Basics
Description
- Rhabdomyolysis is defined as skeletal muscle breakdown resulting from injury.
- Injury may result from many causes including trauma, infection, medications or inherited disorders
- Classic presentation is with a triad of myalgia, weakness, and dark urine.
- Characterized by elevated creatinine kinase (CK) and myoglobinuria
- Release of intracellular contents from damaged muscle cells may cause severe electrolyte disturbances including life-threatening hyperkalemia, hyperphosphatemia, and hypocalcemia.
- The resulting myoglobinuria can cause obstruction of renal tubules and pigment-induced acute kidney injury (AKI), the most serious complication of rhabdomyolysis.
Epidemiology
- Rhabdomyolysis is more common in adults than children, where it is commonly due to illicit or prescription drugs or due to trauma.
- Rhabdomyolysis may be a common clinical problem in a catastrophic disaster (e.g., an earthquake).
- Rhabdomyolysis accounts for 7 " 10% of cases of AKI in the United States.
Risk Factors
Genetics
Many unusual causes of rhabdomyolysis, including muscle enzyme deficiencies, muscular dystrophy, and disorders of mitochondrial metabolism, are heritable disorders.
Etiology
- There are numerous potential causes of rhabdomyolysis, which can be sporadic or recurrent, traumatic, or nontraumatic.
- Muscle trauma is a common cause in both adults and children. This may occur from crush or compression injury (crush syndrome), compartment syndrome, or electric shock.
- The most common cause in children is infection, specifically viral infections. Some of the associated infections include viral (influenza A and B, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus), certain bacterial infections (Legionella species, group A beta-hemolytic streptococci, Salmonella), and protozoa (Malaria).
- Exertion-related rhabdomyolysis may be a common cause for young athletes. Specifically, exercise which is novel, intense, or prolonged, and especially in the presence of extremely hot weather may cause rhabdomyolysis. Seizure, tetany, and alcohol withdrawal syndrome are other causes of exertion-related rhabdomyolysis.
- Certain inherited disorders should be considered with recurrent rhabdomyolysis. Myopathies involving muscle enzyme or energy substrate deficiencies include disorders of lipid metabolism (e.g., carnitine palmitoyltransferase II deficiency), disorders of glycogenolysis (e.g., phosphorylase kinase deficiency, McArdle disease), disorders of glycolysis (lactate dehydrogenase deficiency), and mitochondrial deficiency disorders. Usual triggers for rhabdomyolysis in such conditions are fasting, exertion, or viral illness.
- Rhabdomyolysis is more likely to occur after exertion in association with the dystrophinopathies, which include all forms of muscular dystrophy.
- Illicit drug use including alcohol (alcohol withdrawal syndrome), cocaine, heroin, amphetamines, phencyclidine (PCP), and ecstasy
- Causative prescription medications include lipid-lowering drugs (statins, fibrates) and antipsychotic medications (mostly due to neuroleptic malignant syndrome).
- Prolonged immobilization or loss of consciousness leading to muscle hypoxia. Certain metabolic and electrolyte disorders may result in rhabdomyolysis. These include hypokalemia, hypophosphatemia, hypocalcemia, and hyperosmolar states such as diabetic ketoacidosis.
- Body temperature changes (hyperthermia and hypothermia) may cause rhabdomyolysis.
- Malignant hyperthermia is a rare inherited condition that results in hyperthermia, muscle breakdown, and subsequent rhabdomyolysis on receiving halogenated hydrocarbon " containing anesthetics or muscle relaxants such as succinylcholine.
- Neuroleptic malignant syndrome is a rare neurologic disorder characterized by hyperthermia, rhabdomyolysis, and autonomic changes in patients receiving neuroleptic or antipsychotic medications.
- Other implicated toxins include snake bite, spider venom and vespid venoms, quail, and some mushrooms.
- The list of causes of rhabdomyolysis above is not exhaustive. Any child with sudden onset of muscle pain, tenderness, or weakness should be suspected of having rhabdomyolysis, and any child with dark urine suspected of myoglobinuria.
- The insult may lead to muscle cell destruction with release of intracellular contents including proteins and electrolytes and sequestration of fluids by damaged muscle leading to severe hypovolemia.
- Rhabdomyolysis leads to AKI by direct toxicity of myoglobin to the renal tubules, renal tubular obstruction, and renal ischemia from hypoperfusion.
- Rhabdomyolysis has also been associated with diverse conditions, including status asthmaticus, diabetes mellitus, and thyroid disease. It may also occur in Kawasaki disease, hemolytic uremic syndrome, and adrenal insufficiency, associations which are rare but must not be missed.
Diagnosis
History
- Prior history of any illness or insult associated with rhabdomyolysis should be sought. Rhabdomyolysis may follow certain illnesses (e.g., influenza), insults (e.g., crush injury, severe exertion), and medications (e.g., statins).
- Symptoms of muscle pain or weakness may result from rhabdomyolysis and help suggest diagnosis if present.
- Signs of reddish-brown discoloration of the urine may be present.
Physical Exam
- Palpate muscles for tenderness and, less commonly, swelling or fullness.
- Test for motor strength.
- Elicit reflexes to exclude neuropathy.
- Examine skin and mucous membranes for signs of vasculitis.
- Look for signs suggestive of child abuse.
- Examine for signs of a concomitant precipitating illness.
- The clinical picture is generally consistent with volume depletion given the sequestration of fluids in injured muscle tissue.
Lab
- Serum CK level, specifically the CK-MM isoenzyme, which is found in skeletal muscle, will be elevated to greater than 4 " 5 times the upper limit of normal. CK levels usually rise within 12 hours of the injury and peak within 2 " 3 days. If the CK levels continue to rise, it should raise suspicion for ongoing muscle damage or development of compartment syndrome.
- Serum electrolytes including calcium and phosphorus must be measured given the potential for severe derangements. Abnormalities may include hyperkalemia, hyperphosphatemia, and/or hypocalcemia. There may be metabolic acidosis with a wide anion gap in those conditions associated with lactate production.
- Creatinine level may be elevated out of proportion to that of BUN, secondary to conversion of liberated muscle creatine to creatinine.
- CBC and smear should be obtained because many of the metabolic disorders causing rhabdomyolysis cause a hemolytic anemia as well.
- Patients with rhabdomyolysis are at increased risk for disseminated intravascular coagulation (DIC) secondary to thromboplastin released from the injured myocytes. Therefore, PT/INR, PTT, platelets, and fibrinogen levels should be obtained.
- Serum uric acid may be elevated from release of purines from muscle cells and may contribute to renal tubule obstruction.
- Other muscle enzyme levels (myoglobin, aldolase, lactate dehydrogenase, AST, ALT) will be elevated secondary to muscle injury but are not necessary for diagnosis.
- Urinalysis
- Urine may appear brown and test positive for blood on dipstick without red blood cells on microscopy.
- Granular pigmented casts are common. Low fractional excretion of sodium (<1%) is found in those with AKI.
- Myoglobin in is not generally measured; however, urine myoglobin can be quantitatively measured using an immunoassay. Serum CK levels are more sensitive to assess the degree of ongoing rhabdomyolysis.
- Other tests:
- EKG may reveal changes associated with acute hyperkalemia, such as peak T waves, prolongation of PR, absent P wave with prolonged QRS interval, or even ventricular tachycardia/fibrillation in severe untreated hyperkalemia.
- Metabolic and genetic testing if recurrent or otherwise suspected metabolic myopathy
Imaging
Imaging is not generally required for the diagnosis. Note that use of radiocontrast in imaging studies as part of diagnostic evaluation can worsen acute kidney injury.
Other Diagnostic Procedures
Muscle biopsy: necessary to diagnose metabolic myopathies; should wait several weeks after the clinical event to perform. A biopsy will demonstrate immunohistochemical features of a myopathy. Immunoblotting is helpful in evaluating the dystrophinopathies.
Differential Diagnosis
- Consider other causes of discolored urine such as hematuria and beet ingestion.
- Consider other causes of muscle pain and/or weakness: viral illnesses, Lyme disease, suppurative myositis, Guillain-Barre syndrome, collagen vascular diseases.
Treatment
Initial Stabilization
Aggressive repletion of fluids should be initiated promptly. If an underlying cause is identified, it should be corrected or removed.
General Measures
- Early fluid resuscitation is essential to prevent worsening kidney function. Vigorous hydration with crystalloid IV fluids should be followed by adequate maintenance fluids (e.g., 2 " 3 times maintenance) to provide brisk urine flow (e.g., >2 mL/kg/h or >200 mL/h).
- Alkalinization of the urine is not clearly superior to fluids alone, although risks of alkalinization are minimal.
- Use of diuretics, including furosemide (a loop diuretic), are controversial and use should be limited to fluid-replete patients. Use of mannitol is not clearly beneficial and may actually worsen AKI.
Medication
- Administration of sodium bicarbonate (along with fluids) to correct or prevent acidosis is reasonable. Correction of acidosis is also beneficial in the management of hyperkalemia (potassium is shifted intracellularly).
- With alkalinization, monitor closely for worsening hypocalcemia.
- Use of diuretics is controversial; consider use in fluid-replete patients with AKI to maintain urine output and avoid volume overload (e.g., furosemide 1 " 2 mg/kg/dose IV). Furosemide will also maximize potassium elimination by the kidney.
- Additional treatment for severe hyperkalemia may be necessary and incudes IV calcium gluconate, sodium bicarbonate, insulin and glucose, beta-2-agonist drugs, and Kayexalate.
- Correct hypocalcemia only if symptoms are present or in the setting of severe hyperkalemia in order to prevent the complication of calcium-phosphate deposition and late hypercalcemia.
- Conventional hemodialysis does not remove myoglobin effectively; continuous venovenous hemofiltration may be more effective. Indications for dialysis include acute renal failure with the following:
- Severe hyperkalemia refractory to medical management or rapidly rising potassium
- Severe metabolic acidosis resistant to medical management
- Volume overload/respiratory distress secondary to pulmonary edema
Ongoing Care
Close monitoring of labs with serial measurements of CK levels, creatinine, and electrolytes is essential. The patient 's fluid status should be monitored closely, and volume repletion should be continued until urine is clear and negative for blood. The patient should also be watched closely for signs of ongoing muscle injury, compartment syndrome, or DIC.
Prognosis
- Prognosis is generally good, with acute kidney injury being the major life-threatening complication.
- Prompt cessation of rhabdomyolysis may be expected when the inciting cause is corrected or resolved.
- Although most children recover promptly, severe muscle injury may cause prolonged muscle weakness and warrant follow-up by physical and occupational therapy.
- With resolution of myoglobinuria, acute kidney injury is expected to be reversible.
Complications
- Electrolyte release from muscle can lead to severe hyperkalemia, hyperphosphatemia, and secondary hypocalcemia.
- Electrolyte derangement may result in cardiac arrhythmias.
- AKI occurs in 13 " 50% of patients. Risk factors for AKI include higher CK level (>3,000), concurrent administration of nephrotoxic agents, and volume depletion.
- Compartment syndrome may result from muscle swelling.
- Use of bicarbonate may precipitate symptomatic hypocalcemia.
- Use of calcium therapy for severe hyperkalemia or symptomatic hypocalcemia may result in calcium-phosphate deposition or exacerbate late hypercalcemia.
- Failure to discontinue IV fluids if oligoanuric renal failure develops could produce iatrogenic fluid overload.
Additional Reading
- Bosch X, Poch E, Grau J. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009; 361:62 " 72. [View Abstract]
- Elsayed EF, Reilly RF. Rhabdomyolyis: a review, with emphasis on the pediatric population. Pediatr Nephrol. 2010;25(1):7 " 18. [View Abstract]
- Talving P, Karamanos E, Skiada D, et al. Relationship of creatinine kinase elevation and acute kidney injury in pediatric trauma patients. J Trauma Acute Care Surg. 2013;74(3):912 " 916. [View Abstract]
Codes
ICD09
- 728.88 Rhabdomyolysis
- 958.5 Traumatic anuria
ICD10
- M62.82 Rhabdomyolysis
- T79.5XXA Traumatic anuria, initial encounter
SNOMED
- 240131006 Rhabdomyolysis (disorder)
- 240125008 Muscle crush syndrome (disorder)
- 72960004 Exertional rhabdomyolysis