Rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle breakdown with release of intracellular contents into the circulation, leading to myoglobinuria and potential acute kidney injury (AKI). It is a serious complication of compartment syndrome, crush injuries and other muscle-damaging conditions.

Causes. Orthopaedic practice must recognise crush and acute compartment syndrome, but routine admissions also arise from exertion, drugs, seizures, immobility, infection and inflammatory or metabolic myopathy.

• Compartment syndrome - the most common orthopaedic cause; rhabdomyolysis is a common complication of it, especially if delayed over 6 hours
• Crush injury - prolonged compression, as in earthquakes and building collapse
• Prolonged immobility - the unconscious patient, with pressure necrosis from immobility
• Seizures - muscle damage from convulsions
• Exertion - exercise-induced (exertional) rhabdomyolysis
• Drugs - statins and alcohol
• Heat-related illness - including heat stroke

What the muscle holds. Skeletal muscle contains high concentrations of creatine kinase (CK) and myoglobin, an oxygen-binding protein. Disruption of the muscle cell membrane releases both into the circulation.

The final common pathway. Whatever the trigger (direct trauma, ischaemia, metabolic, toxic), the end result is an uncontrolled rise in intracellular calcium. ATP depletion impairs the Na+/K+ and Ca2+ ATPase pumps, and calcium floods the myocyte, activating proteases and phospholipases that destroy the sarcolemma.

What escapes, and what is sequestered. Membrane rupture releases CK, myoglobin, potassium, phosphate, urate and purines into the circulation. Extracellular fluid and calcium are meanwhile sequestered into the damaged muscle, and this third-spacing causes hypovolaemia and early hypocalcaemia.

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The kidney. Glomeruli filter myoglobin from the blood, and it precipitates in the renal tubules, promoted by acidic urine (pH under 5.6). Tubular obstruction reduces GFR, and the result is acute tubular necrosis and AKI, with hyperkalaemia. Three mechanisms of myoglobinuric AKI are described, all favoured by hypovolaemia and aciduria:

• Renal vasoconstriction and ischaemia - hypovolaemia plus scavenging of nitric oxide by myoglobin reduces medullary blood flow
• Intratubular cast formation - myoglobin precipitates with Tamm-Horsfall protein, especially in acidic urine, obstructing distal tubules
• Direct haem-mediated tubular toxicity - iron-catalysed lipid peroxidation and free-radical injury of proximal tubular cells

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Severity is classified by complication rather than by CK, and the last column of the severity table shows why CK alone fails in each state.

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History. The history is a search for the cause: compartment syndrome, crush with prolonged compression, a period lying unconscious, seizures, exertion, heat exposure, and drugs, statins and alcohol in particular.

Examination. Look for swollen, tender muscles, weakness and myalgia, and for the signs of compartment syndrome if it is present. The systemic signs are dark, tea-coloured urine (myoglobinuria), decreased urine output, ECG changes of hyperkalaemia, and the signs of AKI: oliguria and fluid overload.

The urine. Dark urine is neither required nor specific. It may be myoglobin, haemoglobin, red cells, drugs or diet, and normal-coloured urine does not exclude rhabdomyolysis.

• Dipstick and microscopy - a haem-positive dipstick with few or no red cells supports pigmenturia but cannot by itself distinguish myoglobin from haemoglobin. Confirm pigmenturia with the clinical context, CK and microscopy; haemoglobinuria and haematuria remain alternatives.
• Output - oliguria or anuria is a renal and haemodynamic warning and makes fixed-volume loading hazardous.

Differential Diagnosis

Dark urine and the "blood-positive dipstick with no red cells" picture have a short, high-yield differential. The key discriminators are the serum CK and urine microscopy.

The diagnosis. A compatible muscle injury plus CK elevation above the laboratory upper limit; definitions vary by laboratory and context. At assessment, send CK, potassium, bicarbonate, phosphate, calcium, creatinine and urea, and urinalysis with microscopy, record an ECG when risk warrants, and add tests for the suspected cause and its complications.

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Reading the CK. The trend supports the burden and timing of the injury, but it does not independently choose fluids, ICU or dialysis. Cause, creatinine, potassium, phosphate, bicarbonate, haemodynamics and comorbidity predict immediate risk better than a universal threshold.

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Monitoring. Repeat potassium and ECG, renal function, CK and any other abnormality often enough to act on change. Frequency follows trajectory and organ dysfunction rather than a universal 6-12-hour rule.

Stepping down. Reduce monitoring when all of these hold:

• The cause is controlled
• CK is convincingly falling
• Electrolytes and renal function are stable or improving
• Oral intake is adequate and a safe follow-up plan is in place
• No compartment or systemic complication remains

CK need not fall below a universal 5,000 U/L before de-escalation or discharge; cause, symptoms, renal and electrolyte status and trajectory decide.

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The principle. Treat the cause and the physiology, not a CK band. What kills early is hyperkalaemia, shock, heat illness, sepsis and the underlying injury, and the commonest mistake is treating a CK number while missing source control or causing fluid overload.

Immediate priorities. Physiology comes before the CK number.

1. Stop the cause and assess for heat illness, shock, sepsis, crush injury, acute compartment syndrome, toxin/drug effect or inherited/inflammatory myopathy.
2. Check potassium/ECG, renal function, acid-base status and haemodynamics before focusing on CK.
3. Correct hypovolaemia with isotonic crystalloid; reassess lungs, perfusion, urine and creatinine frequently.
4. Treat hyperkalaemia and other organ emergencies by standard protocols.
5. Involve critical care, nephrology, toxicology, metabolic/neuromuscular or surgery according to the cause and complications.

Fluids. Give isotonic crystalloid early when hypovolaemia, crush injury or renal-risk physiology warrants it, choosing bolus and rate from blood pressure, perfusion, body size, losses, cardiac and renal reserve and response. Reassess lungs, weight and fluid balance, creatinine, urine output and congestion as you go.

No universal urine target. There is no universal 200 mL/hour or 3 mL/kg/hour urine goal; the endpoint is patient-specific, set by perfusion, body size, ongoing losses, renal response and congestion. Anuric patients and those with heart or renal failure can be harmed by fixed high-volume targets. Do not force diuresis in anuria or pulmonary congestion, and stop escalating fluid when anuria, pulmonary oedema or another harm emerges.

Reconciling the crush literature. The crush-injury reviews in the Evidence Base advocate early, vigorous volume loading, up to 12 L a day of alkaline fluid, begun at the scene, before or during extrication. Their enduring lesson is timing, not the composition of the fluid: in crush injury, begin isotonic resuscitation early when hypovolaemia or crush physiology supports it. The volumes come from young, previously well casualties who were closely monitored, and large fixed volumes may harm elderly, cardiac, anuric or delayed patients.

Hyperkalaemia. Record an ECG and repeat the potassium promptly when muscle destruction is substantial. Treatment follows the ECG and emergency severity: membrane stabilisation when indicated, intracellular shift, potassium removal and repeated monitoring. The exact drug and dose follow the current local resuscitation protocol and patient factors, and bicarbonate is not universally effective outside acidotic contexts. Involve nephrology or critical care when hyperkalaemia is refractory or organ failure develops.

Bicarbonate and mannitol. A physiological rationale exists for alkaline urine, but comparative observational data do not show that routine bicarbonate or mannitol improves renal failure, dialysis or mortality beyond volume care. Routine bicarbonate, mannitol or loop-diuretic forced diuresis has no proven renal benefit, and a urine-pH target is not routine rhabdomyolysis therapy. Use either agent only for another defined indication, bicarbonate for an established acid-base or hyperkalaemia indication, with electrolyte, acid-base and volume monitoring.

Renal replacement therapy. Dialysis or continuous therapy is started for the standard AKI indications:

• Refractory hyperkalaemia
• Severe acidosis
• Pulmonary oedema or volume overload
• Uraemic complications
• Otherwise unmanageable organ failure

A CK level, dark urine, or theoretical or prophylactic myoglobin clearance is not by itself an indication.

Rhabdomyolysis itself has no surgical procedure. Operate only for a surgical source such as diagnosed acute compartment syndrome, infected or necrotic muscle, ischaemic nonviable tissue or another limb-threatening lesion.

Diagnosing the compartment. Acute compartment syndrome is diagnosed clinically. Pressure monitoring is an adjunct that supports equivocal or unexaminable cases, and should not be reduced to one number detached from trajectory.

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Fasciotomy. Use the region-specific approach and release every involved compartment while protecting the neurovascular structures. Judge muscle by colour, consistency, contractility and bleeding in context, debride clearly nonviable or infected tissue, and plan re-look surgery when viability is uncertain. Manage the wounds according to swelling, contamination and reconstruction needs.

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The crush or nonviable limb. Limb salvage, fasciotomy, delayed debridement or amputation depends on ischaemia duration, viability, contamination, systemic instability, reconstructability and patient context. An elevated CK is not an amputation indication, and fasciotomy of late nonviable muscle can increase bleeding and infection without restoring function.

The kidney after the event. AKI incidence and recovery vary widely by cause and organ-failure burden. Temporary dialysis is common in some cohorts, but neither complete recovery nor chronic impairment can be promised from CK alone.

After fasciotomy or debridement, manage the limb and the systemic injury in parallel.

• Reassess every compartment and muscle viability when deterioration suggests ongoing ischaemia, necrosis or infection
• Monitor the wound, perfusion, neurology and planned re-look or closure
• Trend potassium and ECG, renal function, acid-base status, CK and fluid balance at intervals matched to instability
• Give crystalloid only to haemodynamic or renal need, for perfusion and ongoing loss, while avoiding pulmonary oedema and anuric overload
• Do not start routine bicarbonate because a fasciotomy has been done

Monitoring steps down by the same criteria as for any patient (see Investigations).

Cause and organ failure decide. Exertional and seizure cases with stable kidneys can recover quickly despite a very high CK, whereas sepsis, heat stroke, crush syndrome, cardiac arrest, DIC or established AKI carry greater risk. CK normalisation time and mortality cannot be summarised by one universal number.

Predicting risk. Outcome is better estimated from admission physiology and multivariable tools such as the McMahon score than from peak CK alone: the cause, the McMahon variables, AKI and electrolytes, and organ failure. The score supports risk communication and level-of-care planning; it is not a fluid or dialysis trigger.

What to track. Survival, renal recovery and dialysis, electrolyte complications, limb and muscle function, recurrent episodes and the underlying diagnosis.

Crush-related rhabdomyolysis remains a disaster-medicine problem, while routine hospital cases more often follow drugs/toxins, exertion, seizures, immobility, infection or inflammatory/metabolic myopathy. AKI risk varies markedly by cause and organ physiology.

Resource-limited settings should prioritise early recognition, basic electrolytes/ECG, careful fluid reassessment, compartment/source control and timely transfer for renal replacement capability. Bicarbonate availability is not the determinant of good care.

Related pages: Compartment Syndrome, Crush Syndrome, Compartment Syndrome of the Leg, Forearm Compartment Syndrome, and Foot Compartment Syndrome.

Much of "classic" rhabdomyolysis management is based on physiology and observational data rather than randomised trials. The exam-relevant debates are:

The etiology table and Scenario 3 both invoke exertional rhabdomyolysis, and the sports-medicine guidance flags screening for "recurrent/atypical cases and inherited metabolic myopathy before return to sport" - but the underlying disease is never developed. This is a distinct, high-yield strand: most exertional cases are self-limiting, but a minority signal a genetic muscle disorder that changes counselling and return-to-play.

Exertional (exercise-induced) rhabdomyolysis typically follows unaccustomed, intense or eccentric exercise, often compounded by heat, humidity, dehydration, sleep deprivation or stimulant/supplement use. Compared with crush injury, CK elevations are usually lower and acute kidney injury is uncommon (McMahon and colleagues found exercise carried one of the lowest rates of dialysis or death). Sickle cell trait is a recognised risk factor for exertional collapse and rhabdomyolysis under extreme exertion, and drugs (statins, especially with fibrates, and alcohol) lower the threshold.

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The "Outcomes and Prognosis" section lists prognostic factors qualitatively ("higher CK = worse prognosis", "delayed treatment = higher AKI risk"). The examinable upgrade is that these have been combined into a validated admission risk score that quantifies who needs intensive monitoring and early nephrology.

The McMahon score was derived and validated in 2,371 patients with CK over 5,000 U/L across two Boston teaching hospitals. It combines eight admission variables: age, female sex, initial creatinine, initial CK, phosphate, calcium, bicarbonate, and the cause of rhabdomyolysis (seizure, syncope, exercise, statin or myositis attracting negative/protective weighting versus other causes). It predicts the composite of renal replacement therapy or in-hospital death - not a treatment threshold - with good discrimination (C-statistic about 0.82-0.83).

• A low score (under 5) carried roughly a 2-3% risk of dialysis or death.
• A high score (over 10) carried roughly a 61% risk - a very different level of care.
• Cause dominates outcome: the highest composite-event rates were after cardiac arrest, sepsis and compartment syndrome, while myositis, exercise and seizures carried the lowest.

This reframes the exam answer: rather than fixating on a single CK cut-off, use the whole admission picture - age, renal function, electrolytes and the cause - to decide who is triaged to ICU, early nephrology and closer surveillance.