Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV
Post-traumatic Renal Insufficiency in Military Casualties
II. Management, Use of an Artificial Kidney, Prognosis*
Captain Lloyd H. Smith, Jr., MC, USAR, Captain Robert S. Post, MC, USAR, Major Paul E. Teschan, MC, USA, First Lieutenant Robert S. Abernathy, MC, USAR, Captain John H. Davis, MC, USAR, Major Dell M. Gray, MC, USA, Captain John M. Howard, MC, USAR, Captain Kenneth E. Johnson, MC, USAR, Captain Edward Klopp, MC, USAR, Captain Roy L. Mundy, MSC, USA, First Lieutenant Maurice P. O`Meara, MC, USAR, and First Lieutenant Ben F. Rush, Jr., MC, USAR
During the past few years there has been widespread interest in the treatment of acute renal failure of diverse origins by medical management alone,1, 2 or by the added use of some means for reversing the chemical changes of uremia, such as the artificial kidney,3 peritoneal lavage,4 and gastric or intestinal lavage.5 The majority of uncomplicated cases of acute renal failure can be successfully maintained until the onset of diuresis by carefully avoiding overhydration and providing sufficient calories to minimize protein catabolism. The artificial kidney has found its chief use in civilian medicine as an adjunct to medical management, occasionally life-saving in cases of spontaneous potassium intoxication or severe uremic intoxication.5
Patients with renal insufficiency following trauma present special problems in management because clinical uremia, high levels of azotemia and kalemia, and myocardial potassium intoxication develop rapidly.6 Conventional methods of therapy are frequently insufficient to limit the rapid progression of uremia either in civilian practice7 of in battle casualties. A mortality rate of approximately 80 to 90 per cent was found in casualties with post-traumatic renal insufficiency in World War II8 and in the Korean War (see below). Because of this excessive mortality rate a Renal Insufficiency Center was established in Korea in an attempt to improve the therapeutic results. An evaluation of the Brigham-Kolff artificial kidney in post-traumatic renal insufficiency was carried out at this center.
Organization of Renal Insufficiency Center
Through the cooperation of the Eighth Army a Renal Insufficiency Center was established at a large evacuation hospital in central Korea
*Previously published in American Journal of Medicine 18: 187, 1955.
32
about 70 miles from the front. The importance of such a location is the accessibility within helicopter range of the forward hospitals, where most of the cases of post-traumatic renal insufficiency occur. The average period of time between wounding and arrival at the center was 3.2 days in the 51 patients admitted during 1952.
Patients who survived remained at the Renal Insufficiency Center until diuresis and sufficient recovery made it possible for them to re-enter the regular chain of evacuation safely. A laboratory capable of carrying out all of the usual clinical chemistries was established. The chemical methods used have been listed in the accompanying paper.6 A Brigham-Kolff type of artificial kidney was utilized, consisting of a partially submerged rotating drum with a continuous helically wound cellophane tube of approximately 20,000 sq. cm. surface area. The technic of operating this type of artificial kidney has been described in detail.9 The usual dialysis was carried out for 6 hours at a blood flow rate of 250 to 350 cc./minute. Occasionally when hyperkalemia was the only indication, dialysis was limited to 3 or 4 hours.
Medical Treatment
The principles of the medical management of acute renal failure have been well described elsewhere.1, 2 Within the limitations imposed by the severity of the wounds in this group of patients, these principles were followed as outlined below:
1. Oliguric Phase
(a) Fluid Restriction. Fluid intake was initially restricted to a maximum of 600 to 800 cc. per 24 hours (a rough estimate of insensible loss) plus the estimated loss of urine, drainage from wounds, and gastric or intestinal suction. The presence of fever, sweating and an unknown amount of endogenous water production from catabolism limited the accuracy of the fluid balance. Careful daily weights taken on a stretcher-type bedside balance were of great value as a check on fluid requirements. An attempt was made to maintain a steady decrease in body weight throughout the oliguric period. A marked loss of body mass occurs during the catabolic phase of acute renal failure, which is often masked by fluid retention until afterdiuresis.10 A program to produce a gradual decline in weight rather than maintenance of the initial weight during the oliguric phase of acute renal insufficiency prevents a "relative overhydration." During their care at the Renal Insufficiency Center almost all of the patients required repeated transfusions or underwent such surgical procedures as ampu-
33
tations or débridements. This placed restrictions on the over-all reliability of daily weights as an index of fluid balance.
(b) Caloric Intake. The end-products of carbohydrate and fat catabolism are CO2 and H2O, both of which can be eliminated by way of the lungs. Protein catabolism imposes the main excretory burden on the kidneys. With the loss of protein there is also loss of other intracellular components, especially potassium. Although the uremic syndrome cannot at present be related to a specific chemical change, the severity of uremic symptoms appeared to vary approximately with plasma NPN concentrations during oliguria. Suppression of protein catabolism by supplying carbohydrate and fat to the metabolic pool should therefore be attempted. Gamble demonstrated that 100 gm. of glucose would prevent ketosis and reduce the negative N balance by 50 per cent in normal fasting men.11 An increase of carbohydrate intake to 200 gm. did not produce a further significant reduction in protein catabolism. An attempt was therefore made to supply at least 100 gm. of glucose per day, giving the daily basal fluid requirement as 15 per cent glucose in a peripheral vein. Repeated observations of profound tissue wasting led to increased use of 50 percent dextrose infused into cannulated major veins. Seventy-one per cent of the patients treated at the Renal Insufficiency Center had abdominal wounds, which restricted attempts to force orally high caloric regimens. Oral feeding was instituted as soon as possible in all cases.
(c) Treatment of Acidosis, Hyponatremia and Hypochloremia. Hyponatremia and hypochloremia were already in evidence in the majority of the 51 patients at time of admission to the Renal Insufficiency Center, an average of 3.2 days after wounding. The average admission plasma values were sodium 133mEq./L. (range of 113 to 164), chloride 87 mEq./L (62 to 108), and carbon dioxide 24.2 mEq./L (14.8 to 43.4). The subsequent values of sodium, chloride and carbon dioxide varied markedly depending on the treatment. Despite rigid fluid restriction, there was a general tendency toward further decreases in plasma sodium and chloride during the oliguric period suggesting intracellular shifts or progressive hydration from endogenous water production. The plasma values were usually returned to normal during dialysis with the artificial kidney, as will be discussed below. Because of the danger of producing pulmonary edema, hypertonic saline was given only as necessary to reduce the toxicity of a concurrent hyperkalemia and to raise plasma sodium levels which had fallen below 115 to 120 mEq./L. There was usually a gradually increasing metabolic acidosis during the oliguric period, reflecting the retention of fixed acids. Here also treatment with sodium lactate or
34
sodium bicarbonate was usually given only if acidosis was severe (CO2 combining power below 12 to 15 mEq./L.). Occasionally metabolic alkalosis secondary to gastric suction was found on admission and in one patient required ammonium chloride therapy. Treatment with the artificial kidneyinvariably returned the acid-base balance toward normal, although this reversal was seldom complete.
(d) Treatment of Anemia. A progressive anemia is a frequent finding in acute renal failure of any origin. Although the mechanism is not entirely understood, it seems probable that both decreased blood formation and increased blood destruction occur during uremia.10 The picture is complicated in the present series of patients by the large amounts (average of 6 liters) of relatively old (2 weeks) type O blood which they had received during resuscitation. A study of the limited survival time of this blood is presented in another paper from the Surgical Research Team.12 In addition, recurrent bleeding from various sites in these patients required large amounts of blood for replacement purposes.6 Despite the fact that their admission hematocrits averaged 40 per cent, the 51 patients in this series required an average of 4,950 cc. (range 0 to 13,000 cc.) of fresh, type-specific blood during an average period at the Renal Insufficiency Center of 12.9 days (3 hours to 33 days). In the first patients transfusions were rarely given electively for a moderate reduction in hematocrit because of the danger of pulmonary edema. When wound healing was a problem, however, packed red cell transfusions were given with increasing frequency to maintain the hematocrit in excess of 35 per cent. These were well tolerated. It was noted on several occasions that patients could tolerate large amounts of blood during and immediately following hemodialysis, despite having previously developed pulmonary edema during the infusion of much smaller volumes of blood.
(e) Treatment of Hyperkalemia. The frequency of hyperkalemia and the rapidity with which it developed in this group of patients have been presented in the accompanying paper (ch. 2).6 Plasma potassium values were measured daily or oftener if they seemed to be rising rapidly. Electrocardiographic tracings were usually obtained at the time of potassium analysis on all patients with significant elevations of plasma potassium, and were relied upon to estimate the seriousness of the medical emergency.
The physiological antagonism between extracellular potassium and sodium or ionized calcium was employed in the emergency treatment of acute potassium intoxication. Hypertonic saline (200 to 400 cc. of a 3 to 5 per cent solution)was given if the plasma Na was below normal. The use of calcium in the treatment of hyperkalemia received a much more thorough evaluation at the Renal Insufficiency Center during
35
the 6 months following the period covered in the present report, and will be presented in a separate communication.13 Also in the treatment of acute hyperkalemia large amounts of 50 per cent glucose and insulin (1 unit per 2 to 3 gm. glucose) were given intravenously, to reduce extracellular potassium by inducing its intracellular deposition with glycogen.14 These measures were temporarily effective at best and were usually followed within a few hours by emergency dialysis on the artificial kidney.
An ammonium carboxylic cation exchange resin* was used both in the treatment of acute potassium intoxication and in an attempt to maintain normal potassium levels after hemodialysis. A dose of 25 gm. of resin as a 10 per cent suspension in water was usually given once or twice daily by retention enema or in divided doses over several hours orally. The high incidence of abdominal wounds (71 per cent) served as a serious limitation on the usefulness of the resins in the group of patients who were the most severely wounded. The use of the resin in the treatment of acute potassium intoxication was disappointing. The plasma potassium levels usually remained elevated or even rose despite the use of the resin in the early phase of the clinical course. In the absence of severe abdominal wounds, when the resin could be regularly employed, it seemed of considerable value in preventing a secondary rise in plasma potassium after normal values had been established by hemodialysis.15
The use of the artificial kidney in the treatment of hyperkalemia will be discussed in the following section.
2. Diuretic Phase
The beginning of diuresis (600 cc. of urine per 24 hours) by no means marks the ends of the therapeutic problems. In the present series one-third of the deaths (9 out of 27) occurred after the onset of diuresis. Several days of diuresis were usually required to bring about significant chemical and clinical improvement. Because of this delayed response, 7 of the 72 dialyses with the artificial kidney were carried out after the onset of diuresis. Fluids were given in proportion to the degree of diuresis, but no effort was made to maintain a constant weight. Most patients lost weight at the time of diuresis, indicating a previous overhydration despite rigid fluid restriction. Urinary sodium was measured and was partially but not quantitatively replaced. As emphasized by Swan and Merrill,10 quantitative replacement of the sodium loss during the early diuretic phase is not necessary and may prolong diuresis. No patient developed clinical or chemical sodium
*SKF #648. This was kindly supplied to us by the Smith, Kline, and French Laboratories.
36
depletion during this phase. The hypernatremia-hyperchloremia syndrome described by Luetscher and Blackman17 was not observed in this series. Most of the deaths during the diuretic phase were attributable to complications of wounding, as will be discussed below.
The Use of the Artificial Kidney
1. Number of Dialyses and Indications
Dialyses with the artificial kidney were carried out 72 times in 31 of the 51 patients treated at the Renal Insufficiency Center. The artificial kidney was not used in 20 patients for a variety of reasons, such as relative mildness of the uremia, or early death from the complications of the attending wounds. This will be considered later under the discussion of prognosis. The number of treatments received by the individual patients varied from one to six: 1 dialysis, 9 patients; 2 dialyses, 10 patients; 3 dialyses, 9 patients; 4 dialyses, 1 patient; 6 dialyses, 2 patients.
Figure 1 presents the time distribution of the dialyses following wounding. Also shown are the primary indications for the individual dialyses-hyperkalemia, 29 dialyses; marked uremia without significant hyperkalemia, 22 dialyses; or marked uremia accompanied by hyperkalemia, 21 dialyses. This classification of the indications is somewhat arbitrary, but demonstrates the trend toward early devel-
37
opment of potassium intoxication. One patient required dialyses for hyperkalemia on the first day after being wounded.
The indications for use of the artificial kidney at the Renal Insufficiency Center were not rigidly defined, but depended on clinical judgment in each case. In general, dialysis was carried out if ECG evidence of myocardial intoxication was marked. Dialysis was almost always carried out if the plasma potassium value was greater than 7.5 mEq./L., since definite ECG changes of myocardial potassium intoxication were then invariably present. The average plasma potassium values at the time of dialysis in both the groups termed "hyperkalemia" and "uremia plus hyperkalemia" were 7.1 mEq./L.It is realized that plasma potassium values of less than 9.0 mEq./L. are seldom fatal. The decision to carry out dialysis in the plasma potassium range of 6.5 to 7.5 mEq./L., even with ECG changes limited to the T wave alone, was based on the observed rapidity with which plasma potassium rose in this series of patients and the usual concomitant presence of hyponatremia and hypocalcemia. Early in this experience, before the establishment of the Renal Insufficiency Center, plasma potassium rose from 8.0 mEq./L. to a fatal level of 11.2 mEq./L. within a day in one patient, despite the use of cation exchange resins. Another patient died in cardiac arrest after his plasma potassium rose from 6.1 mEq./L. to 9.1 mEq./L. within a single day. It was thought advisable, therefore, to carry out dialysis electively at relatively low levels of hyperkalemia to diminish the risk of acute elevations in extracellular potassium concentration and consequent myocardial intoxication.
Twenty-two of the dialyses were carried out for uremia without significant hyperkalemia and 21 dialyses for uremia accompanied by hyperkalemia. At the time of treatment the average NPN values in these two groups were 275 mg. per 100 cc. and 308 mg. per 100 cc. respectively. A decision for the use of the artificial kidney was not based on the level of azotemia, which in one patient was allowed to rise to 504 mg. per 100 cc., but on the severity of the clinical signs and symptoms of uremia, especially clouding of consciousness with inability to clear tracheal secretions by coughing, marked nausea and vomiting with restriction of caloric intake, signs of neuromuscular irritability, and dyspnea. On several occasions dialyses were carried out with milder degrees of uremia or hyperkalemia to prepare an oliguric patient for a major surgical procedure, such as an amputation or extensive débridement.
2. Results of Treatment With the Artificial Kidney
The chemical results of an uncomplicated, 6-hour dialysis in the treatment of uremia can be predicted with reasonable accuracy. The plasma sodium, potassium and chloride concentrations return to nor-
38
mal levels, if there is an initial abnormality. The CO2 combining power, as an index of acidosis, returns toward but does not usually attain a normal value. The NPN level is usually reduced to 75 mg. per 100 cc.to 125 mg. per 100 cc., depending on its initial value and the flow rate of blood maintained through the artificial kidney. The average changes in blood chemistries for the 72 dialyses are shown in Table 1.
Table 1. Average Chemical Results of Dialysis With the Artificial Kidney (Average duration of the 72 dialyses-5.3 hours)
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2 mEq./L. |
|
1. Total dialyses-72 |
|
|
|
|
|
|
Before |
246 |
6.5 |
135 |
92 |
17.2 |
|
After |
108 |
4.3 |
138 |
105 |
21.4 |
|
2. "Hyperkalemia dialyses"-29 |
|
|
|
|
|
|
Before |
191 |
7.1 |
132 |
|
|
|
After |
93 |
4.3 |
139 |
|
|
|
3. "Hyperkalemia plus uremia dialyses"-21 |
|
|
|
|
|
|
Before |
308 |
7.1 |
138 |
|
|
|
After |
123 |
4.4 |
141 |
|
|
|
4. "Uremia dialyses"-22 |
|
|
|
|
|
|
Before |
275 |
5.0 |
143 |
|
|
|
After |
120 |
4.1 |
141 |
|
|
The clinical results of treatment with the artificial kidney are not as easy to appraise. Occasionally there was clinical improvement during the course of the dialysis as shown by an objective clearing of consciousness or decrease in dyspnea, or a spontaneous statement from the patient that he felt much improved. Maximal clinical improvement was usually noted in 12 to 24 hours after treatment, and was particularly evident in loss of nausea and vomiting, a return of appetite, a clearing of consciousness and a decrease in dyspnea. The subjective improvement was sometimes of such a degree that several patients requested another dialysis after the return of uremic symptoms during continued oliguria. Noted previously was the fact that patients were often able to receive transfusions of whole blood during and soon after dialysis without respiratory distress, although smaller amounts of blood given prior to treatment with the artificial kidney led to dyspnea and early pulmonary edema. Not all of the patients treated with the artificial kidney demonstrated noticeable clinical improve-
39
ment despite the usual chemical changes. This clinical refractoriness was found only in patients with unusually severe wounds or complications of wounds.
The results of treatment with the artificial kidney in terms of survival value will be discussed under prognosis.
3. Complications of Dialysis
The use of the artificial kidney is not without risk, especially in such a group of desperately ill patients. Operational difficulties in the dialyses, such as the development of a leak in the dialyzing membrane, or clotting of blood in the return reservoir, were rare and did not seriously affect the completion of dialysis. The complications observed in the patients were:
(a) Hypertension. A progressive hypertension has been previously described as occurring in 10 to 15 per cent of dialyses.3 The hypertension does not invariably occur and cannot be predicted in the individual case. Its cause remains obscure. Excluding dialyses complicated by excessive bleeding and transfusions, in 14 of 49 dialyses without initial hypertension (BP less than 150/90) there was a significant rise of blood pressure from a mean initial value of 135/74 to a mean maximal value of 215/109. In one patient the blood pressure rose from an initial level of 180/100 to 270/130 mm. Hg. The elevation of blood pressure usually occurred progressively, beginning after 1 or 2 hours of treatment with the artificial kidney. Occasionally Apresoline 
was used to lower or prevent further elevations of blood pressure. No clinical complications could be attributed to this hypertensive effect of dialysis in the present series of patients. In several patients with hypotension at the start despite repeated transfusions, blood pressures rose and became stabilized during dialysis.
(b) Periods of Hypotension. Blood pressures less than 100/60 were recorded in 12 of 72 dialyses, excluding those patients who were hypotensive before entering the operating room. The fall in blood pressure usually occurred during cannulation of the artery and vein under local Procaine anesthesia, or during the early period of dialysis when flow through the artificial kidney was being established. Response to transfusion was rapid in most cases with a return to normal blood pressure. Hypotension occurring during dialysis was usually related to bleeding from the patients` wounds, and responded to transfusion.
(c) Bleeding. Many of the patients who received treatment with the artificial kidney had been severely wounded within 72 hours prior to dialysis, followed by extensive, reparative surgical procedures.
40
Furthermore, during their treatment at the Renal Insufficiency Center approximately one of every four patients had bleeding episodes unrelated to previous trauma, such as cutaneous ecchymoses, epistaxes and bleeding from the gastrointestinal tract. During dialysis, intravenous heparin,50 to 120 mg., was given to prevent the blood from clotting during its circulation through the artificial kidney and return reservoir, a period of approximately 2 minutes. The occurrence of hypertension during dialysis has been described above. With this combination of predisposing factors it was anticipated that hemorrhage would be the major complication of dialysis in such a series of recently wounded soldiers. It is therefore surprising that only two patients exhibited bleeding of sufficient degree to cause hypotension and necessitate stopping the dialysis. Brisk bleeding from a wound involving the rectum and urethra in one patient was controlled by packing and the use of protamine sulfate intravenously. The second patient had extensive wounds of the liver, right kidney, diaphragm and jejunum. Three days before dialysis, on the thirteenth day after wounding, an emergency laparotomy had to be performed to control bleeding from the hepatic wounds. During the night prior to dialysis 5 pints of whole blood were required to maintain blood pressure because of bleeding from the abdominal wound and liver. Because of severe uremia and potassium intoxication dialysis was carried out on the sixteenth day after wounding. There was exacerbation of bleeding during the procedure requiring repeated transfusion. The patient died in shock 16 hours after dialysis. Some oozing of blood was frequently seen from open débrided wounds, amputation stumps, and the cutdown sites for cannulation of the artery and the vein. This was easily controlled, however, without interfering with completion of dialysis. Sites from which bleeding could be anticipated were usually packed before beginning the procedure.
(d) Fever. In 55 per cent of the dialyses the oral or axillary temperature rose above 100° F from a previously normal value, and rarely (5 times) the temperature reached 103 to 104°. During six dialyses shaking chills were observed, with no evidence of hemolysis. The fever was probably related to pyrogenic contamination of the water supply obtained under field conditions. This represents a much higher rate of febrile reactions than that observed under more ideal operating conditions.
Surgical Management
A detailed description of the surgical management of these patients cannot be presented here. In practice, however, the limiting factor in survival for most patients was the severity of the initial wound and its subsequent complications (see below), rather than renal damage
41
per se. Radical débridement of wounds, early amputation of areas of gangrene, and continued careful search for localized infection subject to drainage were of the utmost importance in patients with reduced renal function. On a number of occasions the rapid progression of uremia was blunted by the discovery and drainage of an abscess or amputation of a mangled extremity. Also of great practical importance was the frequency of pulmonary complications. In these patients with malnutrition, weakness, clouding of consciousness and nausea over periods of 1 to 3 weeks, atelectasis and bronchopneumonia were constant hazards. Tracheal suction, the use of a Stryker frame, and even tracheotomy were sometimes necessary to maintain adequate pulmonary function.
Prognosis
1. Control Mortality (prior to the arrival of the artificial kidney)
Military casualties with post-traumatic renal insufficiency represent a special problem in therapy. The prognosis is much less favorable in general than in the less complicated civilian patients with acute renal failure. In World War II a mortality rate of 91 per cent was found in casualties who developed oliguria of less than 100 cc. per day.8 On arrival in Korea a survey of the forward hospital units was carried out by the Surgical Research Team to determine the incidence and mortality rate of post-traumatic renal insufficiency among the military casualties. It was found that during the preceding 3 months approximately 50 oliguric patients were treated at these hospitals with a mortality rate of 80 to 90 per cent. During the same period of time Moots reported the death of 8 in 9 patients with post-traumatic renal insufficiency at a single forward hospital.16 Before the artificial kidney was available and the Renal Insufficiency Center was established in Korea, 10 casualties with acute renal failure were treated under the supervision of the Surgical Research Team using the medical regimen discussed above. Eight of these ten patients died, with an average survival time of 6.8 days after wounding. Although these "control" groups are not as large or as strictly comparable as might be wished, it seems likely that the mortality rate of post-traumatic renal insufficiency with oliguria in military casualties approximates 80 to 90 per cent even in patients receiving an intensive medical program. Many of the deaths, however, are not due to uremia per se, but to the severity of the attending wounds, as will be discussed below.
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2. Mortality Rate at Renal Insufficiency Center
During the last 8 1/2 months of 1952 fifty-one patients with post-traumatic renal insufficiency were treated at the Renal Insufficiency Center. Thirty-one of the patients (61 per cent) received one or more dialyses with the artificial kidney, with an average of 2.3 dialyses per patient. Twenty-one of these 31 patients (68 per cent) died, with death occurring at an average time interval of 12.4 days after wounding. Of the 20 patients who were treated without the use of the artificial kidney, 6 died, a mortality rate of 30 per cent. It is to be emphasized that this group of patients in no way represents a control for those treated by dialyses. Only those with the least severe cases of acute renal failure, without marked uremia or dangerous hyperkalemia, were treated by medical management alone. The six patients who died in this medically treated group were found clinically and at autopsy to have either overwhelming infection or hemorrhage, rather than uremia, as the cause of death. The combined mortality rate for the 51 patients was 53 per cent. This is the figure of greatest significance in evaluating the over-all effectiveness of the Renal Insufficiency Center. Table 2 summarizes these mortality figures and includes a summary of the other available figures for comparison.
3. Cause of Death
Approximately two-thirds of the patients with post-traumatic renal insufficiency who were treated with the artificial kidney died. Despite the efficacy of dialysis in returning the chemical abnormalities toward normal and usually in improving the signs and symptoms of uremia, these patients died within a time interval varying from 5 to 28 days after wounding. In almost every case death was attributable to some complication of the initial wound, such as infection or secondary hemorrhage. Six illustrative cases have been listed in Table 3.
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Table 2. Summary of the Mortality Rates and Survival Times of Military Patients With Post-traumatic Renal Insufficiency in This and Other Series
Patients | Lived | Died | Mortality Rate | Av. Survival Time after Wounding of Patients Who Died |
|
(1) Renal Insufficiency Center |
|
|
|
|
|
Treated with Art. Kidney |
10 |
21 |
68% |
12.4 days |
|
Total Group |
24 |
27 |
53% |
12.0 days |
|
(2) "Control Cases" |
2 |
8 |
80% |
6.8 days |
|
(3) Cases of Moots16 |
1 |
8 |
89% |
? |
|
(4) Survey Cases of the Surgical Research Team |
approx. 50-60 cases |
|
ca. 80-90% |
? |
|
(5) World War II8* |
3 |
30 |
91% |
43% within 5 days |
*These figures are for those patients with "anuria," i.e., less than 100 cc. urine on at least one day and in general the severest cases of post-traumatic renal insufficiency. Their over-all mortality rate for "oliguria" (65%) cannot be used here because the group contained all patients with less than 600 cc. of urine for a single day. At least 35% of these transiently oliguric patients did not develop NPN`s greater than 65 mg. per 100 cc. and would not have been included in the other comparative series.
44
Table 3. Causes of Death in Six Patients Who Died Despite Treatment With the Artificial Kidney
(An autopsy was performed in each case)
Case | Initial Wound | No. of Dialyses | Day of Death | Cause of Death |
|
4 |
Abdominal injury by penetrating missile with surgical removal of spleen and left kidney, repair of the stomach, gallbladder and jejunum, and colostomy for perforation of the transverse colon. |
3 |
15 |
Peritonitis, gangrene of a segment of jejunum. Shock following extensive bleeding from the wound of exit and from the infarcted bowel. |
|
5 |
Concussion and contusion of abdomen in a truck accident with rupture of spleen and right kidney, tear of duodenum and avulsion of common bile duct from it, tear of portal vein. Spleen and right kidney were removed at operation and duodenum and portal vein repaired. |
3 |
16 |
Portal vein thrombosis with ascites and hemorrhagic colitis and ileitis. Peritonitis and a small subhepatic abscess. |
|
8 |
Shrapnel wounds with extensive laceration and destruction of the liver, fracture of two ribs and a compound fracture of the right arm. Multiple small wounds of both legs. |
3 |
9 |
Patient died in irreversible shock with hemorrhage into and necrosis of the right lobe of the liver and a bile peritonitis. |
|
18 |
Shrapnel wound penetrating sacrum with laceration of rectum and retroperitoneal hematoma. Multiple wounds of legs, later requiring amputation of the right leg below the knee. At the initial operation, the rectum was repaired and a colostomy performed. |
2 |
5 |
Patient developed irreversible shock despite vigorous transfusion with fresh cross-matched blood. It was felt that the extensive grossly infected wound involving the left buttock and sacrum and extending into the pelvic cavity contributed largely to his shock. |
45
Table 3-Continued
Case | Initial Wound | No. of Dialyses | Day of Death | Cause of Death |
|
24 |
Shell fragments caused laceration of the right diaphragm, liver and shattering of the right kidney. A nephrectomy was done and repair of the diaphragm and liver carried out. |
4 |
25 |
Death seemed attributable to infection-with empyema, bronchopneumonia, atelectasis, and a pneumothorax. Progressive diuresis never occurred during this long course, although the urine volume reached 1,200 cc. on one day. |
|
27 |
Penetrating wound of right lower chest with lacerations of the liver, gallbladder, duodenum, and pancreas. Gallbladder was removed and the other lacerations repaired. |
1 |
14 |
Patient had only 1 dialysis for hyperkalemia (8.4 mEq/L.). Diuresis occurred on the 7th day and was going well when there was death from abdominal hemorrhage secondary to separation of the duodenal laceration and from a penetrating ulcer of the stomach. |
Illustrative Cases
The following two case histories are presented to illustrate (1) the successful use of the artificial kidney, and (2) a failure of dialysis to prevent a fatal outcome despite temporary biochemical improvement.
Case 28. This 25-year-old infantryman was wounded by mortar fire, receiving multiple wounds of both legs and his left arm. Compound fractures of both tibias and fibulas were present as well as numerous soft tissue wounds. Despite a 2,500 cc. transfusion of whole blood prior to and during his operation, the patient`s blood pressure remained at 75 to 100/50 to 70 throughout the 2 1/2-hour procedure at which the fractures were reduced and the wounds dèbrided. During the next few days, marked oliguria was noted. Five days after injury he reached the Renal Insufficiency Center-nauseated, drowsy, and complaining of numbness of his extremities and a feeling of generalized weakness. On physical examination he appeared pale, drowsy and acutely ill. Pulse was 110 and blood pressure 140/80. His hand grip was weak, but reflexes were active. Both legs and his left hand were in casts. An ECG revealed elevation and peaking of the T waves and broadening of the QRS complex, indicative of potassium intoxication. The plasma K was 8.6 mEq./L. Hypertonic glucose and insulin were given as an emergency measure, with reduction of the plasma K to 7.4 mEq./L. Dialysis with the the artificial kidney was carried out for 6 hours with the following results:
46
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2 mEq./L. |
|
Pre-dialysis |
268 |
7.4 |
137 |
90 |
19.8 |
|
Post-dialysis |
76 |
4.2 |
140 |
104 |
25.3 |
During the dialysis the patient showed considerable clinical improvement, with disappearance of his nausea and the feeling of numbness and weakness. He stated that he felt much better. The following day under general anesthesia the patient`s left lower leg was amputated because of early gangrene and his other wounds dèbrided. He tolerated the anesthesia and surgery without difficulty. Severe oliguria continued and over the next 5 days the patient again became weaker and nauseated. Despite the use of 60 gm. of cationic exchange resin by retention enema each day, the plasma K rose to 7.1 mEq./L. with a return of the T wave peaking in the ECG. Another 6-hour dialysis was therefore performed on the tenth day of oliguria, with the following chemical results:
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2mEq./L. |
|
Pre-dialysis |
256 |
7.1 |
135 |
95 |
14.0 |
|
Post-dialysis |
106 |
3.7 |
141 |
102 |
20.0 |
Again there was symptomatic improvement during and immediately following the dialysis. The patient was able to take food by mouth. Four days after this dialysis the urine volume had reached 615 cc. per 24 hours, but there had been a return of nausea, drowsiness and weakness. Again the ECG demonstrated peaking of the T waves and slight broadening of the QRS complex. A third 6-hour dialysis was therefore carried out on this 14th day of oliguria, with the following chemical results:
|
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2 mEq./L. |
|
Pre-dialysis |
322 |
7.5 |
131 |
90 |
14.2 |
|
Post-dialysis |
191 |
4.7 |
140 |
102 |
23.8 |
During this dialysis urea was placed in the bath at a nitrogen concentration of 120 mg. per 100 cc. to maintain an osmotic load on the recovering kidneys during this beginning diuresis. This explains the failure of the NPN to drop as much as usual. The patient described "clearing of his head" and loss of nausea within a few hours after dialysis. The gradual diuresis continued, reaching 1,130 cc. on the sixteenth day but the NPN and plasma K did not begin to fall until the nineteenth day when the urine output reached 3,000 cc. per day. Convalescence thereafter was uneventful.
Comment. This patient had an extended period of oliguria. His renal function was insufficient to lower plasma potassium and NPN until the nineteenth day. During this period hyperkalemia with ECG changes of potassium intoxication occurred three times, despite the use of exchange resins. Each time it was effectively reversed by dialysis. From the experience at the Renal Insufficiency Center it is unlikely that this patient would have survived with medical management alone.
Case 26. This 21-year-old soldier was wounded by grenade fragments, with a penetrating wound of the right flank and right abdomen. At the forward hospital 2,000 cc. of blood was given to combat deep shock. A laparotomy revealed a retroperitoneal hematoma, laceration of the right kidney, a small laceration of the duodenum, and three lacerations of the inferior vena cava, two above the right renal vein and one at the entrance of the left renal vein. The right kidney was removed and the duodenum was repaired. Attempts at repairing the inferior vena cava were unsuccessful, so that clamps were left in place partially
47
occluding the vena cava and the left renal vein and protruding from the anterior abdominal wall. Severe blood loss during the procedure necessitated 8,500 cc. of whole blood to maintain his blood pressure. Because of persistent oliguria the patient was transferred to the Renal Insufficiency Center 3 days after wounding. On entry, the patient was alert and cooperative. Blood pressure was 140/90, and the general physical examination was normal except for the abdominal wounds. The plasma potassium was 7.2 mEq./L., but there were minimal T wave changes in the ECG. Sixty grams of the cation exchange resin was given by retention enema, as well as hypertonic glucose with insulin. The following day there was a definite increase in the amplitude of the T waves and some widening of the QRS complex. A 4-hour dialysis was performed:
|
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2 mEq./L. |
|
Pre-dialysis |
296 |
6.9 |
134 |
78 |
15.3 |
|
Post-dialysis |
174 |
3.9 |
144 |
99 |
23.1 |
During the following 4 days the patient did well clinically, and the daily urine volume gradually rose to 1,000 cc. He received a total of 120 gm. of resin by enema and was maintained on gastric suction in an attempt to prevent the recurrence of hyperkalemia. Despite this therapy the serum K rose again and the ECG revealed signs of potassium intoxication. The patient was drowsy, nauseated and dyspneic. Another 4-hour dialysis was therefore carried out on the eighth day after wounding:
|
| NPN mg. % | K mEq./L. | Na mEq./L. | C1 mEq./L. | CO2 mEq./L. |
|
Pre-dialysis |
304 |
7.5 |
134 |
80 |
10.9 |
|
Post-dialysis |
148 |
4.3 |
139 |
93 |
19.3 |
Following this dialysis the urine volume rose steadily, and the patient was much improved. The NPN and the plasma K rose for two more days, and then gradually fell with the continuing diuresis. Thirteen days after wounding, when plasma K was 3.7 mEq./L. and the NPN 204 mg. per 100 cc., the clamps were removed from the inferior vena cava under general anesthesia. There was transient hypotension, responding to 500 cc. of whole blood. Two days later he complained of generalized abdominal pain and went into shock. A laparotomy was performed and revealed brisk bleeding from the inferior vena cava. Because the vein wall was friable, ligation was performed just below the renal veins. The patient died in irreversible shock several hours later, despite a total of 7,500 cc. of whole blood before, during and after the operation. Autopsy revealed a massive hemoperitoneum with the bleeding originating from a laceration at the junction of the left renal vein with the inferior vena cava.
Comment. This patient seemed to be recovering from acute renal failure when his death was brought about by hemorrhage from his original wound. Until this occurred the artificial kidney seemed to contribute to his survival, especially in the decisive control of potassium intoxication.
Discussion
The therapeutic problems presented by military casualties with post-traumatic renal insufficiency differ only in degree from those that arise during the treatment of acute renal failure in civilian practice. This is an important difference, however, and is reflected in the excessive mortality rate in this group of patients-80 to 90
48
per cent before the establishment of the Renal Insufficiency Center. After the center was organized and the artificial kidney put into operation the mortality rate was still 53 per cent, with the majority of deaths probably attributable to complications of the original wounds. Figures for the mortality rate of acute renal failure in civilian practice vary widely. In a series of 85 cases of acute renal failure at the Peter Bent Brigham Hospital the over-all mortality rate was 48 per cent.10 It is to be emphasized that many of these patients were problem cases, sometimes referred in extremis from other hospitals. In the only other large civilian series reported there was an over-all mortality rate of 31 per cent in 64 cases.18 It is not valid, however, to compare these figures closely with those obtained in the treatment of such a special group of patients as the military casualties presented in this report. The striking feature of these patients with post-traumatic renal insufficiency was the rapidity with which chemical and clinical uremia and potassium intoxication developed, reflecting the marked catabolic response to injury, infection, and the presence of ischemic or devitalized tissue. This accelerated accumulation of nitrogenous waste products and extracellular potassium, documented in the accompanying paper (p. 7), occurred despite an intensive medical regimen, the use of exchange resins, attempts to control infections with antibiotics and surgery, and the early removal of devitalized tissue by dèbridement or amputation.
Before the establishment of the Renal Insufficiency Center the average survival time after wounding of patients who died with acute renal failure was only 6.8 days. The artificial kidney was effective in bringing about both chemical and clinical improvements, but had to be used repeatedly in many patients because of the catabolic load. The average survival time of fatal cases was almost doubled (12.4 days) in those patients treated with the artificial kidney and extended to a period usually sufficient for diuresis to begin, except in the patients with severest renal damage.
The metabolic characteristics of these patients are not peculiar to battle casualties, but are found in severely traumatized patients in any setting, civilian or military. Experience with the relatively benign nature of acute renal failure in uninjured and uninfected patients should not be misapplied to those who have developed renal insufficiency in the course of extensive surgical or accidental trauma.
Regarding future military operations, two questions should be raised: (1) Is a specialty center for the treatment of fluid and electrolyte problems feasible and valuable in a military theater? (2) Should such a center include the use of an artificial kidney? Specialty centers for the treatment of acute neurosurgical problems and
49
the treatment of epidemic hemorrhagic fever were of considerable value in the Korean military theater. Problems in electrolyte and fluid balance arise frequently in military casualties, not only in cases of acute renal failure but in the treatment of patients with burns or abdominal wounds. A specialty center for the treatment of these problems has its main advantage in the associated laboratory capable of carrying out accurate determinations of plasma electrolytes. In the experience presented here such a laboratory was established and operated effectively under field conditions. This work was carried out during the time of a military stalemate. Under mobile combat conditions, however, such a laboratory could be quickly transported in a single truck and re-established during the movement of the parent hospital.
The value of such a center is difficult to establish in statistical terms. Following the establishment of the Renal Insufficiency Center and with the use of the artificial kidney there was a fall in the over-all mortality rate from post-traumatic renal insufficiency of about 30 to 35 per cent (from 80 per cent to 53 per cent). Statistically this is not a very impressive reduction, and the observer is reduced to counting the individual patients who seemed to survive because of the special treatment, such as the use of the artificial kidney. With the use of an artificial kidney the limiting factor in survival in the present series of patients seemed to be the severity of the attending wounds. Because of this it is felt that the mortality rate accompanying acute renal failure in military casualties will be lowered below 50 per cent only with great difficulty and primarily through advances in the surgical care of the wounded.
Summary
(1) The management of 51 patients with post-traumatic renal insufficiency included fluid restriction, attempts to maintain caloric intake, use of cation exchange resins, the treatment of anemia and electrolyte disturbances and the use of a Brigham-Kolff artificial kidney.
(2) Interval surgical care of these patients was of great importance not only because of the severity of their wounds, but particularly because of the necessity for removing necrotic and infected tissue in patients with renal failure.
(3) The mortality rate accompanying acute renal failure in military casualties in Korea was approximately 80 to 90 per cent and a similar mortality rate was found during World War II. After the establishment of a Renal Insufficiency Center and with the use of a Brigham-Kolff-type artificial kidney, the over-all mortality rate in the 51 patients was 53 per cent.
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(4) Dialysis with the artificial kidney was carried out 72 times in31 patients of this series. It was effective in restoring clinical and chemical abnormalities toward normal, and seemed to contribute to the reduction in mortality in this group of patients.
(5) The limiting factor in survival for most military patients with acute renal failure is the extent of the underlying wounds with attending infection and impaired wound healing.
References
1. Thorn, G. W.: Treatment of Renal Insufficiency. J. Urol. 59: 119, 1948.
2. Strauss, M. B.: Acute Renal Insufficiency due to Lower Nephron Nephrosis. New England J. Med. 239: 693, 1948.
3. Merrill, J. P.: Medical Progress: The Artificial Kidney. New England J. Med. 246: 17, 1952.
4. Grollman, A., Turner, L. B., and McLean, J. A.: Intermittent Peritoneal Lavage in Nephrectomized Dogs and Its Application to the Human Being. Arch. Int. Med. 87: 379, 1951.
5. Twiss, E. E., and Kolff, W. J.: Treatment of Uremia by Perfusion of an Isolated Intenstinal Loop. J. A. M. A. 146: 1019, 1951.
6. Teschan, P., Post, R. S., and Smith, L. H., Jr.: Post-traumatic Renal Insufficiency in Military Casualties. I. Clinical Characteristics. Am. J. Med. 18: 172, 1955 (Chapter 2, this volume).
7. Muirhead, E. E., and Stirman, J. A.: Acute Progressive Unrelenting Renal Failure. Surgery 32: 43, 1952.
8. The Board for the Study of the Severely Wounded, The Physiologic Effects of Wounds, page 122. Office of The Surgeon General, Dept. of the Army, 1952.
9. Murphy, W. P., Jr., Swan, R. C., Jr., Walter, C. W., Weller, J. M., and Merrill, J. P.: Use of an Artificial Kidney. III. Current Procedures in Clinical Hemodialysis. J. Lab. and Clin. Med. 40:436, 1952.
10. Swan, R. C., and Merrill, J. P.: The Clinical Course of Acute Renal Failure. Medicine 32: 215, 1953.
11. Gamble, J. L.: Water Requirements of Castaways. Proc. Am. Philos. Soc. 88: 151, 1944.
12. Crosby, W. H., and Howard, J. M.: The Hematologic Response to Wounding and to Resuscitation Accomplished by Large Transfusions of Stored Blood (Chapter 6, Volume II). Blood 9: 430-460 (May), 1954.
13. Meroney, W. H., and Herndon, R. F.: The Management of Acute Renal Insufficiency. J. A. M. A. 155: 877, 1954.
14. Fenn, W. O.: The Role of Potassium in Physiological Processes. Physiol. Rev. 20: 377, 1940.
15. Johnson, K. E., Teschan, P. E., and Post, R. S.: Cation Exchange Resins for Control of Hyperkalemia in Patients with Post-traumatic Renal Insufficiency. (In preparation.)
16. Moots, M. F.: Acute Anuric Uremia. U. S. Armed F. Med. J. 3: 1041, 1952.
17. Luetscher, J. A., Jr., and Blackman, S. S., Jr.: Severe Injury to Kidneys and Brain following Sulfathiazole Administration: High serum sodium and chloride levels and persistent cerebral damage. Ann. Int. Med. 23: 741, 1943.
18. Legrain, M.: Nephrites Aigues Anuriques. G. Doin et Cie. Paris, 1951.
