Management of Severe Rhabdomyolysis

Definition

Rhabdomyolysis is the breakdown of muscle fibres which results in the leakage of potentially toxic cellular contents into the extracellular fluid and the circulation. One of the key compounds is myoglobin.

This can result in:

• Hypovolaemia
• Metabolic acidosis
• Hyperkalaemia
• Acute renal failure essentially due to precipitation of myoglobin in tubules and intravascular volume depletion due to excessive fluid shift into damaged muscle
• Multiple organ failure

Causes

1. Trauma and compression - ‘Crush syndrome’
   • First reported following Sicilian earthquake in 1908
2. Occlusion of muscular vessels
   • Thrombosis, embolism or surgical clamping
3. Strenuous exercise
   • e.g. In untrained individuals in hot climates
4. Electrical injury
5. Hyperthermia
   • Neuroleptic malignant syndrome
   • Malignant hyperpyrexia
6. Metabolic myopathies
   • Inherited diseases that pre-dispose individuals
7. Drugs and toxins
   • Alcohol
   • Ecstasy
   • Heroin
   • Amphetamines / Cocaine
   • HMG CoA reductase inhibitors (statins)
8. Local muscle infection
9. Electrolyte abnormalities
   • Hypokalaemia, hypocalcaemia, hypophosphataemia, hyponatraemia and especially hypernatraemia have all been associated with rhabdomyolysis

Diagnosis

• Precipitating event
• Clinical features

e.g. swollen, painful muscles

• Myoglobinuria

Urinary myoglobin results in a reddish-brown discoloration of urine. Normal coloured urine does not exclude rhabdomyolysis and myoglobinuria may be absent in up to 18% of patients.

Myoglobinuria can be inferred by a positive result on a dipstick test (test for haem) and the absence of red cells on microscopy.

Laboratory measurement of myoglobin can be performed.

·      Creatinine Kinase (CK)

Release of large quantities of CK (>200 u/L), aspartate transaminase (AST) and lactate dehydrogenase (LDH) are seen. The degree of elevation is proportional to the injury.

·      Renal impairment

·      Metabolic acidosis

Markers of severe rhabdomyolysis

1. CK > 5000 u/L
2. Myoglobin in urine >20 mg/ml (>50% develop renal failure)
3. Hyperkalaemia >6.5 mmol/L
4. Severe hypoalbuminaemia
5. Sepsis is the precipitating event
6. Marked dehydration on presentation

Recommended Management

See attached guidelines

The evidence

Level III & IV evidence only.

No human randomised controlled trials performed.

Holt SG, Moore KP. Pathogenesis & treatment of renal dysfunction in rhabdomyolysis. ICM  27:803-811, 2001

Vanholder R, Sever MS. Rhabdomyolysis. J Am Soc Neph 11:1553-1561,2000

Shimazu T, Yoshioka T. Fluid resuscitation and systemic complications in crush syndrome: 14 hanshin-awaji earthquake patients. J Trauma 42(4): 641-646, 1997

Green G. A fatal case of malignant Hyperthermia complicated by generalised compartment syndrome and rhabdomyolysis. Acta Anaseth Scand 47(5): 619-621, 2003

Korantzopoulos P, Papaioannides D. Acute rhabdomyolysis due to prolonged exposure to the cold. Int J Clin Pract 3:243-244, 2003

Morton SE, Mathai M. Influenza A pneumonia with rhabdomyolysis. South Med J 94(1):67-69, 2001

Santos J Jr. Exertional rhabdomyolysis. JAAPA 12(7):46-49,53-55, 1999

Szewczyk D, Ovadia P. Pressure-induced rhabdomyolysis and acute renal failure. J Trauma. 44(2):383-348, 1998

Trimarchi H, Gonzalez J. Hyponatraemia-associated rhabdomyolysis. Nephron 82(3):274-277, 1999

Management of Severe Rhabdomyolysis

Treatment guidelines

1.   Patient must be managed in a critical care environment

2.   Early fluid resuscitation

Aggressive infusion of intravenous fluid (crystalloid or colloid) according to clinical and laboratory parameters.

Central venous pressure monitoring is recommended.

Avoid potassium-containing fluids if K⁺ >4.0 mmol/L

Aim for urine output > 1 ml/kg/hr

3.   Urinary alkalinisation

Increases the solubility of myoglobin within renal tubules and can improve myoglobin washout.

Use 8.4% sodium bicarbonate infusion at a rate of 0-50 mls/hr via central venous catheter (use 2.74% if peripherally administered)

Aim to keep plasma pH between 7.4 – 7.45 AND/OR urinary pH > 6.5

4.   Mannitol

Controversial – as an osmotic diuretic it may:

o   Increase urinary flow

o   Reduce elevated compartment pressures due to muscle swelling

o   Scavenge free-radicals

Can precipitate acute volume overload in patients in renal failure.

Give 100mls 20% mannitol over 20 minutes if:

·      Urine output < 1 ml/kg

·      Evidence of compartment syndrome (see below)

5.   Renal replacement therapy

Use if:

·      Established renal failure

·      Persistent acidosis or hyperkalaemia

6.   Complications of rhabdomyolysis

·      Metabolic disturbance

Rhabdomyolysis accompanied by influx of Ca²⁺ and Na⁺ into muscle and efflux of K⁺, phosphate and other ions.

Hypocalcaemia, hyperkalaemia, hyperphosphataemia and hyperuricaemia occur. Hypercalcaemia can occur later as Ca²⁺ is released from recovering muscles.

·      Disseminated intravascular coagulation

·      Compartment syndrome

Due to muscle cell oedema. High intra-compartmental pressures (> 40 mmHg) provoke necrosis.

Consider if muscle swelling and/or increasing pain.

Immediate surgical referral is necessary for consideration of fasciotomy.

AVOID

Frusemide – Acidifies urine worsening myoglobin precipitation

Calcium – Muscular calcification will occur as initial hypocalcaemia is

       replaced by hypercalcaemia as recovery occurs.