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Rhabdomyolysis

Rhabdomyolyses

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


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.

Limb Pain
  • Abstract 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]
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 chest pain. Your heart is beating faster than usual or has a strange rhythm. Care Agreement You have the right to help plan your care. Learn about your health condition and how it may be treated.[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]
Myopathy
  • KEYWORDS: Exercise; Exertional rhabdomyolysis; Genetic; Myopathy; Rhabdomyolysis; Ryanodine receptor (RyR1); Skeletal muscle ryanodine receptor (RYR1) gene[ncbi.nlm.nih.gov]
  • Zocor Myopathy A number of patients have reported the onset of Zocor myopathy. Zocor myopathy is most common in patients taking the highest dosage of 80 milligrams per day.[drugdangers.com]
  • Vacuolar myopathy (sarcoplasmic reticulum)[neuropathology-web.org]
  • The causes of rhabdomyolysis include drugs and other toxic agents, infections, physical exertion, crush injury, and muscle diseases (dystrophinopathies and metabolic myopathies).[ncbi.nlm.nih.gov]
  • Pain management is warranted for patients with mitochondrial myopathies to enable physical activity. 5, 6 In the future, mitochondrial gene therapy may be a treatment option for patients with mitochondrial myopathies. 5 Conclusion Mitochondrial myopathies[jaoa.org]
Muscle Weakness
  • Abstract Polymyositis is an idiopathic inflammatory myopathy, characterized by proximal muscle weakness and sometimes extramuscular manifestations.[ncbi.nlm.nih.gov]
  • 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]
  • A 71-year-old man was hospitalized because of muscle weakness of the lower limbs that persisted for 1 month. On a physical examination, rapidly progressive lower proximal muscle weakness and bilateral drop foot were observed.[ncbi.nlm.nih.gov]
  • Symptoms of rhabdomyolysis include dark urine, muscle weakness and fatigue. Statins are the most commonly used drugs for prevention and management of dyslipidemia.[ncbi.nlm.nih.gov]
  • If abnormal posture or muscle weakness is observed during the course of gastroenteritis, blood and urinary tests should be performed to rule out rhabdomyolysis.[ncbi.nlm.nih.gov]
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]
  • Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level.[ncbi.nlm.nih.gov]
  • A previously healthy 37-year-old man presented with severe myalgia and dark urine after performing high-intensity exercise. The patient's serum CK level was 95,100 U/L and his urine myoglobin level was 160,000 ng/mL.[ncbi.nlm.nih.gov]
  • In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis[ncbi.nlm.nih.gov]
  • We present a previously healthy adolescent who was admitted to our emergency department with a four-day history of myalgia, muscle weakness and dark urine. At presentation, she was dehydrated.[ncbi.nlm.nih.gov]
Muscle Tenderness
  • 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]
  • tenderness Weakness of the affected muscles Other symptoms that may occur with this disease: Fatigue Joint pain Seizures Weight gain (unintentional) Exams and Tests A physical exam will show tender or damaged skeletal muscles.[mountsinai.org]
Muscle Swelling
  • Symptoms of rhabdomyolysis: Muscle pain, tenderness, or weakness Problems climbing stairs or opening jars Muscle swelling (also known as “compartment syndrome”) Urine that is dark or cola-colored Fever Nausea or vomiting High potassium (hyperkalemia)[schmidtlaw.com]
  • A large number of patients presenting with calf pain or muscle swelling have their diagnosis confounded by other conditions, most notably deep venous thrombosis.[news-medical.net]
  • swelling, and biochemically by elevation of CK, which is proportionate to the extent of myonecrosis.[neuropathology-web.org]
  • If the myositis is allowed to intensify, then irreversible damage may occur, generally from the muscle swelling, which, in turn, causes compression of vessels and nerves and results in massive dissolution of significant quantities of muscle.[cochranfirm.com]
  • The need for fasciotomy may be decreased if mannitol is used, as it can relieve muscle swelling directly.Disseminated intravascular coagulation generally resolves when the underlying causes are treated, but supportive measures are often required.[en.wikipedia.org]
Flaccid Paralysis
  • Neurological examinations revealed symmetrical flaccid paralysis in his lower extremities, but the patient was alert and his sensory system was intact. His initial serum potassium and phosphate level was 1.8 mmol/L and 1.4 mg/dL, respectively.[ncbi.nlm.nih.gov]
Flaccid Paralysis of the Lower Extremity
  • Neurological examinations revealed symmetrical flaccid paralysis in his lower extremities, but the patient was alert and his sensory system was intact. His initial serum potassium and phosphate level was 1.8 mmol/L and 1.4 mg/dL, respectively.[ncbi.nlm.nih.gov]
Kidney Failure
  • Days later these crush injuries can cause kidney failure then death, experts say.[cnn.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]
  • In the event that kidney failure occurs, the patient will undergo dialysis treatment to filter the blood.[drugdangers.com]
  • One patient developed transient kidney failure during rhabdomyolysis. Two received immunosuppressants on suspicion of myositis. None had episodes of malignant hyperthermia. Muscle biopsies were normal, but CT/MRI showed muscle hypertrophy in most.[ncbi.nlm.nih.gov]
  • In 1944 Bywaters demonstrated experimentally that the kidney failure was mainly caused by myoglobin.[en.wikipedia.org]
Dark Urine
  • Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise.[ncbi.nlm.nih.gov]
  • Symptoms of rhabdomyolysis include dark urine, muscle weakness and fatigue. Statins are the most commonly used drugs for prevention and management of dyslipidemia.[ncbi.nlm.nih.gov]
  • A previously healthy 37-year-old man presented with severe myalgia and dark urine after performing high-intensity exercise. The patient's serum CK level was 95,100 U/L and his urine myoglobin level was 160,000 ng/mL.[ncbi.nlm.nih.gov]
  • We present a previously healthy adolescent who was admitted to our emergency department with a four-day history of myalgia, muscle weakness and dark urine. At presentation, she was dehydrated.[ncbi.nlm.nih.gov]
  • Approximately half of patients with rhabdomyolysis present with the triad of myalgias, weakness and dark urine.[ncbi.nlm.nih.gov]
Hematuria
  • Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise.[ncbi.nlm.nih.gov]
  • A urine myoglobulin assay is helpful in patients with coexisting hematuria (confirmed with microscopic hexamination) when the presence of myoglobin is suspected.[symptoma.com]
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.

Ischemic Changes
  • Furthermore, muscle necrosis was localized depending on the arterial distribution, suggesting ischemic changes in the muscles.[ncbi.nlm.nih.gov]

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.

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.

Sex distribution
Age distribution

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

Article

  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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Last updated: 2018-06-22 11:11