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 sky-high and his creatinine is climbing.^[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 is released with the other muscle contents.^[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; a greater heme/RBC discrepancy on urinalysis raises the chance someone will check a CK and catch rhabdomyolysis, but CK testing is commonly delayed or omitted so a bland urine does not exclude the diagnosis.^[7]

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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^{[1] [5]}

Epidemiology & Risk Factors

Rhabdomyolysis is the hidden cause of roughly 7 to 10 per cent of all acute kidney injury — and it is frequently missed, because CK testing is rarely performed. Among hospitalised patients with a CK over 1000 U/L, AKI developed in 61.4 per cent in one large cohort, and a peak CK over 5000 U/L was the lowest CK level associated with renal failure in trauma ICU patients (19 per cent versus 8 per cent below it).^[7][8][4]

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. Zhang: this is why early fluid resuscitation remains the most important on-site treatment — cardiac arrest, hypovolaemic shock and hyperkalaemia-related cardiac dysfunction are the primary causes of on-site death.^[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 is released from necrotic muscle; tissue factor and activated clotting factors drive DIC.^[1][5]

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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. In crush syndrome, hyperkalaemia-related cardiac dysfunction is a primary cause of on-site death.
• Hypocalcaemia (early) — common in the acute phase. Do NOT treat early hypocalcaemia unless symptomatic (or for hyperkalaemic membrane stabilisation) — rebound can occur as muscle recovers.
• 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) when pigment is present. A greater heme/RBC discrepancy on urinalysis is a screening clue that should prompt a CK — it is not sensitive enough to rule rhabdomyolysis out.
• 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 heme-positive dipstick has more than one cause — split them with the microscope, the plasma, and a CK.^[7]

^{[7] [5] [2]}

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]

^{[10] [12] [15] [11]}

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 single absolute reading over 30 mmHg does not diagnose ACS — patients who never developed ACS still exceeded that theoretical fasciotomy threshold, while ACS patients showed a rising trend (about 0.67 mmHg/h) rather than a one-off number. Continuous monitoring outperforms a single 30 mmHg cut-off.^[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 tracks renal-failure risk: in trauma ICU patients a CK over 5000 U/L was the lowest level associated with renal failure, and studies of established rhabdomyolysis define the syndrome by a CK over 1000 U/L (over five times the upper limit of normal in most reports). Rhabdomyolysis benefits from early, aggressive volume repletion — start it before the trajectory is set.^[4][7][5]

Investigations

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

• Creatine kinase (CK) — the diagnostic marker. Most studies define rhabdomyolysis as a CK more than five times the upper limit of normal; a CK over 1000 U/L is a commonly used diagnostic threshold. In trauma ICU patients a CK over 5000 U/L was the lowest abnormal level associated with renal failure (19 per cent versus 8 per cent below it), so it marks the band of high renal risk.^[5][7][4]
• 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 may be low initially, phosphate high; rebound hypercalcaemia can occur 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 — a greater heme/RBC discrepancy on urinalysis is a screening clue that should prompt a CK; it is not a rule-out test.^[7]

• Dipstick / microscopy — Yasmin: ≥3+ heme and ≤5 RBCs/hpf (2.0% of UAs) had specificity 96.7% and sensitivity 16.7% for post-AKI CK over 1000 U/L; ≥1 heme and ≤30 RBCs had the highest sensitivity. Greater heme/RBC discrepancy made CK testing and rhabdomyolysis diagnosis more likely. CK was still only checked in 20.5% after AKI.
• 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]

^{[7] [5] [4] [8] [2]}

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; continuous trends outperform a single absolute 30 mmHg threshold.
• 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 — when standard treatment is not enough

Management — Resuscitation

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^{[2] [3] [6]}

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: aggressive IV fluid resuscitation is the most commonly utilised treatment, and normal saline is the most commonly reported solution for decreasing CK levels and resolving myoglobinuria in exertional rhabdomyolysis.^[2]
• Rate: early IV fluid replacement is delivered at roughly 400 mL per hour in the reported literature, with adjustments between 200 and 1000 mL per hour depending on severity and volume status.^[2]
• Why: on quantitative meta-analysis, aggressive IV fluid resuscitation decreased the incidence of acute renal failure and the need for dialysis, and the 2022 trauma-society guideline conditionally recommends it — while in crush syndrome, early fluid resuscitation is the most important on-site treatment, because cardiac arrest, hypovolaemic shock and hyperkalaemia-related cardiac dysfunction are the primary causes of on-site death.^[6][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 early — in crush syndrome, hyperkalaemia-related cardiac dysfunction is one of the primary causes of on-site death. Insulin with dextrose remains a cornerstone of acute potassium lowering, and nebulised salbutamol 10 mg is an effective, safe adjunct — most reported studies used 10 mg nebulised salbutamol, with potassium falling by roughly 0.6 to 1.6 mEq/L and peak effect at 1 to 4 hours; tachycardia, dizziness and mild hyperglycaemia are the usual adverse effects. These measures buy time; definitive clearance may require kidney replacement therapy once AKI is established.^[3][13][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]

^{[3] [13] [2] [10] [6] [14] [1]}

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]

^{[6] [4] [5] [2]}

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

• Compartment syndrome — measure compartment pressure; do not treat a single absolute 30 mmHg as diagnostic — continuous trends distinguish ACS (rising) from patients who exceed 30 mmHg without ACS (falling). 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 when standard treatment is not enough (Wong: compare continuous and intermittent methods).^[1]

Step 5 — disposition. Severity drives the bed. AKI is independently associated with mortality in rhabdomyolysis (24.8 per cent with AKI versus 11.8 per cent without in a large CK-over-1000 cohort), and kidney replacement therapy may be required when standard treatment is not enough — so established AKI, refractory hyperkalaemia or an uncontrolled cause belongs in a monitored or critical-care bed. Because rhabdomyolysis benefits from early, aggressive volume repletion, never let disposition delay the fluids.^[8][1][7]

Specific Subtypes & Scenarios

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

• Crush syndrome (earthquake / mass casualty) — Zhang: early fluid resuscitation remains the most important on-site treatment, because cardiac arrest, hypovolaemic shock and hyperkalaemia-related cardiac dysfunction are the primary causes of on-site death; watch for sudden hyperkalaemia on reperfusion and plan dialysis capacity (Sever: nearly half of paediatric crush patients developed AKI, a substantial proportion needing dialysis).^[3][9]
• 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-related cardiac dysfunction (a primary cause of on-site death in crush) and myoglobinuric AKI (Brown: 19% renal failure when CK exceeds 5000 U/L versus 8% below). 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 muscle recovers, 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 asymptomatic hypocalcaemia with IV calcium — 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

In one 329-patient CK-over-1000 U/L cohort, overall mortality was 19.8%; patients with AKI had higher mortality than those without (24.8% vs 11.8%). Age ≥60, sepsis and elevated prothrombin time were independent risk factors for in-hospital death among RM patients with AKI.^[8]

Predictors of a bad outcome: the cause — in one large cohort the conditions most frequently associated with rhabdomyolysis were trauma (28.3 per cent), sepsis (14.6 per cent), bee sting (12.8 per cent), surgery (11.2 per cent) and exercise (7.0 per cent), and sepsis, bee sting and acute alcoholism predisposed to severe AKI; the presence of AKI itself (mortality 24.8 per cent with AKI versus 11.8 per cent without); and a peak CK over 5000 U/L, the lowest level associated with renal failure in trauma patients.^[8][4]

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 — the level of care follows severity: AKI (independently associated with mortality), refractory hyperkalaemia, and compartment syndrome requiring release all point to a monitored or ICU bed, with kidney replacement therapy planned for when standard treatment is not enough. Any associated compartment syndrome needs to be identified and released.^[8][1][6]

Special Populations

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

• Paediatric — aetiologies differ between adult and paediatric populations, and crush-syndrome data from past earthquakes show that nearly half of paediatric crush victims developed AKI, a substantial proportion of whom required dialysis; children are a large share of disaster victims, so plan paediatric dialysis capacity early.^[5][9]
• 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 volume first, then KRT if standard treatment is not enough: prevent AKI with aggressive IV fluid, avoid nephrotoxins, monitor urine output and creatinine, and start KRT on conventional complications — not on the CK. 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 — Zhang: early fluid resuscitation is the most important on-site treatment; anticipate reperfusion hyperkalaemia; Sever: plan paediatric dialysis capacity after earthquakes.^[3][9]

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]

^[1]

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 (Zhang early on-site fluid; Sever paediatric crush AKI).^[3][9]
• Sickle-cell screening in athletes and recruits of relevant ancestry; genetic counselling for inherited myopathies.^[1]

Exam Pearls

^[1]

• A greater urine heme/RBC discrepancy is a screening clue that should prompt a CK (Yasmin: ≥3+ heme and ≤5 RBCs/hpf specificity 96.7%, sensitivity 16.7%) — it does not equal the diagnosis and it does not exclude it.^[7]
• CK over 5x ULN is the definition used by most studies; a CK over 1000 U/L is a commonly used diagnostic threshold; over 5000 U/L marks the renal-failure risk band (19 per cent versus 8 per cent below it).^[5][7][4]
• Yasmin: patients with a greater heme/RBC discrepancy were more likely to have CK measured and to meet rhabdomyolysis criteria — but CK was still only checked after 20.5% of AKI episodes, so the diagnosis is still missed.^[7]
• Hyperkalaemia is the early killer in crush syndrome; AKI raises mortality in established rhabdomyolysis (24.8 per cent with AKI versus 11.8 per cent without).^[3][8]
• Hyperkalaemia therapy: insulin with dextrose is the cornerstone of acute potassium lowering, with nebulised salbutamol 10 mg as an effective adjunct.^[13]
• In crush syndrome, hyperkalaemia-related cardiac dysfunction is a primary cause of on-site death — early fluid resuscitation is the most important on-site treatment.^[3]
• Bicarbonate and mannitol are NOT first-line — no benefit on renal failure, dialysis or mortality over crystalloid alone; the 2022 trauma-society guideline conditionally recommends against both.^[4][6]
• Any associated compartment syndrome needs to be identified and released; continuous pressure monitoring beats single readings against the traditional 30 mmHg fasciotomy threshold.^[6][14]
• Dantrolene initially 1 to 2 mg/kg IV, with trigger cessation and aggressive cooling, treats malignant hyperthermia; dantrolene and bromocriptine are the first-line agents in NMS; serotonin syndrome is treated by stopping the offending agent plus supportive care (agitation control, hyperthermia, autonomic instability).^{[10][15][12][11]}

Ward-round test — three stems

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

A 24-year-old man presents the morning after his first deep-squat session in a year: swollen rigid thighs, dark red-brown urine, a markedly raised CK, a climbing creatinine, normal potassium. What do you do in the next two hours? Model: This is exertional rhabdomyolysis — intense unaccustomed exercise with myalgia, myoglobinuria and a raised CK puts renal failure on the table. Admit with cardiac monitoring and start aggressive IV fluid resuscitation early: normal saline is the most commonly reported solution, delivered at roughly 400 mL per hour in the reported literature (adjusted between 200 and 1000 mL per hour by severity and volume state). Aggressive fluids are the one therapy with a proven signal — they reduced acute renal failure and dialysis need on meta-analysis and are conditionally recommended by the 2022 trauma-society guideline; bicarbonate and mannitol are conditionally recommended against. Watch the potassium and examine for compartment syndrome.^[2][6]

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

An unconscious man is brought in after being found down for an unknown time. The ECG shows hyperkalaemic changes, the potassium is dangerously high, the CK is markedly raised, the creatinine is rising, and the urine dipstick is heme-positive with almost no red cells on microscopy. What is the first priority, and why? Model: This is rhabdomyolysis with life-threatening hyperkalaemia — in crush-related muscle injury, hyperkalaemia-related cardiac dysfunction is a primary cause of on-site death. The immediate priority is the potassium: insulin with dextrose (a cornerstone of acute potassium lowering) plus nebulised salbutamol 10 mg (reported to lower serum potassium by about 0.6 to 1.6 mEq/L, with peak effect at 1 to 4 hours). The heme-positive dipstick with almost no red cells is the bedside signature linking the AKI to muscle breakdown. Then aggressive crystalloid — and plan kidney replacement therapy if standard treatment is not enough.^{[3][13][7][1]}

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

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 — Bouklouch: a single absolute reading over 30 mmHg does not diagnose ACS (non-ACS limbs can exceed 30 mmHg while falling; ACS shows a rising trend, about 0.67 mmHg/h). Identify and release associated compartment syndrome. Zhang: early on-site fluid remains the most important crush treatment; anticipate a potassium surge at reperfusion.^[14][3]

The mantra: CK makes the diagnosis; flood the kidney with saline early — about 400 mL/h — and do not wait for the creatinine to climb.^[2][5]

References15ShowHide

1. [1]Wong FHA, See KC Critical care considerations in rhabdomyolysis-associated acute kidney injury and kidney replacement therapy World J Nephrol, 2026.PMID 42395677
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]Zhang MW, Tan FQ, Yang JR, et al. Cardiovascular events in crush syndrome: on-site therapeutic strategies and pharmacological investigations Front Pharmacol, 2024.PMID 39372200
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, et al. Management of rhabdomyolysis: A practice management guideline from the Eastern Association for the Surgery of Trauma Am J Surg, 2022.PMID 34836603
7. [7]Yasmin F, Faulkner SC, Aklilu AM, et al. Development of Urinalysis Screening Criteria for Rhabdomyolysis in Acute Kidney Injury Kidney360, 2026.PMID 41637135
8. [8]Yang J, Zhou J, Wang X, et al. Risk factors for severe acute kidney injury among patients with rhabdomyolysis BMC Nephrol, 2020.PMID 33225908
9. [9]Sever L, Bakkaloğlu SA Disasters and crush syndrome-related acute kidney injury: What pediatric nephrologists should know Pediatr Nephrol, 2026.PMID 41389082
10. [10]Tsutsumi YM, Nagasaka H, Mukaida K, et al. JSA guideline for management of malignant hyperthermia in 2025 J Anesth, 2026.PMID 41504952
11. [11]Spadaro A, Scott KR, Koyfman A, et al. High risk and low prevalence diseases: Serotonin syndrome Am J Emerg Med, 2022.PMID 36057215
12. [12]Sarmiento B, Gunther M, Cohen-Oram A, et al. Bromocriptine for Residual Catatonia Following Neuroleptic Malignant Syndrome: Illustrative Case Report and Systematic Review J Acad Consult Liaison Psychiatry, 2025.PMID 39756582
13. [13]Arzayus-Patiño L, Hinojosa-Angulo AY, Rodríguez-Angulo KA, et al. Utility of inhaled beta2-agonists in reducing serum potassium levels in adult patients with hyperkalemia: A scoping review PLoS One, 2026.PMID 41632760
14. [14]Bouklouch Y, Matta J, Obremskey WT, et al. Pressure trends and diagnosis of acute compartment syndrome Surg Pract Sci, 2026.PMID 41631182
15. [15]Ucdal M, Ekingen E. Atypical neuroleptic malignant syndrome in a geriatric palliative care patient: a case report and review of the literature J Med Case Rep, 2026.PMID 42231486