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Rhabdomyolysis

Up Hepatorenal syndrome IAP measurement Rhabdomyolysis Sepsis & AKI


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

Thomas Li September 2006


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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