Editorial © 1990 S. Kargcr AG, Basel 0028-2766/90/0552-0097S2.75/0
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The Crush Syndrome Revisited (1940-1990) On S. Better Faculty of Medicine and Rappaport Institute, Technion, Israel Institute of Technology, and Rambam Hospital, Haifa. Israel
Key Words. Crush syndrome • Renal failure ■ Rhabdomyolysis
Major seismic catastrophes such as the one that oc curred on December 7, 1988, in Armenia are capable, within seconds, of killing as many people in peacetime as were lost in the entire Korean or the Vietnam wars. Such an enormous toll has also been projected for a possible future earthquake in urban areas of the Pacific rim [1].' In such extensive and overwhelming disasters, where com munications, access and vital public utilities have been disrupted, salvage and rescue work may achieve only limited results. However, in ‘point’ events such as the sudden, unexpected collapse of a populated building due to natural or industrial disasters or caused by intentional bombings, early intensive medical intervention may save a substantial proportion of survivors trapped unter the debris (241 people were trapped under the rubble of the US Marine barracks in Beirut on October 23,1983). Many ' In this context, the author wishes to point out that this paper has been submitted before the recent catastrophe in San Francisco.
of such victims are exposed to devastating, yet potentially preventable or reversible complications of the initial trauma. Chief among them are extensive damage to mus cles, hemodynamic shock, hyperkalemia and acute renal failure (the crush syndrome) [2-4], The question arises: what is the optimal aproach to, and the management of, patients with the crush syndrome and how should the medical profession prepare itself for future catastrophes involving persons trapped under fallen masonry? This review summarized lessons gained at this hospital in the early management of the crush injury [5, 6]. The patho physiology of the crush syndrome will be discussed only where relevant to clinical problems. The causal link between widespread damage to mus cle and acute kidney failure was already known during the first World War. It was, however, Bywaters and Beall [2] who, nearly 50 years ago, during the darkest days of the London blitz, gave the classic definitive description of the crush syndrome. In their hands, survivors with
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Abstract. This article reviews the local and systemic effects of crush injury. Within minutes to hours after extrication of survivors trapped under fallen masonry (and immediately following decompression of limbs), a massive volume of extracellular fluid is lost into the injured muscles, leading to circulatory failure. Solutes leaking out of damaged muscles cause a spectrum of metabolic disturbances. Chief among them are hyperkalemia and hypocal cemia which, synergistically, have a lethal cardiotoxic potential, particularly in hypotensive patients. Early volume replacement, preferably already started at the rescue site, may combat shock and correct the hyperkalemia. If urine flow is established, this regimen should be followed by a forced solute-alkaline diuresis for the prevention of myoglobinuric and uricosuric acute renal failure, which is a common and ominous late complication of crush injury. Preparation for future catastrophes occurring particularly in remote regions where an 'epidemic’ of crush syndrome may be forecast, should include the setting up of a radio communications network to coordinate rescue and salvage operations and the forwarding of intravenous fluid bags and lines to the disaster site. Also, it is advisable to prepare artificial kidney devices which do not require pumps and electricity and which utilize a low dialysate volume for emergency temporary use, until conventional definitive medical facilities and services have been reestablished.
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Table 1. Bidirectional How of solutes and water across skeletal muscle cell membrane in rhabdomyolysis Flow
Consequence
Table 2. Factors contributing to acute renal failure in the crush syndrome [8, 17, 18] Activation of volume-sensitive renal vasoconstrictor hormones; among them: angiotensin II, catecholamines and arginine vasopressin: these result in generalized renal vasoconstriction and mesangial contraction and compromise the filtration process Nephrotoxicity of myoglobinuria and uricosuria potentiated by aciduria and concentration of urine; these compounds damage the tubular epithelium and precipitate as tubular plugs____________ Acute increase in plasma phosphate x calcium product may suppress kidney function [24] _____________ Microthrombi in the glomerular tufts
massive crush injury, who were extricated from under the rubble of bombed buildings, suffered from shock. Hem odynamic stabilization did not prevent death from kid ney failure wihtin 10-14 days following rescue. Postmor tem examination demonstrated the presence of pigment casts predominantly in the distal tubuli of the kidney (‘lower nephron nephrosis’). Still during the war years, Bywaters et al. [3,4] went on to show that in experimental animals extensive muscle injury will lead to extreme hemoconcentration and hemodynamic shock. Viewed retrospectively, this hints to massive internal losses of extracellular fluid into the damaged muscles. In another set of experiments, Bywaters and Stead [4] incriminated myoglobin as the major, though not the exclusive, ne phrotoxic agent linking muscle damage to kidney failure. They showed that alkalinization of the urine will abolish the nephrotoxicity of myoglobinuria in animals. It is conceivable that this regimen will also protect the kidney
from damage due to increased filtered load of urate secondary to rhabdomyolysis and disintegration of mus cle cell nuclei. In the early fifties, Meroney et al. [7] demonstrated that in experimental traumatic rhabdomyolysis in the dog there was a massive influx of calcium from the extracellu lar compartment into the muscles. This was of sufficient magnitude to explain the hypocalcemia of these animals. Moreover, intravenous infusion of calcium failed to cor rect this hypocalcemia. They also showed that the da maged muscle contained more water and sodium chlo ride and less potassium than normal muscle. The subject was then taken up by Knöchel [8, 9] who, on the basis of observations on exertional and metabolic rhabdomyoly sis, suggested that in damaged muscle there was an inter ference with the normal function of sarcolemmal Na-KATPase. This resulted in a diminished extrusion of so dium from the sarcoplasm, which indirectly lowered the efflux of calcium from the cell, particularly when uremia set in. This allowed an increase in intracellular calcium which activated neutral proteases resulting in disruption of myofibrils. Thus, an increase in sarcoplasmic calcium is proposed to be the common final pathway triggering muscle damage in ischemic, traumatic, metabolic or toxic rhabdomyolysis. Similarly, an elevated calcium level in cells has been proposed by Cheung et al. [10] as initiating ischemic damage to the heart, brain and kidney. Yet, how mechanical pressure and immobilization of a limb cause rhabdomyolysis even without clear-cut arterial occlusion is still a mystery. Ischemia may undoubtedly cause muscle damage, and an arterial tourniquet to a limb has been used to produce rhabdomyolysis in experimental animals [3].
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Influx from extracellular compartment into muscle cells Water and NaCI Hypovolemia and hemodynamic shock, prerenal and later acute renal failure Calcium Hypocalcemia [22J, aggravation of hyperkalemic cardiotoxicity. increase in cystolicCa2+, activation _________________ _____________ of cytotoxic protease______________________________________________________________ Efflux from damaged muscle cells Potassium Hyperkalemia, cardiotoxicity aggravated by hypocalcemia and hypotension Purines from distintegration cell nuclei Increase urate load on the kidney and nephrotoxicity Phosphate Hyperphosphatemia (22], aggravation of hypocalcemia and metastatic calcification Latic and other organic acids (23] Metabolic acidosis and aciduria Myoglobin Nephrotoxicity, particularly on the background of oliguria, aciduria, uricosuria Thromboplastin [17] Disseminated intravascular coagulation with thrombi in the glomeruli Creatinine phosphokinase F.xireme elevation of serum levels (lO'-IO6 U/ml) Creatinine Occasional disproportionale rise in blood crealinine/BUN ratio
Yet, extensive rhabdomyolysis may occur in man in limbs where at least the main arterial blood supply is adequate for peripheral circulation and where distal arterial pulses are palpable. Also, the eventual apparently complete recovery of crushed muscles with full-blown rhabdomyo lysis in man, even after immobilization of up to 28 h under the rubble [5], suggests that total warm ischemia of the affected limb of that duration could not have oc curred in these cases. It therefore appears that sustained pressure on the muscles and immobilization by them selves, if prolonged for hours, may cause rhabdomyolysis perhaps triggered by increased influx of calcium into the cells. Indeed, in vitro experiments have shown that me chanical stretch will increase leakiness to calcium ions of the cell membrane in myocytes and in nerve cells [11,12], It is conceivable that a similar process in vivo may cause the intracellular concentration of calcium in muscle cells to rise, resulting in interference with mitochondrial func tion, energy production and membrane integrity. Under this scheme, the early causes of a pathologic influx of calcium into the cells of the affected muscles are different in the traumatic forms of rhabdomyolysis. The disruption of myocyte membrane integrity gives rise to a life-threat ening, bidirectional flux of solutes and water down their electrochemical gradient across the cell membrane (table 1, 2).
Water penetrates the injured muscle driven by a pres sure head that may exceed the mean arterial blood pres sure and at a rapid rate that may build up within minutes of the occurrence of trauma. This has been verified in man by direct intramuscular manometry in exertional myopathy [13]. The cause of this dangerous ‘intracompartmental hypertension' has not been adequately ex plained. It may be due to a disturbance of Starling forces across the sarcolemma membrane brought about by a decrease in the ionic pump extrusion capacity. Such a decrease may leave an unopposed cytosolic osmotic or oncotic activity of intracellular protein and phosphate or an increase in ‘idiogenic osmoles' due to the breakdown of glycogen or peptides into smaller molecules. When intramuscular pressure increases in muscle groups con fined within tight fibrous sheaths, as in the calf, it may exceed arteriolar perfusion pressure and obliterate the circulation to the affected region (muscle tamponade of the ‘compartmental syndrome’) [14,15]. Since the muscles are the largest organ system in the body, approaching 40% of body weight and containing approximately 75% of body potassium [16], the degree of redistribution of the biochemically incompatible fluids and solutes of the intracellular and extracellular com
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partments may reach the most extreme degree seen in clinical practice in salvageable patients. This has a devas tating effect on the volume and composition of the ex tracellular fluid (table 3). Clinical observations in injured man [5] and in experimental animals [3] with extensive muscle damage suggest that the entire extracellular fluid volume may penetrate into the injured muscles (‘third spacing’) within hours to days of injury. It is clear, there fore, that following extensive muscle damage only early aggressive intravenous volume replacement of the inter nally lost volume will prevent irreversible shock. Patients who suffered crush injury often present with flaccid paralysis and sensory loss not related to nerve distribution in the affected limbs. In widespread involve ment they may mimic patients with spiral injury. Neuro logic examination showing an intact anal sphincter and normal urinary bladder function may help to exclude the presence of an acute spinal cord lesion in paralyzed patients with rhabdomyolysis. Despite his excruciating situation, the victim, who has been trapped and immobi lized under fallen masonry, is somehow relatively pro tected from the systemic hemodynamic and metabolic consequences of the muscular lesion. Full extrication of the survivor and decompression of the limbs may, parad oxically, accelerate the onset of shock and hemoconcentration (reminiscent of the profound, adverse systemic hemodynamic effects occurring after the release of a prolonged limb tourniquet in experimental animals [3]). In the first hours after rescue, in victims with the crush syndrome, when blood urea nitrogen and blood creati nine are normal, one may already find hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, met abolic acidosis (table 3,4), hemoconcentration and, occa sionally, thrombocytopenia suggesting the onset of dif fuse intravascular coagulation. If intravenous volume replacement is inadequate or is delayed for more than several hours after extrication, acute renal failure will develop. The causes of this type of renal failure have been extensively reviewed [17,18] and are summarized in table 2. They include both vasomotor and nephrotoxic effects on the kidneys. Prevention of the complications of the crush syn drome dictates very early and vigorous treatment, di rected initially to sustaining the circulation. Replacement of the internal volume losses should start preferably at the site of the extrication of the trapped person. Immedi ately after a limb has been delivered from under the rubble, an intravenous line should be secured, and nor mal saline or lactated Ringer’s solution should be infused at 1.5 liters/h. It may take another 45-60 min and, rarely,
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Tabic 3. Clinical details and outcome in 15 patients with extensive traumatic rhabdomyolysis following trapping under collapsed buildings [5, 6] Year of occurence
1979 1982
Patients in group
Mean duration of trapping
Delay in intravenous infusion
n
h
h
7 7 1
12.0 12.3 5.5
6-10 0 24
Extensive TR
+ + -f
ARF
7 0 1
Fasciotomy
Positive Huid balance, kg/60h
n
mean range
5 0 0
12.5 0.65-18.3
Delay in intravenous infusion = Time elapsed from extrication from under the rubble to institution of intravenous treatment; TR = traumatic rhabdomyolysis; ARF = acute renal failure. Fasciotomy implies 4 compartment fasciotomies of the lower leg. The last column on the right indicates positive fluid balance at the end of the initial 60-hour period of treatment.
Anion gap, mEq/l K, mEq/l P04, mg/dl Ca, mg/dl
Mean
Range
15.0 6.2 8.2 8.6
9.0-22.5 4.5-8.3 6.9-10.0 7.6-10.1
All patients had gross myoglobinuria; all had blood creatine phosphokinase levels above 30,000 IU/1.
up to several hours, before the entire body may be care fully freed and the victim be evacuated to a hospital. Once the systemic hemodynamics have been stabilized and the presence of urine flow has been confirmed, further steps for the prophylaxis against hyperkalemia and acute renal failure should be undertaken. These consist of the induction of mannitol-alkaline diuresis [5, 19]. The suggested regimen is based on an infusion of hypotonic NaCl solution (NaCl 70 mEq/1 in 5% dextrose, NaHCOi 50 mEq/l) to which approximately 120 g/day mannitol are added as a 20% solution. This is infused into a young adult of 75 kg body weight at a rate of approxi mately 12 liters/day forcing a diuresis of approximately 8 liters/day with urinary pH above 6.5 until biochemical tags of myoglobinuria disappear (usually by the third day). This regimen will correct the hyperkalemia, and we feel that it is capable of preventing the occurrence of acute renal failure in the crush syndrome. The use of loop diuretics is not necessary for the successful prevention of acute renal failure in traumatic rhabdomyolysis. Moreover, they have the theoretical dis
advantage of acidifying the urine in circumstances where urine alkalinity is beneficial. On the other hand, when urinary flow is established, the use of mannitol is recom mended. Mannitol infusion may also have some general ized beneficial effects, protecting against cell swelling [ 20].
The use of acetazolamide may be indicated when arterial blood pH rises above 7.45, because it corrects overt metabolic alkalosis during bicarbonate infusion and because it alkalinizes the urine. The theoretical danger of mild metabolic alkalosis with its tendency to enhance metastatic calcification is outweighed by its salutary hypokalemic action and protection of the kidney from the nephrotoxicity of myoglobin and uric acid. Unless there is the danger of hyperkalemic arrhythmia, infusion of calcium is not indicated [9]. Moreover, this measure will correct the hypocalcemia only partly and temporarily unless calcium is constantly infused. Most of the infused calcium may end in the injured muscles and aggravate metastatic calcification [7], It should be remembered that the occurrence of acute renal failure following rhabdomyolysis sharply de creases the survival ot the pateints [21], even in this era of hemodialysis. Efforts to prevent this complication are, therefore, mandatory. The optimal approach to the local injury of the crushed limb is still a matter of hot debate. We feel that the management of the crushed limb should be conserva tive, particularly if the injury is a closed one. The skin has an extraordinary capacity to withstand pressure, and even when bruised over crushed limbs it may still serve as a barrier against infection [6]. One should resist the urge to surgically explore limbs with traumatic rhabdomyolysis, unless there is an urgent overriding reason to do so. Such exploration (i.e. for the
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Table 4. Blood chemistries 2 h after extrication of 7 patients in the 1982 group, described in table 3
purpose of fasciotomy) may convert a closed injury into an open one with a potentially disastrous outcome due to uncontrollable infection in necrotic muscles. The exci sion of noninfected dead muscle is not essential and may delay healing. When the orthopedic surgeon is compelled to perform fasciotomy to relieve intracompartmental pressure as documented by direct manometry, he should bear in mind that intense bleeding is not a proof of the viability of a muscle. Dead muscle may also bleed profusely. There fore, demarcation between dead and live muscle may be made by its response to mechanical or electrical stimula tion [6]. Simple and reliable manometers for the monitoring of intracompartmental pressure are now freely available. Using them as an objective quantitative adjunct to aid in assessing the need for fasciotomy in the compartment syndrome will help to resolve the present vexing con troversy on this topic. The experienced San Diego School recommends that fasciotomy should be performed when intracompartmental pressure exceeds the presumed ar teriolar perfusion pressure of 40 mm Hg or 30 mm Hg lower than systemic diastolic arterial pressure [25], and sustained for more than 8 h [26].
Experience with the Crush Syndrome at the Rambam Hospital The Rambam Hospital is the main evacuation center for casualties from the catchment area of the Lebanese and Syrian theaters. Our close proximity to the front (25 min flying time by helicopter from Beirut, 12 min from Tyre, Lebanon) enabled us to see casualties sometimes immediately after injury. In the last 15 years we have been admitting sporadic patients with traumatic rhabdomyolysis at a rate of several per year. Of particular clinical interest were two groups of pa tients (one in 1979 and the other in 1982) who were brought to us with extensive traumatic rhabdomyolysis as a result of collapse of buildings in Lebanon (previously reported from this institution) [5, 6]. Their case histories are reviewed here briefly (table 3, 4). The two groups together consisted of 15 male patients who had roughly the same degree of extensive crush injury to the lower limbs following a mean trapping time of approximately 12 h. The 7 patients of the 1979 group received the first intravenous infusion after a delay of at least 6 h after extrication. This unfortunate delay was caused by over riding front line obstacles of access. Every one of this
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1979 group developed acute renal failure within the first day of rescue despite adequate, though postponed, vol ume replacement (approx. II i.v. liters/day of saline until central venous pressure began to rise). The outcome following early access to treatment of the other 7 patients, of the 1982 group, offers a striking contrast to the 1979 group. In the 1982 group, institution of intravenous treat ment was started promptly at the site of the disaster, even before the extrication process had been completed. Within less than 2 h of their release they were evacuated to our hospital, where treatment was continued with institution of forced solute-alkaline diuresis. Despite clear-cut clinical and laboratory evidence of extensive rhabdomyolysis, none of these men developed acute re nal failure or even a transitory azotemia. Their blood BUN and creatinine were normal throughout the course of their hospitalization. An 8 patient of this 1982 group may be tentatively viewed as an untreated, unintentional 'control' case. He was buried under the rubble for 5.5 h. Following release he was accidently separated from his group. He was later rerouted to us and reached our team after a delay of 24 h, during which he received only 2 liters of fluids intravenously. By that time he already had an established acute renal failure. He required intensive hemodialysis treatment of I month and eventually rec overed. It thus appears conspicuous that the only casu alty in the 1982 group to develop acute renal failure was the one who did not have the chance to receive an early adequate volume replacement and solute-alkaline diure sis. It is difficult to draw firm conclusions from our un controlled retrospective observations. Yet, several as sumptions may cautiously be made in view of the appar ently favorable response to treatment of our 1982 group: (a) Hyperkalemia, hyperphosphatemia, hypocal cemia and metabolic acidosis appear within hours of the rescue of casualties with traumatic rhabdomyolysis (table 4). These mineral and electrolyte changes appear before renal failure sets in. (b) Very early volume replacement followed by mas sive (12 litres/day i.v.) forced solute-alkaline diuresis may protect the kidney against acute renal failure in traumatic rhabdomyolysis. A delay of at least 6 h in starting intravenous treatment in similar patients may lead to the occurrence of acute renal failure. It is quite possible that some components of the above regimen are redundant (i.e. a lesser diuresis may be adequate to pro tect the kidney and obviate the need for bladder catheter ization). At present, we cannot identify superfluous items in our proposed plan for prophylaxis against acute renal
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Crush Syndrome
failure in the crush syndrome. We feel that this regimen is extremely useful, simple and safe. (c) Our favorable results, as enumerated in table 3, were obtained without resorting to the use of loop diuret ics or to infusion of calcium salts. These measures, there fore, do not appear to be essential for the prophylaxis of acute renal failure in rhabdomyolysis. Correction of hy povolemia and of acidosis and securing diuresis, by themselves, will correct even severe degrees of hyperkal emia in the crush syndrome. (d) In the patients of 1982 with the crush syndrome, the average positive water fluid balance was 12.1 liters [range 0.65-18.3 (!) liters] in the first 60 h of treatment. This positive balance was due to sequestration of fluid in the injured muscles (‘third spacing’) and occurred in the face of the administration of 120 g/day i.v. of mannitol. It appears that such an enormous positive balance is well tolerated in a previously healthy young adult and is an acceptable complication of treatment. (e) In the 1979 group, lower leg fasciotomies were performed in 5 of 7 patients with traumatic rhabdomyoly sis. At that time, the indication had been to perform fasciotomy when the crushed limb became grossly swollen and its muscles were tense to palpation. In retro spect, none of the 1979 patients benefitted from these fasciotomies. Moreover, fasciotomy could have led to loss of limbs and endangered the lives of the patients. Therefore, in the 8 patients of the 1982 group, fasciotomy was avoided, and none of the patients in this group developed compartment syndrome. At present, we re serve early fasciotomy to patients whose compartment syndrome is due primarily to a clear-cut interruption of arterial circulation. When assessing future needs for the allocation of scarce manpower, time and logistics for rescue and sal vage operations for subjects trapped under ruins, the following extrapolations may be made from our experi ence in Tyre, Lebanon 1982 [5]. The sudden total leveling of an 8-story concrete building killed, within minutes, approximately 80% of about 100 people trapped there. The fatality rate was due mainly to trauma to the head and trunk or to immobilization of the chest and asphyxia tion. Approximately 20% survived this catastrophe, of whom 10% of the total emerged unscathed. Most of the other 10% suffered from widespread traumatic rhabdom yolysis of the limbs. Thus, the ratio of wounded/killed subjects of approxi mately 1:5, as a result of a car bomb explosion or the collapse of a building, is reversed as compared with this ratio of 6:1 in surface infantry warfare.
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An intensive search, racing against time, for survivors should be continued for at least 5 days after the beginning of a disaster which buried people alive. A successful ultimate outcome occurred in 2 of our 1982 patients with widespread rhabdomyolysis who were trapped for 24 and 28 h, respectively. An elderly woman who was trapped for 5 days under the rubble but who was not wound ed was saved by the Israeli team to Armenia in Decem ber 1988. Experience from the San Fernando/Sylmar earth quake in California on February 9, 1971 [1], showed that disruption of communications was a key obstacle in the deployment of rescue, salvage and relief operations. Each of the four hospitals that were then seriously da maged by that temblor began discharging and evacuating patients, unaware that its neighboring hospitals had also been destroyed. The community emergency response could, therefore, be coordinated and mounted only with a considerable delay. It thus appears that in a future disaster first priority should be given to the establishment of an independently powered shortwave communication network. Second, access should be provided to rescue personnel and heavy equipment (including water supply, electrical generators and lighting facility). Large quanti ties of intravenous fluid bags and their lines should be forwarded for ready use at the very site of the excavation and rescue operation. Preparations should be made to utilize continuous arterial-venous hemodialysis using bicarbonate solution. This method theoretically allows hemodialysis operation with only 12 liters of water/12-hour period, using dispos ables and obviating the need for delivery systems, pumps and electrical power [1], This method could be used in disasters in a remote area of the globe for patients with the crush syndrome complicated by acute renal failure. Also, this system could serve as a temporary stoopgap measure to save conventional chronic hemodialysis pa tients deprived of access to their dialysis center by the disaster. Indeed, this method has been used to advantage in Armenia following the 1988 earthquake [27]. Where possible in this catastrophe, hemodialysis was utilizing either conventional dialyzers or the Redy/sorbent [28] dialyzer, which requires only several liters of dialysate fluid per dialysis. From the scant data that are presently available in the literature [29-32] about medical support for victims of the crush syndrome in Armenia: it appears that most Western European and USA teams arrived on the scene 1week or later after the earthquake, too late for the institution of any prophylactic treatment for the pre vention of acute renal failure.
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Crush Syndrome
The author is indebted tor the cooperation of the following physicians at the Rambam Hospital who were responsible for the management of the patients with the crush syndrome. They are, in alphabetical order: G. Bar-Joseph, MD; S. Bursztein, MD; M. Michaelson, MD: N.D. Reis, MB. BS, FRCS, and U. Taitelman, MD [5, 6], After submission of this manuscript, details of dialysis treatment for the victims of the Armenian earthquake were published [27], There were 600 patients with acute renal failure following crush injury who required hemodialysis treatment. The American team helped in this effort by flying 36 tons of dialysis equipment and its accessories to Armenia. It appears, however, that the overwhelming magnitude of the catastrophe hampered early prophylactic treat ment against acute renal failure in survivors of this earthquake. The author is grateful to Ms. Ruby Snyder Weiss for secretarial assistance. Supported in part by Michael and Helen Schaffer Military Research Center.
References 1 Duarte RG: Seismic risks in nephrology. Dialysis Transplant 1988;17:530 546. 2 Bywaters F.GL. Beall D: Crush injuries with impairment of renal function. Br Med J 1941 :i:427-432. 3 Bywaters EGL, Popjak G: Experimental crushing injury. Surg Gynecol Obstet 1942:75:612. 4 Bywaters EGL, Stead JK: The production of renal failure fol lowing injection of solutions containing myohaemoglobin. Q J Exp Physiol 1944:33:53. 5 Ron D, Taitelman U, Michaelson M, et al: Prevention of acute renal failure in traumatic rhabdomyolysis. Arch Intern Med 1984:144:277-280. 6 Reis ND. Michaelson M : Crush injury to the lower limbs..I Bone Joint Surg 1986:68 A : 414-418. 7 Meroney WH. Arney GK. Segar WE, et al: The acute calcifica tion of traumatized muscle with particular reference to acute post-traumatic renal insufficiency. J Clin Invest 1957:36: 825-832. 8 Knöchel JP: Rhabdomyolysis and myoglobinuria: in Suki WN, Eknoyan G (eds): The Kidney in Systemic Disease, ed 2. New York, Wiley & Sons, 1981, pp 263 284. 9 Knöchel P: Serum calcium derangement in rhabdomyolysis (editorial). N Engl J Med 1981:305:161-162. 10 Cheung JY, Bonventre JV, Malis CD, et al: Calcium and is chemic injury. N Engl J Med 1982:314:1670 1676. 11 Guharay F, Sachs F: Stretch activated single ion channels cur rents in tissue cultured embryonic chick skeletal muscle. J Phy siol (Lond) 1984;352:685-701. 12 Christensen O: Mediation of cell volume regulation by Ca++ influx through stretch activated channels. Nature 1987;330: 66 - 68.
13 Awbrey BJ. Sienkiewicz PS. Mankin HJ: Chronic exercise-in duced compartment pressure elevation measured with a minia turized fluid pressure monitor. A laboratory and clinical study. Am J Sports Med 1988:16:610-615.
14 Matsen FA: Compartmental syndrome. A unified concept. Clin Orthoped 1975:113:8-14. 15 Whitesides TE, Haney TC, Murimoto K, et al: Tissue pressure measurements as a determinant for the need of fasciotomy. Clin Orthoped 1975:113:43-51. 16 De Fronzo RA. Bia MB: Extrarenal potassium homeostasis: in Seldin DW, Giebisch G (eds): The Kidney: Physiology and Pathophysiology. New York. Raven Press, 1985, pp 1179 1206. 17 Honda N : Acute renal failure and rhabdomyolysis. Nephrology forum Kidney Int 1988:23:888-898. 18 Gabow PA, Kaehny WD, Kelleher SP: The spectrum of rhab domyolysis. Medicine 1982;61:141-152. 19 Eneas JF, Schonfeld PY. Humphreys MFLTheeffect of infusion of mannitol-sodium bicarbonate on the clinical course of myog lobinuria. Arch Intern Med 1979;139:801-805. 20 Powell JW, DiBona DR. Flores J. et al: Effects of hyperosmotic mannitol in reducing ischemic cell swelling and minizing myo cardial necrosis. Circulation 1976;53(suppl I): 145-149. 21 Ward MM : Factors predictive of acute renal failure in rhabdom yolysis. Arch Intern Med 1988:148:1553 1557. 22 Llach F, Felsonfeld AJ, Hausier MR: The pathophysiology of altered calcium metabolism in rhabdomyolysis induced acute renal failure. N Engl J Med 1981:305:117 123. 23 McCarron D, Elliot WC. Rose JS, et al: Severe mixed metabolic acidosis secondary to rhabdomyolysis. Am J Med 1979:67: 905-910. 24 Boles JM. Dutel JL, Briere J, et al: Acute renal failure caused by extreme hyperphosphatemia after chemotherapy of an acute lymphoblastic leukemia. Cancer 1984;53:2425-2429. 25 Owen CA, Mubarak SJ, Hargens AR, et al: Intramuscular pres sures with limb muscle compartment syndrome. N Engl J Med 1979:300:1170-1172. 26 Hargens AR. Akeson SR. Garfin RH, et al: Compartment syn dromes, chapter 7; in Denton J (ed): Practice of Surgery. Philad elphia, Lippincott, 1984, vol I, pp 1-68. 27 Collins AJ: Renal dialysis treatment for victims of the Armenian earthquake. N Engl J Med 1989:320:1291-1292. 28 Mathias T, Sansom A: Successful haemodialysis of crush syn drome victims - the Armenian experience (abstract). 18th Ann Coni' EDTNA-Eur Renal Care Assoc, 1989, p 18. 29 Van Waeleghem JP. Verschoot M. Dewets JM. et al: Nephrology aid after seismic catastrophe in Armenia (abstract). 18th Ann Conf EDTNA-Eur Renal Care Assoc, 1989. p 28. 30 Van Waeleghem JP, Veenstra K, Egiazarian A, et al: Zorab, an earthquake victim with acute renal failure in Armenia (abstract). I8th Ann Conf EDTNA-Eur Renal Care Assoc. 1989. p 28. 31 Better OS, Zinman C, Reis DN, et al:Hypertonic mannitol for compartment syndrome. J Bone Joint Surg (USA), submitted. 32 Better OS, Stein JH: Crush syndrome. New EnglJ Med, in press.
Accepted: October9,1989 Prof. O.S. Better, M D Rambam Hospital 35254 Haifa (Israel)
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Acknowledgements
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Nephron 1990:55:97 103
The Crush Syndrome Revisited (1940-1990) On S. Better Faculty of Medicine and Rappaport Institute, Technion, Israel Institute of Technology, and Rambam Hospital, Haifa. Israel
Key Words. Crush syndrome • Renal failure ■ Rhabdomyolysis
Major seismic catastrophes such as the one that oc curred on December 7, 1988, in Armenia are capable, within seconds, of killing as many people in peacetime as were lost in the entire Korean or the Vietnam wars. Such an enormous toll has also been projected for a possible future earthquake in urban areas of the Pacific rim [1].' In such extensive and overwhelming disasters, where com munications, access and vital public utilities have been disrupted, salvage and rescue work may achieve only limited results. However, in ‘point’ events such as the sudden, unexpected collapse of a populated building due to natural or industrial disasters or caused by intentional bombings, early intensive medical intervention may save a substantial proportion of survivors trapped unter the debris (241 people were trapped under the rubble of the US Marine barracks in Beirut on October 23,1983). Many ' In this context, the author wishes to point out that this paper has been submitted before the recent catastrophe in San Francisco.
of such victims are exposed to devastating, yet potentially preventable or reversible complications of the initial trauma. Chief among them are extensive damage to mus cles, hemodynamic shock, hyperkalemia and acute renal failure (the crush syndrome) [2-4], The question arises: what is the optimal aproach to, and the management of, patients with the crush syndrome and how should the medical profession prepare itself for future catastrophes involving persons trapped under fallen masonry? This review summarized lessons gained at this hospital in the early management of the crush injury [5, 6]. The patho physiology of the crush syndrome will be discussed only where relevant to clinical problems. The causal link between widespread damage to mus cle and acute kidney failure was already known during the first World War. It was, however, Bywaters and Beall [2] who, nearly 50 years ago, during the darkest days of the London blitz, gave the classic definitive description of the crush syndrome. In their hands, survivors with
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Abstract. This article reviews the local and systemic effects of crush injury. Within minutes to hours after extrication of survivors trapped under fallen masonry (and immediately following decompression of limbs), a massive volume of extracellular fluid is lost into the injured muscles, leading to circulatory failure. Solutes leaking out of damaged muscles cause a spectrum of metabolic disturbances. Chief among them are hyperkalemia and hypocal cemia which, synergistically, have a lethal cardiotoxic potential, particularly in hypotensive patients. Early volume replacement, preferably already started at the rescue site, may combat shock and correct the hyperkalemia. If urine flow is established, this regimen should be followed by a forced solute-alkaline diuresis for the prevention of myoglobinuric and uricosuric acute renal failure, which is a common and ominous late complication of crush injury. Preparation for future catastrophes occurring particularly in remote regions where an 'epidemic’ of crush syndrome may be forecast, should include the setting up of a radio communications network to coordinate rescue and salvage operations and the forwarding of intravenous fluid bags and lines to the disaster site. Also, it is advisable to prepare artificial kidney devices which do not require pumps and electricity and which utilize a low dialysate volume for emergency temporary use, until conventional definitive medical facilities and services have been reestablished.
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Table 1. Bidirectional How of solutes and water across skeletal muscle cell membrane in rhabdomyolysis Flow
Consequence
Table 2. Factors contributing to acute renal failure in the crush syndrome [8, 17, 18] Activation of volume-sensitive renal vasoconstrictor hormones; among them: angiotensin II, catecholamines and arginine vasopressin: these result in generalized renal vasoconstriction and mesangial contraction and compromise the filtration process Nephrotoxicity of myoglobinuria and uricosuria potentiated by aciduria and concentration of urine; these compounds damage the tubular epithelium and precipitate as tubular plugs____________ Acute increase in plasma phosphate x calcium product may suppress kidney function [24] _____________ Microthrombi in the glomerular tufts
massive crush injury, who were extricated from under the rubble of bombed buildings, suffered from shock. Hem odynamic stabilization did not prevent death from kid ney failure wihtin 10-14 days following rescue. Postmor tem examination demonstrated the presence of pigment casts predominantly in the distal tubuli of the kidney (‘lower nephron nephrosis’). Still during the war years, Bywaters et al. [3,4] went on to show that in experimental animals extensive muscle injury will lead to extreme hemoconcentration and hemodynamic shock. Viewed retrospectively, this hints to massive internal losses of extracellular fluid into the damaged muscles. In another set of experiments, Bywaters and Stead [4] incriminated myoglobin as the major, though not the exclusive, ne phrotoxic agent linking muscle damage to kidney failure. They showed that alkalinization of the urine will abolish the nephrotoxicity of myoglobinuria in animals. It is conceivable that this regimen will also protect the kidney
from damage due to increased filtered load of urate secondary to rhabdomyolysis and disintegration of mus cle cell nuclei. In the early fifties, Meroney et al. [7] demonstrated that in experimental traumatic rhabdomyolysis in the dog there was a massive influx of calcium from the extracellu lar compartment into the muscles. This was of sufficient magnitude to explain the hypocalcemia of these animals. Moreover, intravenous infusion of calcium failed to cor rect this hypocalcemia. They also showed that the da maged muscle contained more water and sodium chlo ride and less potassium than normal muscle. The subject was then taken up by Knöchel [8, 9] who, on the basis of observations on exertional and metabolic rhabdomyoly sis, suggested that in damaged muscle there was an inter ference with the normal function of sarcolemmal Na-KATPase. This resulted in a diminished extrusion of so dium from the sarcoplasm, which indirectly lowered the efflux of calcium from the cell, particularly when uremia set in. This allowed an increase in intracellular calcium which activated neutral proteases resulting in disruption of myofibrils. Thus, an increase in sarcoplasmic calcium is proposed to be the common final pathway triggering muscle damage in ischemic, traumatic, metabolic or toxic rhabdomyolysis. Similarly, an elevated calcium level in cells has been proposed by Cheung et al. [10] as initiating ischemic damage to the heart, brain and kidney. Yet, how mechanical pressure and immobilization of a limb cause rhabdomyolysis even without clear-cut arterial occlusion is still a mystery. Ischemia may undoubtedly cause muscle damage, and an arterial tourniquet to a limb has been used to produce rhabdomyolysis in experimental animals [3].
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Influx from extracellular compartment into muscle cells Water and NaCI Hypovolemia and hemodynamic shock, prerenal and later acute renal failure Calcium Hypocalcemia [22J, aggravation of hyperkalemic cardiotoxicity. increase in cystolicCa2+, activation _________________ _____________ of cytotoxic protease______________________________________________________________ Efflux from damaged muscle cells Potassium Hyperkalemia, cardiotoxicity aggravated by hypocalcemia and hypotension Purines from distintegration cell nuclei Increase urate load on the kidney and nephrotoxicity Phosphate Hyperphosphatemia (22], aggravation of hypocalcemia and metastatic calcification Latic and other organic acids (23] Metabolic acidosis and aciduria Myoglobin Nephrotoxicity, particularly on the background of oliguria, aciduria, uricosuria Thromboplastin [17] Disseminated intravascular coagulation with thrombi in the glomeruli Creatinine phosphokinase F.xireme elevation of serum levels (lO'-IO6 U/ml) Creatinine Occasional disproportionale rise in blood crealinine/BUN ratio
Yet, extensive rhabdomyolysis may occur in man in limbs where at least the main arterial blood supply is adequate for peripheral circulation and where distal arterial pulses are palpable. Also, the eventual apparently complete recovery of crushed muscles with full-blown rhabdomyo lysis in man, even after immobilization of up to 28 h under the rubble [5], suggests that total warm ischemia of the affected limb of that duration could not have oc curred in these cases. It therefore appears that sustained pressure on the muscles and immobilization by them selves, if prolonged for hours, may cause rhabdomyolysis perhaps triggered by increased influx of calcium into the cells. Indeed, in vitro experiments have shown that me chanical stretch will increase leakiness to calcium ions of the cell membrane in myocytes and in nerve cells [11,12], It is conceivable that a similar process in vivo may cause the intracellular concentration of calcium in muscle cells to rise, resulting in interference with mitochondrial func tion, energy production and membrane integrity. Under this scheme, the early causes of a pathologic influx of calcium into the cells of the affected muscles are different in the traumatic forms of rhabdomyolysis. The disruption of myocyte membrane integrity gives rise to a life-threat ening, bidirectional flux of solutes and water down their electrochemical gradient across the cell membrane (table 1, 2).
Water penetrates the injured muscle driven by a pres sure head that may exceed the mean arterial blood pres sure and at a rapid rate that may build up within minutes of the occurrence of trauma. This has been verified in man by direct intramuscular manometry in exertional myopathy [13]. The cause of this dangerous ‘intracompartmental hypertension' has not been adequately ex plained. It may be due to a disturbance of Starling forces across the sarcolemma membrane brought about by a decrease in the ionic pump extrusion capacity. Such a decrease may leave an unopposed cytosolic osmotic or oncotic activity of intracellular protein and phosphate or an increase in ‘idiogenic osmoles' due to the breakdown of glycogen or peptides into smaller molecules. When intramuscular pressure increases in muscle groups con fined within tight fibrous sheaths, as in the calf, it may exceed arteriolar perfusion pressure and obliterate the circulation to the affected region (muscle tamponade of the ‘compartmental syndrome’) [14,15]. Since the muscles are the largest organ system in the body, approaching 40% of body weight and containing approximately 75% of body potassium [16], the degree of redistribution of the biochemically incompatible fluids and solutes of the intracellular and extracellular com
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partments may reach the most extreme degree seen in clinical practice in salvageable patients. This has a devas tating effect on the volume and composition of the ex tracellular fluid (table 3). Clinical observations in injured man [5] and in experimental animals [3] with extensive muscle damage suggest that the entire extracellular fluid volume may penetrate into the injured muscles (‘third spacing’) within hours to days of injury. It is clear, there fore, that following extensive muscle damage only early aggressive intravenous volume replacement of the inter nally lost volume will prevent irreversible shock. Patients who suffered crush injury often present with flaccid paralysis and sensory loss not related to nerve distribution in the affected limbs. In widespread involve ment they may mimic patients with spiral injury. Neuro logic examination showing an intact anal sphincter and normal urinary bladder function may help to exclude the presence of an acute spinal cord lesion in paralyzed patients with rhabdomyolysis. Despite his excruciating situation, the victim, who has been trapped and immobi lized under fallen masonry, is somehow relatively pro tected from the systemic hemodynamic and metabolic consequences of the muscular lesion. Full extrication of the survivor and decompression of the limbs may, parad oxically, accelerate the onset of shock and hemoconcentration (reminiscent of the profound, adverse systemic hemodynamic effects occurring after the release of a prolonged limb tourniquet in experimental animals [3]). In the first hours after rescue, in victims with the crush syndrome, when blood urea nitrogen and blood creati nine are normal, one may already find hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, met abolic acidosis (table 3,4), hemoconcentration and, occa sionally, thrombocytopenia suggesting the onset of dif fuse intravascular coagulation. If intravenous volume replacement is inadequate or is delayed for more than several hours after extrication, acute renal failure will develop. The causes of this type of renal failure have been extensively reviewed [17,18] and are summarized in table 2. They include both vasomotor and nephrotoxic effects on the kidneys. Prevention of the complications of the crush syn drome dictates very early and vigorous treatment, di rected initially to sustaining the circulation. Replacement of the internal volume losses should start preferably at the site of the extrication of the trapped person. Immedi ately after a limb has been delivered from under the rubble, an intravenous line should be secured, and nor mal saline or lactated Ringer’s solution should be infused at 1.5 liters/h. It may take another 45-60 min and, rarely,
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Tabic 3. Clinical details and outcome in 15 patients with extensive traumatic rhabdomyolysis following trapping under collapsed buildings [5, 6] Year of occurence
1979 1982
Patients in group
Mean duration of trapping
Delay in intravenous infusion
n
h
h
7 7 1
12.0 12.3 5.5
6-10 0 24
Extensive TR
+ + -f
ARF
7 0 1
Fasciotomy
Positive Huid balance, kg/60h
n
mean range
5 0 0
12.5 0.65-18.3
Delay in intravenous infusion = Time elapsed from extrication from under the rubble to institution of intravenous treatment; TR = traumatic rhabdomyolysis; ARF = acute renal failure. Fasciotomy implies 4 compartment fasciotomies of the lower leg. The last column on the right indicates positive fluid balance at the end of the initial 60-hour period of treatment.
Anion gap, mEq/l K, mEq/l P04, mg/dl Ca, mg/dl
Mean
Range
15.0 6.2 8.2 8.6
9.0-22.5 4.5-8.3 6.9-10.0 7.6-10.1
All patients had gross myoglobinuria; all had blood creatine phosphokinase levels above 30,000 IU/1.
up to several hours, before the entire body may be care fully freed and the victim be evacuated to a hospital. Once the systemic hemodynamics have been stabilized and the presence of urine flow has been confirmed, further steps for the prophylaxis against hyperkalemia and acute renal failure should be undertaken. These consist of the induction of mannitol-alkaline diuresis [5, 19]. The suggested regimen is based on an infusion of hypotonic NaCl solution (NaCl 70 mEq/1 in 5% dextrose, NaHCOi 50 mEq/l) to which approximately 120 g/day mannitol are added as a 20% solution. This is infused into a young adult of 75 kg body weight at a rate of approxi mately 12 liters/day forcing a diuresis of approximately 8 liters/day with urinary pH above 6.5 until biochemical tags of myoglobinuria disappear (usually by the third day). This regimen will correct the hyperkalemia, and we feel that it is capable of preventing the occurrence of acute renal failure in the crush syndrome. The use of loop diuretics is not necessary for the successful prevention of acute renal failure in traumatic rhabdomyolysis. Moreover, they have the theoretical dis
advantage of acidifying the urine in circumstances where urine alkalinity is beneficial. On the other hand, when urinary flow is established, the use of mannitol is recom mended. Mannitol infusion may also have some general ized beneficial effects, protecting against cell swelling [ 20].
The use of acetazolamide may be indicated when arterial blood pH rises above 7.45, because it corrects overt metabolic alkalosis during bicarbonate infusion and because it alkalinizes the urine. The theoretical danger of mild metabolic alkalosis with its tendency to enhance metastatic calcification is outweighed by its salutary hypokalemic action and protection of the kidney from the nephrotoxicity of myoglobin and uric acid. Unless there is the danger of hyperkalemic arrhythmia, infusion of calcium is not indicated [9]. Moreover, this measure will correct the hypocalcemia only partly and temporarily unless calcium is constantly infused. Most of the infused calcium may end in the injured muscles and aggravate metastatic calcification [7], It should be remembered that the occurrence of acute renal failure following rhabdomyolysis sharply de creases the survival ot the pateints [21], even in this era of hemodialysis. Efforts to prevent this complication are, therefore, mandatory. The optimal approach to the local injury of the crushed limb is still a matter of hot debate. We feel that the management of the crushed limb should be conserva tive, particularly if the injury is a closed one. The skin has an extraordinary capacity to withstand pressure, and even when bruised over crushed limbs it may still serve as a barrier against infection [6]. One should resist the urge to surgically explore limbs with traumatic rhabdomyolysis, unless there is an urgent overriding reason to do so. Such exploration (i.e. for the
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Table 4. Blood chemistries 2 h after extrication of 7 patients in the 1982 group, described in table 3
purpose of fasciotomy) may convert a closed injury into an open one with a potentially disastrous outcome due to uncontrollable infection in necrotic muscles. The exci sion of noninfected dead muscle is not essential and may delay healing. When the orthopedic surgeon is compelled to perform fasciotomy to relieve intracompartmental pressure as documented by direct manometry, he should bear in mind that intense bleeding is not a proof of the viability of a muscle. Dead muscle may also bleed profusely. There fore, demarcation between dead and live muscle may be made by its response to mechanical or electrical stimula tion [6]. Simple and reliable manometers for the monitoring of intracompartmental pressure are now freely available. Using them as an objective quantitative adjunct to aid in assessing the need for fasciotomy in the compartment syndrome will help to resolve the present vexing con troversy on this topic. The experienced San Diego School recommends that fasciotomy should be performed when intracompartmental pressure exceeds the presumed ar teriolar perfusion pressure of 40 mm Hg or 30 mm Hg lower than systemic diastolic arterial pressure [25], and sustained for more than 8 h [26].
Experience with the Crush Syndrome at the Rambam Hospital The Rambam Hospital is the main evacuation center for casualties from the catchment area of the Lebanese and Syrian theaters. Our close proximity to the front (25 min flying time by helicopter from Beirut, 12 min from Tyre, Lebanon) enabled us to see casualties sometimes immediately after injury. In the last 15 years we have been admitting sporadic patients with traumatic rhabdomyolysis at a rate of several per year. Of particular clinical interest were two groups of pa tients (one in 1979 and the other in 1982) who were brought to us with extensive traumatic rhabdomyolysis as a result of collapse of buildings in Lebanon (previously reported from this institution) [5, 6]. Their case histories are reviewed here briefly (table 3, 4). The two groups together consisted of 15 male patients who had roughly the same degree of extensive crush injury to the lower limbs following a mean trapping time of approximately 12 h. The 7 patients of the 1979 group received the first intravenous infusion after a delay of at least 6 h after extrication. This unfortunate delay was caused by over riding front line obstacles of access. Every one of this
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1979 group developed acute renal failure within the first day of rescue despite adequate, though postponed, vol ume replacement (approx. II i.v. liters/day of saline until central venous pressure began to rise). The outcome following early access to treatment of the other 7 patients, of the 1982 group, offers a striking contrast to the 1979 group. In the 1982 group, institution of intravenous treat ment was started promptly at the site of the disaster, even before the extrication process had been completed. Within less than 2 h of their release they were evacuated to our hospital, where treatment was continued with institution of forced solute-alkaline diuresis. Despite clear-cut clinical and laboratory evidence of extensive rhabdomyolysis, none of these men developed acute re nal failure or even a transitory azotemia. Their blood BUN and creatinine were normal throughout the course of their hospitalization. An 8 patient of this 1982 group may be tentatively viewed as an untreated, unintentional 'control' case. He was buried under the rubble for 5.5 h. Following release he was accidently separated from his group. He was later rerouted to us and reached our team after a delay of 24 h, during which he received only 2 liters of fluids intravenously. By that time he already had an established acute renal failure. He required intensive hemodialysis treatment of I month and eventually rec overed. It thus appears conspicuous that the only casu alty in the 1982 group to develop acute renal failure was the one who did not have the chance to receive an early adequate volume replacement and solute-alkaline diure sis. It is difficult to draw firm conclusions from our un controlled retrospective observations. Yet, several as sumptions may cautiously be made in view of the appar ently favorable response to treatment of our 1982 group: (a) Hyperkalemia, hyperphosphatemia, hypocal cemia and metabolic acidosis appear within hours of the rescue of casualties with traumatic rhabdomyolysis (table 4). These mineral and electrolyte changes appear before renal failure sets in. (b) Very early volume replacement followed by mas sive (12 litres/day i.v.) forced solute-alkaline diuresis may protect the kidney against acute renal failure in traumatic rhabdomyolysis. A delay of at least 6 h in starting intravenous treatment in similar patients may lead to the occurrence of acute renal failure. It is quite possible that some components of the above regimen are redundant (i.e. a lesser diuresis may be adequate to pro tect the kidney and obviate the need for bladder catheter ization). At present, we cannot identify superfluous items in our proposed plan for prophylaxis against acute renal
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Crush Syndrome
failure in the crush syndrome. We feel that this regimen is extremely useful, simple and safe. (c) Our favorable results, as enumerated in table 3, were obtained without resorting to the use of loop diuret ics or to infusion of calcium salts. These measures, there fore, do not appear to be essential for the prophylaxis of acute renal failure in rhabdomyolysis. Correction of hy povolemia and of acidosis and securing diuresis, by themselves, will correct even severe degrees of hyperkal emia in the crush syndrome. (d) In the patients of 1982 with the crush syndrome, the average positive water fluid balance was 12.1 liters [range 0.65-18.3 (!) liters] in the first 60 h of treatment. This positive balance was due to sequestration of fluid in the injured muscles (‘third spacing’) and occurred in the face of the administration of 120 g/day i.v. of mannitol. It appears that such an enormous positive balance is well tolerated in a previously healthy young adult and is an acceptable complication of treatment. (e) In the 1979 group, lower leg fasciotomies were performed in 5 of 7 patients with traumatic rhabdomyoly sis. At that time, the indication had been to perform fasciotomy when the crushed limb became grossly swollen and its muscles were tense to palpation. In retro spect, none of the 1979 patients benefitted from these fasciotomies. Moreover, fasciotomy could have led to loss of limbs and endangered the lives of the patients. Therefore, in the 8 patients of the 1982 group, fasciotomy was avoided, and none of the patients in this group developed compartment syndrome. At present, we re serve early fasciotomy to patients whose compartment syndrome is due primarily to a clear-cut interruption of arterial circulation. When assessing future needs for the allocation of scarce manpower, time and logistics for rescue and sal vage operations for subjects trapped under ruins, the following extrapolations may be made from our experi ence in Tyre, Lebanon 1982 [5]. The sudden total leveling of an 8-story concrete building killed, within minutes, approximately 80% of about 100 people trapped there. The fatality rate was due mainly to trauma to the head and trunk or to immobilization of the chest and asphyxia tion. Approximately 20% survived this catastrophe, of whom 10% of the total emerged unscathed. Most of the other 10% suffered from widespread traumatic rhabdom yolysis of the limbs. Thus, the ratio of wounded/killed subjects of approxi mately 1:5, as a result of a car bomb explosion or the collapse of a building, is reversed as compared with this ratio of 6:1 in surface infantry warfare.
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An intensive search, racing against time, for survivors should be continued for at least 5 days after the beginning of a disaster which buried people alive. A successful ultimate outcome occurred in 2 of our 1982 patients with widespread rhabdomyolysis who were trapped for 24 and 28 h, respectively. An elderly woman who was trapped for 5 days under the rubble but who was not wound ed was saved by the Israeli team to Armenia in Decem ber 1988. Experience from the San Fernando/Sylmar earth quake in California on February 9, 1971 [1], showed that disruption of communications was a key obstacle in the deployment of rescue, salvage and relief operations. Each of the four hospitals that were then seriously da maged by that temblor began discharging and evacuating patients, unaware that its neighboring hospitals had also been destroyed. The community emergency response could, therefore, be coordinated and mounted only with a considerable delay. It thus appears that in a future disaster first priority should be given to the establishment of an independently powered shortwave communication network. Second, access should be provided to rescue personnel and heavy equipment (including water supply, electrical generators and lighting facility). Large quanti ties of intravenous fluid bags and their lines should be forwarded for ready use at the very site of the excavation and rescue operation. Preparations should be made to utilize continuous arterial-venous hemodialysis using bicarbonate solution. This method theoretically allows hemodialysis operation with only 12 liters of water/12-hour period, using dispos ables and obviating the need for delivery systems, pumps and electrical power [1], This method could be used in disasters in a remote area of the globe for patients with the crush syndrome complicated by acute renal failure. Also, this system could serve as a temporary stoopgap measure to save conventional chronic hemodialysis pa tients deprived of access to their dialysis center by the disaster. Indeed, this method has been used to advantage in Armenia following the 1988 earthquake [27]. Where possible in this catastrophe, hemodialysis was utilizing either conventional dialyzers or the Redy/sorbent [28] dialyzer, which requires only several liters of dialysate fluid per dialysis. From the scant data that are presently available in the literature [29-32] about medical support for victims of the crush syndrome in Armenia: it appears that most Western European and USA teams arrived on the scene 1week or later after the earthquake, too late for the institution of any prophylactic treatment for the pre vention of acute renal failure.
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Crush Syndrome
The author is indebted tor the cooperation of the following physicians at the Rambam Hospital who were responsible for the management of the patients with the crush syndrome. They are, in alphabetical order: G. Bar-Joseph, MD; S. Bursztein, MD; M. Michaelson, MD: N.D. Reis, MB. BS, FRCS, and U. Taitelman, MD [5, 6], After submission of this manuscript, details of dialysis treatment for the victims of the Armenian earthquake were published [27], There were 600 patients with acute renal failure following crush injury who required hemodialysis treatment. The American team helped in this effort by flying 36 tons of dialysis equipment and its accessories to Armenia. It appears, however, that the overwhelming magnitude of the catastrophe hampered early prophylactic treat ment against acute renal failure in survivors of this earthquake. The author is grateful to Ms. Ruby Snyder Weiss for secretarial assistance. Supported in part by Michael and Helen Schaffer Military Research Center.
References 1 Duarte RG: Seismic risks in nephrology. Dialysis Transplant 1988;17:530 546. 2 Bywaters F.GL. Beall D: Crush injuries with impairment of renal function. Br Med J 1941 :i:427-432. 3 Bywaters EGL, Popjak G: Experimental crushing injury. Surg Gynecol Obstet 1942:75:612. 4 Bywaters EGL, Stead JK: The production of renal failure fol lowing injection of solutions containing myohaemoglobin. Q J Exp Physiol 1944:33:53. 5 Ron D, Taitelman U, Michaelson M, et al: Prevention of acute renal failure in traumatic rhabdomyolysis. Arch Intern Med 1984:144:277-280. 6 Reis ND. Michaelson M : Crush injury to the lower limbs..I Bone Joint Surg 1986:68 A : 414-418. 7 Meroney WH. Arney GK. Segar WE, et al: The acute calcifica tion of traumatized muscle with particular reference to acute post-traumatic renal insufficiency. J Clin Invest 1957:36: 825-832. 8 Knöchel JP: Rhabdomyolysis and myoglobinuria: in Suki WN, Eknoyan G (eds): The Kidney in Systemic Disease, ed 2. New York, Wiley & Sons, 1981, pp 263 284. 9 Knöchel P: Serum calcium derangement in rhabdomyolysis (editorial). N Engl J Med 1981:305:161-162. 10 Cheung JY, Bonventre JV, Malis CD, et al: Calcium and is chemic injury. N Engl J Med 1982:314:1670 1676. 11 Guharay F, Sachs F: Stretch activated single ion channels cur rents in tissue cultured embryonic chick skeletal muscle. J Phy siol (Lond) 1984;352:685-701. 12 Christensen O: Mediation of cell volume regulation by Ca++ influx through stretch activated channels. Nature 1987;330: 66 - 68.
13 Awbrey BJ. Sienkiewicz PS. Mankin HJ: Chronic exercise-in duced compartment pressure elevation measured with a minia turized fluid pressure monitor. A laboratory and clinical study. Am J Sports Med 1988:16:610-615.
14 Matsen FA: Compartmental syndrome. A unified concept. Clin Orthoped 1975:113:8-14. 15 Whitesides TE, Haney TC, Murimoto K, et al: Tissue pressure measurements as a determinant for the need of fasciotomy. Clin Orthoped 1975:113:43-51. 16 De Fronzo RA. Bia MB: Extrarenal potassium homeostasis: in Seldin DW, Giebisch G (eds): The Kidney: Physiology and Pathophysiology. New York. Raven Press, 1985, pp 1179 1206. 17 Honda N : Acute renal failure and rhabdomyolysis. Nephrology forum Kidney Int 1988:23:888-898. 18 Gabow PA, Kaehny WD, Kelleher SP: The spectrum of rhab domyolysis. Medicine 1982;61:141-152. 19 Eneas JF, Schonfeld PY. Humphreys MFLTheeffect of infusion of mannitol-sodium bicarbonate on the clinical course of myog lobinuria. Arch Intern Med 1979;139:801-805. 20 Powell JW, DiBona DR. Flores J. et al: Effects of hyperosmotic mannitol in reducing ischemic cell swelling and minizing myo cardial necrosis. Circulation 1976;53(suppl I): 145-149. 21 Ward MM : Factors predictive of acute renal failure in rhabdom yolysis. Arch Intern Med 1988:148:1553 1557. 22 Llach F, Felsonfeld AJ, Hausier MR: The pathophysiology of altered calcium metabolism in rhabdomyolysis induced acute renal failure. N Engl J Med 1981:305:117 123. 23 McCarron D, Elliot WC. Rose JS, et al: Severe mixed metabolic acidosis secondary to rhabdomyolysis. Am J Med 1979:67: 905-910. 24 Boles JM. Dutel JL, Briere J, et al: Acute renal failure caused by extreme hyperphosphatemia after chemotherapy of an acute lymphoblastic leukemia. Cancer 1984;53:2425-2429. 25 Owen CA, Mubarak SJ, Hargens AR, et al: Intramuscular pres sures with limb muscle compartment syndrome. N Engl J Med 1979:300:1170-1172. 26 Hargens AR. Akeson SR. Garfin RH, et al: Compartment syn dromes, chapter 7; in Denton J (ed): Practice of Surgery. Philad elphia, Lippincott, 1984, vol I, pp 1-68. 27 Collins AJ: Renal dialysis treatment for victims of the Armenian earthquake. N Engl J Med 1989:320:1291-1292. 28 Mathias T, Sansom A: Successful haemodialysis of crush syn drome victims - the Armenian experience (abstract). 18th Ann Coni' EDTNA-Eur Renal Care Assoc, 1989, p 18. 29 Van Waeleghem JP. Verschoot M. Dewets JM. et al: Nephrology aid after seismic catastrophe in Armenia (abstract). 18th Ann Conf EDTNA-Eur Renal Care Assoc, 1989. p 28. 30 Van Waeleghem JP, Veenstra K, Egiazarian A, et al: Zorab, an earthquake victim with acute renal failure in Armenia (abstract). I8th Ann Conf EDTNA-Eur Renal Care Assoc. 1989. p 28. 31 Better OS, Zinman C, Reis DN, et al:Hypertonic mannitol for compartment syndrome. J Bone Joint Surg (USA), submitted. 32 Better OS, Stein JH: Crush syndrome. New EnglJ Med, in press.
Accepted: October9,1989 Prof. O.S. Better, M D Rambam Hospital 35254 Haifa (Israel)
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Acknowledgements
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