CHAPTER VI
Treatment of Lower Nephron Nephrosis
It should be stated at once that treatment of posttraumatic renal insufficiencyafter the syndrome has become established is disappointing although nothopeless. Evidence has been presented that shock is one factor importantin its etiology. As soon as the patient becomes available for treatment,the shock state can usually be corrected fairly rapidly. Primary treatmentof the wounded should therefore be directed toward prompt and adequateresuscitation of every man in shock in order to prevent, if possible, developmentof serious renal insufficiency.
In presenting our experience in the management of patients with posttraumaticrenal insufficiency, certain therapeutic errors to be avoided will be stressedand the use of various drugs and procedures to stimulate renal function(most of which are of questionable value) will be discussed.
Fluid Intake
Early in the Italian campaign fatal cases of posttraumatic renal insufficiencybegan to appear. Therapy almost universally consisted of intravenous administrationof large quantities of various crystalloids. Practically every known diureticwas also employed, and attempts were frequently made to alkalinize theurine by administering large quantities of available base by mouth or vein.In the absence of adequate output of urine, the renal insufficiency soonbecame complicated by cardiac failure as a result of overloading the circulatorysystem. The majority of patients so treated died rather promptly of pulmonaryedema before they had an opportunity either to die in uremia or to regainadequate renal function.
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Early in the course of our study it was found that those patients withrenal insufficiency almost without exception had increased plasma volumes,as was shown in Chapter V. Here then was an additional explanation forthe frequency of pulmonary edema; we were dealing with patients who, asa result of renal failure, already had a circulating plasma volume largerthan normal. If additional fluids were added, especially those containingsodium, water retention became more severe. The frequency of pulmonaryedema and cardiac failure is therefore not surprising. The therapeuticimplications of these physiologic abnormalities are clear. Patients withthis type of renal insufficiency already have too much extracellular fluidand too large a plasma volume, apparently primarily as a result of thekidney`s being unable to excrete this surplus water. Treatment should thereforeinclude (1) any judicious measures which might possibly encourage the kidneysto excrete more urine, and (2) avoidance of any measures which would furtherincrease plasma volume and secondarily cause cardiac embarrassment.
As was shown in the previous chapter, the critical period in the majorityof patients with renal insufficiency appeared to be the first 10 days afterwounding, when 94 percent of the total deaths occurred. Evidence has beenpresented that renal function had begun to improve after this time in anumber of patients, even though they subsequently died in uremia. Thusthe importance of preventing an early fatal outcome resulting from tooenthusiastic fluid administration cannot be overemphasized. Unfortunatelymost of these patients eventually die in uremia regardless of treatment,but by judicious use of fluids they are at least allowed an opportunityto recover renal function spontaneously and their chance of survival isincreased.
In cases in which fluids were restricted, the incidence of pulmonaryedema was, in our considered judgment, materially lessened, even in thosepatients who subsequently died primarily of renal failure. A few who recovered(Cases 43, 44, and 138) might have died of heart failure if quantitiesof fluid comparable to those previously employed had been given.
Our recommendation on fluid intake for the average patient with oliguriaor anuria is that ordinarily not more than from 500 to 1,000 cubic centimetersin excess of urinary output be given daily. The patients in this studywere seen in the fall, winter, and spring months when the temperature inNorthern Italy was such that extrarenal fluid losses were probably minimal.In hot weather or when sweating is excessive this allowance should probablybe increased. If
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urinary output increases to more than 1 liter daily, it is suggestedthat intake of fluids parallel or slightly exceed output of urine untilretained nitrogen is cleared. Oral fluids, whenever their use is feasible,are preferred to parenteral ones in order to avoid sudden augmentationof the already increased plasma volume. Such parenteral fluids as are usedshould be administered slowly, and the patient should be carefully observedfor signs of pulmonary edema during infusion. For reasons to be mentionedlater under Hypertonic Solutions, the preferred parenteral fluidis an isotonic solution of dextrose.1
We have too little data on sodium to compare the level of this cationin the serum with the sodium intake. Hence it cannot be stated whetherhyponatremia accompanied the hypochloremia, and therefore whether serioussodium depletion ever occurred. It now appears that as a consequence ofthe practice of giving almost no salt parenterally, hypochloremia resultedin some patients, although the outcome in those with decreased plasma chloridesapparently was no different from that in patients with normal chlorides.In our opinion, once posttraumatic renal insufficiency has become established,the danger of producing further edema and circulatory failure exceeds thequestionable benefit to be derived from continued attempts to replenishdeficient sodium by administration of sodium salt. We would therefore nowrecommend that during the oliguric and anuric phase salt be given onlyin quantities sufficient to replace extrarenal salt losses and the smallquantity lost in the urine. These combined losses can only be estimated;they probably would seldom exceed one or two grams of salt daily.
Procedures and Drugs Used to Stimulate Kidney Function
Our experience revealed no positive and sure measures capable of re-establishingkidney function after renal insufficiency had developed. The aim shouldalways be to avoid measures that might be harmful during the period before
1Because of the water-retaining property of the cation in sodium chloride, we suggested that the largest portion of the parenteral fluids given consist of 5- or 10-percent dextrose in distilled water. However, only the 10-percent prepared solution was available during most of the period when these studies were being made. Although 5-percent dextrose can be made up by adding dextrose solution to distilled water, under field conditions and the pressure of work during combat this is troublesome and was not often done.
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the kidneys spontaneously begin to clear retained waste products. Well-knownmethods of stimulating urine flow that were tried will be discussed briefly.It is evident from the results that they were of no value, or at best ofquestionable value.
Hypertonic Solutions
The advisability of giving hypertonic solutions parenterally in thissyndrome is highly debatable. They exert, at least in the presence of normalrenal function, a diuretic effect by (1) temporarily increasing plasmavolume, and (2) by limiting tubular reabsorption of water due to the osmoticeffect of increased concentration of solute in the distal tubules. It isclear that the first of these actions is undesirable, since the circulatingplasma volume is already increased; the second is desirable if tubularreabsorption can be altered in the damaged kidney.
Hypertonic saline (10-percent) solution was used in only one patient--theonly one in our series with a true transfusion incompatability (Case 9).There was no observed effect on urinary output. It might be argued thatearly trial of such a solution would be of value in this type of renalinsufficiency. If there is no response to 500 cc. of 3-percent saline solution,further attempts at diuresis by this method surely are contra-indicatedbecause of the undesirable increase in plasma volume which must resultfrom excessive salt administration.
Either a hypertonic dextrose solution or 5-percent dextrose in isotonicsaline solution was the parenteral fluid most often given to the patientswe observed. When solutions rendered hypertonic by sugar are employed,the osmotic effect on the plasma volume must be transient, lasting onlyuntil the dextrose is metabolized. The dextrose aids in nourishing patientswho, as a rule, are eating poorly or not at all. The concentration of dextroseemployed in hypertonic solution varied from 10 to 50 percent, but the 10-percentsolution was the one most often used. There was little if any evidencefrom extensive use of these forms of hypertonic solutions that they influencedthe output of urine.
In summary, since hypertonic solutions may dangerously increase plasmavolume, and moreover since our data indicate they are ineffective in promotingurinary flow, isotonic solutions would seem to be preferable. If hypertonicsolutions are employed, as they occasionally are in oliguria, dextroseis usually the one of choice; limited trial of hypertonic saline solutionmight be indicated in some cases.
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Alcohol
The known diuretic effect of alcohol, and the suggestion that its administrationmight increase renal blood flow2 prompted a rather extensivetrial of this agent. It was given to 22 patients, 20 of whom subsequentlydied of renal insufficiency and 2 of whom survived through the mechanismof recovery diuresis. Usually is was given intravenously, slowly, as a5-percent solution, the total daily dose being from 50 to 100 cc. of 95-percentethyl alcohol. As an alternative, if the patient could tolerate it, from120 to 180 cc. of whiskey were given by mouth daily. Of the 20 patientswho died, 7 received approximately these doses for 1 day only, 9 for 3to 4 days, and 4 for 5 to 8 days. Records are not available of the totalquantities received by the 2 patients who recovered, but it is known thatthey received similar daily doses. No symptoms due to the alcohol, otherthan occasional mild euphoria and drowsiness, were observed in any patient.
In only 2 of the 20 patients who died (Cases 41 and 52) was there asignificant increase in urinary output following the use of alcohol. The2 patients who recovered had marked diuresis. Other patients showed nosignificant effects, although occasional transitory increases of as muchas 300 cc. per day in urinary output were noted. Similar increases, however,occurred in patients with renal insufficiency who had not been given alcohol.
Mercurial Diuretics
Mercupurin, in doses of 1 or 2 cc., was given to three patients whosubsequently died of renal failure. No diuretic effect was demonstrable.
Aminophylline
No demonstrable diuresis resulted from intravenous administration of0.24 to 0.48 Gm. of this drug to four patients who later died of renalfailure.
Inorganic Ions
The use of sodium chloride has been mentioned under "Fluid Intake" andHypertonic Solutions.
2LAUSON, H. D.; BRADLEY, S. E. and COURNAND, A.: Renal circulation in shock. J. Clin. Investigation 23: 381-402, May 1944.
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Sodium sulfate in isotonic (3.2 percent) or hypertonic (4.2 percent)solution was given to two patients in total doses of 800 cc. and 1,000cc. respectively. Neither any beneficial nor harmful effects were observed.Both patients subsequently died in renal failure.
Magnesium sulfate and potassium chloride were employed on the theorythat these solutions might be effective in reducing edema of renal tubularcells and hence perhaps promoting urinary flow. Magnesium sulfate was usedin four patients (Cases 69, 78, 93, and 95). From 3 to 8 Gm. were givendaily (as 50-percent solution intravenously and intramuscularly) for periodsof from 2 to 5 days. Plasma magnesium levels, determined in two of thesepatients, were 7.0 milliequivalents per liter after 24 Gm. of magnesiumsulfate had been administered in 4 days in one (Case 93), and 3.8 milliequivalentsper liter after 8 Gm. had been given in 2 days in the other (Case 95).This second patient received in addition 10 Gm. of potassium chloride (as0.5-percent solution intravenously) at about the same time. No increasein output of urine was demonstrated in these patients and all four diedof typical renal failure.
Although no definite symptoms of toxicity due to these cations weredemonstrable in these four patients, we believe that the use of magnesiumand potassium in such cases is dangerous. In the presence of renal failure,administration of magnesium results in a rapid rise in the plasma concentrationof this ion. The danger of reaching toxic levels, it is believed, outweighsany possible beneficial effects. We have no data on potassium levels reachedin the one patient who received potassium chloride. However, because thision likewise exerts toxic effects, in our opinion it should not be usedin such cases unless serum potassium levels are known to be normal or low.There is some evidence in the literature to support the contention thatretained potassium may play a lethal role in uremia.3
Alkalis
The effect of alkalis in wounded patients will be discussed in detailin Chapter VII. Alkalis were given, usually in small doses, to many ofthe patients after renal insufficiency had developed. Eleven patients wholater died of uremia were given between 10 and 20 Gm. of sodium bicarbonateper day for 2 or more days, yet in only two of these patients was an alkalineurine observed. The
3HOFF, H. E.; SMITH, P. K., and WINKLER, A. W.: Cause of death in experimental anuria. J. Clin. Investigation 20: 607-624, November 1941.
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dangers of adding sodium to the extracellular fluid have been discussed. Further, the main reason for giving it in renal insufficiency is to produce an alkaline urine, the therapeutic value of which is debatable. We found no evidence that the use of alkalis has any place in the therapy of established posttraumatic renal insufficiency; in fact it may cause further harm.
Spinal Anesthesia
For many years, whenever anuria developed, it had been customary tosuggest that spinal anesthesia be induced in the belief that the kidneyfailure might perhaps be accounted for, at least in part, by reflex vascularspasm and that this could be interrupted by spinal anesthesia. The resultson the whole have been discouraging. Recent information suggests that partof the innervation of the kidney may come from higher origins than wasearlier supposed. For this reason, anesthesia to the level of the claviclewas planned. With sensory anesthesia to this level, it is probable thatvasomotor anesthesia was higher than this, since it is produced by a lowerconcentration of procaine hydrochloride than is required for sensory anesthesia.Pertinent data from four cases4 in this study in which thisprocedure was tried are summarized briefly as follows.
Case Summaries
1. (Case 47)-In 22 hours preceding high spinalanesthesia this patient had voided 30 cc. of urine. The bladder was emptyat the time anesthesia was induced.
0800 hours -Blood pressure 128/90.
0820 " -175 mg. procaine hydrochloride in 4 cc. spinal fluid were injected into the third lumbar interspace. Height achieved by barbotage.
0830 " -Blood pressure 135/88.
0835 " -Blood pressure 118/80.
0843 " -Blood pressure 120/80.
0830 " -Sensory anesthesia (pinprick) was present to the top of the second rib at the sternum.
0850 " -Blood pressure 112/80.
0915 " -Blood pressure 118/80. Sensory anesthesia persisted at the same level as at 0830.
0925 " -Blood pressure 118/80.
0945 " -Sensory anesthesia was beginning to wear off. There was no respiratory impairment at any time.
4Capt. Gerald Shortz of the 2d Auxiliary Surgical Group carried out the spinal anesthesias on three of these patients.
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The patient was catheterized 5½ hours after thespinal anesthesia had been induced. The bladder was still empty. Conclusion:The anesthesia had no diuretic effect.
2. (Case 95)-The details concerning this case aresimilar to those of Case 47, except that in this one anesthesia was obtainedto about the nipple line, where it persisted for 70 minutes. The bloodpressure did not fall during the period of anesthesia. Sixty-five cc. ofurine were present in the bladder just before induction of anesthesia.In the 24 hours following induction of anesthesia there was no formationof urine; this was checked by catheter.
3. (Case 135)-In 8 hours preceding spinal anesthesia65 cc. of urine had formed and were obtained by catheter just before anesthetization.
1410 hours -180 mg. procaine hydrochloride in 10 cc. of spinal fluid were injected into the third lumbar interspace.
1415 " -Anesthesia was present to the eighth cervical vertebra.
1430 " -Anesthesia was present to the fourth thoracic vertebra.
1500 " -Anesthesia was present to the seventh thoracic vertebra.
1515 " -Anesthesia was present to the ninth thoracic vertebra.
1535 " -Anesthesia was present to the second lumbar vertebra.
1600 " -Anesthesia of the saddle area and legs only.
1630 " -Full recovery.
2015 " -85 cc. of urine were obtained by catheterization.
There was no fall of blood pressure during this test. Since 65 cc. of urine had been formed in 8 hours preceding anesthesia, and 85 cc. in 6 hours following, no definite effect could be attributed to the anesthesia.
4. (Case 138)-In 11 hours preceding spinal anesthesia,40 cc. of urine had been formed. The bladder was emptied of this just beforeanesthesia was induced. The blood pressure remained at 120/72 throughoutthe test.
1500 hours -200 mg. procaine hydrochloride were dissolved in 12 cc. of spinal fluid and injected into the third lumbar interspace.
1505 " -Anesthesia was present to the eighth cervical vertebra.
1515 " -Anesthesia was present to the fifth thoracic vertebra.
1535 " -Anesthesia was present to the second lumbar vertebra.
1600 " -Saddle and leg anesthesia only.
1650 " -Complete recovery.
2100 " -60 cc. of urine were obtained by catheterization.
Sixty cc. of urine were excreted in 6 hours following induction of anesthesia and 40 cc. had been formed in 11 hours preceding anesthesia; hence no definite effect of the spinal anesthesia was evident. The patient`s low point in output was 2 days preceding the anesthesia; in other words, a steady increase in urinary output had already begun. This patient was the only one of this group who
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recovered. One cannot say that the spinal anesthesia either did or didnot play a part in his recovery.
No definite evidence was obtained from the four patients studied thatspinal anesthesia influenced the output of urine. We had planned to trythis procedure earlier, that is, soon after the onset of progressive oliguria.These plans were interrupted by the end of the war in Italy.
Kidney Decapsulation, Sympathectomy
This was carried out in one patient (Case 129) 54 hours after initialoperation, during which time the patient had voided 150 cc. of urine. Theright kidney was decapsulated and a periarterial sympathectomy performed.There was no effect on urinary output, and the patient died in uremia 48hours later, having excreted 180 cc. of urine since the second operation.
Correction of Anemia
In instances in which whole blood transfusions were indicated for thecorrection of severe anemia, these were given. Relatively fresh bank bloodwas used to avoid possible pigment insult secondary to intravascular hemolysisof aged cells. No benefit or detriment to the already failing kidney wasobserved.
Nutrition
Ideally, nutritive requirements during the acute phase of the syndromeshould be met by an adequate caloric intake, but with such foods that therewill be minimal destruction of body protein and production of urea nitrogenfrom exogenous proteins. These demands would best be served by a carbohydrateand fat intake sufficient to furnish from 1,500 to 2,000 calories per day.If the patient is unable to take food by mouth, it is practically impossibleto administer enough dextrose intravenously to furnish such a caloric intakeand still adhere to the more important rules of restricting fluids andprohibiting hypertonic solutions. During the acute phase of renal insufficiencyone must be content with merely furnishing the small requirement of sodiumchloride as isotonic saline solution, and with an attempt to meet caloricrequirements by supplying dextrose
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in a 5-percent solution in water in the additional small fluid allowanceremaining--that is, a total daily intake of 500 to 1,000 cc. in excessof total urinary output.
SUMMARY
Various procedures were tried in the treatment of lower nephron nephrosiswhich occurred as a complication in severely wounded men. Among these werecontrol of fluid intake, the use of relatively fresh blood for transfusionsto combat anemia, attempts to make the urine alkaline, spinal anesthesia,kidney decapsulation, and the administration of a number of drugs commonlybelieved to stimulate the excretion of urine. Except for evidence thatavoiding excess fluid administration reduced the incidence of early deathfrom pulmonary edema, all were essentially disappointing, leading to theconclusion that "the best treatment of posttraumatic renal insufficiencyis its prevention." Since shock is known to be a major factor in its development,prompt and adequate resuscitation of every man in shock is most important.
Once renal insufficiency has developed, avoidance of the therapeuticerror of administering too much fluid and hence accentuating an alreadyincreased plasma volume becomes of first importance. Types and quantitiesof fluids to be administered during the period when renal failure is mostsevere (usually the first 10 days after trauma) have been recommended.Although we employed various drugs or procedures directed toward promotingurine flow or improving kidney function, we met with little success intheir use. These measures included the use of hypertonic solutions, alcohol,mercurial and xanthine diuretics, and solutions of various inorganic ions,the induction of spinal anesthesia, and decapsulation of a kidney. Theessential requirement appears to be that of tiding the patient over thecritical period until natural recovery of renal function begins. Dialysisprocedures, which attempt to remove waste products by routes other thanthe kidneys until the kidneys resume their function, offer possibilitiesthat were not tried in this study.
CASES OF SPECIAL INTEREST IN THIS CHAPTER
9 43 47 69 93 129
41 44 52 78 95 135 138
