Prompt recognition and treatment of rhabdomyolysis are vital because severe disease can be associated with life-threatening acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more (AKI) and electrolyte imbalances.
Pathophysiology of Rhabdomyolysis
Normal skeletal muscle function is dependent on appropriate electrolyte exchange, adequate metabolism of adenosine triphosphate (ATP), and intact plasma membrane of the myocytes. In rhabdomyolysis, these processes are disrupted, resulting in the breakdown of skeletal muscle. Destruction of skeletal muscle tissue leads to release of the intracellular components of myocytes into the plasma, including creatine kinase (CK), myoglobin, and various electrolytes. Myoglobinuria and electrolyte abnormalities cause end-organ complications, including acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more .
Etiology of Rhabdomyolysis
Any form of muscle damage can theoretically result in rhabdomyolysis. The most common etiologies include
Mechanical trauma or muscle ischemia (eg, crush injuries, electric shocks Electrical Injuries Electrical injury is damage caused by generated electrical current passing through the body. Symptoms range from skin burns to damage to internal organs and other soft tissues, cardiac arrhythmias... read more , seizures Seizure Disorders A seizure is an abnormal, unregulated electrical discharge that occurs within the brain’s cortical gray matter and transiently interrupts normal brain function. A seizure typically causes altered... read more , or compartment syndrome Compartment Syndrome Compartment syndrome is increased tissue pressure within a closed fascial space, resulting in tissue ischemia. The earliest symptom is pain out of proportion to the severity of injury. Diagnosis... read more )
Drugs and toxins (eg, statins Elevated LDL cholesterol treatment Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis... read more , antibiotics Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more , anxiolytics Anxiolytics and Sedatives Anxiolytics and sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause stupor and respiratory depression, which is managed with intubation and mechanical ventilation... read more , antipsychotics Antipsychotic Drugs Antipsychotic drugs are divided into conventional antipsychotics and 2nd-generation antipsychotics (SGAs) based on their specific neurotransmitter receptor affinity and activity. SGAs may offer... read more , cocaine Cocaine Cocaine is a sympathomimetic drug with central nervous system stimulant and euphoriant properties. High doses can cause panic, schizophrenic-like symptoms, seizures, hyperthermia, hypertension... read more , amphetamines Amphetamines Amphetamines are sympathomimetic drugs with central nervous system stimulant and euphoriant properties whose toxic adverse effects include delirium, hypertension, seizures, and hyperthermia... read more , alcohol Alcohol Toxicity and Withdrawal Alcohol (ethanol) is a central nervous system depressant. Large amounts consumed rapidly can cause respiratory depression, coma, and death. Large amounts chronically consumed damage the liver... read more )
Infection (eg, influenza A and B Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more , coxsackievirus Overview of Enterovirus Infections Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more , Staphylococcus aureus Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more )
Less common etiologies include
Electrolyte disorders (eg, hypokalemia Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more , hypophosphatemia Hypophosphatemia Hypophosphatemia is a serum phosphate concentration 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness... read more )
Endocrine disorders (eg, diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more and nonketotic hyperglycemia)
Genetic disorders (eg, Duchenne muscular dystrophy, Becker muscular dystrophy Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more )
Extreme exercise or prolonged immobilization
Extremes in body temperature (eg, hypothermia Hypothermia Hypothermia is a core body temperature 35° C. Symptoms progress from shivering and lethargy to confusion, coma, and death. Mild hypothermia requires a warm environment and insulating blankets... read more , hyperthermia in neuroleptic malignant syndrome Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is characterized by altered mental status, muscle rigidity, hyperthermia, and autonomic hyperactivity that occur when certain neuroleptic drugs are used. Clinically... read more or malignant hyperthermia Malignant Hyperthermia Malignant hyperthermia is a life-threatening elevation in body temperature usually resulting from a hypermetabolic response to concurrent use of a depolarizing muscle relaxant and a potent,... read more , and heatstroke Heatstroke Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction and often death. Symptoms include temperature > 40° C and altered mental status... read more )
Symptoms and Signs of Rhabdomyolysis
The classic triad of symptoms in rhabdomyolysis is muscle pain, weakness, and reddish-brown urine. However, this trio of symptoms is present in fewer than 10% of all patients with rhabdomyolysis.
Clinical presentation is variable and about 50% of patients have no muscle complaints at all ( 1 Symptoms and signs references Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more ). When present, muscle pain affects proximal muscle groups, such as shoulders, thighs, lower back, and calves. At a high concentration, myoglobin excreted into the urine changes its color to red or brown and can be assessed with a dipstick analysis. However, due to rapid excretion of myoglobin, rhabdomyolysis cannot be excluded in the absence of myoglobinuria or urine discoloration.
Other signs and symptoms vary based on the inciting event and complications (eg, fever is present in patients with infection and altered mental status in cases of intoxication).
Acute kidney injury is reported in 15 to 50% of rhabdomyolysis complications ( 1–3 Symptoms and signs references Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more ), and is higher in patients with concurrent dehydration, sepsis, and creatine kinase level over 15,000 IU/L (250 mckat/L).
Symptoms and signs references
1. Gabow P, Kaehny W, Kelleher SP: The spectrum of rhabdomyolysis. Medicine (Baltimore) 61(3):141-152, 1982. doi: 10.1097/00005792-198205000-00002
2. Melli G, Chaudhry V, Cornblath DR: Rhabdomyolysis: An evaluation of 475 hospitalized patients. Medicine (Baltimore) 84(6):377-385, 2005. doi: 10.1097/01.md.0000188565.48918.41
3. Veenstra J, Smit WM, Krediet RT, et al: Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant 9(6):637-641, 1994. doi: 10.1093/ndt/9.6.637
Diagnosis of Rhabdomyolysis
Serum levels of creatine kinase (CK) >5 times the upper limit of normal
Rhabdomyolysis is suspected based on history, clinical signs, and symptoms. Confirmation is by laboratory testing of elevated CK. Although a cutoff threshold has not been established, a CK level of > 5 times the upper limit of normal is typically required for diagnosis.
Other corroborating laboratory testing includes the presence of myoglobin in urine. Myoglobinuria is detected when urinary myoglobin exceeds 250 mcg/mL. Other laboratory features include rapidly rising serum creatinine, hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There are... read more , hyperuricemia, hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration 8.8 mg/dL ( 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration 4.7 mg/dL ( 1.17... read more , or hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism, vitamin... read more , hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical features... read more , lactic acidosis Lactic Acidosis Lactic acidosis is a high anion gap metabolic acidosis due to elevated blood lactate. Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both. (See also... read more , and thrombocytopenia Overview of Platelet Disorders Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more .
Treatment of Rhabdomyolysis
Treatment of underlying cause
Treatment of complications
In general, treatment is supportive along with treatment of cause and of any resulting complications.
Supportive treatment includes intravascular expansion with IV fluids to prevent acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more as well as other supportive treatments (eg, mechanical ventilation in cases of acute respiratory failure Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is defined as severe hypoxemia (PaO2 (See also Overview of Mechanical Ventilation.) Airspace filling in acute hypoxemic respiratory failure (AHRF) may result... read more ). There is no clear evidence of benefit of urinary alkalinization with sodium bicarbonate, which is particularly contraindicated in cases of alkalosis Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3−) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common... read more or hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration 8.8 mg/dL ( 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration 4.7 mg/dL ( 1.17... read more .
If the inciting event is due to a compartment syndrome Compartment Syndrome Compartment syndrome is increased tissue pressure within a closed fascial space, resulting in tissue ischemia. The earliest symptom is pain out of proportion to the severity of injury. Diagnosis... read more , early fasciotomy is done in addition to supportive therapy. Infections are treated with appropriate antimicrobial agents. Any potential inciting drugs (eg, statins) are discontinued. Electrolyte disturbances are corrected.
Complications such as acute kidney injury are treated with IV fluids and sometimes hemodialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more . Disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more is treated with fresh frozen plasma.
The classic triad of symptoms (myalgias, muscle weakness, and tea-colored urine) is present in < 10% of cases.
A CK level of > 5 times the upper limit of normal is typically required for diagnosis.
Treatment is supportive with IV hydration as well as concurrent treatment of the inciting cause and any resulting complications.
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