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-
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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 state37seen 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.
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Conventional clinical and analytical technics were necessarily modifiedbecause of the primitive environmental conditions. For instance, a constantplasma level of test substances was maintained by vigilantly regulatingtheir infusion rate with an ordinary tunnel clamp. Forty minutes were alwaysallowed to elapse between the injection of priming solutions and subsequentclearance periods; but during resuscitation, rapid adjustments in cardiovasculardynamics precluded any compensation for errors due to urinary dead space10orfor delays in equilibrium between plasma and interstitial fluid.11Urine was obtained through an inlying Foley catheter, each urine collectionperiod being terminated by washing the bladder three or four times with50 cc. aliquots of sterile saline followed by air insufflation. Since manypatients suffered from abdominal wounds, it was infrequently possible toexpress the bladder manually. To reduce errors from this source, the durationof collection periods usually exceeded 30 minutes, and data from threeor more consecutive periods were averaged for final compilation. Heparinizedblood samples were drawn from the most accessible vein or artery at convenientintervals. Plasma concentrations were plotted against time semilogarithmicallyso that mean values could be interpolated 3 minutes before the midpointof 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 than5 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.
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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
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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.
FIGURE1. Renal Function during Resuscitation of Two Casualties.
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Filtration rate (CINin cc./min.) is plotted on the vertical scale against effective renal plasmaflow (CPAH in cc./min.).Each point represents one collection period obtained preoperatively, duringthe resuscitation of six casualties. In this and succeeding charts, clearancevalues are plotted on arithmetical scales. Diagonal dotted lines representfiltration fractions of 40, 20 and 10, respectively. FF was depressed atlow values for CPAH,and rose as clearance values increased. This suggests re-establishmentof glomerular filtration, under conditions of relative renal ischemia byefferent arteriolar constriction.
(as oliguria) in the early postoperative period. Shortly afterward thepatient was transferred to the Renal Insufficiency Center, where followingseveral courses of artificial dialysis, he succumbed to peritonitis 1 monthlater.
Figure 2 relates CIN to CPAHduring the preoperative resuscitation of all six patients. FF was depressedat low clearance levels and became elevated during recovery from shock.This indicates re-establishment of glomerular filtration under conditionsof relative renal ischemia by efferent arteriolar constriction.
It is noteworthy that preoperative transfusions of whole blood usuallyobliterated clinical signs of shock without restoring CINor CPAH to normal. Both CINand CPAH rose progressively with each collectionperiod, but in five of six cases, insufficient time to effect full recoverywas allowed prior to anesthesia. Table 1 compares the glomerular functionof six casualties during actual surgical anesthesia with that of two healthycontrols undergoing circumcision with "simulated major surgical anesthesia."Pentothal, nitrous oxide, oxygen and ether
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Table 1. Renal Hemodynamics During Surgical Anesthesia
Case Number | Period | Blood Pressure mm. Mercury | CPAH cc./min. | CIN |
|
2 |
Immed. preoperatively |
120/70 |
680 |
22 |
|
3 |
Immed. preoperatively |
120/74 |
800 |
18 |
|
4 |
Immed. preoperatively |
120/65 |
410 |
41 |
|
21 |
Immed. preoperatively |
135/80 |
700 |
30 |
|
17 |
Immed. preoperatively |
120/80 |
380 |
24 |
|
23 |
Immed. preoperatively |
145/90 |
400 |
31 |
|
18 |
Immed. preoperatively |
110/65 |
250 |
22 |
|
36 |
Immed. preoperatively |
115/80 |
180 |
14 |
were administered in each case by either of two anesthetists using comparabletechnics. Induction of anesthesia invariably depressed renal function abruptly,the percentage change being inversely related to the preoperative clearancelevel. Since glomerular filtration and renal plasma flow recovered moresluggishly than the general circulatory status would suggest, there issome question as to the urgency with which the depressant effect of surgicalanesthesia should be superimposed. Although immediate surgery is generally41considered an inte-
200
gral part of resuscitation, it apparently constitutes additional trauma;hence, the premature induction of surgical anesthesia may irreversiblycompromise the renal circulation.
Urine Flow during Shock and Resuscitation. Data are availablefrom 52 casualties for hourly urine flow during resuscitation. Table 2compares the mean values and standard deviations for hourly urine excretionwith the degree of injury (estimated by a point scoring system describedbelow). Between admission and operation mildly, moderately and severelyinjured 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 comparedwith lightly wounded men. Figure 3 shows oliguria, at this stage, to reflecta general depression in glomerular filtration. The direct relationshipbetween CIN and urine flow (correlationcoefficient for 47 observations in 6 casualties was 0.74) indicates a relativeincrease in tubular water reabsorption at low filtration rates, as wouldnormally be expected according to current concepts of glomerulo-tubularbalance.4
A phenomenon noted in three minor casualties was the excretion of 300to 500 cc./hour for 1 to 2 hours after admission for no apparent cause.Low U/P ratios for endogenous creatinine (<15) indicated decreased tubularreabsorption, rather than increased glomerular filtration. Presumably somehormonal 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," consistentlymanifest during reaction from anesthesia, was roughly proportional to theseverity of the injury and gave a crude measure of the prevailing clearancelevel. Minor casualties excreted an average of 2 cc./min. during the firsttwo postoperative hours, although their urine flow could be increased tothe range of 10 to 20 cc./min. by concomitant infusions of glucose or saline.Conversely, severely wounded men
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FIGURE3. Urine Flow and Filtration Rate during Resuscitation.
Urine flow (vertical scale), expressed as per cent ofthe filtration rate, is related to the filtration rate itself (CINin cc./min.). Each point represents one collection period, from one ofsix casualties examined during the interval between admission and reactionfrom anesthesia. During this phase, urine flow varied directly with glomerularfiltration, a relative increase in tubular reabsorption occurring at lowvalues for CIN.
excreted less than 2 cc./min. even in the presence of saline or glucoseinfusions. This blunting of recovery diuresis reflected a persistent postoperativedepression of glomerular filtration, despite maintained arterial bloodpressure and regardless of supportive postoperative transfusions. No recoverydiuresis was manifest by any patient (e. g., Cases Number 36, 44 and 45)who subsequently developed fulminating PTRF. These observations give prognosticimportance to the hourly bedside record of urine flow. Impending severerenal failure probably may be predicted within 8 hours of wounding by theabsence 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 CPAHwere variably depressed after recovery from anesthesia, more so in themore severely wounded. Mean values for 376 clearance periods from 78 separateexperiments upon 40 convalescent casualties are summarized in Table 3.These observations are further supported and qualified by additional informationthat is included in this table, but discussed in subsequent pages.
202-207
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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. |
1.0 |
|
Abdomen: |
Stomach, or small bowel, 2 perforations Negative laparotomy
Spleen ligation |
3.0 1.0 1.0-3.0 2.0 3.0 |
|
Extremities: |
Wrist |
1.0 |
|
Fractures: |
Humerus (moderate) (severe) Femur |
1.0 1.0-3.0 3.0 |
Section 2: Magnification of wound damage by delay in therapy
Multiply total score for tissue injury by factor computedas follows:
1.0 + (Hours of Delay/10) = F.
Section 3. Transferred blood volume. A measure of individual variationin 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 |
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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 potentialinfluence of three "vector components" upon postoperative renal function.These are, in order of priority, the systemic insult incurred through damageto a given organ, the length of delay before treatment, and individualsensitivity to injury (degree of "shock"). Section 1 gives a point scorearbitrarily allocated to the more commonly injured organs. It is basedupon the relative physiological priority of their continued undamaged state.For example, destruction of abdominal organs should merit higher pointscores than the loss of an equivalent volume of subcutaneous tissue.
The distribution of wound site among the various grades of PTRI (measuredby the depression of CIN) is given in Table5. As noted by others,5, 6, 22, 23 severe renal insufficiencymost characteristically followed abdominal injuries, being more frequentlyirreversible after damage to more than three solid organs. This type ofinjury can also be seen to give rise to the highest point scores. Mostof the patients in the lowermost ranks of Table 5 would, no doubt, havedied had no facilities for rapid evacuation, resuscitation and surgerybeen immediately available. It should be noted that high, or supernormal,filtration rates probably occurred more frequently than indicated in Table5, since this series of patients was selected according to the probabilityof their developing PTRI. However, the apparent scarcity of PTRF followingthoracic and peripheral wounds seems valid since few, if any, cases escapednotice. Absorption of blood and necrotic debris should theoretically promotepyrogenic renal hyperemia.4 This may, in some measure, havereduced the severity of renal ischemia after thoracic and peripheral injuries.
The passage of time intensifies noxious aspects of trauma, mild hemorrhageculminating in irreversible shock because of delayed replacement.40To compensate for this, wound severity was corrected for delay time betweeninjury and medical attention by multiplying tissue damage score by: (hoursof delay/10) + 1.0, as in section 2 of Table 4.
During resuscitation, it was the custom of attending surgeons eitherto speed up or slow down the rate of blood transfusion depending upon conventionalindices6 of cardiovascular stability. Because identical woundsfrequently effected a variable clinical picture in different soldiers,(different degrees of clinical shock) comparable casualties rarely neededthe same volume of blood. Presumably this variation depended upon unequalvolumes of hemorrhage plus individual differ-
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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 |
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ences in sensitivity to a given wound. Accordingly, the required transfusionvolume may be considered a rough index of these two inseparable componentsof the total wound insult. Their contribution was measured by arbitrarilyadding one point to the total trauma score for each 2.5 liters of transfusedblood (see sec. 3 of Table 4).
In Figure 4 mean values for CIN areplotted against the postoperative time interval. Casualties exposed tomore drastic violence (closed
Filtration rate (CIN incc./min.) is related to the postoperative time interval in hours. In thisand succeeding charts, unless otherwise stated, each point represents theaverage of several urine collection periods. Lines join consecutive observationsfrom the same subjects. Horizontal dotted lines delineate the control rangefor CIN (from sixnon-injured soldiers). The same symbols are used in subsequent charts,although the key for the symbols appears in this figure only. Squares representperipheral wounds; circles, thoracic wounds; the heavy letter K, periphero-abdominalwounds; half-moons, thoraco-abdominal wounds; triangles, abdominal wounds;and the capital letter G, control subjects. The magnitude of injury (seeTable 4) is given by open symbols for less than 30 units of trauma (mildinjury), half-filled symbols for 30 to 40 units of trauma (moderate injury),and closed symbols for more than 40 units of trauma (major injury). Patientswho subsequently died in uremia are indicated by arrows curving over thebaseline. All cases are described in detail in Table 3.
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FIGURE 5.The Effect of Total Wound Insult upon Glomerular Filtration.
Filtration rate (CIN incc./min.) is related to the total wound insult, as computed by the pointtrauma score given in Table 4. Each point represents the average of severalurine collection periods obtained within 48 hours of resuscitation. Symbolsfor wound site are as given in Figure 4. Glomerular filtration was notsignificantly depressed by less than 30 units of trauma. The greatest degreeof PTRI followed abdominal or combined abdominal wounds, where the degreeof trauma exceeded 40 point units.
symbols) suffered more profound and prolonged postoperative depressionin glomerular filtration. Conversely normal or supernormal values for CINfollowed minor wounds (open symbols); moderate injury was followed by intermediateclearance levels. Most patients recovered normal function within 3 weeks,but more severe grades of renal failure were associated with such extensiveinjuries that death usually ensued from secondary causes2 (e.g., peritonitis) before full recovery of renal function occurred. Suchcases are identified in Figure 4 by arrows curving over the baseline.
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In Figure 5 values for CIN, observedwithin 48 hours of injury, are related to the point score computed fromthe total trauma scale shown in Table 4. The data clearly show that postoperativelyglomerular filtration was inversely related to the total wound insult.In Figure 6 the same data for CIN are plottedagainst the volume of transfused blood required to effect resuscitation.There is some indication that at this time CINmay be roughly related to the previous extent of shock, but the data showconsiderable scatter. No single component of the wound insult showed asgood a correlation with postoperative renal function as did the total pointscore. Filtration was frequently reduced (CIN<70cc./min.) following abdominal or peripheral wounds producing little shockand requiring relatively few transfusions. On the other hand, more profoundor prolonged states of peripheral col-
The degree of "shock," measured by liters of blood neededfor resuscitation, is related to the level of glomerular filtration (CINin cc./min.) observed afterwards. Each point represents the average ofseveral urine collections obtained within 48 hours of resuscitation. Symbolsfor wound sites are as given in Figure 4. Mild injuries (open symbols)failed to depress filtration, yet frequently required blood replacementexceeding the normal blood volume. Conversely, filtration was depressedby moderate (half-closed symbols) or severe (closed symbols) injury, whethertransfusion volume was excessive (more than 10 liters), or not.
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FIGURE 7.Effect of Wound Insult upon Plasma Flow and Filtration Fraction.
Effective renal plasma flow (CPAHin cc./min.) below, and filtration fraction CIN/CPAHinper cent) above, are plotted against the total wound insult computed bythe trauma scale given in Table 4. Each point represents the average ofthree to five urine collection periods from one experiment within 48 hoursof wounding. Symbols represent different wound sites given in the key forFigure 4. These data suggest that following mild to moderate trauma, glomerularfiltration was maintained by efferent arteriolar constriction. After morethan 35 point units of trauma this compensatory mechanism apparently failedto prevent greater decrements in filtration than plasma flow. Thus, thefiltration fraction declined to about half the normal value following drasticwounds.
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lapse accompanied major arterial hemorrhage. These commonly followedthoracic wounds, required massive transfusions, yet rarely preceded PTRI.Such critical emergencies were encountered more frequently than the datawould indicate, but after it was realized that renal sequelae were unlikelyto follow, they were seldom documented by laborious clearance measurements.
As shown by the data given in Table 3, the duration of preoperativehypotension was unrelated to the clearance level after surgery. Similarlypostoperative hypotension was prolonged to the same extent in patientswith and without reduced renal function. These observations detract fromthe significance of "shock" per se as an etiological factor in the genesisof PTRI. Similarly, Mallory23 found "patients with mild or noshock and patients with severe shock to have an equal incidence of fatalnephropathy."
With minor grades of injury, FF was inversely related to CPAH,suggesting maintenance of glomerular filtration by efferent arteriolarconstruction; but, as shown in Figure 7, after more than 35 units of trauma,FF progressively declined. Figure 8 indicates that for any given levelof plasma flow, increasingly greater amounts of trauma decreased the relativemagnitude of efferent arteriolar constriction, depressing FF. The mostextreme renal response to trauma appeared to be a reduced filtration fractionat low clearance levels. Conversely, when FF progressively increased withtime at low clearance levels, recovery seemed imminent.
Two theoretical mechanisms conceivably causing erroneous depressionin clearance are tubular back diffusion and decreased extraction by secretorytissues. Although both mechanisms are suspect in pathological states, theobserved low ratios for CIN/CPAHcanbe attributed to neither. Back diffusion should most reasonably be expectedto depress CPAH more than CINbecause 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 explanationfor the low ratios may be a proximal shift in the locus of vasoconstrictionfrom efferent to afferent glomerular arteriole, with progressively greaterdegrees of total wound trauma.
The Effect of Hexamethonium and High Spinal Anesthesia During Convalescence
During hexamethonium infusion (8 subjects) and spinal anesthesia toT5 (2 subjects), mean arterial pressure (taken as the diastolic pressureplus one-third of the pulse pressure24) fell more than CPAH,sug-
216
FIGURE8. Effect of Trauma on the Relation Between FF and Plasma Flow.
Filtration fraction is shown to vary inversely with CPAHin the more lightly wounded (open figures). At comparable levels of plasmaflow, FF was depressed by moderate (half-closed symbols) or severe (closedsymbols) injury. Each point represents the average of several collectionperiods from one postoperative test. Consecutive observations from casualtiesin whom renal failure was precipitated by some postoperative complicationare joined by dotted lines. These three patients, initially suffering frommild PTRI, each showed high values for FF before the postoperative complications.Subsequently FF declined with the onset of severe renal failure (falsePTRI). As CPAH recoveredduring the convalescence of severely wounded patients, FF progressivelyrose, but as CPAH recoveredduring the convalescence of patients with minor wounds, FF progressivelyfell. The key to symbols for wound sites appears in Figure 4. All casesare described in detail in Table 3.
gesting decreased renal vascular resistance. Concomitantly, FF rosein lightly wounded patients, remained unchanged in moderately injured patients,and fell in severely wounded patients. This also suggests that the locusof renal vascular reactivity varies with the degree of trauma.
Renal Clearance Pattern and Postoperative Blood Volumes
Plasma volume (T1824) was measured in14 casualties on the day of clearance determinations as described elsewhere.7After mild to moderate trauma (<40 units), estimated blood volume (butnot red cell mass) correlated roughly with CIN,CPAH, and ERBF (effective renal
217
blood flow, calculated from CPAH andthe hematocrit as follows: ERBF=CPAH ÷1-Hct.).
In contrast to the pattern seen during chronic anemia in dogs74and man,75 FF varied inversely with blood volume (but not redcell mass). Figure 9 shows that during convalescence from lesser wounds(10 cases), progressive improvements in blood volume were associated withcorresponding elevations in renal blood flow. This would suggest that efferentarteriolar constriction may simply represent a com-
FIGURE9. Renal Blood Flow and Blood Volume during Convalescence.
Effective renal blood flow (ERBF in cc./min.) is plottedon the vertical scale against blood volume (as per cent of the normal expectedvalue). Each point is the average of several clearance periods on the dayof blood volume determination. Solid lines join consecutive observationsupon single individuals made on successive postoperative days. After minor(open circles) or moderate (crossed circles) trauma, ERBF was directlyrelated to blood volume. However, the severe renal insufficiency causedby major trauma (>40 point units) was associated with early hypervolemia(solid triangles). The data suggest that the lesser grades of PTRI maybe aggravated by hypovolemia but that hypervolemia developssoon 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) didnot fit this pattern. Although CIN, CPAH,FF and ERBF remained severely reduced following resuscitation, blood volumeappeared to be normal or supernormal. At this stage, the presence of hypervolemiamay 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 tubularmass4 was estimated by the maximal limit to PAH secretion (TmPAH).The results are summarized in Table 3. The virtual volume of plasma clearedper unit functioning tubular tissue was expressed by relating CPAHto TmPAH as shown in Figure 10. Similarlyglomerular function per unit functioning tubular tissue is given in Figure11 by relating CIN to TmPAH.Ratios falling below the normal range (inclosed by
FIGURE10. Renal Plasma Flow and Tubular Mass during Convalescence.
The functioning tubular mass (TmPAHin mg./min.) is plotted on the vertical scale, in relation to the effectiverenal plasma flow (CPAHin cc./min.). Each point represents the average of several urine collectionperiods during one postoperative test. Symbols for wound sites are thesame as in preceding figures. Dotted horizontal lines enclose the normalrange for the ratio CPAH/TmPAH(normal range 6 to 11). Solid lines connecting successive observationson single subjects show that ratios, initially low after wounding, returnedtoward normal during convalescence. Some lightly wounded casualties demonstratedsupernormal values for TmPAHdespite significant reduction in renal plasma flow.
diagonal dotted lines) indicate a greater impairment in glomerular thantubular function. Actually, TmPAH may havebeen even greater than observed because relatively low tubular loads (dueto ischemia) could hardly saturate all functioning nephrons at low clearancerates. Low values for TMPAH may thus reflectvirtual exclusion of normal functioning nephrons by reduced blood flow.It is unlikely that
219
hyperactive residual tubules could cause Tm`s of the observed magnitudeby "vicariously" clearing blood delivered from inert nephrons. Clearly,low ratios for CIN/TmPAHshow relative ischemia of functioning nephrons.
Maintenance of TmPAH precludes reducedtubular extraction and supports the validity of CPAHas an indication of renal ischemia. In the absence of hypotension, thismust reflect locally increased renal
FIGURE 11.Glomerular Filtration and Tubular Mass during Convalescence.
The abcissa is the same as in the preceding figure, glomerularfiltration (CIN incc./min.) being plotted on the horizontal scale. As in Figure 10, ratiosfalling to the left of the dotted diagonal lines (representing the normalrange for the ratio CIN/TmPAHof 1 to 5) indicate a greater impairment in glomerular than in tubularfunction.
vascular resistance. Apparently trauma gives rise to some systemic traceeffect, operating to diminish renal vascular caliber in rough proportionto the degree of systemic insult. High values for TmPAHnoted in lesser grades of PTRI are incompatible with the presence of acutetubular necrosis suggesting that this morphological feature is only secondaryto a continued functional disturbance in renal vascular tone. Accordingto this view, azotemia stems from reduced filtration and tubular necrosisis only a secondary sequela of extreme and protracted post-traumatic renalischemia.
220
Table 6. Hypertonic Parameter in Convalescent Casualties
Case No. | CIN cc./min. | V | Cosm | V | Cosm | TcH2O | TcH2O/CIN |
CIN | CIN | ||||||
|
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 tubularintegrity, the activity of the distal system is reflected by the facultativeparameters25-27 to water reabsorption. Quantitative limitationsto the concentrating mechanism (TcH2O)27 observed during infusions of pitressin and mannitol, atvariably depressed clearance levels, are summarized in Table 6. At load/Tcratios >2, the urine appeared dilute by crude urinometry, although cryoscopicanalysis demonstrated significant hypertonicity. When CINexceeded 70 cc./min., the absolute volume of solute-free filtrate abstractedto effect urinary concentration averaged 5.2 cc./min. This is almost identicalwith that found by Zac, Brun, and Smith (5.1 ± 1.5 cc./min.) inuninjured man.26 At lower values for CIN,the magnitude of TcH2O bore a constant functionalrelationship to the filtration rate, a pattern previously demonstratedduring 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 filtrateat all clearance levels, regardless of the degree of PTRI.
Table 7. Hypotonic Parameters During Convalescence
Case No. | Days Postoperative | CIN | Cosm. cc./min. | V | CH20 | 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 lowvalues for CIN. Comparable data are includedfor three other subjects with high clearance levels. When factored uponthe filtration rate, maximal urinary hypotonicity, measured by the freewater clearance (CH2O)was independent of the filtered, or execreted, urinary solute load. CH2Oconsistently approximated 10 per cent of the filtrate, regardless of thelevel of glomerular function. This would indicate that the relative magnitudeof distal sodium reabsorption (TdNa)27 was
222
comparable to that of normal uninjured man,30 constitutingfurther 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/Pratio declined asymptotically toward 1.0, and plasma NPN exceeded 100 mg.per 100 cc. in all of six cases where this was measured. Comparable patternsof falling urinary specific gravity accompanied by parallel elevation inurine flow and plasma NPN have been illustrated in reports of extrarenalazotemia following transfusion reactions,31 uterine rupturewith shock,32 gastrointestinal hemorrhage33 and otheracci-
FIGURE12. Urine Flow and Filtration Rate during Convalescence.
Daily urine output is expressed on the vertical scaleas per cent of the prevailing filtration rate (CINin cc./min.). Unlike the pattern seen early after injury, tubular waterreabsorption 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 percent of the filtration rate in severe PTRI.
dents. Figure 12 shows that during convalescence (as opposed to thepattern seen early after trauma in Fig. 1) the daily urine output approximated10 per cent of the filtrate in moderate to severe grades of PTRI. Similarly,Howard5 has observed that 14 per cent of massively wounded casualtiesmaintained daily urine outputs over 500 cc. despite clinical evidence ofacute renal failure and uremia.
223
Data in table 6 constitute a strong argument against structural damageto the concentrating mechanism as a basis for isosthenuria. Actually thepattern shown in Figure 12 typifies any osmotic diuresis,4, 34-39thesolute load in this case comprising urea, creatinine, sulfates and phosphates.Teschan2 notes that these osmotically active tissue metabolitesaccumulate four times as fast in PTRF as in uremia of non-traumatic origin.Osmotic loads impeding the proximal reabsorption of more than 4 per centof the filtrate would necessarily obliterate urinary concentration becauseof this quantitative limitation to TcH2O.At high values for Cosm/CIN, the effectof TcH2O would be almost imperceptible,except by freezing point determinations. Evidently, in battle casualtiesthe accelerated accumulation of osmotically active tissue metabolites causedan osmotic diuresis preventing the occurrence of oliguria and masking allbut the most extreme grades of renal failure.
Heme Pigment Metabolism and Renal Function
Gross hematuria has frequently been noted after traumatic injuries inman1, 31, 42, 43 and animals44-46 and has been attributedto glomerular damage46 from ischemic muscle metabolites,47-49as has proteinuria.3, 44-46 The present group of casualtiesinvariably exhibited dense proteinuria and hematuria. Theoretically, theseabnormal urinary constituents alone would provide ample source for theprecipitation3, 23 of heme pigment. But, in addition, the urinarysupernatant was not uncommonly deeply colored, particularly after massivetransfusion. Olney7 found the greatest concentration of freeplasma hemoglobin in patients receiving the largest amounts of the oldestblood, but it disappeared from the plasma within 6 hours and could notexplain persistent postoperative pigmenturia. Free urinary pigment wasnever noted in the absence of extensive muscle injury. On the other hand,many casualties with severe peripheral injuries and extensive muscle damageproduced perfectly clear urine. No correlation was evident between themaximal plasma hemoglobin observed during or after transfusion (25 patientsin Olney`s series) and subsequent renal function. Neither the absoluteamount of pigment excreted nor the per cent of circulating pigment excretedbore a consistent relationship to prevailing or subsequently determinedclearance levels. The most massive intravascular hemolysis probably tookplace in three patients accidentally given distilled water intravenously.Patient Number 7 received 1,000 cc. during débridement of shellfragment wounds of the legs and buttocks. Patient Number 10 received approximately1 liter of distilled water at a battalion aid station prior to
224
admission and Patient Number 37 received 800 cc. on the first postoperativeday. No renal functional impairment was subsequently manifest in eithercase.
Large, coarse, reddish brown granules were frequently present in theurinary sediment of the more severely injured man. They were clearly visibleto the naked eye and experimental mannitol diuresis usually flushed outa shower of these bodies, which disappeared from subsequent urine collections.Oliver3 points out that since these casts originate in, andby inference, obstruct straight collecting tubules, many proximal nephronunits must be rendered impotent by their presence. It has frequently beensuggested23, 50-52 that such bodies might cause renal failureeither by obstruction or irritation. But, in five casualties, the formationof such casts was precluded by instituting a mannitol diuresis (500-2,000gm. of mannitol intravenously) during and after resuscitation. Centrifugedurine from these five patients never revealed large casts, yet the preventionof urinary stasis and precipitation did not measurably improve renal function.Two of the five patients never recovered from PTRF and the three othersshowed clearance patterns comparable to untreated casualties with equivalenttrauma point scores. In view of the above findings, as well as abundantexperimental evidence reviewed elsewhere,3, 4 the role of hemepigment must be relegated to a position of secondary importance insofaras the genesis of post-traumatic renal insufficiency is concerned.
Clinical Statistics
Table 8 gives pertinent data bearing upon the relative incidence ofrenal failure during early convalescence from wounding in 1,000 consecutivemajor surgical patients evacuated through the 8209th Surgical Hospitalbetween April and September, 1952. Only cases of severe renal dysfunctionare included, since it was impossible to document all cases of minor orsubclinical renal insufficiency (less than 30 point units of trauma). Thelatter occurred much more frequently than the present data would indicate.However, it is highly unlikely that severe renal failure had a higher incidencethan given in Table 8, because hospital personnel were alert to its possibleoccurrence and no casualties manifested oliguria or anuria without promptrecognition. Since definitive medical care is, to a large extent, dependentupon terrain and logistics of any military theater, these figures may beconsidered applicable only to this particular sector. Furthermore, it mustbe admitted that the intensified general interest in potential
225
Table 8. Distribution of Severe Renal Insufficiency Among Major SurgicalCases
First Indication | Total Cases | Case Numbers |
|
Blunted Recovery Diuresis Lived more than 48 hours |
4 |
(36, 42, 43, 44) |
|
Oliguria Following Postop. Complication Transfusion reaction |
2 |
(11, 13) |
|
Oliguria, Persistently Depressed CIN,, Hypertension
|
4 |
(18, 24, 25, 42) |
|
Persistently Depressed CIN,, Hypertension, No Oliguria Received artificial dialysis |
1 |
(19) |
|
Grand Total (excluding early deaths) |
16 (1.6 percent of 1,000 consecutive cases) |
|
*Includes 5 unnumbered cases, recorded, but not documentedby clearance studies.
candidates for renal failure may have precluded some factors normallycontributing to its genesis.
It is noteworthy that acute renal failure of non-traumatic origin wasfrequently precipitated by a postoperative complication soon after wounding.Table 9 summarizes pertinent data obtained from all postoperative patientsshowing oliguria (<300 cc. urine/24 hours) who survived more than 48hours beyond resuscitation. The figures show an equal incidence for bothtrue PTRF and renal failure of non-traumatic origin (false PTRF). Sevenof these oliguric patients were subsequently transferred to the Renal InsufficiencyCenter because of uremia. The five most severely injured (>40 point unitsof trauma) showed marked renal functional impairment immediately afterresuscitation, as anticipated from their trauma scores. Here, oliguriaunquestionably originated from wound trauma.
Two of the four other patients exhibited fairly high initial postoperativeclearance values since they had suffered relatively little injury. One(Case Number 39) showed a moderate postoperative depression in clearancevalues because he had been badly injured (33 trauma points). Since thehematocrit 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 | CPAH | Type | Day | Hours Postop. | CIN cc./min. | CPAH | |
|
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 becauseof uremia.
228
15 at the time of study, clearances were presumably depressed73by severe anemia. This patient received dextran wholly in substitute forblood. The transfusion reaction occurred while manifest anemia was beingrectified, after completion of preliminary clearance studies. Shortly afterthe initial postoperative studies, each of the latter group met with unforeseenaccidents. These were recognized too late, in each case, to forestall theonset of acute oliguria. It is not unlikely that during great militaryactivity similar accidents might never have been recognized at all, sincewith heavy casualty loads, meticulous postoperative attention becomes impractical.Under such conditions acute renal failure (of nontraumatic origin) mighteasily be attributed to the wound shock sequence and incorrectly be consideredtrue PTRF. Theoretically, any circumstance favoring the occurrence of suchpostoperative complications would increase the apparent incidence of truePTRF in the field. This may explain, in part, the apparently higher incidencenoted in World War II6, 23 as well as the recognized lack ofcorrelation between wound shock and the subsequent renal outcome.2,6, 23
Discussion
During World War II, "hemoglobinuric nephrosis"23 was foundin 19 per cent of 427 battle casualties autopsied in Italy. An even higherincidence (36 per cent) of "lower nephron nephrosis"54 was observedamong 315 battle casualties autopsied at the 406th General Medical Laboratory22in Tokyo between 1951 and 1952. These figures are at variance with theclinical incidence of PTRF shown in Table 8 as well as with Teschan`s2observation that renal failure was clinically manifest (including transfusionreactions, hemorrhagic fever, etc.) by less than 1 per cent of the 8,000casualties incurred during the 1952 Korean campaign. Clearly, estimatesbased 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 paradoxbetween morphological and clinical statistics. The first thing is thatrenal insufficiency frequently occurs in subclinical form. Newburgh53showed that renal function may be reduced to one-tenth of normal withoutovert clinical manifestations, as is also apparent in the present study.Clinically imperceptible PTRI may predispose towards renal failure of nontraumaticorigin (false PTRF). Secondly, among battle casualties at least, many deathsmay be attributable to other causes and yet bear conventional pathologicalstigmata of "lower nephron nephrosis,"22, 54 "shock kidney,"55"hemoglobinuric nephrosis,"23 etc.
229
Casualties dying within 48 hours of injury (for instance Cases Number26, 33 and 45, included in Table 8) are an obvious source of such confusion.They are typically anuric and azotemic,2, 42, 56 differing fromsurvivors of true PTRF chiefly by their rapid exodus. Serial determinationsof plasma NPN in Case Number 26 showed values of 73 mg. per 100 cc. at6 hours and 105 mg. per 100 cc. by the twelfth postoperative hour. It iswell known that marked structural alterations occur within the kidney ofsuch individuals if they survive for 18 hours.23, 54, 55, 65 Thesepatients do not fit the ambiguous clinical criteria.2, 6 ofPTRF; but the histories of anuria and azotemia, together with the morphologicalfindings,22, 23, 54 force pathologists to classify these caseswith other varieties of post-traumatic tubular necrosis. Hence, necropsymaterial is bound to suggest a higher incidence of renal sequelae.
Current speculation regarding the pathogenesis of PTRF is, in largepart, derived from autopsies of battle23, 54 and air raid42,62 casualties dying in uremia during World War II. The clinical syndromeof PTRI is generally presumed to reflect tubular damage incurred duringshock by renal ischemia57-60 because the most striking morphologicalfindings are limited to the renal tubules. It is inferred that glomerularfiltration is restored upon resuscitation from shock. Uremia is thus attributedto back diffusion57-60 through damaged tubular walls, as observedby Richards61 in the poisoned frog kidney.
Since the extent of tubular necrosis was believed to be proportionalto the severity or duration of hypovolemic shock,17, 42, 56-60, 62-65prompt transfusion was recommended to prevent its occurrence.66This prophylactic program of immediate blood replacement proved entirelyfeasible in the Korean Theater and was enthusiastically applied. Becauseof 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 wasnever encountered by the Surgical Research Team. Under such conditions,hypovolemia became the most easily controlled component of wounding, butthis did not prevent the subsequent development of PTRI.
The present observations fail to support the conventional concept thatPTRI reflects the degree of tubular damage incurred during "shock."57-60In battle casualties, plasma flow and filtration were reduced during traumaticshock, but these indices remained persistently depressed after resuscitationwithout comparable reduction in proximal or distal tubular function. Althoughinfrequently recognized, experimental traumatic shock in animals is followedby a similar per-
230
sistent renal ischemia.64, 67-69 This strongly suggests thatsystemic injury exerts its long-lasting effect primarily upon the renalvasculature rather than the renal tubule. If tubular necrosis occurs, itwould not appear to reflect direct injury received during shock, but ismore likely to result secondarily from a continued interference with renalblood flow during convalescence. The present low ratios for CPAH/TmPAHand the increased renal arterial-venous oxygen saturation difference foundby Breed70 and Bull31 in man argue against the presenceof an intrarenal shunt.71 Since PTRI is not apparently accompaniedby decreased cardiac output72 nor concomitant hypotension, theonly explanation for the persistence of renal ischemia after resuscitationis increased renal vascular resistance.
Normally the kidney maintains an almost constant renal blood flow despitereduced perfusion pressure4 by changes in renal vascular toneproximal to the glomerulus. Experimental evidence73 would indicatethat following severe trauma this autonomy of the renal circulation maybe obliterated or severely impaired. The renal response to minor war woundsmust have entailed chiefly vasoconstriction distal to the glomerulus becauseCIN was maintained or even elevated, despitelow values for CPAH. This pattern seemedinfluenced by postoperative plasma volume. Also, it was exaggerated bydecrements in peripheral blood flow following ganglionic blockage or spinalanesthesia. Hence, the observed efferent arteriolar constriction may conceivablyrepresent part of a prolonged systemic circulatory reaction to trauma.Conversely, CIN was depressed by severeinjury to a greater extent than CPAH. Sincelow ratios for CIN/CPAHcannot be explained either by back diffusion or reduced tubular extraction,they are attributed to a relative increase in vascular resistance proximalto the glomerulus. Evidence of afferent arteriolar spasm has been observedby Sheehan and Moore52 and by Bell65 and is compatiblewith decreased glomerular reactivity postulated by deWardener73to follow serious injury.
Summary
The renal function of military casualties was examined on over 100 separateoccasions, during resuscitation from traumatic shock (6 cases), or duringthe interval between resuscitation and convalescence (40 cases).
The following discrete indices were measured intermittently: urine flow,CIN, CCREAT,CPAH, TmPAHand the hypotonic and hypertonic parameters of urine excretion conventionallydesignated CH2O and TcH2Orespectively. The following components of wounding were examined for arelationship to postoperative renal function: degree and
231
duration of hypotension, transfusion volume, extent of intravascularhemolysis, postoperative blood loss (estimated by T1824 dilution) and thetotal wound insult computed by a point scoring system.
The conclusions drawn are that PTRI is primarily due to functional changeswithin the renal vascular bed, to which tubular disease may be a late secondarysequela, which are roughly proportional to the sum of all components ofwounding 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 resuscitationfrom wounding. In its mild form, PTRI is characterized by relative efferentarteriolar resistance, but with progressive stages of wound severity, proportionatelygreater renal ischemia may reflect an increase in both efferent and afferentresistance and may secondarily result in loss of secretory activity. Excessiveurinary solute loads accompanying azotemia, consequent to increased catabolism,or decreased filtration, or both, probably account for relative polyuriaand isosthenuria, because no impairment in the urinary concentrating mechanism(TcH2O) was demonstrable forat least 3 days after manifest renal insufficiency.
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