Rhabdomyolysis

Introduction

• Mostly from drugs of abuse
• Common final endpoint is failure of Na/K ATPase and Ca pump leading to intracellular calcium accumulation and muscle cell necrosis
• Most common metabolic derangement is hypocalcaemia due to deposition of calcium salts in necrotic tissue
  • Get later hypercalcaemia as calcium is released
• Also get early hyperphosphataemia and late hypophosphataemia
• Hyperuricaemia is seen with crush injuries from muscle cell release of nucleotides, with conversion in the liver to uric acid
• Uric acid levels correlate with CK levels
• Hyperkalaemia
  • Occurs in 10-30% of cases from injured skeletal muscle
  • Presence of renal failure is the most important determinant of hyperkalaemia

Causes

• Alcohol and drugs of abuse – Amphetamines, MDMA, caffeine, cocaine, heroin,LSD, opiates (MOST COMMON CAUSE)
• Medications – Antipsychotics, barbiturates, benzodiazepines, colchicine, corticosteroids, lithium, MAOi, narcotics, salicylates, SSRI, statins, theophylline, TCA, zidovudine
• Muscle disease – Dermatomyositis, polymyositis, compartment syndrome, ischaemic limb
• Trauma – Crush, electrical injury
• Neuroleptic malignant syndrome
• Seizures – Delirium tremens
• Immobility
• Infection – Necrotising fasciitis, viral infection (Coxsackie, EBV, enterovirus, HIV, influenza, rotavirus)
• Strenuous activity – Weight-lifting more than endurance exercise
• Heat-related illness

Alcohol

• Can lead to rhabdo through comatose positioning +
  • Hypokalaemia, hypomagnesaemia, hypophosphataemia all increase risk
• Alcohol and drugs play a role in 80% of rhabdo in adults

Statin-related myopathy

• Myalgia with/without CK rise
• Muscle weakness
• Rhabdomyolysis
  • Rare (1%)
  • Dose-related
  • More common with lostatin (0.19%)

infections

• Influenza is the most common cause
• Legionella is the most frequent bacterial cause

pathophysiology

• Injury to muscle fibres with release of intracellular contents
  • Myoglobin
  • CK
  • Potassium
  • Calcium
  • LDH
  • Aldolase
  • AST
• Common terminal event is failure of Na/K ATPase and calcium transport with rising intracellular calcium concentrations and muscle cell necrosis

Clinical features

• Muscle symptoms (<50%) – Myalgias, stiffness, weakness, malaise, low-grade fever and brown urine
• ALOC can occur due to uraemia
• A minor will show swelling and tenderness of muscle groups and overlying skin haemorrhagic discolouration
• Commonly postural muscles of back, calves and thighs are involved
• Often diagnosed based solely on raised CK or myoglobinuria with minimal clinical findings

diagnosis

• Elevated serum CK is more sensitive and reliable diagnostic indicator
• Degree of CK elevation corresponds to degree of muscle injury and severity of illness but NOT development of renal failure or other morbidity
• Fivefold increase above ULN, in the absence of cardiac or brain injury, is diagnostic
• CK rises within 2-12 hours of muscle injury, peaks at 24-72 hours and declines at constant rate of 39% of previous days value
• If fails to decrease, suggests ongoing muscle injury
• Risk of AKI low if CK <20 000 on admission
• Myglobin levels return to normal within 1-6 hours of muscle necrosis so absence DOES NOT rule out diagnosis (like post-MI)
• Found in only 20% of patients at diagnosis
• Check K, Ca, Phos, urea levels, creatinine 
• Consider baseline coags as DIC is a potential complication

complications

• Acute renal failure (0-50% of patients)
  • Due to hypovolaemia, acidosis, aciduria, tubular obstruction with myoglobin and uric acid crystals and nephrotoxic effect of myoglobin 
  • Ferrihemate is toxic breakdown product of myoglobin – toxic only if hypovolaemic ancd aciduric pH <5.6
  • Rare in exertional rhabdomyolysis unless concomitant hypovolaemia, heat stress, trauma, sepsis, acidosis or sickle cell anaemia
  • Initial elevated urea and creatinine + large base deficit increases risk of acute renal failure in rhabdomyolysis

complications

• Metabolic derangement
  • Hyperkalaemia seen in 10-40%. Greatest determinent is presence of acute renal failure rather than degree of muscle injury itself
  • Hyperuricaemia seen especially with crush injuries due to release of muscle adenosine nucleotides and conversion to uric acid
  • Hyperphosphataemia initially, then later hypophosphataemia
  • Hypocalcaemia early due to deposition of calcium salts in injured muscle, hyperphosphataemia and decreased 1,12-dihydroxcholecalciferol. Get hypercalcaemia later due to release from muscle

Complications

• DIC
  • Usually resolves over days spontaneously
• Mechanical complications e.g. compartment syndrome, peripheral neuropathy
  • Peripheral neuropathy usually resolves within days to weeks

Treatment

• Pre-hospital
  • IV rehydration should be initiated if considered at risk
  • Early and vigorous IV rehydration is the most important determinent in preventing ARF
  • Once a limb is extracted, 1L/hr of N/S
• ED care
  • Continue aggressive IV rehydration for 24-72 hours (2.5mL/kg/hr) targeting UO 2mL/kg/hr (200-300mL/hr in other texts)
  • No proven benefit of urinary alkalinisation or forced diuresis
  • IDC
  • ECG monitoring (for 24-48 hours)
  • Haemodynamic monitoring if comorbidities
  • Serial electrolytes, CK, U&E
  • Hyperphosphataemia should be treated with oral phosphate binders if >7mg/dL (??)
  • Hypophosphataemia should be replaced IV if <1mg/dL (??)
  • Treat hyperkalaemia aggressively if arises – Insulin/dextrose may be less effective than usual due to reduced muscle uptake of K

Last Updated on October 7, 2020 by Andrew Crofton