-traumatic Renal Insufficiency. II. Management and Prognosis. Am. J. Med. 18: 187, 1955 (Chapter 3, this volume).

48. Ziperman, H., formerly Surgical Consultant to the Surgeon, 8th Army: Personal communication.