Medical Science Publication No. 4, Volume 1
OLIGURIA*
MAJOR WILLIAM H. MERONEY,MC
I. General Consideration
Renal insufficiency has been described in association with numerouspathologic conditions which do not involve the kidneys primarily. Insultsto non-renal systems of the body may provoke compensatory responses whichprotect the organism as a whole but damage the kidneys secondarily. Theprime example of this phenomenon is shock, in which blood in shunted awayfrom organs whose functions are not immediately necessary for survival.By the time critical functions are restored, organs with low priority forblood, such as the kidneys, may have undergone ischemic changes of severedegree. Insults to non-renal systems may release to the plasma pigmentor other intracellular materials which are concentrated in the kidneysand produce obstruction or cellular degeneration. There are numerous otherways in which kidneys may be damaged, but these two are considered to beof greatest importance in war or traumatic disaster
Once renal damage has occurred, it may assume greater importance thanthe original condition as a factor in prognosis unless specialized treatmentis instituted. Comprehensive studies by the Board for the Study of theSeverely Wounded in World War II (1) revealed that the degree ofoliguria was correlated with the mortality rate. In a group of 186 severelywounded men with an overall mortality rate of 35 percent, those with aurinary output of 100 to 600 cc. per 24 hours had a mortality rate of 47percent, and those with a urinary output of less than 100 cc. per 24 hourshad a mortality rate of 91 percent. The researches conducted by these andmany other investigators provided a greater understanding of renal failurewhich allowed development of newer methods of treatment which lower themortality rate.
In the Korean war renal failure as a complication in the severely woundedwas comparable with that seen following shock in World War II. Pigmentnephropathies were not recognized as significant causes of renal failurein this study, a fact which is a tribute to the excellence of the bloodreplacement program and which probably also
*Presented 21 April1954, to the Course on Recent Advances in Medicine and Surgery, Army MedicalService Graduate School, Walter Reed Army Medical Center, Washington, D.C.
275
stems from the infrequent occurrence of crushing injuries. Members ofthe Surgical Research Team observed that oliguria occurred most frequentlyin the individuals who were most severely wounded and whose resuscitationwas most difficult. Of the first 10 such patients observed, 9 died of potassiumintoxication.
In April 1952, an artificial kidney was put into operation by the SurgicalResearch team at the Renal Insufficiency Center at Wonju, about 75 milesbehind the main line of resistance. This unit was attached to the 11thEvacuation Hospital and was operated as a joint effort of the Army MedicalService Graduate School in Washington, the 406th Medical General Laboratoryin the Far East Command, and the 8th Army Medical Service in Korea. Duringthe 16 months of its operation this unit received approximately 160 patientswho had, or initially were suspected of having, renal insufficiency. Thegreatest number of patients cared for at any one time was 11, and the averagenumber was about 4. However, the intensive care and study given these patientsrequired that three to five internists, one surgeon, four to six nurses,six to nine corpsmen, and two to four laboratory technicians work fulltime on this effort. In addition, all of the personnel of the hospital,particularly the anesthesiologist, pathologist, laboratory technicians,supply officer and utilities officer, contributed significantly to thiseffort. The operation of the unit centered around the artificial kidneyand the laboratory, but all of the personnel and facilities utilized inthe care of any seriously ill patients were even more concerned for thesepatients.
The immediate net result of this investment was a reduction in overallmortality rate from about 90 percent to about 55 percent. When the biochemicalabnormalities resulting from renal failure were controlled, the degreeof renal failure no longer paralleled the mortality rate. A less tangiblebut probably more important result of the control of renal failure wasthe dissociation of the effects of uremia from the effects of other clinicaldisorders. Upon the completion of 6 hours of treatment with the artificialkidney, a patient is momentarily relieved of uremic symptomatology, andthe remaining symptoms can be traced to their proper source.
If the source of such symptoms can be located and corrected, the symptomsresulting from uremia alone can then be assessed as they reappear in ensuingdays of oliguria. The importance of such maneuvers lies in the difficultyof assessing symptoms and assigning priority to therapeutic proceduresin a man with multiple abnormalities in addition to oliguria. If one isnot to be confounded by the complexities of such a patient, the clinicalpatterns to be expected from each disorder alone must be established. Itwas not uncommon
276
in Korea for a moribund patient to be rushed as an emergency to theRenal Center when, in fact, none of his symptoms were the result of uremia.The surgical care which may have represented the patient's only chancefor survival was not given by those best qualified and in the best situationto give it. Other patients whose threats to life were primarily of renalorigin could have been treated more satisfactorily if the information gainedat the Renal Center had then been available in the forward area. It isthe purpose of this report to outline the concepts and methods employedat the Renal Center which appear to have the greatest practical application,with specific reference to 48 renal and 11 non-renal patients observedby the author. The system presented is subject to revision, as analysesnow pending are completed, as further information becomes available fromother workers, and as any divergent opinions are resolved. A more detailedaccount of individual cases and raw data is recorded elsewhere (2).
II. Recognition and Transfer
The diagnosis of renal insufficiency should be suspected if the urineoutput falls below 500 cc. per 24 hours, about 20 cc. per hour. The patientand his records should then be re-examined with the following possibilitiesin mind:
1. Reflex oliguria. This term is used to designate the transientoliguria which occurs following surgery or other trauma. The conditionmay not be reflex in origin, but it appears to be a normal response tothis type of stress and lasts only a few hours.
2. Hypotension. The blood pressure in the renal artery is anessential component of renal filtration pressure. When hypotension is observedin the arm, renal filtration can be expected to be diminished. The resultingoliguria causes an increase in plasma NPN which can be misleading, becausea patient with persistent hypotension may have central nervous system signswhich resemble those of uremia at a later stage. It is important to distinguishthe conditions because the treatment is quite different. The most practicalapproach to the differential diagnosis is to defer a diagnosis of renalfailure until normal blood pressure is restored. The condition which producedthe hypotension should receive first attention, because it likely willkill or be cured before renal failure, if it be present, requires any treatment.
3. Dehydration. A severe degree of dehydration is required toproduce oliguria of 20 cc. per hour, and either history or physical examinationshould confirm this unusual diagnosis. If any question remains, the highspecific gravity of urine excreted by normal kidneys during dehydrationshould settle the point, because the urine of acute post-traumatic renalfailure characteristically has a low specific grav-
277
ity. The practice of administering a fluid load as a test for dehydrationis dangerous and should not be necessary.
4. Obstruction. In the post-traumatic state urinary tract obstructionis suspected when there is flank pain with genital radiation, when thescanty urine contains crystals of drugs or heme casts, or when there istotal anuria. Even the most severe cases of renal insufficiency usuallyare painless and the patients excrete 30 to 40 cc. of urine per day. Ifthere is no urine whatever, first attention should be given the urethralcatheter, for obstruction by mucus is not uncommon. Daily irrigation ofthe catheter with a bland fluid which is measured when instilled and recoveredshould prevent this complication. If obstruction is still suspected, cystoscopyand catheterization of the ureters are indicated.
5. Acute tubular nephrosis. If a patient with the usual stateof hydration excretes less than 20 cc. of urine per hour after 5 to 10hours of normal blood pressure, and there is no evidence of obstruction,the diagnosis of acute renal failure is justified. Pathologically, thislesion was first described as epithelial necrosis in the lower segmentof the tubule, but subsequent studies indicate that the necrosis occursthroughout the length of the tubule (3). Functionally, there isserious impairment of the capacity of the kidneys to excrete or conserveselectively the substances in excess or in scarce supply. During the acutestage the problem is excretory. All of the plasma substances which normallyappear in the urine accumulate in the plasma, where some of them are toxic.The renal lesion is potentially reversible, and if the patient can be maintainedfor the few days or few weeks required for regeneration of the tubularepithelium, spontaneous diuresis will occur. During the diuretic phase,the problem is lack of conservation. Scarce and essential substances arewashed out in the copious urine flow, and serious chemical deficits canoccur.
Once the diagnosis of renal failure has been made, it is essential thatthe symptomatology be re-appraised to establish which components are uremicin origin. When one is faced with a deteriorating clinical status in apatient with serious wounds and oliguria, there is a strong tendency toblame uremia for all of the symptoms and to neglect other disorders. Withtwo exceptions, the symptoms of uremia do not appear, in our experience,until the fifth to eighth day of anuria when the NPN is 250 to 300 mg.per 100 cc. The first exception is overhydration, which is not really asymptom of the patient's disease but of the doctor's error. The secondexception is severe potassium intoxication, which only occurs as a sequelof incomplete care of other features of the patient's condition. If neitheroverhydration nor potassium intoxication is present, anuria must persistfor many days before it provokes symptoms.
278
It follows that other pathologic processes should be sought in a patientwho is symptomatic during the first few days of anuria. Symptoms whichresemble those of uremia are observed in patients with wound infection,generalized sepsis, or shock, but the offending agents cannot be dialyzedfrom the patient's plasma. There is no gain but potentially total lossin transferring such a patient to a renal center. If the basic conditioncannot be corrected, there is even less chance of success after the delayand trauma of evacuation. If such a patient is to survive, resuscitationand débridement must be completed before transfer, and he must beable to maintain a blood pressure of more than 100 mm. Hg. throughout thejourney without stimulants or infusions. Once these conditions are fulfilled,the oliguric patient can be transferred for definitive care of uremia withgood prospects for success.
III. Management
The methods for management of acute renal failure and allied conditionswhich were developed from the Korean experience have general applicationand are reviewed below. The problems in management are considered in orderrequiring first action by the physician.
A. Immediate Problems.
1. Fluid balance. First and continuing consideration should begiven to the prevention of overhydration. The evils of water intoxicationare well known, yet this preventable complication is quite common. Thetotal fluid intake per 24 hours should be in the range of 500 to 600 cc.plus the measured output, increasing to about 700 to 800 cc. plus the measuredoutput if the weather is hot or the patient is feverish. The measured outputusually is the total of urine and gastric suction, although diarrhea, notpresent in our cases, might increase the output significantly. This averageintake allowed a daily weight loss one-half to one pound without producingclinical evidence of edema or dehydration.
The best route for administration of the fluids is oral if the patientis able to tolerate them. In our patients, however, oral fluids, even whengiven by duodenal tube, provoked vomiting. This complication compoundedthe problems of fluid and electrolyte balance, as well as adding the riskof aspiration pneumonia, and so the intravenous route was used almost exclusively.Restriction of oral fluids can be quite difficult. These patients oftensuffer it cruel thirst, yet their thirst is not an accurate gauge of theirneeds. If allowed to drink all they desire, they will literally drown themselves.When denied fluids they develop great craftiness in pervailing upon compassionateneighbors and attendants for small sips of any fluid or for pieces of ice,which is
279
bountiful and easily-overlooked source of water. When unobserved theywill quaff heartily from flower vases, emesis basins, or urinals with greatstealth and cunning. It is the physician's responsibility to prescribethe proper amount of water and to insure that no violation of his orderoccurs. Careful oral hygiene and unlimited chewing gum together with anexplanation for the reasons which compel the apparent cruelty, are usuallyadequate to control thirst. The amount of water prescribed must containall the solids to be administered during the 24 hours, and these will bediscussed later.
2. Potassium intoxication. The only chemical abnormality whichis likely to kill a patient in the first week of uremia is potassium intoxication.Normally potassium exists in high concentration inside cells but does notexceed 5.5 mEq./liter in the plasma. Normal daily catabolism of cells providesthe plasma with a small quantity of potassium which is readily excreted.This amount of potassium can be handled by an anuric patient for many days,even several weeks, without accumulation of significant quantities in theplasma (4). However, the basic condition which originally producedthe renal insufficiency often is characterized by excessive loss of potassiumfrom cells. This was especially evident in our patients, many of whom hadsuffered extensive tissue damage from trauma or infection, and the plasmapotassium rose to high levels as early as the second day of oliguria. Devitalizedtissue, whether permanently destroyed or temporarily embarrassed by trauma,infection, chemical or physical agents, or hypoxia, gives up potassiumto the plasma (5). In the plasma, not in the tissues, potassiumis exceedingly toxic, and the first and most important evidence of toxicityis cardiac.
The toxic effect of potassium on the heart is recorded on the electrocardiogramlong before any other signs or symptoms appear. The degree of electrocardiographicabnormality produced by a given excess of plasma potassium will vary widely,however, depending upon the activity of other factors. Under experimentalconditions, such as the infusion of potassium into the plasma of normaldogs, it has been shown that the electrocardiographic effects of progressiveincrements of plasma potassium are quite consistent (6). In clinicalsituations, however, the electrocardiogram has not previously been shownto be a reliable gauge of the plasma potassium level (7). The electrocardiogramrecords function of the heart, and the function with respect to potassiumis the result not only of the absolute level of plasma potassium, but also,of factors which influence the effects of potassium. The electrocardiogramis, in fact, an accurate gauge of the plasma level of potassium in man,when there is no abnormality except hyperpotassemia (8). The discrepancieslie in the rarity with which pure hyperpotassemia occurs. In the oliguricpatient, all of the
280
plasma substances which normally are excreted in the urine, of whichpotassium receives first attention, are retained within the body, and someof these substances affect the behavior of potassium.
The retention of inorganic phosphate, though not of itself harmful,regularly produces a fall in the level of plasma calcium during oliguria.Figure 1, which is a graph of random pairs of phosphate and calcium determinationsin oliguric patients, demonstrates the consistency with which a given excessof plasma phosphate produces a predictable deficit of plasma calcium. Adeficit of plasma calcium is of cardinal importance during oliguria, becausecalcium is a specific antagonist of potassium, and hyperpotassemia andhypocalcemia occur at the same time.
As plasma potassium rises, the degree of toxicity recorded by the electrocardiogramis consistent with the plasma level only if plasma calcium is maintained.Otherwise, the electrocardiographic abnormality and the threat to the patient'slife are much more serious. Since, in oliguria, plasma calcium regularlyis depressed by a rise in plasma phosphate at the same time that plasmapotassium rises, the electrocardiogram of the untreated patient bears littlerelationship to the plasma level of potassium. Replacement of the calciumdeficit produces a striking improvement of the electrocardiogram, whichthen is reverted to that degree of abnormality characteristic of the
281
plasma potassium level. Figures 2 and 3 demonstrate the effect of intravenousinfusion of calcium in uremic patients with far-advanced potassium intoxication.
The improvement following a single intravenous injection of calciumis very transient. The plasma concentration of calcium falls quickly fromthe high level immediately after injection to the pre-injection level asgoverned by the phosphate concentration. Raising plasma calcium does notaffect the level of plasma phosphate. Phosphate, unlike calcium, cannotbe driven into the body repositories by such a maneuver. Intravenous glucoseinfusions will cause a slight reduction in plasma phosphate, but not enoughto allow a rise in plasma calcium sufficient to antagonize potassium. Shortof hemodialysis, the only effective way to maintain a normal level of calciumin plasma which is high in phosphate is by continuous intravenous infusionof calcium.
282
The effect of calcium upon potassium toxicity is purely one of antagonism.The measurable level of potassium, as well as phosphate, is unaffectedby raising plasma calcium. Once the calcium deficit is replaced, the electrocardiogramreflects the plasma level of potassium rather accurately, although stillother factors, less apparent in our patients, have been shown to be influential(5, 7, 9).
Digitalis, which was rarely indicated in our patients, antagonizes potassium(4, 10) in a manner similar to calcium. Digitalis and calcium appearto be additive in this respect, and great care should be used if both agentsare administered to the same patient. There is particular danger if theexcess potassium is suddenly removed by hemodialysis (5, 11), allowingdigitalis, enhanced by a high calcium concentration, to exert its toxicitywithout the opposing action of potassium.
Figure 4 demonstrates the electrocardiographic effects of relativelypure potassium excess in man. These tracings were selected from more thanfour hundred examples as most representative of the potassium level indicatedwhen other known causes for abnormality were not present.
283
Small excesses of potassium produce no abnormality except elevationand peaking of the T waves, best seen in the precordial leads. As plasmapotassium increases further, the T wave abnormalities progress in the precordialleads and become obvious in the limb leads, but they have no quantitativesignificance in severe hyperpotassemia. Progressive changes in the QRScomplex, best seen in the limb leads, are much more ominous. In the limbleads the angle between the S wave and the ST segment widens and encroachesupon the horizontal component of the ST segment until it is obliterated.P waves disappear; the T waves diminish in height and become rounded atthe top; and finally, the R-S angle increases, and the smooth biphasiccurves resemble a sine wave.
When the mild intoxication indicated by T wave abnormality only, suddenlyprogresses to the severe intoxication indicated by QRS widening, it usuallyis the result of a fall in plasma calcium. Infusion of calcium should causeinstant reversion of the tracing to its former
284
degree of abnormality. If calcium does not produce an immediate effect,this indicates that the plasma potassium level has increased. Sudden risesin plasma potassium occur during oliguria when tissue cells are subjectedto stress. Hemolysis, infection, or trauma may allow the release of allthe potassium contained in the affected cells. Smaller amounts of potassiummay leave cells temporarily in hypoxic states, only to be recovered bythe cells when normalcy is restored. Hypoxia from hypotension, convulsions,certain types of anesthesia, pulmonary edema and simple breath-holdinghave been observed to cause such a reversible shift of potassium (5).In our experience, a rapid increase in the electrocardiographic evidenceof potassium intoxication which was not responsive to calcium invariablywas associated with a rapid increase of plasma potassium together withone of the above conditions.
Progressive potassium intoxication was asymptomatic in our patientsuntil it had reached the stage at which the electrocardiogram showed severedeterioration similar to that of the fourth tracing in figure 4. Patientswho had symptoms with a less abnormal electrocardiogram were found to haveother causes for their symptoms. Many of the disorders associated withhyperpotasemia, such as those noted above, produce severe symptoms. Correctionof the basic condition relieved the symptoms in our patients, althoughthere were many instances in which the plasma potassium was still greaterthan 8 mEq./L. and the electrocardiogram was appropriately abnormal. PatientD. K. had neither signs nor symptoms at the time of the tracings shownin figure 2. If one attempts to follow the course of the intoxication inthis type of patient by changes in tendon reflexes, respiratory symptoms,or by any known means except electrocardiography or blood chemistry, thepatient likely will be dead before corrective action can be taken.
Another ion which affects the behavior of potassium and should be employedin the practical management of potassium intoxication is sodium. Sodiumand potassium are inversely related in the plasma of the oliguric patient.Raising the plasma sodium concentration causes a fall in plasma potassiumconcentration, and the electrocardiographic effects of potassium intoxicationare modified. Figure 5 demonstrates the beneficial effect of infusionsof sodium bicarbonate upon the plasma potassium concentration and the electrocardiogram.Figure 6 is a similar demonstration of the effects of sodium chloride.Potassium concentration is depressed as sodium concentration rises, independentlyof the other ions, indicating that the agent responsible for the changeis sodium and not the anion. An alkaline salt of sodium is preferred, however,because the retention of organic acids
285
regularly produces acidosis in these patients. The changes in the concentrationof potassium and the other substances are not explained by dilution. Althoughtissue analyses were not performed, it is presumed that raising the plasmasodium concentration forces potassium back into cells.
The improvement in the electrocardiogram which followed a rise in plasmasodium and a fall in plasma potassium was sometimes greater than wouldbe expected from the lower level of potassium. This suggests that sodium,in addition to depressing the plasma concentration of potassium, may alsohave some antagonistic effect similar to calcium. Figure 7 demonstratesthe beneficial effect of raising plasma calcium from 5.9 to 7.8 mg. per100 cc. and further improvement from additional calcium, followed by stillfurther improvement from sodium chloride. The last tracing in this figureis almost normal, although the potassium concentration still is 7.2 mEq./liter.Obvi-
286
ously, all of the factors influencing the response of the electrocardiogramto be given potassium concentration have not been considered. Hypertonicsodium infusions do, however, provide an effective and practical meansfor modifying potassium intoxication. Again it is emphasized that all ofthe patients in this series were young men without known previous cardiovasculardisease, a fact which undoubtedly influenced their responses and shouldbe considered if these methods are applied to dissimilar patients.
Another means for reducing plasma potassium concentration is the infusionof hypertonic glucose (5, 9,12). The metabolism of glucose, whichcan be hastened with exogenous insulin, removes potassium and phosphatefrom the plasma. While calcium antagonizes the effects of potassium withoutchanging the quantity present in the plasma, and sodium lowers plasma potassiumconcentration by some physicochemical means, glucose carries potassiuminto cells by a more active process. As glycogen is formed, potassium,as well as phosphate, is incorporated into the carbohydrate complex, andthis is an effective, though slower, method of controlling potassium intoxication.Re-
287
sults similar to those of a glucose-insulin combination could be expectedfrom the use of fructose, which has the advantage of not requiring insulinfor its early metabolism, but this compound was not used.
If glucose is to be used effectively by the intravenous route, it shouldbe given continuously. Intravenous glucose by intermittent injection causesa sharp spike in blood sugar level followed by hypoglycemia. The hypoglycemicperiod has the double disadvantage of failing to remove potassium duringthat period and of provoking glycolysis with further release of potassiumto the plasma. Also, if nutrition is limited to intermittent intravenousfeedings of glucose, the period between infusions is one of relative starvation,which is characterized by cell destruction and release of potassium.
Prescription
Based upon the above observations a standard solution was devised andfound to be effective in controlling potassium intoxication for many days.
288
| cc. |
Sodium bicarbonate 71/2 | 50 |
Glucose 25 percent in H2O (containing 50 u. regular insulin) | 400 |
Normal saline (or 1/6 M sodium lactate) | Volume of output. |
Give intravenously, preferably through a catheter, in a large vein ata constant rate of 25 cc. per hour.
Water-soluble vitamins should be added to this basic solution (13).Our patients received daily 2 gm. ascorbic acid, 50 mg. thiamine chloride,and 20 mg. vitamin K, but this vitamin prescription was chosen more inthe interests of a concurrent study of wound healing and is not necessarilyoptimal.
If the laboratory can provide frequent determinations of plasma sodium,the sodium content of the fluid should be varied to maintain a plama levelof approximately 140 mEq./L. If not, the amount suggested can be givenempirically without fear. The only complication arising from over-shootingthe desired concentration is aggravation of thirst. This is uncomfortablefor the patient, and if he is allowed excess water he may provoke pulmonaryedema. None of the dire effects attributed to sodium administration (14)were observed in these patients, and it would appear that is is not thesodium alone but the excess water which may accompany it which is dangerous.In patients who are older or who have cardiovascular disease, there maybe additional hazards associated with a high plasma sodium level. It isunlikely, however, that the dosage recommended would have adverse effects.A more likely source of harm is overhydration, and the necessity for waterrestriction must be kept constantly in mind.
If the laboratory can provide frequent determinations of plasma potassium,and it is not elevated, the calcium content of the fluid should be unnecessary.The purpose of the calcium in the infusion is to antagonize an elevatedplasma potassium. If the potassium is not elevated, it follows that additionalcalcium is not needed for this purpose. The only other reason for givingcalcium would be to prevent tetany if plasma calcium were depressed. However,in this type of patient plasma calcium is not depressed unless potassiumis elevated, because the factor which causes hypocalcemia is an elevationof plasma phosphate, and phosphate rises at the same time as potassium.Therefore, calcium should be added to the infusion only if plasma potassiumis elevated. If the laboratory is unable to provide frequent determinationsof potassium, the electrocardiographic changes noted are sufficiently specificto guide logical therapy.
The constituent chemicals of the basic solution should be tailored forthe individual patient when possible. If an item is omitted, its volumeshould be replaced by a normal solution or distilled water.
289
Ion Exchange Resins
Ion exchange resins are effective agents for the withdrawal of potassiumfrom the plasma into the gut under certain circumstances (15). Inthis series of patients, however, those whose potassium was highest wereunable to take anything by mouth. Rectal installation of resins was attemptedrepeatedly, but such intractable concretions were formed that the amountof water necessary to remove them caused water absorption and overhydration.An attempt was made to contain resins in a silk tube which could be insertedand extracted from the rectum mechanically, but the procedure was verypainful for the patient. Also, effective exchange occurred only at thesurface of the resin bolus, even when a silk tube of only 5 mm. diameterwas used, and only 7 mEq. of potassium was extracted by 30 grams of resinleft in the rectum for 24 hours. It was intended to utilize a colostomyfor this method but a suitable patient was not found. The impression wasgained that resins would not be more effective than intravenous therapyas discussed.
Artificial kidney dialysis is the most definitive treatment known forremoving potassium. Dialysis for hyperpotassemia alone is, in our experience,rarely indicated. Recommendations pertinent to this point are offered insection B, 2: Clinical Uremia. The author has had no experience with othermethods for dialysis.
B. Less Urgent Problems
1. Nutrition. Principally fat and carbohydrate are recommendedduring the oliguric phase of acute uremia because of the potential toxicityof protein (4, 16). Maximal caloric intake is desirable to preventthe patient from burning his own tissues to supply his caloric needs, butthe exact quantity of fat or carbohydrate necessary is unknown. Varioushigh-calorie mixtures, such as olive oil and glucose, frozen butter balls,and commercial fat emulsion preparations, were given by mouth and by gastricand duodenal tube. Unfortunately, the patients who needed it most werenauseated by any of the forms of enteral feeding. Intravenous fat was notused in these patients because a satisfactory preparation was not available(17). Caloric intake, in the main, was limited to intravenous glucose,which was administered as outlined in the previous section. This is farfrom ideal but will sustain the patient. Current studies with newer antiemeticdrugs offer hope for successful oral or tube feeding.
2. Clinical Uremia. After a number of days of oliguria, in thisseries 5 to 8 days, the patient develops the syndrome of clinical uremia.He gradually becomes lethargic and shows evidence of mental torpor, yethis extremities are tremulous and hyperreflexic. The nausea,
290
which may have been present for days, now becomes active vomiting andretching. Intractable hiccups are usual. These clinical manifestationsfirst appeared in our patients when plasma NPN was about 250 mg. per 100cc. The consistency with which this figure was associated with the clinicalfindings was remarkable, and it came to be useful in allowing one to predictfrom an NPN value of, say, 200 mg. per 100 cc., that the patient wouldbe symptomatic the following day.
At this juncture artificial kidney dialysis is strongly indicated. Sixhours of dialysis will produce dramatic relief of symptoms as well as restorationof electrolyte balance. It does nothing for renal function, of course,but it clears the plasma of those substances which normally would havebeen excreted in the urine. The patient is then ready to start anew onhis course of uremia, and if he does not diurese within several days, dialysisshould be repeated and repeated again each time he becomes symptomaticuntil renal function is recovered. Dialysis was performed one or more timesin 27 of our 48 patients. Fourteen were dialyzed once, 6 were dialyzedtwice, and 7 were dialyzed 3 times.
It is important to recognize the syndrome of clinical uremia and toknow when to expect it, because similar signs and symptoms can be producedby hypotension or sepsis. In our patients with renal insufficiency theNPN rose gradually to the critical level of 250 mg. per 100 cc. over aperiod of about a week. No patient attained this level or had symptomsof uremia before the fifth day of oliguria, and the average was later.When symptoms appeared, dialysis usually was performed and the symptomsdisappeared. If dialysis was not performed, the symptoms progressed gradually,and 2 or 3 days elapsed before such threatening clinical manifestationsas coma, convulsions and pericarditis appeared. In prerenal azotemia secondaryto shock or sepsis, symptoms appeared at any time, usually within 1 or2 days, and the symptoms were totally unrelated to the NPN level. The onsetoften was abrupt and the progression rapid. Dialysis was quite successfulin restoring chemical balance but produced no beneficial effect upon theclinical manifestations. The rate at which plasma potassium and phosphaterose following dialysis also was quite different in these patients. Withina day, or even a few hours, of a normal post-dialysis level, great incrementof potassium and phosphate were again found in the plasma. The conditionwhich produced the symptoms was still present and it was associated withdevitalization of tissue, which gave up its intracellular materials tothe plasma. Dialysis, therefore, was virtually useless and the time lostin this procedure should have been spent in treating the basic conditionof the patient.
The measures outlined for the treatment of potassium intoxication wereeffective, in our patients without necrotic tissue, for the period
291
prior to the appearance of clinical uremia. In some cases, dialysiswas avoided altogether because diuresis occurred before clinical uremiaappeared, and in others fewer dialyses were necessary. In the presenceof clinical uremia, no attempt was made to control potassium further bymedical means, because the dialysis which was otherwise indicated was superblyeffective in removing potassium.
In an area where an artificial kidney is not available, the medicalmanagement of potassium intoxication may save the patient's life for themoment but should be used with a view to providing time for transport toa renal center. Where an artificial kidney is available, this method willallow dialyses to be performed on a reasonable schedule for clinical uremiaonly and should eliminate the emergency dialyses for potassium intoxication.
3. Anemia and Hemorrhage. Of the various causes for anemia andhemorrhage in post-traumatic renal insufficiency, the only one studiedin this series of patients was the severe purpura similar to that seenin chronic uremia. Bleeding into the skin, nasopharynx and bowel appearedafter 12 to 15 days and was related only to the duration, not the severity,of the uremia. Unlike the other manifestations of uremia, the hemorrhagictendency was entirely unaffected by artificial kidney dialysis or by diuresis.To the contrary, the most severe bleeding in our series occurred severaldays after the onset of diuresis. The only positive temporal relationshipwas the cessation of bleeding with the resumption of normal diet. However,the absence of hemorrhagic diathesis during pure starvation discouragesspeculation on this point.
A search for the cause of the bleeding revealed no intrinsic clottingdefect, only capillary fragility. The condition was unrelated to abnormalityof plasma electrolytes and was unaffected by vitamins C or K or fresh bloodtransfusions. The replacement of the blood lost was considered desirable,yet transfusions were feared because a minor reaction might have exaggeratedsignificance in a patient so ill. Nevertheless, small transfusions, 200to300 cc. daily, were given regularly without apparent harmful effect.
The presence of bleeding from whatever cause was originally considereda contraindication to artificial kidney dialysis, because of the necessityfor heparinization before and during the procedure. On several occasions,however, dialysis was performed as a life-saving procedure on patientswho were bleeding. During the procedure large quantities of blood wereavailable for immediate use if bleeding should be aggravated, and followingthe neutralization of heparin with protamine at the end of the procedure,packed erythrocytes were given. No alarming bleeding occurred, and so itbecame the practice to dialyze any patient who had an indication regardlessof hemor-
292
rhagic tendencies. The risk of dialysis in the presence of hemorrhagewas considered to be less than the risk of the complications of uremiaif dialysis were withheld, and subsequent experience supported this view.
4. Infection and Antibiotics. The specific infections encounteredin these battle wounds (18) will not be reviewed here. In general,their successful management was dependent mainly upon thorough and frequentdébridement. The amount of devitalized tissue and infection whichmay be acceptable in a patient with normal renal function may be lethalin the oliguric patient. Small amounts of tissue, particularly muscle,contain sufficient potassium to kill if it is released into plasma whichis not being cleared by the kidney. Removal of such tissue must be promptand thorough, and the approach must be much more radical than is customarywith good surgeons. If the point at which devitalized tissue merges withnormal tissue is not apparent to the surgeon, he should débridefurther. Excessive débridement may cost the patient precious tissue,but inadequate débridement may cost his life.
Remnants of devitalized tissue usually can be suspected if the plasmapotassium and phosphate are inordinately high with respect to NPN. Whenthe measures for controlling potassium outlined in Section A, 2 are employed,potassium does not rise as rapidly as it would if untreated. Plasma phosphate,however, is little affected by such measures and it is a useful index ofthe presence of necrosis. A plasma P/NPN ratio in excess of 0.06 indicatedsevere muscle destruction in our patients, and on several occasions deepnocrosis underlying a wound with a clean surface was first suspected fromthis relationship (19).
In devitalized tissue antibiotics cannot be relied upon to control infection.Also, the proper methods for administration of antibiotics have not beenclarified. The principal route for excretion of antibiotics is the urine,and during oliguria tremendous concentrations accumulate in the blood ifusual doses are given. The importance of this fact was not investigatedin our patients, but recent reports of serious toxicity from certain antibioticsrequire that great caution be employed (20).
The systemic infection most often seen in this type of patient is pneumonia.This complication is particularly apt to occur if the syndrome of clinicaluremia is present and is not interrupted by hemodialysis. The hazard ofpneumonia was combatted in our patients by deep-breathing exercises, voluntarycoughing, frequent turning and good general nursing care. Patients whosecooperation was doubtful because of associated wounds or illnesses wereplaced up on Stryker frames where turning and drainage could be assured.
293
The diagnosis of oliguria automatically puts a patient into a groupwith a poor prognosis, although the renal lesion itself is usually reversible.The onset of infection may well be enough additional insult to cause adeath which would not otherwise have occurred. The seriousness and thepotential reversibility of the illness demand that no effort be sparedin preventing or treating the complication of infection.
5. Salt Wasting during Diuresis. The onset of diuresis was arbitrarilydefined in our patients as the day on which urine volume exceeded 1 liter.Once this volume was reached, the output increased rapidly, often 100 percentor more on successive days until a peak volume of 3 to 6 liters was attained.As the urine volume increased, the urinary concentration of nonproteinnitrogen, sodium, potassium and phosphate changed very little, and thetotal output of salts reached high values within 1 or 2 days. At this stagethe kidneys excrete salts wantonly, without regard for the body's needs.Fortunately, appetite and food tolerance have now returned and salt depletionis partially offset by food intake. Daily supplements of sodium and potassium,however, must be added to prevent serious depletion. Sodium chloride 4to 6 gm. and potassium chloride 1 to 2 gm. added to a regular diet dailyfor about a week were found to be adequate. Fluids were administered adlib., without noticeable aberrations of fluid balance.
IV. Summary
Recommendations based upon experience with 48 patients with acute post-traumaticrenal insufficiency and 11 patients with mimicking conditions have beenpresented.
The diagnosis of renal insufficiency is justified when a patient withouthypotension, dehydration or urinary tract obstruction excretes less than500 cc. of urine per 24 hours. Symptoms which appear within the first 2days are not the result of uremia but commonly arise from incomplete resuscitation,incomplete débridement, or sepsis. If the surgical problems arecontrolled, haste in transfer to a renal center is unnecessary.
Management of renal failure consists of restriction of total fluid intaketo 500 to 800 cc. plus the obvious output per 24 hours; emergency controlof potassium intoxication by intravenous infusions of calcium salts; continuedcontrol of hyperpotassemia by maintenance of a normal level of plasma sodiumand the continuous infusion of hypertonic glucose with insulin; maintenanceof maximal caloric intake with protein-free, potassium-free foods or carbohydrateinfusions (within the limits of the fluid balance); control of clinicaluremia by hemodialysis; maintenance of the hematocrit at 30 percent ormore;
294
control of infection by good nursing care, frequent dressing changes,radical débridement and judicious use of antibiotics; and preventionof salt deficits during diuresis by administration of sodium and potassium.
Application of this system of management should prevent deaths fromrenal failure and provide surgeons with patients better able to withstanddefinitive treatment of the primary disorders.
References
1. The Board for the Study of the Severely Wounded: ThePhysiologic Effects of Wounds. U. S. Govt. Printing Office, Washington,D. C., 1952.
2. Meroney, W. H.: Activities Report of the Renal InsufficiencyCenter, Feb. to Aug., 1953. Army Medical Service Graduate School, WalterReed Army Medical Center, Washington, D.C.
3. Moon, V. H.: Acute Tubular Nephrosis, a Complicationof Shock. Ann. Int. Med. 39: 51, 1953.
Oliver, Jean: Correlations of Structure and Function andMechanisms of Recovery in Acute Tubular Necrosis. Am. J. Med. 15:535, 1953.
Lucké, B.: Lower Nephron Nephrosis. Mil. Surgeon99: 371, 1946 (renal lesions of the crush syndrome, of burns transfusions,and other conditions affecting lower segment of nephrons).
4. Welt, L. G., and Peters, J. P.: Acute Renal Failure:Lower Nephron Nephrosis. Yale J. Biol. & Med. 24: 220, 1951.
Hopper, J., Jr., O'Connel, B. P., and Fluss, H. R.: SerumPotassium Patterns in Anuria and Oliguria. Ann. Int. Med. 38: 935,1953.
Stock, R. J.: Acute Urinary Suppression: Observationsin Twenty-two Patients. Am. J. Med. 7: 45, 1949.
Borst, J. G. G.: Protein Katabolism in Uremia: Effectsof Protein Free Diet. Infections, and Blood Transfusions. Lancet 1:824, 1948.
5. Fenn, W. O.: The Role of Potassium in PhysiologicalProcesses. Physiol. Rev. 20: 377, 1940.
Meroney, W. H.: Unpublished observations.
6. Winkler, A. W., Hoff, H. E., and Smith, P. K.: ElectrocardiographicChanges and Concentration of Potassium in Serum following Intravenous Injectionof Potassium Chloride. Am. J. Physiol. 124: 478, 1938.
7. Tarail, R.: Relation of Abnormalities in Concentrationof Serum Potassium to Electrocardiographic Disturbances. Am. J. Med. 5:828, 1948.
Nadler, C. S., Bellet, S., and Lanning, M.: Influenceof Serum Potassium and Other Electrolytes on the Electrocardiogram in DiabeticAcidosis. Am. J. Med. 5: 838, 1948.
Levine, H. D., Vazifdar, J. P., Lown, B., and Merrill,J. P.: "Tent-shaped" T Waves of Normal Amplitude in PotassiumIntoxication. Am. Heart J. 43 : 437, 1952.
8. Herndon, R. F., Meroney, W. H., and Pearson, C. M.:Unpublished observations.
9. Darrow, D. C.: Medical Progress: Body Fluid Physiology:The Role of Potassium in Clinical Disturbances of Body Water and Electrolytes.N. E. J. Med. 242: 978, 1014, 1950.
295
Abrams, W. B., Lewis, D. W., and Bellet, S.: The Effectsof Acidosis and Alkalosis on the Plasma Potassium Concentration and theElectrocardiogram of Normal and Potassium Depleted Dogs. Am. J. Med. Sc.222: 506, 1951.
Marks, L. J., and Feit, E.: Flaccid Quadriplegia, Hyperkalemia,and Addison's Disease. Arch. Int. Med. 91: 56, 1953.
Roberts, K. E., and Magida, M. G.: ElectrocardiographicAlterations Produced by a Decrease in Plasma pH, Bicarbonate, and Sodiumas Compared with Those Seen with a Decrease in Potassium. Circ. Res. 1:206, 1953.
Magida, M. G., and Roberts, K. E.: ElectrocardiographicAlterations Produced by an Increase in Plasma pH, Bicarbonate, and Sodiumas Compared with Those Seen with a Decrease in Potassium. Circ. Res. 1:214, 1953.
Keating, R. E., Weichselbaum, T. E., Alanis, M., Margraf,H. W., and Elman, R.: The Movement of Potassium during Experimental Acidosisand Alkalosis in the Nephrectomized Dog. S. G. & O. 96: 323,1953.
Talbot, N. B., Butler, A. M., and MacLachlan, E. A.: Effectof Testosterone and Allied Compounds on Mineral, Nitrogen, and CarbohydrateMetabolism of a Girl with Addison's Disease. J. Clin. Invest. 22:583, 1943.
Danowski, T. S., and Elkinton, J. R.: Exchanges of PotassiumRelated to Organs and Systems. Pharmacol. Rev. 3: 42, 1951.
10. Cohen, B. M.: Digitalis Poisoning and its Treatment.N. E. J. Med. 246: 254, 1952.
Zwemer, R. L., and Lowenstein, B. E.: Cortin-like Effectsof Steroid Glycosides on Potassium. Science 91 : 75, 1940.
Burstein, S. G., Bennett, L. L., Payne, F. E., and Hopper,J., Jr.: Effects of Potassium and Lanatoside-C on the Failing Heart inHeart-Lung Preparations. Fed. Proc. 6: 20, 1949.
11. Lown, B., Weller, J. M., Wyatt, N., Hoigne, R., andMerrill, J. P.: Effects of Alterations of Body Potassium on Digitalis Toxicity.J. Clin. Invest. 31: 648, 1952.
12. Fenn, W. O.: Deposition of Potassium and Phosphatewith Glycogen in Rat Livers. J. B. C. 128: 297, 1939.
Seldin, D. W., and Tarail, R.: Effect of Hypertonic Solutionson Metabolism and Excretion of Electrolytes. Am. J. Physiol. 159:160, 1949.
Tarail, R., Seldin, D. W., and Goodyer, A. V. N.: Effectsof Injection of Hypertonic Glucose on Metabolism of Water and Electrolytesin Patients with Edema. J. Clint. Invest. 30: 1111, 1951.
Kolff, W. J.: Serum Potassium in Uremia; Report of SixteenCases, Some with Paralysis. J. Lab. & Clin. Med. 36: 719, 1950.
13. Pollack, H., and Halpern, S.: Therapeutic Nutrition.U. S. National Research Council, 1952.
14. Swann, R. C., and Merrill, J. P.: The Clinical Courseof Acute Renal Failure. Medicine 32: 215, 1953.
15. Elkinton, J. R., Clarm, J. K., Squires, R. D., Bluemle,L. W., Jr., and Crosley, A. P.: Treatment of Potassium Retention in Anuriawith Cation Exchange Resin. Am. J. Med. Sc. 220: 547, 1950.
Danowski. T. S., Greenman, L., Peters, J. H., Mateer,F. M., Wiegand, F. A., and Tarail, R.: The Use of Cation Exchange Resinsin Clinical Situations. Ann. Int. Med. 35: 529, 1951.
Greenman, L., Frey, W. A., Lewis, R. E., Sakol, M. J.,and Danowski, T. S.: Biochemical Changes in Serum and Feces during Ingestionof Carboxylic, Sulfonic, and Anion Exchange Resins. J. Lab. & Clin.Med. 41: 236, 1953.
296
16. Kolff, W. J.: Treatment of Uremia with Forced High-calorieLow-protein Diet. Nut. Rev. 11: 193, 1953.
Kolff, W. J.: Forced High-calorie, Low-protein Diet andthe Treatment of Uremia. Am. J. Med. 12: 667, 1952.
17. Creditor, M. C.: Some Observations of Effects of IntravenousFat Emulsions on Erythrocyte Fragility. Proc. Soc. Exp. Biol. & Med.83: 83, 1953.
18. Balch, H. H., and Meroney, W. H.: Unpublished observations.
19. Meroney, W. H.: The P: NPN Ratio In Plasma as an Indexof Muscle Devitalization during Oliguria. Submitted for publication.
20. Bateman, J. C., Barberio, J. R., Grice, P., Klopp,C. T., and Pierpont, H.: Fatal Complications of Intensive Antibiotic Therapyin Patients with Neoplastic Disease. Arch. Int. Med. 90: 763, 1952.
