INTRODUCTION — Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. The clinical manifestations and diagnosis of rhabdomyolysis will be reviewed here. The causes of rhabdomyolysis; the clinical features and diagnosis of acute kidney injury (AKI) due to rhabdomyolysis; the management of patients with rhabdomyolysis, including methods to prevent AKI and related metabolic complications; and the prevention and management of acute compartment syndrome are discussed in detail separately:
Rhabdomyolysis: Epidemiology and etiology
Clinical features and diagnosis of heme pigment-induced acute kidney injury
Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)
Crush-related acute kidney injury
Acute compartment syndrome of the extremities
CLINICAL MANIFESTATIONS — Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. Creatine kinase (CK) levels are typically markedly elevated, and muscle pain and myoglobinuria may be present. The severity of illness ranges from asymptomatic elevations in serum muscle enzymes to life-threatening disease associated with extreme enzyme elevations, electrolyte imbalances, and acute kidney injury (AKI).
Symptoms and signs — Rhabdomyolysis is characterized clinically by the triad of myalgias, muscle weakness, and red to brown urine due to myoglobinuria . Biochemically, several serum muscle enzymes are elevated, including CK. The degree of muscle pain and other symptoms varies widely.
Most of the symptoms of rhabdomyolysis are nonspecific.
Classic triad — The characteristic triad of complaints in rhabdomyolysis is muscle pain, weakness, and dark urine [2-5]. However, the full triad is observed in only 1 to 10 percent of cases [3,5-10].
Muscle — When present, muscle symptoms of rhabdomyolysis may develop over hours to days .
●Pain – In hospitalized patients with rhabdomyolysis, muscle pain affects 23 to 80 percent of patients [3,7,11,12]. Muscle pain, when present, is typically most prominent in proximal muscle groups, such as the thighs and shoulders, and in the lower back and calves [2,5]. Other muscle symptoms include stiffness and cramping.
●Weakness – Muscle weakness may be present depending upon the severity of muscle injury and affects 12 to 70 percent of hospitalized patients with rhabdomyolysis [3,7,11,12]. Weakness usually occurs in the same muscle groups affected by pain or swelling, with the proximal legs most frequently involved.
●Swelling – Muscle swelling affects 8 to 52 percent of patients with rhabdomyolysis [3,11,12]. When it occurs, detectable swelling in the extremities generally develops with fluid repletion. Swelling is less common on hospital admission . Swelling may be due to either:
•Myoedema, which is nonpitting and is apparent at presentation or develops after rehydration
•Peripheral edema, which is pitting and occurs with rehydration (particularly in patients with AKI)
Limb induration is occasionally present.
Urine — Dark-colored urine (red to brown, "tea-colored," "cola-colored") is one of the classic signs of rhabdomyolysis (see 'Classic triad' above), but it occurs in ≤10 percent of cases [3,7,9,13]. Urinalysis is required to distinguish myoglobinuria (from rhabdomyolysis) from hematuria. (See "Urinalysis in the diagnosis of kidney disease" and 'Urine findings and myoglobinuria' below.)
Myoglobin, a heme-containing respiratory protein, is released from damaged muscle in parallel with CK. Myoglobin is a monomer that is not significantly protein bound and is therefore rapidly excreted in the urine, often resulting in the production of red to brown urine. It appears in the urine when the plasma concentration exceeds 1.5 mg/dL . Visible changes in the urine only occur once urine levels exceed from approximately 100 to 300 mg/dL, although it can be detected by the urine (orthotolidine) dipstick at concentrations of only 0.5 to 1 mg/dL [3,14].
Hemoglobin, the other heme pigment capable of producing pigmented urine, is much larger (a tetramer) than myoglobin and is protein bound. As a result, much higher plasma concentrations are required before red to brown urine is seen, resulting in a change in plasma color.
Skin — Skin changes caused by ischemic tissue injury, such as discoloration or blisters, may also be seen but are present in <10 percent of patients [5,14].
Systemic — Additional symptoms that are more common in severely affected patients include malaise, fever, tachycardia, nausea and vomiting, and abdominal pain .
Associated manifestations — Other manifestations of rhabdomyolysis include fluid and electrolyte abnormalities, many of which precede or occur in the absence of kidney failure, and hepatic injury ; additionally, cardiac dysrhythmias and risk of cardiac arrest may result from the severe hyperkalemia that occurs with significant myonecrosis . Later complications include AKI, compartment syndrome, and, rarely, disseminated intravascular coagulation.
Fluid and electrolyte abnormalities — Hypovolemia and abnormalities in serum electrolytes and uric acid are common in patients with rhabdomyolysis [3,16,17]:
●Hypovolemia results from "third-spacing" due to the influx of extracellular fluid into injured muscles and increases the risk of AKI .
●Hyperkalemia and hyperphosphatemia result from the release of potassium and phosphorus from damaged muscle cells. Levels of potassium may increase rapidly, but the levels of potassium and phosphate decrease as they are excreted in the urine. Hyperkalemia is more common in patients with oliguric AKI .
●Hypocalcemia, which can be extreme, occurs in the first few days because of entry into damaged myocytes and both deposition of calcium salts in damaged muscle and decreased bone responsiveness to parathyroid hormone [19,20]. During the recovery phase, serum calcium levels return to normal and may rebound to significantly elevated levels due to the release of calcium from injured muscle, mild secondary hyperparathyroidism from the acute renal failure, and an increase in calcitriol (1,25-dihydroxyvitamin D) [19,20]. (See "Etiology of hypocalcemia in adults", section on 'Extravascular deposition' and "Etiology of hypercalcemia", section on 'Rhabdomyolysis and acute renal failure'.)
●Severe hyperuricemia may develop because of the release of purines from damaged muscle cells and from reduced urinary excretion if AKI occurs .
●Metabolic acidosis is common, and an increased anion gap may be present.
Acute kidney injury — Acute kidney injury (AKI, acute renal failure) is a common complication of rhabdomyolysis. The reported frequency of AKI ranges from 15 to over 50 percent [3,22,23]. The risk of AKI is lower in patients with CK levels at admission less than 15 to 20,000 units/L; risk factors for AKI in patients with lower values include dehydration, sepsis, and acidosis . Volume depletion resulting in renal ischemia, tubular obstruction due to heme pigment casts, and tubular injury from free chelatable iron all contribute to the development of renal dysfunction. Reddish-gold pigmented casts are often observed in the urine sediment. AKI in patients with rhabdomyolysis is discussed separately. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)
Compartment syndrome — Compartment syndrome is a potential complication of severe rhabdomyolysis that may develop after fluid resuscitation, with worsening edema of the limb and muscle. Compartment syndrome can also be a cause of rhabdomyolysis, as may occur after traumatic (eg, tibial fractures) or nontraumatic (eg, prolonged limb compression) etiologies.
Compartment syndrome exists when increased pressure in a closed anatomic space threatens the viability of the muscles and nerves within the compartment due to compromised perfusion and local ischemia. Capillary ischemia in compartment syndrome exacerbates muscle and nerve tissue injury. Compartment syndrome is discussed in detail separately. (See "Pathophysiology, classification, and causes of acute extremity compartment syndrome" and "Acute compartment syndrome of the extremities" and "Idiopathic systemic capillary leak syndrome", section on 'Compartment syndrome'.)
Disseminated intravascular coagulation — Infrequently, severe rhabdomyolysis may be associated with the development of disseminated intravascular coagulation due to the release of thromboplastin and other prothrombotic substances from the damaged muscle [5,24,25]. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)
Cardiac dysrhythmias — Cardiac dysrhythmias and risk of cardiac arrest may result from hyperkalemia and hypocalcemia associated with rhabdomyolysis [6,26].
Other organ involvement
●Liver injury – Liver dysfunction, typically reversible, occurs in up to 25 percent of patients with rhabdomyolysis [15,25-28]. It must be distinguished from transaminase elevations originating from injured muscle.
●Neurologic – Altered mental status (eg, confusion, agitation) may result from the underlying etiology (eg, toxins, drugs, trauma, or electrolyte abnormalities) of rhabdomyolysis .
●Pulmonary – Respiratory failure or acute respiratory distress syndrome may accompany rhabdomyolysis due to the underlying etiology (infection, illicit drugs, metabolic myopathy) [29,30].
EVALUATION AND DIAGNOSIS
When to suspect rhabdomyolysis — Rhabdomyolysis should be suspected in patients presenting with the triad of muscle pain, weakness, and dark-colored urine, but few patients have all three classic symptoms (see 'Classic triad' above). Thus, a diagnostic evaluation should be performed in individuals with both myalgias and pigmenturia. Additional scenarios where rhabdomyolysis should be suspected include the following:
●Patients with a potential cause, triggering event, or increased risk of rhabdomyolysis (table 1), with or without myalgias or pigmenturia, as symptoms may be vague or absent in up to 50 percent of patients, including those without a reliable medical history (eg, patients found down, or with coma, sedation, or delirium). (See "Rhabdomyolysis: Epidemiology and etiology", section on 'Classification'.)
●Patients with acute muscle weakness and marked elevation of creatine kinase (CK). (See 'Creatine kinase elevation' below.)
History and examination — The history should focus on factors that may cause or predispose to rhabdomyolysis, including traumatic, nontraumatic exertional, and nontraumatic nonexertional etiologies . These include (see "Rhabdomyolysis: Epidemiology and etiology"):
●Prescription medications with attention to myotoxic agents
●Alcohol and/or substance abuse
●Infection or sepsis
●Strenuous or unaccustomed physical exertion or exercise
●Heat exposure or hyperthermia of any cause
●History of myopathy or muscular dystrophy
●History of exercise intolerance
●Prior episodes of rhabdomyolysis
The examination should focus on signs that suggest muscle injury, including muscle weakness and tenderness, limb edema, and evidence of trauma or compartment syndrome.
Initial laboratory studies — We obtain the following key diagnostic laboratory studies:
●Serum CK, the standard biomarker for rhabdomyolysis (see 'Creatine kinase elevation' below)
●Urinalysis of a fresh urine specimen, including centrifugation with dipstick evaluation of the supernatant and microscopic evaluation of the sediment, for evidence of myoglobinuria (see "Urinalysis in the diagnosis of kidney disease" and 'Urine findings and myoglobinuria' below)
We also obtain the following tests, which may help in prompt recognition of other potentially dangerous manifestations, in differential diagnoses, and in identifying the cause of rhabdomyolysis  (see 'Associated manifestations' above and 'Identifying the cause' below and 'Differential diagnosis' below):
●Complete blood count, differential, and platelet count, for evidence of infection or hemolysis
●Blood urea nitrogen, and creatinine, for renal function and evidence of acute kidney injury (AKI)
●Routine electrolytes plus calcium and phosphate, for hyperkalemia, hypocalcemia, and hyperphosphatemia
●Liver function tests, particularly aspartate aminotransferase (AST) and alanine aminotransferase (ALT), for evidence of hepatic impairment, though both AST and ALT elevations can suggest release from muscle due to rhabdomyolysis
●Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and fibrinogen, for evidence of disseminated intravascular coagulation
●Arterial blood gas, for metabolic acidosis
●Serum albumin, for hypoalbuminemia, which can be seen with systemic capillary leak syndrome (see "Idiopathic systemic capillary leak syndrome", section on 'Compartment syndrome')
●Electrocardiography, for cardiac dysrhythmias secondary to hyperkalemia and hypocalcemia
●Blood cultures and infection work-up if febrile or suspicion for infection
●Alcohol level and toxicology screen, if suspicion for alcohol or drugs as the primary or contributing cause of rhabdomyolysis (see "Clinical assessment of substance use disorders" and "Screening for unhealthy use of alcohol and other drugs in primary care")
Additional testing, such as electromyography (EMG), magnetic resonance imaging (MRI), molecular genetic studies, or muscle biopsy, is not required for the diagnosis of rhabdomyolysis. These studies are generally reserved for patients in whom an underlying myopathy is suspected. (See 'When to suspect an inherited cause' below and 'Differential diagnosis' below.)
Laboratory findings — The hallmark of rhabdomyolysis is an elevation in CK and other serum muscle enzymes. The other characteristic finding is the reddish-brown urine of myoglobinuria, but because this may be observed in only a small percentage of cases, its absence does not exclude the diagnosis.
Creatine kinase elevation — Serum CK levels at presentation of rhabdomyolysis are usually at least five times the upper limit of normal, but range from approximately 1500 to over 100,000 units/L. In a series of 475 hospitalized patients with rhabdomyolysis, the mean peak CK reported for each of a variety of different causes and for patients with both single and multiple causes ranged from approximately 10,000 to 25,000 units/L ; exceptions were three patients with malignant hyperthermia, whose values averaged almost 60,000 units/L. Premorbid CK level is also important in patients with genetic underlying muscular disorders.
The serum CK begins to rise within 2 to 12 hours following the onset of muscle injury and reaches its maximum within 24 to 72 hours. A decline is usually seen within three to five days of cessation of muscle injury. CK has a serum half-life of approximately 1.5 days and declines at a relatively constant rate of approximately 40 to 50 percent of the previous day's value [5,14,32]. In patients whose CK does not decline as expected, continued muscle injury, an underlying muscle disease, or the development of a compartment syndrome may be present.
The CK is generally entirely or almost entirely of the MM or skeletal muscle fraction; a small proportion of the total CK may be from the MB or myocardial fraction. The presence of MB reflects the small amount found in skeletal muscle rather than the presence of myocardial disease.
Urine findings and myoglobinuria — Evidence of myoglobinuria should be sought by routine urine dipstick evaluation combined with microscopic examination of the urinary sediment. The utility of urinalysis for confirming myoglobinuria is limited by suboptimal sensitivity and specificity.
Testing of the unspun urine or the supernatant of the centrifuged urine will be positive for heme on dipstick if myoglobinuria is present, even if red to reddish-brown urine is not evident macroscopically. However, a positive dipstick for heme may result not only from free myoglobin but also from urinary red blood cells (RBCs) or free hemoglobin (algorithm 1). The visual and microscopic examination of the sediment from a fresh urine specimen is required to exclude the presence of RBCs as the cause of positive testing. RBCs in an older specimen may hemolyze over time, confounding the results.
●What constitutes a positive test for myoglobinuria? – Myoglobinuria is present when both of the following are present :
•Urine supernatant tests positive for heme by dipstick after centrifugation, while the urine has a normal color.
•Urinary sediment shows few or no RBCs (<5 RBCs per high-powered field). (See "Urinalysis in the diagnosis of kidney disease", section on 'Red to brown urine'.)
●Suboptimal sensitivity and specificity of myoglobinuria – Myoglobinuria lacks sensitivity as a test for rhabdomyolysis; it is not detected in >65 percent of patients with rhabdomyolysis due to the more rapid clearance of myoglobin, compared with CK, following muscle injury. In addition, both hemoglobin and myoglobin can be detected on the urine dipstick as "blood;" thus, the specificity of testing for myoglobin is limited if RBC or hemolysis is present .
●Time course of myoglobin release and clearance – Myoglobin has a half-life of only two to three hours, much shorter than that of CK (36 hours). Because of its rapid excretion and metabolism to bilirubin, serum myoglobin levels may return to normal within six to eight hours after release from muscle.
Thus, it is not unusual for CK levels to remain elevated in the absence of myoglobinuria . In rhabdomyolysis, myoglobin appears in the plasma before CK elevation occurs and disappears while CK is still elevated or rising. Rhabdomyolysis does not occur unless CK is elevated five times or more above the upper limit of normal (see 'Creatine kinase elevation' above). Pigmenturia will be missed in rhabdomyolysis if the filtered load of myoglobin is insufficient or has largely resolved before the patient seeks medical attention due to its rapid clearance.
●Other urine findings – Proteinuria may be present, due to the release of myoglobin and other proteins by the damaged myocytes . In one study, it was detected by dipstick in 45 percent of patients . The urine sediment may show myoglobin casts and dead epithelial cells.
Other serum enzymes — In addition to elevation of the CK, other enzymes indicative of muscle injury are typically elevated with rhabdomyolysis (eg, aldolase, aminotransferases, lactate dehydrogenase). Such findings can cause confusion with liver disease but do not inform the diagnosis when clinical features and other findings support rhabdomyolysis. Gamma-glutamyl transferase (GGT) and bilirubin are not found in muscle, and in this context, demonstrating a CK elevation and a normal serum GGT or bilirubin level will help to refocus the evaluation on muscle injury and avoid unnecessary work-up of liver.
Serum aminotransferases are nonspecific markers of tissue injury that can result from muscle injury or from liver injury. In one study, AST was elevated in 93 percent and ALT in 75 percent of rhabdomyolysis cases in which the CK was greater than or equal to 1000 units/L . In only one instance was the ALT greater than the AST, although the AST declines faster than the ALT as the rhabdomyolysis resolves, such that the two may equalize after a few days . (See "Muscle enzymes in the evaluation of neuromuscular diseases".)
Making the diagnosis — We make the diagnosis of rhabdomyolysis when the following criteria are present :
●One or more causative or triggering factors, such as trauma, crush injury, compartment syndrome, extreme exertion, severe heat exposure/hyperthermia, prolonged immobilization, or intoxication (table 1), or
●Characteristic symptoms and signs, particularly muscle weakness and dark-colored urine (see 'Symptoms and signs' above), or
●Urinalysis consistent with myoglobinuria: heme positive by dipstick with <5 RBCs on microscopic examination (see 'Urine findings and myoglobinuria' above)
●A marked acute elevation in serum CK
While no absolute cut-off value for CK elevation can be defined, the CK is typically at least five times the upper limit of normal and is usually greater than 5000 units/L. The degree of CK elevation should be considered in the clinical context of the history and examination findings, including premorbid CK values when available. (See 'Creatine kinase elevation' above.)
IDENTIFYING THE CAUSE
Evident from presentation — In many cases, acquired causes of rhabdomyolysis are obvious and can be easily ascertained from the history and physical examination (eg, trauma, extreme physical exertion, prolonged immobilization) and/or initial laboratory studies (eg, infections, electrolyte abnormalities) (table 1). An inherited cause should be considered when the initial evaluation is unrevealing.
When to suspect an inherited cause — The possibility of an inherited cause or susceptibility for rhabdomyolysis (eg, metabolic myopathies, muscular dystrophies) should be evaluated if the cause is not apparent from the history, physical examination, and initial laboratory studies .
There are subtle differences in the clinical manifestations of the various metabolic myopathies, but these conditions should be suspected when the following clinical circumstances are present:
●There are recurrent episodes of rhabdomyolysis after exertion or in association with fasting or a viral illness. The last two associations occur most commonly with carnitine palmitoyltransferase deficiency and other disorders of lipid metabolism.
●There is a history of exercise intolerance, recurrent cramps, and fatigue beginning in childhood, as well as episodes of pigmenturia occurring in adolescence. Recurrent cramping and rhabdomyolysis may suggest a glycogen storage disorder. Marked fatigue and exercise intolerance may suggest a diagnosis of mitochondrial myopathy.
●There is a family history of rhabdomyolysis or exercise intolerance.
Genomic analysis can be pursued as a first-line test, especially if the clinical history is suggestive of a metabolic myopathy. Histochemical analysis of a muscle biopsy specimen may be necessary if genomic testing is unrevealing or detects variants of unknown significance. Regardless of the etiology, muscle affected by a metabolic disorder will be depleted of energy during an acute rhabdomyolysis event. Hence, when metabolic myopathy is suspected, muscle biopsy, if needed, should be delayed by at least one month.
The diagnostic approach to a suspected metabolic myopathy is discussed separately. (See "Approach to the metabolic myopathies", section on 'Evaluation and diagnosis' and "Approach to the patient with muscle weakness".)
DIFFERENTIAL DIAGNOSIS — The differential diagnoses of myalgia, elevated creatine kinase (CK) and other muscle enzymes, and dark urine are fairly extensive. Additionally, the following conditions may be considered, depending upon the combination of findings that are present, but distinctions can usually be made with readily available information from the medical history as well as the physical and laboratory examinations:
●Strenuous or unaccustomed muscular activity – The line between a normal physiologic response to exercise and clinically meaningful rhabdomyolysis is not clear, as CK elevation up to and exceeding 2000 units/L and myalgias commonly occur after certain types of prolonged or strenuous exercise . However, when the CK elevation is marked and acute and when myoglobinuria is present, the diagnosis of rhabdomyolysis can generally be made with confidence.
●Delayed-onset muscle soreness (DOMS) – Approximately two to three days after strenuous exercise or typically unaccustomed or eccentric exercise, pain can be severe with potentially extensive myofiber damage. Symptoms resolve five to seven days postexercise . This condition may signify a very mild form of rhabdomyolysis, in which muscle proteins are released into the blood stream. These patients do not have an identifiable muscle enzyme defect.
●Myocardial infarction – Although serum CK also rises acutely with myocardial infarction, patients with rhabdomyolysis alone do not have ischemic chest pain or electrocardiogram (ECG) signs of myocardial infarction. Additionally, the CK-MM fraction is elevated, while little or no CK-MB is present. Assays for cardiac troponins (both the I and T isoforms) are highly sensitive and specific for cardiac muscle injury, although both isoforms can sometimes be elevated in patients with rhabdomyolysis [38-40].
The basis for this elevation is not clear but may relate to nonischemic cardiac events that may occur in patients with rhabdomyolysis, including seizures, sepsis, and renal failure , or, in the case of troponin T, to cross-reaction with diseased skeletal muscle [39,42]. (See "Troponin testing: Clinical use" and 'Creatine kinase elevation' above and "Diagnosis of acute myocardial infarction" and "Troponin testing: Analytical considerations".)
●Hematuria and hemoglobinuria – Both hematuria and hemoglobinuria (due to hemolysis) may result in red to reddish-brown urine and may be confused with myoglobinuria. Careful examination of the urine for red blood cells (present in hematuria, by definition), of serum for evidence of hemolysis, and of the CK (which is not elevated in hemolysis, or most patients with hematuria) will help distinguish these conditions. Other causes of red to brown urine include various foods and drugs, but such patients lack evidence of skeletal muscle injury, including CK elevation. (See 'Urine findings and myoglobinuria' above and 'Evaluation and diagnosis' above and "Etiology and evaluation of hematuria in adults", section on 'Red to brown urine'.)
●Inflammatory myopathy – Patients with inflammatory myopathy can also exhibit myalgias and elevated CK and may exhibit myoglobinuria . These patients can be differentiated from patients with rhabdomyolysis by the chronicity of disease, usually symmetric proximal muscle weakness developing over weeks to months, relative stability of the laboratory abnormalities compared with patients with rhabdomyolysis, prolonged duration of known CK elevation, and the systemic features associated with the inflammatory myopathies, such as dermatomyositis, immune-mediated necrotizing myopathy, and the antisynthetase syndrome.
Patients with rhabdomyolysis generally do not exhibit electromyographic or histologic changes suggestive of myositis except in rare patients in whom both are present [44-46]. Concurrent statin therapy may be a risk factor for self-limited toxic muscle injury or, alternatively, subacutely progressive immune-mediated necrotizing myopathy that requires immunosuppression . (See 'Evaluation and diagnosis' above and "Clinical manifestations of dermatomyositis and polymyositis in adults".)
Patients on statin medications may develop an immune-mediated necrotizing myopathy with markedly elevated levels of CK and weakness that does not improve with discontinuation of statins but that does respond to long-term combination immunosuppressive or immunomodulatory therapies [48-51]. These patients can be distinguished from patients with rhabdomyolysis by the persistence of symptoms and findings, including the elevation in CK, in the absence of treatment with immunosuppressives, and by their serum autoantibody profiles and muscle histopathologic changes. (See "Pathogenesis of inflammatory myopathies", section on 'Immune-mediated necrotizing myopathy' and "Statin muscle-related adverse events".)
●Renal colic – In patients presenting with back pain, rhabdomyolysis may be confused with renal colic. Additionally, urine dipstick testing may be positive for blood. However, urolithiasis is not associated with marked elevations of the CK, and myoglobinuria is not present. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis".)
MANAGEMENT — The major issues in the treatment of patients with rhabdomyolysis, which are discussed in detail separately, include:
●Recognition and management of fluid and electrolyte abnormalities, which should be initiated regardless of renal function and which may prevent severe metabolic disturbances and acute kidney injury (see "Clinical features and diagnosis of heme pigment-induced acute kidney injury" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)")
●Identification of the specific causes and the use of appropriate countermeasures directed at the triggering events, including discontinuation of drugs or other toxins that may be etiologic factors (see "Rhabdomyolysis: Epidemiology and etiology", section on 'Classification')
●Prompt recognition, evaluation, and treatment of compartment syndrome in patients in whom it is present (see "Crush-related acute kidney injury" and "Acute compartment syndrome of the extremities")
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Rhabdomyolysis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Main clinical manifestations – The clinical manifestations of rhabdomyolysis include myalgias, weakness, red to brown urine due to myoglobinuria, and elevated serum muscle enzymes, including creatine kinase (CK). The degree of myalgias and other symptoms varies widely, and some patients are asymptomatic. Fever, malaise, tachycardia, and gastrointestinal symptoms may be present. Muscle swelling may occur with rehydration. (See 'Symptoms and signs' above.)
●Associated manifestations – Other manifestations include fluid and electrolyte abnormalities; hypovolemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, and metabolic acidoses may be seen. Hyperkalemia may result in cardiac dysrhythmias. Later complications include acute kidney injury (AKI), hypercalcemia, compartment syndrome, and, rarely, disseminated intravascular coagulation. (See 'Associated manifestations' above and 'Fluid and electrolyte abnormalities' above and 'Acute kidney injury' above and 'Compartment syndrome' above and 'Disseminated intravascular coagulation' above.)
●When to suspect rhabdomyolysis – Rhabdomyolysis should be suspected in patients presenting with the triad of muscle pain, weakness, and dark-colored urine, but few patients have all three classic symptoms. Therefore, suspicion should be raised for patients with a potential cause, triggering event, or increased risk of rhabdomyolysis (table 1), with or without myalgias or pigmenturia, as symptoms may be vague or absent in up to 50 percent of patients, including those without a reliable medical history (eg, patients found down, or with coma, sedation, or delirium).
●Evaluation – The history should focus on factors that may cause or predispose to rhabdomyolysis, and the examination on signs of muscle injury; these points and the initial laboratory studies are outlined above. (See 'History and examination' above and 'Initial laboratory studies' above.)
●Characteristic laboratory findings – The laboratory findings that characterize rhabdomyolysis include an acute elevation in the CK and other muscle enzymes and a decline in these values within three to five days of cessation of muscle injury. The other characteristic finding is the reddish-brown urine of myoglobinuria, but this finding is often absent because of the relative rapidity with which myoglobin is cleared. The serum CK is generally entirely or almost entirely of the MM or skeletal muscle fraction, although small amounts of the MB fraction may be present. (See 'Laboratory findings' above and 'Creatine kinase elevation' above and 'Urine findings and myoglobinuria' above.)
●Diagnosis – We diagnose rhabdomyolysis in a patient with one or more causative or triggering factors (table 1), or characteristic symptoms and signs, particularly muscle weakness and dark-colored urine (see 'Symptoms and signs' above), or urinalysis consistent with myoglobinuria, and a marked acute elevation in serum CK; the CK is typically at least five times the upper limit of normal and is frequently greater than 5000 units/L. Key diagnostic laboratory studies include the CK and urinalysis with dipstick and microscopic evaluation. Myoglobinuria results in a positive urine dipstick test for blood and less than five red blood cells on microscopic examination of the urine sediment. (See 'Evaluation and diagnosis' above.)
●Identifying the cause – In many cases, acquired causes of rhabdomyolysis are obvious or can be easily ascertained from the history and physical examination (eg, trauma, extreme physical exertion, prolonged immobilization) and/or initial laboratory studies (eg, infections, electrolyte abnormalities) (table 1). An inherited cause should be considered when the initial evaluation is unrevealing. (See 'Identifying the cause' above.)
●Differential diagnosis – The differential diagnosis depends upon the combination of findings present. It includes myocardial infarction, other causes of red or brown urine, inflammatory myopathy, genetic muscle disorders (muscular dystrophy, metabolic myopathy, and mitochondrial cytopathies), and local causes of pain, such as deep vein thrombosis or renal colic. (See 'Differential diagnosis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc L Miller, MD, who contributed to an earlier version of this topic review.
19 : The pathophysiology of altered calcium metabolism in rhabdomyolysis-induced acute renal failure. Interactions of parathyroid hormone, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol.
20 : Hypocalcemia and hypercalcemia in patients with rhabdomyolysis with and without acute renal failure.
21 : Rhabdomyolysis following status epilepticus with hyperuricemia: A case report and literature review.
23 : Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis.
26 : An evidence-based narrative review of the emergency department evaluation and management of rhabdomyolysis.
32 : Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis.
33 : Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury.
39 : Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T.
41 : Elevated cardiac troponins: the ultimate marker for myocardial necrosis, but not without a differential diagnosis.
42 : Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: implications for the diagnosis of myocardial infarction.
47 : Polymyositis evolving after rhabdomyolysis associated with HMG-CoA reductase inhibitors: a report of two cases.
48 : A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.
49 : Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.
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