Rhabdomyolysis refers to a clinical syndrome characterised by skeletal muscle necrosis.

Rhabdomyolysis is a condition that develops due to skeletal muscle necrosis and the release of toxic intracellular contents including myoglobin and electrolytes. It is characterised by markedly elevated levels of creatinine kinase (CK).

Rhabdomyolysis is a potentially life-threatening condition. The full clinical syndrome is characterised by evidence of myoglobinuria from muscle breakdown and acute tubular necrosis (ATN) causing acute kidney injury (AKI).

It is a common condition in the adult population that occurs from a variety of causes including trauma and prolonged immobilisation (e.g. following a fall in the elderly).


The aetiology of rhabdomyolysis is very broad, but it is classically seen in crush injuries, following prolonged immobilisation or secondary to medications.

The cause of rhabdomyolysis can broadly be divided into three groups:

  • Traumatic: usually the result of muscle compression from a crush injury or prolonged immobilisation.
  • Non-traumatic (exertional): marked exertion (typically untrained person) or metabolic myopathy.
  • Non-traumatic (non-exertional): infections, drugs, toxins or electrolytes derangements.

The actual cause is usually suggested from the history and examination. For example, a patient presenting with a traumatic injury, an elderly patient presenting after a long period of immobilisation following a fall, or a patient recently started on a statin.


Crush injuries (e.g. following a car accident) may lead to rhabdomyolysis.

Crush injury

Patients with crush injuries may be at risk of compartment syndrome. This often occurs during treatment of rhabdomyolysis as intravenous fluids cause the compartment to swell.

  • Trapped following a car accident or natural disaster
  • Polytrauma


This commonly occurs in elderly patients who have been unable to move from a single position for many hours. This may occur following a fall and subsequent fracture or due to general frailty.

Prolonged muscle compression

May be seen during a surgical operation that involves muscle compression or tourniquet use to restrict blood supply.

Compartment syndrome

This refers to increased pressure in a fascial compartment that leads to restricted blood flow. The reduced blood supply damages surrounding tissue including muscle and nerves. It is associated with severe pain.

Compartment syndrome leading to muscle necrosis and subsequent rhabdomyolysis is commonly seen with lower extremity fractures (e.g. tibial fracture).

High voltage electrical injuries

Causes direct damage to muscle. Examples include lightning strike or touching a powerline. Similar effects are seen with severe burns.

Non-traumatic (exertional)

Rhabdomyolysis in this context can occur when there is an energy supply/demand mismatch to the muscles.

Marked physical exertion

Most commonly occurs in untrained individuals who subsequently undergo marked physical exertion (e.g. marathon).

Often concurrent risk factors are present such as:

  • Extremely hot conditions (causes an exertional heat stroke - failure of thermoregulation)
  • Impaired sweating
  • Sickle cell trait
  • Hypokalaemia

Hyperkinetic states

This refers to conditions that markedly increase, and typically sustain muscle contraction.

  • Status epilepticus
  • Amphetamine overdose
  • Delirium tremens

Metabolic myopathies

These are inherited disorders of metabolism, typically due to a mutation in an enzyme that governs glycogenolysis, glycolysis or lipid metabolism.

Examples include:

  • Myophosphorylase deficiency (McArdle disease)
  • Lactate dehydrogenase deficiency
  • Carnitine deficiency

Thermal extremes

Both high and low temperatures can cause rhabdomyolysis due to the loss of thermoregulation.

  • Neuroleptic malignant syndrome: abnormal reaction to psychotic medication causing fever, rigidity and confusion.
  • Near drowning
  • Hypothermia
  • Malignant hyperthermia: due to inherited abnormalities in the muscle ryanodine receptor. Classically precipitated by inhalation anaesthetics or succinylcholine.

Non-traumatic (non-exertional)

A wide variety of drugs, infections, toxins and electrolyte disturbances can induce rhabdomyolysis.


These can precipitate rhabdomyolysis by several mechanisms.

  • Direct toxic effects: colchicine (disrupts tubulin formation). Used to treat inflammatory conditions like gout.
  • Induction of malignant hyperthermia: succinylcholine
  • Toxic in the context of drug interaction or co-morbidity: in those taking statins, medications or conditions that delay clearance from the body increase the risk of rhabdomyolysis.

Illicit drugs

Many illicit drugs have been implicated in rhabdomyolysis by various mechanisms

  • Develop of coma leading to immobilisation: alcohol, opioids, benzodiazepines
  • Induction of hyperkinetic state (e.g. agitation, seizures, dystonia): amphetamine, cocaine


A variety of viral, bacterial and other pathogens can cause rhabdomyolysis

  • Viruses: Influenza, Coxsackievirus, EBV, CMV or Adenovirus among others.
  • Bacterial: Mycoplasma pneumoniae, Legionella, E. coli or Streptococcus among others.
  • Others: e.g. Plasmodium falciparum


  • Snake venom: usually from snakes in Asia, Africa or South America
  • Haff disease: development of rhabdomyolysis within 24 hours of ingestion of an unidentified toxin in certain fish.
  • Insect venoms
  • Mushroom toxins (e.g. Tricholoma equestre)

Electrolyte disturbances

Hypokalaemia and hypophosphataemia are the main disturbances that can lead to rhabdomyolysis

  • Hypokalaemia: low levels (<2.5 mmol/L) can decrease blood flow to muscles during exercise. This creates a supply/demand mismatch.
  • Hypophosphataemia: rhabdomyolysis due to low phosphate is typically seen in the context of refeeding syndrome. Refeeding syndrome refers to rapid shifts in serum electrolytes following the reintroduction of food after a period of malnourishment or starvation


Injury to myocytes leads to ATP depletion, increased intracellular calcium and leakage of intracellular contents.

Muscle injury

In rhabdomyolysis, regardless of aetiological mechanisms, there is a final common pathway leading to muscle injury and the leakage of intracellular content including CK and myoglobin.

Myocyte injury leads to depletion of adenosine triphosphate (ATP), which is the main cellular source of energy. This causes increased intracellular calcium due to dysfunction of the normal Na/K-ATPase and Ca2+ATPase pumps. This requires ATP to function and maintain myocyte integrity.

High levels of intracellular, and mitochondrial, calcium cause a series of events that result in muscle necrosis including activation of proteases, muscle cell contractility, mitochondrial dysfunction and production of damaging reactive oxygen species (ROS). These events result in loss of myocyte integrity and leakage of intracellular content.

Renal injury

Myoglobin is an important protein within myocytes. Release into the circulation results in haptoglobin binding to prevent toxic effects. However, this buffer system is overburdened in massive muscle injury. The excess myoglobin is filtered through the kidneys where it causes damage.

Myoglobin damages the kidneys in three ways:

  • Intrarenal vasoconstriction
  • Direct nephrotoxicity
  • Renal tubular obstruction due to precipitation

Collectively, this enhances renal tubular ATP loss leading to ATN and AKI. In severe cases, this may require dialysis. The risk of AKI is highest with higher levels of CK as this suggests more extensive muscle necrosis. CK levels below 15,000-20,000 are less likely to cause AKI unless there is concurrent pathology (e.g. hypovolaemia, sepsis, acidosis).

Clinical features

Rhabdomyolysis is characterised by a triad of myalgia, muscle weakness and dark urine (due to myoglobin).

Presenting clinical features may be suggestive of the underlying cause. For example, a recent tibial fracture or crush injury. Clinical features of rhabdomyolysis itself are often vague with generalised myalgia and muscle weakness.

The classic triad of myalgia, muscle weakness and dark urine is only seen in around 50% (much less common in children).


  • Myalgia
  • Muscle weakness (calves, lower back most common)
  • Fever/hypothermia
  • Nausea & vomiting
  • Abdominal pain


  • Dark urine (often described as coca cola)
  • Altered mental status
  • Soft tissue swelling
  • Muscle weakness
  • Skin changes (usually from ischaemic injury)
  • Limb deformity (seen in crush injury)

Diagnosis & investigations

Serum CK is the principle investigation for the diagnosis of rhabdomyolysis.

Anyone at risk, or suspected of having, rhabdomyolysis should have a serum CK. This includes unexplained AKI, following a long period of immobilisation, crush injury, consistent electrolyte disturbances or muscle tenderness.

Creatine kinase

CK is an important marker of skeletal muscle breakdown and used to define rhabdomyolysis.

An elevation in CK > 5x the upper limit of normal is suggestive of rhabdomyolysis. However, the range of elevation is highly variable (1500 to > 100,000 IU/L) and this usually depends on the extent of the injury.

There are different isoforms of CK (three cytosolic and two mitochondrial) but in rhabdomyolysis, the rise in CK is almost entirely from the skeletal muscle isoform (CK-MM). The rise in CK usually occurs within 12 hours of the muscle injury and peaks within 24-72 hours. When the muscle injury has resolved, CK falls over 3-5 days.

Urinary findings

The key finding in the urine is the identification of myoglobin, which causes it to change colour to the characteristic dark red/coca-cola. Myoglobin is rapidly excreted from the urine and therefore myoglobinuria may only be identified in 50% of patients.

On urine dipstick, both haemoglobin and myoglobin are detected as ‘blood’. However, much larger quantities of blood are required to invoke a colour change. Under the microscope, features supportive of myoglobinuria would be a significant colour change with minimal red blood cells.

Renal function

Approximately 15-50% of patients with rhabdomyolysis have evidence of AKI. The risk of AKI increases with higher concentrations of CK and in patients with risk factors such as sepsis, dehydration or acidosis. All patients with suspected rhabdomyolysis need an urgent renal function.


  • Bedside: urine dip + microscopy, ECG (at risk of electrolyte abnormalities and therefore arrhythmias)
  • Bloods: FBC, U&E, LFT (rise in transaminases may be seen in rhabdomyolysis), bone profile (phosphate/calcium/magnesium), uric acid (increased release of intracellular purines)
  • Imaging: renal ultrasound to exclude obstructive uropathy if AKI.
  • Special: further investigations guided by aetiology (e.g. toxin screen).


Fluid resuscitation is essential to prevent and treat acute kidney injury.

Management of rhabdomyolysis should focus on the treatment of the underlying cause, usually by removing the offending agent or trigger and preventing severe renal injury.

Fluid resuscitation

In patients with suspected rhabdomyolysis it is critical to correct dehydration and prevent worsening ATN. This involves early, and aggressive, administration of intravenous fluids.

Intravenous fluids help in multiple ways:

  • Enhance renal perfusion
  • Increase urinary flow rate
  • Limit myoglobin cast formation
  • Increase urinary potassium excretion

There is no set administration of fluid volume or rate. Usually, it is advised to give 1-2 litres over the first hour in severe cases at risk of AKI. However, this should be decided based on the suspected volume deficit, co-morbidities of the patients (e.g. heart failure, chronic liver disease) and the severity of illness. It requires close monitoring of the patient with regular assessment of fluid balance.

Once CK levels are < 5000 IU/L, further fluid resuscitation purely for rhabdomyolysis is not required as the risk of AKI is low.


In patients with severe AKI, dialysis may be needed. Indications for dialysis are the same as for other causes of renal failure:

  • Refractory hyperkalaemia
  • Refractory metabolic acidosis
  • Refractory fluid overload
  • Uraemic complications

Additional pharmacotherapy

Additional therapeutic options exist for the treatment of rhabdomyolysis, but this should be a senior or ITU-led decision as specific parameters are usually required prior to administration and some are not without risk.

  • Intravenous bicarbonate
  • Loop diuretics (usually reserved for volume overload)
  • Mannitol (undefined benefit)


Rhabdomyolysis can be a life-threatening condition.

Electrolyte derangements

Patients with rhabdomyolysis are at risk of dangerous electrolyte disturbances due to the release of intracellular content that has a high concentration of phosphate and potassium.

  • Hyperkalaemia: occurs due to the release of intracellular potassium and is exacerbated by acidosis. Can lead to dangerous cardiac arrhythmias. Treatment should follow the usual protocols.
  • Hyperphosphataemia: occurs due to the release of intracellular phosphate. The main concern is that it can bind to serum calcium leading to profound secondary hypocalcaemia. Calcium-phosphate binding can precipitate in the kidneys which worsens AKI.
  • Hypocalcaemia: occurs due to its binding with excess phosphate. Increases risk of cardiac arrhythmias and neurological complications.

Other complications

  • Severe AKI
  • Compartment syndrome
  • Hypovolaemic shock
  • Hyperuricemia (patients may require allopurinol to prevent renal damage)
  • Disseminated intravascular coagulation
  • Death

Last updated: May 2021
Author The Pulsenotes Team A dedicated team of UK doctors who want to make learning medicine beautifully simple.

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