Review articleThe syndrome of rhabdomyolysis: Complications and treatment
Introduction
Rhabdomyolysis refers to the traumatic, ischemic, pharmaceutical, toxic, metabolic, or infectious skeletal muscle cell damage that influences the integrity of plasma membrane (sarcolemma) and leads to the release of toxic intracellular material into the systemic circulation [1], [2], [3], [4]. The causes of rhabdomyolysis are divided into hereditary and acquired ones. The hereditary causes are mainly related to a lack or insufficiency of enzymes that participate in the catabolism of different energy macromolecules (e.g., carbohydrates, lipids) [1]; the most frequent cause in this category is McArdle's disease [5]. The acquired causes are classified as traumatic and non-traumatic. The traumatic ones, such as crush syndrome, accidents, natural disasters, or intense exercise, cause direct muscle injury and rupture of the sarcolemma [6], [7], [8]. The non-traumatic causes are the most common ones during peacetime and include alcohol abuse, medicines (e.g., statins, amphetamines, anti-psychotics, diuretics), seizures, and coma [9], [10], [11], [12], [13], [14], [15].
Despite the great diversity in the etiology of rhabdomyolysis, the final pathogenetic pathway is common and includes an increase in free ionized calcium in the cytoplasm (sarcoplasm) [3], [4], [6]. The increased cytoplasmic calcium initiates a complex network of intracellular processes, such as the activation of phospholipase A2, prolonged contraction of muscle cells, mitochondrial dysfunction, and production of reactive oxygen species, which eventually promote muscle cell damage and the release of various substances (e.g., myoglobin, creatine phosphokinase, potassium, organic acids, and other enzymes and electrolytes) into the systemic circulation, thereby leading to the clinical manifestation of rhabdomyolysis [16], [17], [18], [19], [20]. Typically, rhabdomyolysis presents with muscle pain, weakness, and reddish-brown urine due to myoglobinuria [21]. Nevertheless, more than half of the patients do not report muscular symptoms. In more severe cases of rhabdomyolysis, general symptoms, such as malaise, fever, tachycardia, nausea, and vomiting, may also occur [22]. The severity of rhabdomyolysis varies from an asymptomatic increase in creatine phosphokinase to heavy complications, such as acute renal failure (ARF), cardiac arrhythmias, compartmental syndrome, and disseminated intravascular coagulopathy [21], [23].
In this review, we summarize the existing literature regarding the major complications of rhabdomyolysis, as well as their treatment. An enhanced understanding and awareness of these complications is necessary to enable the clinician to recognize and treat them promptly and successfully.
Section snippets
Acute renal failure
Baywaters and Beall [24] first described rhabdomyolysis-induced ARF in 1941 after they followed the progress of four victims who had developed ARF during the London bombardment in 1940. Although the authors attributed the ARF to rhabdomyolysis as a result of compression, they did not reveal the actual pathogenetic mechanism underlying this observation. A few decades later, it was found that the nephrotoxic effect of myoglobin, which is released by the disrupted muscle cells, is responsible for
Management of rhabdomyolysis
The major therapeutic interventions in rhabdomyolysis are conservative and include treatment of the underlying cause, prevention of ARF, early correction of potentially lethal electrolyte disorders (e.g., severe hyperkalemia), treatment of metabolic acidosis, and management of other coexisting complications (Table 1). Upon failure of conservative treatment and onset of ARF, patients should undergo hemodialysis.
Prognosis of rhabdomyolysis
Acute renal failure and hyperkalemia are the major complications that worsen the prognosis of rhabdomyolysis and require special attention. However, in most cases, ARF is completely reversible [55], [75]. Due to the fact that rhabdomyolysis is a rather rare syndrome and that few studies with large series of patients exist, it is difficult to reveal the true prognosis of the syndrome and its complications. Patients with severe injury who develop rhabdomyolysis-induced ARF have a mortality of
Conclusions
Rhabdomyolysis is a rather rare syndrome with serious potential complications. Although the prognosis of the syndrome is generally good, complications such as ARF and hyperkalemia are accompanied by high mortality. With regard to treatment, it is crucial that there is prompt and aggressive fluid replacement in combination with urine alkalization and close clinical follow-up of the patient. As rhabdomyolysis is the cause of ARF in a considerable percentage of cases, physicians should be well
Learning points
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Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation.
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The main complications of rhabdomyolysis include acute renal failure, electrolyte disorders such as hyperkalemia, hyperphosphatemia, early hypocalcemia, and late hypercalcemia, metabolic acidosis, compartmental syndrome, and disseminated intravascular coagulopathy.
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The management of myoglobinuric acute renal failure includes aggressive fluid
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