What Causes Rhabdomyolysis?

Patient Presentation
A 6-year-old male came to the emergency room with rhinorrhea, fever, and malaise. He also had muscle aches and a cough that were getting worse for 2-3 days. Schoolmates had had similar problems. The past medical history was non-contributory. The pertinent physical exam showed an ill-appearing male with temperature of 101.8 degrees, and normal vital signs. Growth parameters were 25-50%. HEENT showed clear rhinorrhea and an erythematous pharynx. Chest showed some crackles at the right base. Heart had a normal S1, S2 without murmur. Abdomen was mildly tender diffusely that appeared more muscular. There was no hepatosplenomegaly or masses. Muscles were diffusely tender. There was no rash.

The laboratory evaluation included a complete blood count with a white blood count of 12.8 x 1000/mm2 and some toxic vacuoles. A rapid strep test and rapid influenza test were negative. The radiologic evaluation of a chest radiograph showed a small infiltrate at the right base. The patient was diagnosed with community-acquired pneumonia but during discharge needed to urinate and produced brown-colored urine. The laboratory evaluation included a urinalysis that showed a specific gravity of 1.020, significant protein and no red blood cells. His liver function tests, protein and albumin were normal. Electrolytes were normal except for a potassium of 4.7 mg/dl, BUN of 35 mg/dl and creatinine of 2.1 mg/dl. His creatine kinase was 8735 U/L and the diagnosis of rhabdomyolysis was made. Over the next 12 hours, he was aggressively treated with intravenous fluids with bicarbonate, but developed oliguria. He also became more tachypnea and required oxygen, but did not develop any arrhythmias. He was started on ceftriaxone and azithromycin to treat for possible staphylococcus, streptococcus and mycoplasma. He then developed a pericardial effusion and was transferred to the intensive care unit. During his hospital stay he was diagnosed with Mycoplasma pneumoniae based upon polymerase chain reaction and IgM antibodies. His clinical course included developing pericarditis, myocarditis, oliguria without renal failure and hemolytic anemia in addition to the rhabdomyolysis. He recovered and was doing well 2 years later.

Rhabdomyolysis was first described in 1881, and in 1941 a case series of crush victims from the Battle of Britain described rhabdomyolysis and subsequent acute renal failure.

Injury to the skeletal muscle that results in leakage of the intracellular content into the plasma defines rhabdomyolysis or literally the dissolution of the skeletal muscle. Causes of the initial injury are numerous (see below). Rhabdomyolysis in adults is classically described by muscle weakness, myalgia and dark urine. But this triad is not common in children. In a 2005 study of 210 children, 45% had myalgia, 38% had muscle weakness, and 3.6% had dark urine. Only 1 patient had all 3 symptoms. Other signs and symptoms include fever, nausea, emesis, abdominal tenderness and decreased reflexes.

Laboratory testing for rhabdomyolysis includes creatine kinase (CK) which usually rises within 12 hours, peaks at 24-36 hours and then decreases 35-40% per day. Therefore levels that are not decreasing after the appropriate time indicate continued insult. The peak CK may be predictive of acute renal failure. Urine myoglobin may be helpful when hematuria co-exists but is not as reliable as CK.

Treatment of the underlying cause is obviously important. Aggressive hydration with initial bolus hydration and then 2-3 times maintenance is usually recommended. Intravenous fluid with sodium bicarbonate to alkalinize the urine is often used. Mannitol may also be used for diuresis. Consultations with nephrology, genetics, rheumatology, surgery, critical care, and others can assist in managing the insult and the treatment of rhabdomyolysis. Dialysis is used to treat acute renal failure. Electrolyte abnormalities including hyperphosphatemia, hyperkalemia, hypocalcemia, hyperuricemia, hypoalbuminemia must be aggressive monitored for and managed. Other complications include disseminated intravascular coagulation, cardiac abnormalities, seizures and death.

Learning Point
The list of causes of rhabdomyolysis is extensive. In the pediatric population common causes are viral (especially Influenza A and B), trauma and connective tissue disease.
Causes of rhabdomyolysis include:

  • Infectious
    • Bacterial
      • Bacillus cereus
      • Borrelia burgdorferi
      • Clostridium perfringens
      • Clostridium tetani
      • Francisella tularensis
      • Escherichia coli
      • Legionella
      • Leptospira
      • Mycoplasma
      • Staphylococcus epidermidis
      • Streptococcus
      • Salmonella
      • Vibrio family
    • Fungal
      • Aspergillus
      • Candida
    • Viral
      • Adenovirus
      • Cytomegalovirus
      • Echovirus
      • Epstein-Barr virus
      • Herpes family
      • Human immunodeficiency virus
      • Influenza A
      • Influenza B
      • Parainfluenza
      • West Nile virus
    • Parasite
      • Plasmodium
      • Rickettsia
    • Pyomyositis
    • Sepsis
  • Drugs (reactions, overdose or abuse)
    • Amphetamine
    • Amphotericin B
    • Aminocaproic acid
    • Anesthetics
    • Anticholinergic agents
    • Antihistamines
    • Antilipemics including statins
    • Antipsychotics
    • Caffeine
    • Corticosteroids
    • CO poisoning
    • Ethanol
    • Ethylene glycol
    • Fibric acid derivatives
    • Heroin
    • Hemlock
    • Isopropranol
    • Ketamine
    • MDMA or Ectasy
    • Lysergic acid diethylamide or LSD
    • Methanol
    • Narcotic – especially cocaine
    • Nutritional supplements
    • Phenylcyclidine
    • Propofol
    • Protease inhibitors
    • Quinine
    • Salicylates
    • Sedatives
    • Selective serotonin reuptake inhibitors
    • Sympathomimetic agents
    • Theophylline
    • Toluene
  • Genetic
    • Carnitine deficiency
    • Carnitine palmityl transferase deficiency
    • Glycogen phosphorylase deficiency
    • Mitochondrial respiratory chain enzyme deficiencies
    • Myoadenylate deaminase deficiency
    • Neuroleptic malignant syndrome
    • Malignant hyperthermia
    • Phosphofructokinase deficiency
    • Phosphoglycerate mutase deficiency
    • Phosphoglycerate kinase deficiency
    • Porphyria
  • Metabolic
    • Diabetic ketoacidosis
    • Hypokalemia
    • Hypo- or hypernatremia
    • Hypophosphatemia
    • Hypo- or hyperthyroidism
    • Non-ketotic hyperosmolar diabetic coma
  • Neurological
    • Dystonia
    • Guillain-Barre syndrome
    • Muscular dystrophy
    • Myalgias
    • Seizures
  • Rheumatological
    • Inflammatory myositis
    • Systemic lupus erythematosis
    • Sarcoid
  • Trauma
    • Asphyxia
    • Burns
    • Compartment syndrome
    • Crush injury
    • Electric shock
    • Envenomation (snake or insect)
    • Exertion – particularly if deconditioned
    • Heat related injuries – both hypo- and hyper-thermia
    • Near drowning
    • Lightening strike
    • Shaken-baby syndrome
  • Miscellaneous
    • Acute psychosis
    • Hyperosmotic conditions
    • Prolonged immobilization
    • Status asthmatics

    Questions for Further Discussion
    1. What are the clinical manifestations of mycoplasma?
    2. How common is rhabdomyolysis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Pneumonia and Muscle Disorders.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Bywaters EG, Beall D. Crush injuries with impairment of renal function. Br Med J. 1941;1:427-432.

    Bywaters EG, Stead J. The production of renal failure following injection of solution containing myohaemoglobin. Q J Exp Physiol. 1944;33:53-70.

    Kasik JW, Leuschen MP, Bolam DL, Nelson RM. Rhabdomyolysis and Myoglobinemia in Neonates. Pediatrics 1985;76;255-258.

    Berger RP, Wadowksy RM, Rhabdomyolysis Associated With Infection by Mycoplasma pneumoniae: A Case Report. Pediatrics 2000:105;433-436.

    Mannix R, Tanb ML, Wright R, Baskin M. Acute Pediatric Rhabdomyolysis: Causes and Rates of Renal Failure. Pediatrics 2006:118;2119-2125.

    American Academy of Pediatrics. In Pickering LD, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2009;227,731.

    Muscal E, Morales de Guzman M, Rhabdomyolysis. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/1007814-overview (rev. 4/27/2010, cited 1/31/11).

    Craig S, Rhabdomyolysis. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/827738-overview (rev. 12/6/2010, cited 1/31/11).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

    Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital