Approach Considerations
Assess the ABCs (A irway, B reathing, C irculation), and provide supportive care as needed. Ensure adequate hydration, and record urine output. Insert a Foley catheter for careful monitoring of urine output. Identify and correct the inciting cause of rhabdomyolysis (eg, trauma, infection, or toxins). [79]
General recommendations for the treatment of rhabdomyolysis include fluid resuscitation and prevention of end-organ complications (eg, acute renal failure [ARF]). Other supportive measures include correction of electrolyte imbalances. [1, 80] Obtain an ECG to monitor effects of hyperkalemia and other electrolyte disturbances.
Serial physical examinations and laboratory studies are indicated to monitor for compartment syndrome, hyperkalemia, acute oliguric or nonoliguric renal failure, and disseminated intravascular coagulation (DIC). Compartment syndrome necessitates immediate orthopedic consultation for fasciotomy. DIC should be treated with fresh frozen plasma, cryoprecipitate, and platelet transfusions. Monitor cardiac function. Monitor creatine kinase (CK) levels to show resolution of rhabdomyolysis.
Once the patient’s condition has been stabilized and life- and limb-threatening conditions have been addressed, he or she may be transferred to another facility if necessary. Follow the guidelines of the Consolidated Omnibus Budget Reconciliation Act (COBRA) and the Emergency Medical Treatment and Labor Act (EMTALA). In natural disasters, patients often have to be evacuated out of affected areas and transported to locations that can provide dialysis services. [1]
Once they are well hydrated, patients with normal renal function, normal electrolyte levels, alkaline urine, and an isolated cause of muscle injury may be discharged and monitored as outpatients. Any diagnostic or genetic tests during inpatient stay should be communicated to primary care or outpatient specialty physicians.
Fluid Resuscitation
Expansion of extracellular volume is the cornerstone of treatment and must be initiated as soon as possible. No randomized trials of fluid repletion regimens in any age group have been done. [3] Retrospective studies of patients with severe crush injuries resulting in rhabdomyolysis suggest that the prognosis is better when prehospital personnel provide fluid resuscitation. [80] Support of intravascular volume increases the glomerular filtration rate (GFR) and oxygen delivery and dilutes myoglobin and other renal tubular toxins.
Patients with a CK elevation in excess of 2-3 times the reference range, appropriate clinical history, and risk factors should be suspected of having rhabdomyolysis. Obtain intravenous (IV) access with a large-bore catheter. For adults, administer isotonic fluids at a rate of approximately 400 mL/h (may be up to 1000 mL/h based on type of condition and severity) and then titrate to maintain a urine output of at least 200 mL/h. [3]
Because injured myocytes can sequester large volumes of extracellular fluid, crystalloid requirements may be surprisingly large. In patients with CK levels of 15,000 IU/L or greater, higher volumes of fluid, on the order of at least 6 L in adults, are required. [81] (Consider central venous pressure measurement or Swan-Ganz catheterization in patients with cardiac or renal disease. These invasive studies can assist in the assessment of the intravascular volume.) Repeat the CK assay every 6-12 hours to determine the peak CK level.
Aggressive and early hydration with isotonic sodium chloride solution is important for the prevention of pigment-associated renal failure. The composition of repletion fluid is controversial and may also include sodium bicarbonate. Initial fluid use in young children has been recommended to be 20 mL/kg; in adolescents, 1-2 L/h has been recommended. Subsequent hydration at a level 2-3 times maintenance may be sufficient. [11, 82] Few studies of fluid repletion regimens in children are available. [11]
Prevention of Acute Kidney Injury and Renal Failure
ARF develops in 30-40% of patients with rhabdomyolysis. Suggested mechanisms include the following:
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Precipitation of myoglobin and uric acid crystals within renal tubules
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Decreased glomerular perfusion
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Nephrotoxic effect of ferrihemate
Ferrihemate and globin are the breakdown products of myoglobin when pH levels fall to less than 5.6. Ferrihemate is one of the agents responsible for acute tubular necrosis (ATN). It contains iron, a transition element, which is free to accept and donate electrons. This results in the generation of free radicals, which cause direct renal cell injury. Heme-proteins may also affect nitrous oxide (NO), endothelin receptors, and cytokines. [14]
Suggested predictors of the development of AKI and potentially renal failure include the following [70] :
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Peak CK level higher than 6000 IU/L
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Dehydration (hematocrit >50, serum sodium level >150 mEq/L, orthostasis, pulmonary wedge pressure < 5 mm Hg, urinary fractional excretion of sodium < 1%)
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Sepsis
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Hyperkalemia or hyperphosphatemia on admission
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Hypoalbuminemia
AKI has occasionally developed in severely dehydrated patients with peak CK levels as low as 2000 IU/L. To prevent renal failure, many authorities advocate urinary alkalization, mannitol, and loop diuretics.
Alkalization of urine is believed to be helpful and is based on the observation that acidic urine is necessary to cause ATN. Alkalinization may also reduce the occurrence of cast formation (ferrihemate and myoglobin). Some authorities believe that aggressive hydration sufficiently causes a solute diuresis that alkalizes the urine. Evidence for the use of these agents is mostly from animal studies and retrospective adult studies. There is no supporting evidence in the pediatric literature regarding alkalinization of urine. [10] It is recommended for patients with rhabdomyolysis and CK levels higher than 6000 IU/L.
Urinary alkalization should be considered earlier in patients with acidemia, dehydration, or underlying renal disease. A suggested regimen for adult patients is isotonic sodium chloride solution (0.9% NaCl) with 1 ampule of sodium bicarbonate administered at 100 mL/h. Sodium bicarbonate is used with care because it may potentiate hypocalcemia. The IV bicarbonate concentration is often adjusted to achieve a urine pH higher than 6.5-7.0. This level of alkalization inhibits precipitation of myoglobin and hemoglobin in the tubules. If the pH of urine less than 6.5, alternate each liter of normal saline with 1 L of 5% dextrose plus 100 mmol of bicarbonate.
If urine output is inadequate, consider the use of diuretics such as mannitol (in adults) and furosemide. Mannitol, acting as an osmotic diuretic, is thought to increase urinary flow and reduce myoglobin cast obstruction in renal tubules. [1] Its efficacy has not been adequately compared with that of aggressive hydration regimens. [3, 14, 83] Loop diuretics such as furosemide may be used to enhance urinary output in patients who are oliguric despite adequate intravascular volume. It is recommended that aggressive volume expansion is to be maintained until myoglobinuria is cleared. Prospective multicenter studies may be necessary to understand the efficacy of bicarbonate and mannitol in patients with rhabdomyolysis.
Correction of Electrolyte, Acid-Base, and Metabolic Abnormalities
Frequently monitor serum electrolyte levels, urine pH levels, and acid-base status. [1, 80] Metabolic abnormalities should also be addressed.
Treatment of hyperkalemia consists of IV sodium bicarbonate, glucose, and insulin; oral or rectal sodium polystyrene sulfonate; and hemodialysis. These measures transiently shift potassium from extracellular to intracellular compartments. [11, 77] Administer IV calcium chloride for patients who are hemodynamically compromised and hyperkalemic.
Hypocalcemia is noted early in the course of rhabdomyolysis and generally is not of clinical significance. Correct hypocalcemia only if the patient has cardiac dysrhythmias or seizures. Calcium may combine with phosphate, forming a metastatic calcification, often intramuscularly. Calcium supplementation is not recommended, as hypercalcemia may be seen in the recovery phase (late).
Hyperuricemia and hyperphosphatemia rarely are of clinical significance and rarely require treatment. Control of hyperphosphatemia, if required, is achieved by using alkaline diuresis. Hypercalcemia may develop during the recovery phase, especially if there is acute kidney injury.
Other Medical Treatment Measures
Dialysis may be required in patients with oliguric renal failure, persistent hyperkalemia, other electrolyte abnormalities, pulmonary edema, congestive heart failure, and persistent metabolic acidosis.
The role of free-radical scavengers and antioxidants in rhabdomyolysis (eg, pentoxifylline, vitamin E, and vitamin C) has been studied in animal models of ischemia-reperfusion injuries. Controlled studies evaluating the efficacy of these agents have not been performed, and their clinical use remains unclear. [14, 3]
With adequate hydration ensured, no specific outpatient medications are needed. Inciting myotoxic agents should be stopped.
Fasciotomy and Treatment of Fractures
Surgical care may be necessary, depending on the cause of rhabdomyolysis. [1]
Compartment pressures should be measured when significant muscle injury has occurred (see Workup). Muscle injury results from decreased tissue perfusion, which is caused by increased pressure within the affected space. High intracompartmental pressures mediate further ischemia, damage, and necrosis. When the intracompartmental pressure exceeds 30 mm Hg, a fasciotomy is advocated. Prolonged elevated intracompartmental pressure may lead to irreversible peripheral nerve injury. [1]
Limb fractures may require surgical and orthopedic treatment. [84]
Diet
Dietary modification may help to reduce the symptoms associated with some of the metabolic disorders and inborn errors of metabolism. [12]
Dietary supplementation with glucose or fructose may decrease the pain and fatigue associated with phosphorylase deficiency. The muscle pain and myoglobinuria due to carnitine palmityl transferase deficiency may be reduced with frequent meals and a low-fat, high-carbohydrate diet. Substitution of medium-chained triglycerides may also be helpful.
Dietary modification does not seem to change the muscle symptoms of phosphofructokinase deficiency or phosphoglycerate mutase deficiency.
Activity
Strenuous activities (eg, competitive sports) should be avoided if they cause recurrent myalgias, myopathy, or rhabdomyolysis. [12] Children and adolescents with recurrent rhabdomyolysis related to exertion require further medical evaluation.
High-school coaches and trainers must ensure proper hydration and maintain fluid balance during practice sessions and games. Signs and symptoms of heat exhaustion must be evaluated in a timely fashion during hot and humid conditions. [61]
Prevention
Once a preventable inciting cause of rhabdomyolysis is identified, the patient must make an effort to avoid it. Exercise should be reduced or avoided if it is causing or exacerbating rhabdomyolysis. [85]
Alcohol should be avoided. Overdose of narcotics, sedative-hypnotics, or any other drugs known to cause immobilization and, hence, pressure necrosis should be avoided. Proper mental health and drug rehabilitation services should be offered to individuals with substance use disorders. Use of stimulants (eg, cocaine, amphetamines, or Ecstasy) should be discouraged.
Compliance with seizure and asthma medications may reduce status epilepticus, status asthmaticus, or both.
Any risky behavior that results in trauma should be avoided.
Consultations
Consult a nephrologist for patients who have significant rhabdomyolysis, show evidence of renal failure, or require dialysis. Indications for hemodialysis include hyperkalemia that is persistent despite therapy, severe acid-base disturbances, refractory pulmonary edema, and progressive renal failure.
Consult a neurologist for patients with status epilepticus or new-onset seizures.
Consult an orthopedic surgeon for patients with a limb fracture or suspected compartment syndrome.
Notify the poison control center in cases of overdose or snake/insect envenomation.
Consult a geneticist or metabolism specialist for patients with genetic or metabolic abnormalities. Diagnosis of inborn errors of metabolism and prompt metabolic interventions may be life-saving.
Consult a rheumatologist for patients with suspected inflammatory myopathies, systemic lupus erythematosus, or sarcoidosis.
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Rhabdomyolysis is associated with the release of myoglobin into plasma. Shown here is a model of helical domains in myoglobin (protein linked to kidney damage in rhabdomyolysis).
