Rhabdomyolysis CCC

Reviewed and revised 25 May 2016

OVERVIEW

Rhabdomyolysis is the breakdown of skeletal muscle fibers with leakage of potentially toxic intracellular contents into the systemic circulation, characterised by elevated plasma creatine kinase, myoglobinuria and risk of renal impairment

CAUSES

• Metabolic and endocrine
  • thyroid storm, phaeochromocytoma, myxoedema, DKA, HONK
• Ischaemia
  • compartment syndrome, prolonged immobilisation (e.g. coma, drug overdose), prolonged tourniquet use, post aortic clamp operations, reperfusion injuries.
• Trauma
  • crush injury, burns, electrocution
• Excessive physical activity
  • prolonged exertion, prolonged seizures
• Infection
  • viral (e.g. severe influenza), clostridium, persistent high fever
• Autoimmune
  • polymyositis, dermatomyositis
• Electrolytes
  • hypokalaemia, hypophosphataemia
• Hyperthermia and hypothermia
• Drugs and toxins
  • hyperthermia toxidromes: sympathomimetics (e.g. cocaine, amphetamines), malignant hyperthermia, serotonin syndrome, neuroleptic malignant syndrome, salicylism
  • statins / HMG-CoA reductase inhibitors
  • sedatives (e.g. opiates, alcohol) causing coma/ prolonged immobilisation
  • myonecrosis from non-depolarising neuromuscular blockers
  • envenomation (e.g. snake)
• Rare genetic disorders (e.g. carbohydrate or lipid metabolic disorders, myopathies)

PATHOPHYSIOLOGY

Mechanisms of muscle injury

• chemical injury
  • e.g. direct drug effect, metabolic derangement, abnormal electrolytes
• physical injury
  • e.g. trauma, thermal injury, excessive muscular activity
• biological injury
  • e.g. toxins, infections, immune-mediated effects

Mechanisms of renal failure due to rhabdomyolysis

• renal vasoconstriction
• intraluminal cast formation
• direct haem-protein induced cytotoxicity

Complications

• Hyperkalemia (early)
• Hypocalcemia (secondary to increased phosphate)
• Myoglobin release leading to acute renal failure (late)
• DIC due to release of thromboplastins (rare)
• Shock, due to “third space” losses from extravasation of fluid from extensively damaged muscle (if severe)

CLINICAL FEATURES

Varies depending on underlying cause and the severity of rhabdomyolysis:

• Muscle pain (~50%); can be painless
• Dark discolored urine (myoglobinuria)
• history of underlying cause
  • e.g. drugs/ toxins, metabolic/ endocrine derangement, trauma, physical activity, seizures, immobility, previous episodes and family history
• evidence of complications

INVESTIGATIONS

Bedside

• ECG (hyperkalemia, hypocalcemia)
• blood gas (hyperkalemia, metabolic acidosis)

Laboratory

• elevated CK
  • peaks <24h, then decreases by ~40% per day after the initial insult
  • if > 5,000 -> 50% chance of AKI
  • may rise into many hundreds of thousands in severe cases
  • persistent or increasing CK suggests ongoing cause/ precipitant or development of a compartment syndrome)
• FBC
• UEC
• Coagulation profile
• urine myoglobin (dipstick may indicate presence of blood)

Further investigations as appropriate to determine underlying cause and detect susepcted complications

MANAGEMENT

Resuscitation

• A – may require intubation and ventilation for pain relief, procedures or encephalopathy
• B – may develop ARDS and require ventilation
• C
  • aggressive fluid therapy and inotropic support to combat SIRS response given that much fluid enter affected limb
  • risk of cardiac arrest from hyperkalaemia and hypocalaemia
  • maintain urine output

Specific therapies

• IV fluid therapy
  • aiming for hypervolaemia to haemodilute blood being presented to the glomerulus
• Hyperkalaemia
  • calcium gluconate/ chloride, insulin-dextrose, B2 agonists, NaHCO3
• Forced alkaline diuresis (e.g. frusemide, mannitol)
  • increases tubular flow and increases pH to prevent precipitation of myoglobin in tubules
• RRT
  • helps with hyperkalaemia and acidosis
  • clears low molecular weight renal toxins
• Plasma exchange has no demonstrable benefit

Seek and treat underlying cause

• Procedures
  • minimise ischaemic time (remove cross clamp and tourniquets)
• If undergone a crush injury
  • may require elective intubation and fluid therapy prior to release of trapped limbs (in order to optimally manage cardiac arrest, analgesia, fluid therapy)
• Malignant hyperthermia
  • cease trigger, give dantrolene
• Cool if hyperthermia (e.g. T>39C)
• Treat infections
• Compartment syndromes
  • perform fasciotomies
• Correct electrolyte abnormalities (e.g. hypokalemia, hypophosphatemia)

Seek and treat complications

• Hyperkalaemia
  • from muscle breakdown – treat with medical therapy +/- RRT
• Renal failure from myoglobinuria
  • institute RRT
• Metabolic acidosis
  • normal anion gap if caused by lactate, may develop high anion gap after from release of inorganic acids into the circulation
• Hyperphosphataemia
  • resuscitate
• Hypocalaemia
  • supplement
• Hyperuricaemia
  • consider allopurinol

Disposition

• mild cases without renal failure can be monitored in a ward environment until CK is falling and the underlying cause is resolved
• patients at risk of significant electrolyte disturbance, renal failure or have a serious underlying cause are best monitored in an HDU/ ICU setting

References and Links

Journal articles

• Coban YK. Rhabdomyolysis, compartment syndrome and thermal injury. World J Crit Care Med. 2014 Feb 4;3(1):1-7. doi: 10.5492/wjccm.v3.i1.1. PMC4021149
• Hohenegger M. Drug induced rhabdomyolysis. Curr Opin Pharmacol. 2012 Jun;12(3):335-9. PMC3387368.
• Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med. 2009 Oct;67(9):272-83. PMID: 19841484.
• Sanghavi R, Aneman A, Parr M, Dunlop L, Champion D. Systemic capillary leak syndrome associated with compartment syndrome and rhabdomyolysis. Anaesth Intensive Care. 2006 Jun;34(3):388-91. PMID: 16802499.