Introduction

The syndrome of muscle pain, weakness and brown urine was first described in 1910 by Meyer-Betz, a German physician.¹ (NB: there is an alternative attribution in the Concise Oxford Textbook of Medicine to Hans Meyer and Vladimir Betz, although both were deceased by 1895.)

Aetiology

Rhabdomyolysis is seen commonly as a consequence of strenuous exercise. Case reports have included military basic training,² weight lifting,³ and in both recreational and professional marathon runners.⁴

There appears to be an increased risk in patients with sickle cell trait.⁵

Pathogenesis

Rhabdomyolysis, particularly that associated with exertion, predominantly damages red (type 2) muscle fibres. Myoglobin is released along with other cellular contents after muscle damage and necrosis.

• Normal values for plasma myoglobin concentration are 0 to 0.003 mg/dL.
• The renal threshold for myoglobin is 0.5 to 1.5 mg/dL.
• The urine level of myoglobin must exceed 100 mg/dL before the urine becomes discoloured.
• The serum myoglobin level will rise before serum creatine kinase level. It will rise within hours of onset of injury and return to normal 1- 6 hours after cessation of injury, with rapid renal excretion and metabolism to bilirubin.
• Metabolic acidosis, acute renal failure (ARF), respiratory failure, cardiac arrhythmias and disseminated intravascular coagulation (DIC) all may complicate rhabdomyolysis.

Epidemiology

Incidence figures are not available for the general population, but screening of 337 military recruits for myoglobin serum levels, showed rhabdomyolysis in 40%.⁶ It is more common in men, particularly well-educated professionals, who arrange work schedules to allow for daily running. This lead to the term 'white collar rhabdomyolysis'.⁷

In another series, exercise-induced rhabdomyolysis accounted for 47% of the admissions with rhabdomyolysis.⁸

Presentation

Symptoms

The most common symptoms include:

• Muscle pain, weakness, tenderness and stiffness.
• 50% of patients present with symptoms in the large muscles of the thigh, calves and the lower back.⁹ Change in colour of the urine, usually to red initially, then brown.
• Constitutional symptoms vary on the cause; the most common are generalised malaise, fever and nausea.
• The associated electrolyte disturbance can lead to agitation and confusion.

Signs

• The affected muscles become swollen and tender on palpation and, occasionally, on beginning fluid therapy, due to extravasation of fluids.
• The muscles involved become stiff and occasionally develop contractures.
• Myoglobinuria.
• Tachycardia.
• Altered mental state.
• Low urine output.

Differential diagnosis

• Sickle cell anaemia.
• Compartment syndrome.
• Disseminated intravascular coagulation (DIC).
• HIV/AIDS.
• Myopathies.
• Inborn errors of metabolism:
  • Abnormal carbohydrate metabolism, e.g. McArdle's disease, Tarui's disease.
  • Abnormal lipid metabolism, e.g. carnitine deficiency.
• Toxicity, e.g. drugs of abuse, neuroleptics, selective serotonin reuptake inhibitors (SSRIs).

Investigations

• Raised white cell count.
• Raised LFTs.
• Features of disseminated intravascular coagulation (DIC).
• Hypoxia.

Diagnosis is made by muscle biopsy, raised creatine kinase and serum myoglobin levels.

Management

General measures

• Input/output chart.
• Weighing the patient.
• Assessment for fluid overload and for onset of acute renal failure (ARF).
• Careful monitoring of pressure within muscle compartments.

Pharmacological

• Hydration: large quantities of fluid should be given to maintain urine output at 300 ml/hour until the urine is free of myoglobin. The rate of administration depends on the severity of myoglobinuria. Sodium-depleted albumin may be used for volume expansion.
• Alkalinisation of urine with bicarbonate: to prevent dissociation of myoglobin into its nephrotoxic metabolites. Urinary pH should be >6.5.
• Diuretic therapy: mannitol and loop diuretics are preferred.
• Treatment for electrolyte disturbance: e.g. hyperkalaemia, hyperphosphataemia.
• Dialysis: may be required in the event of uncontrolled hyperkalaemia, acidosis, fluid overload or uraemic encephalopathy.
• Disseminated intravascular coagulation (DIC): may require therapy if associated with bleeding.

Surgical

Decompressive fasciotomy may be required to prevent local tissue necrosis.

Complications

As previously mentioned:

• Acute renal failure (ARF); reports show the incidence of ARF in rhabdomyolysis to range from 17% to 40%.^10,11
• Respiratory failure.
• Cardiac arrhythmias.
• Disseminated intravascular coagulation (DIC).
• Compartment syndrome.

Prognosis

If supportive therapy is given promptly, a good recovery can be made.¹²

Document references

1. Meyer-Betz F; Beobachtugen an einem eigenartigen mit muskellahmungen verbundenen fall von hamoglobinurie. Dtsc Arch Klin Med.1910;101:85-127.Original descriptive article.
2. Tietjen DP, Guzzi LM; Exertional rhabdomyolysis and acute renal failure following the Army Physical Fitness Test. Mil Med. 1989 Jan;154(1):23-5. [abstract]
3. Hurley JK; Severe rhabdomyolysis in well conditioned athletes. Mil Med. 1989 May;154(5):244-5. [abstract]
4. Schiff HB, MacSearraigh ET, Kallmeyer JC; Myoglobinuria, rhabdomyolysis and marathon running. Q J Med. 1978 Oct;47(188):463-72. [abstract]
5. Makaryus JN, Catanzaro JN, Katona KC; Exertional rhabdomyolysis and renal failure in patients with sickle cell trait: is it time to change our approach? Hematology. 2007 Aug;12(4):349-52. [abstract]
6. Olerud JE, Homer LD, Carroll HW; Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury. Arch Intern Med. 1976 Jun;136(6):692-7. [abstract]
7. Knochel JP; Catastrophic medical events with exhaustive exercise: "white collar rhabdomyolysis". Kidney Int. 1990 Oct;38(4):709-19.
8. Sinert R, Kohl L, Rainone T, et al; Exercise-induced rhabdomyolysis. Ann Emerg Med. 1994 Jun;23(6):1301-6. [abstract]
9. Gabow PA, Kaehny WD, Kelleher SP; The spectrum of rhabdomyolysis. Medicine (Baltimore). 1982 May;61(3):141-52.
10. Ward MM; Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988 Jul;148(7):1553-7. [abstract]
11. Akmal M, Valdin JR, McCarron MM, et al; Rhabdomyolysis with and without acute renal failure in patients with phencyclidine intoxication. Am J Nephrol. 1981;1(2):91-6. [abstract]
12. Melli G, Chaudhry V, Cornblath DR; Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). 2005 Nov;84(6):377-85. [abstract]

Internet and further reading

• Craig S; Rhabdomyolysis in Emergency Medicine, Medscape, Dec 2010
• Line RL, Rust GS; Acute exertional rhabdomyolysis. Am Fam Physician. 1995 Aug;52(2):502-6. [abstract]

Acknowledgements