Rhabdomyolysis

Etiology

The etiology of rhabdomyolysis can be classified into two broad categories. Traumatic or physical causes and nontraumatic or nonphysical causes.[12]

A careful history, physical examination, and laboratory workup can help identify the cause of rhabdomyolysis. In addition, multiple cohort studies have shown different causes at different frequencies for rhabdomyolysis depending on the hospital location and community behaviors. 

Traumatic or Physical Causes

Traumatic/physical compression rhabdomyolysis can occur in different settings. In general, rhabdomyolysis from traumatic causes has a poor prognosis when compared to non-traumatic. Subclinical elevation of creatinine phosphokinase, myoglobin in serum, and myoglobinuria following physical exertion is widespread.

1. Victims of polytrauma, motor vehicle accidents, mining accidents, and earthquakes, particularly those trapped, are prone to crush syndrome and may develop severe compartment syndrome.
2. Prolonged immobilization due to coma, intoxication with alcohol and opiates, hip fracture, and surgeries requiring specific positions for a long duration.[13]
3. Abuse, torture, and physical restraints for a longer duration are commonly seen in children.
4. Fractures of lower extremities (tibial fracture), arterial occlusion from prolonged immobilization, tourniquet, and surgical clamping.[14]
5. Fire accidents and explosions.
6. High voltage electric shock and lightning can cause direct injury to the sarcoplasmic membrane, with massive calcium influx along with severe rhabdomyolysis.[15]
7. Strenuous muscular exercise, especially in untrained individuals, lifting heavy weights and performing under scorching hot and humid conditions, status epilepticus, delirium tremors, phencyclidine overdose, tetanus, and rarely sepsis.[16]

Nontraumatic or Nonphysical Causes

Nontraumatic causes of rhabdomyolysis can be from a mismatch between oxygen supply and demand, electrolyte changes, and metabolic abnormalities.

1. Medications-alcohol, colchicine, carbon monoxide, statins, daptomycin, cocaine, corticosteroids, amphetamines, ecstasy, electrolytes, zidovudine, fibrates, diuretics, antimalarials, anticholinergics, intravenous and intramuscular illicit drug use.
2. Infections-pyomyositis (MRSA), septic shock, toxic shock syndrome, Mycoplasma, Legionella, malaria, HIV, coxsackievirus, Salmonella, tularemia, ehrlichiosis, and influenza.
3. Electrolyte abnormalities-hypokalemia, hypophosphatemia, hyperosmolar conditions, hypo and hypercalcemia, and severe dehydration.[17]
4. Endocrine-hyperosmolar hyperglycemic state, severe diabetic acidosis with coma, myxedema.
5. Myopathies - Disorders of glycogenolysis [Myophosphorylase deficiency(McArdle disease), phosphorylase kinase deficiency], disorders of glycolysis [phosphofructokinase deficiency, phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, lactate dehydrogenase deficiency], disorders of purine metabolism [myoadenylate deaminase deficiency], disorders of lipid metabolism [carnitine deficiency, carnitine palmitoyltransferase deficiency, short and long-chain acyl-CoA dehydrogenase deficiency, lipin-1 deficiency] and Brody myopathy (calcium adenosine triphosphatase [CAT] deficiency).[18]
6. Insect bite and snake venom, hornet bite, carbon monoxide, Haff disease, and mushroom poisoning.[19]
7. Autoimmune myositis-polymyositis, dermatomyositis.
8. Hemoglobinopathy-sickle cell trait.
9. Dysregulated body temperature-neuroleptic malignant syndrome, malignant hyperthermia (inhaled anesthetic agents with or without succinylcholine), near drowning, hypothermia, and frostbite.[20][21]
10. Supplements for Physical performance-enhancing and weight-loss.
11. Capillary leak syndrome and drug withdrawal-like baclofen.

The most common causes of rhabdomyolysis are trauma, immobilization, sepsis, and cardiovascular surgeries. With the increased use of lipid-lowering drugs, the incidence of rhabdomyolysis from HMG Co-A inhibitors is rising. Muscle toxicity from statins ranges from myopathy, myalgia, myositis, and rhabdomyolysis. Multiple pathophysiologic mechanisms contribute to statin-related muscle damage. Discontinuation of statins is an effective method in the treatment of statin-induced rhabdomyolysis. Persistent elevation of CPK even after discontinuation of statins should raise concern for necrotizing autoimmune myopathy. Concomitant use of other drugs which can potentiate muscle injury should be avoided. Use of the lowest tolerable statin dose is recommended in patients with a history of drug-induced rhabdomyolysis. Patients may have one or more concomitant risk factors for the development of rhabdomyolysis. 5 to 10% of rhabdomyolysis cases may not have a definitive cause. 

Epidemiology

Approximately 25,000 cases of rhabdomyolysis are reported each year in the USA. The prevalence of acute kidney injury in rhabdomyolysis is about 5 to 30%. There is a large variation in the incidence of acute kidney injury (AKI) in rhabdomyolysis settings because of multiple definitions of KI And with varying severity of rhabdomyolysis.[22] Acute kidney injury from rhabdomyolysis constitutes 15% of the total cases of acute kidney injury.[23] Rhabdomyolysis can occur at any age, but the majority of cases are seen in adults. Males, African-American race, obesity, age more than 60 are factors that demonstrate a higher incidence of rhabdomyolysis. The most common cause of rhabdomyolysis in children is infection (30%). Two or more risk factors might be present in adults with rhabdomyolysis. Acute kidney injury in rhabdomyolysis contributes to significant morbidity and mortality. Rhabdomyolysis with significant elevation in CPK and admission to ICU significantly affects the outcome. Even without acute kidney injury, the mortality rate is about 20%, and with kidney injury, mortality is about 50%.[24][25]

The incidence of crush syndrome is between 30 to 50% with traumatic rhabdomyolysis. Children are at low risk for crush syndrome and have better mortality compared to adults. Crush injury-related acute kidney injury and dialysis requirements varied across multiple studies. 6 to 10% of patients with crush syndrome with acute kidney injury in survivors of the Bam earthquake in Iran required hemodialysis, and there is a correlation between the severity and duration of crush injury and the need for hemodialysis.[26] During natural calamities like earthquakes, early fluid resuscitation, extrication, and immediate hospitalization with a multidisciplinary team approach reduce acute kidney injury, morbidity, and mortality.

In 2002, the American College of Cardiology (ACC), the National Heart-Lung and Blood Institute, and the American Heart Association jointly released a clinical advisory. It defined statin associated rhabdomyolysis as muscle symptoms with increased creatine kinase, typically more than 11 times the upper limit of normal (myonecrosis) with elevated serum creatinine consistent with pigment induced nephropathy and myoglobinuria.[27] About 0.5% of patients taking statins might develop clinically significant myonecrosis.[28] Concurrent use of other medications like gemfibrozil, cyclosporine, cytochrome P450 inhibitors, and steroids poses an increased risk for statin-induced rhabdomyolysis. Clinically significant rhabdomyolysis requiring hospital admission was noted in about 0.44 per 10000 patients treated with atorvastatin, simvastatin, and pravastatin as monotherapy. Even though the incidence of rhabdomyolysis is very low with statin use, in clinical practice, muscle-related side effects are the frequent cause for discontinuation of statin therapy.

The incidence of rhabdomyolysis secondary to immobilization, alcohol intoxication, fractures, strenuous muscle exercises, and insect bites is not precise, as these are isolated and sporadic incidents. 

Pathophysiology

There are multiple causes for rhabdomyolysis, but the final common pathway resulting in muscle injury and necrosis is direct myocyte injury or energy supply failure in the muscle cell.[29] The sodium-potassium pump and sodium-calcium exchanger on the sarcoplasmic membrane maintain low intracellular/sarcoplasmic Na+, Ca 2+, and high K+ concentration in the resting muscle. At rest, calcium is stored in sarcoplasmic reticulin. Muscle contraction is an active process using adenosine triphosphate (ATP) where there is excess calcium influx into the sarcoplasm, resulting in actin-myosin linkage. Any insult that disrupts the ATP, Ion channels, and plasma membrane results in a loss of intracellular electrolyte equilibrium.

The muscle injury (trauma, exercise, thermal dependent syndromes) or lack of ATP (Medicines, electrolytes, hereditary and metabolic disorders, intense exercise, ischemia) in a muscle cell results in intracellular sodium and calcium influx. Water is drawn into the cell along with sodium, causing cell swelling and disruption of intracellular and membraneous structures. Excessive intracellular calcium leads to activation of actin-myosin cross-linkage, myofibrillar contraction, and depletion of ATP. Excessive intracellular calcium also activates calcium-dependent phospholipases and proteases, promoting cell membrane dissolution and disruption of ion channels (Na+K+ pump and Na+Ca2+ exchangers). With reperfusion, leukocytes migrate into the damaged muscle and cause an increased number of cytokines, prostaglandins, and free radicals, causing further myolysis, necrosis of muscle fibers, and release muscle breakdown products like potassium and myoglobin, creatine kinase, phosphate, uric acid, and various organic acids into the bloodstream.[30] This leads to the complications of hyperkalemia and hyperphosphatemia. In rhabdomyolysis, hypocalcemia is observed initially, followed by hypercalcemia. This is because calcium first moves into the myocyte during injury, and then it leaks out into extracellular spaces after cell lysis. Disseminated intravascular coagulation (DIC) is thought to be due to thromboplastin released during muscle injury.[31][32] 

Myoglobinuria is only seen in rhabdomyolysis. Myoglobin is freely filtered through the glomerulus and reabsorbed in the renal tubule by endocytosis in a normal, healthy state. Myoglobin has no nephrotoxic effect in the tubules in alkaline urine. The proximal convoluted tubule (PCT) of the kidney has limited ability to convert iron to ferritin. Urine acidification in rhabdomyolysis and excess myoglobin delivery to PCT causes ferrihemate accumulation. The globin chain readily dissociates from the iron-containing ferrihemate portion of myoglobin and is rapidly converted to ferritin. Ferritin generates oxygen-free radicals, leading to excess oxidative stress and Proximal convoluted tubular cell injury.[33] The reabsorption of excess myoglobin is limited in distal convoluted tubule (DCT) in rhabdomyolysis. The presence of vasoconstriction and hypovolemia with excess water reabsorption in DCT further concentrates myoglobin in DCT; all of these promote cast formation and obstruction of DCT.[6] 

Acute kidney injury (AKI) from rhabdomyolysis is multifactorial. Muscle breakdown and water sequestration within the muscle cause volume depletion and activation of the Renin-angiotensin-aldosterone and antidiuretic hormone secretion. Myoglobin, a heme protein with ferrous oxide (Fe2+) in circulation, oxidizes to ferric oxide (Fe3+) and generates hydroxyl free radicals, which are counteracted by effective intracellular antioxidants in a normal, healthy state. Excess myoglobin released from rhabdomyolysis causes oxidative injury to lipids. It allows the excess release of endothelin, thromboxane A2, necrotic tumor factor-alpha, isoprostanes (vasoconstrictors), and decreased nitric oxide (vasodilators), resulting in direct renal vasoconstriction. Excess myoglobinuria during rhabdomyolysis exceeds the renal metabolic threshold and manifests as brown-reddish tea-colored urine called myoglobinuria. The presence of volume depletion, intrarenal vasoconstriction, ischemia, direct cellular injury in PCT, and precipitation of the Tamm–Horsfall protein–myoglobin complex obstructing DCT all play a role in developing the AKI.

Trauma involving muscle groups located in specific compartments is at high risk for the development of compartment syndrome because of muscle swelling, which further causes additional pressure-related damage like arterial occlusion and muscle necrosis. Persistently raised compartment pressure may lead to irreversible peripheral nerve palsy. Compartment pressure of more than 30 mmHg produces significant muscle ischemia, and measurement of compartmental pressure is helpful in decision-making for fasciotomy. Rhabdomyolysis victims with severe blood loss and hypotension are at increased risk for muscle ischemia even with lesser compartment pressures.[34]

Histopathology

Muscle biopsy in rhabdomyolysis is a necessary test when suspected metabolic myopathies. The timing of muscle biopsy is crucial in the identification of appropriate diseases. Excessive muscle fiber necrosis (hematoxylin and eosin stain) is associated with rhabdomyolysis, and obtaining a biopsy during acute injury may miss an underlying myopathy. The current literature recommends muscle biopsy only after complete recovery from rhabdomyolysis. EFNS panel of muscle specialists patients with muscle pain, weakness with 2 to 3 times CPK elevation, myoglobinuria, hypertrophic or atrophic muscles, and EMG suggestive of myopathy can undergo muscle biopsy at the time of presentation.[35] Specific stains are helping to identify different types of myopathies. His glycogen storage disorders can be identified by para-aortic acid Schiff and hematoxylin and eosin staining showing glycogen-containing vacuoles. Succinyl dehydrogenase SDH and a cytochrome oxidase COX staining, along with Gomori trichrome staining, identify ragged red fibers in patients with mitochondrial myopathies. Immunohistochemistry can identify enzyme deficiencies like phosphokinase and myophosphorylase deficiencies.[36]

Kidney biopsy in patients with acute kidney injury from rhabdomyolysis shows multiple lesions. The earliest findings with tubular changes can be seen as early as 1 hour to 12 hours with a light microscope, like dilated bowman space with the ruptured membrane at the glomerulus and reduced glomerular tufts with flattened podocytes. Significant necrosis with loss of microvilli and reduction in basal infolding is seen in the proximal convoluted tubule. Electron microscopy clearly shows electron-dense casts occupying the entire distal, tubular lumen.[37]

History and Physical

Even though muscle pain, weakness, and tea-colored urine are the characteristic triad of rhabdomyolysis, more than 50% of patients do not have all of these specific symptoms. Muscle pain Is the most common presenting symptom and is presented in about 50% of adults with rhabdomyolysis, and dark-colored urine is seen in about 30 to 40%.[12] Weakness typically involves proximal muscle groups. Nonspecific symptoms like muscle cramps, stiffness, muscle swelling, weakness, malaise, abdominal pain, nausea, palpitations, and fever might be present. Depending on the cause of rhabdomyolysis, patients may provide a history of illicit drugs, insect bites, heat exertion, recent surgical procedures, accidents, recent increasing dosages of regularly used medications, antibiotic use, and over-the-counter body enhancing supplements. In myopathies, weakness is the most common complaint in adults but not much in children. Patients may have atrophic or hypertrophic muscles. A detailed history of the nature of the incident, duration of exposure, surrounding enlargement, previous similar hospital admissions, and starting new drugs should be obtained, and a high index of suspicion should be present when thinking of rhabdomyolysis. 

The clinical features of rhabdomyolysis are very nonspecific, and the course depends on the underlying cause. Rhabdomyolysis has both local and systemic features, with early and late complications. The local features include muscle pain, weakness, bruising, swelling, and tenderness. Systemic features include fever, malaise, nausea, confusion, agitation, delirium, tea-colored urine, or anuria.[38] In trauma patients with rhabdomyolysis, a detailed examination of distal pulses and the peripheral nerve should rule out limb ischemia and peripheral neuropathy. Look for signs of dehydration, including dry oral mucosa and decreased skin turgor. In an unconscious patient with tea-colored urine, the ortho toluidine portion of the urine dipstick turns blue in hemoglobin or myoglobin. Myoglobinuria is confirmed in the absence of RBC in urine. Early recognition of rhabdomyolysis is critical to preventing complications. 

Evaluation

The hallmark of acute rhabdomyolysis is elevated CPK levels. In addition, reddish-brown urine from myoglobinuria may be present a 50% of cases. After triage and obtaining vital signs, basic labs, including complete blood count, basic metabolic panel, liver function test, CRP, ESR, CPK levels, urinalysis, EKG, and chest X-ray, should be obtained.

Normal CPK levels are 20 to 200 IU/L. Elevated levels, usually at least five times the upper limit of normal, are considered rhabdomyolysis. CPK exists in four significant isoenzymes: CK-MM, CK-MB, and CK-BB. The CK-MM is specific for skeletal muscle, CK-MB 1 and 2 are specific for cardiac muscle, and CK BB for the brain. Its half-life is 36 hours. Serum CPK levels begin to rise within 2 to 12 hours after the injury and peak within 1 to 5 days. It declines after 3 to 5 days in the absence of muscle injury. The suspect continued muscle injury and compartment syndrome in cases of Persistently elevated CPK levels[39]

With the release of an excess amount of myoglobin, heme-containing myoglobin is excreted in urine, resulting in tea-colored urine. Its half-life is about 2 to 4 hours, and it is metabolized into bilirubin. Only 50% of patients with rhabdomyolysis may have reddish-brown color urine; myoglobinemia can be detected before the elevation of CPK. Because of the shorter half-life and rapid metabolism, myoglobinuria may not always be detected. Urine dipstick detects hemoglobin and myoglobin as blood; a follow-up microscopic evaluation for RBC should be done to rule out hemoglobinuria. The sensitivity of myoglobinuria in rhabdomyolysis is less than 25%.[40] Sometimes, proteinuria may also be seen secondary to proteins released by damaged myocytes and changes in the glomerulus. Various biomarkers are being investigated for early diagnosis of heme-containing pigment-induced AKI.[41]

Excessive tissue breakdown from rhabdomyolysis causes third spacing of extracellular fluid into myocytes along with electrolyte changes like serum potassium and phosphate levels. Acute kidney injury can be complicated with resistant hyperkalemia. Excessive calcium influx into the myelocytes causes hypocalcemia, which may be severe depending on the nature of the injury. Excessive cell breakdown causes increased uric acid levels. Rhabdomyolysis can also cause hypovolemia, tissue damage, impaired perfusion, and release of organic acids like lactic acid and contribute to metabolic acidosis with or without an anion gap.[12] Elevated intra-myocyte enzymes like aminotransferase, aldolase, and LDH elevation are observed even without liver disease.

EKG may show peaked T waves, prolonged PR interval, wide QRS interval with or without conduction blocks, ventricular tachycardia, and asystole secondary to hyperkalemia. Hypocalcemia can manifest as QTC prolongation. Leukocytosis, elevated ESR, and CRP might be present in rhabdomyolysis. 

Acute kidney injury can be from hypovolemia, drugs, dehydration, hypoperfusion, pigment induced distal tubular damage. AKI is the most common complication of rhabdomyolysis. The risk of AKI is less in patients with CPK levels less than 20,000 IU/L. Patients with CK levels of more than 40,000 IU/L have an increased risk of acute kidney injury. The best predictors for developing acute kidney injury appear to be a state of hydration, high initial serum creatine, low serum bicarbonate, low serum calcium, and increased serum phosphate. Hypoalbuminemia and increased BUN have also been associated with the development of acute kidney injury. 

Disseminated intravascular coagulation (DIC) is another dreadful complication of rhabdomyolysis and is associated with increased prothrombin time, Activated thromboplastin time, INR, D-dimer, and a decrease in platelet count and fibrinogen levels. 

Plain radiographs can explain underlying bone fractures, dislocation of the joints, and sometimes soft tissue swelling. CT scanning of the involved muscle group can identify compartment syndrome.[42] Diagnosis of acute compartment syndrome is primarily clinical; it can also be confirmed by measuring intra-compartmental pressure (invasive) or near-infrared spectroscopy(noninvasive). Additional testing like MRI, muscle biopsy, and electromyography is not required for the diagnosis of rhabdomyolysis. Muscle biopsy is generally done after complete recovery from rhabdomyolysis and helps identify inflammatory myopathy. Inflammatory and metabolic myopathies are considered in the differential diagnosis in patients with recurrent rhabdomyolysis, poor exercise tolerance, muscle cramps, easy fatigue, and positive family history.

Treatment / Management

The goal of rhabdomyolysis management is to maintain adequate fluid resuscitation and prevent acute kidney injury. Identifying the underlying cause of rhabdomyolysis and its removal is the first step in managing patients. Management of rhabdomyolysis should include continuous assessment of airway, breathing, and circulation, frequent examinations, appropriate hydration to improve end-organ perfusion, close monitoring of urine output, correction of electrolyte abnormalities, identification of complications like compartment syndrome, and disseminated intravascular coagulation. 

Management of Traumatic Rhabdomyolysis

In patients with crush injury, the initiation of IV hydration/fluid resuscitation should begin as early as possible at the site of injury, even before relieving injury if possible. Hydration should be continued during the transport. Delay in fluid resuscitation may cause worsening hypovolemia secondary to third spacing. A liberal amount of fluids should be given up to 10 to 20 L to maintain adequate intravascular volume and diuresis.[43]

Multiple studies have shown the benefit of large volume resuscitation in patients with crush injury related to rhabdomyolysis to prevent acute kidney injury and the need for hemodialysis. For patients who were trapped for longer hours, appropriate fluid resuscitation might be challenging, and they are at risk for the development of AKI by the time they present to the hospital. With aggressive fluid resuscitation, patients who are already in acute kidney injury are prone to volume overload.[44] Unfortunately, no studies have directly compared the outcomes of different types and rates of fluid resuscitation. Currently, guidelines from the International Society of Nephrology renal disaster relief task force, recommend using isotonic saline rather than alkaline fluids in The field. The addition of dextrose to normal saline can be beneficial in supplying some calories and minimizing hyperkalemia. A rate of 1 L/h is given over 2 hours, followed by 500 ml/hr in a well-built adult. The rate of fluid administration is also dependent on age, gender, body habitus, the possibility of bleeding, and the nature of trauma. Potassium-containing IV fluids like Ringer's lactate are generally avoided in the management of rhabdomyolysis.(B2)

Once the patient is in the hospital, close monitoring of urine output is essential. After obtaining labs confirming the absence of alkalosis and confirming urine output, consideration should be given to the alkalinization of urine to prevent the precipitation of myoglobin in the distal convoluted tubule. Urine alkalinization also decreases the precipitation of uric acid, corrects underlying metabolic acidosis, and reduces the risk of hyperkalemia. Most of the data from the alkalinization of the urine are from uncontrolled case series. Adding 50 mEq of sodium bicarbonate to half-normal saline is traditionally used for the alkalinization of urine. Alkalinization with a bicarbonate infusion is associated with the precipitation of hypocalcemia can trigger tetany and seizures. The goal of alkaline fluid infusion is to maintain a serum pH not to exceed 7.5 and a urine pH just above 6.5. Prompt discontinuation of bicarbonate in IV fluids should be done When serum pH is at 7.5.[45]

Mannitol is commonly used to improve the urine output in patients with a crush injury. This should be used only after the patient maintains adequate urine output of at least 20 mL/h. The Renal Disaster Relief Task Force-European renal best practice has no specific conscientious guidelines regarding mannitol administration. A trial of intravenous infusion of 60 mL of 20% mannitol given over 5 minutes can be used to assess for increased urine output. If there is an increase in urine output of 30 to 50 mL/h compared to the baseline, more mannitol can continue.[46] Mannitol should be avoided in acute kidney injury, oliguria, and anuria. Adverse events associated with mannitol use are volume overload state and hyperosmolality. The current literature does not support the concomitant use of mannitol and bicarbonate to prevent pigment-induced acute kidney injury.[47][48] (B2)

Every attempt is made to prevent the development and further worsening of hyperkalemia. Avoid potassium-containing IV fluids like Ringer's lactate. A combination of oral sodium polystyrene sulfate and sorbitol is commonly given to crash victims with hyperkalemia. The role of new potassium binding agents is not very clear because of the lack of studies. Appropriate use of point-of-care devices and EKG should be utilized in patients with suspected hyperkalemia.[49]

All patients with crush syndrome should have a Foley catheter placed; IV fluids should be given to maintain 200 to 300 ml urine output per hour. Adequate IV fluid resuscitation should be continued until myoglobinuria is wholly resolved and CPK levels are down-trending. Foley catheters should be used for the shortest time to minimize complications like infection. Consideration should be given to loop diuretics in patients with volume overload states. Appropriate use of hemodialysis can be used with anuric acute kidney injury, hyperkalemia, and volume overload state after conservative measures failed. Peritoneal dialysis is not preferred because of trauma.

Management of Nontraumatic Rhabdomyolysis

Rhabdomyolysis from non-traumatic causes is managed similarly. Adequate and appropriate fluid resuscitation with normal isotonic saline should be provided depending on the underlying cause of rhabdomyolysis. Management includes removing the offending agent at the time of diagnosis and titration of IV fluids to maintain a urine output of 200 to 300 mL/h and serial monitoring of CPK levels daily to document downtrend levels. As mentioned earlier, CPK levels of more than 5,000 IU/L have increased the risk of the development of AKI. In patients with CPK levels, less than 5,000 IU/L extensive volume fluid resuscitation is discouraged as they are less likely to develop AKI.[50] Forceful alkaline diuresis can be considered in severe cases where the CPK is more than 30,000 IU/L in the absence of oliguria, anuria, and acute kidney injury. Mannitol is not commonly used in nontraumatic rhabdomyolysis. Loop diuretics can be considered in the setting of a volume overload state from aggressive fluid resuscitation. Patients who remain oliguric or anuric, even with aggressive fluid resuscitation, developed AKI should be considered for hemodialysis. The role of dialysis in the removal of myoglobin is not demonstrated.[51](B3)

Management of Electrolytes Abnormalities in Rhabdomyolysis

Rhabdomyolysis is associated with hyperkalemia, hypocalcemia, hyperuricemia, and hyperphosphatemia. Hyperkalemia with potassium levels less than 6 mEq/L without EKG changes should be managed with potassium binders and avoiding potassium-containing IV fluids (lactated Ringer's) and the use of bicarbonate in the fluids. Hyperkalemia with potassium levels 6 mEq/L or above with or without EKG changes should be treated with an ampule of D50 followed by zero units of regular insulin and IV sodium bicarbonate. In general, calcium gluconate or calcium chloride is commonly used in the emergency room with hyperkalemia. However, rhabdomyolysis, especially from trauma, is associated with late occurrences of hypercalcemia, so calcium should be used with caution in the management of hyperkalemia. 

Symptomatic hypocalcemia like tetany, seizures, and arrhythmias should be treated with IV calcium gluconate. Excessive calcium replacement can precipitate hypercalcemia during the recovery phase. Hyperuricemia from rhabdomyolysis should be managed with allopurinol; it is only used if uric acid is more than 8 mg/dL. Patients with volume overload, severe acidosis, uremia, and refractory hyperkalemia need hemodialysis. Peritoneal dialysis may not be sufficient to correct the excess amount of electrolyte changes and rhabdomyolysis.

Other Supportive Care

Appropriate use of antibiotics and vasopressors is needed when concomitant sepsis is present. Malignant hyperthermia should be treated with dantrolene sodium. Steroids are used in inflammatory myopathies. Emergent orthopedic consultation is required in the management of compartment syndrome. DIC is managed with fresh frozen plasma, cryoprecipitate, and platelet transfusion.

Diet in Metabolic Myopathies

Dietary changes may Improve symptoms associated with Hereditary myopathies. Pain and fatigue associated with phosphorylase deficiency can be decreased with glucose and fructose supplementation. Frequent meals with a high carbohydrate, low-fat diet improve muscle pain and myoglobinuria from carnitine palmityl transferase deficiency. The dietary modifications Have no effect on symptoms of phosphofructokinase deficiency or phosphoglycerate mutase deficiency.

Differential Diagnosis

• Hypothermia
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Sepsis
• Inflammatory myositis
• Inherited myopathies
• Guillain-Barré syndrome
• Hyperosmolar conditions

Prognosis

The prognosis of rhabdomyolysis varies depending on the underlying cause. However, even with AKI, most patients have favorable outcomes with complete recovery of kidney function.[3]

Complications

• Acute kidney injury
• Electrolyte abnormalities
• Arrhythmias
• Compartment syndrome
• Disseminated intravascular coagulation 
• End-stage renal disease requiring renal replacement therapy
• Infections from a prolonged hospital stay