Overview
Rhabdomyolysis
1. Clinical Overview
Summary
Rhabdomyolysis is a potentially life-threatening syndrome resulting from skeletal muscle cell breakdown (Necrosis) with release of intracellular contents (Myoglobin, Creatine Kinase (CK), Potassium, Phosphate, Uric acid) into the circulation. The most serious complication is Acute Kidney Injury (AKI) caused by Myoglobin-induced tubular toxicity, occurring in 10-50% of cases. Causes are broadly categorised as Traumatic (Crush injury, Prolonged immobilisation, Surgery) and Non-Traumatic (Exertional, Drugs/Toxins including Statins, Infections, Electrolyte disturbances, Temperature extremes). The clinical triad is Myalgia, Weakness, and Dark (Tea-coloured) Urine, though all three may not be present. Diagnosis is based on Markedly Elevated Serum CK (Typically >5x ULN or >1000 U/L). Management involves Aggressive IV Fluid Resuscitation to prevent and treat AKI, Correction of Electrolyte Abnormalities (Especially Hyperkalaemia), and Treatment of the Underlying Cause. Renal Replacement Therapy (Dialysis) may be required for severe AKI. [1,2,3]
Clinical Pearls
"CK >5x ULN = Rhabdomyolysis": CK is the diagnostic marker. Levels can reach tens of thousands.
"Dark Urine + Positive Dipstick for Blood, But No RBCs on Microscopy = Myoglobinuria": Myoglobin is detected as "blood" on dipstick.
"Fluids, Fluids, Fluids": Aggressive IV crystalloid is the cornerstone. Aim for high urine output.
"Watch for Hyperkalaemia": Potassium released from damaged muscle can cause fatal arrhythmias.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Incidence | ~26,000 cases/year in US. Under-reported. |
| Age | Any age. Depends on cause (Exertional in young, Falls/Immobility in elderly). |
| Sex | Male > Female (More likely to engage in extreme exertion, Trauma). |
Causes (Aetiology)
| Category | Examples |
|---|---|
| Traumatic / Compressive | Crush injury (Earthquakes, Building collapse). Prolonged immobilisation (Unconscious, Post-operative, Falls in elderly). Compartment syndrome. |
| Exertional | Extreme exercise (Marathon, CrossFit, Military training). Seizures. Status epilepticus. |
| Drugs / Toxins | Statins (Especially with Fibrates, CYP3A4 inhibitors). Alcohol. Cocaine. Amphetamines. Heroin. Neuroleptic malignant syndrome (NMS). Serotonin syndrome. Carbon monoxide. Snake/Spider envenomation. |
| Infections | Influenza. COVID-19. Legionella. EBV. Coxsackie. Bacterial myositis. |
| Electrolyte Disturbances | Hypokalaemia. Hypophosphataemia. Hyponatraemia. |
| Temperature Extremes | Hyperthermia (Heat stroke, Malignant hyperthermia, NMS). Hypothermia. |
| Endocrine | Hypothyroidism. Diabetic ketoacidosis. |
| Genetic / Metabolic Myopathies | McArdle disease. CPT II deficiency. (Recurrent rhabdo). |
3. Pathophysiology
Muscle Cell Injury
- Initiating Event: Trauma, Ischaemia, Toxins, Metabolic → Muscle cell membrane damage.
- Calcium Influx: Uncontrolled Ca²⁺ entry into myocyte.
- ATP Depletion: Mitochondrial dysfunction.
- Persistent Muscle Contraction: Increases energy demand.
- Cell Necrosis: Membrane breakdown.
- Release of Intracellular Contents: Myoglobin, CK, K⁺, PO₄³⁻, Uric acid, LDH, AST.
Myoglobin-Induced AKI
- Myoglobinaemia: Myoglobin released into blood.
- Filtration: Myoglobin is filtered by glomeruli.
- Tubular Toxicity:
- Direct Tubular Toxicity: Myoglobin → Iron (Fe²⁺) → Free radicals → Oxidative injury.
- Tubular Obstruction: Myoglobin precipitates as casts with Tamm-Horsfall protein (Especially in acidic urine).
- Renal Vasoconstriction: Myoglobin scavenges nitric oxide → Vasoconstriction → Ischaemia.
- Acute Tubular Necrosis (ATN): Resulting AKI.
Factors Worsening AKI Risk
- Dehydration / Hypovolaemia.
- Acidic Urine (Promotes myoglobin precipitation).
- Pre-existing Renal Impairment.
- Very High CK (>15,000-20,000 U/L).
4. Clinical Presentation
Classic Triad
| Feature | Notes |
|---|---|
| Myalgia | Muscle pain. May be absent. |
| Muscle Weakness | May be profound. |
| Dark Urine | Tea-coloured, Cola-coloured. Myoglobinuria. |
Note: Full triad present in less than 10%. Many are asymptomatic or present with AKI.
Symptoms
| Symptom | Notes |
|---|---|
| Muscle Pain | Thighs, Calves, Back common. May be diffuse. |
| Weakness | Generalised or focal. |
| Dark Urine | Red-brown (Myoglobin). |
| Nausea / Vomiting | |
| Confusion | Electrolyte disturbance, Uraemia. |
| Oliguria / Anuria | If AKI. |
Examination Findings
| Finding | Notes |
|---|---|
| Muscle Tenderness | |
| Muscle Swelling | May be compartment syndrome. |
| Dehydration | Dry mucous membranes, Reduced skin turgor, Tachycardia, Hypotension. |
| Reduced Urine Output | |
| Confusion / Altered GCS |
Complications to Look For
| Complication | Notes |
|---|---|
| Hyperkalaemia | Life-threatening. Arrhythmias. Cardiac arrest. |
| AKI | 10-50%. May require RRT. |
| Compartment Syndrome | Especially in traumatic/Compressive causes. Emergency fasciotomy needed. |
| DIC | Rare. |
| Hypocalcaemia (Early) | Calcium sequesters in damaged muscle. |
| Hypercalcaemia (Recovery) | Calcium mobilises from muscle during recovery. |
5. Investigations
Laboratory
| Test | Findings |
|---|---|
| Serum CK (Creatine Kinase) | Markedly Elevated. Diagnostic if >5x ULN or >1000 U/L. Can reach >100,000 U/L. Peaks 24-72h. |
| Urine Dipstick | Positive for "Blood" (Myoglobin cross-reacts). |
| Urine Microscopy | Few or NO Red Blood Cells. (Dipstick positive, Micro negative = Myoglobinuria). |
| U&Es | Urea and Creatinine elevated (AKI). Hyperkalaemia. Hyperphosphataemia. Hyperuricaemia. |
| Calcium | Early: Hypocalcaemia. Late (Recovery): Hypercalcaemia. |
| LFTs | AST, ALT elevated (From muscle, Not liver). |
| Lactate | May be elevated. |
| FBC | Variable. |
| Coagulation | Check for DIC (PT, APTT, Fibrinogen, D-dimer). |
| ABG | Metabolic acidosis. |
Urinalysis
| Finding | Notes |
|---|---|
| Colour | Tea-coloured, Cola-coloured (Myoglobin). |
| Dipstick | Haem positive (Myoglobin reacts with dipstick like haemoglobin). |
| Microscopy | No or Few RBCs (Differentiates from haematuria). May see brown granular casts. |
Imaging
| Indication | Modality |
|---|---|
| Compartment Syndrome | Clinical diagnosis primarily. Compartment pressure measurement if uncertain. |
| Underlying Cause | CT/MRI if trauma, Tumour suspected. |
6. Management
Management Algorithm
RHABDOMYOLYSIS SUSPECTED
(Muscle pain/Weakness, Dark Urine, CK >5x ULN)
↓
IMMEDIATE ASSESSMENT
- Airway, Breathing, Circulation
- IV Access (Large bore x2)
- ECG (Hyperkalaemia signs?)
- Bloods: CK, U&Es, Ca, PO4, LFTs, FBC, Coag, ABG
- Urine: Dipstick, Microscopy
- Assess urine output
↓
IDENTIFY AND TREAT CAUSE
- Trauma/Crush → Fluid resuscitation, Exclude compartment syndrome
- Drug-induced → Stop offending drug (Statins)
- Infection → Antibiotics
- Hyperthermia → Active cooling
- Seizures → Treat seizures
- Electrolyte disturbance → Correct
↓
AGGRESSIVE IV FLUID RESUSCITATION (KEY TREATMENT)
┌──────────────────────────────────────────────────────────┐
│ **CRYSTALLOID (0.9% Saline or Balanced solution)** │
│ - Early, Aggressive │
│ - Initial: 1-2 L bolus │
│ - Target: Urine Output **200-300 mL/hour** (3-5 mL/kg/hr)│
│ - Typical rate: 400-1000 mL/hour initially │
│ - Continue until CK falling and AKI resolving/Prevented │
│ - Monitor for fluid overload (Especially elderly, │
│ Cardiac, Renal patients) │
│ - May need 6-10+ L/day in severe cases │
└──────────────────────────────────────────────────────────┘
↓
CORRECT ELECTROLYTE ABNORMALITIES
┌──────────────────────────────────────────────────────────┐
│ **HYPERKALAEMIA (PRIORITY)** │
│ - ECG changes? → Emergency treatment │
│ - Calcium Gluconate 10% 10mL IV (Cardioprotection) │
│ - Insulin 10 units + Glucose 50mL 50% IV │
│ - Salbutamol nebulised │
│ - Calcium Resonium / Patiromer (Eliminate K) │
│ - Dialysis if refractory │
│ │
│ **HYPOCALCAEMIA** │
│ - Generally do NOT correct unless symptomatic │
│ (Tetany, Seizures, Cardiac symptoms) │
│ - Calcium replacement can deposit in damaged muscle │
│ and cause late hypercalcaemia │
│ │
│ **HYPERPHOSPHATAEMIA** │
│ - Often corrects with fluids and diuresis │
│ - Phosphate binders if severe │
└──────────────────────────────────────────────────────────┘
↓
URINARY ALKALINISATION (CONTROVERSIAL)
┌──────────────────────────────────────────────────────────┐
│ - Sodium Bicarbonate IV may reduce myoglobin │
│ precipitation in acidic urine │
│ - Target urine pH >6.5 │
│ - **NOT routinely recommended** – Limited evidence │
│ - Risk of worsening hypocalcaemia │
│ - Focus on volume resuscitation │
└──────────────────────────────────────────────────────────┘
↓
COMPARTMENT SYNDROME SUSPECTED?
- 5 Ps: Pain (Out of proportion, On passive stretch),
Pressure, Pallor, Pulselessness (Late), Paraesthesia
- **EMERGENCY FASCIOTOMY**
↓
RENAL REPLACEMENT THERAPY (RRT)
- For severe AKI (Refractory hyperkalaemia, Acidosis,
Fluid overload, Uraemic symptoms)
- Continuous RRT (CVVH) often preferred in ICU
- Dialysis does NOT clear myoglobin effectively
(High molecular weight) but treats AKI consequences
Monitoring
| Parameter | Notes |
|---|---|
| CK | Serial. Should fall by ~50% every 24-48 hours. If rising = Ongoing injury. |
| U&Es / Creatinine | Monitor AKI. |
| Urine Output | Target 200-300 mL/hour. |
| Potassium | Frequent. Treat promptly. |
| Fluid Balance | Watch for overload. |
7. Complications
| Complication | Management |
|---|---|
| AKI (10-50%) | IV fluids. RRT if severe. Usually recovers. |
| Hyperkalaemia | As above. Cardiac arrest risk. |
| Compartment Syndrome | Fasciotomy. |
| DIC | Supportive. FFP, Platelets, Cryoprecipitate. Treat underlying cause. |
| Cardiac Arrhythmias | From hyperkalaemia, Hypocalcaemia. |
| Hypercalcaemia (Recovery) | Monitor. Usually self-limiting. |
8. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Mortality | ~5-10% overall. Higher with AKI, DIC. |
| AKI Recovery | Most patients recover renal function (If survive acute phase). ~5-10% require long-term dialysis. |
| Recurrence | Consider metabolic myopathy if recurrent unexplained episodes. Genetic testing. |
| CK Trends | Peak 24-72h. Should halve every 1-2 days with treatment. |
9. Evidence and Guidelines
Key Guidelines
| Guideline | Notes |
|---|---|
| No specific formal guideline | Management based on consensus and case series. |
Key Principles (Evidence-Based)
- Early Aggressive Fluids: Cornerstone. Prevents AKI.
- Bicarbonate: Not routinely recommended.
- Mannitol: Limited evidence. May worsen volume depletion if not given with fluids.
10. Patient and Layperson Explanation
What is Rhabdomyolysis?
Rhabdomyolysis is a condition where muscle breaks down and releases its contents into the blood. This can damage the kidneys and cause other serious problems.
What causes it?
- Severe injury or crush injuries.
- Extreme exercise (Especially if not used to it).
- Certain medications (Especially statins in some people).
- Alcohol or drug use.
- Infections.
- Being unconscious for a long time (Pressure on muscles).
What are the symptoms?
- Muscle pain and weakness.
- Dark urine (Tea or cola coloured).
- Feeling unwell.
- Reduced urination.
How is it treated?
- IV fluids: Large amounts of fluid through a drip to flush the kidneys.
- Monitoring: Blood tests to check kidney function and potassium levels.
- Treating the cause: Stopping offending medications, Treating infections.
- Dialysis: In severe cases if the kidneys fail.
Is it serious?
Yes, Rhabdomyolysis can be life-threatening if not treated promptly. With early treatment, Most people make a full recovery.
11. References
Primary Sources
- Huerta-Alardín AL, et al. Bench-to-bedside review: Rhabdomyolysis – An overview for clinicians. Crit Care. 2005;9(2):158-169. PMID: 15774072.
- Bosch X, et al. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62-72. PMID: 19571284.
- Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy. Crit Care. 2014;18(3):224. PMID: 25043142.
12. Examination Focus
Common Exam Questions
- Diagnostic Marker: "What is the key laboratory marker for rhabdomyolysis?"
- Answer: Serum Creatine Kinase (CK) – Markedly elevated (>5x ULN or >1000 U/L).
- Urine Findings: "What is the classic urine finding?"
- Answer: Dipstick positive for blood, But microscopy shows no/Few RBCs (Myoglobinuria).
- Key Treatment: "What is the cornerstone of rhabdomyolysis management?"
- Answer: Aggressive IV Fluid Resuscitation (Crystalloid, Aim for urine output 200-300 mL/hour).
- Life-Threatening Electrolyte Abnormality: "Which electrolyte disturbance is most immediately dangerous?"
- Answer: Hyperkalaemia (Risk of cardiac arrhythmias and arrest).
Viva Points
- Triad: Myalgia, Weakness, Dark urine (But often incomplete).
- Myoglobin Causes AKI: Direct toxicity, Tubular obstruction (Acidic urine), Vasoconstriction.
- Don't Correct Asymptomatic Hypocalcaemia: Can worsen later hypercalcaemia.
- Compartment Syndrome: May cause or result from rhabdomyolysis. Emergency fasciotomy.
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