Rhabdomyolysis
Skeletal muscle breakdown releasing myoglobin, CK, potassium, and phosphate into the circulation. Myoglobin causes direct renal tubular obstruction and toxicity → AKI. The three killers: hyperkalemia, AKI, and compartment syndrome. Treatment is aggressive IV hydration -dilute the myoglobin before it destroys the kidneys.
🔍 Overview
Definition
Rhabdomyolysis: Skeletal muscle necrosis with release of intracellular contents (myoglobin, CK, potassium, phosphate, uric acid, LDH) into the circulation. Defined as CK > 5× upper limit of normal (typically > 1,000 U/L, often > 5,000–10,000 in clinically significant cases). CK levels > 10,000 carry a high risk of AKI.
Pathophysiology
Myocyte necrosis (any cause) → release of myoglobin into bloodstream → myoglobin filtered by glomerulus → in acidic urine, myoglobin precipitates as ferrihemate casts → direct renal tubular obstruction + oxidative injury to tubular epithelium + renal vasoconstriction → acute tubular necrosis (ATN) → AKI. Simultaneously, massive release of intracellular K⁺ → life-threatening hyperkalemia, and PO₄ release → hypocalcemia (calcium binds to damaged muscle and phosphate).
Common Causes
- Trauma/crush injury -earthquakes, prolonged immobilization, surgery
- Immobilization -found down (overdose, stroke, fall), prolonged surgery
- Drugs of abuse -cocaine, amphetamines, MDMA, PCP, synthetic cannabinoids
- Medications -statins (especially + fibrates or CYP3A4 inhibitors), daptomycin, colchicine, antipsychotics (NMS)
- Seizures -prolonged/status epilepticus
- Extreme exertion -marathon, military training, CrossFit (especially in heat)
- NMS / Serotonin syndrome -see NMS vs Serotonin Syndrome
- Heat stroke -see Heat Stroke
- Metabolic -hypokalemia, hypophosphatemia, hypothyroidism, DKA
- Infections -influenza, HIV, Legionella, group A strep
Clinical Example
Case
22M found down after a party (likely substance use + prolonged immobilization). Presenting with diffuse myalgias, dark brown urine, and oliguria. Labs: CK 45,000, K⁺ 6.2, Cr 3.4, Ca²⁺ 7.1, PO₄ 6.8, uric acid 12. UA: positive for blood on dipstick but 0 RBCs on microscopy (= myoglobinuria). ECG shows peaked T-waves.
🚨 Management
Treatment Protocol
The THREE killers in rhabdo: (1) Hyperkalemia -can be rapid and fatal, check K⁺ q4–6h. (2) AKI -from myoglobin-induced tubular necrosis. (3) Compartment syndrome -if a limb is involved, check compartment pressures.
| Priority | Intervention | Details |
|---|---|---|
| 1. Aggressive IV fluids | NS or LR at 200–300 mL/hr | Target UOP 200–300 mL/hr (much higher than standard resuscitation). Goal: dilute myoglobin and prevent tubular precipitation. Most patients need 6–10 L in first 24h. Foley catheter mandatory for strict I&Os. |
| 2. Treat hyperkalemia | Calcium gluconate, insulin + D50, kayexalate/patiromer | Check K⁺ q4–6h. If K⁺ > 6.0 or ECG changes → calcium gluconate 1g IV for cardiac membrane stabilization → insulin 10 units + D50 for K⁺ shift → kayexalate or patiromer for removal. See Hyperkalemia. |
| 3. Bicarb (controversial) | Sodium bicarbonate 150 mEq in 1L D5W | Goal: urine pH > 6.5 to keep myoglobin soluble. Controversial -theoretical benefit but no strong RCT evidence. May worsen hypocalcemia (alkalosis binds ionized Ca). Consider if urine pH < 6.5. |
| 4. Compartment check | Measure compartment pressures | If limb injury involved or tense/swollen extremity. Pressure > 30 mmHg or within 30 mmHg of diastolic → emergent fasciotomy. Ortho/surgery consult. |
| 5. Dialysis (if needed) | Continuous RRT (CRRT) preferred | Indications: refractory hyperkalemia, volume overload, severe acidosis, uremia. Standard HD does NOT clear myoglobin (too large). CRRT may have theoretical benefit. |
Do NOT give calcium for hypocalcemia in rhabdo (unless symptomatic with tetany or ECG changes) -calcium deposits in damaged muscle and worsens injury. The calcium will correct on its own as muscles heal.
🧪 Workup
Laboratory Workup
- CK (creatine kinase) -diagnostic. Serial q6–12h until trending down. Peak usually at 24–72h. CK > 5,000 = significant rhabdo risk for AKI.
- BMP -K⁺ (hyperK!), Ca²⁺ (hypoCa), PO₄ (hyperPhos), Cr/BUN (AKI), bicarb (metabolic acidosis)
- Urinalysis -dipstick positive for blood but NO RBCs on microscopy = myoglobinuria. This is a classic boards question. The heme pigment on the dipstick cross-reacts with myoglobin.
- LDH -elevated (nonspecific muscle injury marker)
- Uric acid -often elevated (cell lysis)
- Coags (PT/INR, aPTT, fibrinogen) -DIC risk with severe rhabdo
- Lactate -tissue hypoperfusion marker
- Urine myoglobin -can confirm but not widely available and clears quickly. UA dipstick is adequate.
- Toxicology screen -if etiology unclear (cocaine, amphetamines)
- ECG -hyperkalemia changes (peaked T-waves, wide QRS)
AST/ALT Pattern in Rhabdo, Looks Like Hepatitis but Isn't
Rhabdo routinely produces ↑ AST (often 200–800 U/L) and ↑ ALT (smaller bump), with AST > ALT. AST is leaked from lysed myocytes, not made by injured liver (skeletal muscle is constitutively rich in AST; ALT is present in muscle but at lower concentration). If CK is high, attribute the LFT abnormality to muscle and don't chase viral hepatitis serologies. AST/ALT will trend down as CK drops.
Why it matters: A patient with AST 400 / ALT 250 / AST > ALT after a found-down event or seizure does not need a hepatitis B/C panel. Check CK first. Wasted serology workup delays the only thing that helps the kidneys, aggressive hydration to UOP 200–300 mL/hr.
Red flags that argue for true hepatic injury (look elsewhere if any are present): AST/ALT in the thousands without matching CK, ↑ INR, ↑ bilirubin out of proportion to CK, encephalopathy, or AST/ALT not tracking CK on serial labs (real liver injury usually means ischemic hepatitis from shock, drug-induced injury, or alcoholic hepatitis).
Why it matters: A patient with AST 400 / ALT 250 / AST > ALT after a found-down event or seizure does not need a hepatitis B/C panel. Check CK first. Wasted serology workup delays the only thing that helps the kidneys, aggressive hydration to UOP 200–300 mL/hr.
Red flags that argue for true hepatic injury (look elsewhere if any are present): AST/ALT in the thousands without matching CK, ↑ INR, ↑ bilirubin out of proportion to CK, encephalopathy, or AST/ALT not tracking CK on serial labs (real liver injury usually means ischemic hepatitis from shock, drug-induced injury, or alcoholic hepatitis).
Myoglobin vs Hemoglobin, Same Heme but Different Fate
Both proteins contain heme, but their clinical signatures diverge sharply, and this is a common point of confusion:
Myoglobin → kidney → urine (causes AKI, not jaundice). Filtered freely by the glomerulus (~17 kDa, small enough to pass). In acidic urine it precipitates as ferrihemate casts → tubular obstruction + oxidative injury to tubular epithelium + renal vasoconstriction → acute tubular necrosis. This is why rhabdo presents with tea-colored urine and AKI, the myoglobin gets excreted in urine before it can be metabolized to anything else.
Hemoglobin → spleen → bilirubin (causes jaundice when pathologic). Senescent RBCs are phagocytosed by splenic macrophages. Heme oxygenase converts heme to biliverdin; biliverdin reductase converts biliverdin to unconjugated bilirubin, which then travels to the liver for conjugation and biliary excretion. This pathway accounts for ~80% of daily bilirubin production.
Why the distinction matters: Myoglobin technically can yield trace bilirubin via the same heme-oxygenase pathway (the chemistry is identical), but clinically it doesn't produce jaundice because it's excreted in urine first. If a rhabdo patient is jaundiced, look elsewhere, hemolysis (free hemoglobin overwhelming haptoglobin → bilirubin surge), ischemic hepatitis from shock (AST in the thousands, ↑ LDH, ↑ INR), or drug-induced hepatic injury. Don't blame the myoglobin.
Myoglobin → kidney → urine (causes AKI, not jaundice). Filtered freely by the glomerulus (~17 kDa, small enough to pass). In acidic urine it precipitates as ferrihemate casts → tubular obstruction + oxidative injury to tubular epithelium + renal vasoconstriction → acute tubular necrosis. This is why rhabdo presents with tea-colored urine and AKI, the myoglobin gets excreted in urine before it can be metabolized to anything else.
Hemoglobin → spleen → bilirubin (causes jaundice when pathologic). Senescent RBCs are phagocytosed by splenic macrophages. Heme oxygenase converts heme to biliverdin; biliverdin reductase converts biliverdin to unconjugated bilirubin, which then travels to the liver for conjugation and biliary excretion. This pathway accounts for ~80% of daily bilirubin production.
Why the distinction matters: Myoglobin technically can yield trace bilirubin via the same heme-oxygenase pathway (the chemistry is identical), but clinically it doesn't produce jaundice because it's excreted in urine first. If a rhabdo patient is jaundiced, look elsewhere, hemolysis (free hemoglobin overwhelming haptoglobin → bilirubin surge), ischemic hepatitis from shock (AST in the thousands, ↑ LDH, ↑ INR), or drug-induced hepatic injury. Don't blame the myoglobin.
💊 Medications
Rhabdomyolysis Medications
| Drug | Dose | Route | Role |
|---|---|---|---|
| Normal Saline or LR | 200–300 mL/hr | IV | FIRST-LINE -aggressive volume resuscitation to target UOP 200–300 mL/hr. LR may be preferred (less hyperchloremic acidosis) but avoid if K⁺ > 6.0 (contains 4 mEq/L K⁺). |
| Sodium bicarbonate | 150 mEq in 1L D5W | IV infusion | Urine alkalinization (target pH > 6.5). Controversial -no RCT evidence of benefit. Consider if urine pH < 6.5. |
| Calcium gluconate | 1–2 g IV over 10 min | IV | ONLY for hyperkalemia with ECG changes. Do NOT give for asymptomatic hypocalcemia. |
| Insulin (regular) + D50 | 10 units IV + 25g D50 | IV | K⁺ shifting for hyperkalemia. Onset 15–30 min, lasts 4–6h. |
| Kayexalate / Patiromer | Kayexalate 30g PO; Patiromer 8.4g PO | PO | K⁺ removal (delayed onset). Patiromer preferred (fewer GI side effects). |
Monitoring Parameters
| Parameter | Frequency | Target / Action |
|---|---|---|
| Urine output | Hourly (Foley required) | Target 200–300 mL/hr. If not meeting target, increase IV rate. If oliguric despite adequate fluids → nephrology consult. |
| CK (creatine kinase) | q6–12h | Trend to peak and decline. Stop aggressive IVF when CK trending down and < 5,000. |
| BMP (K⁺, Ca, PO₄, Cr) | q6h initially | K⁺ is the most dangerous -check frequently. Cr trend for AKI progression. |
| Urine pH | q6h if giving bicarb | Target > 6.5 if alkalinizing urine. |
| Compartment checks | q2–4h if limb involved | Tense, painful, swollen limb → measure pressures → fasciotomy if > 30 mmHg. |
| Vitals | q4h floor, q1–2h ICU | Watch for fluid overload with aggressive resuscitation. |
Related Topics
Acid-Base DisordersCalciphylaxis (Calcific Uremic Arteriolopathy)Chronic Kidney Disease (CKD)Contrast-Induced NephropathyDialysis IndicationsHypernatremia
📋 On Rounds
Why is the UA positive for blood but shows no RBCs on microscopy?
The urine dipstick detects the heme pigment (peroxidase activity) -it cannot distinguish between hemoglobin and myoglobin. In rhabdomyolysis, myoglobin is filtered by the glomerulus and appears in the urine. The dipstick reads this as "blood positive," but when you spin the urine and look under the microscope, there are no red blood cells. This combination -dipstick + for blood, no RBCs on micro -is the classic finding of myoglobinuria.
When should you start dialysis in rhabdomyolysis?
Standard indications for dialysis (AEIOU): Acidosis (severe, refractory to bicarb), Electrolytes (refractory hyperkalemia despite medical management), Ingestion (toxic), Overload (volume overload not responding to diuretics), Uremia (encephalopathy, pericarditis, bleeding). In rhabdo specifically, the most common indication is refractory hyperkalemia. Note: conventional hemodialysis does NOT efficiently clear myoglobin (molecular weight ~17 kDa)
Why should you avoid giving calcium for hypocalcemia in rhabdomyolysis?
In rhabdomyolysis, calcium is sequestered in damaged muscle tissue (binds to necrotic myocytes) and is also bound by elevated phosphate. This causes a transient hypocalcemia that is expected and self-limited -it will correct on its own as muscles heal and release the sequestered calcium (often causing rebound hypercalcemia in the recovery phase).
Clinical Examples
📋 Case 1, Found Down with Rhabdomyolysis
Patient: 34M found unresponsive on floor for unknown duration. PMH opioid use disorder. GCS 10 on arrival. Dark brown urine noted on Foley insertion.
Key findings: CK 85,000 IU/L. K+ 6.2. Cr 3.1 (baseline unknown). UA: dipstick positive for blood, no RBCs on microscopy (myoglobinuria). R gluteal compartment firm and tender.
Management:
- Aggressive IV crystalloid (NS or LR) 200-300 mL/hr targeting UOP 200-300 mL/hr
- Treat hyperkalemia: calcium gluconate 3g IV (ECG changes present), insulin 10 units + D50, kayexalate
- Do NOT give calcium for hypocalcemia (will worsen muscle injury), only for hyperK with ECG changes
- Monitor CK, K+, Cr, phosphorus q4-6h
- Orthopedic surgery consult for compartment pressure measurement
Teaching point: Immobilization ("found down") is one of the most common causes of rhabdomyolysis. The three killers are hyperkalemia (check K+ q4-6h), AKI (myoglobin tubular necrosis), and compartment syndrome. Dipstick positive for blood with no RBCs on microscopy is the classic myoglobinuria finding.
📋 Case 2, Statin-Induced Rhabdomyolysis
Patient: 68F, PMH hyperlipidemia, CKD stage 3. Started simvastatin 80 mg 3 weeks ago (recently added clarithromycin for pneumonia). Presents with diffuse myalgias, weakness, tea-colored urine.
Key findings: CK 22,000. Cr 2.8 (baseline 1.6). K+ 5.4. Phosphorus 6.1. Simvastatin + clarithromycin = CYP3A4 drug interaction causing toxic statin levels.
Management:
- Stop simvastatin AND clarithromycin immediately
- IV fluids 200-300 mL/hr (adjust for CKD, monitor for volume overload)
- Target UOP 200-300 mL/hr
- Avoid calcium for asymptomatic hypocalcemia
- When recovered: switch to rosuvastatin or pravastatin (not CYP3A4 metabolized)
Teaching point: Statins metabolized by CYP3A4 (simvastatin, atorvastatin, lovastatin) have dangerous interactions with CYP3A4 inhibitors (macrolides, azole antifungals, protease inhibitors). Rosuvastatin and pravastatin are safer alternatives because they are not CYP3A4 substrates.
📋 Case 3, Rhabdomyolysis with Compartment Syndrome
Patient: 25M after crush injury to R leg (motor vehicle accident). CK 120,000. R anterior leg tense, exquisitely painful with passive stretch of toes. Distal pulses present.
Key findings: Compartment pressure measurement: 38 mmHg (normal < 10). Delta pressure (diastolic BP - compartment pressure) = 22 mmHg (< 30 = concerning). Classic 5 P's: pain out of proportion, pain with passive stretch, pressure, paresthesias (late), pulselessness (very late).
Management:
- Emergent fasciotomy, this is a surgical emergency
- Do NOT wait for all 5 P's, pulselessness means irreversible damage has occurred
- Continue aggressive IV fluids for rhabdomyolysis
- Monitor for reperfusion injury after fasciotomy (may worsen hyperkalemia transiently)
- Serial CK and K+ monitoring post-fasciotomy
Teaching point: Compartment syndrome is a clinical/manometric diagnosis. Delta pressure (diastolic BP - compartment pressure) < 30 mmHg is an indication for emergent fasciotomy. Pulses may be preserved even with critical compartment pressures, do not rely on distal pulses to rule out compartment syndrome.
⚡ Summary
Rhabdomyolysis -Key Points
Diagnose It on CK Plus Context
CK above about 5 times the upper limit, typically above 1,000, with muscle pain, weakness and dark urine. A urine dipstick positive for blood with no red cells on microscopy is myoglobinuria, and that mismatch is the fastest bedside confirmation. CK peaks at 24 to 72 h and falls with a predictable half-life, so a plateau or a second rise means ongoing injury.
Fluids Are the Treatment
Aggressive isotonic IV fluid, starting at 1 to 2 L/h in severe cases, titrated to a urine output of 200 to 300 mL/h. The point is to dilute the myoglobin and flush it through the tubules before it obstructs and poisons them. The volume required is far larger than instinct suggests, because muscle sequesters enormous amounts of fluid.
The Three Killers
Hyperkalemia, which can be rapid and fatal, so check potassium every 4 to 6 h. Acute kidney injury from myoglobin-induced tubular necrosis. Compartment syndrome, so check compartment pressures if a limb is involved and remember it can develop after fluid resuscitation, not just before it.
Do Not Give Calcium for the Hypocalcemia
Unless there is tetany or ECG change. Calcium deposits in damaged muscle and worsens the injury, and it is then released later as the muscle heals, producing rebound hypercalcemia. The calcium corrects itself.
Read the Transaminases as Muscle
AST and ALT are both released from muscle, so they rise in rhabdomyolysis and look like hepatitis. AST rises higher and falls faster than ALT, and the bilirubin and alkaline phosphatase stay normal. Recognizing this stops an unnecessary hepatitis workup in a patient whose problem is entirely muscular.
Know the Causes
Trauma and crush injury, prolonged immobilization (the elderly patient found down), seizures, extreme exertion, hyperthermia including NMS and malignant hyperthermia, drugs (statins, especially with a fibrate or an interacting CYP inhibitor; cocaine; alcohol), infections, and electrolyte disturbances. Recurrent unexplained rhabdomyolysis after modest exertion suggests an inherited metabolic myopathy and warrants referral.
Bicarbonate and Mannitol Are Not Established
Neither has convincing evidence over adequate isotonic fluid alone. Urinary alkalinization is a reasonable adjunct in severe cases if the pH allows, but it risks worsening hypocalcemia. Do not let a debate about them delay or displace volume resuscitation, which is the intervention that works.
Know When Dialysis Is Needed and When to Stop Fluids
Dialyze for the usual indications: refractory hyperkalemia, refractory acidosis, volume overload and uremia, not for the CK level itself, since standard hemodialysis clears myoglobin poorly. Stop the aggressive fluids once CK is falling and urine output is established, since continuing them into a patient with established oliguric AKI causes pulmonary edema.
