Medline ® Abstracts for References 3,4,8

Rhabdomyolysis is a common and potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. Myoglobinuria is the most significant consequence, leading to acute renal failure (ARF) in 15%-33% of patients with rhabdomyolysis. Rhabdomyolysis occurs from inherited diseases, toxins, muscle compression or overexertion, or inflammatory processes, among other disorders. In some cases, no cause is found. We describe 475 patients from the Johns Hopkins Hospital inpatient records between January 1993 and December 2001 for the following discharge diagnosis codes: myoglobinuria, rhabdomyolysis, myopathy, toxic myopathy, malignant hyperthermia, neuroleptic malignant syndrome, and polymyositis. Of 1362 patients, 475 patients with an acute neuromuscular illness with serum creatine kinase (CK) more than 5 times the upper limit of normal (>975 IU/L) were included. Patients with recent myocardial infarction or stroke were excluded. The etiology was assigned by chart review. For all, the highest values of serum CK, serum creatinine and urine myoglobin, hemoglobin, and red blood cells were recorded. Forty-one patients had muscle biopsy within at least 2 months from the onset of rhabdomyolysis.Of the 475 patients, 151 were female and 324 were male (median age, 47 yr; range, 4-95 yr). Exogenous toxins were the most common cause of rhabdomyolysis, with illicit drugs, alcohol, and prescribed drugs responsible for 46%. Among the medical drugs, antipsychotics, statins, zidovudine, colchicine, selective serotonin reuptake inhibitors, and lithium were the most frequently involved. In 60% of all cases, multiple factors were present. In 11% of all cases, rhabdomyolysis was recurrent. Underlying myopathy or muscle metabolic defects were responsible for 10% of cases, in which there was a high percentage of recurrence, only 1 etiologic factor, and a low incidence of ARF. In 7%, no cause was found. ARF was present in 218 (46%) patients, and 16 died (3.4%). A linear correlation was found between CK and creatinine and between multiple factors and ARF, but there was no correlation between ARF and death or between multiple factors and death. Urine myoglobin detected by dipstick/ultrafiltration was positive in only 19%. Toxins are the most frequent cause of rhabdomyolysis, but in most cases more than 1 etiologic factor was present. Patients using illicit drugs or on prescribed polytherapy are at risk for rhabdomyolysis. The absence of urine myoglobin, by qualitative assay, does not exclude rhabdomyolysis. With appropriate care, death is rare.

IMPORTANCE: Rhabdomyolysis ranges in severity from asymptomatic elevations in creatine phosphokinase levels to a life-threatening disorder characterized by severe acute kidney injury requiring hemodialysis or continuous renal replacement therapy (RRT).

OBJECTIVE: To develop a risk prediction tool to identify patients at greatest risk of RRT or in-hospital mortality.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 2371 patients admitted between January 1, 2000, and March 31, 2011, to 2 large teaching hospitals in Boston, Massachusetts, with creatine phosphokinase levels in excess of 5000 U/L within 3 days of admission. The derivation cohort consisted of 1397 patients from Massachusetts General Hospital, and the validation cohort comprised 974 patients from Brigham and Women's Hospital.

MAIN OUTCOMES AND MEASURES: The composite of RRT or in-hospital mortality.

RESULTS: The causes and outcomes of rhabdomyolysis were similar between the derivation and validation cohorts. In total, the composite outcome occurred in 19.0% of patients (8.0% required RRT and 14.1% died during hospitalization). The highest rates of the composite outcome were from compartment syndrome (41.2%), sepsis (39.3%), and following cardiac arrest (58.5%). The lowest rates were from myositis (1.7%), exercise (3.2%), and seizures (6.0%). The independent predictors of the composite outcome were age, female sex, cause of rhabdomyolysis, and values of initial creatinine, creatine phosphokinase, phosphate, calcium, and bicarbonate. We developed a risk-prediction score from these variables in the derivation cohort and subsequently applied it in the validation cohort. The C statistic for the prediction model was 0.82 (95% CI, 0.80-0.85) in the derivation cohort and 0.83 (0.80-0.86) in the validation cohort. The Hosmer-Lemeshow P values were .14 and .28, respectively. In the validation cohort, among the patients with the lowest risk score (<5), 2.3% died or needed RRT. Among the patients with the highest risk score (>10), 61.2% died or needed RRT.

CONCLUSIONS AND RELEVANCE: Outcomes from rhabdomyolysis vary widely depending on the clinical context. The risk of RRT or in-hospital mortality in patients with rhabdomyolysis can be estimated using commonly available demographic, clinical, and laboratory variables on admission.