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Rhabdomyolysis
Rhabdomyolyses
Rhabdomyolysisis the dissolution and disintegration of striated muscle fibers. It is characterized by myoglobinemia and myoglobinuria.

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WIKIDATA, CC BY-SA 3.0
WIKIDATA, CC BY-SA 3.0

Presentation

Rhabdomyolysis presents with triad of muscle weakness, myalgias and myoglobinuria. However, the presentation varies considerably. Additional nonspecific symptoms like fever, nausea and vomiting may be present. In most cases, the antecedent history reflects the inciting cause (alcohol use and a state of agitation, poor responses and drug abuse, overuse of prescription drugs, heat stroke).

Infection and trauma are important causes in children.
The physical examination may be nonspecific. Patients may have muscular pain, tenderness, decreased muscle strength, soft tissue oedema and skin changes consistent with pressure necrosis [7].

The calf muscle and the other lower limb muscles are the most common group involved. Tense and tender muscle compartments suggest compartment syndrome (compression of nerves and blood vessels due to increased pressure in the part of the body). Hyperthermia, hypothermia and electrical burn injuries [8] are known to cause rhabdomyolysis and can be detected by physical examination.

Entire Body System

  • Pain

    A 27-year-old woman, gravida 4 para 2, presented with swelling and pain of the mons pubis and abdominal pain after intense powerlifting 2 days prior. A computed tomography scan was performed, revealing abdominal wall inflammation. [ncbi.nlm.nih.gov]

    […] in urine color and severe muscle pain often set this condition apart and should be taken very seriously. [bsmpg.com]

  • Fatigue

    BACKGROUND Muscular symptoms, including stiffness, myalgia, cramps, and fatigue, are present in the majority of the patients with symptomatic hypothyroidism, but rhabdomyolysis, the rapid breakdown of skeletal muscle, is a rare manifestation. [ncbi.nlm.nih.gov]

    Other signs and symptoms of Rhabdomyolysis may include fatigue, weak muscles, and seizures (in some cases) Rhabdomyolysis is generally diagnosed through a physical examination; complications, such as shock and kidney failure, could ensue, if Rhabdomyolysis [dovemed.com]

    However, some people continue to have problems with fatigue and muscle pain. [mountsinai.org]

  • Limb Pain

    A 32-year-old man presented to the emergency department with severe right lower limb pain and swelling of three days' duration. He had multiple prior admissions for recurrent seizures and suicide attempts. [ncbi.nlm.nih.gov]

    The calves and low back are the most general muscle groups that are affected. [2] According to the author Efstratiadis, back pain and limb pain are the most frequent sites in patients with rhabdomyolysis. [3] However, over 50% of the patients with rhabdomyolysis [physio-pedia.com]

  • Severe Pain

    In one case, CK levels reached 21,000 U/L after weight-lifting (this subject also had severe muscle pain). [athleteinme.com]

    Severe pain may limit passive limb movement and there may be a reduction in the range of active movement. In compartment syndrome or crush injury, the muscles may be tense and swollen, leading to nerve injury with sensory loss. [academic.oup.com]

  • Arm Pain

    Roughly 18 hours after doing negative curls, this athlete experienced severe biceps pain and could not fully extend his arms. [athleteinme.com]

Gastrointestinal

  • Nausea

    Cannabis hyperemesis syndrome (CHS) is a condition in which some patients with long-term, frequent use of cannabis paradoxically develop recurrent episodes of nausea and vomiting. [ncbi.nlm.nih.gov]

    It may also be used to treat severe nausea and vomiting. Corticosteroids. This is a group of medicines used to treat or prevent inflammation. Phenytoin. This is used to prevent and control seizures. Toxins. [northshore.org]

    […] checking all patients for the following signs and symptoms: Abnormal urine color (dark, red, or cola colored) Decreased urine production General weakness Muscle pain & tenderness Weakness & swelling of the affected muscles Low blood pressure Shock - Nausea [onedayhike.org]

    The 33-year-old Bronx resident brushed off her symptoms of nausea and light-headedness and went on with her day. But within days, Peterson's thighs were painful and swollen, and her urine had become darker. [self.com]

  • Diarrhea

    CASE PRESENTATION: The patient, a 2-year-old boy with fever, diarrhea, and vomiting, was referred to our hospital with dysstasia and transaminitis. He was diagnosed with rhabdomyolysis. [ncbi.nlm.nih.gov]

    Case Presentation Case 1: A 27 year old African American male presented to the emergency room with pain in both legs, nausea, vomiting, and diarrhea. [omicsonline.org]

    Excessive vomiting or diarrhea, diabetes, or problems of hyperthyroidism (thyroid storm) may also injure your muscles. Temperature extremes, such as hyperthermia (very high body temperature) or hypothermia (very low body temperature). [drugs.com]

Cardiovascular

  • Chest Pain

    METHODS: 138 patients with symptoms of acute onset (such as chest pain, muscle pain) and high myocardial enzymes were assigned as the Haff disease group and myocardial injury group, respectively. [ncbi.nlm.nih.gov]

    You have pain, swelling, or weakness in your arms or legs that does not go away or gets worse. You are urinating less than usual or not able to urinate. You have chest pain. Your heart is beating faster than usual or has a strange rhythm. [drugs.com]

    Chest pain and increased CK levels plus elevated CK-MB indicate that it is likely that a person has recently had a heart attack. Levels that drop, then rise again may indicate a second heart attack and/or ongoing heart damage. [labtestsonline.org]

Musculoskeletal

  • Myopathy

    In addition, we summarize all cases reported in the literature of inflammatory myopathy-associated rhabdomyolysis. [ncbi.nlm.nih.gov]

    Risk Factors Sickle Cell Anemia Immbolization (e.g. casted joints) Myopathy Statin use V. [fpnotebook.com]

    Vitamin E and selenium deficiency Toxic myopathy Ionophore toxicity Pasture myopathies Rayless goldenrod/white snakeroot Cassia occidentalis Atypical myoglobinuria Traumatic myopathy Compressive anesthetic myopathy Trauma Genetic myopathies Glycogen [web.archive.org]

  • Myalgia

    CONCLUSION: Mutations in RYR1 should be considered as a significant cause of rhabdomyolysis and myalgia syndrome in patients with the characteristic combination of rhabdomyolysis, myalgia and cramps, creatine kinase elevation, no weakness and often muscle [ncbi.nlm.nih.gov]

    (myalgias) Muscle Weakness Localized swelling or Bruising Constitutional symptoms Fever Malaise Nausea or Vomiting Confusion, Agitation, or Delirium Urinary tract symptoms Tea-colored urine (present in only 3-4% of cases) Anuria VII. [fpnotebook.com]

    […] performed Survived [15] 42 M Myalgias, Abdominal pain, and diarrhea 63800 1480 No urine drug screen performed Survived [16] 20 M Myalgias, fever, pharyngitis, and LN 11016 462 Acute HIV/CMV coinfection Survived [17] 51 M Myalgias, emesis, and fever 32720 [omicsonline.org]

  • Muscle Weakness

    Abstract A 91-year-old male was admitted to the hospital for worsening muscle weakness, muscle pain, and unexplained soreness for the past 10 days. [ncbi.nlm.nih.gov]

    Signs Precautions Have a high index of suspicion for screening in those at high risk of Rhabdomyolysis Classic triad of Muscle Weakness, myalgias, tea-colored urine is only present in 10% of cases Less than 50% report muscle pain or weakness Muscle pain [fpnotebook.com]

  • Muscle Tenderness

    The patient presented with muscle tenderness over the lower limbs and dark brown-to-red colored urine. [ncbi.nlm.nih.gov]

    Symptoms include muscle tenderness, stiffness, or weakness, and abnormal urine color. Who gets Rhabdomyolysis? Anyone can get rhabdomyolysis. There are many causes, both traumatic and nontraumatic. [aanem.org]

    Rhabdomyolysis may cause such symptoms as dark, red, or cola-colored urine, muscle tenderness, generalized or specific muscle weakness, and muscle stiffness or aching. [diabetesselfmanagement.com]

    If patients on statins develop myositis (muscle pain, muscle tenderness and weakness) or myalgia then the statin should be stopped and CK checked urgently. [patient.info]

  • Fracture

    The occurrence of acute compartment syndrome in the absence of trauma or fracture, though rare, can have devastating consequences following delays in treatment. AECS requires prompt diagnosis and surgical intervention to prevent these consequences. [ncbi.nlm.nih.gov]

    Abstract Objectives: To review the efficacy of the current diagnostic methods of acute compartment syndrome (ACS) after leg fractures. [doi.org]

    Findings are not specific because similar findings are sometimes caused by the fracture itself. Many trauma patients have altered mental status due to other injuries and/or sedation. [msdmanuals.com]

    Orthopedic trauma including compartment syndrome and fractures may result in rhabdomyolysis. High voltage electrical injury, burns, near drowning can all lead to rhabdomyolysis. [symptoma.com]

Psychiatrical

  • Delusion

    Due to delusions of central nervous system toxoplasmosis, he ingested 300 mg of monensin. His laboratory studies revealed severe rhabdomyolysis without renal dysfunction. Total creatine kinase (CK) peaked above 100,000 U/L. [ncbi.nlm.nih.gov]

Neurologic

  • Hyporeflexia

    On admission, the patient was afebrile, hypotensive, tachycardic, cyanotic with generalized skeletal muscle pain, and with paresis of all extremities and hyporeflexia. [thefreelibrary.com]

Urogenital

  • Dark Urine

    As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. [ncbi.nlm.nih.gov]

    Symptoms and signs are varied, but a classic triad of muscle pain, weakness, and dark urine are described. Etiology Most common causes reported in Western adult populations is trauma/crush injury, exercise, cocaine and immobilization. [radiopaedia.org]

  • Kidney Failure

    STORY HIGHLIGHTS Haiti earthquake survivors are experiencing kidney failure, a major health concern When a muscle ruptures it releases particles that get trapped in kidneys Rhabdomyolysis can lead to kidney failure and death if a patient is not hydrated [cnn.com]

    In the event that kidney failure occurs, the patient will undergo dialysis treatment to filter the blood. [drugdangers.com]

    Rhabdomyolysis treatment Rhabdomyolysis is usually treated in hospital, with intravenous fluids to help you produce enough urine and prevent kidney failure. Rarely, dialysis is needed if kidney function is poor. [healthdirect.gov.au]

    Rhabdomyolysis is the cause for a significant percentage of patients with kidney failure. [emedicinehealth.com]

  • Oliguria

    Due to oliguria, renal replacement therapy was initiated. An etiological investigation revealed a beta-oxidation defect. Metabolic diseases are a known cause of rhabdomyolysis. [ncbi.nlm.nih.gov]

    Patients may need dialysis if oliguria is present. [nrsng.com]

    Indications: Low Urine pH in Rhabdomyolysis Theory: Myoglobin is less nephrotoxic in a more alkaline environment Protocol Saline 0.45% (1/2 NS) with Sodium Bicarbonate 40 meq (1 to 2 ampules) and Mannitol 10 grams per liter Contraindications Persistent Oliguria [fpnotebook.com]

    Persistent oliguria/anuria and metabolic disturbance will require renal-replacement therapy. [ceaccp.oxfordjournals.org]

  • Red Urine

    [Reference] Age/sex Symptoms CPK peak, U/L AST Remarks Outcome [14] 18 M Sore throat, red urine, myalgias, pharyngitis, and LN 5750 165 No urine drug screen performed Survived [12] 29 M Sore throat, fever, pharyngitis, and LN 4224 250 No urine drug screen [omicsonline.org]

Workup

In the evaluation of blunt trauma in children, it is essential to remain vigilant for child abuse (non accidental injury). Consider rhabdomyolysis in cases of child abuse as differential diagnosis, drug overdoses, events which are heat related and pediatric orthopedic injuries.

Failure to consider these symptoms can lead to missed diagnosis and could result in acute renal failure.

Useful laboratory tests include:

  • Complete blood count (CBC)
  • Serum electrolytes, blood urea nitrogen, creatinine, glucose, calcium, phosphate, uric acid and liver function tests
  • Prothrombin time (PT), activated partial thromboplastin time (aPTT)
  • Serum aldolase
  • Lactate dehydrogenase (LDH)

Hyperkalemia [9] occurs in 10-40% of cases, it can be severe and can cause life threatening dysrhythmias and death. Hypocalcemia is noticed early in the course of rhabdomyolysis. Supplemental calcium is not suggested to be given in these patients. Increased purine metabolism causes hyperuricemia(increased uric acid levels in the blood). Specific therapy with uricosuric agents or allopurinol will not be helpful.

The blood urea nitrogen/creatinine ratio may be decreased because of conversion of liberated creatine to creatinine.
The most reliable and sensitive indicator of muscle injury is enzyme creatine kinase (CK) levels. CK levels rise within 12 hours, peak in 24-36 hours and decrease at a rate of 30-40% per day. CK levels decline 3-5 days after resolution of muscle injury. Failure of CK levels to decrease suggests ongoing muscle injury or development of a compartment syndrome. The peak CK levels when higher than 15000U/L may be predictive of renal failure. CK levels 5 times the reference range suggests rhabdomyolysis.

Plasma myoglobin values are not reliable because myoglobin has a half life of 1-3 hours and is cleared from plasma within 6 hours. Urine myoglobin levels are therefore preferable. A urine myoglobulin assay is helpful in patients with coexisting hematuria (confirmed with microscopic hexamination) when the presence of myoglobin is suspected. Urine dipstick is positive in fewer than 50% of patients with rhabdomyolysis, thus a normal test does not rule out this condition.

Treatment

Assess the airway, breathing and circulation. Ensure adequate hydration and record the output of urine adequately. Identify and correct the inciting cause of rhabdomyolysis (e.g. trauma, infection or toxins) [10].

General recommendations for the treatment of rhabdomyolysis include fluid restriction and prevention of end organ complications (e.g. acute renal failure). Other supportive measures include correction of electrolyte imbalance.

Monitor and check for compartment syndrome, hyperkalemia (high phosphate levels), oliguric/ non oliguric renal failure and disseminated intravascular coagulation.

Surgical care may be required to relieve pressure in compartment syndrome cases in the form of fasciotomy (removing of fascia), orthopedic treatment is required in cases of crush injuries and fractures.

Dietary supplementation with glucose or fructose may decrease the pain and fatigue associated with phosphorylase deficiency. The muscle pain and myoglobinuria is basically due to carnitine palmitoyl transferase deficiency which will be reduced with low fat and high carbohydrate diet.

Prognosis

The overall mortality for patients with rhabdomyolysis is approximately 5%; however, the risk of death for any patient is dependent on the underlying cause and existing comorbidities.

Rapid intervention and appropriate supportive treatment of rhabdomyolysis related kidney injury and renal failure improves outcomes dramatically in traumatic crush injuries [6].

Etiology

Rhabdomyolysis has many etiologies and is often multifactorial.

  • Infection and inherited disorders appear to be the most prevalent etiologies in children. The treating doctor should be prompt and alert to diagnose rhabdomyolysis to prevent acute renal failure.
  • Trauma and muscle compression [2] cause rhabdomyolysis through direct injury to muscle. Orthopedic trauma including compartment syndrome and fractures may result in rhabdomyolysis.
  • High voltage electrical injury, burns, near drowning can all lead to rhabdomyolysis.
  • Prolonged immobilization (prolonged surgical procedure, stroke) leads to muscle necrosis.
  • Metabolic: hypothyroidism, hyperthyroidism, diabetic ketoacidosis (a state which occurs when a diabetic person is fasting) and nonketotic hyperosmolar coma have been associated with rhabdomyolysis. Carnitine deficiency and glycogen storage disorders also can cause rhabdomyolysis.
  • Anaesthesia: Malignant hyperthermia (due to succinyl choline in cholinesterase deficient patients) and neuroleptic malignant syndrome (due to dopamine agonists).
  • Connective tissue disorders: Polymyositis, dermatomyositis and Systemic Lupus erythromatosis can cause rhabdomyolysis.
  • Drugs and myotoxins: Any drug that impairs skeletal muscle ATP production or increases energy requirements may cause rhabdomyolysis.

Exertional activity may cause rhabdomyolysis in untrained individuals. Such events occur in hot and humid climate and are related to exertional heat stress and heat stroke.

Many factors that increase the risk of exertional rhabdomyolysis are renal failure include dehydration, use of nutritional supplements, drug abuse, sickle cell trait, malignant hyperthermia.

Epidemiology

Rhabdomyolysis is a common condition in adults and understudied in pediatrics. About 26,000 cases occur annually. Most cases are due to abuse of illicit drugs or alcohol, muscular trauma, crush injuries and myotoxic effects of prescribed drugs.

The incidence of rhabdomyolysis induced kidney injury [3] ranges from 17-35%. Rhabdomyolysis is more common in adults, though it can occur in infants as well as adolescents who have inherited enzyme deficiencies of carbohydrate or lipid metabolism or who have inherited myopathies. The incidence is higher in males compared to females.

Pathophysiology

Skeletal muscle injury causes disruption of the sarcolemmal [4] membrane and release of intracellular myocyte components. ATP depletion due to muscle hypoxia leads to sarcolemmal membrane injury. This results in electrolyte disturbances. Increase in intracellular calcium results in hyperactivity of proteases and proteolytic enzymes and generation of free oxygen radicals. The consequent damage to cell membrane causes release of intracellular contents into plasma.

An inflammatory cascade and reperfusion injury cause muscle damage and degeneration. Myoglobin is an important myocyte compound released into plasma after muscle injury. Excess myoglobin precipitates in glomerular filtrate and can cause acute kidney injury [5].

Prevention

Once a preventable inciting cause is identified, efforts should be made to avoid it. Strenuous physical exercises should be avoided by untrained athletes. Alcohol should be avoided. Overdose of narcotic, sedative hypnotic drugs should be stopped. Any risky behavior that may result in trauma should be avoided.

Summary

Rhabdomyolysis is a serious syndrome produced by injury to skeletal muscles involving leakage of large quantities of potentially toxic intracellular contents into plasma. It is characterized by a triad of muscle weakness [1], myalgias and myoglobinuria.

Life threatening complications like renal failure and disseminated intravascular coagulation (DIC) are dreaded symptoms of this disorder.

Patient Information

Rhabdomyolysis is a serious medical disorder caused due to injury to skeletal muscles and is characterized by triad of muscle weakness, muscle pain and dark urine. Life threatening renal failure and disseminated intravascular coagulation (DIC) are potential complications if the condition is not corrected soon.

Infection and inherited disorders appear to be the most prevalent etiologies in children. Trauma and muscle compression cause rhabdomyolysis through direct injury to muscle. Other causes include high voltage electrical injury, burns, near drowning, prolonged immobilization (prolonged surgical procedure, drug abuse, sedative overdose, alcohol intoxication, stroke), metabolic causes and connective tissue disorders. Exertional activity may cause rhabdomyolysis in untrained individuals.

The condition is usually diagnosed on the basis of antecedent history of inciting injury and predisposing factors. The most reliable and sensitive indicator of muscle injury is enzyme creatine kinase (CK) levels.

Rapid intervention and appropriate supportive treatment of rhabdomyolysis related kidney injury and renal failure improves outcomes dramatically.

References

  1. Beetham R. Biochemical investigation of suspected rhabdomyolysis. Ann Clin Biochem. 2000 Sep;37 ( Pt 5):581-7. Review
  2. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72.
  3. Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore). 1982 May;61(3):141-52
  4. Elsayed EF, Reilly RF. Rhabdomyolysis: a review with emphasis on pediatric population. Pediatr Nephrol. 2010 Jan;25(1):7-18.
  5. Huerta- Alardin AL, Varon J, Marik PE. Bench to bedside review: Rhabdomyolysis an overview for clinicians. Crit Care. 2005 Apr;9(2):158-69.
  6. Malinoski DJ, Slater MS, Mullins RJ. Crush injury and rhabdomyolysis. Crit Care Clin. 2004 Jan;20(1):171-92. Review.
  7. Knochel JP. Hypophosphatemia and rhabdomyolysis. Am J Med. 1992 May;92(5):455-7.
  8. Sinert R, Kohl L, Rainone T, Scalea T. Exercise-induced rhabdomyolysis. Ann Emerg Med. 1994 Jun;23(6):1301-6.
  9. Salluzzo RF. Rhabdomyolysis. In: Rosen P, Barkin R, editors. Emergency medicine: concepts and clinical practice. 4th ed. St. Louis: Mosby-Year Book; 1997. p. 2478-87.
  10. Finnish Medical Society Duodecim. Rhabdomyolysis. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; Apr 12. 2007
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