Rhabdomyolysis

Despite their highly varied histories, profound rhabdomyolysis developed in each of the critically ill patients described in the "Patient Profiles" (see box). What is rhabdomyolysis? Why does it occur in such dissimilar populations? Which patients are at risk? What are the signs and symptoms? And how is it treated?

Definition

Myo refers to muscle, rhabdo means striated (as in striated or skeletal muscle), and lysis is breakdown. Therefore, rhabdomyolysis (pronounced rab'-do-mi-ol'-i-sis) (1) is a dissolution of skeletal muscles that produces a nonspecific clinical syndrome that causes extravasation of toxic intracellular contents from the myocytes into the circulatory system. Regardless of the initial precipitating factor, leaky skeletal muscle cells constitute the common rhabdomyolysis pathway. (2-6)

Although somatic muscles account for 40% to 50% of total body mass, these tissues are so resilient that skeletal muscle disease is rarely a primary indication for admission to an intensive care unit. (3,7) Nonetheless, when pushed beyond their tolerance or capacity for self-repair, skeletal muscles undergo acute destruction. This destruction leads to electrolyte disturbances, hypovolemia, metabolic acidosis, coagulopathies, and myoglobinuric renal failure. Although rhabdomyolysis is occasionally the chief complaint, it is more commonly only one of several interrelated diagnoses in a critically ill patient. (8)

Pathophysiology

Understanding rhabdomyolysis requires an awareness of normal intracellular and extracellular distribution of ions and what happens when this precise balance is disrupted. Electrolyte allocation between the myocyte's internal and external environments is markedly different (Table 1). Ions in the body are either predominately intracellular or extra-cellular; no electrolyte has an equal distribution. Sodium, calcium, chloride, and bicarbonate ions are chiefly extracellular, whereas potassium, magnesium, aim phosphate ions are largely intracellular. (11) For the body to function optimally, the relative differences in the concentrations of these ions inside and outside the muscle cells must be preserved. Myocytes also contain proteins and molecules that differentiate them from other cells and from the contents of the extracellular space. (3,9,10)

Three important mechanisms maintain the distinction between intracellular and extracellular molecules (Table 2). The first of these is the cell membrane, which physically contains the larger particles of the myocyte. Damage to this essential structure allows intracellular contents to escape and extracellular contents to enter. (10) Direct injury to the cell membrane can occur as a result of crushing, tearing, burning, pounding, poisoning, or dissolving. (3,12)

Second, the sodium-potassium pump plays an important role in preserving essential intracellular-extracellular distribution of electrolytes. However, this pump is energy dependent, fueled by adenosine triphosphate (ATP). (9,12) A steady supply of oxygen is required to produce sufficient quantities of ATP. Therefore, under anaerobic conditions, both the pump and the cell membrane it is designed to maintain, quickly break down. (3) Hypoxia can be induced in muscle cells by a number of conditions, such as shock states, vascular occlusion, and tissue compression. Additionally, in patients experiencing excessive use of energy, due to such causes as seizures, strenuous exercise, hyperthermia, or prolonged sympathetic stimulation, oxygen delivery and ATP production may simply be unable to keep up with demand, and pump dysfunction swiftly ensues. (4,9)

Cell membranes can also be disrupted as a consequence of severe electrolyte imbalances, most commonly copious losses of sodium or potassium, that upset the delicate sodium-potassium pump. Significant potassium deficits can be precipitated by vomiting, diarrhea, or extensive diuresis. (12) Serum hyponatremia occurs as a result of water intoxication. (13)

Whenever the cell membrane breaks down, either physically or functionally, a massive influx of sodium occurs (Table 3). Where sodium goes, water follows, rapidly swelling the cells. (9,12,14) Large amounts of intravascular fluid (up to 12 L) can leave the circulation and become sequestered as edematous fluid in damaged muscle tissues. This fluid shift produces an intravascular hypovolemia and subsequent hemodynamic instability. (7,15) The dramatic decrease in plasma volume then leads to vasoconstriction, prerenal failure, and, eventually, acute intrarenal failure. (11) Chloride and calcium also move into the cells, causing serum hypocalcemia and calcium deposition in skeletal muscle and renal tissues. (4) Intracellular calcium levels in the myocytes of patients with exertional rhabdomyolysis can be up to 11 times the normal value. (16) This deposition of calcium in soft tissues can be so pronounced that it is detectable on images obtained by computed tomography, (17) magnetic resonance imaging, (18) technetium-99 bone scanning, (19) and sonography. (20)

Among the intracellular components that leak out of damaged skeletal muscle, (15) the most immediately important one is potassium. (16) Because the electrolyte is shifting from an intracellular area of high concentration into the serum, where a low concentration is the norm, lethal hyperkalemia can rapidly develop. (21) Patients with hyperkalemia are at risk for cardiotoxic effects and dysrhythmias, which are further aggravated by coexisting hypocalcemia and hypovolemia. (7) Phosphate also leaves the cells, producing hyperphosphatemia. Because hyperphosphatemia potentiates hypocalcemia, still more calcium is driven from the serum and into damaged muscle and kidney tissue. (4,7,14)

Injured myocytes also leak lactic acid and other organic acids, promoting metabolic acidosis and aciduria. (15) Purines released from disintegrating cells are metabolized to uric acid and can lead to hyperuricemia. (10,22) Furthermore, purines are nephrotoxic, directly damaging fragile renal tubules on contact. (3)

Myoglobin is the dark red protein that gives muscles their characteristic red-brown color. Like hemoglobin, myoglobin is an oxygen-carrying molecule that supplies oxygen to the myocytes. (4) Lysis of as little as 100 g of skeletal muscle results in myoglobinuria. (15) Destruction of 200 g of muscle causes a noticeable reddish-brown discoloration of the urine. (8) Unfortunately, myoglobin is also nephrotoxic in patients with coexisting oliguria and aciduria. (10)

Both thromboplastin (a clot-promoting agent) and tissue plasminogen (a thrombolytic substance) are released from injured muscle tissue, making patients with rhabdomyolysis susceptible to disseminated intravascular coagulation. (9,10,15,22-24) Rhabdomyolysis also produces extreme increases in the serum levels of creatine kinase (CK). CK has no toxic effects, and elevated plasma levels of the kinase are simply a marker of increased permeability of muscle membranes. (21) However, grossly high values are pathognomonic for rhabdomyolysis, because no other condition will cause such extreme CK elevations. (8,25)

Associated Conditions

A basic understanding of the pathophysiology of rhabdomyolysis indicates why this abnormality is associated with more than 100 seemingly unrelated disorders (8) (Table 4). Although initially recognized solely as a posttraumatic sequela, nontraumatic causes of rhabdomyolysis are now estimated to be at least 5 times more frequent than traumatic causes. (3) Importantly, however most patients who eventually experience rhabdomyolysis have several risk factors. (4,9,21) In a study by Gabow et al, (26) 59% of the subjects had a history of multiple associated conditions.

Direct Muscle Injury

Some of the earliest reported cases of rhabdomyolysis occurred during the bombing of London in World War II. Acute renal failure commonly developed in patients wounded in building collapses. (8,27) This condition came to be known as the "crush injury syndrome," and this term is often used to refer to rhabdomyolysis despite current understanding of other precipitating factors. (4,15) Direct muscle trauma after natural or human-made disasters remains responsible for large-scale occurrences of rhabdomyolysis. (3,7) For example, after the 1988 Armenian earthquake, more than 1000 cases of rhabdomyolysis-induced myoglobinuric renal failure were reported; 323 of these patients required dialysis. (28) Such numbers have important implications for disaster planners in bomb-or earthquake-prone regions. (9,28,29)

Other common causes of crushing injuries are farm and industrial accidents and motor vehicle collisions. Particularly at risk for rhabdomyolysis are patients who are entrapped and whose access to care is delayed. (14) Bite injuries can macerate and devitalize large areas of muscle tissue; in one instance, rhabdomyolysis occurred after a wolf attack. (30) Deep burns are another source of direct muscle damage. (31) Electrical injuries, including lightning strikes, are associated with a particularly high occurrence of rhabdomyolysis because electrical current travels through the body, devitalizing tissue all along the path of the current. (9,14,32) The acute necrotizing myopathy of certain carcinomas can also destroy enough muscle mass to initiate rhabdomyolysis?

Both beatings and sport fighting, such as boxing and karate, can cause rhabdomyolysis. (5) Tortured or assaulted patients, particularly those admitted to the hospital from jail, where attacks tend to be prolonged and vicious, should be considered at risk for rhabdomyolysis, (4) as should victims of severe child abuse. (33) Indeed, persons subject to repetitive blows of any kind are at risk. Incidents of rhabdomyolysis have occurred in bongo drum players, (4) personal watercraft riders, (34) computer keyboard users, (35) jackhammer operators, and mechanical bull riders. (25) Direct muscle injury can also be due to iatrogenic interventions. For example, a patient had rhabdomyolysis and myoglobinuric renal failure after 15 cardio-version attempts and prolonged chest compressions. (36)

Excessive Physical Exertion

Excessive physical exertion results in a state in which ATP production cannot keep up with demand, subsequently exhausting cellular energy supplies and disrupting muscle cell membranes. (3,4,12) Rhabdomyolysis can be caused by any kind of intense physical exercise and has been documented in weight lifters, marathon runners, police cadets, and military recruits in boot camp. (5,12,37-41)

Protracted tonic-clonic seizures not only pound the muscles repeatedly but also exert a tremendous metabolic demand that predisposes patients to rhabdomyolysis. (4,12) Rhabdomyolysis due to extreme hyperactivity can occur in psychotic patients, both those with mania and those with drug-induced psychoses. (42-44) Rhabdomyolysis developed in an agitated patient after restraint in a straitjacket, (43) in patients with delirium tremens, (25) and in a patient with pronounced decerebrate posturing. (45) Even racehorses are subject to a form of exertional rhabdomyolysis. (46)

Muscle Ischemia

Muscle ischemia, whatever its cause, interferes with oxygen delivery to the cells, thereby limiting production of ATP. Generalized ischemia from shock and hypotension are common factors contributing to rhabdomyolysis in trauma patients. (9) By binding to hemoglobin, carbon monoxide causes a total body ischemia. (4) Severe status asthmaticus, (47) inhalation of hydrocarbons, (48) and near-drowning also produce profound systemic hypoxemia, (49) and each of these conditions can precipitate rhabdomyolysis.

Skeletal muscle ischemia can also be caused by localized compression? Sources include intraoperative use of tourniquets, (50) tight dressings or casts, and prolonged application of air splints or pneumatic antishock garments, (9) particularly in patients with hypotension.

Rhabdomyolysis can be caused by tissue compression due to extended periods of immobilization. (2) This etiology includes immobilization related to intraoperative positioning, particularly the lithotomy position. (51-52) Cases of rhabdomyolysis are common in intoxicated or comatose persons "found down" and in elderly patients unable to rise after a fall. (53) Rhabdomyolysis has also been reported in a patient immobilized because of an acute spinal cord injury. (54)

Compartment syndrome is both a cause and a complication of rhabdomyolysis. As pressure within the fascial compartment increases, blood flow decreases, tissues become necrotic, and the dying muscle cells release osmotically active particles that draw additional water into the compartment, further exacerbating the condition. (4-6,12)

As devastating as ischemia is to tissue, evidence suggests that many of the events that eventually lead to myolysis occur during the reperfusion phase. Once circulation is restored, large amounts of toxic intracellular contents are released into the bloodstream. (3,9,55) This ischemia-reperfusion treatment dilemma is a clinical conundrum for practitioners.

Muscle ischemia precipitated by arterial or venous occlusions has several causes. White clot syndrome due to severe heparin-induced throm-bocytopenia, (56) air emboli from diving injuries, (57) and microvascular occlusion of severe sickle cell crisis or vasculitis can all affect blood flow to the tissues enough to cause muscle cell death. (5,39,58)

Temperature Extremes

Both heat and cold can precipitate rhabdomyolysis. (12) By reducing muscle perfusion, cold induces tissue ischemia and freezing causes cellular destruction. Conversely, excess heat, regardless of its cause, also destroys myocytes. (4,5) In addition to the effects of direct thermal injury, every 1[degrees]C increase in body temperature increases metabolic demand by approximately 10% (3%) When oxygen delivery can no longer keep up with increasing requirements, cellular hypoxia ensues. These findings explain why exertional hyperthermia in particular is associated with the development of rhabdomyolysis. (38,59)

Certain patients have a hereditary, idiopathic reaction to halothane anesthetics. When these patients are given these agents, profound malignant hyperthermia ensues, causing body temperature to soar and simultaneously producing widespread muscle destruction. (21,38) Less severe, yet similar to malignant hyperthermia, is neuroleptic malignant syndrome. This syndrome is triggered by certain psychotropic medications such as haloperidol (Haldol) and chlorpromazine (Thorazine). (3,14,21) Both malignant hyperthermia and neuroleptic malignant syndrome can quickly induce rhabdomyolysis.

Electrolyte and Serum Osmolality Abnormalities

Although rhabdomyolysis related to chronic hypophosphatemia, hyponatremia, and sodium replacement therapy has been reported, (13) chronic hypokalemia is the most common precipitating electrolyte abnormality. (3,4,12) Because it is the chief intracellular ion, a significant total body loss of potassium will disrupt the sodium-potassium pump, causing the cell membrane to fail while allowing toxic intracellular contents to escape from muscle cells. Overuse of diuretic (13) or cathartic drugs can lead to massive total-body potassium depletion. (60) Importantly, this depletion can occur even in the presence of normal or elevated serum potassium levels, which are maintained by the ongoing release of potassium from dying myocytes. (3)

Hyperemesis gravidarum produces major electrolyte losses that can be associated with rhabdomyolysis. (61) Interestingly, several cases of rhabdomyolysis after chronic consumption of black licorice have been reported. This popular candy contains a mineralocorticoid-type agent that, when consumed in large quantities, causes renal potassium wasting. (62,63) Some drugs (eg, amphotericin B) and certain chemicals (eg, toluene) produce renal tubular acidosis, which interferes with electrolyte reabsorption and can lead to potassium wasting. (4,5,64)

Rhabdomyolysis has also been attributed to hyperosmolar states such as hyperglycemic hyperosmolar nonketotic coma (65) and to aggressive mannitol therapy in a patient with an isolated head injury and concomitant diabetes insipidus. (66)

Endocrinologic Disorders

Endocrine disorders associated with rhabdomyolysis are either electrolyte wasting or hypermetabolic conditions. Diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic coma, and hyperaldosteronism are all potassium-wasting states, (4,12,65,67) whereas Addison disease produces a hyponatremic condition. (68) Thyroid storm and pheochromocytoma both dramatically increase sympathetic stimulation and metabolic demands (similar to those of cocaine or amphetamine abuse), forcing the body to a level of extreme hypermetabolism that cannot be sustained indefinitely. (12,69)

Genetic and Autoimmune Disorders

A few, unusual genetic conditions stimulate rhabdomyolysis, including disorders of carbohydrate and lipid metabolism. (4,5,70) Muscular dystrophies generally cause chronic muscle wasting, but occasionally acute exacerbation results in rhabdomyolysis. (5,21) The autoimmune disorders polymyositis and dermatomyositis are also chronic conditions that progress to rhabdomyolysis in rare instances. (4,5,12)

Infections

Pneumococcal and Staphylococcus aureus sepsis, salmonella and listeria infections, leptospirosis, tularemia, legionnaire disease, gas gangrene, tetanus, and necrotizing fasciitis are among the many infectious conditions that can destroy marked quantities of muscle tissue through generation of toxins or direct bacterial invasion. (3,4,12,71-73) Historically, advanced malaria was referred to as "black water disease" in reference to the dark urine produced in this parasite-induced form of rhabdomyolysis. (74) Viral causes include influenza viruses A and B, varicella-zoster virus, (23) HIV, (75,76) and various enteroviruses. (4,5,77)

Drugs, Toxins, and Venoms

Drugs, toxins, and venoms are the largest category of causes of rhabdomyolysis; ethanol is the foremost rhabdomyolysis-inducing agent in this class. (4,5) In addition to its depressant effect on the central nervous system, which can lead to periods of prolonged immobility, alcohol has a primary toxic effect on myocytes, and cases of rhabdomyolysis after binge drinking without convulsions or coma have been reported. (2,3,78)

Recreational use of drugs, such as heroin, (4,5) lysergic acid diethyllamide, (25) and glue, (64) has been linked to rhabdomyolysis, but the abnormality is particularly common after ingestion of agents that either mimic or stimulate the sympathetic nervous system, including cocaine, methamphetamines, N-methyl-D-aspartate (ecstasy), and phencyclidine. (2,6,39,79-83) Even overdoses of legal stimulants such as caffeine, (84) aminophylline, (85) and pseudoephedrine (86) have been associated with the development of rhabdomyolysis.

Many chemicals (87) and toxic plants are linked to rhabdomyolysis, including hemlock, (88) certain mushrooms, (89) and the ingredients of blowpipe dart poison. (90) Because snake venoms are designed to both immobilize prey and start the digestive process, they contain lyric enzymes that dissolve myocytes. (91,92) Rhabdomyolysis after multiple stings by wasps, (93) bees, or hornets (22) and after envenomation by the giant desert centipede (94) has been reported.

A long list of pharmaceutical agents are associated with the development of rhabdomyolysis. These include such common drugs as benzodiazepines, corticosteroids, narcotic analgesics, immunosuppressants, salicylates, paralytics, lipid-lowering statins, antibiotics, antidepressants, and antipsychotics. (22,95-98) Cases of rhabdomyolysis have occurred with both therapeutic aim toxic doses of these substances. However, patients with drug-related rhabdomyolysis often have several other risk factors, making it difficult to identify a single precipitating cause. (22)

Some substances have a primary toxic effect on the myocytes, whereas others (eg, barbiturates and opiates) chiefly induce muscle ischemia through central nervous system depression, prolonged immobility, and tissue compression. (12) Several medications routinely administered to critically ill patients are among those implicated in the development of rhabdomyolysis, including succinylcholine, (21) haloperidol, (99) propofol, (100) streptokinase, (101) amphotericin B, (25) and certain chemotherapeutic agents. (102)

Prevalence

No comprehensive data on the overall prevalence of rhabdomyolysis are available because occurrence is highly dependent on the underlying cause. Whereas rhabdomyolysis is strongly associated with malignant hyperthermia, major crush injuries, and extensive electrical burns, it is extremely rare with such conditions as sickle cell anemia, muscular dystrophy, and routine use of salicylates. (14, 39)

Clinical Findings Signs and Symptoms

The initial manifestations of rhabdomyolysis can be subtle (Table 5), and early detection requires a high index of suspicion. (3,25,103) A history of significant risk factors should suggest the possibility of rhabdomyolysis. (3) At particular risk are patients with evidence of tissue crushing, bruising, ischemia, peripheral neuropathies, serious infections, or deep burns. (5) Early indications of rhabdomyolysis may be limited to muscle weakness and tenderness, generalized malaise, and nausea. (3,8,12) These findings can easily be unrecognized in critically ill patients. Most commonly, the initial clinical sign of rhabdomyolysis is the appearance of discolored urine, with a specific gravity greater than 1.025, indicating large quantities of excreted myoglobin. (5,8,9) Urine can range from pink tinged, to cola colored, to thick and black. (4,9,12) Critical care nurses are often the first healthcare providers to observe this finding.

Laboratory findings

Although history and physical examination can provide clues, the actual diagnosis of rhabdomyolysis is confirmed by laboratory studies. (4) CK levels are the most sensitive indicator of myocyte injury in rhabdomyolysis. (12) Normal CK enzyme levels are 45 to 260 U/L. (10) Patients with chronic muscular disorders, patients who recently had surgery, and any one who just completed a marathon may have a CK level of several hundred. With rhabdomyolysis, however, total CK levels are massively elevated; values are anywhere from 10 000 to 200 000 U/L. In extreme cases, the CK level may be 3 million U/L (4) Levels this high are diagnostic for rhabdomyolysis; no other condition will cause such extreme CK elevations. (8,25)

Because CK-MM, the isoenzyme released from damaged skeletal muscle, accounts for the bulk of serum CK even in patients without rhabdomyolysis, determining levels of this isoenzyme is of no benefit in patients who have rhabdomyolysis. (12,14) Serum levels of myoglobin also increase markedly, but this increase is not a reliable indicator of rhabdomyolysis because myoglobin is rapidly cleared from the plasma. (9,12,14) Arterial blood gas analysis is helpful for detecting underlying hypoxia and acidosis and for monitoring sodium bicarbonate therapy. (10,12) Both acute renal failure and increased release of creatinine from skeletal muscle cause the serum concentrations of urea nitrogen and creatinine to increase in rhabdomyolysis. However, creatinine is elevated to a greater extent, narrowing the normal 10:1 ratio of urea nitrogen to creatinine to 6:1 or less. (4,12,25)

A classic pattern of changes in serum electrolytes occurs in rhabdomyolysis. At the outset, serum levels of potassium and phosphate increase as these components are released from the cells; levels then decrease as they are excreted in the urine. Serum concentration of calcium initially decreases as calcium moves into the cells and then gradually increases. Electrolyte levels in each patient depend on the severity of the rhabdomyolysis, where the patient is in the course of the disease, and what interventions have been initiated. (14) Clotting studies are useful for detecting indications of disseminated intravascular coagulation, (11) and toxicological screens should be performed if drugs are a suspected causal agent.

Urinalysis in patients with rhabdomyolysis will reveal the presence of protein, brown casts, and uric acid crystals and may reflect electrolyte wasting consistent with renal failure. (4) Urine dipsticks are a quick way to screen for myoglobinuria, because the reagent on the dipsticks that reacts with hemoglobin also reacts with myoglobin. (15) Therefore, a hemoglobin-negative reading indicates the absence of both hemoglobin and myoglobin. However, if the test is positive, hemoglobin, myoglobin, or both are present, and further investigation is needed to detect the presence or absence of erythrocytes. (3,4,12)

Complications

Most of the clinical findings of rhabdomyolysis are related to its complications. These include disturbances in electrolyte levels in serum and urine, metabolic acidosis, hypovolemia, myoglobinuric renal failure, disseminated intravascular coagulation, and acute muscle wasting.

Disturbances in serum electrolytes, particularly hyperkalemia, are the most immediately life-threatening consequence of rhabdomyolysis. (4) Treatment is complicated because although patients are acutely hyperkalemic, they have an underlying deficit in total-body potassium. Metabolic acidosis in rhabdomyolysis is due to a combination of increases in lactic acid, uric acid, phosphate, sulfate, and potassium in the circulation. (3)

Patients who survive the initial hyperkalemic and hypovolemic phases of rhabdomyolysis are still susceptible to death due to myoglobinuric renal failure. (7) Up to 33% of patients with rhabdomyolysis progress to acute renal failure? In fact, rhabdomyolysis accounts for 7% to 15% of all cases of acute renal failure in the United States. (3,4,104)

Myoglobinuric renal failure can be either oliguric or nonoliguric and damages the kidneys in several ways. (25) The breakdown of myoglobin produces a pigment-induced nephropathy with subsequent sloughing of the tubular epithelium. (4,12,104) This exfoliate, together with large myoglobin molecules (which are freely filtered in the glomerulus), (4) results in the formation of brown casts that obstruct the renal tubules, causing an increase in intratubular pressure and the development of interstitial edema. (3)

Low urinary pH (<5.6) (12) not only facilitates formation of casts but also promotes the dissociation of myoglobin molecules into cytotoxic components. In an acidic medium, the globin chain splits from the iron-containing ferrihemate part of the myoglobin molecule. Once myoglobin is broken into its component parts, the iron in ferrihemate generates oxygen-free radicals that lead to lipid peroxidation and renal cell injury. (9,104,105) However, despite high concentrations, if myoglobin can pass through the kidneys unchanged, it is harmless (4) Each of these patho-physiological processes is aggravated by hypovolemia and subsequent renal vasoconstriction. (3,4,14) Therefore, keeping both urine volume and pH high is an important component of rhabdomyolysis therapy. (37)

Release of clot and anticlot factors from tissues predisposes patients to serious bleeding disorders, particularly patients already at risk for disseminated intravascular coagulation. (10,15,23) Although rhabdomyolysis classically attacks skeletal muscles, acute wasting of the heart, diaphragm, and intracostal muscles call occur in patients with rhabdomyolysis. These changes contribute to both cardiac and respiratory failure. (63)

Interventions

In patients at high risk for rhabdomyolysis, prevention and early recognition of the abnormality are the first steps in treatment. (4) Although prompt intervention is important, both muscle and renal cells are fairly resilient. (10) This resiliency allows time to first address any immediate airway, breathing, or circulatory needs (Table 6).

Limiting Further Muscle Damage

The next step in therapy is minimizing the amount of muscle damage in order to limit the ongoing release of intracellular contents. This step is possible in some patients, such as those with rhabdomyolysis due to compartment syndrome, but not in others, such as those with rhabdomyolysis due to the toxic effects of drugs. (12) Interventions include expeditious extrication of entrapped patients and rapid transport to a hospital. Immobilization on a backboard should be limited, and pneumatic antishock garments should be removed and tight casts and dressings loosened as soon as possible. Escharotomies, fasciotomies, and debridement of burns and other wounds should be facilitated. (6,7,9,31) Other interventions include monitoring compartment pressures in injured extremities, (9,14,15) administering antivenin or antidotes, and providing antibiotics as indicated by each specific cause.

Enhancing Clearance of Toxins

The next step in treatment is to enhance clearance of toxic intracellular contents from the circulation and from the kidneys. Although investigators agree that volume expansion, alkalinization, and mannitol infusion are each important interventions, no consensus exists on volume, amount, and timing. (22) The Figure illustrates one institution's rhabdomyolysis treatment algorithm. Experts agree, however, that the single most important intervention to prevent acute renal failure in rhabdomyolysis is restoring intravascular volume and inducing a solute diuresis. (3,4,7,9,12,15) Expanding the intravascular volume maximizes renal excretion by flushing out tubular debris and limiting the time nephrotoxins are in contact with renal tissues. (10) In adult patients, the goal of isotonic crystalloid volume replacement therapy is an hourly urine output of 150 to 300 mL. (4,7,9,15,37) Maintaining an output this high may require intravenous infusions of fluid of 500 to 1000 mL/h, (7) and all patients should have a urinary catheter placed in order to adequately monitor fluid output. (12)

[FIGURE OMITTED]

Additionally, the urine is alkalinized to a pH of 6.0, (22) 6.5, (25) 7.0, (4,15) or even 7.5 (37) to prevent the dissociation of myoglobin into its nephrotoxic components. Akalinization is achieved by adding sodium bicarbonate to the intravenous crystalloid infusion. (9) Mannitol is given to promote diuresis, keep the kidneys flushed, and prevent formation of casts in the tubules. (4,7,9,14) If fluids and mannitol are insufficient to maintain a brisk urine output, furosemide (Lasix) can be added to the regimen, (4,7) but it may acidify the urine. (9) When the kidneys do not respond to other interventions, emergency hemodialysis is necessary for the management of oliguria, persistent electrolyte derangements, resistant metabolic acidosis, uremic encephalopathy, or fluid overload. (4,9) Some researchers (10,14,59) suggest that renal replacement therapy by continuous venovenous hemofiltration dialysis is equally effective. Although mentioned in the literature, neither plasmapheresis nor hemodiafiltration has been successful in patients with myoglobinuric renal failure. Fortunately, most patients eventually regain normal kidney function. (4)

Providing Ongoing Nursing Care

Ongoing nursing care of patients with rhabdomyolysis includes sequential monitoring of urine output (ie, checking volume, color, and specific gravity) to guide further fluid resuscitation. In order to prevent fluid overload and the development of pulmonary edema and congestive heart failure, (3) patients should be monitored closely fur the development of oliguric renal failure (daily urine output <400 mL). (15) Patients with rhabdomyolysis may benefit from invasive arterial and pulmonary artery pressure monitoring to assist with assessment of volume status. (10)

Urine pH must be serially tracked to ensure that it remains high, and arterial pH is monitored on a regular basis to prevent potential overalkalinization (pH >7.5) due to aggressive administration of sodium bicarbonate. (9,12) Other interventions include limiting the use of nephrotoxic antibiotics (eg, amino-glycosides) and iodinated radiocontrast medium to minimize further kidney damage. (9)

CK levels should be determined every 6 to 12 hours. The level most likely will peak dramatically in the first 12 to 36 hours and then steadily decrease during the next several days. (12,15,39) Importantly, eventual renal outcome is largely dependent on the speed and efficacy of treatment and not on the CK level itself. (3) Patients with CK values greater than 800 000 U/L who receive early and aggressive treatment may experience no subsequent renal failure. (21) Conversely, even patients with CK levels less than 10 000 U/L can have permanent impairment if care is delayed or inadequate.

Serum electrolytes must be monitored closely, and life-threatening abnormalities must be addressed promptly. Potassium levels generally peak 12 to 36 hours after injury, (8) and elevations are treated with standard hyperkalemic therapy. (3,4) Unless patients are symptomatic, administration of exogenous calcium to correct hypocalcemia is not recommended. With hydration, calcium remobilizes from the soft tissues and can cause hypercalcemia. (10,14,15) All patients with rhabdomyolysis require continuous electrocardiographic monitoring for signs of hyperkalemia or cardiac irritability. (4,10) Compartment pressures may be measured in patients at risk for rhabdomyolysis due to extremity trauma. (9)

Prognosis

Skeletal muscles can recover from episodes of rhabdomyolysis with surprisingly minimal permanent damage, (21) and overall survival after rhabdomyolysis is approximately 77%. (4) When access to aggressive treatment, including hemodialysis, is timely, most deaths are related to patients' other injuries or disease states and are not a direct result of rhabdomyolysis.

Summary

Rhabdomyolysis is a clinical syndrome in which the contents of injured muscle cells leak into the circulation. This leakage results in electrolyte abnormalities, acidosis, clotting disorders, hypovolemia, and acute renal failure. More than 100 conditions, both traumatic and non-traumatic, can lead to rhabdomyolysis. Intervention consists of early detection, treatment of the underlying cause, volume replacement, urinary alkalinization, and aggressive diuresis or hemodialysis. Patients with rhabdomyolysis often require intensive care, and critical care nurses are instrumental in both the early detection and the ongoing management of this life-threatening syndrome.

Patient Profiles

L.T., an 82-year-old widow, was removing a chicken from the oven when she slipped backward onto the open oven door, sustaining deep burns to her buttocks. Mrs T. then tumbled forward, landed in the roasting pan, and seared her chest as well. Unable to move, she lay on the floor for 2 days until found by her daughter. Upon arrival at the hospital, Mrs T. was badly burned, was dehydrated, and had a potassium level of 79 mmol/L (7.9 mEq/dL).

While scaling a razor wire fence in an attempt to flee the police, 34-year-old S.G. fell 2.4 m (8 ft) to the pavement. When paramedics arrived, they noted that he was extremely tremulous, covered with lacerations, and had 4+ nystagmus. His level of consciousness was significantly altered. Electrocardiography in the emergency department revealed tall, peaked T waves. He had a rectal temperature of 41.2[degrees]C (106.1[degrees]F), and the toxicological screen of his urine was positive for cocaine. Twelve hours after admission, compartment syndrome of the right forearm developed.

R.K., a 55-year-old man, was installing a large television antenna on his roof when the 0antenna fell backward, contacting both R.K.'s head and a power line behind the house. After inflicting deep electrical injuries to his scalp and right hand, the energy traveled through R.K.'s body and exited by blowing off his right foot. He was having seizures when found by his wile, and he was unconscious when he arrived at the trauma center. After insertion of a urinary catheter, a small amount of thick, black urine drained.

CE Test Questions Rhabdomyolysis: Pathophysiology, Recognition, and Management

1. Which one of the following defines rhabdomyolysis?

a. Myoglobin-induced renal failure

b. Breakdown of skeletal muscle with the release of myoglobin

c. Electrolyte abnormalities caused by muscle damage

d. Multiple organ failure caused by crushing injuries

2. Which of the following electrolytes are extracellular?

a. Potassium, sodium, calcium

b. Phosphate, magnesium, potassium

c. Sodium, calcium, chloride

d. Sodium, chloride, potassium

3. Which of the following are important in the physiology of intracellular and extracellular homeostasis?

a. Cell membrane integrity, adenosine triphosphate, sodium-potassium pump

b. Fluid volume, cell integrity, adenosine triphosphate

c. Oxygenation status, fluid shifts, energy production

d. Severe vomiting, adenosine triphosphate, water intoxication

4. Which clotting factors are released when myocytes are damaged?

a. Factor VIII, calcium

b. Thrombin, plasminogen

c. Thromboplastin, tissue plasminogen

d. Factor IX, thrombin

5. Which of the following patients are at high risk of rhabdomyolysis?

a. A child with a single dog bite

b. A woman who does aerobic exercise 5 times a week

c. A young man who has been hinging on alcohol for 1 week

d. An elderly man who has been immobilized for 2 hours

5. What is the most common precipitating electrolyte abnormality leading to rhabdomyolysis?

a. Hypophosphatemia

b. Hypernatremia

c. Hypercalcemia

d. Hypokalemia

7. Which of the following candies have been linked to renal potassium wasting?

a. Black licorice

b. Sugar-free candies

c. Low-carbohydrate bars

d. Salt water taffy

8. Which of the following toxins is the most commonly producing rhabdomyolysis?

a. Coral snake

b. Cocaine overdose

c. Ethanol toxicity

d. Pseudoephedrine overdose

9. Which one of the following patients has the highest statistical chance of getting rhabdomyolysis?

a. A patient with prolonged hypothermia

b. A patient with a small electrical burn

c. A patient who ran a marathon and collapsed

d. A patient with crush injuries to both legs

10. Which of the following are clinical signs of rhabdomyolysis?

a. Tea-colored urine

b. Nausea and vomiting

c. Peaked T waves

d. Constant diarrhea

11. Which of the following laboratory test values are the most indicative of rhabdomyolysis?

a. Creatinine

b. Serum urea nitrogen

c. Creatine kinase

d. Arterial pH

12. Which of the following is the most common life-threatening complication of rhabdomyolysis?

a. Renal failure

b. Hyperkalemia

c. Hypovolemia

d. Metabolic acidosis

13. Which of the following would be a goal of rhabdomyolysis therapy?

a. Urine pH of 5.0

b. Daily urine output of 400 mL

c. Intravenous fluids at 200 mL/h

d. Clear urine at 175 mL/h

14. How is alkalinization of the urine achieved?

a. Boluses of sodium bicarbonate every 8 hours

b. Mannitol every 6 hours

c. Massive fluid resuscitation

d. Adding sodium bicarbonate to intravenous fluids

Acknowledgments

I thank Richard Mullins, MD, chief of the trauma/critical care section, and Mary Meininger, RN, MN, manager of the pain management center, Oregon Health & Science University, for generously sharing the rhabdomyolysis treatment algorithm they coauthored.

* This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives:

1. Describe rhabdomyolysis

2. Outline the risk factors for rhabdomyolysis

3. Discuss the treatment plan for rhabdomyolysis

References

(1.) O'Toole M, ed. Miller-Keane Encyclopedia and Dictionary, of Medicine, Nursing, and Allied Health. 6th ed. Philadelphia, Pa: WB Saunders Co; 1997.

(2.) Richards J. Rhabdomyolysis and drugs of abuse. J Emerg Med. 2000;19:51-56.

(3.) Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin. 1999;18:415-428.

(4.) Russell TA. Acute renal failure related to rhabdomyolysis: pathophysiology, diagnosis, and collaborative management. Nephrol Nuts J. 2000;27:567-577.

(5.) Rush C, Thomas J. A 42-year-old man with rhabdomyolysis gem substance abuse. J Emerg Nurs. 1999;25:7-11.

(6.) Carriere S, Elsworth T. Found down: compartment syndrome, rhabdomyolysis, and renal failure. J Emerg Nurs. 1998;24:214-217.

(7.) Abassi A, Hoffman A, Better O. Acute renal failure complicating muscle crush injury. Semin Nephrol. 1998;18:558-565.

(8.) Dayer-Berenson L. Rhabdomyolysis: a comprehensive guide. ANNA J. 1994;21:15-18.

(9.) Slater MS, Mullins RJ. Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: a review. J Am Coll Surg. 1998;186:693-716.

(10.) Haskins N. Rhabdomyolysis and acute renal failure in intensive care. Nurs Crit Care. 1998;3:283-288.

(11.) Bullock J, Boyle J III, Wang MB. Physiology. 2nd ed. Baltimore, Md: Harwal Publishing Co; 1992. National Medical Series for Independent Study.

(12.) Moghtader J, Brady WJ, Bonadio W. Exertional rhabdomyolysis in an adolescent athlete. Pediatr Emerg Care. 1997;13:382-385.

(13.) Trimarchi H, Gonzalez J, Olivero J. Hyponatremia-associated rhabdomyolysis. Nephron. 1999:82:274-277.

(14.) Vanholder R, Sever M, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000;11:1553-1561.

(15.) Cheney P. Early management and physiologic changes in crush syndrome. Crit Care Nurs Q. August 1994;17:62-73.

(16.) Lopez JR, Rojas B, Gonzalez MA, Terzic A. Myoplasmic C[a.sup.2+] concentration during exertional rhabdomyolysis. Lancet. 1995;345:424-425.

(17.) Barloon T, Zachar C, Harkens K, Honda H. Rhabdomyolysis: computed tomography findings. J Comput Tomogr. 1988;12:193-195.

(18.) Kakuda W, Naritomi H, Miyashita K, Kinugawa H. Rhabdomyolysis lesions showing magnetic resonance contrast enhancement. J Neuroimaging. 1999;9:182-184.

(19.) Sanders JA. Rhabdomyolysis detected by bone imaging. Clin Nucl Med. 1989;14:431-432.

(20.) Steeds RP, Alexander PJ, Muthusamy R, Bradley M. Sonography in the diagnosis of rhabdomyolysis. J Clin Ultrasound. 1999;27:531-533.

(21.) Gronert GA. Cardiac arrest after succinylcholine: mortality greater with rhabdomyolysis than receptor upregulation. Anesthesiology. 2001;94:523-529.

(22.) Curry SC, Chang D, Connor D. Drug--and toxin-induced rhabdomyolysis. Ann Emerg Med. 1989:18:1068-1084.

(23.) Hollenstein U, Thalhammer F, Burgmann H. Disseminated intravascular coagulation (DIC) and rhabdomyolysis in fulminant varicella infection: case report and review of the literature. Infection. 1998;26:306-308.

(24.) Riggs J, Schochet S, Parmar J. Rhabdomyolsis with acute renal failure and disseminated intravascular coagulation: association with acetaminophen and ethanol. Mil Med. 1996;161:708-709.

(25.) Harper J. Rhabdomyolysis and myoglobinuric renal failure. Crit Care Nurse. March 1990:19:32-36.

(26.) Gabow PA Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore). 1982;61:141-192.

(27.) Bywaters E, Beall D. Crush injuries with impairment of renal function. Br Med J. 1941:1:427-432.

(28.) Vanholder R, Sever M, De Smet M, Erek E, Lameire N. Intervention of the Renal Disaster Relief Task Force in the 1999 Marmara, Turkey, earthquake. Kidney, Int. 2001;59:783-791.

(29.) Lambert MC, Larno L, Stragier W, Sirault B. The European Task Force for Disaster Relief: a multi-disciplinary team approach. EDTNA ERCA J. April-June 1997;23:47-49.

(30.) Smith C, Moir C, Mucha P. Rhabdomyolysis and renal failure following a wolf attack: case report. J Trauma. 1991;31:423-425.

(31.) Lazarus D, Hudson D. Fatal rhabdomyolysis in a flame burn patient. Bums. 1997:23:446-450.

(32.) Brumback R, Feeback D, Leech R. Rhabdomyolysis following electrical injury. Semin Nephrol. 1995;15:329-334.

(33.) Mukherji S, Siegel M. Rhabdomyolysis and renal failure in child abuse. A JR Am J Roentgenol. 1987;148:1203-1204.

(34.) Ziskind A, Huang P. Jet-ski rhabdomyolysis. JAMA. 1986;255:1879-1880.

(35.) Jolly B, Talbot-Stern J. Rhabdomyolysis secondary to keyboard overuse: occupational hazard of the computer age. Am J Emerg Med. 1995;13:644-646.

(36.) Hojs R, Sinkovic A, Hojs-Fabjan T. Rhabdomyolysis and acute renal failure following cardioversion and cardiopulmonary resuscitation. Ren Fail. 1995;17:765-768.

(37.) Kruse D. "Tyson squats" as a cause of rhabdomyolysis. J Emerg Nurs. 1998;24:116-117.

(38.) Kochling A, Wappler F, Winkler G, Schulte am Esch JS. Rhabdomyolysis following severe physical exercise in a patient with predisposition to malignant hyperthermia. Anaesth Intensive Care 1998;26:315-318.

(39.) Walsworth M, Kessler T. Diagnosing exertional rhabdomyolysis: a brief review and report of two cases. Mil Med. 2091;166: 275-277.

(40.) Danis D. Exercise-related rhabdomyolysis and renal failure. J Emerg Nurs. 1991;17:171-172.

(41.) Morocco P. Atraumatic rhabdomyolysis in a 20 year-old bodybuilder. J Emerg Nuts. 1991;17:370-372.

(42.) Manchip S, Hurel S. Rhabdomyolysis due to mania. Br J Psychiatry. 1995:167:118.

(43.) Mercieca J, Brown E. Acute renal failure due to rhabdomyolysis associated with use of a straitjacket in lysergide intoxication. Br Med J (Clin Res Ed). 1984;288:1949-1950.

(44.) Lahmeyer HH. PCP, physical restraint, and rhabdomyolysis. J Clin Psychiatry. 1983;44:234.

(45.) Briggs T, Smith R. Exertional rhabdomyolysis associated with decerebrate posturing. Neurosurgery. 1986:19:297-299.

(46.) Valberg SJ, Mickelson JR, Gallant EM, MacLeay JM, Lentz L, de la Corte F. Exertional rhabdomyolysis in quarter horses and thoroughbreds: one syndrome, multiple aetiologies. Equine Vet J Suppl. 1999;30:533-538.

(47.) Li AM, Li CC, Chik KW, Shing MM, Fok TF. Rhabdomyolysis following status asthmaticus. J Paediatr Child Health. 2001:37:409-410.

(48.) Betrosian A, Palamarou C. Rhabdomyolysis and suicidal hydrocarbon inhalation. Ann Emerg Med. 1997;29:301-302.

(49.) Bonnor R, Siddiqui M, Ahuja T. Rhabdomyolysis associated with near-drowning. Am J Med Sci. 1999;318:201-202.

(50.) Williams J, Tucker D, Read J. Rhabdomyolysis-myoglobinuria: consequences of prolonged tourniquet. J Foot Surg. 1983;22:52-56.

(51.) Mathes D, Assimos D, Donofrio P. Rhabdomyolysis and myonecrosis in a patient in the lateral decubitus position. Anesthesiology. 1996;84:727-729.

(52.) Biswas S, Gnanasekaran I, Ivatury R, Simon R, Patel A. Exaggerated lithotomy position-related rhabdomyolysis. Am Surg. 1997;63:361-364.

(53.) Haapanen E, Partanen J, Pellinen T. Acute renal failure following nontraumatic rhabdomyolysis. Stand J Urol Nephrol. 1988;22:305-308.

(54.) Prall J. Breeze R. Rhabdomyolysis following spinal cord injury: case report. J Trauma. 1995;39:367-368.

(55.) Defraigne JO, Pincmail J. Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle: physiopathology and prevention. Acta Chir Belg. 1998;98:176-186.

(56.) Hartnett S. Heparin-induced thrombocytopenia as the cause of gluteus muscle necrosis: a case study describing the benefits of multidisciplinary physical and psychosocial intervention. Ostomy Wound Manage. 2001;47:18-26.

(57.) Shank E, Muth C. Diver with decompression injury, elevation of serum transaminase levels, and rhabdomyolysis. Ann Emerg Med. 2001;37:533-536.

(58.) Browne R. Sickle cell trait and sudden death. Sports Med. 1994;18:373-374.

(59.) Schenk M, Beck D, Nolte M, Kox W. Continuous veno-venous hemofiltration for the immediate management of massive rhabdomyolysis after fulminant malignant hyperthermia in a body builder. Anesthesioloqy. 2001;94:1139-1141.

(60.) Brucato A, Bonati M, Gaspari F, et al. Tetany and rhabdomyolysis due to surreptitious furosemide: importance of magnesium supplementation. J Toxicol Clin Toxicol. 1993;31:341-344.

(61.) Fukada Y, Ohta S, Mizuno K, Hoshi K. Rhabdomyolysis secondary to hyperemesis gravidarum. Acta Obstet Gynecol Scand. 1999;78:71.

(62.) Heidemann H, Kruezfelder E. Hypokalemic rhabdomyolysis with myoglobinuria due to licorice ingestion and diuretic treatment. Kiln Wochenschr. 1983;61:303-305.

(63.) Saito T, Tsuboi Y, Fuisawa G, et al. An autopsy case of licorice-induced hypokalemic rhabdomyolysis associated with acute renal failure: special reference to profound calcium deposition in skeletal and cardiac muscle. J pn J Nephrol. 1994;36:1308-1314.

(64.) Kao K, Tsai Y, Lin M, Huang C, Tsao C, Chen Y. Hypokalemic muscular paralysis causing acute respiratory failure due to rbabdomyolysis with renal tubular acidosis in a chronic glue sniffer. J Toxicol Clin Toxicol. 2000;38:679-681.

(65.) Chang PT, Lin CK, Tsai MD, Chien BI, Cheng TI, Lin CS. Rhabdomyolysis associated with hyperosmolar non-ketotic coma: a case report. Zhonghua Yi Xue Za Zhi (Taipei). 1988;41:309-310.

(66.) Chen C, Chen J, Kao M. Severe rhabdomyolysis with good recovery in a patient with head injury: case report. Neurosurgery. 1997;41:293-296.

(67.) Nishihara G, Higashi H, Matsuo S, Yasunaga C, Sakemi T, Nakamoto M. Acute renal failure due to hypokalemic rhabdomyolysis in Gitelman's syndrome. Clin Nephrol. 1998;50:330-332.

(68.) Jolobe O, Sen I. Hyponatraemic rhabdomyolysis in Addison's disease. Postgrad Med J. 1995;71:574.

(69.) Alshanti M, Eledrisi MS, Jones E. Rhabdomyolysis associated with hyperthyroidism. Am J Emerg Med. 2001;19:317.

(70.) Lofberg M, Jankala H, Paetau A, Harkonen M, Somer H. Metabolic causes of recurrent rhabdomyolysis. Acta Neurol Scand. 1998;98:268-275.

(71.) Byrd RJ, Roy T, Rhabdomyolysis and bacterial pneumonia. Respir Med. 1998;92:359-362.

(72.) van Tol KM, Sluiter HE. Legionnaires' disease with rhabdomyolysis and acute renal failure. Neth J Med. 1998;53:43-44.

(73.) Neau D, Delamas Y, Merville P, et al. Rhabdomyolysis and Salmonella enteritidis infection. Eur J Clin Microbiol Infect Dis. 2000;19:973-975.

(74.) Mehta K, Halanker A, Makwana P, Torane P, Satija P, Shah V. Severe acute renal failure in malaria. J Postgrad Med. 2001;47:24-26.

(75.) Rastegar D, Claiborne C, Fleisher A, Matsumoto A. A patient with primary human immunodeficiency virus infection who presented with acute rhabdomyolysis. Clin Infect Dis. 2001;32:502-504.

(76.) Joshi MK, Liu H. Acute rhabdomyolysis and renal failure in HIV-infected patients: risk factors, presentation, and pathophysiology. AIDS Patient Care STDS. 2000;14:541-548.

(77.) Morton S, Mathai M, Byrd RJ, Fields C, Roy T. Influenza A pneumonia with rhabdomyolysis. South Med J. 2001:94:67-69.

(78.) Muthukumar T, Jha V, Sud A, Wanchoo A, Bambery P, Sakhuja V. Acute renal failure due to nontraumatic rhabdomyolysis following binge drinking. Ren Fail. 1999;21:545-549.

(79.) Richards J, Johnson E, Stark R, Derlet R. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med. 1999;17:681-685.

(80.) van der Woude F. Cocaine use and kidney damage. Nephrol Dial Transplant. 2000;15:299-301.

(81.) Ruttenber AJ, McAnally HB, Wetli CV. Cocaine-associated rhabdomyolysis and excited delirium: different stages of the same syndrome. Am J Forensic Med Pathol. 1999:20:120-127.

(82.) Cunningham M. Ecstasy-induced rhabdomyolysis and its role in the development of acute renal failure. Intensive Crit Care Nurs. 1997;13:216-223.

(83.) Bakir A, Dunea G. Renal disease in the inner city. Semin Nephrol. 2001;21:334-345.

(84.) Wrenn K, I. Rhabdomyolysis induced by caffeine overdose. Ann Emerg Med. 1989;18:94-97.

(85.) Stevens PE, De Verteuil JA, Rainford DJ. Acute renal failure secondary to rhabdomyolysis following self-poisoning with aminophylline. J R Army Med Corps. 1988;134:79-80.

(86.) Salmon J, Nicholson D. DIC and rhabdomyolysis following pseudoephedrine overdose. Am J Emerg Med. 1988;6:545-546.

(87.) Fanton L, Buperret S, Guillaumee F, Miras A, Vallon J, Malicier D. Fatal rhabdomyolysis in arsenic trioxide poisoning. Hum Exp Toxicol. 1999;18:640-641.

(88.) Rizzi D, Basile C, Di Maggio A, et al. Rhabdomyolysis and acute tubular necrosis in coniine (hemlock) poisoning. Lancet. 1989;2:1461-1462.

(89.) Lee PT, Wu ML, Tsai WJ, Ger J, Deng JF, Chung HM. Rhabdomyolysis: an unusual feature with mushroom poisoning. Am J Kidney Dis. 2001;38:E17.

(90.) Ho L, Cheong I, Jalial H. Rhabdomyolysis and acute renal failure following blowpipe dart poisoning. Nephron. 1996;72:676-678.

(91.) Bush S, Jansen P. Severe rattlesnake envenomation with anaphylaxis and rhabdomyolysis. Ann Emerg Med. 1995;25:845-848.

(92.) Sitprija V, Gopalakrishnakone P. Snake bite, rhabdomyolysis, and renal failure. Am J Kidney Dis. 1998;31:1-1ii.

(93.) Chao S, Lee Y. Acute rhabdomyolysis and intravascular hemolysis following extensive wasp stings, Int J Dermatol. 1999;38:135-137.

(94.) Logan J, Ogden D. Rhabdomyolysis and acute renal failure following the bite of the giant desert centipede Scolopendra heros. West J Med. 1985;142:549-550.

(95.) Lilley LL, Guanci R. Drug interaction triggers weakness. Am J Nurs. April 1998;98:10.

(96.) Shuster J. Olanzapine and rhabdomyolysis. Nursing. September 2000;30:87.

(97.) Moghadasian MH, Mancini GB, Frohlich JJ. Pharmacotherapy of hypercholesterolaemia: statins in clinical practice. Expert Opin Pharmacother 2000;1:683-695.

(98.) Su K, Lee Y, Lee M. Severe peripheral polyneuropathy and rhabdomyolysis in lithium intoxication: a case report. Gen Hasp Psychiatry. 1999;21:136-137.

(99.) Yoshikawa H, Watanabe T, Abe T, Oda Y, Ozawa K. Haloperidol-induced rhabdomyolysis without neuroleptic malignant syndrome in a handicapped child. Brain Dev. 2000;22:258-258.

(100.) Cannon M, Glazier S, Bauman L. Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion. J Neurosurg. 2001;95:1053-1056.

(101.) Emmett LM, Patel NC, Thanakirshnan K, Van der Wall H, Magee M, Allman KC. Extensive rhabdomyolysis after streptokinase therapy for acute myocardial infarction demonstrated by Tc-99m PYP scintigraphy. Clin Nucl Med. 1999;24:991-992.

(102.) Levy R, Sparano J, Khan G. Rhabdomyolysis: an unusual complication of cytotoxic chemotherapy. Med Oncol. 1995;12:219-222.

(103.) Reha W, Mangano F, Zeman R, Pahira J. Rhabdomyolysis: need for high index of suspicion. Urology. 1989;34:292-296.

(104.) Holt S, Reeder B, Wilson M, et al. Increased lipid peroxidation in patients with rhabdomyolysis. Lancet. 1999;353:1241.

(105.) Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol. 2000;8:72-76.

Laura Criddle is the clinical nurse specialist for the emergency department and the trauma/neuro intensive care unit at Oregon Health & Science University, Portland, Ore.

Author of Rhabdomyolysis: Pathophysiology, Recognition, and Management, Laura Criddle is the clinical nurse specialist for the emergency department and the trauma/neuro intensive care unit at Oregon Health & Science University, Portland, Ore.

COPYRIGHT 2003 American Association of Critical-Care Nurses
COPYRIGHT 2004 Gale Group