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“Rhabdomyolysis is the rupture and subsequent necrosis of striated muscle, with the consequent release of intracellular contents into the circulatory system. Some of the components released include myoglobin, potassium, sodium, phosphorus, nucleosides, and creatine.”1,2


Rhabdomyolysis can occur because of physical or nonphysical causes.1-6

  • Physical causes include trauma, compression, excessive physical activity, prolonged bedrest, vascular occlusion, hypoperfusion, electrical current, neuroleptic malignant syndrome, and sepsis.
  • Nonphysical causes include metabolic myopathies (ie, McArdle disease), medications (eg, statins, corticosteroids), alcohol, illicit drugs, toxins, infections, electrolyte abnormalities, endocrine disorders, polymyositis, and dermatomyositis.


Rhabdomyolysis is more common in adults, with a higher incidence in men than women. “The most common causes in adults are abuse of illicit drugs or alcohol, muscular trauma, crush injuries, and myotoxic effects of prescribed drugs.”7 “In the pediatric population, common causes include infections, trauma, metabolic conditions, and muscle diseases. Viral myositis is more common between 0 and 9 years of age, and trauma is more common between 9 and 18 years of age.”8 An estimated 10%-40% of patients with rhabdomyolysis develop acute kidney injury (AKI), and up to 15% of all cases of AKI can be attributed to rhabdomyolysis.3 The mortality for those who develop AKI is estimated at 7%.3-6 “The mortality rate is higher for patients with rhabdomyolysis who develop acute renal failure than patients with rhabdomyolysis who do not develop AKI (59% vs 22%).”2


Both the physical and non-physical etiologies of rhabdomyolysis lead to adenosine triphosphate (ATP) depletion which disrupts the normal delicate balance of intracellular electrolyte concentration and will create an excessive intracellular influx of sodium ions and calcium ions. “The increased amount of intracellular sodium drives water into cell and increased intracellular elevation of calcium ions activates sustained myofibrillar contraction and further depletes ATP. Additionally, the elevation in calcium activates calcium-dependent proteases and phospholipases which causes breakdown and lysis of the cellular membrane. Intracellular muscle contents are released into bloodstream and extracellular space which including potassium, myoglobin uric acid, creatine kinase, aldolase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. Increased concentration of myoglobin, hypovolemia/dehydration, and aciduria will precipitate the myoglobin in the glomerular filtrate, producing pigmented casts, tubular obstruction, renal failure, and possible cardiac arrhythmias and seizures.”1-6

Specific secondary or associated conditions and complications

  • Early complications: electrolyte abnormalities, cardiac arrest and arrhythmias, compartment syndrome, hyperkalemia, hypocalcemia, elevated liver enzymes, acute renal failure, and disseminated intravascular coagulation.1-6
  • Late complications: fatigue, muscle contractures, and nerve damage related to compartment syndrome.



Assess for risk factors, including trauma, prolonged immobilization, alcohol, cocaine, narcotics, diuretics, statins, toxins, inflammatory disorders, genetic disorders, and metabolic disorders. Is there any history of seizures? What is the patient’s mental status, both at baseline and currently? What symptoms are/were present, including muscle pain, weakness, urine color, signs or symptoms of dehydration, heat exposure, and access to water?

“The classic triad of symptoms of rhabdomyolysis comprises of myalgia, weakness and tea-colored urine. Dark or tea-colored urine was reported in only 3.6% of cases. However, the classic triad is observed in less than 10% of patients and most patients do not complain of muscle pain or weakness. In pediatric rhabdomyolysis common presenting symptoms include muscle pain, fever and viral prodromes.”2-5

Physical examination

  • General manifestations include malaise, fever, tachycardia, nausea, and vomiting.
  • Musculoskeletal manifestations include myalgias, weakness, and tenderness. Muscles may be tender and swollen. Skin changes, such as nonblanchable erythema of intact skin, partial or full thickness skin loss, and necrotic tissue may indicate pressure necrosis. There may be contractures further out from the acute insult.
  • The clinical manifestations of AKI, disseminated intravascular coagulation, and multi-organ failure may subsequently appear. A high index of suspicion is important in the initial presentation of the disease.

Functional assessment

In some patients, the history is nonspecific and unreliable for a diagnosis. Caregivers may provide additional information. With muscle weakness and pain, one needs to assess to what degree mobility and self-care and independent living skills are affected. It is important to determine the patient’s prior functional status regarding ADLs and IADLs, current residence status (i.e home vs. apartment, stairs to enter, stairs inside the home, first floor set-up) and family/friend support.

Laboratory studies

Studies to confirm the diagnosis or complications include the following3-5:

  • CK levels: “Normal CK enzyme levels are 45–260 U/L most sensitive; no established cut-off; however, concentration 5 times the upper limit is diagnostic). CK rises in rhabdomyolysis within 12 hours of the onset of muscle injury, peaks in 1–3 days, and declines 3–5 days after the cessation of muscle injury. The half-life is 1.5 days (longer than serum myoglobin).
  • Serum/urine myoglobin levels: Usually elevated initially but normalizes after 6-8 hours due to its short half-life. It turns urine into a dark red–brown color when the concentration exceeds 100 mg/dl.
  • Carbonic anhydrase III: More specific for skeletal muscle injury since it is not found in the myocardium.
  • Aldolase: Elevated aldolase and CK levels are highly suggestive of rhabdomyolysis. Found in the skeletal muscle, liver and the brain.
  • Urine dipstick and urine microscopy: Examine for the presence of protein, brown casts and uric acid crystals.
  • Complete blood count (CBC): A decrease in hemoglobin and platelets may be seen.
  • Complete metabolic profile (CMP)
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT): If clinical presentation is suggestive of DIC.
  • Lactate dehydrogenase (LDH): Elevated due to release from destroyed muscle cells.” 3-5

Supplemental assessment tools3-5

Additional tests are important in order to monitor possible complications.

  • Electrocardiographic (EKG) evaluation is needed in patients with hyperkalemia or hypocalcemia to determine if there are any acute changes on EKG.
  • Electromyography may help to differentiate from polymyositis (sharp waves and fibs are usually not present in rhabdomyolysis).
  • New markers of kidney injury include urine/serum neutrophil gelatinase-associated lipocalin. This polypeptide is one of the substances most rapidly released from the kidney after an ischemic or toxic event.5
  • Compartment pressure measuresments in the affected limb after trauma.
  • Muscle biopsy may be helpful in the diagnosis of congenital, inflammatory and toxic myopathies.

Early predictions of outcomes

  • Hypovolemia and aciduria are risk factors for the development of renal failure in patients with rhabdomyolysis.6 The early administration of intravenous fluids therapy decreases the probability of renal injury. Delaying fluid replacement increases the risk of renal failure. The outcome of patients with rhabdomyolysis with renal failure is worse than rhabdomyolysis without renal compromise, as previously mentioned.
  • Abnormal coagulation times (PT, PTT, international normalized ratio) and low platelet counts are indicators for DIC and indicate a worse prognosis.2-5
  • Rhabdomyolysis and multiorgan dysfunction syndrome with renal failure and DIC have higher mortality rates and worse outcomes.

Social role and social support system

Older adults who live alone should be recommended to purchase an alert alarm system in case they fall and cannot stand up. Also, family, friends and neighbors should frequently check on the well-being of older adults living by themselves.

Professional Issues

The list of potential medications which may cause rhabdomyolysis is extensive (eg, amitriptyline, haloperidol, thiazides, benzodiazepines, diphenhydramine, hyperlipidemic agents). Patients taking these medications who have additional risk factors for rhabdomyolysis (alcohol, immobilization, dehydration, etc) will have a higher chance of potentiating the process of muscle breakdown. Prescribers should keep this in mind when prescribing these medications, and encourage their patients to always stay well hydrated in order to reduce the risk of complications developing.3-5

If the patient has developed renal insufficiency, a nephrology consultation will assist to determine the need for possible temporary dialysis.


Available or current treatment guidelines

The two most important goals in the treatment of rhabdomyolysis are treating the underlying cause and preventing renal failure.1,6,8,10,11 It is important to identify high-risk groups of patients and then implement preventive measures, such as promotion of fluid intake, avoidance of nonsteroidal medications, follow-up of CK levels, kidney function tests, and urine dipstick.

Patients with severe trauma will benefit from an early and aggressive fluid resuscitation, trying to prevent renal failure. However, a careful evaluation for the development of fluid overload must be implemented at the same time.

Monitoring of electrolyte abnormalities is critical and should be implemented as soon as rhabdomyolysis is suspected.

At different disease stages

New onset/acute10-13

  • Vigorous fluid replacement with normal saline and dextrose 5%.
  • Correction of electrolyte and acid base balance. Monitoring of CK levels and myoglobin.
  • Alkalinization of urine to prevent nephrotoxic effects of myoglobinuria and hyperuricosuria. However, there have been no studies that clearly show that alkalinization helps prevent AKI.
  • Muscle decompression either with fasciotomies or by mobilizing intramuscular edema with mannitol. Mannitol is contraindicated in patients with anuria.
  • A high urine output should be maintained. If not, furosemide should be administered.
  • In the presence of metabolic acidosis, a bolus of acetazolamide may be helpful.
  • Potassium or lactate containing solutions should be avoided.
  • In the presence of disseminated intravascular coagulation (DIC) and hemorrhagic complications, platelets, vitamin K, and fresh frozen plasma may be necessary.4-5


  • Continued monitoring of electrolyte and acid balance.
  • Continued monitoring of CK levels and myoglobin and renal function.
  • Administration of allopurinol will reduce the production of uric acid and also acts as a free radical scavenger.
  • If renal failure or severe hyperkalemia or acidosis has been established, continuous hemodialysis or hemofiltration have to be implemented.


  • Recurrent rhabdomyolysis has been described. Patient must be mindful of risks if performting strenuous activities.
  • Patients who have had fasciotomies may require skin grafting.
  • Physical therapy and occupational therapy: initially, a prevention of contractures program with range of motion exercises (active and passive) occurs, followed by aerobic training and gradual resistance training in order to maintain functional activity. The current best evidence supports a submaximal strengthening program in order to prevent a recurrent exertional rhabdomyolysis.13

Coordination of care

Appropriate and vigorous fluid resuscitation in the field by rescue teams, continued by emergency room personnel, will assure a lower rate of complications in patients who had severe trauma, or patients with risk factors for rhabdomyolysis.10 There is the need to prevent secondary sequelae, such as contractures, and work on strengthening muscles in a gentle fashion that involves nursing, therapists, and the patient and the family when the patient is out of the hospital.

Patient & family education

Athletes, family, and coaching staff must be aware of signs and symptoms of heat exhaustion. Adequate hydration during games or practices is needed to reduce the risk of rhabdomyolysis.

Patients and families with inherited metabolic disorders have an increased risk for rhabdomyolysis. They need counseling and careful follow-up after physical activities.14

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • High index of suspicion in patients with risk factors.
  • Vigorous fluid resuscitation in patients with crush injuries, severe trauma, or with risk factors for rhabdomyolysis.
  • Proper hydration during games and practices.
  • Be aware of signs and symptoms of exhaustion.
  • Avoid potassium or lactate containing solutions.


Cutting edge concepts and practice

Antioxidant therapy with L-carnitine, bicarbonate, or other oxygen free radical scavengers have been studied in animals as a treatment for rhabdmyolysis.12 Other antioxidants, such as vitamin E, vitamin C, lazaroids, minerals, such as zinc, manganese, and selenium, are being studied as oxygen free radical scavengers in rhabdomyolysis.6 Pentoxyphylline is a xanthine derivative and has been used to improve microvascular blood flow.3



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  2. Cervellin G, Comelli I, Lippi G. Rhabdomyolyisis: historical background, clinical, diagnostic, and therapeutic features. Clin Chem Lab Med. 2010;48:749-756.
  3. Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015 Spring;15(1):58-69
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  5. Kahn, FY. Rhabdomyolosis: A Review of the literature. The Netherlands Journal of Medicine. October 2009 Vol 67 No. 9
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  10. Better O, Abassi Z. Early fluid resucitation in patients with rhabdomyolysis. Nat Rev Nephrol. 2011;7:416-422.
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  14. Landau M, Kenney K, Deuster P, Campbell W. Exertional rhabdomyolysis: a clinical review with a focus on genetic influences. J Clin Neuromuscul Dis. 2012;13:122-136.


Hohenegger M. Drug induced rhabdomyolysis. Curr Opin Pharmacol. 2012;12:335-339.

Quinlivan R, Jungbluth H. Myopathic causes of exercise intolerance with rhabdomyolysis. Dev Med Child Neurol. 2012;54:886-891.

Reese J, Fisher S, Robbins D. Exertional rhabdomyolysis: attrition through exercise. J Spec Oper Med. 2012;12:52-56.

Original Version of the Topic

German Ojeda Correal, MD; Jose Mena, MD. Rhabomyolysis. 09/20/2013

Author Disclosure

Dominique Vinh. MD
Nothing to Disclose

Daniel Sova, MD
Nothing to Disclose