Management of postoperative acute renal failure

Management

of Postoperative Renal

Acute

Failure

GEORGEAUSTEN,JR., M.D., Boston, Massachusetts

From the Department of Urology, Boston University School of Medicine, and the Department of Urology, Boston City Hospital, Boston, Massachusetts.

RENAL FAILUREiS a general term for A CUTE the sudden development of impairment of renal function to a degree that normal metabolic and biochemical homeostasis can no longer be maintained. Its principal early clinical manifestation is a reduction in urinary output, classified by the term oliguria when the daily output is less than 300 to 400 ml. of urine and by the term anuria when the twenty-four hour urine output is zero or close to it. On the other hand, it is well to remember that urinary output alone is not the sole early indication of acute renal failure, for azotemia and clinical uremia, with secondary circulatory insufficiency and electrolyte alterations, may sometimes develop rapidly despite a relatively normal urinary output. Although it is not a frequent complication of surgery, acute renal failure in the immediate or early postoperative period is an urgent and serious clinical problem which, if not recognized and treated promptly, has resulted in the past in an over-all mortality of well above 75 per cent although in recent series has been reduced to less than 50 per cent. Our early understanding of acute renal failure was first stimulated by the description of the crush syndrome, a result of bombing injuries incurred in England during World War II [l]. In recent years, sufficient progress has been made in knowledge of the pathogenesis, the basic pathophysiology, and the sequelae of acute renal insufficiency so that the modern surgeon, whether general or specialist, should be familiar with current methods of prevention, of early diagnosis,

especially of reversible causes, and of major principles of immediate active management. Previous common causes of a lethal outcome of acute renal failure such as cardiac failure with pulmonary edema, hyperkalemia, and uremia can be avoided, and death from acute renal failure today should therefore occur most often only as a result of inability to correct the underlying disease, pre-existing or recently acquired, or because of complicating infection. Thus, even though the first manifestations of postoperative renal failure may be those of a reversible functional rather than an irreversible anatomic renal deficit, and no matter how benign the initial inciting insult or subsequent early course of the syndrome, immediate recognition and treatment are essential to prevent an otherwise disastrous outcome. In the absence of pre-existing renal disease due to other causes, the most common and characteristic form of acute renal failure is due to damage to renal parenchyma, so-called acute tubular necrosis. Based on the classic and still tenable observations of Oliver, McDowell, and Tracy [Z] and Oliver [3], two principal categories of lesion may occur, that is, the ischemic and the nephrotoxic. The parenchymal lesion produced by a nephrotoxic agent consists of uniform necrosis of the epithelium of the tubules down to but not including the basement membrane, whereas the lesion due to ischemia alone shows evidence of fragmentation and rupture of the basement membrane, with complete disintegration of the tubular structure and leakage of the tubular contents into the renal interstices. Although Lucke [P] believed that the ischemic lesion occurred primarily in the distal portion of the nephron, and therefore described the syndrome as “lower nephron 346

The American

Journal

of Surgery

Acute

Renal

nephrosis,” studies by Oliver and others have demonstrated that the lesion can and does occur in any part of the nephron. Pathologic changes are not diffuse but patchy, with damaged areas being interspersed in areas of normal tubular epithelium. These changes are most prominent in the medulla, possibly secondary to a juxtamedullary shunt. Grossly the kidneys in acute tubular necrosis appear enlarged and swollen, with a tense capsule and parenchyma which bulges through the cut surface of the capsule. In Oliver’s studies, the cortex appeared pale and the medullary area was congested, changes suggesting the presence of interstitial edema of considerable degree. Although postmortem sections frequently show edema of the renal interstitium, results of renal biopsies during life have been inconsistent, some revealing interstitial edema whereas others have shown none. The presence or absence of interstitial edema has been a critical point of argument concerning the cause of oliguria in acute renal failure, as has also been the role of intraluminal tubular obstruction by casts. Neither finding has been constant, and it is possible that their presence or absence may be dependent largely on the type, degree, and duration of the primary ischemic or nephrotoxic factor in the individual case. There is good evidence to indicate that the nephrotoxic and ischemic lesions are not completely separable since in many kidneys damaged by nephrotoxins the lesions typical of ischetnia may also occur. Although glomeruli are generally uninvolved in acute tubular necrosis, a number of postmortem and biopsy studies have demonstrated glomerular involvement varying from hyalinization of glomeruli to periglomerular fibrosis [5,6]. These changes have been found in biopsies performed months after apparent recovery from the episode of acute renal failure. Similarly, in the healing process, tubular repair tnay be complete, with resorption of interstitial edema and restoration of tubular epithelium or, in instances of more severe damage, with tubular atrophy and fibrosis, interstitial fibrosis, and permanent loss of tubular integrity. Since the blood supply to the tubules comes via the glomerulus, it would seem evident that decrease in renal blood flow should first involve the postglomerular structures, that is, the tubules. However, because the areas involved may alternate with uninvolved areas, recovery of a considerable or major degree of renal funcVol. 116, Se~lember 1968

Failure tion may be possible even with total disruption of some of the affected nephrons. In the more diffuse and severe instances of vascular insufficiency, such as that which occurs in symmetrical cortical necrosis or obstruction of the main renal artery, the entire kidney may be infarcted; recovery is then largely dependent on both the degree and duration of vascular obstruction. In general surgical practice, the majority of cases of acute renal failure result from renal ischemia. The complex mechanism by which this ischemia leads to renal damage is by no means settled, particularly the role of circulatory dynamics [7,8]. Decreased blood flow, mechaintrarenal shunts, vasoconstrictive nisms, circulating amines, and increased renal resistance are all possible primary etiologic factors. Milder forms of decreased renal blood flow may create a functional disturbance of reduced tubular flow with diminished urine volume and changes in the concentration of urine and excretion of solute but without demonstrable parenchymal damage. More severe or prolonged renal ischemia, on the other hand, is followed by actual necrosis of tubular cells, with loss of normal tubular anatomy and function and with probable tubular obstruction secondary to compression by interstitial edema and/or intraluminal blockage due to the formation of tubular casts or the precipitation of normally soluble proteins. The latter picture is that of “acute tubular necrosis.” Normally the kidneys receive from S:i to 30 per cent of the cardiac output. When the cardiac output decreases, as a result of either primary impairment of cardiac contractility or diminished volume of blood or extracellular fluid, the renal share of cardiac output may decrease, with subsequent alterations in renal circulation, urinary volume and concentration, and solute excretion. Marked decreases in cardiac output of variable origin are frequent precursors of acute renal failure. However, although the resulting reduction in filtration rate is characterized by modifications in the volume and composition of urine simulating changes secondary to destruction of renal parenchyma, these modifications are entirely reversible when the primary circulatory disorder has been corrected. Providing decreases in filtration rate do not exceed 30 per cent, the effects of major surgical procedures, anesthesia, and trauma, accompanied by increased secretion of anti-

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diuretic hormone, produce similar functional changes in renal dynamics, with reduced urine volume and increased urinary concentration. With further more marked decrease in renal blood flow, however, renal ischemia severe enough to cause necrosis and edema will result. Although supporting clinical data are lacking, there is experimental evidence which suggests that the renal blood Aow must drop to less than 5 per cent before renal parenchymal damage occurs [9 1. In dealing with reversible renal failure, clinical concern is centered on the division between urinary suppression due to a temporary decrease in renal blood flow through normal parenchyma and that caused by damage to functioning renal tissue. When damage to renal parenchyma has occurred, restoration of blood volume or cardiac output may not result in increased urine flow, and efforts to force a diuresis may result only in overloading with fluid and in pulmonary edema and death. It is important, therefore, to establish criteria which may help to differentiate these two conditions. When the filtration rate is decreased below 30 per cent or more of control values, the reduced volume output is no longer characterized by an increased solute concentration (osmolality) and a decreased concentration of sodium. The urine becomes diluted and the urinary sodium concentration rises. In other words, organic damage to the kidney has occurred; moreover, if the situation continues, acute renal failure in its typical form will be manifest. Prior to this, however, restoration of more normal blood flow to the kidneys may reverse the situation and prevent prolonged oliguria due to tubular necrosis. From a clinical standpoint, and as a means of guiding selection of specific therapy, acute renal failure may be divided into three general diagnostic groups : prerenal, postrenal, and renal [10,11]. This approach is simple and rapid and brings the patient to appropriate treatment in a minimal amount of time. The major reversible causes of this accident in each of these categories are outlined in Table I. This division emphasizes the fact that only in the third category is there renal parenchymal damage adequate to cause in itself functional failure. Likewise, it indicates that pre- and postrenal factors may be immediately remediable by specific treatment whereas acute lesions of the renal parenchyma must heal spontaneously. It

TABLE I MAJOR CAUSES OF ACUTE RENAL FAILURE I.

II.

Prerenal(circulatoryinsufficiency)

A. Plasmavolume deficiency 1. Hemorrhage 2. Fluid and electrolyte depletion 3. Hypoproteinemia, severe B. Circulatory collapse (shock) 1. Plasma volume deficiency 2. Cardiogenic: myocardial infarction, etc. 3. Peripheral: septicemia Postrenal (obstruction) A. Urethral stricture or valves B. Prostatism:benignprostatichypertrophy, C. D. E. F. G. H. I.

III.

cancer, and fibrosis

Bladder tumor Other pelvic or retroperitoneal tumors Calculi: ureter or renal pelvis Tumors: intrinsic ureteral or pelvic Ureteropelvic junction obstruction, congenital Retroperitoneal fibrosis Ureteral obstruction after surgery or instrumentation J. Lntrarenalobstruction: sulfa, urates, etc. Renal (primary renal injury) A. Acute tubular necrosis and cortical necrosis 1. Ischemic: circulatory inadequacy and postsurgical/obstetric 2. Nephrotoxins 3. Combined: hemolysis, crush injury, and burn B. Acute glomerulonephritis C. Arterial obstruction: emboli and thrombosis D. Venous obstruction : renal vein thrombosis E. Acute pyelonephritis 1. Papillary necrosis 2. Diffuse abscesses F. Hypercalcemia, severe

is obvious that prerenal factors, if severe or prolonged, as well as postrenal factors such as lower urinary tract obstruction, may cause renal parenchymal damage. Conversely, it should be emphasized that a presumptive or even positive diagnosis of acute parenchymal renal failure does not rule out concomitant obstructive uropathy or prerenal elements which may be remedied. PREVENTION ACUTE

OF POSTOPERATIVE RENAL

FAILURE

Although acute renal failure is not uncommon prior to surgery (such as in severe trauma, burns, severe infections, and obstructive uropathy), the majority of cases of acute renal failure in surgical practice occur either during or after surgical manipulation. In some instances, because of either the type or complicated nature of the procedure, the development of acute renal insufficiency may not be The American

Journal

of Surgqv

Acute Renal Failure unexpected. On the other hand, in many cases, particularly in the older person, the potential for development of this event might have been anticipated, and preoperative preventive measures could have been instituted to minimize its occurrence in the period of stress during and after surgery. Thus, it may be fair to say that the first approach to the management of postoperative renal failure is prophylactic. Such a program may be affected with completeness and without undue waste of time in elective cases be somewhat curtailed but may, of necessity, in semi-emergency and emergency cases. A thorough understanding of the pathogenesis of acute renal failure and recognition of the principal basic factors initiating its development are fundamental to the prevention of renal failure during surgical therapy and to the treatment of failure should it occur. Since the target organ is the kidney and its functional status, and since the basic mechanism leading to acute functional and organic damage to this organ is a reduction in effective renal perfusion, it is essential that a routine specific preoperative screening procedure be adopted for patients, especially those in the older age group or with underlying chronic disease, who are to be subjected to all but relatively minor procedures. Primary attention should be directed to cardiopulmonary efficiency and the state of renal function antedating operation as well as to the restoration of deficits of blood plasma and extracellular fluid. A complete but by no means complex study of renal function should include a careful history and physical examination, complete urine examination (and urine culture if indicated), complete blood count, determination of blood urea nitrogen and/or creatinine as well as serum electrolytes, serum total protein, body weight, and blood volume if indicated. If abnormalities predisposing to, or indicative of, defective renal function are noted in these preliminary studies, and providing emergency operation is not imperative, more detailed examination of the functional and anatomic status of the urinary tract should be performed. Relatively simple but somewhat more precise estimates of renal function may be determined by use of the phenolsulfonphthalein test, the concentration and dilution test, and by the urea or preferably the endogenous creatinine clearance test. Since none of these procedures provides information concerning the anatomy

3-k!)

of the urinary tract, preoperative intra.venous urography should always be performed when other preliminary tests, including history or physical examination, are suggestive of abnormal kidney function. Clearance studies for evaluation of renal blood flow, glomerular filtration rate, and tubular secretory activity are of no practical value in the management of acute postoperative renal failure. It has long been recognized that acute renal failure occurs with much greater frequency under conditions of antidiuresis. In recent years it has become apparent that an important factor contributing to the development of postoperative acute renal failure is the common practice of restricting food and fluid intake for considerable periods of time prior to general anesthesia and surgery. Furthermore, many patients who are to undergo surgery, especially emergency surgery, may have volume depletion due to vomiting or diarrhea, chronic blood loss, or protein depletion. This may be difticult to recognize and may predispose to acute renal failure particularly when the blood pressure falls with the administration of anesthesia. Current opinion indicates that postoperative oliguria is not a normal event but an artifact related to the pre- and intraoperative fluid management of the patient. It is now recognized that the character as well as t.he quantity of fluid administered is important [ 12 --I 7 1. In contrast to the effects of administration of salt-free water in surgical patients in whom a decrease of renal plasma flow, glomerular filtration rate, and urine flow is generally observed, the administration of saline or similar balanced salt solutions, such as lactated Ringer’s solution, before and during anesthesia and operation is associated with little or no reduction in these parameters of kidney function, and significant postoperative oliguria is infrequent. Rigid control of the quantity of saline administered must be exercised, for there may be danger in giving an intravenous saline load to certain patients, particularly those with edema, pulmonary insufficiency, and marginal cardiac function. In these patients as well as in poorer risk patients in whom potentially complicated or prolonged operations are undertaken, it is important when indicated to monitor urine volume, arterial pressure, and central venous pressure carefully throughout surgery and during the critical early postoperative period. The role of an osmotic diuretic such as

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mannitol as a continued therapeutic means of promoting prolonged diuresis and thereby preventing acute renal failure has been the object of considerable study and some controversy [18-211. Mannitol is essentially glucose that, unlike glucose, does not enter the cells, and therefore its osmotic action resembles that of saline. Glucose solutions are distributed evenly throughout total body water whereas mannitol is distributed in the extracellular spaces and even in small volume extracts from cells its volume equivalent of water. Except for its temporary use as a tool to assay the ability of the kidney to respond to a diuretic test load (reversible functional versus irreversible parenchymal damage), there is little evidence that the effect of mannitol as a preventive measure is superior to that of an adequate amount of salt and water except in certain rather specific situations in which an initial infusion of the diuretic in conjunction with appropriate fluid therapy is followed by its continued use for a controlled period [22,23]. The latter clinical situations include acute trauma with severe tissue damage, open heart surgery, aortic cross-clamping, and surgery on the kidney or renal vasculature in which temporary occlusion of the renal artery is necessary. To be effective in these as well as in occasional other circumstances, mannitol should be given before or simultaneous with the event which might otherwise precipitate acute tubular necrosis. On the other hand, even though administration of the drug is delayed but an apparent response to its use is noted, it may be advisable to continue the infusion at a rate necessary to sustain urine output at least at a minimal effective level of 20 to 40 ml. per hour. Intravascular hemolysis, whether spontaneous, due to mismatched blood, or to infusion of distilled water, may lead to acute renal failure. In the majority of cases this accident should be entirely preventable by proper care in crossmatching for transfusion and by avoiding the use of distilled water either as an infusion or as an irrigating fluid during transurethral surgery [10,17]. If the event is recognized promptly, immediate use of mannitol may be advised to abort incipient renal failure. Similarly, the intravenous administration of an alkali such as sodium bicarbonate or lactate solution has been suggested as a valuable adjunct under these circumstances on the basis of the fact that acid hematin is more soluble in an alkali than

in an acid urine. However, it is well to remember that if one wishes to alkalinize the urine in such an instance, the administration of alkali presupposes the ability of the kidney to elaborate an alkaline urine in response to this alkali load. It is obvious that if the kidneys are already damaged and unable to respond in this fashion, such treatment will be futile. If they can respond, the intravenous administration of no more than 5 to 6 gm. of either solution is necessary to achieve this result since the infusion of larger amounts may result in a sodium load which cannot be excreted and which may contribute to pulmonary edema or tetany as renal failure continues. The intravenous infusion of Diamox@ (carbonic anhydrase inhibitor acetazolamide) under such circumstances may achieve the same degree of prompt although brief alkalinization of the urine with equal success but without the administration of excess sodium. The occurrence of acute renal failure after oral cholecystography utilizing bunamiodyl as a contrast medium and after intravenous urography, particularly in patients with myeloma, has been reported in a small but significant number of cases [24,25]. Acute depression of renal function may also occur after aortography and renal angiography and also after lower urinary tract instrumentation or catheterization of ureters. In the latter instance, acute urinary suppression is the result either of lower ureteral obstruction due to edema and/or ureteral spasm or of the development of diffuse sepsis. Although relatively infrequent, occasional cases of oliguria developing after these common preoperative diagnostic procedures call attention to the importance of routinely checking urine output for at least twenty-four to forty-eight hours after such examinations, particularly during the twenty-four hours prior to planned operation. In the presence of a significantly reduced urine output, early operation may serve only to convert a potentially reversible functional deficit into a more serious parenchymal deficit. Unfortunately, a simple and accurate monitoring program of fluid intake and output is difficult to institute except in the critically ill patient. Nevertheless, adequate hydration after these studies should be stressed to all concerned with the care of such patients; moreover, since one third of pure water ingested orally becomes trapped in the extracellular space, consideration must be given The American

Journal of Suvgery

Acute Renal Failure to the administration of additional supplemental fluids. A number of other common surgical conditions are not infrequently complicated by acute renal insufficiency. Acute hemorrhagic pancreatitis is frequently associated with acute renal failure due in large part probably to associated shock but to some extent perhaps to liberation of pancreatic enzymes into the circulating blood stream. Although the concept of such an entity is disappearing, the so-called hepatorenal syndrome (fever, shock, jaundice, and anuria) is likewise commonly accompanied by renal failure. Again, although derangements of liver function may be followed by specific alteration of renal hemodynamics and function [%I, the cause of acute renal failure in this particular circumstance may be only the result of shock or overwhelming infection after biliary surgery. Intestinal obstruction associated with substantial alterations in circulating blood volume and perhaps the elaboration of toxins may also be complicated by renal failure. The prevention of acute renal failure in these various conditions is dependent primarily on appropriate treatment of the underlying disease, avoidance of shock, and control of infection. Every precaution should be taken in both the pre- and postoperative period to control infection and prevent endotoxic shock, particularly in older patients and those who are chronically debilitated or the victims of severe trauma. Similarly, early detection and correction of acidosis, whatever the cause, will require attention to prevent decrease in renal blood flow. In many patients a depletion of potassium and perhaps some hypercalcemia either will be present or may develop in the course of their surgical career. Although there is no definite knowledge of the mechanisms involved, it is postulated that these alterations may predispose to a greater susceptibility to acute tubular necrosis. Their correction may be of some preventive value. The preoperative correction of partial renal insufhciency in patients with pre-existing renal disease and marginal stable renal function is of particular importance in the prevention of acute postoperative renal failure not only in the general surgical patient but more specifically in the urologic patient who must undergo surgery on any portion of the urinary tract and especially when kidney surgery is contemplatetl. Unless properly prepared, these paVd

I Ifi, September 1968

tients tolerate surgery poorly. I-Io\vever. with careful attention to appropriate measures to stabilize renal function at its maximal level of efficiency, surgery can usually be performed with little risk even when preoperative azotemia is present. The primary aim of preoperative therapy in the obstructive uropathies is directed toward relief of urinary obstruction, restoration of renal circulation, prevention of spreading infection, and correction of fluid, electrolyte, protein, and red cell imbalances. In patients with severely compromised renal function, peritoneal dialysis or hemodialysis may be necessary to prepare the patient for surgery. Renal and cardiorespiratory equilibrium having been attained and other defects having been corrected insofar as possible, it is now well to consider what operative and postoperative measures can be taken to actively prevent acute renal failure after operation. The principal operative factors initiating the lnechanisms producing acute renal failure are destruction of tissue, destruction of blood, development of hypotension and/or shock, loss of blood and or fluid, loss of electrolytes, and decreased cardiac output. It is obvious, therefore, that meticulous consideration of the details of optinlal conduct of the surgical procedure itself is of great sixnificance. In complicated or dificult cases the maintenance of optimal conditions may of necessity become impossible, and factors predisposing to acute renal failure may intervene. Nevertheless, the surgical team must at all times insure the provision of all means to prevent such an accident. These include adequate analgesia, appropriate anesthesia, avoidance of anoxemia, minimal tissue trauma, control of blood loss, maintenance of blood volume and pressure, appropriate antiseptics. and when indicated, maintenance of urinary tract drainage. Constant attention to the principles outlined in the previous phases of the patient’s surgical career must be continued postoperatively. Unfortunately, despite all precautionary measures, acute failure may supervene. Prompt recognition of the onset of the event may frequently be the key to successful restoration of adequate renal function. EARLY

RECOGNITION

AND

DIAGNOSIS

Careful monitoring of the urine volume after surgery is necessary for early diagnosis. The earliest manifestations of impending or es-

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tablished renal failure in the postoperative patient are on the one hand the occurrence of oliguria or anm-ia and on the other hand the perhaps incidental discovery of a rising blood urea nitrogen or creatinine level even in patients in whom urinary output appears normal. In the latter regard, it is well to remember that azotemia (not creatinemia) may often be due to increased catabolism secondary to bleeding into the intestinal tract or other body compartments, to necrosis of tissue, or to infection; in these circumstances it is therefore not necessarily evidence of actual renal failure. Overt clinical symptoms of uremia are generally absent in early acute renal failure unless acute failure is superimposed on a preexisting state of moderate or marked chronic renal insufficiency. Many of the more common causes of acute renal failure seen in the nonoperative patient, such as acute glomerulonephritis, renal vasculitis, periarteritis, lupus erythematosus, and intrarenal precipitation of sulfa and mate crystals, need no comment in the present discussion. Similarly, except for certain toxic antibacterial agents such as polymyxin, neomycin, and sulfa, the usual nephrotoxic agents associated with acute failure (carbon tetrachloride, ethylene glycol, and mercuric chloride) likewise may generally be excluded as diagnostic considerations in the postoperative patient. Thus, one of the more important aims in the management of this postoperative actident is to look for reversible or specifically treatable causes of acute renal failure, such as circulatory insufficiency, obstructive uropathy, acute py~onephritis (papillary necrosis or diffuse renal inflammation superimposed on pre-existing acquired or congenital disease such as polycystic kidney), renal arterial or venous obstruction, intravascular hemolysis, certain nephrotoxins, and hypercalcemia. Of these potential etiologic factors, immediate attention should be focused on the most likely and frequent causes of postoperative renal failure, such as prerenal circulatory inadequacy and postrenal obstructive uropathy. The history and physical examination, although frequently and often necessarily abbreviated by particular circumstances of the postoperative state, are essential to recognition of the type of renal failure and selection of a successful course of therapy. The history may reveal obvious but apparently unrecog-

nized and untreated preoperative deficiencies conducive to critical depression of renal blood flow at operation or it may indicate evidence of complications during the operative procedure and in the immediate postoperative period suggestive of obvious stimuli to reduction of renal perfusion and subsequent ischemia. Although the contributing factor to acute failure secondary to prerenal circulatory insufficiency can often be documented, the accident may be the sequel of hypotensive episodes mild enough to have passed unnoticed. In either instance, pain in the renal area and hematuria are generally absent unless surgery has involved the urinary passages or unless failure is due to acute prerenal arterial or venous obstruction of the kidney itself. Renal arterial obstruction is usually embolic from intracardiac thrombi whereas thrombosis of the renal artery may be associated with blunt trauma or underlying arteriosclerosis. Total occlusion of a renal artery is associated with severe renal pain, gross hematuria, and suppression of urine formation by the involved kidney. Incomplete arterial occlusion can also produce total functional failure of the affected kidney by reflex vasoconstriction of the remaining vasculature. However, except in rare instances of bilateral renal arterial obstruction, anuria and acute renal failure will not be manifest unless there is nonfunction of the contralateral kidney due to preexisting congenital or acquired disease or unless the affected organ represents the patient’s only kidney [27]. Thrombosis of the renal vein in the adult may occur with the nephrotic syndrome [ZS], but is mainly seen in women, is usually secondary to extension of clot in the inferior vena cava from pelvic thrombophlebitis, and is often bilateral in nature. It is generally associated with renal pain, hematuria, rapid development of a tender renal mass, fever and leukocytosis, and anuria. Prognosis in the adult is generally poor, surgical exploration is of questionable value, and the only treatment is immediate institution of anticoagulant therapy. Occasional cases of primary unilateral renal vein thrombosis in the infanr due to severe diarrhea with dehydration or to severe sepsis with adequate function of the opposite kidney may be treated successfully by nephrectomy if the diagnosis is established early and operation is carried out promptly. The American

Journal

ofSurgery

Acute

Renal

Excluding the specific and infrequent renovascular occlusions previously mentioned, symptoms and physical signs in the majority of patients with prerenal circulatory kidney failure are usually absent except for oliguria snd,‘or anuria. Examination may reveal evidence of dehydration such as soft eyeballs, decreased turgor of skin, dry axillae, and parched tongue, but few other clues may be detected. Acute renal failure due to postrenal causes, on the other hand, is often but not always accompanied by symptoms or physical signs which may provide a number of diagnostic clues. The category of postrenal failure comprises only a relatively small number of disorders. Nevertheless, it is an important group because it is constituted largely of those cases in which urinary suppression is due to obstruction of the urinary tract and in which prompt diagnosis will permit immediate relief of obstruction and restoration of urinary outflow. Total vesical retention is a common event in the postoperative period and may occur as a result of either pre-existing but unrecognized partial outlet obstruction or early acute postoperative overdistention in the patient who is obtunded or who is unable to recognize the normal desire to void because of sedation or the greater discomfort of an abdominal incision, and so forth. In the patient with a previously compensated bladder, total vesical retention should be readily detected by symptoms of suprapubic pain and urgency and by palpation of a tensely distended bladder, in conjunction with incidental findings perhaps of some distal urethral abnormality or enlargement of the prostate by rectal examination. In the patient with a previously badly decompensated bladder, however, the recognition of postoperative total retention may be delayed unless the physician is aware of this possibility. Under such circumstances, pain of overdistention may be minimal or absent, the flabby distended vesical outline may not be clearly evident on abdominal palpation, and the only manifestations of retention are total anuria or oliguria in the form of overflow dribbling. The diagnosis in either instance will be established easily by urethral catheterization which should always be performed promptly if there is any doubt as to the patency of the lower urinary tract. Although bladder neck and intrinsic urethral obstruction by Vol. 116, Sefmnber

1968

Failure prostatic disease or urethral stricture are by far the most common causes of postoperative lower tract obstruction, bladder dysfunction may freand interference with drainage quently occur after various types of pelvic surgery, as the result of either direct injury to the urethra or bladder or interference to normal outflow by extrinsic dist.ortion and compression from adjacent pelvic edema, hematoma, or abscess. The most dramatic example of ureteral obstruction as a cause of acute renal failure is seen with bilateral ligation of the ureters incurred during the course of pelvic or retroperitoneal surgery. The lumen of the ureter may be totally occluded or may be simply angulated and kinked, but the immediate result in either case is usually total anuria. Extrinsic compression of the ureters by postoperative retroperitoneal hematoma, extravasation, or even preexisting retroperitoneal nodal disease may likewise produce either total or partial obstruction and subsequent renal failure. A nonobstructing calculus may become dislodged and impacted in obstruction, the ureter with consequent whereas intraluminal obstruction may also result from ureteral clots secondary to trauma to the upper part of the urinary tract or even active spontaneous bleeding from an otherwise unsuspected renal source such as a tumor. Obstruction of the ureters due to the deposition of sulfonamide crystals is rarely seen in the postoperative period, but deposition of uric acid crystals may cause obstruction of the collecting system after the use of one of the uricosuric agents or after radiation or drug therapy of lymphoma when alkalinization of the urine and adequate urine volume have not been maintained. It would seem unnecessary but it is perhaps well to note that if obstruction is above the level of the bladder, it must be bilateral to cause renal failure unless there is absence or untreatable complete functional destruction of the contralateral kidney. If the patency of the urinary tract has not been clearly established prior to surgery, and/or if there is any question of urinary tract obstruction as a cause of acute renal failure, immediate diagnostic study to determine the status of the urinary tract is imperative. X plain x-ray film of the abdomen is obtained and may reveal absence of a renal outline, abnormalities or discrepancies in the size and contour of the kidneys, or evidence of an opaque stone. Other

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helpful clues to be derived from roentgenograms of the kidneys, ureters, and bladder are evidence of a large bladder shadow or areas of increased opacity suggestive of retroperitoneal or pelvic hematoma as well as skeletal lesions such as prostatic metastases. The film will not show such causes of obstruction as radiolucent uric acid calculi, idiopathic retroperitoneal fibrosis, or sloughed renal papillae. If the functional status of the bladder cannot be determined or is obviously at fault, the next step is catheterization of the bladder per urethra. If little or no urine is obtained, excretory urography, particularly by the rapid infusion technic, may be of some value at this point in the investigation. However, if renal perfusion and function are moderately to markedly depressed, little information may be gained and the injected contrast material may only serve as a further potential insult to the renal parenchyma. Accordingly, under these circumstances and if the clinical picture so indicates, excretory urography should be omitted. Immediate cystoscopy and ureteral catheterization with or without the retrograde injection of a small amount (1 to 3 cc.) of contrast medium should be performed and will most expeditiously establish the presence or absence of ureteral obstruction. This procedure, if performed with proper technic, can be carried out with safety at any time in the postoperative period and even in the majority of the more critically ill patients. If postrenal obstructive factors can be excluded as the cause of acute postoperative renal failure, diagnostic efforts must then be directed to a distinction between prerenal and renal factors as the initiating and underlying cause of the failure. A differential diagnosis between the two is not always easy or possible, but there are some clues which, when demonstrable, may be of distinct aid. The usual nephrotoxins causing acute renal insufficiency in the nonsurgical patient generally need not be considered as precipitating factors in postoperative failure. Therefore, since therapy for one may be quite inappropriate for the other, the principal aim of diagnostic study now is to determine whether the anuria is potentially reversible (prerenal failure) or whether it is potentially and at least immediately irreversible (renal failure, that is, acute tubular necrosis). The parenchymal damage of acute renal failure is not generally or necessarily an irreversible lesion, but once it is

established the lesion must heal by itself; in this situation vigorous attempts to stimulate renal function in the absence of any response may result in hypervolemia, pulmonary edema, electrolyte imbalance, and death. Some diagnostic information may or may not be gained from knowledge of the duration of the original insult, if recognized, and from a review of the clinical setting at the time of the insult. After the onset of renal failure, information concerning the character of the urine output and urine volume may be helpful in the differential diagnosis. Prerenal failure is commonly associated with a gradually tapering oliguria in which the daily volume output infrequently becomes less than 350 ml., whereas renal failure is more likely to be manifest by a rather sudden reduction in daily output to levels less than 350 ml. but with a subsequent gradual increase in daily volume output. Total anuria in both instances is rare unless there has been a more or less prolonged episode of profound shock. On the other hand, complete anuria is a common manifestation of obstruction, and it is likely also to occur in massive vascular accidents to the kidney, in cortical necrosis, and occasionally in acute glomerulonephritis. Large and irregular variations in daily output suggest variable degrees of obstruction. An infrequent but diagnostic history which is characteristic for obstructive uropathy is total anuria followed by twenty-four hours or more of polyuria and then a sudden return to anuria. Another extremely valuable clue in the differential diagnosis is afforded by determination of the urine specific gravity and by examination of the urinary sediment, the latter study usually being the more helpful of the two. The simplicity of measurement of specific gravity is appealing but does not offset other inadequacies which render it a somewhat less accurate index of concentrating ability than the preferred measurement of the osmolality of the urine. However, in ordinary clinical practice osmolality measurement may not be readily possible and in these circumstances determination of specific gravity will suffice. In prerenal failure in which the kidney is still capable of responding to dehydration by attempting to conserve water, the specific gravity is usually 1.020 or more whereas in renal failure with parenchymal damage (ATN) the specific gravity is generally less than 1.018. Unfortunately, because of the known limitation of concentrating capacity The American

Journal of Surgevy

Acute Renal Failure TABLE

II

DISTINCTIVE URINE FISDINGS IN ACUTE RENAL FAILURE

Urine [Jrine Crine Urine

specific gravity osmolality* (mOsm./L.) sodium (mEq./L.) sediment

* Unreliable,

especially

Renal

>1.018 350-500+ <15 Hyaline and fine granular casts

<1.018 300 > l&-20+ Renal tubular cells, tubular cell casts, and coarsely granular casts (red blood cells, red blood cell casts, and hemoglobin casts)

variable variable Tormal

1.015f to >

Sormal

in older patients.

that occurs in older patients [29], and since the urine obtained for examination in the individual patient may have been elaborated some hours before the accident, use of urine specific gravity or osmolality as a diagnostic guide is unreliable. The urine sediment, on the other hand, may give important information. In prerenal failure, the sediment may be normal but often will contain moderate numbers of hyaline and finely granular casts. In contrast, the sediment of acute tubular necrosis is characterized by the appearance of renal tubular cells, renal tubular cell casts, and coarsely granular casts. If intravascular hemolysis has occurred, red cells, red cell casts, and hemoglobin casts may be seen, and in acute glomerulitis similar findings are also typically present. The urinary sediment of obstructive failure may be normal or may contain white cells, red cells, and hyaline and finely granular casts. Perhaps the most significant test in differentiating prerenal failure from acute tubular necrosis is the determination of the sodium concentration in a “spot” specimen of urine [11,30]. Although a critical dividing point is dit’ticult to fix, it has been our experience that the urine sodium concentration in prerenal failure is generally less than 15 mEq./L. whereas in acute tubular necrosis it is usually above 15 to 20 mEq./L. If the tested urine specimen has been passed subsequent to the onset of oliguria, the result of this particular study is generally more reliable than are determinations of urine osmolality or specific gravity ; moreover, in conjunction with the sediment examination and the clinical setting it may be considered as a reasonably accurate criterion of the immediate state of functional capacity of the kidneys. Table II summarizes some of the distinctive urine findings associated with the three major categories of etiologic factors producing acute renal failure. Vol. 116, Sefitember 1968

Postrenal

Prerenal

IMMEDIATE

TREATMENT RENAL

OF ACI!TE

FAILURE

Once the diagnosis of acute renal failure is suspected or established, the immediate institution of daily or more frequent measurements of significant parameters of renal function and body homeostasis is essential to form guidelines not only for therapy but also for following the course of the disease. Accurate recordings of fluid intake and output, hourly if indicated, and interval determinations of body weight are of particular importance. In addition to the hematocrit and other usual blood chemistry studies (including serum proteins) that are routinely performed, the determination of blood pH and osmolality may be indicated occasionally. Continuous monitoring of central venous pressure by means of an ind\velling plastic cathseter is of great value as an index of effective circulating volume and to some extent of cardiac tone. The use of central venous pressure recording in the early phases of acute renal failure , although not routinely indicated, is advisable especially in the severely traumatized or critically ill patient, in the elderly or chronically debilitated patient, and in any other instances when control of circulating fluid volume is of paramount importance. The more exact technics of measurement of cardiac output and arterial pressure found in a few intensive care study units would be useful but are generally not readily available or of practical clinical use. The immediate goal of early treatment of acute renal failure irrespective of cause is the restoration of adequate renal perfusion and renal function and the prevention of the metabolic consequences of anuria. In contrast to the nonsurgical patient in whom a variety of uncontrollable initiating factors are encountered, acute renal failure in the postoperative patient is generally secondary in a broad sense

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to only one of two principal mechanisms of injury, that is, either postrenal obstruction or prerenal and renal circulatory insufficiency. Depending on the nature, severity, and duration of the initial insult as well as on the preoperative status of the kidneys, the latter mechanism may produce only transient and readily reversible impairment of renal function or it may lead to actual parenchymal damage (acute tubular necrosis) and the establishment of more prolonged failure of function which may persist for days or weeks and may even be permanent. The immediate threats to life in anuria are cardiovascular insufficiency and potassium intoxication. Today, both of these may hopefully be prevented or controlled by the prompt application of appropriate early treatment. Concomitant with maintenance or restoration of fluid balance and institution of measures to control excessive hyperkalemia and/or acidosis, plans for the treatment of postrenal urinary obstruction can generally be affected as soon as the diagnosis is established. The major objective of treatment is provision of free urinary drainage. When renal failure is secondary to bladder outlet or urethral disease, adequate drainage of the bladder can usually be accomplished by simple urethral catheterization. If a catheter cannot be passed, diversionary drainage via a perineal urethrostomy or suprapubic cystostomy is indicated. In instances of ureteral obstruction due to angulation, edema, or external compression by pelvic or retroperitoneal hematoma or other masses, successful cystoscopic passage of ureteral catheters above the site of obstruction, with subsequent inlying catheter drainage, will often tide the patient over the immediate crisis; after resolution of edema and hematoma later removal of the catheters may be followed by no further difficulties. Complete obstruction of the ureters due to ligature occlusion, on the other hand, must be recognized promptly to provide best results. Fortunately, this accident is usually manifest by total anuria which should be noted shortly after pelvic surgery. If the diagnosis is made within twenty-four to forty-eight hours after operation, and providing there are no other critical contraindications to repeated anesthesia, re-exploration and ureteral lysis should be performed. Delay in diagnosis and surgical intervention will only lead to increasingly se-

rious circulatory and metabolic alterations, often with complicating acute renal infection and with rapid deterioration of the patient’s condition to the point where direct surgical intervention for relief of obstruction might be unwise and even lethal. Under these circumstances and irrespective of the exact cause of ureteral obstruction such as ligature or calculus, simple nephrostomy with the patient under local anesthesia is the procedure of choice and may well be life-saving. Ureteral obstruction secondary to unexpected or previously unrecognized calculous disease is an occasional cause of acute postoperative renal failure. However, it is well to remember that anuria and renal failure in this instance will occur only if there is bilateral obstruction or, in the case of unilateral obstruction, if there is a solitary kidney with an absent or nonfunctioning mate. If the patient’s condition is grave or if the calculus is small and in such position that its eventual passage might be expected, cystoscopic passage of a ureteral catheter beyond the site of obstruction may be sufficient. On the other hand, if the calculus is of such size that subsequent descent seems unlikely, if a catheter cannot be passed above the stone for relief of obstruction, and if the patient’s condition is satisfactory, open surgical removal of the calculus is advisable. Acute postoperative renal failure secondary to intrarenal obstruction from deposition of sulfa or urate crystals in the collecting tubules and pelvis is uncommon. There is no effective treatment for widespread intrarenal obstruction. However, providing extensive tubular lesions have not already occurred, increased hydration, alkalinization of the urine, and, in occasional more severe cases, lavage of the renal pelves with warm sodium bicarbonate solution instilled through ureteral catheters may solve the problem. The second major category of patients with acute postoperative renal failure consists of those in whom acute depression of renal function is primarily due either to prerenal (reversible) circulatory insufficiency resulting from plasma volume deficiency or from circulatory collapse and shock, or to direct renal (irreversible) injury. In many of the latter group of patients, either with or without pre-existing congenital or acquired renal disease, ischemia secondary to general or local circulatory inadequacy frequently plays an important role in The American Jouvnal of Suwry

Acute Renal Failure initiating renal failure even though actual parenchymal damage may still be of relatively minor proportions. The distinction between simple functional or impending reversible renal failure and established irreversible renal failure (acute tubular necrosis) is often difficult or almost impossible to make. Important diagnostic features of the clinical and laboratory findings in each instance have been presented previously, and if definite differential diagnostic criteria are available, appropriate volume replacement therapy of primary circulatory insufficiency may be initiated with a reasonable expectancy of a favorable response, provided cardiac reserve is satisfactory and precautions are taken to avoid overloading vascular capacity. The hypotension precipitating renal failure after hemorrhage, fluid and electrolyte myocardial infarction, and septidepletion, cemia is well known, and principles of treatment, although often ineffective, are well recognized. In case of primary renal injury, however, when the extent of parenchymal damage and potential for functional recovery may be initially obscure, treatment of the early manifestations of the accident (hypotension and oliguria or anuria) by aggressive volume replacement may only serve to complicate the to injury.” From problem and add “insult a therapeutic viewpoint, it would seem evident in this situation that deficits in fluid and electrolyte balance should be specifically repaired. However, this must be carried out with caution and with full understanding that correction of the deficit itself may not entirely correct the deficit in renal function. The clinical status of the patient and accurate measurement of urine flow as well as of central venous pressure and arterial pressure should indicate when the deficit has been reasonably replaced and whether the renal defect is or is not immediately reversible. Lack of response to these initial measures of treatment necessitates that a plan of therapy be utilized which will permit appropriate restoration of circulating blood volume and at the same time provide information concerning the ability of the kidney to respond to more normal perfusion demands. A plan for initial fluid replacement therapy constructed and perhaps modified along the following lines would seem reasonable and, in our experience, has proved satisfactory and practical. Imtnediately on the discovery of Vol.

110.

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oliguria or other clinical evidence of hypovolemia such as hypotension, an intravenous needle is inserted and administration of 3 per cent glucose in normal saline or a balanced salt solution as indicated is started. If there is obvious evidence of blood loss or deficit, whole blood transfusion is added. The amount and rapidity with which fluid is infused will depend largely on an estimate of the existing volume deficit, the severity and duration of the initiating insult, and the patient’s vital signs. Constant monitoring of central venous pressure is probably the best immediat.e guide for control of the rate and quantity of infusion. If the patient is obtunded or critically ill, or if there is any question concerning the ability of the bladder to empty voluntarily and completely, an indwelling catheter in the bladder is necessary. Otherwise, catheterization tnay be avoided unless hourly or more frequent measurements of urine output are desired. Experience has shown that if parenchymal renal injury has not occurred and if circulatory insulhciency is remedied within approximately four hours, there will be a gratifying urine output and subsequent renal damage will be avoided. Unfortunately, the renal response to adequate volume replacement in prerenal and early renal failure is not always predictable, and in a number of cases no diuresis will result even with evidence of good perfusion in other organs. As has been noted, it is often difficult initially to differentiate between prerenal failure and established renal failure. Furthermore, if anatomic parenchymal damage is not severe, it seems likely that induction of an active diuresis may prevent further damage and actually reverse the course of otherwise progressive renal insufficiency. Mannitol has long been used under these circumstances as a diagnostic tool to assay the ability of the kidney to respond, but experience in recent years would suggest that it may also serve in some instances both as a preventive as well as a therapeutic agent. When used with full understanding of its physiologic action and recognition of the precautions to be observed in its use, administration of this osmotic diuretic may be extremely helpful and perhaps even life-saving. Under ordinary circumstances in the postoperative period, it has proved most effective when given simultaneous with or iumediately after the event that would otherwise lead to acute tubular necrosis, although

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on occasions it may be used later if there is an apparent response to it. Fluid replacement also should be instituted at the time of or before the mannitol infusion to avoid further hypovolemia and electrolyte loss if a diuretic response is evoked. Except under unusual circumstances a test dose of mannitol is given to every postoperative patient with prerenal and suspected renal failure. A dose of 12.5 or 25 gm. in a 50 or 100 cc. solution is given intravenously directly from a syringe over a three minute period or as a 25 gm. infusion in 150 to 200 cc. over a somewhat longer period of a half hour. After rapid syringe injection a positive response is usually evident within thirty minutes and is manifest by increase in urinary volume to approximately 100 ml. per hour during the next one to three hours. Such a response will occur unless the patient remains markedly hypotensive, if dehydration is severe, or if acute tubular damage is already existent. Although a urinary output of 100 ml. per hour is desirable, an increase in volume of no less than 30 to 40 ml. per hour may be obtained but will be adequate if sustained thereafter. If the test dose produces an adequate response, the mannitol infusion is continued as a 10 (rarely 20) per cent solution until fluid volume deficit is corrected, the patient is hemodynamically stable, and the urine output is maintained at a level of 60 to 100 ml. per hour. Other fluid and electrolyte solutions may be infused through the other arm of a standard U infusion set so that the rate of mannitol infusion may be altered as needed. Whenever urine formation falls below 1 ml. per minute the rate of mannitol administration is increased and when urine flow is again adequate the speed of administration is reduced. No more than 100 gm. of mannitol per twenty-four hour period should be given, and in most circumstances its use can be discontinued within this time. However, repetition of mannitol administration at low dosage within twentyfour to thirty-six hours may occur as seems indicated, particularly in patients who have undergone aortic surgery or who have had intravascular hemolysis after a transfusion. The use of mannitol requires careful monitoring by central venous pressure determinations and by continuous weighing. Its prolonged use is hazardous because of the tendency to provoke hypovolemia and urinary loss of electrolytes, particularly sodium and bicarbonate.

THERAPEUTIC THE

CONSIDERATIONS ANURIC

IN

PHASE

If there is no response to a test dose of mannitol, and if oliguria persists despite adequate restoration of blood volume and electrolytes, attempts to force diuresis by additional mannitol infusion are contraindicated. It can be assumed that the patient now has at least temporarily irreversible renal failure or acute tubular necrosis. Attention must then be turned to considerations of therapy associated with the management of continuous oliguria. It is not the intent of this discussion to review in detail the various phases of the care of the oliguric patient, but a few points concerning some general principles of management deserve emphasis. Treatment of the anuric phase of acute renal failure requires close liaison between the physician, surgeon, and nursing staff. Prevention of death during the acute oliguric phase depends largely on the prophylaxis and appropriate management of major complications such as circulatory collapse or overhydration, potassium intoxication, infection and acidosis, gastrointestinal hemorrhage, or respiratory failure. With optimal treatment, patients may be maintained for two to four weeks or longer with the prospect of complete recovery. In contrast to earlier years when deaths most commonly resulted either from excessive hydration and subsequent cardiovascular insufficiency with pulmonary edema or from potassium intoxication, death in acute renal failure today occurs principally from infection, gastrointestinal hemorrhage, or respiratory failure during the later phases of therapy. Experience has indicated that precautionary measures to prevent these complications are not only feasible but also may play a significant role in the reduction of the mortality of potentially reversible renal failure. Isolation technics, although not mandatory, are advisable. Sources of introduction of outside infection such as inlying urethral catheters, intestinal tubes, and long-indwelling venous cannulas can often be avoided by early ambulation, institution and maintenance of oral feedings as soon as tolerated, and improvement of pulmonary hygiene by mechanical aids. Since urinary sepsis usually secondary to the use of the catheter was formerly one of the most common causes of death in acute renal failure, it should be emphasized that intermittent or inlying catheter drainage The American Journal

of Surgery

Acute Renal Failure today should be avoided and is rarely necessary unless satisfactory voluntary micturition is impossible because of bladder outlet obstruction or inability of the bladder to respond adequately to normal voiding stimuli. The principal features of the therapeutic program for management of established renal failure are well recognized. They are directed primarily to maintenance of a restricted water balance, elimination of protein, sodium, and administration of basal potassium intake, caloric requirements, the control of electrolyte alterations and cardiovascular abnormalities, the treatment of anemia, and the prevention and treatment of infection. Fluid intake should be restricted to a volume equivalent to urine output plus extrarenal losses (diarrhea, vomitus, and drainage) plus an allowance of 400 to 500 ml. per day for insensible loss. Accurate recordings of intake and output as well as frequent weights are essential to gauge fluid needs. Rigid fluid restriction even in acute renal failure can lead to dehydration with serious consequences, but overhydration is still by far a more important problem. The diet given to patients with acute renal failure is designed to minimize protein breakdown from exogenous and endogenous sources. Exogenous protein intake is eliminated, and endogenous protein breakdown can be minimized by feeding an appropriate amount of carbohydrate. Caloric requirements are supplied by administration of at least 150 gm. of carbohydrate in the daily fluid intake. If oral feedings are tolerated, this can be supplied in the form of a palatable mixture of high carbohydrate content made from equal volumes of light Karo syrup and ginger ale, served chilled. When nausea or vomiting preclude oral feedings, a slow intravenous infusion of hypertonic glucose solution will serve the same purpose. By diminishing protein catabolism, an adequate carbohydrate intake thereby reduces the rate of development of azotemia, acidosis, and hyperkalemia. In the properly managed patient, the rate at which urea nitrogen rises should not exceed 15 to 20 mg. per 100 ml. per day whereas the daily rise in potassium should not exceed 0.3 to 0.5 mEq./L. Serum levels of potassium are not as accurate an index of potassium intoxication as the electrocardiographic findings, and monitoring in this fashion is important. In addition to dietary control, further suppression of protein catabolism may be achieved Vol. 116, SePlember

1968

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by the use of an anabolic agent such as tcstosterone or norethandrolone, either of which may be given by mouth or parenterally in doses of 30 to 50 mg. per day. Rapid rises in blood urea nitrogen or potassium in acute renal failure suggest an additional catabolic process such as damaged tissue or in fection. Prompt debridement of necrotic tissue and drainage of localized pus or hematoma should be performed early. Prevention of infection is equally important since this complication is now the most frequent cause of death in acute renal failure. The use of isolation technics, scrupulous care of surgical wounds and intravenous catheters, and special attention to prevention of pulmonary atelectasis and infection should be encouraged. The prophylactic use of antibiotics in the otherwise uncomplicated anuric phase is not indicated. If infection occurs, prompt treatment is indicated, drugs being chosen with due consideration of excretory route and nephrotoxicity as well as efficacy [31,32]. Chloramphenicol, chlortetracycline, and erythromycin can generally be given in the usual doses if indicated. Penicillin is likewise relatively safe, but do;age should be moderately reduced. Streptomycin, tetracycline, kanamycin, and polymyxin are particularly hazardous and should be used if indicated only in greatly reduced amounts. Nephrotoxic drugs such as kanamycin and polymyxin should be used only if no effective alternatives :are available. The cardiovascular abnormalities that occur in acute renal failure and that contribute appreciably to mortality consist primarily of congestive heart failure, hypertension, and arrhythmias. The first two conditions are commonly due to fluid overloading, may be prevented by careful salt and water restriction, and can be treated by hypertonic dialysis, or, in instances of acute pulmonary edema, by phlebotomy. Digitalis is not effective in the treatment of this type of congestive heart failure, and if the drug must be used for other indications it should be prescribed in reduced dosage [33]. Fortunately, the anuric patient does not often require this drug. However, when used, it is well to remember that it may cause arrhythmias and that digitalis intoxication is masked by hyperkalemia. Most arrhythmias occurring in the anuric patient are caused by electrolyte alterations, the most common of which is hyperkalemia.

Austen The oliguric phase of acute renal failure may be of only a few days’ duration or it may be prolonged for weeks. Cases with prolonged failure may be well controlled for a time by careful attention to the standard principles of management previously mentioned. However, if the course is prolonged, clinical and chemical deterioration are inevitable and the signs of uremia become apparent. Rapid deterioration may occur suddenly because of increased catabolism due to the effects of damaged tissue or infection, or it may occur with equal abruptness for no obvious reason. Because of the progressive increment in blood levels of the toxic products of protein catabolism, dialysis is usually required to reduce the blood concentration of these substances and to stabilize hemodynamic function. Even though the technics of dialysis, both hemodialysis and peritoneal dialysis, are now refined to the level where they can be performed with relative safety, there still exists some controversy concerning the exact point in the patient’s career when dialysis should be instituted. Although there are justifiable arguments for early dialysis as well as for delayed dialysis, it would appear that a middle-road approach to this problem answers some of the arguments on either side of the discussion and at the same time seems to be clinically effective in most cases. In essence, the preferable time for dialysis is just before it becomes necessary. If the anuric phase of acute renal failure is brief, dialysis is usually not necessary. Otherwise, it seems reasonable to institute dialysis at the earliest clinical signs of uremia or when the blood urea nitrogen reaches a level of 100 mg. per 100 ml., even though the clinical condition is still satisfactory. The occurrence of other circumstances, however, dictates the necessity of flexibility in these broad indications for dialysis. For example, dialysis may well be necessary before the blood urea nitrogen reaches 100 mg. per 100 ml. in cases in which sudden increased catabolism becomes evident or in those in which conservative measures are ineffective for control of hyperkalemia or excess fluid accumulation. Likewise, in patients with chronic malnutrition, earlier dialysis may be indicated to maintain nutrition by allowing the patient to feed and water himself rather than by restricting these elements. Finally, in instances in which the period of renal shutdown would appear to be a long one such as in

bilateral cortical necrosis, early dialysis is advisable. SUMMARY

A brief outline of the principal mechanisms initiating acute renal failure in the postoperative patient is presented, and the major causes of this accident are reviewed. Emphasis is placed on an accurate preoperative evaluation, particularly as it concerns the status of the urinary tract, and measures have been stressed to prevent the occurrence of renal failure after surgery. Methods of differential diagnosis and principles of initial therapy of this accident are discussed. Obviously, many perils threaten the surgical patient both before and during the course of acute renal failure. The mortality of acute renal failure from all causes varies from 40 to 50 per cent. The severity of the underlying disease together with associated complications is the major factor in prognosis, but a carefully planned therapeutic approach to the problem will profoundly influence the ultimate outcome. REFERENCES

1. BYWATERS, E. G. L. and BEALL, D. Crush injuries with impairment of renal function. Brit. M. J., 1: 427, 1941. 2. OLIVER, J., MCDOWELL, M., and TRACY, A. The pathogenesis of acute renal failure associated with traumatic and toxic injury. Renal ischemia, nephrotoxic damage and the ischemic episode. J. czin. Invest., 30: 1307, 1951. 3. OLIVER, J. Correlations of structure and function and mechanisms of recovery in acute tubular necrosis. Am. J. Med., 15: 535, 1953. 4. LUCKE, B. Lower nephron nephrosis. The renal lesions of the crush syndrome, of burns, transfusions, and other conditions affecting the lower segments of the nephrons. Mild. Surgeon, 99: 371, 1946. 5. SEVITT, S. Pathogenesis of traumatic uraemia. Lancet, 2: 135, 1959. 6. PRICE, J. D. E. and PALMER, R. A. A function and morphological follow-up study of acute renal failure. A&z. Int. Med., 105: 114, 1960. 7. SHALDON. S. and COOK, G. (Ed.) Acute Renal Failure. A Symposium.‘Philadelphia, 1964. F. A. Davis Co. 8. BREST, A. N. and MOYER, J. H. (Ed.) Renal Failure. A Symposium. Philadelphia, 1967. J. B. Lippincott Co. 9. PHILLIPS, R. A., DOLE, V. P., HAMILTON, P. B., EMERSON, K., JR., ARCHIBALD, R. M., and VAN DYKE, D. D. Affects of acute hemorrhagic and traumatic shock on renal function of dogs. Am. J. Physiol., 145: 314, 1945. 10. MERRILL, J. P. The Treatment of Renal Failure, 2nd ed. New York, 1967. Grune & Stratton, Inc. 11. LBVINSKY, N. G. Management of emergencies. v. Acute renal failure. New England J. Med., 274: 1016, 1966. The American

Jouvnal

of Surgery

:3ti1

Acute Renal Failure 12. SHIRES. 'I.,WILLIAMS, J., and BROWN, F. Acute changes in extracellular fluids associated with major surgical procedures. Ann. .%rg., 154: 803, 1961. 13. SHIRES, T. The role of sodium-containing solutions in the treatment of oligemic shock. S. C&z. North A me&n, 45: 365, 1965. 14. RUSH, B. F., FISHBEIN, R., and WILDER, R. J. Effect of operative trauma upon renal function in older patients. Ann. Surg., 162: 863, 1965. 15. BARRY, K. G., MAZZE, R. I., and SCHWARTZ, F. D. Prevention of surgical oliguria and renal hemodynamic suppression by sustained hydration. New Eneland J. Med.. 270: 1371. 1964. 16. SHUBIN, c. and WEIL, ‘M. H. The mechanism of shock following suicidal doses of barbiturates, narcotic and tranquilizer drugs, with observations on the effects of treatment. Am. J. Med., 38: 853, 1965. 17. MUELLER, C. B. The mechanism of acute renal failure after injury and transfusion reaction and its prevention by solute diuresis. S. Cl&. North 13merica, 45: 499, 1965. 18. BARRY, K. G. and MALLORY, J. P. Oliguric renal failure: evaluation and therapy by the intravenous infusion of mannitol. J.A.M.A., 179: 510, 1962. 19. PARRY, W. L., SCHAEFER, J. A., and MUELLER, C. B. Experimental studies of acute renal failure. I. The protective effect of mannitol. J. Ural., 89: 1, 1963. 20. BOBA, A., LANDMESSER,C. M., and POWERS, S. R.,

JR. Prophylactic aspects of post-traumatic and post-operative renal failure. New York J. Med., 63: 812, 1963. 21. POWERS, S. R., JR., BOBA, A., HASTRICK, W., and STEIN, A. Prevention of post-operative acute renal failure with mannitol in 100 cases. Surgery, 55: 15, 1964. 22. BARRY, K. G., COHEN, A., KNOCHEL, J. P., WHELAN, T. J., JR., BEISEL, W. R., VARGARS, C. A., and LEBLANC, P. C., JR. Mannito! infusion. II. The prevention of acute functional renal failure during resection of an aneurysm of the abdominal aorta. New England J. Med., 264: 967, 1961. 23. MUELLER, C. B. Mechanism and use of mannitol diuresis in major surgery and in trauma. South. I@. J., 59: 408, 1966. 24. SETTER, J. G., MAHER, J. F., and SCHREINER,G. E. Acute renal failure following cholecystography. J.A.M.A., 184: 102, 1963. 25. PERILLIE, P. E. and CONN, H. 0. Acute renal failure after intravenous pyelography in plasma cell mveloma. J.A.M.A.. 167: 2186. 1958. 26. PAPPER, S., BELSKY, j. L., and ‘BLEIFER, K. H. Renal failure in Laennec’s cirrhosis of the liver. I. Description of clinical and laboratory features. Ann. Int. Med., 51: 759, 1959. 27. BREST, A. N., BOWER, R., and HEIDER, C. Renal functional recovery following anuria secondary to renal artery embolism. J.A.M.A., 187: 540, 1964. 28. MORRIS, J. F., GINN, H. E., and THOMPSON, D. D. Unilateral renal vein thrombosis associated with the nephrotic syndrome. Am. J. Med., 34: 867,

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29. SPORS, I. S., LANCESTREMERE,R. G., and PAPPER. S. Differential diagnosis of oliguria in aged patients. New England J. Med., 267: 130, 1962. 30. MAHER, J. F., O’CONNELL, J. M. B., and SCHREINER, G. E. Traumatic acute renal failure. Postgrad. Med., 39: 70, 1966. 31. ATUE, H. O., MOSCA, A., and KUNIN, C. hf. The use of potentially toxic antibiotics in the treatment of gram negative infections in uremic patients. Ann. Int. Med., 60: 28, 1964. 32. KUNIN, C. M. A guide to use of antibiotics in patients with renal disease. A table of recommended doses and factors governing serum levels. Ann. Int. Med., 67: 151, 1967. 33. DOHERTY, J. E., PERKINS, W. H., and WILSON, M. C. Studies with tritiated digoxin in renal failure. Am. .1. Med., 37: 536, 1964.

DISCUSSION JOHN M. HOWARD (Philadelphia, Pa.): I should like to make three points in discussing Dr. Austen’s comprehensive review. The first is that on two occasions in the past two months, we have seen patients who, immediately after resection of a ruptured aneurysm or operation for a massively bleeding peptic ulcer, failed to excrete any urine for several hours after completion of operation. In these two instances, ethacrynic acid was given. The urinary output rose from essentially 0 to 40 to 50 ml. per hour and remained satisfactory. This observation may not stand the test of time but deserves evaluation at this point. The second point centers around the fact that during the Korean conflict we set up a center to which were flown by helicopters all the Cnited Nations casualties with acute post-traumatic renal insufficiency. In a blind study, one fine pathologist agreed to study histologically the kidneys of those casualties dying of acute renal failure as compared to the kidneys of persons dying immediately after massive craniocerebral or other injuries. His purpose was to describe the specific histologic changes of acute renal failure. After a few months he gave up because he could not distinguish histologically the kidney of those dying of acute renal failure from the kidney of those dying without acute renal failure. The third point is that acute renal failure is not an all or nothing phenomenon. A rise in the blood urea nitrogen level is a frequent postoperative occurrence, particularly in older patients. It occurs despite a normal output of urine. In young patients with severe injuries, the blood urea nitrogen has occasionally risen to a level over 100 mg. per cent in patients who did not excrete less than 1,000 ml. of urine per day. Dr. Michael Ladd demonstrated that many of these patients who had azotemia without oliguria had a marked reduction in the glomerular filtration rate, so that figuratively speaking they were excreting glomerular filtrate. Given careful attention, the mortality remained relatively low in the azotemic, nonoliguric patient.