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Rhabdomyolysis
Thomas ST Li
Updated in September, 2006
Definition
Causes
Pathophysiology
Clinical manifestations
Laboratory findings
Management
References
Definition
Rhabdomyolysis is destruction or disintegration of striated muscles with
leakage of muscle intracellular contents into circulation and extracellular
fluid
Causes of rhabdomyolysis
Trauma and compression
- Crush injuries
- Prolonged immobilization
- Physical torture
- Struggle against restraints
Occlusion of vessels
- Thromboembolism
- Prolonged use of tourniquet use
Excessive muscle activities
- overexertion such as long distance running
- status epilepticus
- delirium tremens
- amphetamine overdose
Electrical injury
Hyperthermia
- Neuroleptic malignant syndrome
- Malignant hyperthermia
- Heat stroke
Toxins
- Insect venoms
- Snake venoms
Drugs
- Alcohol
- HMG-CoA reductase inhibitors (interfere with ATP
production by reducing levels of coenzyme Q, may develop weeks, months,
years after initiating therapy
- Cocaine
- Cyclosporine
- LSD
- Phencyclidine
- Cocaine
- Heroin
Infections
- Legionella
- Streptococcus
- Falciparum malaria
- HIV
- Salmonella
- Tetanus
- Influenza
- Herpes virus infection - herpes simplex virus,
Epstein-Barr virus, cytomegalovirus
Electrolyte disturbances
- Hypokalaemia
- Hypophosphataemia
- Hyponatraemia
- Hypocalcaemia
- Hypernatraemia
- Hyperosmotic conditions
Endocrine diseases
- Hypothyroidism
- Thyroid storm
- Ketoacidosis
- Hyperaldosteronism
- Phaeochromocytoma
Autoimmune disease
- Polymyositis
- Dermatomyositis
Inherited disorders of metabolism
- McArdle disease
- Mitochondrial enzyme deficiencies
Pathophysiology
Mechanisms of muscle injury
- Leakage of extracellular calcium into intracellular space, increasing
cytosolic ionized calcium level
- Pathologic interaction of actin and myosin
- Activation of cellular proteases causing muscle destruction and
necrosis of fibers
- Major increase in cellular permeability
- Release of potassium, phosphate, myogloin, CK and urate
Mechanisms of acute renal failure
- Contributing factors: hypovolaemia/ dehydration and aciduria
- Myoglobin causes tubular obstruction, renal vasoconstriction and
tubular damage by oxidative injury
- Urine acidity promotes the precipitation of Tamm-Horsfall protein and
formation of brown granular casts
- Tubular obstruction may also be caused by urate crystals in tubules
- Myoglobin may cause pH-dependent renal vasoconstriction
- Myoglobin may scavenge nitric oxide, which is important in regulation
of renal blood flow
Clinical manifestations
- Classic triad of symptoms: muscle pain, weakness and dark urine
- not often present in all patients
Musculo-skeletal signs
- Muscle pain, weakness, tenderness and contracture can be specific to
muscle groups or generalized
- Most common muscle groups: back muscles and calves
- May be difficult to distinguish from renal colic, deep vein
thrombosis or even angina
General manifestations
- Fever, tachycardia, nausea, vomiting and malaise
Complications
Early complications
- Hyperkalaemia, hypocalcaemia, elevation of hepatic enzymes (caused by
release of protease from injured muscles), cardiac arrhythmia and even
cardiac arrest
Late complications
- Acute renal failure (ARF) and disseminated intravascular coagulation
(DIC)
Laboratory findings
Elevation of serum creatinine kinase (CK)
- At least 5 times upper limit of normal
- t1/2 = 1.5 days
- Rise occurs within 12 hours
- Peak occurs in 1 to 3 days
- Decline over 3 to 5 days after resolution of muscle injury
- Peak level is predictive of development of ARF
- Peak level > 5000 U/l is related to ARF
Serum and urine myoglobin
- Myoglobin t1/2 = 2 to 3 hours
- Rapidly excreted via renal route
- Metabolized to bilirubin
- Filtered in kidney and appear in urine
- Dark red brown colour in urine
- May be useful in early phase
- Routine dipstick only detects haem, not
possible to differentiate, haematuria, haemoglobinuria and myoglobinuria
- Myoglobin is rapidly metabolized by liver,
absence of myoglobinuria or myoglobinaemia does not exclude rhabdomyolysis
Serum creatinine and urea
- Creatinine is elevated more than blood urea
nitrogen
Others
- hyperkalaemia
- hypocalcaemia
- hyperphosphataemia
- hyperuricaemia
- elevated serum lactate dehydrogenase
- elevated serum aminotransferase
- abnormal clotting studies if DIC
- Toxicological screening for drugs induced
rhabdomyolysis
Management
Stabilization and resuscitation of patients
Control the precipitating factors of
rhabdomyolysis
Specific treatment of rhabdomyolysis
Early aggressive fluid replacement with saline
for volume expansion
- Avoid Ringer lactate sodium because it
contains potassium
- Considerable amount of fluid may be
sequestered in damaged muscles
- Maintain urine output > 100 - 150 ml per
hour
Diuretics
- So far no randomized controlled trials to
support
- Consider mannitol and sodium bicarbonate
after initial resuscitation with saline
- Theoretical advantage of mannitol in
minimizing heme deposition in renal tubules, acting as free radical
scavenger and reducing blood viscosity
- Use of diuretics remains controversial
Alkalinization
- Increase the solubility of Tamm-Horsefall
protein-myoglobin complex
- May decrease risk of cast deposition in
renal tubules
- May inhibit myoglobin-induced lipid
peroxidation
- Also useful for correcting metabolic
acidosis and hyperkalaemia
- Infusion of 1.26%sodium bicarbonate (Na
concentration: 150mmol/l) aiming urine pH > 7
- May cause hypocalcaemia
Renal replacement therapy and extracorporeal
removal
- normalization of plasma potassium level
- correction of acidosis
- correction of fluid overload
- peritoneal dialysis is inadequate to remove
large solute load
- In 30% of patients, hypercalcaemia develops
in recovery phase of renal failure. Calcium administration should be avoided
unless patient has severe hypocalcaemia or severe hyperkalaemia
- Extracorporeal removal of myoglobin is
difficult
- Molecular mass of myoglobin is 17 kDa
- non-spherical and electrical charges
- Low diffusion coefficient
- Transport by convection
- Rejected by membrane pores
- Standard cellulosic membranes are
impermeable to the molecules
- High flux membranes have to be used
Antioxidants and free radical scavengers
- Pentoxyphyllin- improves microvascular
blood flow, decreases neutrophil adhesion and cytokine release
- Vitamin C, E
- Trace elements like zinc, manganese and
selenium
References
1)Bench-to-bedside
review: Rhabdomyolysis- an overview for clinicians. Critical Care 2005
2)Rhabdomyolysis.
Continuing Education in Anaesthesia, Critical Care & Pain 2006
3)Extracorporeal
therapies in acute rhabdomyolysis and myoglobin clearance. Critical Care 2005
Ó Thomas Li September 2006
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