Rhabdomyolysis

Meet the patient

A 24-year-old man who has not trained in a year does a hundred deep squats on his first day back at the gym. By morning his thighs are swollen and rigid, he cannot straighten up to stand, and the toilet bowl is dark red-brown. His CK is over 50,000 U/L and his creatinine is climbing.[1][2]

Two questions decide his next hour, and they decide every rhabdomyolysis you will ever see: which electrolyte will arrest his heart first? (hyperkalaemia — the early killer) and can you flush the kidney before the myoglobin precipitates in the tubules? (aggressive saline — the one treatment that actually works). Hold those two and the rest of the page slots in.[1][5]

Overview & Definition

Rhabdomyolysis is a final-common-pathway emergency: muscle dies, its contents leak, and the kidney and the heart pay the bill. The sarcolemma ruptures — or ATP runs out — and myoglobin, creatine kinase, potassium, phosphate and urate pour into the circulation. Myoglobin is small enough to filter at the glomerulus and toxic to the tubule; potassium stops the heart; phosphate strips the calcium.[1]

Every "different" emergency on the take-in board converges on this one pathway — the earthquake crush victim, the untrained squatter, the status-epilepticus, the statin user, the cocaine or MDMA overdose, the heat-stroke casualty, the Russell's viper bite, the patient found unconscious on the floor. One cheap biomarker makes the call — creatine kinase, CK — and one cheap treatment changes the outcome: saline, early and fast.[1]

The classic trap: the textbook picture of muscle pain, weakness and cola urine is unmistakable — and present in only a minority. The unconscious, the sedated and the elderly walk in with no muscle story at all. The first clue is often a creatinine that has jumped for no reason; the second is a urine dipstick positive for blood with no red cells on microscopy. Miss that pairing and you miss the diagnosis.[1]

Etymology for viva gold: rhabdo- from the Greek rhabdos, "rod"; -myo from mys, "muscle"; -lysis, "a loosening" or "dissolution". The rod-shaped skeletal myocyte dissolves. Myoglobin — the muscle sibling of haemoglobin — is the molecule that poisons the tubule.[1]

Classification

Classify by cause — because treating the cause is as important as the fluid. One pathological endpoint, a very broad aetiology; the classification examiners want is by precipitant. Name the group and you name the antidote.[1][5]

The MUSCLES groups — memorise the clusters, not the list:[1]

• Trauma, crush and ischaemia — earthquake and building collapse (crush syndrome), prolonged immobilisation (the patient on the floor, prolonged coma, overdose), compartment syndrome, arterial occlusion, tourniquet, burns, electrical injury and lightning.
• Exertion — strenuous exercise in the untrained (squats, Spin, military training, marathons), status epilepticus, delirium or agitation, severe asthma, tetany; worse when hot, dehydrated or at altitude.
• Drugs and toxins — statins are the single commonest drug cause (high-dose, or with fibrates, macrolides, cyclosporin, azole antifungals, daptomycin); fibrates; alcohol (direct toxicity plus withdrawal and electrolyte shifts); cocaine, amphetamines and MDMA; neuroleptic malignant and serotonin syndromes; succinylcholine (especially in burns, denervation or prolonged immobility).
• Infection — influenza A and B, coxsackievirus, EBV, HIV, legionella, Streptococcus pyogenes (necrotising myositis), Clostridium perfringens (gas gangrene), malaria (Plasmodium falciparum — blackwater fever), and any severe sepsis.
• Electrolyte and endocrine — hypokalaemia (the commonest silent precipitant, because it predisposes muscle to ischaemia), hypophosphataemia, hyponatraemia, hypothyroidism (myxoedema myopathy), DKA and HHS (hypokalaemia and hypophosphataemia on top of osmotic diuresis).
• Temperature extremes — heat stroke, hypothermia, malignant hyperthermia (anaesthetic-triggered).
• Inherited and metabolic myopathies — McArdle disease (myophosphorylase deficiency), CPT II deficiency, mitochondrial myopathies, muscular dystrophies. Suspect these when rhabdomyolysis is recurrent, exertion-triggered, or in a child or young adult with a family history.
• Inflammatory — polymyositis, dermatomyositis.
• Others — snake bite (Russell's viper, sea snake), hornet or wasp sting, electrocution, prolonged tourniquet, sickle-cell trait (exertional sickling).[1][2]

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Epidemiology & Risk Factors

Rhabdomyolysis is the hidden cause of roughly 7 to 15 per cent of all adult AKI — and the number is underestimated, because the mild cases are never sent a CK. Among those who present with established disease, AKI develops in 15 to 33 per cent, and the risk steepens the moment peak CK crosses 5000 U/L.[5][6]

The commonest single cause in the adult emergency department is prolonged immobilisation — the patient found on the floor — followed by drugs and toxins, then exertion. In children the script flips: viral myositis (especially influenza B) and exertion dominate.[1]

Who is most likely to develop it (the susceptibility list):[1]

• Prior statin or fibrate use — high-dose, or with interacting drugs (fibrates, macrolides, cyclosporin, azole antifungals); add hypothyroidism.
• Dehydration, heat, exertion at altitude — each amplifies exertional injury.
• Electrolyte disturbance, especially hypokalaemia and hypophosphataemia.
• An underlying inherited or inflammatory myopathy — lowers the threshold.
• Sickle-cell trait — predisposes to exertional sickling, rhabdomyolysis and sudden death in athletes and recruits.
• Chronic kidney disease — any given muscle injury tips into dialysis-requiring AKI sooner.
• Male sex and young age — exertional cases cluster in young men; the untrained weekend warrior is the classic stem.[2][5]

The mass-casualty trap — crush syndrome: when a limb is crushed under rubble, the muscle dies under pressure. The killing blow comes at reperfusion, when the weight is lifted and a wave of potassium and myoglobin floods the circulation — sudden lethal hyperkalaemia and AKI. This is why the Renal Disaster Relief Task Force protocol starts saline before extrication, not after.[3]

Pathophysiology

Whatever the trigger, the final pathway is one event: calcium floods the dying myocyte, and the cell's own enzymes digest it. Sarcolemma rupture (mechanical, thermal, electrical, ischaemic or toxin) or ATP depletion (ischaemia, glycolytic defect) raises free intracellular calcium, which switches on calpains and phospholipases — and they eat the contractile apparatus and the membrane from the inside.[1]

The cascade, step by step:[1]

1. Insult damages the sarcolemma directly (crush, exertion, toxin, heat) and/or depletes ATP (ischaemia, glycolytic defect).
2. The Na/K and Ca pumps fail — they are ATP-dependent. Sodium and water rush in (oedema); calcium rushes in.
3. Calcium accumulation activates calpains (proteases) and phospholipase A2, which digest the contractile proteins and the membrane itself.
4. Myonecrosis releases the intracellular cargo — myoglobin, CK, potassium, phosphate, urate and lactate dehydrogenase — into the circulation.
5. Volume sequesters into the oedematous muscle, producing hypovolaemia that compounds renal hypoperfusion.
6. Myoglobin reaches the kidney and causes pigment nephropathy (three mechanisms, below).
7. Potassium drives hyperkalaemic arrhythmia; phosphate precipitates calcium; tissue factor and activated clotting factors drive DIC.[1][5]

Why myoglobin is the kidney-killer — three mechanisms of pigment nephropathy:[1][5]

• Renal vasoconstriction — myoglobin scavenges nitric oxide; the vasoconstriction, on top of hypovolaemia, cuts renal blood flow and glomerular filtration.
• Tubular cast obstruction — at acidic urine pH, myoglobin (its ferrihemate moiety) precipitates with Tamm-Horsfall protein into pigmented granular casts that block the distal tubule.
• Free-radical cytotoxicity — free iron from myoglobin generates reactive oxygen species that injure the tubular epithelium and produce acute tubular necrosis.[1]

The electrolyte derangements — and the reason each one matters:[1]

• Hyperkalaemia — potassium released from dead muscle, compounded by AKI and acidosis. The commonest cause of EARLY death: arrhythmia.
• Hypocalcaemia (early) — calcium precipitates as calcium-phosphate in necrotic muscle, driven by the hyperphosphataemia. Do NOT treat early hypocalcaemia unless symptomatic — it rebounds.
• Rebound hypercalcaemia (late, in recovery) — the deposited calcium is remobilised as the muscle heals.
• Hyperphosphataemia and hyperuricaemia — released from muscle; each worsens tubular injury.
• High anion-gap metabolic acidosis — released organic acids plus the failing kidney.[1]

The compartment-syndrome vicious cycle: muscle oedema inside a tight fascial compartment raises interstitial pressure, occludes venous then capillary flow, deepens the ischaemia, and extends the injury. A swollen, tight, painful limb in rhabdomyolysis is not "just swollen" — it wants a pressure measurement and, if positive, a fasciotomy.[1]

Clinical Presentation

The classic triad — muscle pain, weakness and dark urine — is the minority presentation. Many patients, especially the unconscious or sedated, have no muscle symptoms at all. The first clue is the toilet, the creatinine, or the potassium.[1]

What you actually see:[1]

• Muscle — aching, tenderness, swelling and stiffness, most often in the calves, thighs, lower back and shoulders; proximal weakness, sometimes ascending. Exertional cases localise to the worked group.
• Urine — dark, tea- or cola-coloured (myoglobin). Dipstick positive for "blood" but microscopy shows no, or very few, red cells — the cardinal bedside clue.
• General — fever, nausea, vomiting, malaise, dehydration (fluid has sequestered into the muscle).
• Compartment features — a swollen, tense, tender compartment, pain on passive stretch, paraesthesia (see below).
• Hyperkalaemia features — palpitations, chest pain, and the ECG: peaked T waves, PR prolongation, QRS widening, sine-wave VT, then collapse.[1][5]

The presentations that get missed — learn them by name:[1]

• The patient found on the floor — no history; the first clue is dark urine, a raised CK, hyperkalaemia or AKI on the admission bloods.
• The septic or ICU patient — rhabdomyolysis hidden under the primary illness; the CK is sent for an unexplained AKI or a potassium that keeps climbing.
• The elderly or diabetic — silent muscle injury (neuropathy, immobility); presents with falls and confusion.
• The child with influenza and a limp — benign acute childhood myositis (calf pain, refusal to walk) can progress to genuine rhabdomyolysis.[1]

Differential Diagnosis

Dark urine plus a dipstick positive for "blood" has four causes — split them with the microscope and the plasma.[1]

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A raised CK is not always rhabdomyolysis — know the other reasons, and reach for troponin when the heart is in question.[1]

• Cardiac — CK-MB fraction, or better, troponin. Rhabdomyolysis can co-raise CK-MB through skeletal-muscle MM cross-reactivity; troponin is cardiac-specific.
• Recent exercise, IM injection, seizure, prolonged immobility, hypothyroidism — all lift CK modestly without true rhabdomyolysis.
• Inflammatory myopathy (polymyositis, dermatomyositis), muscular dystrophy, MELAS or mitochondrial disease — chronic, with weakness but a smaller CK rise.
• Macro-CK — a benign macro-enzyme artefact; the cause of a persistently unexplained CK in an asymptomatic adult.[1]

Three hyper-metabolic syndromes produce rhabdomyolysis — the discriminator is the trigger, the speed, and the drug that reverses it.[1]

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Clinical & Bedside Assessment

ABCDE first — then hunt the cause and the two life-threats: hyperkalaemia and compartment syndrome. Put the cardiac monitor on at the door; hyperkalaemia kills in minutes, and the ECG will show it before the lab does.[1]

Vital signs drive the whole admission — heart rate, blood pressure, respiratory rate, oxygen saturation, temperature, GCS, and hourly urine output via a catheter. Watch the ECG for peaked T waves, PR prolongation, QRS widening and sine-wave ventricular tachycardia; any of them is a cardiac arrest in progress.[1]

The 5 Ps of acute compartment syndrome — reproduced verbatim:[1]

• Pain — severe, out of proportion to the injury, worse on passive stretch of the compartment muscles. The earliest and most sensitive sign.
• Paraesthesia — early; numbness in the distribution of the nerves traversing the compartment.
• Pallor, Poikilothermia, Pulselessness — late and ominous.
• Confirm with compartment pressure measurement: a delta pressure (diastolic BP minus compartment pressure) under 30 mmHg, or an absolute pressure over 30 mmHg, mandates urgent fasciotomy.[1]

The classic trap: a pulse is still present until very late in compartment syndrome. "The pulse is fine" must never reassure you — by the time the pulse goes, the muscle is already dead. Pain out of proportion and pain on passive stretch are the signs that matter; pulselessness is a sign of failure.[1]

Bedside assessment of cause — history and examination for trauma, exertion, drugs (prescribed and recreational), infection, seizure, endocrine or electrolyte disturbance, hypothyroidism, snake or insect bite, heat or cold exposure, and a family history of recurrent exertional rhabdomyolysis (inherited myopathy).[1]

Bedside assessment of severity — the peak CK loosely tracks AKI risk and sets the fluid intensity. Any CK over 1000 U/L, any hyperkalaemia, any oliguria, or any sign of compartment syndrome is an immediate admission for aggressive IV fluids.[1][5]

Investigations

First-line bloods — CK is the diagnostic marker; potassium is the lethal one.[1][5]

• Creatine kinase (CK) — the diagnostic marker (normal under 200 U/L). Rises within 12 hours, peaks at 1 to 3 days, and declines over 3 to 5 days (longer with ongoing injury). A value over 5 times the upper limit of normal (often stated as over 1000 U/L) with the right clinical context is diagnostic; over 5000 U/L marks high AKI risk, and levels above 15,000 to 20,000 U/L carry a very high risk of AKI.
• Urea and electrolytes — potassium elevated (the lethal early derangement); creatinine elevated disproportionate to urea (a creatinine-to-urea ratio that looks "too high" for the dehydration is a classic clue — myoglobin is an extra substrate).
• Calcium, phosphate, magnesium — calcium low initially (precipitation), phosphate high; rebound hypercalcaemia later in recovery.
• AST and ALT — both elevated (released from muscle, not just liver); a "transaminitis" in rhabdomyolysis does not necessarily mean liver injury.
• Urate, LDH — elevated (released from muscle).
• Venous blood gas / lactate — high anion-gap metabolic acidosis, raised lactate.
• Coagulation (PT, aPTT, fibrinogen, D-dimer) — to detect DIC.
• Troponin — to separate cardiac from skeletal-muscle injury.
• FBC — leucocytosis, thrombocytopenia (DIC).
• TSH, cortisol — if an endocrine precipitant is suspected.
• Blood cultures, viral serology (influenza PCR) — when infection is the trigger. [1]

Urine — the bedside signature is dipstick-positive for blood with no red cells on microscopy.[1]

• Dipstick — positive for blood (orthotolidine reacts with the haem of myoglobin).
• Microscopy — no (or very few) red cells; pigmented granular casts are characteristic. This dipstick-positive / microscopy-negative pattern is the bedside signature of pigment nephropathy.
• Urine myoglobin — qualitative, slow, NOT routinely needed (serum myoglobin peaks at 6 to 8 hours and clears by 24 hours, so it is often normal by the time the diagnosis is suspected). CK is cheaper, universally available and tracks severity — that is why CK, not myoglobin, is the diagnostic and monitoring marker.[1]

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Imaging and procedures — none of them diagnoses rhabdomyolysis; the CK does. Imaging finds the cause and the complications.[1]

• ECG — mandatory, looking for hyperkalaemic changes (peaked T waves, PR prolongation, QRS widening, sine-wave, VT/VF).
• Compartment pressure measurement — when compartment syndrome is suspected (delta pressure under 30 mmHg is diagnostic).
• Ultrasound / CT — to identify an abscess, necrotising infection, vascular occlusion, or underlying cause; no imaging is needed to diagnose rhabdomyolysis itself (CK is the test).
• Renal ultrasound — to exclude obstruction as a contributor to AKI. [1]

Renal replacement therapy — the A-E-I-O-U indications

Management — Resuscitation

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Resuscitation is ABCDE plus three non-negotiables: a cardiac monitor, aggressive saline, and a catheter for hourly urine. Two large-bore cannulae; bloods including CK, potassium, creatinine, calcium, phosphate, coagulation and troponin; a urethral catheter from the moment of arrival.[1]

The cornerstone is aggressive IV crystalloid — and the reason is mechanical: flush myoglobin through the kidney before it precipitates in the tubules. Muscle oedema has sequestered litres of volume; saline restores perfusion, lifts glomerular filtration, and dilutes the pigment. Start early, start fast.[1][5]

• Fluid: 0.9 per cent saline or balanced crystalloid (Lactated Ringer's / Plasma-Lyte); alternating saline with a balanced solution avoids hyperchloraemic acidosis.
• Rate: 1 to 1.5 L/h initially (up to 1 L/h even before extrication in crush), titrated to a target urine output of 1 to 3 mL/kg/h — roughly 200 to 300 mL/h in an adult (about 300 mL/h) — until the CK is clearly falling. Patients commonly need 6 to 12 L in the first 24 hours; monitor hourly fluid balance to avoid pulmonary/cerebral oedema.
• When to ease back: when the CK is falling, urine output is established, electrolytes are stable — typically at 24 to 72 hours.[1][3]

Consultant confession: the single thing that separates the patient who ends up on dialysis from the one who does not is how early the saline went in — not which crystalloid, not bicarbonate, not mannitol. I have never regretted starting fluids too early; I have regretted waiting for the creatinine to climb.[1][4]

Treat hyperkalaemia the moment the ECG changes — do not wait for the lab. IV calcium gluconate 10 per cent, 10 mL over 2 to 5 minutes (membrane stabilisation), then insulin-dextrose (10 units soluble insulin in 25 to 50 g IV dextrose), nebulised salbutamol 10 to 20 mg, and sodium bicarbonate — especially useful here, where the patient is acidotic. You are buying time by shifting potassium into cells; definitive removal needs RRT once the AKI is established.[1]

Stop every nephrotoxin on the chart — NSAIDs, ACE inhibitors, angiotensin-receptor blockers, iodinated contrast, aminoglycosides, metformin — and the culprit drug, usually the statin.[1]

The first-hour bundle — order matters; calcium before fluids if the ECG shows hyperkalaemia:[1][5]

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Management — Definitive & Stepwise

Step 1 — treat the cause. This is non-negotiable; fluids alone will not save the patient whose statin is still running or whose heat stroke is still cooking.[1]

• Stop the offending drug (statin, fibrate, cocaine, neuroleptic).
• Treat infection (influenza antivirals, sepsis bundle, antimalarials for falciparum).
• Correct electrolyte and endocrine derangement (potassium, phosphate, thyroid replacement).
• Control seizures, cool the heat-stroke patient, warm the hypothermic patient.
• Give dantrolene for malignant hyperthermia or NMS; cyproheptadine for serotonin syndrome.
• Give snake antivenom for elapid/viper envenomation per regional protocol.[1][1]

Step 2 — aggressive fluid therapy, as above. The cornerstone, repeated because it bears repeating.[3]

Step 3 — adjuncts (bicarbonate and mannitol): controversial, and not first-line. Modern trauma-society practice is fluid-first.[1]

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Step 4 — manage the complications. Compartment syndrome, DIC, and AKI each have their own move.[1]

• Compartment syndrome — measure compartment pressure; delta pressure under 30 mmHg (or absolute over 30 mmHg) mandates urgent fasciotomy. Restore volume and correct coagulopathy BEFORE fasciotomy to avoid catastrophic bleeding and reperfusion; anticipate a potassium/myoglobin surge at the moment of release.[1]
• DIC — supportive; blood-product support as guided by coagulation and bleeding.
• AKI — fluids (the prevention), avoid nephrotoxins, renal replacement therapy for the A-E-I-O-U indications (intermittent haemodialysis or continuous RRT in the haemodynamically unstable).[1]

Step 5 — disposition. Admit any CK over 1000 U/L, any hyperkalaemia, any AKI, any compartment concern, any unstable cause. Discharge only when the CK is falling, electrolytes and renal function are stable, the cause is addressed, and the patient is mobile. Never re-challenge the culprit statin. For recurrent or exertional cases in the young, start the inherited-myopathy workup — forearm exercise test, metabolic and genetic studies.[2]

Specific Subtypes & Scenarios

The scenarios that change the script — learn each one's specific move:[1]

• Crush syndrome (earthquake / mass casualty) — the Renal Disaster Relief Task Force / Sever protocol: start isotonic saline before extrication (1 L/h during and after release), watch for sudden hyperkalaemia on reperfusion, anticipate a large fluid sequestration into injured muscle, and plan for mass-casualty dialysis resources.[3]
• Exertional rhabdomyolysis (the "weekend warrior") — unaccustomed intense exercise (squats, Spin, military training, marathons), worse in heat, dehydration, sickle-cell trait and at altitude. Most recover with fluids; the rare fatal cases are from hyperkalaemia or compartment syndrome. Gradual training progression, hydration and heat acclimatisation prevent recurrence.[2]
• Statin-associated rhabdomyolysis — the single commonest drug cause; risk rises with high dose, age, hypothyroidism, low body mass, and interacting drugs (fibrates, macrolides, cyclosporin, azole antifungals, daptomycin). Present with muscle pain and a rising CK on a statin. Stop the statin, give fluids, do NOT re-challenge. Immune-mediated necrotising myopathy (anti-HMGCR antibody) is a rare, persistent variant needing immunosuppression.[1]
• Heat stroke — core temperature over 40 degrees C with CNS dysfunction; multi-organ failure includes rhabdomyolysis. Rapid cooling (evaporative, ice-water immersion, intravascular) plus standard fluid management.
• Snake bite (Russell's viper, sea snake, krait) — direct myotoxins cause rhabdomyolysis; species-specific antivenom plus supportive care, AKI management and ventilatory support as needed.[1]
• Status epilepticus / delirium — sustained muscle activity injures muscle; control seizures/agitation and give fluids.
• Malignant hyperthermia / NMS / serotonin syndrome — stop trigger, give dantrolene (MH/NMS) or cyproheptadine/benzodiazepines (serotonin), cool, support.[1]
• Inherited myopathy (McArdle, CPT II) — recurrent exertional rhabdomyolysis in a young person; workup with forearm exercise test, metabolic and genetic studies; counsel on avoiding fasting and prolonged intense exertion.[2]

Complications & Pitfalls

Two killers compete for the early rhabdomyolysis patient: hyperkalaemia (the commonest cause of early death, by arrhythmia) and AKI (the commonest cause of overall death). Around them cluster hypocalcaemia, compartment syndrome, hepatic dysfunction (raised AST and ALT from muscle, sometimes genuine shock liver), DIC, metabolic acidosis, and fluid overload — pulmonary and cerebral oedema from the very resuscitation that is saving the kidney.[1]

The late and reperfusion complications are the price of survival: rebound hypercalcaemia as deposited calcium mobilises, calcium-phosphate deposition, progression of AKI to chronic kidney disease, infection of necrotic muscle or fasciotomy wounds, and critical-illness myopathy or neuropathy in the ventilated patient.[5]

The classic pitfalls — each one a preventable harm:[1]

• Failing to start fluids early — the single most preventable cause of AKI.
• Treating early hypocalcaemia with IV calcium — it precipitates more calcium-phosphate and sets up rebound hypercalcaemia; treat only if symptomatic or for membrane stabilisation in hyperkalaemia.
• Using mannitol in an oliguric/anuric or hypovolaemic patient — it causes AKI and pulmonary oedema.
• Missing compartment syndrome behind the more visible AKI — the swollen, tight, painful limb needs pressure measurement, not just fluids.
• Re-challenging the culprit statin — never re-challenge; switch class or use a non-statin strategy after review.
• Believing a "normal-looking limb" excludes rhabdomyolysis — the unconscious patient may have no external signs; send a CK on every unexplained AKI.[1][4]

Prognosis & Disposition

Overall mortality is 5 to 10 per cent — and it climbs fast with AKI, dialysis, sepsis, multi-organ failure and extremes of age. Crush-syndrome AKI without dialysis carries a very high mortality; with dialysis support it falls to around 15 to 20 per cent.[3]

Predictors of a bad outcome: the cause (sepsis, trauma), a high peak CK (especially over 15,000 to 20,000 U/L), the presence and severity of AKI and the need for dialysis, hyperkalaemia, compartment syndrome, DIC, and comorbidity.[5]

Recovery is the rule in survivors — the CK falls over 3 to 5 days and renal function recovers over 2 to 3 weeks — though a minority progress to chronic kidney disease.[1]

Disposition — admit any CK over 1000 U/L, hyperkalaemia, AKI, compartment concern or unstable cause to a monitored bed; ICU for severe hyperkalaemia, acidosis, compartment syndrome needing fasciotomy, multi-organ failure, or AKI needing RRT. Discharge when the CK is falling, electrolytes and renal function are stable, the patient is mobile, and the cause is addressed — with renal follow-up, a medication review, and an inherited-myopathy workup for recurrent exertional cases in the young.[2]

Special Populations

Five groups change the thresholds — know what is different in each:[1]

• Paediatric — commonest causes are viral myositis (influenza B — the child with calf pain and a limp) and exertion; give weight-based fluids (target urine 1 to 3 mL/kg/h with a maintenance component). Recurrent or exertional rhabdomyolysis in a child mandates a workup for inherited metabolic myopathy and a consideration of non-accidental injury.[2]
• Pregnancy — physiological volume expansion is partly protective, but hyperemesis, magnesium sulfate (for pre-eclampsia), and trauma all raise risk; manage with the same fluid-first approach, adjusting for uterine displacement and foetal monitoring in the third trimester.
• Elderly — less muscle mass raises the CK-to-muscle-mass signal; dehydration, polypharmacy (statins, diuretics) and falls dominate; lower threshold to admit.
• Chronic kidney disease — any muscle injury tips into dialysis-requiring AKI earlier; lower threshold for fluids and for nephrology input.
• Athletes / military recruits — exertional cases cluster in heat, dehydration, sickle-cell trait and at altitude; gradual training progression, hydration, heat acclimatisation and sickle-cell screening prevent recurrence.[2]

Evidence, Guidelines & Regional Differences

The framework is KDIGO AKI guidance applied to pigment nephropathy: prevent AKI with volume, avoid nephrotoxins, monitor urine output and creatinine, and dialyse for the A-E-I-O-U indications. There is no rhabdomyolysis-specific drug beyond fluids.[1]

EAST 2022 (Sawhney et al.) — the modern evidence-graded trauma-society guideline: early aggressive isotonic crystalloid is conditionally recommended to prevent AKI; routine bicarbonate and mannitol are NOT recommended over saline alone; fasciotomy for established compartment syndrome.[6]

Crush syndrome, mass casualty — the Renal Disaster Relief Task Force (Sever, Vanholder) protocol: saline before extrication, anticipate reperfusion hyperkalaemia, plan mass-casualty dialysis.[3]

The bicarbonate-and-mannitol controversy — the historical practice of forced alkaline-mannitol diuresis is not supported by randomised evidence. A systematic review and the Brown et al. J Trauma 2004 retrospective series found no clear survival benefit of bicarbonate and mannitol over saline alone. Modern practice is fluid-first: bicarbonate reserved for severe acidosis, mannitol rarely and never in anuria or hypovolaemia.[4][5]

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Prevention

Prevention is cause-specific — but most of it is three rules: stop the trigger, progress the training, and plan for the crush.[1]

• Avoid triggers in susceptible people — stop or reduce the statin, avoid interacting drugs, treat hypothyroidism, correct electrolytes.
• Gradual exercise progression for athletes and recruits — no sudden spikes in volume or intensity; heat acclimatisation, hydration and rest breaks in hot weather.[2]
• Hydration before, during and after exertion, especially in heat and at altitude.
• Statin monitoring — baseline CK, warn about muscle symptoms, check CK if symptomatic; avoid the statin-fibrate or statin-macrolide combination.
• Crush-scenario planning — pre-position saline and dialysis capacity for earthquakes and mass-casualty events (Renal Disaster Relief Task Force).[3]
• Sickle-cell screening in athletes and recruits of relevant ancestry; genetic counselling for inherited myopathies.[1]

Exam Pearls

[1]

• Urine dipstick blood-positive with NO red cells on microscopy equals rhabdomyolysis (or haemoglobinuria). The single most examinable bedside clue.[1]
• CK over 5x ULN is diagnostic; over 5000 U/L marks high AKI risk; over 15,000 to 20,000 U/L is very high risk.[5]
• The creatinine rises DISPROPORTIONATE to urea (myoglobin is a substrate) — a classic biochemical stem clue.
• Hyperkalaemia is the commonest cause of EARLY death; AKI is the commonest cause of OVERALL death.
• Calcium gluconate first for hyperkalaemic ECG changes (membrane stabilisation), then insulin-dextrose, salbutamol, bicarbonate.
• Do NOT treat early hypocalcaemia (it rebounds); treat only if symptomatic or for membrane stabilisation.
• Start IV fluids BEFORE extrication in crush (Renal Disaster Relief Task Force / Sever protocol).[3]
• Bicarbonate and mannitol are NOT first-line — no proven survival benefit over saline; reserve bicarbonate for severe acidosis, never give mannitol in anuria/hypovolaemia.[4][6]
• Delta pressure under 30 mmHg = compartment syndrome = urgent fasciotomy.
• A-E-I-O-U = indications for emergency dialysis (Acidosis, Electrolytes, Ingestion, Overload, Uraemia/Oliguria).[1]
• Dantrolene for malignant hyperthermia and NMS; cyproheptadine for serotonin syndrome; antivenom for snake bite.

Ward-round test — three stems

Stem 1 — the weekend warrior with cola-coloured urine (answer)

A 24-year-old man presents the morning after his first deep-squat session in a year: swollen rigid thighs, dark red-brown urine, CK over 50,000 U/L, creatinine climbing, potassium normal. What do you do in the next two hours? Model: This is exertional rhabdomyolysis. Admit, two large-bore cannulae, cardiac monitor, urethral catheter for hourly urine. Start aggressive IV crystalloid — 0.9 per cent saline or balanced solution at 1 to 1.5 L/h — titrated to a target urine output of 1 to 3 mL/kg/h (about 300 mL/h) until the CK is clearly falling; anticipate 6 to 12 L in the first 24 hours. Stop any statin and every nephrotoxin. Recheck CK and potassium every 6 to 12 hours and examine for compartment syndrome. Bicarbonate and mannitol are not first-line. The potassium is normal now — it will not stay that way.[1][2]

Stem 2 — found on the floor, peaked T waves, CK over 50,000 (answer)

An unconscious man is brought in after being found down for an unknown time. The ECG shows peaked T waves and a widened QRS, potassium is 7.1 mmol/L, CK is over 50,000 U/L, creatinine is rising, and the urine dipstick is blood-positive with no red cells on microscopy. What is the first drug, and why? Model: This is rhabdomyolysis with life-threatening hyperkalaemia — the early killer. The first drug is IV calcium gluconate 10 per cent, 10 mL over 2 to 5 minutes, to stabilise the myocardial membrane — give it before the fluids. Then insulin-dextrose (10 units in 25 to 50 g), nebulised salbutamol 10 to 20 mg, and sodium bicarbonate (he is acidotic). Then aggressive saline. Do NOT treat the early hypocalcaemia with calcium as replacement — but for hyperkalaemic ECG changes, calcium gluconate is membrane stabilisation, not calcium replacement. Plan for RRT on the A-E-I-O-U criteria.[1][5]

Stem 3 — the tense, swollen calf after a crush (answer)

A man is pulled from a collapsed building with a crushed leg. The leg is swollen, tense and exquisitely tender; passive stretch of the toes is agonising; the pedal pulse is present. What is the diagnosis, the confirmation, and the move? Model: This is acute compartment syndrome on top of crush-related rhabdomyolysis. The classic trap: a pulse is still present until very late — "the pulse is fine" must not reassure you; pain out of proportion and pain on passive stretch are the signs that matter. Confirm with compartment pressure measurement — a delta pressure (diastolic minus compartment) under 30 mmHg, or an absolute pressure over 30 mmHg, mandates urgent fasciotomy. Restore volume and correct coagulopathy before release, and anticipate a potassium and myoglobin surge at the moment the compartment opens. Start saline before extrication per the Renal Disaster Relief Task Force protocol.[1][3]

The mantra: Dipstick-positive, microscopy-negative — flood the kidney with saline before the casts precipitate.[1][5]

References

1. [1]Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury N Engl J Med, 2009.PMID 19571284
2. [2]Manspeaker S, Henderson K, Riddle D. Treatment of exertional rhabdomyolysis in athletes: a systematic review JBI Database System Rev Implement Rep, 2016.PMID 27532656
3. [3]Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters N Engl J Med, 2006.PMID 16525142
4. [4]Brown CV, Rhee P, Chan L, Evans K, Demetriades D, Velmahos GC. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma, 2004.PMID 15211124
5. [5]Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice Crit Care, 2016.PMID 27301374
6. [6]Sawhney JS, Kasotakis G, Goldenberg A, Abramson S, Dodgion C, Patel N. Management of rhabdomyolysis: A practice management guideline from the Eastern Association for the Surgery of Trauma Am J Surg, 2022.PMID 34836603