Overview of Exertional Rhabdomyolysis
Sickle cell trait (SCT) is a genetic blood disorder involving mutations of the beta-globin gene that is seen primarily in the African American population.1 Patients with SCT seem to be particularly predisposed to develop acute rhabdomyolysis after prolonged periods of physical exertion.2
Rhabdomyolysis is a breakdown of striated muscles, causing the release of muscle contents including myoglobin, calcium, and potassium into the systemic circulation. This rapid breakdown of skeletal muscle fibers leads to leakage of potentially toxic cellular content (eg, creatine kinase [CK], organic acids with free oxygen radicals, and intracellular electrolytes), causing electrolyte imbalances, myoglobinemia, myoglobinuria, and impaired renal function.3
Patients with rhabdomyolysis usually present with muscle pain, limb weakness, swelling of the affected muscles, and tea-colored urine. In severe cases, rhabdomyolysis can result in life-threatening hyperkalemia and myoglobin-induced acute kidney injuries.4 Clinical examination, complete history, laboratory studies, muscle biopsy, and genetic testing are useful tools for the diagnosis of rhabdomyolysis. These methods also can assist in differentiating between acquired and inherited causes of rhabdomyolysis.
The Causes of Rhabdomyolysis
In patients with homozygous sickle cell disease, rhabdomyolysis can occur in the setting of intravascular coagulation in sickle cell crisis. This may be triggered by a number of factors,5 including stress, illness, metabolic acidosis, and dehydration.
Rhabdomyolysis with acute renal failure, and sometimes sudden death, has been reported in athletes and military recruits with this trait (homozygous sickle cell trait) after intense exertion or heat illness.6 (See related article) While some cases of rhabdomyolysis are caused by congenital metabolic myopathies, the condition also can be caused by the following factors:
- Exertion. Prolonged physical exertion can lead to rhabdomyolysis, particularly if the patient is not used to strenuous activity.
- Trauma and immobility. Direct muscle injury leading to rhabdomyolysis can be caused by crush injuries, trauma, burns, electrocution, or prolonged immobilization.
- Ischemia. Rhabdomyolysis is known to occur in individuals who are physically active at a high altitude, where decreased oxygen pressure can lead to erythrocyte sickling and subsequent vascular occlusion and muscle ischemia.7,8
- Extremes of body temperature. Having a very high body temperature, referred to as hyperthermia, or suffering from heat stroke has been known to cause rhabdomyolysis.
Medications Linked to Rhabdomyolysis
Many medications are associated with rhabdomyolysis in adults,4,5 including antidepressants, antihistamines, antipsychotics, antiretrovirals, colchicine, depakote, lithium, ofloxacin/levofloxacin, and tatins.
Antipsychotic medications can triple the risk of exertional rhabdomyolysis, according to a new study featured in the New England Journal of Medicine.9 Using retrospective data of military health records, researchers found recent use of a statin or antipsychotic medication seriously increased the risk of a soldier developing exertional rhabdomyolysis, at hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P=0.001 and hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P=0.008, respectively.
Exertional rhabdomyolysis is not a novel medical issue for service personnel. Over 40 years ago, exertional rhabdomyolysis first was reported in the military population as a complication of SCT. But it was only recently that the first longitudinal evidence showed the sickle cell trait indeed was an increased risk factor for developing the syndrome.9
Because of this, researchers maintain that the recognition of SCT as a risk factor for rhabdomyolysis only reinforces the need for an effective screening program for the active duty military population and civilians alike.10
For the practitioner, it seems obvious there must be an awareness of rhabdomyolysis, how it can be diagnosed, and all of the precipitating factors that can be associated with its onset. SCT is simply 1 precipitating factor. Other precipitating factors can include tobacco use, obesity (as determined by BMI >30), statin use, and antipsychotic medication use. As in all pain management cases, treatment cannot be initiated until the proper diagnosis and causation are determined.