CHAPTER XI
The Crush Syndrome in Battle Casualties
In preceding chapters examples of the crush syndrome have been included,frequently with little or no distinction from the more usual types of battlecasualties. This group of cases, however, presents certain distinctivefeatures which require separate consideration. Moreover, though cases werereported in the German literature among casualties of World War I, andthough Bywaters1 and others2 3 have made carefulclinical and biochemic studies of many civilian casualties during the "Battleof Britain," few thoroughly studied cases have been recorded among thebattle casualties of World War II.
In this chapter the clinical, physiologic, biochemic, and pathologicfeatures and the results of treatment will be discussed on the basis ofnine cases, five of which were fatal. All of the patients were crushedwithin stone houses typical of the Italian countryside. (It is perhapsnot a coincidence that the first known description of the syndrome camefrom Italy in 1908 as a report of casualties of the earthquake at Messina.)Five of the buildings in which the injuries occurred, one of them housinga medical collecting company, were struck by artillery shells. Two of thecasualties resulted when a demolition charge exploded and the remainingtwo were incurred when a house about two hundred yards from our laboratorywas struck by a bomb from a German raider at dawn. It was consequentlypossible to observe the patients virtually from the moment of release fromthe rubble in which they were partially buried. All nine are listed, togetherwith pertinent data, in Table 95.
1BYWATERS, E. G. L.: Ischemic muscle necrosis; crushing injury, traumatic edema, crush syndrome, traumatic anuria, compression syndrome: a type of injury seen in air raid casualties following burial beneath débris. J.A.M.A. 124: 1103-1109, April 15, 1944.
2DOUGLAS, J. W. B.: Incidence of signs of renal injury following prolonged burial under débris in an unselected series of 764 air-raid casualties admitted to hospital. Brit. J. Urol. 17: 142-147, December 1945.
3DUNN, J. S.; GILLESPIE, M., and NIVEN, J. S. F.: Renal lesions in 2 cases of crush syndrome. Lancet 2: 549-552, November 8, 1941.
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TABLE 95.-DATA CONCERNING9 PATIENTS WITH CRUSH SYNDROME
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Clinical Features
The clinical features of crush syndrome can be divided into two categories:primary and secondary. The primary features, comprising the direct effectsof crushing injury, were common to all nine cases. The secondary features,seen only in the five fatal cases, were the usual signs and symptoms ofposttraumatic renal insufficiency described in Chapters IV and V.
Primary Phase
Shock.-Shock, as judged by the usual clinical criteria, was notcharacteristic of the majority of.our patients with the crush syndromeand was never seen in patients observed within 10 hours of release fromthe compressing agents. One patient (Case 70), for instance, looked sowell when examined 30 minutes after release that he was evacuated to therear without treatment. He nevertheless died 4½ days later. Onlyone patient (Case 93) was in shock when first examined and this was 13hours after release. He had had no previous medical attention. A diagnosisof slight shock was made in Case 78 twenty hours after release, and thoughdiagnoses of shock were never made in Cases 69 and 132, transitory episodesof impalpable pulse and unmeasurable blood pressure were recorded in thecase histories (at 19 hours in Case 69 and at 14 and 23 hours in Case 132).In Case 70 and in all the surviving patients, hypotension was never observed.
Nausea and Vomiting.-Nausea or vomiting was recorded in onlythree cases, all of which terminated fatally. Nausea with hiccuping wasobserved in one patient (Case 70). This occurred on the first and seconddays after release when the nonprotein nitrogen concentration was 83 to104 mg. per 100 cc. of plasma. Vomiting was recorded twice. One patient(Case 93) vomited while he was still pinned down by masonry but not afterward.The second patient (Case 78) had troublesome vomiting on the second andthird days after release from compression. On those days the nonproteinnitrogen of the plasma was 92 mg. per 100 cc. and occasionally higher.
Local Changes.-Commonly the appearance of the skin gave no indicationof the changes in the underlying muscle. In some patients, however, therewere bruises and areas of ecchymosis and lividity of the overlying skin(Fig. 23). Immediately after release from compression the affected partsbegan to swell. The swelling took place first within the fascial compartmentsand resembled
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FIGURE 23. Bruising, ecchymosis,and swelling of extremity (Case 78).
the swelling of the calf muscles following interruption of the poplitealartery. The affected areas became hard, tense, and brawny. Only later,usually after the third day, did soft, pitting subcutaneous edema appear.Distribution of lesions was variable. The extremities were most often involved,particularly the legs, and the muscles of the buttock were frequently included.In one patient (Case 132) the muscles of the shoulder and neck were mostaffected, and edema of the neck was so great that a tracheotomy provednecessary.
During the first few days of the syndrome, the patients might have nocomplaints or they might complain of stiffness, soreness, aching, and tendernessin the involved areas. Symptoms were often inversely proportional to theseverity of injury. In relatively mild lesions, pain was elicited by pressureon the affected area; more severe lesions were insensitive to pressure.Some patients complained of numbness of the skin of the toes and over theinvolved muscles. Examination revealed patchy areas of hypesthesia or anesthesiaof the skin, a "stocking" type of anesthesia of the limbs, and absent reflexes.Involved muscle groups were paralyzed or sometimes temporarily spastic.It was sometimes impossible to feel pulsations in the arteries of the affectedlimbs, reminding one of the early phase of Volkmann`s contracture. In onepatient (Case 78) a fasciotomy was done for that reason. The leg was soinsensitive that it was possible to perform the operation without anesthesia.
Fractures.-Rather surprisingly, in view of the nature of theinitial trauma,
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no major fractures were observed. The only fracture recorded (of thezygoma) could be considered only coincidental.
Secondary Phase
One patient (Case 132) died 56 hours after release from compression;the other four lived from 4 to 13 days after release. One died suddenly,apparently of acute cardiac failure, the others more slowly, with progressivelethargy and drowsiness but no typical uremic coma. Drowsiness was particularlymarked in one patient (Case 78) who had been treated with magnesium. Noneof the patients in this group had convulsions at any time during theirillness. The mechanism of death appeared to be pulmonary edema, exceptin one patient (Case 93) in whom lobar pneumonia developed on the thirteenthday shortly after the appearance of a diuresis had led to hope for hisrecovery.
All of the patients who died showed the usual signs and symptoms ofa lower nephron nephrosis previously described (Chapters IV and V). Theinitial urine specimens were deeply pigmented and reacted positively withthe benzidine test; oliguria was marked and, except in Cases 69 and 93,progressive (see Table 97). The urine, with one exception, was persistentlyacid and the specific gravity was constantly low from the third day onward.The nonprotein nitrogen level in the plasma rose progressively, and onthe third or fourth day mild hypertension developed. Details of the chemicalabnormalities of the blood and urine follow.
Physiologic and Biochemic Features
Blood
Blood Volume.-The blood volume was determined immediately uponarrival at the hospital in only two patients with crush injury. The first(Case 93) was the only patient of the group thought to be in severe shock.He had lost one-third of his total blood volume, apparently entirely inthe form of plasma, for he showed no evidence of diminution of the totalhemoglobin or red-cell mass. The hemoconcentration might have been partlyresponsible for the clinical picture of shock, as severe shock was generallyassociated with a loss of circulating blood greater than one-third of thenormal volume. The second patient
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CHART 39. HEMATOCRITVALUES* IN FATALCRUSH SYNDROME
(Case 124) showed no evidence of shock clinically and no decrease wasfound in the volume of circulating blood.
In three patients (Cases 69, 78, and 93) the blood volume was determinedduring their course. It was abnormal in only one of them (Case 78), beingincreased by about two liters 24 hours after the patient`s release fromcompression. During that period he had received 600 cc. of plasma (2 units),400 cc. of 4-percent sodium bicarbonate, and 1,000 cc. of 5-percent dextrosein isotonic saline solution intravenously. He had taken 800 cc. of liquidsby mouth and had voided 350 cc. of urine. He died 3 days later with severepulmonary edema. In Case 93, the patient received no more fluid intravenouslythan was necessary to correct his blood volume deficit. He died of lobarpneumonia 13 days after release. The blood and plasma volumes in Case 69were within normal limits on the second and ninth days. In retrospect,from rough fluid-balance calculations, this patient was given perhaps 2,000cc. more parenteral fluid, including large doses of sodium bicarbonate,than optimal. The fact that severe peripheral edema developed indicatesthat total body water, if not circulating blood volume, was probably increased.
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CHART 40. HEMATOCRITVALUES* IN NONFATALCRUSH SYNDROME
Hematocrit Value and Plasma Proteins.-The most striking featureof the immediate findings in the blood of patients with the crush syndromewas the hemoconcentration in those who subsequently died. It was chieflyamong these patients with the crush syndrome that hemoconcentration wasfound in our series of seriously wounded. In one patient (Case 70) thehematocrit value was 80 percent 9 hours after his release from the crushingforce. It is noteworthy that the clinical evaluation of this man failedto reveal evidence of shock. All of our patients with crush syndrome whodied had initial hemoconcentration (Chart 39 and Table 96). It was, however,transitory and the hematocrit value was within normal limits by the endof the second day. None of those who survived had hematocrit levels abovenormal limits4 (Chart 40 and Table 96).
Plasma proteins were within normal limits5 in six of theeight patients on whom early determinations were made. One initial determinationin a patient who lived and four determinations made in the first 24 hoursafter release
4Normal: 47. Range: 42 to 52 percent.
5Normal: 6.5. Range: 6 to 7 Gm. per 100 cc.
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TABLE 96.-HEMATOCRIT VALUEIN RELATION TO PATIENTS`COURSE
from compression in a fatal case were moderately elevated (Table 97).Again, as was the case in the hematocrit values, the elevated plasma proteinconcentration soon returned to normal. Although our data are too few topermit of interpretation, it is probable that a consistently high plasmaprotein concentration in the first 24 hours is indicative of a poor prognosis.
In these crush cases the initial concentration of red blood cells wasrelatively greater than the concentration of plasma protein, as may beseen in Chart 41. These findings suggest that with release of compressionand re-establishment of circulation to the injured areas, there is promptoutpouring of plasma into
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TABLE 97.-PLASMA PROTEINCONCENTRATION IN RELATION TOPATIENTS` COURSE
the affected tissues, manifested clinically by the rapid developmentof swelling in the affected parts. With the loss of plasma from the circulatingblood, the concentration of the red blood cells is increased. If, as islikely, the plasma lost into the tissues contains less protein than normalplasma, an explanation of the early increases in the concentration of plasmaproteins in some severe cases is afforded. The rapid disappearance of thehemoconcentration (and of the elevated plasma protein level in two instances)is in part accounted for by the intravenous administration of plasma andcrystalloids, but this is not the only factor, for the dilution occurredin the absence of intravenous therapy. The effect could be explained bythe reabsorption of extravasated plasma.
During the later stages of the syndrome in the fatal cases, the hematocrit
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CHART 41. RELATIONSHIPBETWEEN PLASMA PROTEIN ANDHEMATOCRIT LEVELS IN CRUSHSYNDROME
value remained within low normal limits except in Cases 78 and 93 inwhich it fell below 40, eventually dropping to 21.9 on the day of deathin the latter case. There was greater variability in the concentrationof the plasma proteins during the course of the disease. Two determinationsin patients who survived and seven determinations in patients who dieddropped below 6 Gm. per 100 cc., three of them being below 5.5 (Table 97).
Plasma Nonprotein Nitrogen.-Among the patients who survived,concentration of the nonprotein nitrogen in the plasma was essentiallynormal throughout the course of the illness. Among those who died, it waselevated from the start and rose progressively at an almost linear rate(Chart 42). No determinations were made in one fatal case. The concentrationof phosphorus in the plasma rose more slowly and appeared to reach itsasymptote earlier.
Plasma Chlorides.-The plasma chloride concentrations were essentiallynormal among the patients who survived. Among those in whom fatal crush
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CHART 42. PLASMANONPROTEIN NITROGEN CONCENTRATIONIN CRUSH SYNDROME*
syndrome developed, however, there was a progressive drop in the concentrationof plasma chlorides except in one patient (Case 93) who developed a diuresisand showed evidence of improving renal function although he subsequentlydied (Chart 43). At necropsy lower nephron nephrosis and lobar pneumoniawere demonstrated. No determinations were made in one fatal case. Concomitantwith the fall in plasma chloride level, there was generally a fall in thealkali reserve of the blood as suggested by the lowering of its CO2combining power. These changes in plasma carbon-dioxide combining powerand chloride levels were entirely comparable to those seen in renal insufficiencyfollowing other types of trauma (Chapter V).
Plasma Pigment.-Blood specimens taken shortly after release fromcompression revealed abnormal quantities of a free pigment in the plasmawhich reacted positively to the benzidine test. Blood samples were collectedin carefully dried, but not oiled, syringes and needles. With this technique,a free plasma "hemoglobin" concentration up to 15 mg. per 100 cc. was consideredwithin the normal range. Chart 44 shows the values obtained in the first5 days after injury both in the patients who died and in those who survived.All but
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CHART 43. PLASMACHLORIDE CONCENTRATION* IN CRUSHSYNDROME
two of the determinations we were able to obtain during the first 24hours were above the limits accepted as normal; the exceptions were determinationsmade in Case 99, nine and sixteen hours after release. Only one of thepatients showed a heme concentration of over 40 mg. per 100 cubic centimeters.Data were available on eight cases. Of particular interest, from thosedata, is that, like the return of the hematocrit level and the plasma proteinconcentration to normal, the concentration of the free benzidine-positivesubstance in the plasma tended to be within normal limits by the end ofthe second day. As in the case of the hemoconcentration, then, the presenceof free benzidine-positive substance in the plasma might have been missedif specimens had not been collected soon after the patients` release fromthe crushing force.
The nature of this substance, free in the plasma and giving the reactionof a heme, could not be settled. The quantities present were not largeenough to make spectroscopic analysis possible in the instrument availableto us. Chemical examination of the urine of these patients (Chapter VIII)showed that both hemoglobin and myoglobin were excreted in large amounts,the proportions of each varying widely from case to case. It is reasonableto assume, therefore, that both pigments were represented in the plasmaas well.
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CHART 44. FREEBENZIDINE-POSITIVE SUBSTANCEIN PLASMA IN CRUSH SYNDROME*
Urine
Gross abnormalities were found only in the urine specimens collectedsoon after release from the compression force. Table 98 indicates the durationof some of the abnormalities in the urine. It will be observed that myoglobinwas not found in the urine more than a day and a half after release fromthe crushing force. Abnormality in the color of the urine lasted somewhatlonger (up to 3 days), and albuminuria to a significant degree was detectedfor as long as 9 days after release from the crushing influence.
Output.-None of the patients who survived the injury had anydiminution in volume of urinary output below the limits of normal. In allof those who died (Table 99) urinary output was diminished from the start.All had oliguria. In one instance (Case 70) anuria (an output of less than100 cc.) was recorded during the 24 hours beginning the day after release.Two other patients were oliguric until the second 24-hour period, whenthe output dropped below 100 cc. a day. The remaining two patients (Cases93 and 78) were oliguric but never became anuric. In one (Case 69) diuresishad just begun to develop when he suddenly died; in another (Case 93, Table99) an excellent diuresis was estab-
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lished and the patient might have survived the injury had he not diedof lobar pneumonia.
TABLE 98.-DURATION (DAYS)OF ABNORMALITIES IN THE URINEOF 9 PATIENTS WITH CRUSHSYNDROME
TABLE 99.-URINARY OUTPUTIN 5 FATAL CASES OF CRUSHSYNDROME
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Color.-Yellow and straw color were considered to be the normalcolors of urine. An amber color was considered on the borderline of abnormality.All of the patients who died had abnormal urinary color varying from redto red-brown, or mahogany to dark amber; this lasted 2 or 3 days. Amongthe patients who survived, the color varied from "ruddy" to amber; butthis did not persist longer than 1 day.
Benzidine-Positive Pigment.-The grossly abnormal color of theurine in patients with the crush syndrome was found to be caused by thepresence of a pigment which reacted positively to the benzidine test. Bythe technique described in Appendix C, this pigment was thought to consistof myoglobin as well as hemoglobin in three of the five patients who diedof the crush injury. In the fourth patient no attempt was made to distinguishbetween the two pigments, and in the fifth patient the benzidine test wasnot made on the dark-amber urine. Results of the tests for myoglobin werenever positive in urine specimens obtained later than 24 to 36 hours afterrelease from the crushing force. Benzidine-positive substance was foundlater than the second day and up to the eighth day after release, but insuch small amounts that it was impossible to employ the test to distinguishbetween myoglobin and hemoglobin. Qualitative spectroscopic examinationssuggested the presence of myoglobin in the specimens obtained in fatalCases 69, 70, and 93.
Albumin.-Two of the patients who survived showed some albuminuria.In neither case did it last more than 1 day, and in only one (Case 56)of the two was it of any degree of severity. All of the patients who diedhad marked albuminuria. Up to 4 or 6 days it persisted unchanged or withincreased severity. If the patient lived longer, the degree of albuminuriathen decreased, as in Cases 69 and 93. In the latter the urine containedonly a faint trace of albumin by the time the patient died of lobar pneumonia13 days after release from the crushing force.
Sediment.-The urinary sediment was remarkable because findingswere so scarce. In one patient who survived (Case 124), no record was madeof the examination of the organized sediment. Of the other three patientswho lived, only one (Case 73) showed casts in the urinary sediment. Onthe first day after injury his urine showed occasional coarse and finelygranular casts; 2 days later the sediment was normal. Two of the five patientswho died had no casts in the urine, although a rare red blood cell anda few white blood cells were found; three did show coarse and finely granularcasts in the urinary
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sediment, but these casts were not abundant, even in centrifuged specimens.
Specific Gravity.-For the first day or two of the illness, thespecific gravity of the urine was normal in all cases. After the secondto fourth days, however, the specific gravity of the urine fell and appearedto become fixed at 1.012 to 1.013. Urine concentration tests were not donein these patients, but as in other cases of posttraumatic renal insufficiencyearly impairment of ability to reabsorb water by the renal tubules is surelya characteristic feature (Chapter V).
Reaction.-With one exception, the patients passed acid urineat all times throughout the illness. This one exception (Case 69) was apatient whose urine was on the alkaline side of neutral (pH 7.2) on twooccasions on the seventh and eighth days of the illness. At all other timesthe urine of this patient was acid, despite administration of sodium bicarbonatein doses thought adequate for alkalinization of the urine (16 to 36 Gm.per 24 hours). As had been found in the study of patients who had renalinsufficiency from other causes, alkalinization of the urine by means ofadministration of sodium bicarbonate was inconsistent with safety.
CHART 45. BROMSULFALEINEXCRETION IN PATIENTS WITH FATALCRUSH SYNDROME
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CHART 46. PLASMABILIRUBIN CONCENTRATION IN CRUSHSYNDROME
(FIRST 6 DAYS)
Liver Function
The function of the liver was tested in one of the four patients whosurvived and in four of the five patients who died. The examination consistedof a test of the ability of the liver to excrete bromsulfalein injectedintravenously. Dosage was calculated on the basis of 5 milligrams of bromsulfaleinper kilogram of body weight (Chapter II). By this method, retention ofthe dye up to 3 percent of the injected dose after 45 minutes was consideredthe upper limit of normal. In the patient who survived the function ofthe liver was found to be normal as tested by this method. In all of thepatients who died liver function was found to be impaired (Chart 45). Theaverage dye retention in the four fatal cases was 12.77 percent, exclusiveof one determination made in Case 93, which showed 26-percent retentionon the day the patient died of lobar pneumonia.
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The concentration of bilirubin in the plasma was increased in thosepatients in whom fatal crush syndrome developed and in one patient (Case56) who survived (Chart 46). Data were obtained on eight cases. Sufficientinformation was not available to distinguish between increased productionof bilirubin and decrease in its elimination.
Pathology
The important findings at postmortem examination were confined to thelungs, the liver, the skeletal muscles, and the kidneys.
Lungs.-All of the five fatal cases showed slight to extensivepulmonary edema, both grossly and microscopically. The weight of the twolungs together was recorded in four of the five fatal cases. The weightsvaried from 1,075 to 1,600 grams. Blood as well as edema fluid appearedon cut surfaces of the lungs in Case 132 and, microscopically, large numbersof alveoli were packed with red blood cells. This patient had had a tracheotomyand the blood may have been aspirated. Another patient (Case 78) was unusualin that even the visceral pleura was edematous. Fluid poured from the cutsurfaces without the necessity of compression, and the tracheobronchialtree was filled with nonbloody fluid. In Case 93 death was due primarilyto lobar pneumonia involving the left upper lobe. Microscopically, in additionto the typical pneumonia process, some areas showed edema with spreadingpneumonic involvement.
Liver.-In view of the decreased liver function, as measured byability to excrete bromsulfalein and as indicated by the elevated plasmabilirubin and the abnormally low ratio of urea nitrogen to total nonproteinnitrogen, some histologic changes were expected in the liver. Surprisinglyfew were found. The liver was microscopically normal in Case 70, and showedonly scattered vacuoles in Case 132. In Case 69 occasional mitotic figureswere observed in hepatic cells, and in Case 93, in which there had beenterminally a rising bilirubin concentration in the blood and a terminalbromsulfalein retention of 26 percent, the only histologic changes foundwere mild nuclear atypicality in the cells at the centers of the lobules.
Skeletal Muscles.-The gross changes in the involved muscles wereconspicuous. In the involved areas the normal pigment had disappeared,leaving muscle bundles with the appearance of fish or rabbit flesh. Sometimesan entire muscle was decolorized, more commonly only segmental areas, particularlyre-
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gions close to major bony structures (Fig. 24). In Figure 25 (Case 93)complete depigmentation of the distal half of the forearm muscles is apparent,whereas the proximal half is normally colored. The transition from normallycolored to depigmented areas was sharp, particularly in the cases of longersurvival, and in Case 93 (13 days` survival) the junction was marked bya narrow white band 2 to 3 mm. broad (Fig. 25). In spite of the loss ofcolor, the
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tissue remained moist, capillary oozing appeared from cut surfaces,and no thrombi could be discovered in any grossly visible vessels. Hemorrhageand edema were extremely irregular in extent and intensity, absent fromsome lesions, and marked in others. The gross depigmentation correlatedwith chemical assays showing almost complete loss of myoglobin in the affectedareas (Table 100).
Microscopic sections were available from four cases 4, 5, 10, and 13days respectively after injury. In the acute cases hematoxylin and eosinstains showed relatively inconspicuous changes. Evidences of muscle-celldegeneration were, however, present. Some cells were swollen, hyaline,and more strongly acidophilic than normal. More commonly the cells stainedless intensely than normal, cross-striations were exaggerated, occasionalfractures and clefts were present, and the sarcolemma nuclei appeared decreasedin number (Fig. 26). Though edema and hemorrhage were apparent in someareas, there was no inflammatory reaction, either polymorphonuclear orhistiocytic. With the Masson and phosphotungstic acid hematoxylin stains,the changes were far more conspicuous. Some of the swollen hyaline fibersstained intensely red with the Masson, or blue with the phosphotungsticstain, but the great majority responded feebly or not at all to the specificstaining reactions. In sections across the border of a depigmented areait was evident that the loss of specific staining reaction correspondedclosely with the margin of depigmentation (Fig. 27 a). It was of interestthat the cells with exaggerated cross-striations usually failed to stainspecifically.
TABLE 100.-MYOGLOBIN CONTENTOF MUSCLE AND KIDNEY IN4 PATIENTS WHO DIED FROM CRUSHSYNDROME
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In the cases of longer duration (10 and 13 days), changes were conspicuouswith all staining methods but particularly with hematoxylin and eosin.Many swollen, necrotic muscle cells had become intensely basophilic owingto the precipitate of innumerable fine granules staining like calium throughoutthe sarcoplasm (Fig. 27 b). In other cells the precipitate was intensein the central portion but absent at the periphery (Fig. 28 a). Anothercommon type of degenerative change was a coarse hydropic vacuolation whichfrequently produced an appearance suggestive of vegetable cells (Fig. 27c). Other degenerating cells showed varying degrees of infiltration withhistiocytes. (Figs. 27 b and c). The sarcolemma nuclei in many cells showedamitotic division, with chains of touching nuclei 5 to 10 elements in length(Fig. 28 b). About many of these, viable cytoplasm was present in long,slender masses suggesting regeneration of muscle cells. The interstitialconnective tissue was slightly edematous and densely infiltrated with histiocytes(Fig. 28 b). No definite evidence of fibroblastic proliferation could bemade out. Blood vessels still remained free from thrombi or inflammatoryreaction.
Kidneys.-In all but one patient (Case 70) the kidneys were enlargedat necropsy. In three of the five fatal cases the combined weights of thetwo kidneys were recorded; they were respectively 500, 550, and 625 grams.The capsules stripped easily. In some there were ecchymoses beneath thecapsule. Focal
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FIGURE 27, a. Muscle fromCase 70 (4 days` survival). Phosphotungstic acid hematoxylin stain. Sectiontaken from a partially
depigmented area. The musclecells stain irregularly and striations are difficult to see. The most severelyinvolved cells are stained a faint brown. The interstitial tissue is edematousbut shows little inflammatory infiltrations.
b. Muscle from Case 69(10 days` survival). Hematoxylin and eosin stain. This low-power view showsfocal calcification as well
as fibrosis of the interstitialtissue and a chronic inflammatory infiltrate. A cell just below centermanifests marked vacuolar degeneration.
c. A higher magnificationfrom the same section shown in b. Masson trichrome stain. Coarsevacuolar degeneration of a muscle cell in the lower portion of the photomicrographis evident. Several muscle cells in the center no longer stain red in normalfashion and have been invaded by histiocytes.
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FIGURE 28, a. A focus ofintense calcification involving almost every muscle cell. There is markedincrease in interstitial fibrous tissue with an occasional focus of lymphocyticinfiltration. Section from Case 93 (13 days` survival).
b. Section from the samecase. Hematoxylin and eosin stain. A regenerating muscle cell shows longchains of touching sarcolemma nuclei. The fibrosis and the patency of theblood vessels are noteworthy. Partial calcification of some muscle cellsat the periphery of the field is evident.
hemorrhages and fibrin deposits were commonly found beneath and on theepithelium of the renal pelvis (see Fig. 20 in Chapter IX). When the kidneyswere cut, with one exception (Case 70), the renal parenchyma pouted throughthe cut, rolling outward and forming a rounded instead of a sharp edge.
Characteristically, the cut surface of the parenchyma showed pallorof the cortex and darkening of the pyramids to a dark brown or mahoganycolor (Figs. 19 to 22 in Chapter IX). The thickness of the cortex was normalor increased, never decreased.
The microscopic appearance of the kidneys from patients who died fromcrush syndrome have been described and illustrated in Chapter IX as a "lowernephron nephrosis," and it will be sufficient merely to list the salientfeatures here.
Microscopic Features of the Kidney.-Most conspicuous was thepresence of densely pigmented casts in the distal convoluted and the collectingtubules. These could not be distinguished in stained or unstained sectionsfrom the pigmented casts in Case 9, a known transfusion reaction. Proximalto the pigmented casts, usually in the ascending limbs of Henle`s loops,hyaline nonpigmented casts were numerous. In cases with survival periodsof 4 days, these hyaline casts were frequently extruded into the stromaand formed foci for granulomatous reactions. Degenerative changes in therenal parenchyma were limited to the lower nephron segments, usually theascending limbs, less often the distal convoluted tubules.
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Glomeruli were uniformly normal except for the presence of granularprecipitate in the capsular space. The proximal convoluted tubules weresometimes moderately dilated and their lumens contained granular precipitate,but the epithelial cells were normal and brush borders were well preserved.Interstitial inflammatory reaction was always present at the corticomedullaryjunction, and in two cases of 10 and 13 days` duration, a narrower zoneof interstitial inflammatory reaction was seen beneath the capsule. Inthe same two cases nonocclusive thrombi were present in some of the veinsat the corticomedullary junction.
Treatment of Crush Syndrome
The results of treatment of patients with crush syndrome were disappointing.(Our ministrations were certainly less effective than those of Saint Benedict,whose successful treatment of a monk crushed beneath the masonry of a wallat Monte Cassino is depicted on page 254.) In general, efforts during thefirst 48 hours were directed toward correction of the hemoconcentrationand attempts at alkalinization of the urine. Subsequently the treatmentwas that for renal insufficiency as described for patients with renal insufficiencyfrom other causes (Chapter VI).
Correction of Hemoconcentration.-Hemoconcentration was treatedby administration of plasma and crystalloid solutions during the first48 hours. Beyond this time, the degree of hemoconcentration was no longera serious problem, for reabsorption had probably begun to exceed transudation.Only two of the nine patients received whole blood. One of the two (Case69) received only 250 cc. of blood, administered before the hemoconcentrationhad been recognized. The other (Case 132) was given 1,500 cc. of wholeblood when he became pulseless and no blood pressure could be determinedin his extremities.
Alkalinization of the Urine.-According to Bywaters`6hypothesis, alkalinization should be started at the time the casualty isfound, immediately after or even before release from compression. Thiswas not possible in any of our patients. The seriousness of the injurywas not recognized by the aid-men. As a matter of fact, the diagnosis wasnot made by the medical officers until, through an educational campaign,they had been made aware of the possibility of the syndrome in any crushinjury.
6See footnote 1.
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CHART 47. EFFECTOF ALKALITHERAPY IN A PATIENTWITH CRUSHSYNDROME
(CASE 69)
After admission to the hospital, however, all but two of the nine patientsreceived alkali therapy. Four of the five patients who died were treatedwith alkali, one starting promptly upon admission to the hospital, onestarting during the first 24-hour period after release from the crushingforce, and two during the second 24-hour period. No beneficial effectswere observed that could be attributed to the alkali. As a matter of fact,the most striking feature was the failure, in the fatal cases, to succeedin alkalinizing the urine. A pH of 7.2 was attained in only two specimensof urine in Case 69 (Chart 47). This patient had received larger dosesof sodium bicarbonate than the other patients. One patient in this group(Case 124) did have an alkaline urine (pH 8.4) 4 hours after intravenousadministration of sodium bicarbonate, and it was kept alkaline by the administrationof 3 Gm. of the bicarbonate every 4 hours. This patient had a minimal renallesion and survived. Administration of sodium bicarbonate was done cautiouslyor abandoned altogether, because of unfortunate experiences with vigorousattempts at alkalinization in patients with renal insufficiency from othercauses (Chapter VII).
Diuretics.-Alcohol was used with the hope that it would promoteblood
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flow through the kidney and serve as a diuretic. It was used intravenously(total dose: 50 to 100 cc. of 95-percent ethyl alcohol as a 5-percent solutionin dextrose or isotonic saline solution), and as whiskey by mouth (60 to180 cc. per day). No beneficial effects were detected that could be attributeddirectly to the alcohol. Three of the patients were given 10-percent dextrosein distilled water intravenously, and one received 50-percent dextroseintravenously as a diuretic, but no effect was noted in any of them thatcould be attributed to the medication. The failure of both alcohol andhypertonic solutions of dextrose to promote urine flow or improve kidneyfunction confirmed the findings in patients with renal insufficiency fromother causes (Chapter VI). Not only did concentrated solutions fail toinduce a diuresis, but in three cases (Cases 70, 78, and 132) the hypertonicdextrose solution may have hastened the onset of pulmonary edema. Mercurialdiuretics were not tried in patients with the crush syndrome.
Dehydrating Agents.-On the hypothesis that swelling and edemaof the kidney may be in part responsible for failure of function, the useof potassium and magnesium solutions was recommended by Barker7to reduce the tissue swelling and to promote diuresis. Potassium chloridewas not available to us for clinical use, but magnesium sulfate was usedintravenously and intramuscularly. It was employed in three cases (Cases69, 78, and 93) in doses of 4 to 8 Gm. daily for 3 to 5 days, which wassufficient to elevate the concentration of magnesium in the blood as indicatedin the two patients in whom such analyses were made (Cases 78 and 93).In these three patients there was no definite effect upon urinary output,and it is impossible to attribute any beneficial effect to the use of magnesium.Undue drowsiness in Case 78 could well have been caused by the magnesiumtherapy, for his serum concentration of magnesium was 5.8 milliequivalentsper liter at necropsy. The serum magnesium reached a level of 6.8 milliequivalentsper liter at one stage during the course of treatment in Case 93. For thesame reasons stated in Chapter VI, it is our opinion that neither magnesiumnor potassium solutions should be used in the treatment of this syndrome.
Other Measures.-Study of these nine patients taught us littleas to possible means of preventing anuria or inducing diuresis. Generallyaccepted methods failed. On the hypothesis that injury to the kidney maybe produced when reabsorption of extravasated fluid takes place, pressurebandages were considered worthy of trial and were applied in one case (Case78) without apparent effect.
7BARKER, MARION H.: Personal communication.
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In this case, however, serious extravasation into the tissues had alreadyoccurred before the patient reached the hospital. Cold applications mightprevent rapid flooding of the kidney with large quantities of muscle-breakdownproducts, inasmuch as cold is known to inhibit the flow of lymph from theperiphery into the general circulation. This therapy was not tried. Again,however, to be effective it would have to be started immediately afterrelease from compression. Therapeutic amputation of the involved extremitieswas thought to be out of the question for the same reason.
What was learned from the patients with crush syndrome, as well as fromthose with renal insufficiency from other causes, was that it is very easyto bring about an increase in plasma volume in these patients by too vigorousattempts at inducing a diuresis with intravenous crystalloids. Once oliguriaor anuria is established, it is best to withhold fluid, allowing, preferablyby mouth, just enough fluid to compensate for loss from the gastrointestinaltract, and for insensible loss through the skin, from the lungs, and fromthe sweat glands. Under ordinary circumstances, these requirements canbe met by 1,000 cc. or less of fluid daily; more must be allowed if excessiveextra-renal losses occur. In general, patients with renal insufficiencyhave been found to be over-hydrated rather than under-hydrated, and thisaccounts for the fact that pulmonary edema is a common cause of death.
SUMMARY AND CONCLUSIONS
A laboratory and clinical study was made of nine patients who receivedcrushing injuries; four of the patients survived, five died. It is emphasizedthat the crush syndrome develops insidiously in patients who appear wellwhen first seen. All patients who have suffered compression interferingwith the circulation of muscle masses for periods of an hour, and perhapseven less, should be observed carefully for development of features ofthe syndrome; namely, tense swelling of the affected parts, hemoconcentration,benzidine-positive pigment (presumably myoglobin) free in the plasma andurine, and oliguria or anuria. If examinations are not made within 24 or48 hours, the hemoconcentration and the myoglobinuria may be missed. Thevolume of urinary output should be watched closely, for significant oliguriamay easily be overlooked.
The principal pathologic findings are in the compressed muscles andin the kidneys. In the former the normal pigment, myoglobin, was rapidlymobilized
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and absorbed, and extensive necrosis of muscle developed which tendedto heal with calcification if the patient survived a week or longer. Inthe kidney a pigment nephropathy was found, which was indistinguishablefrom that which develops following other forms of severe trauma. A commonterminal finding was severe pulmonary edema.
The treatment applied to these nine cases has been described. In thepresence of oliguria or anuria, it was impossible to alkalinize the urinewith doses of sodium bicarbonate which could be administered without dangerof producing severe metabolic alkalosis. It is particularly important notto flood the circulatory system with intravenous solutions in an attemptto induce diuresis, once oliguria or anuria have become established. Whenexcessive fluid is administered, the patients may die of pulmonary edemabefore fatal uremia develops.
That a recovery diuresis may develop in these cases is evidenced bytwo patients in this series in whom recovery diuresis had begun beforedeath; in one of them it was well developed.
CASES OF SPECIAL INTEREST IN THIS CHAPTER
Fatal
69 70 78 93 132
Nonfatal
56 73 99 124
CASES OF SPECIAL INTEREST IN CHAPTER IX
Nonfatal
13 27 29 37 44 54 60 71 72 81 87
104 109 112 125 130133 138 150
Fatal
9 12 22 24 25 26 31 41 47 49
52 55 65 66 74 80 85 8688
95 97 98 108 116 117 118 120
122 123 129 131 136 A-30
Crush Syndrome
69 70 78 93 132
