Rhabdomyolysis
Syndrome of skeletal muscle breakdown with release of intracellular contents (myoglobin, CK, potassium, phosphate) into the circulation. A major cause of AKI due to myoglobin-induced tubular obstruction and toxicity. Requires aggressive IV fluid resuscitation.
Key Facts
Rhabdomyolysis is characterised by CK >5× ULN (typically >5,000 IU/L, often >10,000 IU/L) with muscle pain, weakness, and dark urine Common causes: trauma/crush injury, immobilisation, excessive exercise, drugs (statins, cocaine, ecstasy), seizures, hyperthermia AKI develops in 20-40% due to myoglobin toxicity: tubular obstruction, vasoconstriction, and oxidative injury Dark brown/cola-coloured urine that is dipstick-positive for blood but no red cells on microscopy (myoglobinuria) Hyperkalaemia is a major early life-threatening complication (K+ released from damaged muscle) Treatment: aggressive IV 0.9% NaCl (200-1000 mL/hr initially; target urine output >200-300 mL/hr) Sodium bicarbonate: controversial; may be added to alkalinise urine (pH >6.5) to reduce myoglobin precipitation; evidence limited Dialysis if refractory hyperkalaemia, acidosis, or severe AKI
Overview
Key Facts
Rhabdomyolysis is a common cause of AKI, particularly in trauma and recreational drug use. Early aggressive fluid resuscitation is the key intervention to prevent renal failure.
Epidemiology
- ~26,000 cases/year in the US; UK data limited but common
- AKI develops in 20-40% of cases
- Mortality: 5-10% overall; higher in trauma and multi-organ failure
Aetiology
Traumatic: crush injury, compartment syndrome, surgery, immobilisation, falls Non-traumatic: excessive exercise, seizures, drugs (statins, fibrates, cocaine, ecstasy/MDMA, amphetamines, alcohol), infections (influenza, COVID-19, Legionella), metabolic (hypokalaemia, hypophosphataemia), hyperthermia (NMS, serotonin syndrome, malignant hyperthermia), hypothermia, metabolic myopathies (McArdle disease)
Pathophysiology
- Muscle cell membrane damage → uncontrolled calcium influx → mitochondrial dysfunction → cell death
- Release of intracellular contents: myoglobin, CK, potassium, phosphate, urate, LDH
- Myoglobin nephrotoxicity: direct tubular toxicity, tubular obstruction (myoglobin casts), renal vasoconstriction
- Acidic urine promotes myoglobin precipitation (ferrihemate form)
- Hyperkalaemia (early, life-threatening), hyperphosphataemia, hypocalcaemia (calcium deposited in damaged muscle)
- Late hypercalcaemia during recovery phase (mobilisation of calcium from muscle)
Clinical Presentation
Classic Triad
- Muscle pain/tenderness: localised or generalised
- Weakness: may be profound
- Dark brown/tea-coloured urine (myoglobinuria)
Other Features
- Swelling of affected muscle groups
- Compartment syndrome: severe pain, tense compartment, pain on passive stretch
- AKI: oliguria, fluid overload
- Systemic: malaise, fever, tachycardia, nausea
Metabolic Complications
- Hyperkalaemia: early and dangerous (cardiac arrest risk)
- Hyperphosphataemia: early
- Hypocalcaemia: early (calcium deposition in muscle)
- Hyperuricaemia: tumour lysis-like picture
- Metabolic acidosis: lactic acidosis from muscle ischaemia
- DIC: in severe cases
Red Flags
- Hyperkalaemia >6.5 → emergency management
- Compartment syndrome → urgent fasciotomy
- Anuria + massively elevated CK → early dialysis consideration
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Acute myocardial infarction | CK-MB and troponin elevated, chest pain | ECG, troponin |
| Inflammatory myopathy | Proximal weakness, rash (dermatomyositis) | CK, EMG, biopsy |
| Statin myopathy | Muscle pain on statins, CK mildly elevated | Drug history, CK |
| Hypothyroidism | Fatigue, mildly elevated CK, slow relaxation | TFTs |
| Haemoglobinuria | Dark urine, haemolysis | Blood film, haptoglobin, Coombs |
| Porphyria | Dark urine on standing, abdominal pain | Urine porphyrins |
Diagnosis / Investigation
Bloods
- CK: markedly elevated (>5× ULN; often >10,000 IU/L; can exceed 100,000)
- U&Es: potassium (high), creatinine (elevated in AKI), sodium
- Calcium: initially low (deposited in muscle); may rebound high during recovery
- Phosphate: elevated
- Urate: elevated
- LDH: elevated
- ABG: metabolic acidosis, lactate
- FBC: may show haemoconcentration
- Coagulation: DIC screen if severe
- Myoglobin: serum and urine (clears faster than CK; may be normal by time of presentation)
Urine
- Dipstick: positive for blood (myoglobin cross-reacts with haem on dipstick)
- Microscopy: no red cells (distinguishes myoglobinuria from haematuria)
- Urine myoglobin: if available
Imaging
- Compartment pressure monitoring: if compartment syndrome suspected (pressure >30mmHg or within 30mmHg of diastolic)
- CT/MRI: not routine; may show muscle oedema
Management
Emergency Management
- Aggressive IV fluid resuscitation: 0.9% NaCl at 200-1000 mL/hr initially
- Target urine output: 200-300 mL/hr (some guidelines say ≥3 mL/kg/hr)
- Large volumes required (often 6-10L in first 24 hours)
- Treat hyperkalaemia urgently: calcium gluconate, insulin-dextrose, salbutamol, dialysis if refractory
- Monitor: hourly urine output, 4-hourly U&Es, CK 12-hourly
Supportive
- Sodium bicarbonate 1.26%: controversial; some advocate to alkalinise urine (target pH >6.5) to prevent myoglobin precipitation; limited evidence
- Avoid calcium replacement for hypocalcaemia unless symptomatic (tetany, seizures) – as calcium deposits in damaged muscle and rebounds during recovery
- Mannitol: some evidence for increasing renal blood flow; not standard
- Dialysis: for refractory hyperkalaemia, severe acidosis, fluid overload, or uraemia
Specific
- Compartment syndrome: emergency fasciotomy (within 6 hours)
- Stop causative drug: statins, cocaine, etc.
- Treat underlying cause: sepsis, seizures, hyperthermia
- Dantrolene: for malignant hyperthermia, NMS
Referral
- Severe rhabdomyolysis (CK >10,000) → nephrology involvement
- Compartment syndrome → orthopaedic surgery
- Recurrent unexplained rhabdomyolysis → metabolic myopathy workup
Prognosis
- Overall mortality: 5-10%; higher in trauma and multi-organ failure
- AKI requiring dialysis: mortality 20-30%
- Most AKI is reversible with adequate fluid resuscitation
- CK peak at 24-72 hours; levels >15,000-20,000 IU/L associated with higher AKI risk
- Compartment syndrome: if untreated, leads to permanent muscle/nerve damage and limb loss
- Recurrent rhabdomyolysis: consider metabolic myopathy (McArdle disease, CPT-II deficiency)
Other Relevant Information
Causes of Rhabdomyolysis (Mnemonic: CRUMPLED)
| Letter | Cause |
|---|---|
| C | Crush injury, compartment syndrome |
| R | Running (extreme exercise) |
| U | Uncontrolled seizures |
| M | Medications (statins, recreational drugs) |
| P | Pyrexia (NMS, malignant hyperthermia) |
| L | Lying on hard surface (immobilisation, overdose) |
| E | Electrolyte abnormalities (hypokalaemia) |
| D | Dermatomyositis/polymyositis |
CK Levels and Risk
| CK Level | AKI Risk |
|---|---|
| <5,000 | Low (<5%) |
| 5,000-15,000 | Moderate (10-20%) |
| >15,000 | High (>30%) |
| >50,000 | Very high (>50%) |