Medicine – Rhabdomyolysis

Rhabdomyolysis is a syndrome caused by rapid breakdown and necrosis of skeletal muscle fibres, resulting in the release of intracellular muscle contents into the circulation.

Important substances released include:

Myoglobin.

Creatine kinase – CK.

Potassium.

Phosphate.

Uric acid and other intracellular constituents.

The most important complications are acute kidney injury (AKI) and potentially life-threatening hyperkalaemia.

1. Basic Pathophysiology

Skeletal muscle injury causes disruption of the muscle-cell membrane.

As muscle cells break down, their intracellular contents enter the bloodstream.

Therefore:

Muscle injury → muscle-cell necrosis → release of CK + myoglobin + potassium + phosphate → systemic complications.

2. Myoglobin Release

Myoglobin is an oxygen-binding protein found within skeletal muscle.

When large amounts of skeletal muscle are damaged, myoglobin enters the:

Bloodstream

and is subsequently filtered through the:

Glomeruli.

Large quantities of filtered myoglobin can contribute to:

Acute tubular injury and AKI.

3. Acute Kidney Injury

The older term:

Acute renal failure – ARF

should now be replaced by:

Acute kidney injury – AKI.

AKI is one of the most important complications of severe rhabdomyolysis.

4. Mechanisms of AKI

Several mechanisms contribute simultaneously.

Myoglobin can cause:

Direct tubular toxicity.

Intratubular cast formation and obstruction.

Oxidative tubular injury.

In addition, fluid moves into injured muscle, producing:

Intravascular volume depletion.

Renal vasoconstriction and reduced renal perfusion further increase the risk of:

AKI.

5. Hypovolaemia

Damaged muscles can become markedly:

Oedematous.

Large quantities of fluid may move from the circulation into injured muscle.

This produces:

Third-space fluid loss → reduced circulating volume → reduced renal perfusion.

Therefore, hypovolaemia contributes importantly to kidney injury.

6. Clinical Presentation

The classic symptoms are:

Muscle pain.

Muscle weakness.

Muscle swelling.

Dark urine.

However, the complete classic presentation is not present in every patient.

Some patients have few obvious muscular symptoms and are diagnosed because of:

Markedly elevated CK.

7. Muscle Pain

Patients may develop:

Myalgia

or severe muscle tenderness.

The muscles affected depend on the underlying cause.

For example, prolonged compression may produce localised severe muscle injury, whereas seizures can cause more widespread muscle breakdown.

8. Muscle Weakness

Muscle injury may produce:

Generalised or localised weakness.

Weakness may be accompanied by:

Tenderness

and

Swelling.

9. Dark Urine

Myoglobin filtered into the urine can produce:

Dark brown

or

Tea/cola-coloured urine.

This is called:

Myoglobinuria.

10. Myoglobinuria and Urine Dipstick

An important examination finding is:

Urine dipstick positive for “blood”

but

Urine microscopy showing few or no red blood cells.

This occurs because the dipstick detects the haem pigment in:

Myoglobin

as well as haemoglobin.

11. High-Yield Urine Pattern

Therefore:

Dark urine + positive dipstick for blood + few/no RBCs on microscopy → think myoglobinuria from rhabdomyolysis.

However, this finding is not sufficiently sensitive to exclude rhabdomyolysis when absent.

12. Creatine Kinase

The most important biochemical marker is:

Creatine kinase – CK.

Rhabdomyolysis produces a:

Marked elevation of CK.

CK may reach:

Thousands or tens of thousands of units per litre

in severe cases.

13. Diagnostic CK Elevation

There is no single CK value that perfectly defines every case, but rhabdomyolysis is commonly considered when CK is approximately:

>5 times the upper limit of normal

in an appropriate clinical setting.

The greater the muscle injury, the higher CK generally becomes.

14. CK versus Myoglobin

Myoglobin rises and disappears from the circulation relatively quickly.

CK remains elevated for longer.

Therefore:

CK is generally more useful for diagnosis and monitoring than serum or urinary myoglobin.

15. Hyperkalaemia

Skeletal muscle contains large amounts of intracellular:

Potassium.

Muscle-cell destruction releases potassium into the circulation.

Therefore rhabdomyolysis can produce:

Hyperkalaemia.

16. Why Hyperkalaemia Is Dangerous

Severe hyperkalaemia can cause:

Cardiac conduction abnormalities.

Ventricular arrhythmias.

Cardiac arrest.

Therefore potassium should be assessed urgently in significant rhabdomyolysis.

17. Hyperphosphataemia

Muscle cells also contain large amounts of:

Phosphate.

Cell destruction releases phosphate into the bloodstream, causing:

Hyperphosphataemia.

18. Hypocalcaemia

During the early phase of rhabdomyolysis, calcium may move into damaged muscle and precipitate with phosphate.

This can cause:

Hypocalcaemia.

Therefore the typical early biochemical pattern may include:

↑ Potassium.

↑ Phosphate.

↓ Calcium.

19. Calcium During Recovery

During recovery, calcium deposited in damaged muscle may return to the circulation.

Some patients can therefore develop:

Rebound hypercalcaemia.

This is an important reason calcium abnormalities can change during the course of rhabdomyolysis.

20. Uric Acid

Breakdown of muscle cells and nucleic acids can increase:

Uric acid.

Hyperuricaemia may further contribute to renal tubular injury in severe disease.

21. Creatinine

The original notes state:

“Creatinine raised disproportionately to urea.”

This can occur because skeletal muscle breakdown releases:

Creatine and creatinine precursors.

Therefore creatinine may rise relatively rapidly compared with urea.

However, this is not required for diagnosis and should not replace CK measurement and assessment of kidney function.

22. Other Laboratory Abnormalities

Rhabdomyolysis may also produce:

Raised AST.

Raised LDH.

Metabolic acidosis.

AST can originate from skeletal muscle, so an elevated AST does not necessarily indicate primary liver injury.

23. Major Causes

Rhabdomyolysis has many causes.

They can broadly be grouped into:

Traumatic.

Exertional.

Drug-related.

Toxic.

Metabolic.

Seizure-related.

Thermal.

Infectious.

24. Trauma and Compression Injury

Severe:

Trauma

or

Compression injury

can cause extensive muscle necrosis.

Examples include:

Crush injuries.

Building collapse.

Road traffic trauma.

Prolonged entrapment.

25. Crush Syndrome

When extensive compression produces rhabdomyolysis together with systemic complications, the condition may be described as:

Crush syndrome.

After the pressure is released, large amounts of:

Potassium, myoglobin and other intracellular substances

may rapidly enter the circulation.

This can cause severe:

Hyperkalaemia

and

AKI.

26. Prolonged Immobilisation

Prolonged pressure on muscle can also occur when a person remains unconscious or immobile for many hours.

Examples include prolonged immobilisation associated with:

Drug intoxication.

Alcohol intoxication.

Coma.

This causes:

Pressure-induced muscle ischaemia and necrosis.

27. Seizures

The original term:

“Uncontrolled fitting”

is better expressed as:

Prolonged or repeated generalised seizures.

Intense repetitive skeletal-muscle contraction can cause extensive muscle breakdown.

Therefore:

Status epilepticus → muscle injury → rhabdomyolysis.

28. Excessive Exercise

Severe or unaccustomed physical exertion can cause:

Exertional rhabdomyolysis.

Risk is increased by:

Extreme exercise.

Heat.

Dehydration.

Underlying metabolic or genetic muscle disorders.

29. Statins

Statins can rarely cause severe muscle injury leading to:

Rhabdomyolysis.

More commonly they cause milder:

Myalgia

or

CK elevation.

True statin-associated rhabdomyolysis is uncommon but potentially serious.

30. Risk Factors for Statin-Associated Rhabdomyolysis

Risk may increase with:

High statin exposure.

Drug interactions that increase statin concentrations.

Advanced age.

Renal impairment.

Hypothyroidism.

Certain combinations of lipid-lowering drugs.

31. Drugs and Toxins

Many other substances can cause rhabdomyolysis.

Examples include:

Cocaine.

Amphetamines.

Some antipsychotic-related syndromes.

Alcohol, particularly with prolonged immobilisation.

The mechanism varies between:

Direct toxicity, hyperthermia, seizures, agitation and immobilisation.

32. Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome can cause:

Severe muscle rigidity.

Hyperthermia.

Autonomic instability.

Marked CK elevation.

Rhabdomyolysis can therefore be an important complication.

33. Burns

Severe:

Burns

can produce extensive muscle and tissue injury.

They may therefore be associated with:

Rhabdomyolysis

particularly when the injury is deep or associated with electrical damage.

34. Electrical Injury

Electrical injury is particularly important because substantial deep muscle damage can occur even when external skin injury appears relatively limited.

Therefore:

Electrical injury → deep muscle necrosis → rhabdomyolysis → hyperkalaemia + AKI.

35. Heat-Related Illness

Severe hyperthermia, particularly:

Heatstroke,

can cause extensive skeletal-muscle injury.

Heatstroke-associated rhabdomyolysis may coexist with:

Neurological dysfunction.

Coagulopathy.

Hepatic injury.

AKI.

36. Infections

Some severe infections can precipitate rhabdomyolysis.

Both:

Viral

and

Bacterial infections

have been associated with muscle breakdown.

The mechanism may involve direct muscle injury, inflammation, fever and systemic illness.

37. Metabolic and Electrolyte Causes

Severe electrolyte abnormalities may occasionally cause rhabdomyolysis.

Examples include marked disturbances of:

Potassium.

Phosphate.

Sodium.

Endocrine abnormalities such as severe:

Hypothyroidism

can also predispose to muscle injury.

38. Inherited Muscle Disorders

Recurrent episodes of rhabdomyolysis, particularly after exercise or fasting, may suggest an underlying:

Metabolic myopathy.

Examples include disorders of:

Glycogen metabolism.

Fatty-acid oxidation.

Mitochondrial metabolism.

These become particularly relevant when episodes are recurrent without an obvious acquired cause.

39. Compartment Syndrome

Severe muscle swelling can increase pressure within a closed fascial compartment.

This may produce:

Compartment syndrome.

Increasing pressure compromises:

Muscle and nerve perfusion.

This creates further ischaemia and muscle necrosis.

40. Compartment Syndrome Is an Emergency

Features include:

Severe pain, especially pain out of proportion to the injury.

Pain on passive stretch.

Tense swollen compartment.

Neurological abnormalities as disease progresses.

Suspected acute compartment syndrome requires:

Urgent surgical assessment.

41. Major Complications

Important complications of rhabdomyolysis include:

Acute kidney injury.

Hyperkalaemia.

Hyperphosphataemia.

Early hypocalcaemia.

Metabolic acidosis.

Cardiac arrhythmias.

Compartment syndrome.

Disseminated intravascular coagulation in severe systemic disease.

42. Initial Assessment

Investigation should determine both:

The severity of muscle injury

and

The presence of complications.

Important tests include:

CK.

Creatinine and renal function.

Potassium.

Phosphate.

Calcium.

Bicarbonate.

Urinalysis.

43. ECG

Because hyperkalaemia can be rapidly fatal, an:

ECG

is important when significant hyperkalaemia is present or suspected.

ECG abnormalities may include:

Peaked T waves.

PR prolongation.

QRS widening.

Progression to malignant arrhythmias.

44. Management

The cornerstone of treatment is:

Early intravenous crystalloid fluid administration

when clinically appropriate.

The aim is to:

Correct intravascular volume depletion.

Maintain renal perfusion.

Promote urinary excretion of myoglobin.

45. Intravenous Fluids

Fluid therapy is generally based on:

Isotonic crystalloid.

The exact volume and rate should be individualised according to:

Severity of rhabdomyolysis.

Urine output.

Haemodynamic status.

Cardiac function.

Renal function.

46. Avoid Fluid Overload

Aggressive fluid replacement must be used carefully in patients who develop:

Oliguric AKI

or who have:

Heart failure.

If the kidneys cannot excrete the administered fluid, excessive treatment may cause:

Pulmonary oedema.

Therefore fluid therapy requires close monitoring.

47. Treat the Underlying Cause

The precipitating cause should be identified and corrected.

Examples include:

Stopping an offending drug.

Treating seizures.

Treating hyperthermia.

Correcting severe electrolyte abnormalities.

Treating infection.

Managing trauma or compartment syndrome.

48. Hyperkalaemia Treatment

Severe hyperkalaemia requires:

Urgent treatment.

Management depends on potassium concentration, ECG findings and clinical severity.

The key principle is:

Rhabdomyolysis + severe hyperkalaemia = medical emergency.

49. Calcium Replacement

Although early hypocalcaemia may occur, asymptomatic hypocalcaemia is not necessarily corrected routinely, because calcium may later rebound during recovery.

Calcium treatment is generally reserved for appropriate clinical indications such as:

Symptomatic hypocalcaemia

or particular emergency circumstances.

50. Bicarbonate and Mannitol

Older protocols sometimes routinely recommended:

Urinary alkalinisation with bicarbonate

and

Mannitol.

These are not routinely required for every patient, because evidence of benefit over appropriate crystalloid resuscitation is limited.

The central treatment remains:

Appropriate IV fluids + electrolyte management + treatment of the cause.

51. Dialysis

Some patients develop severe AKI requiring:

Kidney replacement therapy – dialysis.

Dialysis may be required for standard indications such as:

Refractory hyperkalaemia.

Severe metabolic acidosis.

Refractory fluid overload.

Severe uraemic complications.

52. Dialysis Is Not Based on CK Alone

A massively elevated CK does not by itself indicate a need for dialysis.

The decision is based primarily on:

Renal function and complications.

Therefore:

High CK ≠ automatic dialysis.

53. Monitoring

Patients with significant rhabdomyolysis require repeated assessment of:

CK.

Creatinine.

Urine output.

Potassium.

Calcium.

Phosphate.

Acid-base status.

Monitoring is particularly important because electrolyte abnormalities can change rapidly.

54. Rhabdomyolysis – Causes Note Form

Traumatic:

Crush injury.

Major trauma.

Prolonged compression.

Prolonged immobilisation.

Muscular overactivity:

Generalised seizures.

Status epilepticus.

Extreme exercise.

Severe agitation.

Drugs and toxins:

Statins.

Cocaine.

Amphetamines.

Alcohol-associated immobilisation.

Other myotoxic drugs.

Thermal/electrical:

Burns.

Electrical injury.

Heatstroke.

Other:

Severe infections.

Electrolyte abnormalities.

Hypothyroidism.

Metabolic myopathies.

Inherited muscle disorders.

55. Rhabdomyolysis – Laboratory Pattern Note Form

Creatine kinase:

Massively elevated.

Most useful biochemical marker.

Potassium:

Raised because damaged muscle releases intracellular potassium.

Potentially life-threatening.

Phosphate:

Raised because phosphate is released from damaged muscle.

Calcium:

Often low early.

May become high during recovery.

Creatinine:

May rise rapidly, particularly when AKI develops.

Urine:

Dark because of myoglobin.

Dipstick may be positive for blood despite few or no RBCs on microscopy.

56. Rhabdomyolysis – Management Note Form

First:

Identify and remove the cause.

Fluids:

Early appropriate IV crystalloid.

Maintain circulating volume and renal perfusion.

Monitor carefully for fluid overload.

Electrolytes:

Monitor potassium, phosphate and calcium.

Treat severe hyperkalaemia urgently.

Kidneys:

Monitor creatinine and urine output.

Watch for AKI.

Compartment syndrome:

Urgent surgical assessment if suspected.

Dialysis:

Use when standard indications develop, particularly refractory hyperkalaemia, severe acidosis or fluid overload.

57. Important Corrections to the Original Notes

The term:

“ARF”

should be replaced by:

ACUTE KIDNEY INJURY – AKI.

The definition:

“Muscle damage or necrosis leading to myoglobin release”

is correct but can be expanded to:

SKELETAL MUSCLE BREAKDOWN → RELEASE OF MYOGLOBIN + CK + POTASSIUM + PHOSPHATE AND OTHER INTRACELLULAR CONTENTS.

The statement:

“Creatinine raised disproportionately to urea”

can occur but is not a defining diagnostic feature.

The most important biochemical marker is:

MARKEDLY ELEVATED CK.

The original biochemical features should also include:

EARLY HYPOCALCAEMIA

and potentially:

LATER REBOUND HYPERCALCAEMIA.

The cause:

“Uncontrolled fitting”

is better expressed as:

PROLONGED OR REPEATED GENERALISED SEIZURES / STATUS EPILEPTICUS.

Key Clinical Pattern

The central sequence is:

SKELETAL MUSCLE NECROSIS

↓

↑ CK + MYOGLOBIN RELEASE

↓

MYOGLOBINURIA

↓

TUBULAR INJURY + HYPOVOLAEMIA

↓

ACUTE KIDNEY INJURY

At the same time:

MUSCLE NECROSIS → ↑ POTASSIUM + ↑ PHOSPHATE → ↓ CALCIUM EARLY.

The classic examination clues are:

MUSCLE PAIN/WEAKNESS + DARK URINE + MASSIVELY ↑ CK.

And remember:

URINE DIPSTICK POSITIVE FOR BLOOD + FEW/NO RBCs = THINK MYOGLOBIN.

The most immediately dangerous biochemical complication is:

HYPERKALAEMIA → ARRHYTHMIA.

The cornerstone of management is:

EARLY APPROPRIATE IV CRYSTALLOID + TREAT THE CAUSE + MONITOR/TREAT ELECTROLYTES + WATCH FOR AKI.