Rhabdomyolysis

Abstract

Q1 What is rhabdomyolysis and how does it present?

The term rhabdomyolysis describes skeletal muscle breakdown regardless of the underlying cause. Clinical presentations range from an asymptomatic incidental finding on blood or urine testing, to muscle aches with dark coloured urine (myoglobin) through to a severe illness involving AKI requiring renal replacement therapy. The frequency of AKI in rhabdomyolysis is variable, being reported at 15–50 %.

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• Q1 What is rhabdomyolysis and how does it present?

The term rhabdomyolysis describes skeletal muscle breakdown regardless of the underlying cause. Clinical presentations range from an asymptomatic incidental finding on blood or urine testing, to muscle aches with dark coloured urine (myoglobin) through to a severe illness involving AKI requiring renal replacement therapy. The frequency of AKI in rhabdomyolysis is variable, being reported at 15–50 %.

• Q2 What are the causes of rhabdomyolysis?

A recent review identified three physical and six non-physical causes. The physical causes are direct muscle injury, exertion or ischaemia. The non-physical causes comprise a diverse group of conditions including temperature extremes, electrolyte abnormalities, auto-immune disease, infections, drugs and toxins. Figure 11.1 shows the causes of rhabdomyolysis in a consecutive series of 92 patients with CK >10,000 iu/L in south west Scotland.

Fig. 11.1

Causes of rhabdomyolysis in 92 consecutive patients with serum CK >10,000 iu/l (Unpublished observations)

• Q3 How does rhabdomyolysis lead to AKI?

Large quantities of electrolytes, enzymes and protein (myoglobin) are released into the circulation following damage to skeletal muscle. Myoglobin is thought to be the main culprit, leading to AKI by intra-tubular cast formation and a direct cytotoxic effect, though it does not do so in every case. Some patients have very high levels of CK in their serum and do not succumb to AKI. It seems likely that both hypovolaemia and aciduria must be present for AKI to occur.

• Q4 What clinical clues would make you consider rhabdomyolysis?

There are usually a few clinical pointers towards this diagnosis. The history may reveal a period of immobility due to frailty or decreased conscious level – usually in the context of drug or alcohol use. A recent infective history, the addition of a new drug likely to cause or interact with current medication to cause rhabdomyolysis or strenuous unaccustomed exercise (e.g. marathon running) should always prompt the clinician to look for evidence of muscle damage. Visibly dark urine (“coke-coloured”) is likely to be caused by myoglobinuria in the context of a compatible history. Incidentally, myoglobinuria will test positive for blood on the urine dipstick test without there being any red blood cells on microscopy

The cause of rhabdomyolysis in the following case history was a previously unsuspected drug interaction between atorvastatin and fusidic acid, diagnosed on the basis of muscle weakness and grossly raised CK. The patient was oligoanuric at the time so that it was not possible to test for myoglobinuria.

FormalPara Case Report

A 69 year old man presented with multi organ failure secondary to left lower lobe consolidation for which he required ventilation, dialysis and inotropic support. One week previously he had been prescribed flucloxacillin 2 g per day and fusidic acid 2.25 g per day following the excision of an infected hip prosthesis. He had a myocardial infarction previously and his routine medications included atorvastatin 40 mg per day. We were able to withdraw ventilatory and circulatory support after 3 days, although the patient remained dialysis dependent and slow to mobilise. We observed at this point that he could not sit up unaided and went on to demonstrate proximal muscle weakness with serum CK 21,652 iu/l (normal range 0–195). Both atorvastatin and fusidic acid were stopped. The patient was unable to walk for a further 4 days and remained dialysis dependent for another 10 days. When reviewed at the clinic 2 months after his initial presentation muscle power had returned to normal and serum creatinine was 105 μmol/l.Teckchandani, et al. Rhabdomyolysis following co-prescription of fusidic acid and atorvastatin. J R Coll Phys Edinb. 2010;40:33–6; with kind permission of the Royal College of Physicians of Edinburgh

• Q5 Is the risk of rhabdomyolysis the same with all statins?

No. Statins are an important non-physical cause of rhabdomyolysis particularly when prescribed with drugs that interfere with their metabolism. The risk of rhabdomyolysis varies with the extent an individual statin is dependent for its metabolism on cytochrome P450 and the degree to which this enzyme’s activity is inhibited by a particular antimicrobial as shown in the table below. The risk of rhabdomyolysis with simvastatin and clarithromycin is particularly important because patients with exacerbation of COPD and pneumonia who happen to be taking simvastatin are frequently given clarithromycin following admission to hospital. The case history described above suggests a further adverse interaction, this time between atorvastatin and fusidic acid (Fig. 11.2).

Fig. 11.2

Statins and risk of rhabdomyolysis (Reproduced by kind permission © 2010 Royal College of Physicians Edinburgh. J R Coll Physicians Edinb. 2010;40:33–6)

• Q6 What biochemical clues would make you consider rhabdomyolysis?

Serum CK is not part of the routine biochemical blood screen which means that a diagnosis of rhabdomyolysis may be missed unless specifically considered. Fortunately, there may be other clues. Skeletal muscle also contains AST, ALT, LDH, aldolase, potassium, phosphate and uric acid. Elevated transaminases with normal bilirubin in a patient with unexplained AKI make a diagnosis of rhabdomyolysis worth considering and should prompt a request for serum CK. Serum AST will always be greater than serum ALT when rhabdomyolysis is present – another important clue to diagnosis.

• Q7 How do you confirm rhabdomyolysis?

A diagnosis of rhabdomyolysis is not always as easy to establish as it ought to be. The triad of muscle pain and/or weakness with myoglobinuria and elevated creatinine kinase (CK) is diagnostic, but muscle pain/weakness is present in only 50 % of cases while myoglobinuria has a short half-life of only 2–3 h and is detected in only 20 % of cases. Furthermore, there is no agreed diagnostic cut-point for serum CK – some say five or ten times upper limit of the normal range of 0–195 iu/l, others greater than 5,000 iu/l or greater than 10,000 iu/l (Fig. 11.3).

Fig. 11.3

Diagnostic triad for rhabdomyolysis

• Q8 What is Compartment Syndrome and how might this be treated?

Compartment syndrome can be both a cause and a complication of rhabdomyolysis. Crush injuries may cause the affected muscles to swell while muscles damaged by one of the non-physical causes may swell too. Muscles in the forearm, lower leg and some other body areas are surrounded by fibrous bands, creating distinct compartments. These fibrous bands cannot stretch to accommodate the swollen muscles, leading to irreversible nerve and muscle injury if the swelling is left untreated. Surgical fasciotomy may then be indicated. It is important therefore to examine patients thoroughly and consider compartment syndrome in all patients with rhabdomyolysis.

• Q9 How would you manage a patient with rhabdomyolysis?

Patients with rhabdomyolysis are usually volume deplete due to sequestration of water in damaged muscle and because of this volume repletion is the mainstay of therapy. Some recommend alkalinisation of urine because myoglobin is more likely to precipitate in the renal tubules when urine is acidic, though randomised trials of alkalinisation have failed to establish benefit. Hyperkalaemia is more likely to occur than in other forms of AKI because potassium is released from damaged muscles, and should be treated accordingly (see Chap. 18). The indications for dialysis in rhabdomyolysis induced AKI are the same as for other forms of AKI.

1 Objectives: Rhabdomyolysis

After reading this chapter, you should be able to answer the following:

• Q1 What is rhabdomyolysis and how does it present?

• Q2 What are the causes of rhabdomyolysis?

• Q3 How does rhabdomyolysis lead to AKI?

• Q4 What clinical clues would make you consider rhabdomyolysis?

• Q5 Is the risk of rhabdomyolysis the same with all statins?

• Q6 What biochemical clues would make you consider rhabdomyolysis?

• Q7 How do you confirm rhabdomyolysis?

• Q8 What is Compartment Syndrome and how might this be treated?

• Q9 How would you manage a patient with rhabdomyolysis?