Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV
The Role of Surgery in the Treatment of Post-traumatic, Acute Renal Failure*
First Lieutenant Benjamin Rush, Jr., MC, USAR
Major Paul E. Teschan, MC, USA
Captain Roy L. Mundy, MSC, USA
In the past decade many publications have dealt with acute renal failure,** describing its clinical manifestations, plasma electrolyte changes, complications and therapy.12, 14, 29, 30, 32 Recently much stress has been laid on the occurrence of hyperkalemia in this syndrome.6, 7, 8, 13, 15, 18 It is recognized that potassium intoxication is in some cases the major cause of death.15, 18, 32 A number of methods were devised to reduce the serum potassium in patients so threatened.4, 11, 20, 33 One of these methods which has met with considerable success in hemodialysis by means of the artificial kidney,1, 16, 28 The artificial kidney is also used to reduce the level of diffusible catabolites which have accumulated in the extracellular fluids and can modify the symptoms of uremia.14, 17, 18
The following studies were carried out at a specialized treatment center in Korea where casualties who developed post-traumatic renal insufficiency were referred. An artificial kidney was employed as an adjunct in controlling uremia. Frequently, extensive areas of nonviable tissue were not or could not be removed in the initial surgery of these patients at forward surgical hospitals. It is our purpose to describe the clinical and laboratory course of some of these patients and to show that certain serum electrolyte disturbances were more rapid in onset and perhaps greater in magnitude than serum electrolyte deviations seen in patients who develop renal insufficiency of non-traumatic etiology, and to illustrate how these differences in clinical and chemical tempo lead to a somewhat changed approach in the medical and especially in the surgical management.
*In press: Surgery, Gynecology and Obstetrics
**This term is used in the sense defined by Oliver, et al.,21 to include lesions previously called lower nephron nephrosis, crush syndrome, hemoglobin uric nephrosis, traumatic anuria and necrotizing nephrosis.
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Methods
Serum potassium and sodium were determined by the flame photometer using an internal lithium standard,2 serum chloride by the method of Schales and Schales,27 serum CO2 combining power by the manometric method of Van Slyke,22 plasma nonprotein nitrogen and nonprotein nitrogen of the artificial kidney bath by selenium-sulfuric acid digestion and Nesslerization of the protein-free filtrate. Hematocrits were measured by the method of Wintrobe.34
The term oliguria is used to indicate a urinary output of less than 500 cc. per day. Diuresis indicates a rise in the urinary output above 1,000 cc. per day following a period of oliguria. All patients with oliguria were treated according to a basic medical regimen which included fluid intake restriction, intake of at least 400 calories per day, ambulation within the limits of tolerance, digitalis as indicated, testosterone propionate in an attempt to reduce the rate of protein catabolism,17, 19 antibiotics, electrocardiograms daily or oftener, and daily plasma nonprotein nitrogen and electrolyte determinations.
To aid in the control of hyperkalemia S. K. F. Special Resin No. 648,* a cross-linked, polyacrylic, ammonium carboxylate, cation exchange resin was employed, whenever possible, orally or by retention enema. When hyperkalemia could not be controlled by resin therapy, when ECG changes progressed in spite of medical measures, or when the symptoms of uremia became severe an artificial kidney was used. The artificial kidney employed was the modification of Kolff`s model14 described by Merrill, Thorn, et al.16 Intravenous glucose solutions, insulin and hypertonic sodium chloride were often used as an emergency therapy of potassium intoxication.18
The following case reports are presented in three groups: Group I: Moderately wounded patients, free of any great amount of tissue damage or infection who have developed acute renal failure as the result of transfusion reactions. This is considered a control group. Group II: Patients with acute renal failure complicated by the presence of massive tissue necrosis and infection in whom the necrosis or infection could not be removed. Group III: Patients with acute renal failure associated with severe necrosis of tissue or infection in whom the infection or necrosis could be removed.
For the sake of conciseness vital signs and laboratory studies obtained on admission are listed together in Table 1.
*This material was provided by Smith, Kline and French Laboratories, Philadelphia.
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Table 1. Admission Data, Renal Insufficiency Center
|
| Vital Signs | Laboratory Studies | |||||||||
|
|
|
|
|
|
|
|
|
|
|
| |
|
Group I A |
20 |
120/70 |
74 |
18 |
99.6 |
128 |
3.8 |
91.2 |
23.5 |
88.6 |
29 |
|
B |
22 |
106/70 |
100 |
|
97.0 |
128 |
6.1 |
89.6 |
|
203 |
14 |
|
Group II A |
20 |
84/60 |
120 |
52 |
100.8 |
137 |
6.6 |
92.5 |
21.6 |
87 |
|
|
B |
21 |
120/70 |
88 |
|
99.6 |
125 |
6.1 |
88 |
27 |
88.2 |
40 |
|
C |
21 |
150/90 |
125 |
28 |
99.6 |
129 |
7.5 |
88 |
28 |
191 |
42 |
|
D |
21 |
120/70 |
110 |
20 |
|
128 |
7.3 |
79.5 |
|
174 |
27 |
|
Group III A |
22 |
120/90 |
110 |
32 |
101.5 |
113 |
6.2 |
82 |
21 |
144 |
30 |
|
B |
23 |
170/105 |
90 |
16 |
|
116 |
6.6 |
88 |
21.9 |
163 |
30 |
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Case Histories
Group I. Patients with acute renal failure unaccompanied by marked infection or gross amounts of devitalized tissue.
Case A. An exploding land mine inflicted a traumatic amputation of the right foot and penetrating wounds of the right wrist, left thigh and left knee to this patient. At a Mobile Army Surgical Hospital (MASH) 2 hours after injury, admission blood pressure was 120/80. Guillotine amputation of the right lower leg, arthrotomy of the left knee joint and débridement of the other wounds were performed, during which 2,500 cc. of dextran and 1,000 cc. of whole blood were given. The patient did well on the first three postoperative days but was repeatedly transfused because of a low hematocrit. On the fourth postoperative day a hemolytic transfusion reaction developed. In the following 12 hours the urinary output was only 100 cc. A water load test of 1,000 cc. of 5 per cent dextrose in water produced no increase in urinary output after rapid infusion. Because of his oliguria the patient was evacuated to the Renal Insufficiency Center (RIC) where he arrived 24 hours after the reaction.
Physical Examination. The only abnormality found on examination was the postoperative state described above.
Hospital Course. The 24-hour urinary output, which was 100 cc. on the first day, gradually increased, exceeding 1 liter on the eighth post-reaction day. Serum potassium never rose above 5.0 mEq./L. Nonprotein nitrogen rose gradually, reaching a maximum of 273 on the ninth post-reaction day. Following the onset of diuresis, the NPN gradually dropped, returning to normal on the sixteenth post-reaction day. The patient`s wounds remained clean, and granulations began to appear as the NPN returned to normal. He was evacuated on the eighteenth post-reaction day.
Case B. This Turkish soldier received shell fragment wounds to both thighs. At operation 71/2 hours after injury, a severed right femoral artery was repaired by end-to-end anastomosis. The patient`s other wounds were débrided. Hypotension did not occur either before or during the procedure. Postoperatively he made excellent progress. His right foot remained pink with a good dorsalis pedis pulse. On the seventh postoperative day during a secondary closure of his wounds, the patient received a pint of mismatched blood which resulted in a hemolytic reaction associated with hypotension, cyanosis and a hemorrhagic diathesis. Despite transfusions the patient remained hypotensive during most of the first 24 hours following the reaction. His urine was noted to be scant and dark. Because of the hypotension and oliguria the patient was evacuated to the RIC on the second post-reaction day.
Physical Examination. The patient was alert; sclerae were icteric; heart and lungs were normal. Examination of his legs revealed the secondarily closed thigh wounds, moderate edema of the right leg and bilaterally palpable dorsalis pedis pulses. The ECG showed evidence of early potassium intoxication.
Hospital Course. Because of his very low hematocrit the patient was given 1,000 cc. of fresh whole blood on admission. On the fourth post-reaction day be became lethargic, confused and vomited frequently. Serum potassium rose to 6.3 mEq./L. and the ECG indicated increasing potassium intoxication. For these reasons dialysis by means of the artificial kidney was performed during which serum potassium fell to 3.6 mEq./L. and the NPN fell to 83 mg. per 100 cc. On the fifth post-reaction day he was alert and cooperative and vomiting had ceased. Ion-exchange resins were started by mouth. During 12 days of oliguria the NPN rose in small increments to 284 mg. per 100 cc. and potassium remained normal.
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Management of the diuretic phase was complicated by urine volumes between 6,000 and 8,000 cc. for 8 days accompanied by vomiting, but he was evacuated in good condition on the thirtieth post-reaction day. This patient`s wounds remained clean but showed no signs of healing during the period of oliguria; with the onset of diuresis granulations formed rapidly and the wounds healed.
Group II. Cases with acute renal failure complicated by massive wounds or infections in which the infection could not be controlled or the devitalized tissue thoroughly removed.
Case A. This patient sustained a rifle bullet wound in the epigastrium with much loss of tissue from the abdominal wall, transection of the transverse colon and a large laceration in the right lobe of the liver. Blood pressure on admission to a hospital 24 hours after wounding was 90/68. At surgery the liver was sutured and the colon was exteriorized through the wound of entry since this defect could not be closed in any other way. During the first 24 hours postoperatively the systolic pressure remained below 90 despite transfusions of 5,500 cc. of blood, 850 cc. of plasma and 200 cc. of albumin. Urine output on the first post-wound day was 200 cc. A water load test produced a minimal response. Because of his oliguria the patient was transferred to the RIC 36 hours after operation.
Physical Examination. The patient appeared critically ill with a flushed face, mental confusion, and shallow, rapid respirations. Heart and lungs were normal. A portion of the exteriorized colon was black and necrotic. The abdomen was silent. The ECG showed moderate peaking of the T waves and shortening of the S-T segment without QRS prolongation.
Hospital Course. On admission the colostomy was opened and the necrotic bowel débrided. Because plasma potassium had reached a level of 6.6 mEq./L. with ECG changes only 36 hours after operation, dialysis was undertaken for 3 hours against a bath in which the potassium had been omitted. Plasma potassium was reduced to 3.8 mEq./L. and NPN fell to 61.4 mg. per 100 cc. Blood pressure rose to 128/74 by the end of dialysis, and the patient appeared clinically improved. Immediately after the dialysis 60 gm. of cation-exchange resin was given by rectum.
As indicated in Figure 1, plasma NPN rose precipitously. Paralleling this change the patient deteriorated clinically with development of disorientation and a uremic frost. Dialyses on the sixth and ninth post-wound days were followed by brief clinical improvement and abrupt relapse. Following the third diaylsis plasma potassium rose 2.7 mEq./L. and the NPN rose 117mg. per 100 cc. in less than 24 hours. Daily urine output gradually increased to a maximum of 425 cc. on the ninth post-injury day. Evidence of peritonitis with a distended silent abdomen and rectal temperatures of 100° to103° were present throughout the patient`s course despite appropriate therapy. On the tenth post-wound day the patient`s blood pressure became unobtainable and he died. Serum potassium taken 8 hours before death was8.6 mEq./L.
Gross Autopsy Findings. Extensive generalized peritonitis was found with 100 cc. of purulent exudate lying free in the pelvis. No perforation of the bowel was found except in the exteriorized segment. There was a 6 cm. laceration of the right lobe of the liver surrounded by some fibrin. Not more than 2 per cent of the liver was involved. The kidneys weighed 250 gm. each and showed a dark purple medulla with some thickening of the cortex.
Case B. This patient was injured by a land mine, and when he reached a MASH 3 hours after injury blood pressure was unobtainable. The patient was resuscitated with 5,000 cc. of whole blood. At surgery a left supracondlylar
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103
amputation, right orchidectomy and extensive débridement of a large avulsed area of skin and muscle over the right anterior thigh were carried out; wounds of the right buttock and right arm were débrided. A posterior splint was applied to the right arm for a compound, comminuted fracture of the right radius. Surgery was well tolerated without hypotension. However, on the first post-injury day urine output was only 200 cc. Early on the second post-wound day a water load test produced no diuresis and the patient was transferred to the RIC for treatment.
Physical Examination. The patient`s wounds were as described above. The avulsion over the right thigh was massive with the loss of skin and some muscle over an area of 18 by 18 cm. The right forearm was quite edematous over the fracture site and crepitation of the bone fragments was felt. The lungs were clear and the heart was normal. Active peristaltic sounds were present. Two Penrose drains had been left in the deep wound of the right buttock. Rectal examination was negative. The ECG was essentially normal.
Hospital Course. Because of the lowered sodium and elevated potassium on admission, 300 cc. of 3 per cent saline was given intravenously and 60 gm. of cation-exchange resin was administered by rectum. Plasma potassium dropped to 5.1 mEq./L. on the day following admission. Diuresis began on the sixth post-injury day and the patient continued todo well until the tenth post-wound day, when a rectal temperature of 102.8°, leukocytosis of 22,500 cells per cu. mm., and increasing lethargy were noted. All dressings were changed and the wounds were found to be relatively clean although draining profusely. A long arm cast was applied to the right arm replacing the posterior splint. There was no abdominal distention and the patient continued to take fluids well by mouth. On the eleventh and twelfth days he deteriorated clinically and became disorientated. Despite an output of 4,000 cc. of urine on the eleventh day his serum potassium increased slowly to 6.0 mEq./L. and his NPN reached 205 mg. per 100 cc. On the thirteenth day some foul drainage appeared on the long arm cast. The cast was removed revealing a large abscess in an inadequately débrided wound track which extended from the right wrist to the elbow. This abscess was opened widely and 300 cc. of foul pus was removed; cultures grew Aerobacter aerogenes and Staphylococcus aureus. The patient showed little improvement following the procedure, and in the afternoon of the thirteenth day he suddenly and rather unexpectedly died. Plasma potassium that morning was 7.1 mEq./L. None of his wounds showed evidence of granulations or other signs of healing.
Gross Autopsy Findings. One of the perforating wounds of the buttock communicated with a compound fracture of the tip of the sacrum and a perirectal abscess which extended to the peritoneal floor of the pelvis. The bowel was intact. Muscles of the right forearm were soft, friable and purple red. The brachial artery was thrombosed at the level of the mid-humerus. There was marked cerebral edema. Renal congestion was noted.
Case C. This patient was wounded by mortar fire sustaining comminuted fractures of the right tibia, fibula and femur and multiple large penetrating soft tissue wounds of both legs, and left buttock and the right flank with extensive muscle damage. On admission to MASH 2 hours after injury, blood pressure was 100/40 and the urine was grossly bloody. In the course of débridement under anesthesia the patient`s blood pressure became unobtainable and surgery was discontinued. A total of 14,000 cc. of blood, 50 cc. of plasma and 200 cc. of albumin were given on the day of injury, followed by 2,500 cc. of blood on the second post-injury day. Hypotension persisted, however, and the average uri-
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nary output was 100 cc. per day. The patient was, therefore, transferred to the RIC.
Physical Examination. The patient was acutely ill but oriented. Massive destruction of the musculature of both legs and the left buttock was noted. The right lower leg and foot were cold. Heart, lungs and abdomen were normal. The ECG showed characteristic evidence of potassium intoxication.
Hospital Course. Dialysis by means of the artificial kidney was begun within 4 hours after admission. During this 6-hour treatment plasma potassium fell from 7.6 to 5.3 mEq./L. and NPN fell from 191 to52 mg. per 100 cc.; the patient seemed much improved. Six hours after dialysis a right below-knee amputation with extensive débridement of both legs anteriorly and posteriorly was done. The wound of the right flank was explored and the right kidney was found to be lacerated. It was left in place and the renal bed was drained. The patient tolerated the procedure well and returned to the ward in good condition. In spite of oral resin therapy plasma potassium rose within 48 hours after the first dialysis to 7.1 mEq./L.; NPN rose to 163 mg. per 100 cc. A second dialysis reduced the potassium to 4.1 mEq./L. and the NPN to 67 mg. per 100 cc. Thirty-six hours later, on the eighth post-injury day, potassium intoxication had recurred and the patient developed a silent, tender, distended abdomen and jaundice. Bile peritonitis was suspected and exploratory laparotomy seemed necessary. A third dialysis was undertaken in preparation for surgery but was interrupted by the development of cardiac arrest. The chest was opened and cardiac massage was carried out. Cardiac function resumed after15 minutes of massage. Blood pressure rose to 180/70 during the next hour as dialysis was continued and serial ECG`s showed disappearance of potassium intoxication. Although regular heart action continued, the patient`s blood pressure began to fall after the first hour. Repeated small transfusions were of temporary benefit only. Dialysis was continued for 6 hours. The patient was returned to the ward in poor condition and died early on the ninth post-injury day.
Gross Autopsy Findings. A major portion of the posterior muscle groups of both thighs and the left calf were absent. Despite the extensive débridement much necrotic muscle remained. No evidence of wound healing was present. Both kidneys were enlarged with a combined weight of more than 500 gm. The right kidney contained a laceration 6 cm. long and was surrounded by a large hematoma.
Case D. This patient was wounded by mortar fire sustaining a traumatic amputation of the left upper thigh at the hip, multiple penetrating wounds of both buttocks and of the lumbar region and avulsion of most of the skin and much muscle tissue over the left buttock. He arrived at a MASH 9 hours post-injury with a blood pressure of 80/40. At operation a compound, comminuted fracture of the lower sacrum was found with multiple perforations of the rectum and a large amount of feces in the wound. A large hematoma was found in the pelvis surrounding the bladder and rectum. The bladder was intact. A double-barreled sigmoid colostomy was performed, and the wounds were débrided. During the operation the patient`s blood pressure was unobtainable for 45 minutes. It finally rose to 86/40.In the first 6 hours postoperatively the blood pressure varied between 90/60 and 70/40. The patient received a total of 8,000 cc. of whole blood on the day of operation. On the first post-injury day urinary output was only 200 cc.; the patient was transferred to the RIC on the second post-wound day.
Physical Examination. The patient was alert, well hydrated and there was no edema. Wounds were as described above, and in addition there was a com-
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pound, comminuted fracture of the right fibula. The wounds of the buttock contained much foul-smelling necrotic tissue. Heart and lungs were normal. Reflexes were equal and active. ECG findings of widened QRS complexes and high peaked T waves indicated marked potassium intoxication.
Hospital Course. Prior to dialysis the patient received hypertonic sodium chloride and glucose-insulin infusions; plasma potassium fell to 6.8 mEq./L. During a 5-hour dialyis, plasma potassium fell to 5.1 mEq./L. and the NPN to 97.8 mg. per 100 cc. Sixty grams of cation-exchange resin was then given orally. At this time bowel sounds were present and active. He took oral feedings well and continued to do so throughout his course. During the next 12 hours (third post-injury day)the plasma potassium rose 2.5 mEq./L. to a level of 7.6 mEq./L. again with marked, characteristic ECG changes. A second dialysis for 4 hours reduced the serum potassium to 4.0 mEq./L. Soon after dialysis, débridement of the large avulsed area of the left buttock was begun. The entire left gluteus maximus, most of the gluteus medius and minimus and the remaining hamstring muscles were black and necrotic. There was no evidence of gas in the tissue planes and it was felt that this extensive gangrene of muscle was due to blast effect. All of the involved muscle groups were resected as thoroughly as possible, exposing portions of the ileum and the posterior portion of the capsule of the hip joint. The lower third of the sacrum was found to be partially avulsed exposing the retrorectal space. This area was drained. A large wound of the right buttock was also débrided. The patient withstood the procedure fairly well and was returned to the ward in fair condition. Another 60 gm. of cation exchange resin was given orally.
As indicated in Figure 2, the plasma concentrations of potassium and NPN continued to be remarkably labile. Despite a second and third débridement on the fifth and twelfth post-injury days, all of the necrotic tissue could not be removed. Dialysis was repeated on the sixth, eleventh and fourteenth post-wound days with relief in each instance of disorientation, stupor and nausea but with a subsequent relapse in 24to 72 hours. During the fourteenth post-wound day the plasma potassium rose from 4.7 to 7.8 mEq./L. or 3.1 mEq./L. in a 24-hour period; in the same interval the NPN rose 144 mg. per 100 cc. The patient became semi-comatose and his blood pressure became unstable. Emergency treatment with hypertonic saline, glucose and insulin lowered the plasma potassium to 7.4 mEq./L. Following this sixth dialysis the plasma potassium was 5.1 mEq./L. and the NPN 131 mg. per 100 cc. However, despite digitalization, nasal oxygen, small amounts of whole blood, 20 cc. of adrenal cortical extract and nor-adrenalin, the patient`s blood pressure was labile and at times unobtainable during and after the dialysis. After dialysis the blood pressure continued at very low levels despite all supportive measures and the patient died, 6hours after dialysis, on his sixteenth post-wound day. The maximal daily urine volume never exceeded 400 cc.
Gross Autopsy Findings. The muscle tissue of the left hip and in the area over both buttocks had undergone extensive destruction. It was estimated that two-thirds of the skin over the left buttock and one-third of the skin over the right buttock was missing. The remaining muscle was soft, hemorrhagic and necrotic in many places. The muscles and retroperitoneal tissue of the pelvic floor showed extensive destruction and necrosis. A rubber drain was noted extending into the retropubic space where a well localized, well drained abscess cavity was present. Sinus tracts communicated through the shattered sacrum and coccyx with the perirectal space. Little or no granulation tissue was present. The right kidney weighed165 gm.; the left, 190 gm. Both kidneys showed congestion of the renal medullae.
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Group III. Patients with acute renal failure complicated by the presence of infection or large amounts of necrotic tissue in which the infection could be controlled or the devitalized tissue removed.
Case A. This patient was injured by a land mine, sustaining extensive, macerating wounds of both legs with compound, comminuted fractures of both tibiae and fibulae. He arrived at a MASH 11/2 hours after injury at which time he was thought to be moribund. Blood pressure and pulse were unobtainable. In the first 24 hours after wounding the patient received 6,500 cc. of blood but his blood pressure remained unstable and at hypotensive levels for 12 hours. At operation his wounds were débrided and long leg casts were applied bilaterally. During the first post-injury day the patient`s urinary output was 980 cc., but renal clearance studies done by a research unit attached to the MASH showed a marked reduction of renal clearance. On the second post-injury day the patient became delirious and violent. His temperature rose to 103° rectally. Renal clearances were further reduced and total urine output for the day was only 320 cc. Because of the progressive depression of renal function the patient was transferred to the RIC. At the time of evacuation it was noted that the left foot was cold, and it was thought that amputation might be necessary.
Physical Examination. The patient was semi-comatose. Reflexes were hypoactive but present symmetrically. Heart, lungs and abdomen were normal. Long leg casts were present on both legs and were soaked by foul-smelling drainage. On removal of the casts, both legs to the knees were seen to be severely mangled and markedly necrotic, with subcutaneous emphysema. Cultures were taken which later showed Clostridium welchii. The ECG showed changes indicative of moderate potassium intoxication.
Hospital Course. In the presence of advanced bilateral gas gangrene it was felt that immediate operation was indicated. Because of the patient`s elevated plasma potassium and lowered plasma sodium, emergency therapy in the form of intravenous hypertonic saline, glucose and insulin was given. However, an ECG obtained following this therapy showed an increase in potassium effect with widening of the QRS complex and increased peaking of the T waves. Another hemodialysis was in progress at this time and there seemed no alternative but to proceed with the operation. The patient underwent bilateral above-knee amputation done by two teams working simultaneously. The patient was hypotensive throughout the procedure with a blood pressure of 90/60 despite transfusion. He returned to the ward in very poor condition. Immediately postoperatively his temperature rose to 107.5° rectally and remained between 105° and 107° despite iced alcohol baths and rectal aspirin. He was completely comatose and areflexic. The pupils were dilated and did not respond to light. Respirations were Cheyne-Stokes and gasping in character. At one point the patient was apneic for 1 minute but after artificial respiration spontaneous respirations resumed. Repeat ECG showed marked progression of potassium intoxication. The patient`s pulse reached 150 per minute and arrythmias on the basis of ectopic auricular foci developed. Another infusion of saline, glucose and insulin was given. Serum analysis following this showed that the sodium had risen to 132 mEq./L. but the potassium had also risen to 7.4 mEq./L., an increase of 1.2 mEq./L.in 8 hours despite vigorous emergency therapy.
Dialysis was started as soon as the artificial kidney was available for use. At this time the patient was still comatose. His pulse was weak and at times unobtainable. Blood pressure was 96/62. After2 hours of dialysis during which small amounts of blood were given the blood pressure was 116/70 and the patient responded weakly to vocal stimuli. At the end of the 6-hour dialysis blood pres-
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sure was 160/80, the patient was fully conscious and talking although still somewhat disoriented. The NPN had fallen from 144 to 53.4mg. per 100 cc. with the removal of 86 gm. Plasma potassium had dropped from 7.4 to 3.6 mEq./L. with the removal of 300 mEq./L. Temperature was102° rectally and respirations were 24 and regular. The patient was returned to the ward in good condition and given 60 gm. of cation-exchange resin by rectum. The remainder of the patient`s course was uneventful. Diuresis started on the seventh post-injury day. NPN rose to a peak of 168 mg. per 100 cc. on the eighth post-injury day and fell rapidly thereafter. The plasma potassium remained under good control, never rising above normal limits after the dialysis. The amputation stumps remained clean and granulation tissue began to appear on the tenth post-injury day. The patient was evacuated on the sixteenth post-injury day.
Case B. This patient, wounded by mortar fire, was admitted to a MASH 3 hours after injury with penetrating wounds of both knees and thighs, most extensive on the left with transection of the left superficial femoral and left popliteal arteries. Blood pressure was 90/50. At operation his wounds were débrided and re-anastomosis of the injured femoral and popliteal arteries was performed. Before and during operation the patient received 4,500 cc. of blood. After operation the left foot was cold and mottled and its survival was considered unlikely. On the first post-injury day the urine output was 480 cc.; the patient was nauseated, restless and apprehensive. On the second post-injury day he vomited all oral intake. The 24-hour urine volume was only 150 cc. Because of the persistent oliguria the patient was evacuated to the RIC.
Physical Examination. The patient was fairly well oriented but was hiccuping and gagging. His wounds were as described above. The left foot and lower leg to the level of the mid-calf were cold and mottled; the left dorsalis pedis and popliteal pulses were absent. Heart and lungs were not remarkable. Good peristaltic sounds were heard. The ECG showed changes indicative of early potassium intoxication.
Hospital Course. Although the patient`s chemical state did not constitute an emergency, a dialysis was decided upon as the quickest method of returning his high potassium and lowered sodium to normal, stopping his vomiting and rendering his course more manageable. Dialysis was carried out for 5 hours on the third post-wound day. Serum sodium rose to 141 mEq./L., potassium fell to 3.9 mEq./L and NPN to 71 mg. per 100 cc. On the fourth post-injury day the patient was much improved and no longer nauseated. Thirty grams of cation-exchange resin was given by mouth. On the fifth post-injury day, only 24 hours after dialysis, the serum potassium was found to have risen 1.9 mEq./L. to a level of 5.8 mEq./L. despite resin therapy. NPN had risen to 124 mg. per 100 cc. The left lower leg remained cold and mottled to the mid-calf although no definite line of demarcation was in evidence. Because of the rapidly rising potassium and NPN, immediate amputation was deemed advisable without waiting for further demarcation. At operation a below-the-knee approach was first attempted, but it was found that all muscles of the posterior compartment of the leg were necrotic and supracondylar amputation was done. The patient withstood the procedure well. By the following day the serum potassium had fallen to 4.8 mEq./L. Thereafter the potassium and NPN rose only in small increments. By the thirteenth post-injury day the NPN was 253 mg. per 100 cc. and the serum potassium, 5.6 mEq./L. The patient was drowsy, confused and vomiting frequently. In order to control these symptoms another dialysis was performed. Potassium was reduced to 3.2 mEq./L. and NPN to 120 mg. per 100 cc. The
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patient`s clinical condition became much improved. Diuresis began on the eighteenth post-injury day after which plasma NPN gradually fell to normal levels. The amputation stump and other wounds remained clean but there were few signs of healing until about the eighteenth or nineteenth day when granulation tissue appeared and began rapidly to fill in the wounds. The patient was evacuated in good condition.
Discussion
Since the potassium concentration of intracellular fluid is normally about 150 mEq./L. compared to the 4.0 mEq./L. found in extracellular fluids, potassium intoxication is avoided only by unknown mechanisms at the cell membrane which maintain the physiological concentration gradient. The maintenance of this gradient requires work and it is likely that an injured cell will be less able and a dead cell unable to prevent free diffusion of this ion.
Recent clinical and experimental evidence appears to support this hypothesis: Bywaters3 emphasized the rapid development of marked uremia and hyperkalemia in war casualties who have acute renal failure. He found that patients suffering from crushing wounds of the extremities complicated by oliguria frequently died in the first week after injury, most often on the sixth day. Death occurred very suddenly and was frequently preceded by cardiac irregularities. The electrocardiogram showed changes indicative of potassium intoxication and the serum potassium level was often twice normal. Blood urea levels rose as high as 400 to 500 mg. per 100 cc. in a relatively brief period. Mortality exceeded 80 per cent. It was Bywaters` impression that these changes were due to the release of large amounts of potassium and nonprotein nitrogen from necrotic muscle in the absence of a renal excretion route. Samples of necrotic muscle taken from the patients at autopsy showed a loss of 66 per cent of potassium and 70 per cent of creatinine compared to samples of undamaged muscle from the same body.
In patients who have had the circulation to a limb occluded by a tourniquet for 30 minutes to 1 hour, Rewell24, 25 noted an increase in serum potassium following the release of the tourniquet. He concluded that the anoxic cells release potassium or an agent which produced potassium release from cells elsewhere in the body.
In the experimental animal, muscle injury and necrosis from heat, cold or trauma results in major shifts of fluid and electrolytes.9, 23,26 Injured muscles lose potassium and gain sodium while uninjured cells throughout the body gain potassium and lose sodium. The loss of potassium from injured cells is progressive and parallels the disinte-
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gration of the cells. Pirozynski and Webster23 showed that the severity of the injury was directly related to the electrolyte change.
The characteristic differences between the three groups of patients presented here suggest that undébrided, dead or injured tissue in the presence of renal insufficiency is associated with increased rates of potassium and nonprotein nitrogen accumulation in the extracellular fluid. In Group I acute renal failure occurred as the result of transfusion reactions which took place some time after the patients were wounded. Little injured tissue or infection complicated the picture of renal insufficiency. It should be emphasized that although oliguria persisted for 8 days in one case and 12 days in the other the nonprotein nitrogen rose only in small increments over this period and the level of serum potassium was easily controlled. In case IB the patient had a moderate hyperkalemia on admission secondary perhaps to potassium liberation during the hemolytic episode. After one dialysis no further hyperkalemia occurred.
The patients in Group I may be contrasted with those in Group II in whom undébrided necrotic tissue remained. Patients in Group II rapidly accumulated plasma potassium and nonprotein nitrogen in three instances despite repeated dialyses and the administration of ion-exchange resins in all (Figs. 1 and 2). This was most marked in case IID where the plasma potassium rose as much as 3.1 mEq./L. and the NPN 144 mg. per 100 cc. in24 hours.
In case IIA the patient had little apparent direct tissue damage but suffered from advanced infection. In case IIC large amounts of crushed and injured tissue were not sufficiently débrided while infection played an ostensibly minor role. Patient IID had massive tissue injuries associated with very rapid accumulation of potassium and non-protein nitrogen. Following vigorous débridement of the dead tissues the plasma potassium concentration seemed better controlled for several days. Another period of rapidly increasing uremia and hyperkalemia followed, probably due to uncontrolled infection and progressive necrosis of tissue in the pelvic floor. Case IIB is of special interest: a progressive rise of plasma potassium up to 7.1 mEq./L. occurred despite a diuresis of 4,000 cc. of urine per day containing up to 42 mEq./L. of potassium. This is in sharp contrast with most previous experience among patients with renal failure, namely, that hyperkalemia is rare if the urinary output exceeds 500 cc. per day.17
If we accept the concept that the presence of infected and necrotic tissue is associated with a rapid and dangerous development of potassium intoxication and clinical uremia in the oliguric patient, then early surgical removal of this tissue would seem a logical step in treat-
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ment. The third group of patients presented demonstrate the use of surgical measures to aid recovery. In patients IIIA and IIIB hyperkalemia and uremia were much more easily controlled after large areas of non-viable and infected tissue were removed. In patient IIIB, serum potassium and nonprotein nitrogen rose rapidly after dialysis, but following amputation of the avascular extremity, non-protein nitrogen rose only in small increments and potassium was easily controlled by ion-exchange resins throughout 18 days of oliguria. It should be noted that in both these cases the entire portion of non-viable tissue was contained in the extremities and could be removed in toto at a single operation.
The proper treatment of patients with post-traumatic renal insufficiency requires a well coordinated team of internists and surgeons skilled in the use of fluid and electrolyte therapy. Because of the traumatic nature of their lesions such patients will usually be seen and treated first by surgeons, who must be alert to the possibilities of a complicating acute renal failure. Whereas hypokalemia is a frequently emphasized and well recognized postoperative complication,19 renal failure with a rapidly developing dangerous hyperkalemia following trauma has received little emphasis; that it can be considered as an indication for operation is a new concept. Needless to say, post-surgical potassium therapy is emphatically contraindicated under these circumstances.
Basic surgical principles are modified only in that they are even more vigorously and energetically applied in the presence of acute renal failure. When an area of infected or injured tissue is suspected by the appearance of the earliest suggestive symptoms or signs, drainage or débridement should promptly be performed. Application of this principle would dictate removal of all doubtful tissue in the course of débridement rather than following a "wait and see" policy despite the temptation to be less radical in a patient who is critically ill. This applies also to patients who have lost the blood supply to a limb and in whom a line of demarcation is sought prior to amputation. With normal kidney function the products of decomposition of ischemic tissue are excreted readily without clinical signs of change in the plasma electrolyte; waiting for demarcation is justifiable. In the oliguric patient under the same circumstances the products of tissue breakdown cannot be excreted and the dangers of fulminating uremia and hyperkalemia may render any delay extremely hazardous.
In the reverse situation a sudden increase in the rate of accumulation of plasma nonprotein nitrogen or potassium concentrations in the oliguric patient may indicate occult infection or necrosis. A careful
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examination of the patient may show an early subphrenic abscess, a pelvic abscess, or an area of infection hidden by a cast (as in case IIB).
A striking feature in patients with acute renal failure was the delayed appearance of granulation tissue and wound healing. This was true in all the groups presented. Frequently the onset of diuresis and a fall in the serum nonprotein nitrogen seemed to coincide with a sudden increase of granulation tissue and accelerated wound healing. Whether this finding may be explained by the accumulation of metabolic end-products which inhibit the healing process or by the state of "excessive response" described by Moore19 is not known. In any case, the expectation of delayed healing must be kept in mind when the wounds of these patients are being treated or operation is contemplated. Dehiscence occurs frequently. When suture material is selected it should be of the type that will retain its strength and can be left in place until kidney function returns and uremia abates.
Delayed wound healing may result in a vicious cycle: Deficient tissue repair and poor localization of infection contribute to further infection with increased tissue injury and necrosis; this tissue injury in turn contributes to a greater degree of uremia, thus wound healing is further delayed and the opportunity for further infection and necrosis is enhanced.
Surgery is of course of the greatest help in those patients with necrosis and infection confined to the extremities. Here the entire area affected can be removed, leaving the smallest possible surface exposed to reinfection. Such patients should have the best prognosis and it has already been noted that both patients in our third group were of this type.
Post-traumatic renal insufficiency is seen only occasionally in civilian practice: Renal failure following accidental crush injuries, traffic accidents with massive trauma or shock, and occasionally renal failure superimposed on radical surgery are examples. However, in event of a civil catastrophe or war such problems can become commonplace. A full understanding of the problems of therapy will help to reduce mortality in these circumstances.
Summary and Conclusions
1. The case histories of eight patients with acute renal failure have been presented. In two of these cases renal insufficiency followed transfusion reactions. In six cases the renal insufficiency occurred after trauma.
2. Accumulation of potassium and nonprotein nitrogen in the serum of patients with renal insufficiency is accelerated in the presence of
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large amounts of necrotic tissue or infection. Fatal myocardial potassium intoxication may develop rapidly and is a recurrent hazard.
3. Control of the hyperkalemia and uremia in these patients is accomplished only through frequent use of the artificial kidney, and the patient`s clinical condition often rapidly deteriorates unless the necrotic tissue is removed or the infection brought under control. Amputation, débridement and drainage, therefore, must be undertaken at the earliest evidence of abscess or necrosis even though the patient may be critically ill.
4. Wound healing is delayed in these patients. This should not deter surgery but should be considered as a factor in the type of approach and materials used.
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