What is rhabdomyolysis?

Rhabdomyolysis is rapid breakdown of skeletal muscle — releasing myoglobin, CK, potassium, phosphate and uric acid into the blood. Myoglobin is toxic to kidney tubules. CK >1,000 IU/L confirms rhabdomyolysis; severe cases have CK >50,000-100,000 IU/L. Classic presentation: muscle pain, weakness + dark "coca-cola" urine (myoglobinuria). AKI develops in approximately 15-50% of significant cases.

How is rhabdomyolysis treated?

Aggressive IV fluid resuscitation is the cornerstone — Lactated Ringer's preferred. Target urine output: 200-300mL/hour. Rate: 500mL-1L/hour initially, then titrate. Continue until CK clearly declining and urine clearing. Monitor: daily CK, creatinine, electrolytes (hyperkalaemia, hyperphosphataemia, hypocalcaemia), urine output, urine dipstick. Stop causative agent. Compartment syndrome: emergency fasciotomy. RRT if AKI and oliguric.

Can statins cause rhabdomyolysis?

Yes, but rare (<0.1%). Risk highest with: simvastatin 80mg (FDA restricted); CYP3A4 inhibitors co-prescribed (clarithromycin, erythromycin, azoles, diltiazem, verapamil, amiodarone, ciclosporin, HIV protease inhibitors — increase statin levels up to 10-fold); gemfibrozil + any statin (10× risk — use fenofibrate instead). Always check for CYP3A4 interactions; counsel patients to report muscle pain or dark urine immediately.

What is compartment syndrome?

Compartment syndrome occurs when swelling within a fascial compartment raises pressure beyond capillary perfusion pressure → ischaemia → necrosis → rhabdomyolysis. Clinical: severe pain on passive muscle stretch + tense compartment. Measure ICP: fasciotomy when ICP >30 mmHg or within 30 mmHg of diastolic BP. Delayed fasciotomy = irreversible damage. Most common: anterior compartment of the leg.

How does GMJ News cover rhabdomyolysis?

GMJ News covers CK thresholds, AKI mechanisms (tubular toxicity, casts, vasoconstriction), IV fluid protocol, compartment syndrome (5 Ps + fasciotomy), statin rhabdomyolysis (CYP3A4, gemfibrozil), exertional rhabdomyolysis, heat stroke, sickle cell trait risk, KDIGO AKI staging, and RRT indications.

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Rhabdomyolysis

Q: Can statins cause rhabdomyolysis?

Yes, but rare (<0.1%). Risk highest with: simvastatin 80mg (FDA restricted); CYP3A4 inhibitors co-prescribed (clarithromycin, erythromycin, azoles, diltiazem, verapamil, amiodarone, ciclosporin, HIV protease inhibitors — increase statin levels up to 10-fold); gemfibrozil + any statin (10× risk — use fenofibrate instead). Always check for CYP3A4 interactions; counsel patients to report muscle pain or dark urine immediately.

Q: What is compartment syndrome?

Compartment syndrome occurs when swelling within a fascial compartment raises pressure beyond capillary perfusion pressure → ischaemia → necrosis → rhabdomyolysis. Clinical: severe pain on passive muscle stretch + tense compartment. Measure ICP: fasciotomy when ICP >30 mmHg or within 30 mmHg of diastolic BP. Delayed fasciotomy = irreversible damage. Most common: anterior compartment of the leg.

GMJ News knowledge hub · last reviewed August 2026 · Georgian Medical Journal

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Rhabdomyolysis — the rapid breakdown of skeletal muscle with release of intracellular contents (myoglobin, CK, potassium, phosphate) into the bloodstream — is a potentially life-threatening condition whose clinical spectrum ranges from asymptomatic CK elevation to acute kidney injury (AKI) from myoglobin-induced tubular toxicity in approximately 15-50% of severe cases, caused by an extraordinarily diverse set of triggers including crush injury, extreme exercise, statins, alcohol, illicit drugs (cocaine, MDMA, amphetamines), snake venom, seizures, hyperthermia, hypokalaemia and viral infections (WHO). The cornerstone of treatment is aggressive early IV fluid resuscitation with Lactated Ringer's or normal saline targeting urine output of 200-300mL/hour — with the goal of washing myoglobin through the tubules before it crystallises and causes irreversible AKI.

Key messages

CK >1,000 IU/L = rhabdomyolysis; >10,000 = significant AKI risk

CK (creatine kinase): the primary diagnostic marker. CK >1,000 IU/L confirms rhabdomyolysis. CK >5,000-10,000 IU/L: significant AKI risk. CK >100,000 IU/L: severe — may require renal replacement therapy. CK peaks at 24-72 hours then falls. Monitor daily until clearly trending down.

Aggressive IV fluids — target urine output 200-300mL/hour

Lactated Ringer's or normal saline at 500mL-1L/hour initially. Goal: dilute myoglobin in tubules and maintain flow to prevent crystallisation. Continue until CK clearly trending down AND urine clearing. Urinary alkalinisation (NaHCO3): no longer universally recommended (inconsistent evidence). Key endpoint: urine output 200-300mL/hour.

AKI — three mechanisms of myoglobin toxicity

Renal injury from myoglobin: (1) Direct tubular toxicity — ferryl myoglobin generates hydroxyl radicals in proximal tubule; (2) Cast formation — myoglobin precipitates with Tamm-Horsfall protein in acidic urine → tubular obstruction; (3) Renal vasoconstriction — volume depletion + myoglobin-scavenged nitric oxide → afferent arteriole constriction → ischaemia.

Causes — extraordinarily diverse

Traumatic: crush injury (earthquake, RTA); compartment syndrome. Exertional: extreme exercise; CrossFit; military training; heat stroke. Drugs/toxins: statins (dose-dependent — highest risk simvastatin 80mg); cocaine; MDMA; alcohol; heroin. Metabolic/infection: hypokalaemia; DKA; influenza; COVID-19; legionella. Inherited: McArdle disease; fatty acid oxidation defects.

Compartment syndrome — surgical emergency within rhabdomyolysis

5 Ps: Pain (especially on passive stretch); Pressure (tense woody compartment); Paraesthesia; Paresis; Pallor/Pulselessness (late signs). ICP >30 mmHg OR within 30 mmHg of diastolic = FASCIOTOMY. Surgical emergency — delayed fasciotomy → irreversible muscle and nerve ischaemia → massive rhabdomyolysis.

Statin rhabdomyolysis — CYP3A4 interaction vigilance

Risk highest with: simvastatin 80mg (FDA restricted 2011); CYP3A4 inhibitors (clarithromycin, erythromycin, azoles, diltiazem, verapamil, amiodarone, ciclosporin, HIV PIs) — increase statin levels up to 10-fold; gemfibrozil + any statin (10× rhabdomyolysis risk — use fenofibrate instead). Always check CYP3A4 interactions when prescribing statins.

Key statistics

>1,000 IU/L

CK threshold confirming rhabdomyolysis

Clinical/BMJ

15-50%

of severe rhabdomyolysis develops AKI

KDIGO/BMJ

200-300mL/h

urine output target with aggressive IV fluid resuscitation

KDIGO

<0.1%

rhabdomyolysis risk with standard statin doses; highest with CYP3A4 interactions

FDA

ICP >30mmHg

compartment pressure threshold for fasciotomy

BOAST/AO

10× risk

rhabdomyolysis from gemfibrozil + any statin combination — use fenofibrate instead

FDA/MHRA

Rhabdomyolysis — CK level and AKI risk correlation

Source: Clinical/Nephrology. Higher CK = higher AKI risk. Aggressive early fluids are the critical intervention.

Glossary of key terms

Myoglobin renal toxicity
Nephrology/BiochemistryMyoglobin (17.8 kDa haem protein) filtered at glomerulus → myoglobinuria (cola/tea-coloured urine). Dipstick: positive for "blood" without RBCs (myoglobin cross-reacts with haem test — clue to diagnosis). Three toxicity mechanisms: (1) Ferryl myoglobin → hydroxyl radicals → tubular oxidative damage; (2) Acidic urine → myoglobin-Tamm-Horsfall cast formation → obstruction; (3) Volume depletion + NO scavenging → renal vasoconstriction → ischaemia. All three explain why aggressive early hydration is the only evidence-based intervention.

Compartment syndrome
Surgery/EmergencyIncreased pressure within a closed fascial compartment → ischaemia. Classic 5 Ps: Pain (passive stretch most sensitive); Pressure (firm, woody compartment); Paraesthesia; Paresis; Pallor/Pulselessness (late, ominous signs). ICP measurement: Stryker device or arterial line transducer with needle. Fasciotomy indications: ICP >30 mmHg OR delta pressure (diastolic BP − ICP) <30 mmHg. Most common compartments: anterior leg; other leg compartments; forearm.

Exertional rhabdomyolysis
Sports medicineFrom extreme/unaccustomed exercise — increasingly with CrossFit, military training, marathon. Triggers: eccentric contractions (downhill running, heavy lowering); heat + dehydration; sickle cell trait at altitude. CK can reach >100,000. Most resolve with rest and hydration; severe cases require hospitalisation. Sickle cell trait: high-intensity military/athletic training → sickling crisis → rhabdomyolysis → sudden death risk.

Statin myopathy spectrum
PharmacologyMyalgia (no CK rise — approximately 5-10%); Myopathy (CK 3-10× ULN); Rhabdomyolysis (<0.1%). Risk factors: high-dose statin; older age; female; hypothyroidism; CKD; CYP3A4 inhibitors. Simvastatin 80mg restricted by FDA 2011 for new patients. Gemfibrozil + any statin = 10× rhabdomyolysis risk (inhibits CYP2C8 statin glucuronidation — not just CYP3A4). Use fenofibrate + statin instead.

Heat stroke and rhabdomyolysis
Emergency medicineHeat stroke complicates rhabdomyolysis in approximately 25-30% of cases. The triad: hyperthermia + rhabdomyolysis + AKI + coagulopathy (DIC) = severe heat stroke. Treatment: rapid whole-body cooling (ice water immersion most effective — target <39°C within 30 minutes) + aggressive IV fluids. Exertional heat stroke in athletes: core temperature measurement (rectal — most accurate), immediate ice water immersion, stop exercise.

KDIGO AKI staging
NephrologyAKI (KDIGO 2012): serum creatinine rise ≥26.5 μmol/L within 48h OR ≥1.5× baseline in 7 days OR urine output <0.5mL/kg/h for 6h. Stage 1: Cr 1.5-1.9× baseline; Stage 2: 2.0-2.9×; Stage 3: ≥3× or Cr ≥353.6 μmol/L or RRT needed. Rhabdomyolysis AKI: peaks 3-5 days; most recover without dialysis; approximately 10-20% of severe cases need CRRT.

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