both liver and muscle tissue, are also usually increased; this can lead to the condition being confused with acute liver injury, at least in the early stages. the incidence of actual acute liver injury is 25% in people with non-traumatic rhabdomyolysis; the mechanism for this is uncertain. high potassium levels tend to be a feature of severe rhabdomyolysis. electrocardiography (ecg) may show whether the elevated potassium levels are affecting the conduction system of the heart, as suggested by the presence of t wave changes or broadening of the qrs complex. low calcium levels may be present in the initial stage due to binding of free calcium to damaged muscle cells. as detectable levels of myoglobinemia and myoglobinuria occur, blood tests and urine tests may show elevated levels of myoglobin. for example, a urine test strip may reveal a positive result for "blood", even though no red blood cells can be identified on microscopy of the urine; this occurs because the reagent on the test strip reacts with myoglobin. the same phenomenon may happen in conditions that lead to hemolysis, the destruction of red blood cells; in hemolysis the blood serum is also visibly discolored, while in rhabdomyolysis it is normal. if kidney damage has occurred, microscopy of the urine also reveals urinary casts that appear pigmented and granular. complications compartment syndrome is a clinical diagnosis, i.e., no diagnostic test conclusively proves its presence or absence, but direct measurement of the pressure in a fascial compartment, and the difference between this pressure and the blood pressure, may be used to assess its severity. high pressures in the compartment and a small difference between compartment pressure and blood pressure indicate that the blood supply is likely to be insufficient, and that surgical intervention may be needed. disseminated intravascular coagulation, another complication of rhabdomyolysis and other forms of critical illness, may be suspected on the basis of unexpected bleeding or abnormalities in hematological tests, such as a decreasing platelet count or prolongation of the prothrombin time. the diagnosis can be confirmed with standard blood tests for dic, such as d-dimer. underlying disorders if an underlying muscle disease is suspected, for instance, if there is no obvious explanation or there have been multiple episodes, it may be necessary to perform further investigations. during an attack, low levels of carnitine in the blood and high levels of acylcarnitine in blood and urine may indicate a lipid metabolism defect, but these abnormalities revert to normal during convalescence. other tests may be used at that stage to demonstrate these disorders. disorders of glycolysis can be detected by various means, including the measurement of lactate after exercise; a failure of the lactate to rise may be indicative of a disorder in glycolysis, while an exaggerated response is typical of mitochondrial diseases. electromyography (emg) may show particular patterns in specific muscle diseases; for instance, mcardle's disease and phosphofructokinase deficiency show a phenomenon called cramp-like contracture. there are genetic tests available for many of the hereditary muscle conditions that predispose to myoglobinuria and rhabdomyolysis. muscle biopsy can be useful if an episode of rhabdomyolysis is thought to be the result of an underlying muscle disorder. a biopsy sample taken during an episode is often uninformative, as it will show only evidence of cell death or may appear normal. taking the sample is therefore delayed for several weeks or months. the histopathological appearance on the biopsy indicates the nature of the underlying disorder. for instance, mitochondrial diseases are characterized by ragged red fibers. biopsy sites may be identified by medical imaging, such as magnetic resonance imaging, as the muscles may not be uniformly affected. treatment the main goal of treatment is to treat shock and preserve kidney function. initially this is done through the administration of generous amounts of intravenous fluids, usually isotonic saline (0.9% weight per volume sodium chloride solution). in victims of crush syndrome, it is recommended to administer intravenous fluids even before they are extracted from collapsed structures. this will ensure sufficient circulating volume to deal with the muscle cell swelling (which typically commences when blood supply is restored), and to prevent the deposition of myoglobin in the kidneys. amounts of 6 to 12 liters over 24 hours are recommended. the rate of fluid administration may be altered to achieve a high urine output (200–300 ml/h in adults), unless there are other reasons why this might lead to complications, such as a history of heart failure. while many sources recommend additional intravenous agents to reduce damage to the kidney, most of the evidence supporting this practice comes from animal studies, and is inconsistent and conflicting. mannitol acts by osmosis to enhance urine production and is thought to prevent myoglobin deposition in the kidney, but its efficacy has not been shown in studies and there is a risk of worsening kidney function. the addition of bicarbonate to the intravenous fluids may alleviate acidosis (high acid level of the blood) and make the urine more alkaline to prevent cast formation in the kidneys; evidence suggesting that bicarbonate has benefits above saline alone is limited, and it can worsen hypocalcemia by enhancing calcium and phosphate deposition in the tissues. if urine alkalinization is used, the ph of the urine is kept at 6.5 or above. furosemide, a loop diuretic, is often used to ensure sufficient urine production, but evidence that this prevents kidney failure is lacking. electrolytes in the initial stages, electrolyte levels are often abnormal and require correction. high potassium levels can be life-threatening, and respond to increased urine production and renal replacement therapy (see below). temporary measures include the administration of calcium to protect against cardiac complications, insulin or salbutamol to redistribute potassium into cells, and infusions of bicarbonate solution. calcium levels initially tend to be low, but as the situation improves calcium is released from where it has precipitated with phosphate, and vitamin d production resumes, leading to hypercalcemia (abnormally high calcium levels). this "overshoot" occurs in 20–30% of those people who have developed kidney failure. acute kidney impairment a hemofiltration machine kidney dysfunction typically develops 1–2 days after the initial muscle damage. if supportive treatment is inadequate to manage this, renal replacement therapy (rrt) may be required. rrt removes excess potassium, acid and phosphate that accumulate when the kidneys are unable to function normally and is required until kidney function is regained. three main modalities of rrt are available: hemodialysis, continuous hemofiltration and peritoneal dialysis. the former two require access to the bloodstream (a dialysis catheter) and peritoneal dialysis is achieved by instilling fluid into the abdominal cavity and later draining it. hemodialysis, which is normally done several times a week in chronic kidney disease, is often required on a daily basis in rhabdomyolysis. its advantage over continuous hemofiltration is that one machine can be used multiple times a day, and that continuous administration of anticoagulant drugs is not necessary. hemofiltration is more effective at removing large molecules from the bloodstream, such as myoglobin, but this does not seem to confer any particular benefit. peritoneal dialysis may be difficult to administer in someone with severe abdominal injury, and it may be less effective than the other modalities. other complications compartment syndrome is treated with surgery to relieve the pressure inside the muscle compartment and reduce the risk of compression on blood vessels and nerves in that area. fasciotomy is the incision of the affected compartment. often, multiple incisions are made and left open until the swelling has reduced. at that point, the incisions are closed, often requiring debridement (removal of non-viable tissue) and skin grafting in the process. 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. for instance, if the platelet count drops significantly and there is resultant bleeding, platelets may be administered. prognosis the prognosis depends on the underlying cause and whether any complications occur. rhabdomyolysis complicated by acute kidney impairment in patients with traumatic injury may have a mortality rate of 20%. admission to the intensive care unit is associated with a mortality of 22% in the absence of acute kidney injury, and 59% if kidney impairment occurs. most people who have sustained kidney impairment due to rhabdomyolysis fully recover their kidney function. epidemiology the exact number of cases of rhabdomyolysis is difficult to establish because different definitions have been used. in 1995, hospitals in the u.s. reported 26,000 cases of rhabdomyolysis. up to 85% of people with major traumatic injuries will experience some degree of rhabdomyolysis. of those with rhabdomyolysis, 10–50% develop acute kidney injury. the risk is higher in people with a history of illicit drug use, alcohol misuse or trauma when compared to muscle diseases, and it is particularly high if multiple contributing factors occur together. rhabdomyolysis accounts for 7–10% of all cases of acute kidney injury in the u.s. crush injuries are common in major disasters, especially in earthquakes. the aftermath of the 1988 spitak earthquake prompted the establishment, in 1995, of the renal disaster relief task force, a working group of the international society of nephrology (a worldwide body of kidney experts). its volunteer doctors and nurses assisted for the first time in the 1999 i̇zmit earthquake in turkey, where 17,480 people died, 5392 were hospitalized and 477 received dialysis, with positive results. treatment units are generally established outside the immediate disaster area, as aftershocks could potentially injure or kill staff and make equipment unusable. acute exertional rhabdomyolysis happens in 2% to 40% of people going through basic training for the united states military. in 2012, the united states military reported 402 cases. another group at increased risk is firefighters. history investigations of people injured in collapsed buildings during the blitz of london led to numerous discoveries in the mechanisms underlying kidney impairment in rhabdomyolysis. the bible may contain an early account of rhabdomyolysis. in numbers 11:4–6,31–33, the pentateuch says that the jews demanded meat while traveling in the desert; god sent quail in response to the complaints, and people ate large quantities of quail meat. a plague then broke out, killing numerous people. rhabdomyolysis after consuming quail was described in more recent times and called coturnism (after coturnix, the main quail genus). migrating quail consume large amounts of hemlock, a known cause of rhabdomyolysis. in modern times, early reports from the 1908 messina earthquake and world war i on kidney failure after injury were followed by studies by london physicians eric bywaters and desmond beall, working at the royal postgraduate medical school and the national institute for medical research, on four victims of the blitz in 1941. myoglobin was demonstrated in the urine of victims by spectroscopy, and it was noted that the kidneys of victims resembled those of patients who had hemoglobinuria (hemoglobin rather than myoglobin being the cause of the kidney damage). in 1944 bywaters demonstrated experimentally that the kidney failure was mainly caused by myoglobin. already during the war, teams of doctors traveled to bombed areas to provide medical support, chiefly with intravenous fluids, as dialysis was not yet available. the prognosis of acute kidney failure improved markedly when dialysis was added to supportive treatment, which first happened during the 1950–1953 korean war. etymology and pronunciation the word rhabdomyolysis ( /ˌræbdoʊmaɪˈɒlɪsɪs/) uses the combining forms rhabdo- + myo- + -lysis, yielding "striated muscle breakdown". other animals rhabdomyolysis is recognized in horses. horses can develop a number of muscle disorders, many of which may progress to rhabdomyolysis. of these, some cause isolated attacks of rhabdomyolysis (e.g., dietary deficiency in vitamin e and selenium, poisoning associated with pasture or agricultural poisons such as organophosphates), while others predispose to exertional rhabdomyolysis (e.g., the hereditary condition equine polysaccharide storage myopathy). 5–10% of thoroughbred horses and some standardbred horses have the condition equine exertional rhabdomyolysis; no specific cause has been identified, but an underlying muscle calcium regulation disorder is suspected. rhabdomyolysis affecting horses may also occur in outbreaks; these have been reported in many european countries, and later in canada, australia, and the united states. it has been referred to as "atypical myopathy" or "myoglobinuria of unknown etiology". no single cause has yet been found, but various mechanisms have been proposed, and a seasonal pattern has been observed. very high creatine kinase