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.

• 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]

  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]

• 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]

  Michael Ray describes symptoms as “generalized muscle pain, nausea and vomiting, abdominal cramping, and in significant cases, dark red Coca-Cola urine.” That last bit is an instant ticket to the ER – don’t mess around – GO! [crossfit053.com]

  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]

• Acute Abdomen

  Abdominal wall muscle injury resulting in rhabdomyolysis can imitate an acute abdomen in a healthy woman presenting with abdominal pain and swelling. [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

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

  Vacuolar myopathy (sarcoplasmic reticulum) [neuropathology-web.org]

  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]

  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]

• 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]

• Muscle Weakness

  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]

• 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]

• 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]

  Only a minority of patients had muscle swelling on exam, and this sign often was only apparent after the patient received IV fluids, so re-examining the patient after IV hydration may be useful. [clinicaladvisor.com]

• 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]

• 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]

• 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]

  In 1944 Bywaters demonstrated experimentally that the kidney failure was mainly caused by myoglobin. [en.wikipedia.org]

  Both mechanisms can lead to kidney failure (the major complication of rhabdomyolysis). [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]

  […] toxicity of heme. ( 2, 9 ) The precipitation of calcium phosphate and appearance of hypocalcemia should be monitored closely. ( 9 ) The best regimen and rate of bicarbonate administration are unknown. ( 9 ) Fluids should be carefully given once ARF and oliguria [scielo.br]

• 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]

• Cesarean Section

  At 31 weeks, premature rupture of the membranes occurred, necessitating cesarean section, yielding a baby with weak tonus, and the presence of infantile muscle diseases was suspected. [ncbi.nlm.nih.gov]

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.

• Hypertriglyceridemia

  Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults. [ncbi.nlm.nih.gov]

• Base Deficit

  Factors identified as having potential to differentiate patients at high and low risk for ARF include the amount of muscle damage, base deficit, renal function (GFR, creatinine, urea), and presence of myoglobin in the urine. [doi.org]

• Fibrinoid Necrosis

  A femoral muscle-biopsy specimen showed fibrinoid necrosis of medium-sized vessels and disruption of the elastic lamina of the vessel wall in fascia. [ncbi.nlm.nih.gov]

• Ischemic Changes

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

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.

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].

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.

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.

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].

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.

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.

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.

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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