Myoglobinuria

Myoglobin is found in muscles and its main function is to carry oxygen to muscle cells. It has similarities to haemoglobin, in that it is a protein chain containing haem, however it is structurally different.¹

Myoglobinuria is the presence of myoglobin in the urine and usually represents muscle damage.

Once muscles are damaged e.g. trauma, myoglobin is released in the circulation. There are usually very low levels of myoglobin in the urine. Once myoglobin is released from muscles it is taken up by haptoglobins - a process that becomes rapidly saturated. Any free myoglobin then enters renal tubules to be excreted; however it may precipitate leading to obstruction and subsequent acute renal failure.¹

• Myoglobin in the urine usually darkens the urine.
• Myoglobinuria can cause a positive urine dipstick for blood, thus being confused with haematuria.
• The next step is to obtain urine microscopy specifically looking for red blood cells (RBC's). A lack of RBC's with a positive dipstick for blood indicates myoglobin.
• There are also direct tests for myoglobinuria such as immunoassays.

Any cause of muscle breakdown, for example:

Patients with myoglobinuria alone may have very few problems, however if myoglobinuria is severe they can develop complications. Sometimes the words myoglobinuria and rhabdomyolysis are used interchangeably.

Definition

Rhabdomyolysis can be defined as a syndrome associated with breakdown of skeletal muscle fibres leading to release of muscle contents into the circulation resulting in multiple complications including hyperkalaemia and cardiac arrest.

Epidemiology

The exact incidence of rhabdomyolysis varies with the underlying cause.¹ Rhabdomyolysis accounts for 7% of all cases of acute renal failure.

Aetiology

Causes are similar as for myoglobinuria - the commonest causes being

The substances released are

• Potassium
• Phosphate
• Myoglobin
• Creatine kinase
• Urate

Presentation

• Many features are non-specific and therefore a high index of clinical suspicion is required.
• There may be features relating to the underlying cause e.g. swollen, painful, paraesthesia of limbs in compartment syndrome or muscle tenderness.
• Fever and malaise may be present.
• Elderly may present with confusion, agitation and delirium.
• Patients may be anuric.
• Tea coloured urine may be present.

Diagnosis

• Based on clinical grounds e.g. supportive case history.
• Urine - tea coloured and positive for blood on dipstick testing.
• Urine microscopy to detect lack of RBC's, which with a positive dipstick indicates presence of myoglobin.
• Creatine kinase - will be raised, may be up to several 10,000's.
• Electrolytes - high potassium, low calcium, high phosphate.
• Investigations to delineate the underlying cause may be indicated e.g. muscle biopsy.

Complications

The complications of rhabdomyolysis are the cause of mortality and morbidity in these patients.

These include

• Hyperkalaemia causing arrhythmias and cardiac arrest.
• Hypocalcaemia (worsened by hyperphosphataemia).
• Hepatic abnormalities - but AST may be high representing muscle AST.
• Metabolic acidosis.
• Acute renal failure from precipitation and obstruction of renal tubules by myoglobinuria and hypovolaemia.
• Disseminated intravascular coagulation.
• Pooling of fluid in the damaged muscle which adds to hypovolaemia and can lead to a compartment syndrome.

There may also be complications resulting from the original insult e.g. burns associated with sepsis.

Treatment

• Fluid rehydration - needs to be prompt.
• Treat hyperkalaemia - calcium gluconate (if indicated) and dextrose-insulin infusions.
• Diuretics - mannitol has been used but its use is contentious. Other diuretics have not been shown to improve renal impairment. Diuretics should not be used until hypovolaemia is corrected.⁴
• Alkaline diuresis - alkalinisation of the urine with bicarbonate can reduce the risk of acute renal failure - however, there is no clear evidence as to its benefit or whether it is any better then simple aggressive hydration with intravenous fluids.⁴
• If renal function fails to improve patients are at risk of acute tubular necrosis in which case haemodialysis may be necessary.⁵
• Hypocalcaemia and hyperphosphataemia need not be corrected unless dangerously low - they improve as CK falls.

• Statins are widely used and their use has been associated with a reduction in mortality and morbidity in ischaemic heart disease and cerebrovascular disease.
• They are associated with muscle aches and pains and can cause myositis and rhabdomyolysis which can be fatal.^6,7,8
• Cerivastatin was the most frequently used statin with associated rhabdomyolysis and was subsequently withdrawn.^9,10
• The risk of rhabdomyolysis with statins is increased in the elderly, with use of interacting medications (e.g. fibrates) and hypothyroidism.
• If patients on statins develop myositis (muscle pain, muscle tenderness and weakness) or myalgia then the statin should be stopped and CK checked urgently. If CK level is normal consider changing to another member or restart at a lower dose with cautious monitoring. Presence of rhabdomyolysis will require termination of treatment and management as described above.