Many of the causes of myonecrosis have already been mentioned in this chapter, including acute inflammatory myopathy, several types of glycogenoses, CPT deficiency, and as a result of poisoning or therapeutic use of a vast array of drugs (including the combination of steroids and pancuronium in critically ill patients, discussed earlier), environmental toxins, and venoms. Myoglobinuria is an important feature of many other medical conditions: crush injury; extensive infarction of muscle that occurs in cases of vascular disease and of diabetes; in cases of severe acute alcohol intoxication, excessive use or repeated injury to muscles in status epilepticus, generalized tetanus, malignant hyperthermia, malignant neuroleptic syndrome, prolonged marching, electrical and lightning injuries; or simply excessive exercise—although muscle necrosis after exercise suggests an underlying metabolic disease of muscle.
Regardless of the cause of the rhabdomyolysis, the affected muscles become painful and tender within a few hours and their power of contraction is diminished. Sometimes, the skin and subcutaneous tissues overlying the affected muscles (nearly always of the limbs and sometimes of the trunk) are swollen and congested. There is a marked elevation of CK in the serum and there may be a low-grade fever and a reactive leukocytosis. If myoglobinuria is mild, recovery occurs within a few days and there is only a residual albuminuria. When severe, renal damage may ensue and lead to anuric renal failure requiring dialysis. The mechanism of the renal damage is not entirely clear; it is not simply a mechanical obstruction of tubules by precipitated myoglobin (although this does occur).
Treatment of myoglobinuria Alkalinization of the urine by ingestion or infusion of sodium bicarbonate is said to protect the kidneys by preventing myoglobin casts, but in severe cases it is of doubtful value and the sodium may actually be harmful if anuria has already developed. Diuresis induced by mannitol or by loop diuretics such as furosemide and by the administration of intravenous fluids reduces the chances of anuric renal failure if given in time. Therapy is much the same as for the anuria that follows shock (see Harrison’s Principles of Internal Medicine). In cases of focal muscle injury, for example, as occurs in diabetics or from vascular occlusion, surgical decompression of the overlying fascia and skin may be necessary to prevent ongoing ischemia, the “compartment syndrome.”
With the widespread use of these lipid-lowering medications, myotoxicity has become a well-described but possibly overrated problem. Symptoms range in severity from mild muscular aches with slightly elevated CK concentrations in the serum to a rare but potentially fatal rhabdomyolytic syndrome. (Myalgias alone are as common in patients taking placebo as in those taking stains). The incidence of true myopathy with statins has been estimated to be approximately 1 in 10,000 people treated per year. There appear to be two types of mypathy—one idiosyncratic and associated with direct toxicity and another, now thought to be more common, due to an antibody reaction. The first generation of these drugs were fungal metabolites (lovastatin, pravastatin, simvastatin) and were infrequently implicated in muscle damage, but the newer synthetic ones (atorvastatin, fluvastatin, cerivastatin) are more frequently toxic, especially when given with gemfibrozil (which has reportedly led to a small number of deaths from myoglobinuric renal failure and has been removed from the market). Few cases are this dramatic. The subject has been reviewed by Thompson and associates and by Mammen. Drugs in the statin class with higher lipid solubility appear to have a greater potential for toxicity as a result of their increased muscle penetration.