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Chapter 11

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

Renal Sequelae of War Wounds in Man

Functional Patterns of Shock and Convalescence

First Lieutenant Michael Ladd, MC, USAR

Introduction

Acute renal failure, secondary to systemic pathological conditions, presents a bizarre challenge to all branches of clinical medicine. That following physical violence is frequently progressive and unrelenting,1 showing the most accelerated course with a mortality rate of close to 80 per cent.2 This form may be expected to increase in incidence and severity, both in civilian life and in the military theater, with increasingly successful methods of resuscitation from traumatic shock. Because of its unpredictable incidence and capricious nature, post-traumatic renal failure (PTRF) is a most frustrating postoperative complication.

The enigmas associated with this clinical syndrome seem largely due to a prevailing ignorance of its pathogenesis.3, 4 Obviously, much of the apparent mystery should resolve upon clarification of etiological mechanisms. The present investigation was planned to elucidate which primary derangement in renal function was ultimately responsible for the subsequent occurrence of PTRF. Accordingly, the early response to systemic injury was traced through convalescence in battle casualties in the forward Korean military theater. The observed sequence of discrete renal functional events, linking wound shock to subclinical states of post-traumatic renal insufficiency (PTRI) or manifest PTRF, is summarized below.

Clinical Methods

Data were collected from United Nations casualties evacuated through the 8209th Mobile Army Surgical Hospital between April and September, 1952, while this unit was situated in the Yangu Valley on the Eastern Korean front.

The subjects were of varied nationality, aged 18 to 27 years, and had been wounded in combat approximately 3 hours prior to admission. Emergency first aid administered at a collecting station before helicopter (or rarely ambulance) evacuation has been described else-


194

where.5 Except for urethral catheterization and intermittent blood sampling, study patients were treated routinely by attending medical personnel. Resuscitation from traumatic shock was preceded by a delay period between wounding and medical attention, that (except for three instances of 6, 7, and 12 hours respectively) ranged between 1 and 5 hours, averaging 3 hours. As pointed out by Howard,5 this differed significantly from the situation on the Western Korean front, as well as that described for World War II.6 Admission to the hospital was followed by massive transfusion, roentgenography and intestinal intubation in preparation for surgery. During surgical anesthesia, blood transfusion was continued as indicated by changes in blood pressure and pulse. Seven to ten liters of whole blood was often administered intravenously or intra-arterially within the preoperative period (average duration 2 hours). The total amount received during the entire period of resuscitation (average duration was 6 hours to completion of surgery) exceeded 10 liters in 9 of the 40 cases studied. The properties and various components of this banked blood, which was almost exclusively 10 to 20 days old, were concurrently under study by Olney7 and have been reviewed elsewhere.8 An occasional casualty could only be transiently resuscitated by continuous transfusions, amounting to as much as 20 liters of whole blood. This represents the only situation where a parallel may be drawn to the irreversible shock state37 seen in animals.

Renal function was studied at intervals during resuscitation and surgery and during the first postoperative week. The clearance of inulin (CIN) was used to measure glomerular filtration and that of PAH (CPAH) as an index of effective renal plasma flow. The clearance of endogenous creatinine (CCREAT) has been proposed as a more convenient measure of glomerular filtration.9 However, in 68 simultaneous clearance comparisons during convalescence, the ratio CCREAT/CIN averaged 0.8 (range 0.7 to 1.3 in nine patients) when CIN fell below 90 cc./min. It averaged 1.0 (range 0.9 to 1.2 in five subjects) when CIN exceeded 100 cc./min. During resuscitation of one subject, CCREAT/CIN increased progressively from 0.6 to 1.2. Evidence of altered tubular permeability as well as the tendency for analytical artifact18 to become exaggerated by metabolic sequelae of wounding, make the endogenous creatinine clearance highly unreliable under such circumstances. Proximal tubular function was measured by the maximal excretory capacity for PAH (TmPAH)4 and distal tubular function by the facultative ability to concentrate and dilute the glomerular filtrate.


195

Conventional clinical and analytical technics were necessarily modified because of the primitive environmental conditions. For instance, a constant plasma level of test substances was maintained by vigilantly regulating their infusion rate with an ordinary tunnel clamp. Forty minutes were always allowed to elapse between the injection of priming solutions and subsequent clearance periods; but during resuscitation, rapid adjustments in cardiovascular dynamics precluded any compensation for errors due to urinary dead space10 or for delays in equilibrium between plasma and interstitial fluid.11 Urine was obtained through an inlying Foley catheter, each urine collection period being terminated by washing the bladder three or four times with 50 cc. aliquots of sterile saline followed by air insufflation. Since many patients suffered from abdominal wounds, it was infrequently possible to express the bladder manually. To reduce errors from this source, the duration of collection periods usually exceeded 30 minutes, and data from three or more consecutive periods were averaged for final compilation. Heparinized blood samples were drawn from the most accessible vein or artery at convenient intervals. Plasma concentrations were plotted against time semilogarithmically so that mean values could be interpolated 3 minutes before the midpoint of each urine collection period.

Analytical Methods

PAH and inulin were measured in unyeasted cadmium sulfate filtrates of plasma and diluted urine, the former by the method of Smith et al.,12 and the latter according to Schreiner's modification13 of Roe's resorcinol method. For calculations of TmPAH, the F. W. factor was corrected for plasma protein (determined by the method of Phillips et al.14 and plasma PAH concentration using Taggart's nomogram,15 and assuming an A/G ratio of 2.5. Subsequently it was found16 that one lot of ampuled inulin
(U. S. Std. Products # 2341A) contained significant quantities of fermentable chromogen. Experiments in which this material was used have been deleted, and the present data were obtained with preparations containing less than 5 per cent fermentable chromogen (William Warner lot # 019101 and 023090 and U. S. Std. Products # 237Al). Plasma inulin concentrations were always greater than 30 times the concentration of blank reducing substances, and were raised to levels ranging between 200 and 300 mg. per 100 cc. whenever low urine flows necessitated excessive dilution with bladder washout fluid. Repeated plasma and urine recoveries showed less than 3 per cent of chemical analyses to have an error exceeding ±5 per cent.


196

Osmolarity of plasma and urine samples was calculated from their freezing point depression as recommended by Wesson,19 using a Leeds and Northrup Wheatstone bridge with a Western Electric Thermistor No. 14B mounted on a leucite stirring rod. All clearance data were converted to 1.73 square meters surface area.

Results

Renal Function During Resuscitation From Wound Shock

Clearance Measurements during Resuscitation. The renal clearance of inulin (CIN) and PAH (CPAH) was measured throughout resuscitation in six variably wounded casualties. In general, the results were similar to those previously reported by Lauson,17 supporting an identity between the immediate renal response to traumatic shock in civilian and military casualties.

Figure 1 compares renal clearance patterns in two casualties during the period from admission to recovery from anesthesia. Patient Number 17 (Fig. 1a) was a Turkish soldier who stepped upon a land mine 6 hours before admission. He sustained a traumatic amputation of the forearm, compound fractures of both tibiae and fibulae and extensive soft tissue destruction about the arms and legs. His course typifies that of mildly wounded men, developing little post-traumatic renal insufficiency. Moderate "shock" (classified according to the criteria presented by Beecher et al.6 was present on admission. He responded well to 2.5 liters of whole blood transfused during 2 hours of preoperative preparation. With induction of anesthesia, clearance values dropped abruptly from high preoperative levels, returning slowly thereafter. The ratio CIN/CPAH (filtration fraction, hereafter referred to as FF) remained above normal throughout in all such lightly wounded men. Of considerable interest is the elevation in urine flow seen in such cases during reaction from anesthesia, a phenomenon to be discussed subsequently.

Patient Number 36 (Fig. 1b) exemplifies the response to more profound injury. This American soldier sustained major shell fragment wounds of the chest, abdomen and extremities 7 hours before admission. He was given both plasma and blood at a battalion aid station within 30 minutes of wounding and presented only moderate shock on admission to the hospital. His condition proved to be less stable than that of Patient Number 17 and 25 points of blood were required during resuscitation. Although pulse and blood pressure were well controlled before surgery was undertaken, neither urine flow nor clearance levels responded as quickly. During an extensive thoraco-abdominal exploration, very little urine appeared and no recovery diuresis was manifest during reaction from anesthesia. Clearance levels never rose following induction of anesthesia, renal failure becoming evident


197

Data from a lightly wounded casualty (Case No. 17) are shown in Figure la. The course of a more severely wounded soldier (Case No. 36) is shown for comparison in Figure 1b. Clearance ordinates are plotted logarithmically. Filtration Fraction (CIN/CPAH) is expressed in per cent; arterial blood pressure in mm. of mercury. Normal averages are used as baselines. Arrows each represent 500 cc. whole blood transfusions. Vertical dotted lines enclose the period of anesthesia. Each patient presented moderate peripheral circulatory insufficiency on admission, but recovered a stable blood pressure and pulse rate preoperatively. Clearance values and urine flow rose progressively during resuscitation, more so in Case No. 17 (Fig. 1a). However, the preoperative time interval was insufficient to allow complete recovery of renal function in either case. Induction of anesthesia depressed clearances and urine flow abruptly. This cessation of renal function proved reversible in Case No. 17 (Fig. 1a), but was irreversible for Case No. 36 (Fig. 1b). During reaction from anesthesia, no recovery diuresis was manifest by the latter.

FIGURE 1. Renal Function during Resuscitation of Two Casualties.


198

FIGURE 2. Relationship Between CIN and CPAH during "Shock."

Filtration rate (CIN in cc./min.) is plotted on the vertical scale against effective renal plasma flow (CPAH in cc./min.). Each point represents one collection period obtained preoperatively, during the resuscitation of six casualties. In this and succeeding charts, clearance values are plotted on arithmetical scales. Diagonal dotted lines represent filtration fractions of 40, 20 and 10, respectively. FF was depressed at low values for CPAH, and rose as clearance values increased. This suggests re-establishment of glomerular filtration, under conditions of relative renal ischemia by efferent arteriolar constriction.

(as oliguria) in the early postoperative period. Shortly afterward the patient was transferred to the Renal Insufficiency Center, where following several courses of artificial dialysis, he succumbed to peritonitis 1 month later.

Figure 2 relates CIN to CPAH during the preoperative resuscitation of all six patients. FF was depressed at low clearance levels and became elevated during recovery from shock. This indicates re-establishment of glomerular filtration under conditions of relative renal ischemia by efferent arteriolar constriction.

It is noteworthy that preoperative transfusions of whole blood usually obliterated clinical signs of shock without restoring CIN or CPAH to normal. Both CIN and CPAH rose progressively with each collection period, but in five of six cases, insufficient time to effect full recovery was allowed prior to anesthesia. Table 1 compares the glomerular function of six casualties during actual surgical anesthesia with that of two healthy controls undergoing circumcision with "simulated major surgical anesthesia." Pentothal, nitrous oxide, oxygen and ether


199

Table 1. Renal Hemodynamics During Surgical Anesthesia

Case Number
Operative Procedure

Period

Blood Pressure mm. Mercury

CPAH cc./min.

CIN
CPAH

2
(Circumcision)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

120/70
80/50
140/82
130/80

680
500
540
700

22
16
20
30


(Circumcision)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

120/74
100/60
130/70
120/80

800
440
500
710

18
25
25
24

4
(Débridement of buttocks)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

120/65
150/70
90/50
120/90

410
88
400
700

41
14
20
38

21
(Laparotomy, closed reduction of femur)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

135/80
80/50
120/75
140/80

700
170
800
380

30
8
20
30

17
(Débridement of legs, open reduction tibia)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

120/80
100/70
100/65
110/66

380
42
320
410

24
30
34
30

23
(Débridement of buttocks, legs, ligat. vena cava)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

145/90
60/40
115/60
110/60

400
80
300
450

31
11
20
19

18
(Débridement and casting legs and buttocks)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

110/65
80/40
70/40
100/50

250
80
100
300

22
12
18
20

36
(Extensive thoraco-abdominal exploration)

Immed. preoperatively
Induction
Surgery
Immed. postoperatively

115/80
90/60
100/60
120/60

180
40
80
60

14
8
10
15

were administered in each case by either of two anesthetists using comparable technics. Induction of anesthesia invariably depressed renal function abruptly, the percentage change being inversely related to the preoperative clearance level. Since glomerular filtration and renal plasma flow recovered more sluggishly than the general circulatory status would suggest, there is some question as to the urgency with which the depressant effect of surgical anesthesia should be superimposed. Although immediate surgery is generally41 considered an inte-


200

gral part of resuscitation, it apparently constitutes additional trauma; hence, the premature induction of surgical anesthesia may irreversibly compromise the renal circulation.

Urine Flow during Shock and Resuscitation. Data are available from 52 casualties for hourly urine flow during resuscitation. Table 2 compares the mean values and standard deviations for hourly urine excretion with the degree of injury (estimated by a point scoring system described below). Between admission and operation mildly, moderately and severely injured casualties excreted essentially equal amounts of urine. However, during and after surgery, the more

Table 2. Hourly Urine Flow During Resuscitation (as cc. Per Hour)

Grade of Injury

Preoperative

During Surgery

Postoperative

2d Hour

4th Hour

6th Hour

Mild, 0-30 points (25 cases)

20±9

120±50

130±8

108±9

70±10

Moderate, 30-40 points (15 cases)

65±18

40±8

110±12

29±11

90±3

Severe, > 40 points (12 cases)

21±12

19±3

71±7

22±5

23±3

severely wounded showed a significant depression in urine flow as compared with lightly wounded men. Figure 3 shows oliguria, at this stage, to reflect a general depression in glomerular filtration. The direct relationship between CIN and urine flow (correlation coefficient for 47 observations in 6 casualties was 0.74) indicates a relative increase in tubular water reabsorption at low filtration rates, as would normally be expected according to current concepts of glomerulo-tubular balance.4

A phenomenon noted in three minor casualties was the excretion of 300 to 500 cc./hour for 1 to 2 hours after admission for no apparent cause. Low U/P ratios for endogenous creatinine (<15) indicated decreased tubular reabsorption, rather than increased glomerular filtration. Presumably some hormonal or neurogenic component of the wound sequence initiated this phenomenon, since it was not dependent upon either oral or intravenous fluid administration.

Recovery Diuresis after Anesthesia. A "recovery diuresis," consistently manifest during reaction from anesthesia, was roughly proportional to the severity of the injury and gave a crude measure of the prevailing clearance level. Minor casualties excreted an average of 2 cc./min. during the first two postoperative hours, although their urine flow could be increased to the range of 10 to 20 cc./min. by concomitant infusions of glucose or saline. Conversely, severely wounded men


201

FIGURE 3. Urine Flow and Filtration Rate during Resuscitation.

Urine flow (vertical scale), expressed as per cent of the filtration rate, is related to the filtration rate itself (CIN in cc./min.). Each point represents one collection period, from one of six casualties examined during the interval between admission and reaction from anesthesia. During this phase, urine flow varied directly with glomerular filtration, a relative increase in tubular reabsorption occurring at low values for CIN.

excreted less than 2 cc./min. even in the presence of saline or glucose infusions. This blunting of recovery diuresis reflected a persistent postoperative depression of glomerular filtration, despite maintained arterial blood pressure and regardless of supportive postoperative transfusions. No recovery diuresis was manifest by any patient (e. g., Cases Number 36, 44 and 45) who subsequently developed fulminating PTRF. These observations give prognostic importance to the hourly bedside record of urine flow. Impending severe renal failure probably may be predicted within 8 hours of wounding by the absence of a recovery diuresis (in the presence of normal arterial pressures). Anuria at this time justifies top priority in the evacuation chain.

The Wound Shock Sequence and Postoperative Renal Hemodynamics

CIN and CPAH were variably depressed after recovery from anesthesia, more so in the more severely wounded. Mean values for 376 clearance periods from 78 separate experiments upon 40 convalescent casualties are summarized in Table 3. These observations are further supported and qualified by additional information that is included in this table, but discussed in subsequent pages.


202-207

Table 3.


208

Table 4. Quantitative Estimation of Trauma

Section 1: Physiological loss incurred through damage to organ

Location of Wound

Organ Injured

Point Score

Subcutaneous Tissue:

Devitalized volume equivalent to one closed fist.21

0.5

Chest:

Hemothorax necessitating simple tap.
Thorocotomy

1.0
3.0

Abdomen:

Stomach, or small bowel,

    2 perforations
    >2 perforations

Negative laparotomy
Colon
Rectum
Bladder
Liver,

small laceration
mod. laceration
large laceration

Spleen
Pancreas
Vena cava, 

primary closure
ligation
 

3.0
3.0-7.0

1.0
1.5
2.0
1.5
 

1.0-3.0
3.0-5.0
5.0-7.0

2.0
3.0
 

3.0
7.0

Extremities: 
(Traumatic amputations:)

Wrist
Foot
Arm
Below knee
Knee
Thigh

1.0
2.0
2.0
5.0
6.0
7.0

Fractures:

Humerus
Tibia
Tibia and fibula
Pelvis

(simple)
(moderate)
(severe)

Femur

1.0
1.3
1.5
 

1.0-3.0
3.0-7.0
7.0-10.0

3.0

Section 2: Magnification of wound damage by delay in therapy


Multiply total score for tissue injury by factor computed as follows:

1.0 + (Hours of Delay/10) = F. 


Section 3. Transferred blood volume. A measure of individual variation in response, and the degree of "shock"

Volume of Blood

Point Score

5 bottles (2.5 liters)

1.0

10 bottles (5 liters)

3.0

15 bottles (7.5 liters)

5.0

20 bottles (10 liters)

7.0

25 bottles (12.5 liters)

10.0


209

Churchill20 has defined the magnitude of a battle wound as "the vector sum of its many components acting in the direction of deterioration." Table 4 gives a point-scoring system constructed to quantitate the potential influence of three "vector components" upon postoperative renal function. These are, in order of priority, the systemic insult incurred through damage to a given organ, the length of delay before treatment, and individual sensitivity to injury (degree of "shock"). Section 1 gives a point score arbitrarily allocated to the more commonly injured organs. It is based upon the relative physiological priority of their continued undamaged state. For example, destruction of abdominal organs should merit higher point scores than the loss of an equivalent volume of subcutaneous tissue.

The distribution of wound site among the various grades of PTRI (measured by the depression of CIN) is given in Table 5. As noted by others,5, 6, 22, 23 severe renal insufficiency most characteristically followed abdominal injuries, being more frequently irreversible after damage to more than three solid organs. This type of injury can also be seen to give rise to the highest point scores. Most of the patients in the lowermost ranks of Table 5 would, no doubt, have died had no facilities for rapid evacuation, resuscitation and surgery been immediately available. It should be noted that high, or supernormal, filtration rates probably occurred more frequently than indicated in Table 5, since this series of patients was selected according to the probability of their developing PTRI. However, the apparent scarcity of PTRF following thoracic and peripheral wounds seems valid since few, if any, cases escaped notice. Absorption of blood and necrotic debris should theoretically promote pyrogenic renal hyperemia.4 This may, in some measure, have reduced the severity of renal ischemia after thoracic and peripheral injuries.

The passage of time intensifies noxious aspects of trauma, mild hemorrhage culminating in irreversible shock because of delayed replacement.40 To compensate for this, wound severity was corrected for delay time between injury and medical attention by multiplying tissue damage score by: (hours of delay/10) + 1.0, as in section 2 of Table 4.

During resuscitation, it was the custom of attending surgeons either to speed up or slow down the rate of blood transfusion depending upon conventional indices6 of cardiovascular stability. Because identical wounds frequently effected a variable clinical picture in different soldiers, (different degrees of clinical shock) comparable casualties rarely needed the same volume of blood. Presumably this variation depended upon unequal volumes of hemorrhage plus individual differ-


210

Table 5. Number of Cases in Each Grade of Functional Impairment

% of Normal Function (estimated by CIN)

Peripheral Injuries

Peripheral w/ Abdominal Injuries

Thoracic Injuries

Thoraco-abdominal Injuries

Abdominal Injuries

1 Organ

2 Organs

3 Organs

Higher than normal

2

1

1

1

0

0

0

Normal

8

3

4

0

3

0

0

50-80% of normal

1

1

0

2

1

0

0

25-50% of normal

1

1

0

0

0

0

0

5-25% of normal

1

1

0

0

1

1

0

<5% of normal

0

0

0

2

1

0

2

Total

13

7

5

5

6

1

2


211

ences in sensitivity to a given wound. Accordingly, the required transfusion volume may be considered a rough index of these two inseparable components of the total wound insult. Their contribution was measured by arbitrarily adding one point to the total trauma score for each 2.5 liters of transfused blood (see sec. 3 of Table 4).

In Figure 4 mean values for CIN are plotted against the postoperative time interval. Casualties exposed to more drastic violence (closed

FIGURE 4. Glomerular Filtration during Convalescence.

Filtration rate (CIN in cc./min.) is related to the postoperative time interval in hours. In this and succeeding charts, unless otherwise stated, each point represents the average of several urine collection periods. Lines join consecutive observations from the same subjects. Horizontal dotted lines delineate the control range for CIN (from six non-injured soldiers). The same symbols are used in subsequent charts, although the key for the symbols appears in this figure only. Squares represent peripheral wounds; circles, thoracic wounds; the heavy letter K, periphero-abdominal wounds; half-moons, thoraco-abdominal wounds; triangles, abdominal wounds; and the capital letter G, control subjects. The magnitude of injury (see Table 4) is given by open symbols for less than 30 units of trauma (mild injury), half-filled symbols for 30 to 40 units of trauma (moderate injury), and closed symbols for more than 40 units of trauma (major injury). Patients who subsequently died in uremia are indicated by arrows curving over the baseline. All cases are described in detail in Table 3.


212

FIGURE 5. The Effect of Total Wound Insult upon Glomerular Filtration.

Filtration rate (CIN in cc./min.) is related to the total wound insult, as computed by the point trauma score given in Table 4. Each point represents the average of several urine collection periods obtained within 48 hours of resuscitation. Symbols for wound site are as given in Figure 4. Glomerular filtration was not significantly depressed by less than 30 units of trauma. The greatest degree of PTRI followed abdominal or combined abdominal wounds, where the degree of trauma exceeded 40 point units.

symbols) suffered more profound and prolonged postoperative depression in glomerular filtration. Conversely normal or supernormal values for CIN followed minor wounds (open symbols); moderate injury was followed by intermediate clearance levels. Most patients recovered normal function within 3 weeks, but more severe grades of renal failure were associated with such extensive injuries that death usually ensued from secondary causes2 (e. g., peritonitis) before full recovery of renal function occurred. Such cases are identified in Figure 4 by arrows curving over the baseline.


213

In Figure 5 values for CIN, observed within 48 hours of injury, are related to the point score computed from the total trauma scale shown in Table 4. The data clearly show that postoperatively glomerular filtration was inversely related to the total wound insult. In Figure 6 the same data for CIN are plotted against the volume of transfused blood required to effect resuscitation. There is some indication that at this time CIN may be roughly related to the previous extent of shock, but the data show considerable scatter. No single component of the wound insult showed as good a correlation with postoperative renal function as did the total point score. Filtration was frequently reduced (CIN<70 cc./min.) following abdominal or peripheral wounds producing little shock and requiring relatively few transfusions. On the other hand, more profound or prolonged states of peripheral col-

FIGURE 6. The Effect of "Shock" upon Glomerular Filtration.

The degree of "shock," measured by liters of blood needed for resuscitation, is related to the level of glomerular filtration (CIN in cc./min.) observed afterwards. Each point represents the average of several urine collections obtained within 48 hours of resuscitation. Symbols for wound sites are as given in Figure 4. Mild injuries (open symbols) failed to depress filtration, yet frequently required blood replacement exceeding the normal blood volume. Conversely, filtration was depressed by moderate (half-closed symbols) or severe (closed symbols) injury, whether transfusion volume was excessive (more than 10 liters), or not.


214

FIGURE 7. Effect of Wound Insult upon Plasma Flow and Filtration Fraction.

Effective renal plasma flow (CPAH in cc./min.) below, and filtration fraction CIN/CPAH in per cent) above, are plotted against the total wound insult computed by the trauma scale given in Table 4. Each point represents the average of three to five urine collection periods from one experiment within 48 hours of wounding. Symbols represent different wound sites given in the key for Figure 4. These data suggest that following mild to moderate trauma, glomerular filtration was maintained by efferent arteriolar constriction. After more than 35 point units of trauma this compensatory mechanism apparently failed to prevent greater decrements in filtration than plasma flow. Thus, the filtration fraction declined to about half the normal value following drastic wounds.


215

lapse accompanied major arterial hemorrhage. These commonly followed thoracic wounds, required massive transfusions, yet rarely preceded PTRI. Such critical emergencies were encountered more frequently than the data would indicate, but after it was realized that renal sequelae were unlikely to follow, they were seldom documented by laborious clearance measurements.

As shown by the data given in Table 3, the duration of preoperative hypotension was unrelated to the clearance level after surgery. Similarly postoperative hypotension was prolonged to the same extent in patients with and without reduced renal function. These observations detract from the significance of "shock" per se as an etiological factor in the genesis of PTRI. Similarly, Mallory23 found "patients with mild or no shock and patients with severe shock to have an equal incidence of fatal nephropathy."

With minor grades of injury, FF was inversely related to CPAH, suggesting maintenance of glomerular filtration by efferent arteriolar construction; but, as shown in Figure 7, after more than 35 units of trauma, FF progressively declined. Figure 8 indicates that for any given level of plasma flow, increasingly greater amounts of trauma decreased the relative magnitude of efferent arteriolar constriction, depressing FF. The most extreme renal response to trauma appeared to be a reduced filtration fraction at low clearance levels. Conversely, when FF progressively increased with time at low clearance levels, recovery seemed imminent.

Two theoretical mechanisms conceivably causing erroneous depression in clearance are tubular back diffusion and decreased extraction by secretory tissues. Although both mechanisms are suspect in pathological states, the observed low ratios for CIN/CPAHcan be attributed to neither. Back diffusion should most reasonably be expected to depress CPAH more than CIN because PAH possesses a smaller molecule and a greater diffusion coefficient. Reduced tubular extraction should also elevate the ratio CIN/CPAH, because only PAH depends on tubular secretion.4 A possible explanation for the low ratios may be a proximal shift in the locus of vasoconstriction from efferent to afferent glomerular arteriole, with progressively greater degrees of total wound trauma.

The Effect of Hexamethonium and High Spinal Anesthesia During Convalescence

During hexamethonium infusion (8 subjects) and spinal anesthesia to T5 (2 subjects), mean arterial pressure (taken as the diastolic pressure plus one-third of the pulse pressure24) fell more than CPAH, sug-


216

FIGURE 8. Effect of Trauma on the Relation Between FF and Plasma Flow.

Filtration fraction is shown to vary inversely with CPAH in the more lightly wounded (open figures). At comparable levels of plasma flow, FF was depressed by moderate (half-closed symbols) or severe (closed symbols) injury. Each point represents the average of several collection periods from one postoperative test. Consecutive observations from casualties in whom renal failure was precipitated by some postoperative complication are joined by dotted lines. These three patients, initially suffering from mild PTRI, each showed high values for FF before the postoperative complications. Subsequently FF declined with the onset of severe renal failure (false PTRI). As CPAH recovered during the convalescence of severely wounded patients, FF progressively rose, but as CPAH recovered during the convalescence of patients with minor wounds, FF progressively fell. The key to symbols for wound sites appears in Figure 4. All cases are described in detail in Table 3.

gesting decreased renal vascular resistance. Concomitantly, FF rose in lightly wounded patients, remained unchanged in moderately injured patients, and fell in severely wounded patients. This also suggests that the locus of renal vascular reactivity varies with the degree of trauma.

Renal Clearance Pattern and Postoperative Blood Volumes

Plasma volume (T1824) was measured in 14 casualties on the day of clearance determinations as described elsewhere.7 After mild to moderate trauma (<40 units), estimated blood volume (but not red cell mass) correlated roughly with CIN, CPAH, and ERBF (effective renal


217

blood flow, calculated from CPAH and the hematocrit as follows: ERBF=CPAH ÷ 1-Hct.).

In contrast to the pattern seen during chronic anemia in dogs74 and man,75 FF varied inversely with blood volume (but not red cell mass). Figure 9 shows that during convalescence from lesser wounds (10 cases), progressive improvements in blood volume were associated with corresponding elevations in renal blood flow. This would suggest that efferent arteriolar constriction may simply represent a com-

FIGURE 9. Renal Blood Flow and Blood Volume during Convalescence.

Effective renal blood flow (ERBF in cc./min.) is plotted on the vertical scale against blood volume (as per cent of the normal expected value). Each point is the average of several clearance periods on the day of blood volume determination. Solid lines join consecutive observations upon single individuals made on successive postoperative days. After minor (open circles) or moderate (crossed circles) trauma, ERBF was directly related to blood volume. However, the severe renal insufficiency caused by major trauma (>40 point units) was associated with early hypervolemia (solid triangles). The data suggest that the lesser grades of PTRI may be aggravated by hypovolemia but that hypervolemia develops soon after the onset of extreme renal insufficiency.

pensatory adjustment to hypovolemia, long known to follow major surgery.7, 21 However, the four cases of massive trauma (>40 point units) did not fit this pattern. Although CIN, CPAH, FF and ERBF remained severely reduced following resuscitation, blood volume appeared to be normal or supernormal. At this stage, the presence of hypervolemia may distinguish fulminating1 renal failure (solid triangles) from reversible PTRI (open and crossed circles).


218

Tubular Function During Convalescence

In 35 experiments upon 17 casualties, functioning, proximal tubular mass4 was estimated by the maximal limit to PAH secretion (TmPAH). The results are summarized in Table 3. The virtual volume of plasma cleared per unit functioning tubular tissue was expressed by relating CPAH to TmPAH as shown in Figure 10. Similarly glomerular function per unit functioning tubular tissue is given in Figure 11 by relating CIN to TmPAH. Ratios falling below the normal range (inclosed by

FIGURE 10. Renal Plasma Flow and Tubular Mass during Convalescence.

The functioning tubular mass (TmPAH in mg./min.) is plotted on the vertical scale, in relation to the effective renal plasma flow (CPAH in cc./min.). Each point represents the average of several urine collection periods during one postoperative test. Symbols for wound sites are the same as in preceding figures. Dotted horizontal lines enclose the normal range for the ratio CPAH/TmPAH (normal range 6 to 11). Solid lines connecting successive observations on single subjects show that ratios, initially low after wounding, returned toward normal during convalescence. Some lightly wounded casualties demonstrated supernormal values for TmPAH despite significant reduction in renal plasma flow.

diagonal dotted lines) indicate a greater impairment in glomerular than tubular function. Actually, TmPAH may have been even greater than observed because relatively low tubular loads (due to ischemia) could hardly saturate all functioning nephrons at low clearance rates. Low values for TMPAH may thus reflect virtual exclusion of normal functioning nephrons by reduced blood flow. It is unlikely that


219

hyperactive residual tubules could cause Tm's of the observed magnitude by "vicariously" clearing blood delivered from inert nephrons. Clearly, low ratios for CIN/TmPAH show relative ischemia of functioning nephrons.

Maintenance of TmPAH precludes reduced tubular extraction and supports the validity of CPAH as an indication of renal ischemia. In the absence of hypotension, this must reflect locally increased renal

FIGURE 11. Glomerular Filtration and Tubular Mass during Convalescence.

The abcissa is the same as in the preceding figure, glomerular filtration (CIN in cc./min.) being plotted on the horizontal scale. As in Figure 10, ratios falling to the left of the dotted diagonal lines (representing the normal range for the ratio CIN/TmPAH of 1 to 5) indicate a greater impairment in glomerular than in tubular function.

vascular resistance. Apparently trauma gives rise to some systemic trace effect, operating to diminish renal vascular caliber in rough proportion to the degree of systemic insult. High values for TmPAH noted in lesser grades of PTRI are incompatible with the presence of acute tubular necrosis suggesting that this morphological feature is only secondary to a continued functional disturbance in renal vascular tone. According to this view, azotemia stems from reduced filtration and tubular necrosis is only a secondary sequela of extreme and protracted post-traumatic renal ischemia.


220

Table 6. Hypertonic Parameter in Convalescent Casualties

Case No.

CIN cc./min.


cc./min.

Cosm

V

Cosm
cc./min.

TcH2O
cc./min.

TcH2O/CIN
per cent

CIN
per cent

CIN
per cent

43

5

0.4

11.7

8.9

0.5

0.1

2.8

2

84

10.5

16.9

12.6

14.1

3.6

4.3

41

47

5.6

18.0

11.9

8.5

2.9

6.1

38

16

3.2

24.8

19.8

4.0

0.8

5.0

10

166

8.5

10.8

5.1

17.9

9.5

5.7

35

76

12.5

21.0

16.4

16.0

3.5

4.6

17

230

39.6

19.5

17.2

44.7

5.3

2.3

25

61

9.6

25.5

15.9

15.4

5.8

9.6

21

194

33.3

19.9

17.2

38.6

5.3

2.9

29

122

7.3

10.8

6.0

13.2

5.9

4.8

5

106

26.0

28.9

24.7

30.7

4.5

4.2

6

146

19.0

15.8

13.0

23.1

4.1

2.8

31

104

9.8

14.4

9.3

15.0

5.3

5.1

18

36

6.3

22.0

17.5

7.9

1.3

4.5

45

4

0.9

26.4

22.3

1.0

0.2

4.1

42

24

3.3

17.7

13.9

9.3

0.9

3.8


221

Just as TmPAH measures proximal tubular integrity, the activity of the distal system is reflected by the facultative parameters25-27 to water reabsorption. Quantitative limitations to the concentrating mechanism (TcH2O )27 observed during infusions of pitressin and mannitol, at variably depressed clearance levels, are summarized in Table 6. At load/Tc ratios >2, the urine appeared dilute by crude urinometry, although cryoscopic analysis demonstrated significant hypertonicity. When CIN exceeded 70 cc./min., the absolute volume of solute-free filtrate abstracted to effect urinary concentration averaged 5.2 cc./min. This is almost identical with that found by Zac, Brun, and Smith (5.1 ± 1.5 cc./min.) in uninjured man.26 At lower values for CIN, the magnitude of TcH2O bore a constant functional relationship to the filtration rate, a pattern previously demonstrated during experimentally reduced filtration in the uninjured dog and seal.28, 29 Thus, the normal degree of urinary concentration was achieved (in all 16 casualties) by abstracting approximately 4 per cent of the filtrate at all clearance levels, regardless of the degree of PTRI.

Table 7. Hypotonic Parameters During Convalescence

Case No.

Days Postoperative

CIN 
cc./min.

Cosm. cc./min.


cc./min.

CH2
(V-Cosm)
cc./min.

CH20/CIN Per Cent

7

2

148

0.8

12.8

12.0

8

18

2

80

4.4

11.2

6.8

9

13

2

94

3.1

15.3

12.2

13

19

2

25

8.4

11.2

2.8

11

15

3

130

1.4

15.3

13.9

11

5

5

140

2.0

18.0

16.0

9

10

Table 7 gives the maximal volume of osmotically unbound water25, 30 excreted during water diuresis by three casualties showing low values for CIN. Comparable data are included for three other subjects with high clearance levels. When factored upon the filtration rate, maximal urinary hypotonicity, measured by the free water clearance (CH2O) was independent of the filtered, or execreted, urinary solute load. CH2O consistently approximated 10 per cent of the filtrate, regardless of the level of glomerular function. This would indicate that the relative magnitude of distal sodium reabsorption (TdNa)27 was


222

comparable to that of normal uninjured man,30 constituting further evidence for preservation of tubular integrity.

It is noteworthy that within 48 hours of >35 units of battle trauma, the osmolar clearance (Cosm)25-30 increased, the osmotic U/P ratio declined asymptotically toward 1.0, and plasma NPN exceeded 100 mg. per 100 cc. in all of six cases where this was measured. Comparable patterns of falling urinary specific gravity accompanied by parallel elevation in urine flow and plasma NPN have been illustrated in reports of extrarenal azotemia following transfusion reactions,31 uterine rupture with shock,32 gastrointestinal hemorrhage33 and other acci-

FIGURE 12. Urine Flow and Filtration Rate during Convalescence.

Daily urine output is expressed on the vertical scale as per cent of the prevailing filtration rate (CIN in cc./min.). Unlike the pattern seen early after injury, tubular water reabsorption was depressed in casualties showing low filtration rates. Azotemia, consequent to increased catabolism, or decreased filtration, or both, presumably accounts for the osmotic diuresis approaching 10 per cent of the filtration rate in severe PTRI.

dents. Figure 12 shows that during convalescence (as opposed to the pattern seen early after trauma in Fig. 1) the daily urine output approximated 10 per cent of the filtrate in moderate to severe grades of PTRI. Similarly, Howard5 has observed that 14 per cent of massively wounded casualties maintained daily urine outputs over 500 cc. despite clinical evidence of acute renal failure and uremia.


223

Data in table 6 constitute a strong argument against structural damage to the concentrating mechanism as a basis for isosthenuria. Actually the pattern shown in Figure 12 typifies any osmotic diuresis,4, 34-39 the solute load in this case comprising urea, creatinine, sulfates and phosphates. Teschan2 notes that these osmotically active tissue metabolites accumulate four times as fast in PTRF as in uremia of non-traumatic origin. Osmotic loads impeding the proximal reabsorption of more than 4 per cent of the filtrate would necessarily obliterate urinary concentration because of this quantitative limitation to TcH2O. At high values for Cosm/CIN, the effect of TcH2O would be almost imperceptible, except by freezing point determinations. Evidently, in battle casualties the accelerated accumulation of osmotically active tissue metabolites caused an osmotic diuresis preventing the occurrence of oliguria and masking all but the most extreme grades of renal failure.

Heme Pigment Metabolism and Renal Function

Gross hematuria has frequently been noted after traumatic injuries in man1, 31, 42, 43 and animals44-46 and has been attributed to glomerular damage46 from ischemic muscle metabolites,47-49 as has proteinuria.3, 44-46 The present group of casualties invariably exhibited dense proteinuria and hematuria. Theoretically, these abnormal urinary constituents alone would provide ample source for the precipitation3, 23 of heme pigment. But, in addition, the urinary supernatant was not uncommonly deeply colored, particularly after massive transfusion. Olney7 found the greatest concentration of free plasma hemoglobin in patients receiving the largest amounts of the oldest blood, but it disappeared from the plasma within 6 hours and could not explain persistent postoperative pigmenturia. Free urinary pigment was never noted in the absence of extensive muscle injury. On the other hand, many casualties with severe peripheral injuries and extensive muscle damage produced perfectly clear urine. No correlation was evident between the maximal plasma hemoglobin observed during or after transfusion (25 patients in Olney's series) and subsequent renal function. Neither the absolute amount of pigment excreted nor the per cent of circulating pigment excreted bore a consistent relationship to prevailing or subsequently determined clearance levels. The most massive intravascular hemolysis probably took place in three patients accidentally given distilled water intravenously. Patient Number 7 received 1,000 cc. during débridement of shell fragment wounds of the legs and buttocks. Patient Number 10 received approximately 1 liter of distilled water at a battalion aid station prior to


224

admission and Patient Number 37 received 800 cc. on the first postoperative day. No renal functional impairment was subsequently manifest in either case.

Large, coarse, reddish brown granules were frequently present in the urinary sediment of the more severely injured man. They were clearly visible to the naked eye and experimental mannitol diuresis usually flushed out a shower of these bodies, which disappeared from subsequent urine collections. Oliver3 points out that since these casts originate in, and by inference, obstruct straight collecting tubules, many proximal nephron units must be rendered impotent by their presence. It has frequently been suggested23, 50-52 that such bodies might cause renal failure either by obstruction or irritation. But, in five casualties, the formation of such casts was precluded by instituting a mannitol diuresis (500-2,000 gm. of mannitol intravenously) during and after resuscitation. Centrifuged urine from these five patients never revealed large casts, yet the prevention of urinary stasis and precipitation did not measurably improve renal function. Two of the five patients never recovered from PTRF and the three others showed clearance patterns comparable to untreated casualties with equivalent trauma point scores. In view of the above findings, as well as abundant experimental evidence reviewed elsewhere,3, 4 the role of heme pigment must be relegated to a position of secondary importance insofar as the genesis of post-traumatic renal insufficiency is concerned.

Clinical Statistics

Table 8 gives pertinent data bearing upon the relative incidence of renal failure during early convalescence from wounding in 1,000 consecutive major surgical patients evacuated through the 8209th Surgical Hospital between April and September, 1952. Only cases of severe renal dysfunction are included, since it was impossible to document all cases of minor or subclinical renal insufficiency (less than 30 point units of trauma). The latter occurred much more frequently than the present data would indicate. However, it is highly unlikely that severe renal failure had a higher incidence than given in Table 8, because hospital personnel were alert to its possible occurrence and no casualties manifested oliguria or anuria without prompt recognition. Since definitive medical care is, to a large extent, dependent upon terrain and logistics of any military theater, these figures may be considered applicable only to this particular sector. Furthermore, it must be admitted that the intensified general interest in potential


225

Table 8. Distribution of Severe Renal Insufficiency Among Major Surgical Cases

First Indication

Total Cases

Case Numbers

Blunted Recovery Diuresis

Lived more than 48 hours
Died within 48 hours

 

4
8*

 

(36, 42, 43, 44)
(26, 33, 45)

Oliguria Following Postop. Complication

Transfusion reaction
Intest. obst. and pneumonia
Overhydration, pulmonary edema Total (excluding early deaths)

 

2
1
1
8

 

(11, 13)
(38)
(39)

Oliguria, Persistently Depressed CIN,, Hypertension

Not dialyzed

 

4

 

(18, 24, 25, 42)

Persistently Depressed CIN,, Hypertension, No Oliguria

Received artificial dialysis
Received no dialysis Total

 

1
3
8

 

(19)
(35, 40, 41)

Grand Total (excluding early deaths)

16 (1.6 percent of 1,000 consecutive cases)

 

*Includes 5 unnumbered cases, recorded, but not documented by clearance studies.

candidates for renal failure may have precluded some factors normally contributing to its genesis.

It is noteworthy that acute renal failure of non-traumatic origin was frequently precipitated by a postoperative complication soon after wounding. Table 9 summarizes pertinent data obtained from all postoperative patients showing oliguria (<300 cc. urine/24 hours) who survived more than 48 hours beyond resuscitation. The figures show an equal incidence for both true PTRF and renal failure of non-traumatic origin (false PTRF). Seven of these oliguric patients were subsequently transferred to the Renal Insufficiency Center because of uremia. The five most severely injured (>40 point units of trauma) showed marked renal functional impairment immediately after resuscitation, as anticipated from their trauma scores. Here, oliguria unquestionably originated from wound trauma.

Two of the four other patients exhibited fairly high initial postoperative clearance values since they had suffered relatively little injury. One (Case Number 39) showed a moderate postoperative depression in clearance values because he had been badly injured (33 trauma points). Since the hematocrit in the fourth patient was only


226

Table 9. Distribution of Patients With Severe Oliguria

(Urine output less than 300 cc./24 hours)

Oliguria First Noted After Resuscitation

(True PTRF)

First Test

Complication

Subsequent Test

Outcome

Case No.

Point Units of Trauma

Hours after Surgery

CIN
cc./min.

CPAH
cc./min.

Type

Day

Hours Postop.

CIN cc./min.

CPAH
cc./min.

44

43

46

1

5

 

 

 

 

 

Died 3 weeks**

36

45

4

4

29

 

 

 

 

 

Died 3 weeks**

43

43

36

5

21

 

 

 

 

 

Died 2 weeks**

42

42

14

5

26

 

 

360

144

667

Recovered 4 weeks**

25

44

8

22

180

 

 

72

88

400

Evac. on 5th day, eviscerated, died uremia, 2d week.


227

Oliguria First Noted After Complication

(False PTRF)

First Test

Complication

Subsequent Test

Outcome

Case No.

Point Units of Trauma

Hours after Surgery

CIN cc./min.

CPAH cc./min.

Type

Day

Hours Postop.

CIN cc./min.

CPAH cc./min.

13*

*12

*24

*87

*289

Transf. React.

4

96

3

19

Recovered 5 weeks**

11

11

84

146

501

Transf. React.

8

200

1

12

Recovered 4 weeks**

39

33

9

74

246

Overhydration

2

50

2

11

Recovered 3 weeks**

38

15

13

120

353

Intestinal obstruction

4-5

200

16

59

Died 12 days

*Resuscitated with dextran wholly in place of blood.
**Transferred to the Artificial Kidney Center because of uremia.


228

15 at the time of study, clearances were presumably depressed73 by severe anemia. This patient received dextran wholly in substitute for blood. The transfusion reaction occurred while manifest anemia was being rectified, after completion of preliminary clearance studies. Shortly after the initial postoperative studies, each of the latter group met with unforeseen accidents. These were recognized too late, in each case, to forestall the onset of acute oliguria. It is not unlikely that during great military activity similar accidents might never have been recognized at all, since with heavy casualty loads, meticulous postoperative attention becomes impractical. Under such conditions acute renal failure (of nontraumatic origin) might easily be attributed to the wound shock sequence and incorrectly be considered true PTRF. Theoretically, any circumstance favoring the occurrence of such postoperative complications would increase the apparent incidence of true PTRF in the field. This may explain, in part, the apparently higher incidence noted in World War II6, 23 as well as the recognized lack of correlation between wound shock and the subsequent renal outcome.2, 6, 23

Discussion

During World War II, "hemoglobinuric nephrosis"23 was found in 19 per cent of 427 battle casualties autopsied in Italy. An even higher incidence (36 per cent) of "lower nephron nephrosis"54 was observed among 315 battle casualties autopsied at the 406th General Medical Laboratory22 in Tokyo between 1951 and 1952. These figures are at variance with the clinical incidence of PTRF shown in Table 8 as well as with Teschan's2 observation that renal failure was clinically manifest (including transfusion reactions, hemorrhagic fever, etc.) by less than 1 per cent of the 8,000 casualties incurred during the 1952 Korean campaign. Clearly, estimates based upon pathological material seem to exaggerate the actual incidence, and by implication, the importance of this complication in military medicine.

There are at least two possible explanations for this apparent paradox between morphological and clinical statistics. The first thing is that renal insufficiency frequently occurs in subclinical form. Newburgh53 showed that renal function may be reduced to one-tenth of normal without overt clinical manifestations, as is also apparent in the present study. Clinically imperceptible PTRI may predispose towards renal failure of nontraumatic origin (false PTRF). Secondly, among battle casualties at least, many deaths may be attributable to other causes and yet bear conventional pathological stigmata of "lower nephron nephrosis,"22, 54 "shock kidney,"55 "hemoglobinuric nephrosis,"23 etc.


229

Casualties dying within 48 hours of injury (for instance Cases Number 26, 33 and 45, included in Table 8) are an obvious source of such confusion. They are typically anuric and azotemic,2, 42, 56 differing from survivors of true PTRF chiefly by their rapid exodus. Serial determinations of plasma NPN in Case Number 26 showed values of 73 mg. per 100 cc. at 6 hours and 105 mg. per 100 cc. by the twelfth postoperative hour. It is well known that marked structural alterations occur within the kidney of such individuals if they survive for 18 hours.23, 54, 55, 65 These patients do not fit the ambiguous clinical criteria.2, 6 of PTRF; but the histories of anuria and azotemia, together with the morphological findings,22, 23, 54 force pathologists to classify these cases with other varieties of post-traumatic tubular necrosis. Hence, necropsy material is bound to suggest a higher incidence of renal sequelae.

Current speculation regarding the pathogenesis of PTRF is, in large part, derived from autopsies of battle23, 54 and air raid42, 62 casualties dying in uremia during World War II. The clinical syndrome of PTRI is generally presumed to reflect tubular damage incurred during shock by renal ischemia57-60 because the most striking morphological findings are limited to the renal tubules. It is inferred that glomerular filtration is restored upon resuscitation from shock. Uremia is thus attributed to back diffusion57-60 through damaged tubular walls, as observed by Richards61 in the poisoned frog kidney.

Since the extent of tubular necrosis was believed to be proportional to the severity or duration of hypovolemic shock,17, 42, 56-60, 62-65 prompt transfusion was recommended to prevent its occurrence.66 This prophylactic program of immediate blood replacement proved entirely feasible in the Korean Theater and was enthusiastically applied. Because of the liberal supply and free use of huge (up to 20 liters per patient) quantities of whole blood, hypovolemia was quickly and easily reversed. Thus Howard5 notes that "irreversible shock"40 was never encountered by the Surgical Research Team. Under such conditions, hypovolemia became the most easily controlled component of wounding, but this did not prevent the subsequent development of PTRI.

The present observations fail to support the conventional concept that PTRI reflects the degree of tubular damage incurred during "shock."57-60 In battle casualties, plasma flow and filtration were reduced during traumatic shock, but these indices remained persistently depressed after resuscitation without comparable reduction in proximal or distal tubular function. Although infrequently recognized, experimental traumatic shock in animals is followed by a similar per-


230

sistent renal ischemia.64, 67-69 This strongly suggests that systemic injury exerts its long-lasting effect primarily upon the renal vasculature rather than the renal tubule. If tubular necrosis occurs, it would not appear to reflect direct injury received during shock, but is more likely to result secondarily from a continued interference with renal blood flow during convalescence. The present low ratios for CPAH/TmPAH and the increased renal arterial-venous oxygen saturation difference found by Breed70 and Bull31 in man argue against the presence of an intrarenal shunt.71 Since PTRI is not apparently accompanied by decreased cardiac output72 nor concomitant hypotension, the only explanation for the persistence of renal ischemia after resuscitation is increased renal vascular resistance.

Normally the kidney maintains an almost constant renal blood flow despite reduced perfusion pressure4 by changes in renal vascular tone proximal to the glomerulus. Experimental evidence73 would indicate that following severe trauma this autonomy of the renal circulation may be obliterated or severely impaired. The renal response to minor war wounds must have entailed chiefly vasoconstriction distal to the glomerulus because CIN was maintained or even elevated, despite low values for CPAH. This pattern seemed influenced by postoperative plasma volume. Also, it was exaggerated by decrements in peripheral blood flow following ganglionic blockage or spinal anesthesia. Hence, the observed efferent arteriolar constriction may conceivably represent part of a prolonged systemic circulatory reaction to trauma. Conversely, CIN was depressed by severe injury to a greater extent than CPAH. Since low ratios for CIN/CPAH cannot be explained either by back diffusion or reduced tubular extraction, they are attributed to a relative increase in vascular resistance proximal to the glomerulus. Evidence of afferent arteriolar spasm has been observed by Sheehan and Moore52 and by Bell65 and is compatible with decreased glomerular reactivity postulated by deWardener73 to follow serious injury.

Summary

The renal function of military casualties was examined on over 100 separate occasions, during resuscitation from traumatic shock (6 cases), or during the interval between resuscitation and convalescence (40 cases).

The following discrete indices were measured intermittently: urine flow, CIN, CCREAT, CPAH, TmPAH and the hypotonic and hypertonic parameters of urine excretion conventionally designated CH2O and TcH2O respectively. The following components of wounding were examined for a relationship to postoperative renal function: degree and


231

duration of hypotension, transfusion volume, extent of intravascular hemolysis, postoperative blood loss (estimated by T1824 dilution) and the total wound insult computed by a point scoring system.

The conclusions drawn are that PTRI is primarily due to functional changes within the renal vascular bed, to which tubular disease may be a late secondary sequela, which are roughly proportional to the sum of all components of wounding but are independent of any single component, such as "shock." The predominant, measurable, renal abnormality is intractable ischemia, due to persistently increased renal vascular resistance following resuscitation from wounding. In its mild form, PTRI is characterized by relative efferent arteriolar resistance, but with progressive stages of wound severity, proportionately greater renal ischemia may reflect an increase in both efferent and afferent resistance and may secondarily result in loss of secretory activity. Excessive urinary solute loads accompanying azotemia, consequent to increased catabolism, or decreased filtration, or both, probably account for relative polyuria and isosthenuria, because no impairment in the urinary concentrating mechanism (TcH2O) was demonstrable for at least 3 days after manifest renal insufficiency.

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