Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice

Abstract

Background: Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream. There is a great heterogeneity in the literature regarding definition, epidemiology, and treatment. The aim of this systematic literature review was to summarize the current state of knowledge regarding the epidemiologic data, definition, and management of rhabdomyolysis.

Methods: A systematic search was conducted using the keywords "rhabdomyolysis" and "crush syndrome" covering all articles from January 2006 to December 2015 in three databases (MEDLINE, SCOPUS, and ScienceDirect). The search was divided into two steps: first, all articles that included data regarding definition, pathophysiology, and diagnosis were identified, excluding only case reports; then articles of original research with humans that reported epidemiological data (e.g., risk factors, common etiologies, and mortality) or treatment of rhabdomyolysis were identified. Information was summarized and organized based on these topics.

Results: The search generated 5632 articles. After screening titles and abstracts, 164 articles were retrieved and read: 56 articles met the final inclusion criteria; 23 were reviews (narrative or systematic); 16 were original articles containing epidemiological data; and six contained treatment specifications for patients with rhabdomyolysis.

Conclusion: Most studies defined rhabdomyolysis based on creatine kinase values five times above the upper limit of normal. Etiologies differ among the adult and pediatric populations and no randomized controlled trials have been done to compare intravenous fluid therapy alone versus intravenous fluid therapy with bicarbonate and/or mannitol.

Keywords: Acute kidney injury; Myoglobinuria; Myopathy; Rhabdomyolysis.

Fig. 1

Flowchart for study selection

Fig. 2

Injury mechanisms of rhabdomyolysis. (1) Energy (ATP) depletion inhibits Na⁺/K⁺ ATPase function, thus increasing intracellular sodium. (2) The 2Na⁺/Ca²⁺ exchanger increases intracellular calcium. (3) Ca²⁺ ATPase is not able to pump out intracellular calcium due to energy depletion. (4) Intracellular calcium activates proteases such as phospholipase 2 (PLA2), which destroy structural components of the cell membrane, allowing the entrance of more calcium. (5) Calcium overload disrupts mitochondrial integrity and induces apoptosis leading to muscle cell necrosis

Fig. 3

Acute kidney injury in rhabdomyolysis. Enzymes*: creatine kinase, aldolase, lactate dehydrogenase. After muscle destruction, myoglobin and enzymes released into the circulation damage capillaries, leading to leakage and edema. Hypovolemia and the decrease in renal bood flow is associated with acute kidney injury. Myoglobin cytotoxicity affects the kidney by lipid peroxidation and production of reactive oxygen species. Tubular obstruction by myoglobin is also associated with AKI