Rhabdomyolysis and crush syndrome

Diagnostic approach

• ABCDE survey
• Targeted clinical evaluation
• CPK
• Myoglobin (if available)
• CMP
• CBC
• ABG
• Coagulation studies
• Urine dipstick and sediment
• Uric acid
• ECG

Myoglobinuria causes a false-positive result for blood on urine dipstick.

Diagnostic criteria

• There is no specific CPK threshold for the diagnosis of rhabdomyolysis.
• Commonly used: CPK > 5× the ULN or > 1000 IU/L

Red flag features

• Hypovolemia
• Shock
• Cardiac arrhythmias
• ECG findings in hyperkalemia
• ECG findings in hypocalcemia
• Compartment syndrome
• Crush syndrome
• AKI
• Increased risk for complications (e.g., age > 65 years, CPK > 40,000 U/L)

Management checklist

• Aggressive IV fluid resuscitation with ≥ 10–12 L/day (e.g., normal saline )
• Target urine output 1–3 mL/kg/hour (up to 300 mL/hour).
• Consider urine alkalinization if urinary pH is < 6.5 and output is adequate.
• Consider continuous cardiac monitoring.
• Serial CPK monitoring
• Monitor potassium every 4 hours.
• Manage hyperkalemia.
• Correct symptomatic hypocalcemia.
• Stop offending medications.
• Provide supportive care for AKI.
• Consult nephrology early.
• Assess for indications for acute dialysis.

Rhabdomyolysis is the breakdown of skeletal muscle tissue that results in the release of intracellular contents, such as myoglobin, potassium, phosphate, creatine phosphokinase (CPK), and urate, into the blood and extracellular space. Rhabdomyolysis has many causes, including trauma and crush injuries, drugs, overexertion, temperature extremes, infections, and prolonged immobility. The classic presenting triad of myalgia, generalized weakness, and tea-colored urine is seen in a minority of patients. The diagnosis is confirmed in patients with an elevated serum CPK, typically > 5× the upper limit of normal. Serious complications include acute kidney injury from myoglobin-induced tubular damage, cardiac arrhythmias and arrest from electrolyte derangements, and compartment syndrome. Crush syndrome is the systemic manifestation of a crush injury. It typically manifests with signs of volume depletion (hypovolemia, shock) and compartment syndrome of the affected extremity, and it is often associated with acute kidney injury. Treatment of rhabdomyolysis includes aggressive fluid resuscitation and the correction of metabolic abnormalities. In cases of renal failure, renal replacement therapy may be indicated.

• Rhabdomyolysis: breakdown of skeletal muscle tissue
• Crush injury: localized injury to the skeletal muscle by a crushing force ^[1]
• Crush syndrome: systemic manifestation of crush injury ^[1]

• Traumatic ^[2][3][4]
  • Crush injury
  • Direct injury
  • Electric injury
  • Significant burns
  • Prolonged downtime/immobilization (e.g., after a fall, overdose, coma)
  • Resistance to physical restraints
  • Envenomation (e.g., snake bite)
• Nontraumatic ^[2][3][4]
  • Seizures
  • Overexertion (e.g., strenuous exercise) ^[2]
  • Prolonged fasting ^[5]
  • Psychosis, extreme agitation
  • Heatstroke
  • Intoxication (e.g., cocaine, heroin, amphetamines, MDMA, alcohol, carbon monoxide, phencyclidine)
  • Skeletal muscle ischemia ^[6]
  • Infection
  • Adverse drug reactions (e.g., neuroleptics, statins)
  • Malignant hyperthermia

Recurrent episodes of rhabdomyolysis may indicate an underlying inherited metabolic myopathy. ^[2]

• Rhabdomyolysis → release of the following substances: ^[1][7]
  • Creatine phosphokinase (CPK) and serum myoglobin → pigment nephropathy → acute tubular necrosis → acute kidney injury (intrinsic)
  • Potassium → cardiac arrhythmia
  • Lactic acid → metabolic acidosis
• Hypovolemia → ↓ renal perfusion → acute kidney injury (prerenal) ^[8]
• Reperfusion syndrome → compartment syndrome

Rhabdomyolysis

• Classic triad
  • Myalgia
  • Generalized weakness
  • Darkened urine (red to brown)
• Nonspecific symptoms: fever, nausea, vomiting
• Signs of complications: : e.g., AKI, compartment syndrome, cardiac arrhythmias (see “Complications” for details)

Many patients are asymptomatic on presentation. The classic triad of myalgia, generalized weakness, and tea-colored urine is seen in a minority of patients. ^[9]

Crush syndrome

• In addition to signs of rhabdomyolysis: hypovolemia and shock ^[7]

General principles ^[4]

• Rhabdomyolysis is a biochemical diagnosis based on ↑ CPK levels.
• Clinicians should have a low threshold for checking serum CPK levels in patients with supportive clinical features and/or those who are at risk (see “Etiology”). ^[9]
• Further diagnostic studies should focus on identifying complications of rhabdomyolysis.
• The McMahon score for rhabdomyolysis helps identify patients at risk of death or requiring renal replacement therapy. ^[10]

Acute kidney injury is a complication that suggests a poor prognosis in patients with rhabdomyolysis. ^[8]

While there is no specific CPK threshold for the diagnosis of rhabdomyolysis, a concentration of CPK > 5× the ULN or > 1000 IU/L is commonly used. ^[9][11]

Diagnostic studies

• Blood work ^[8][10][12]
  • ↑ CPK > 5× the ULN or > 1000 IU/L ^[10][11]
    • CPK peaks within 24–72 hours of injury and declines after 3–5 days.
    • Sustained elevation should raise concern for compartment syndrome or ongoing muscle injury.
  • CMP
    • ↑ BUN, ↑ Creatinine, ↓ BUN:Cr ratio
    • ↑ Potassium, ↑ Phosphate, ↓ Calcium (ionized Ca) ^[8]
    • ↑ Lactate dehydrogenase
  • CBC
  • ↑ Uric acid
  • ↑ Myoglobin ^[9][12]
  • ABG: anion gap metabolic acidosis
  • Coagulation studies
• Urine studies ^[8]
  • Urine dipstick: may show a pH < 6.5 and be false-positive for blood (due to myoglobinuria)
  • Urine sediment: negative for RBCs, positive for pigmented granular casts
  • FENa: variable
• ECG: may show ECG findings of hyperkalemia or ECG findings of hypocalcemia

Myoglobinuria causes a false-positive result for blood on urine dipstick. Suspect myoglobinuria if urine dipstick is positive for blood in the absence of red blood cells in urine sediment.

Elevated serum myoglobin or myoglobinuria are not required to establish a diagnosis but may be useful to confirm the presence of rhabdomyolysis if there is diagnostic uncertainty.

Approach ^{[4][8][9][11][13]}

• Provide prompt IV fluid resuscitation.
• Consider stopping medications associated with rhabdomyolysis. ^[14]
• Identify and treat all reversible causes of rhabdomyolysis.
• Monitor and manage complications.
  • Perform serial laboratory monitoring (e.g., CPK, urine dipstick, BMP).
  • Correct electrolyte derangements when indicated.
  • Provide supportive care for acute kidney injury; , consult nephrology early, and assess for indications for acute dialysis.

Fluid resuscitation is indicated in all patients with CPK > 5× the ULN or > 1000 IU/L and should be continued until CPK levels decrease to below this level. ^[3]

Fluid management ^{[4][8][9][11]}

• Immediate IV fluid resuscitation (e.g., ≥ 10–12 L/day)
  • Indicated for all patients to prevent complications
  • Aggressively infuse crystalloid solutions (e.g., normal saline ).
• Urine alkalinization: not routinely recommended ^[4][11]
  • Consider for patients with a urinary pH < 6.5 if urine output is adequate.
  • Target a urine pH > 6.5 using an isotonic bicarbonate solution.
  • Avoid inducing metabolic alkalosis and/or hypokalemia. ^[2]
• Monitoring
  • Begin strict input/output monitoring and target a high initial urine output (e.g., 1–3 mL/kg/hour up to 300 mL/hour). ^[11]
  • Carefully monitor respiratory and volume status in patients with anuria or high risk for volume overload.
  • Begin de-escalation of fluid therapy once serum CPK is < 1000 U/L, urine is clear, and urine dipstick is negative for blood. ^[3]

The longer it takes for IV fluids to be started, the more likely it is that acute renal failure will develop. ^[8]

Diuretics ^[4][11][12]

The following therapies are not routinely recommended but may be considered under specialist guidance. Their use remains controversial. ^[11]

• Loop diuretics (e.g., furosemide): may be considered to force diuresis only after the patient's volume has been expanded.
• Mannitol: may be considered under specialist guidance

Management of electrolyte derangements ^[4][6][12]

• Correct hyperkalemia aggressively
  • Take a therapeutic approach to hyperkalemia based on the risk of hyperkalemic emergency.
  • Monitor potassium levels every 4 hours until normalized.
• Consider treatment for:
  • Hypocalcemia: Take a cautious approach to calcium replacement, e.g., only for symptomatic patients and those with severe hyperkalemia.
  • Hyperphosphatemia: Consider oral phosphate binders.
  • Hyperuricemia: Consider urate-lowering therapy (e.g., allopurinol).

Disposition ^[2][3]

• Admission
  • Typically required for IV fluid therapy, monitoring, and management of complications
  • Consider ICU admission for patients with: ^[4][8][10]
    • Crush syndrome
    • Complications (e.g., AKI, compartment syndrome)
    • Significant comorbidities (e.g., cardiovascular disease, CKD)
    • Increased risk for complications (e.g., age > 65 years, CPK > 40,000 U/L)
• Discharge can be considered in otherwise healthy patients with all of the following:
  • Adequate oral or IV fluid replacement
  • Exertional rhabdomyolysis without complications
  • Discharge instructions

Early complications ^[4][9]

• Electrolyte abnormalities
  • Hyperkalemia
  • Hypocalcemia
  • Hyperphosphatemia
• Hepatitis ^[12]
• Hypovolemia
• Cardiac arrhythmias, cardiac arrest (due to electrolyte derangements) ^[15]

Late complications ^[4][9]

• Hypercalcemia
• Acute kidney injury: can be oliguric or anuric
• Disseminated intravascular coagulation ^[12]
• Compartment syndrome: may develop as a result of direct muscle injury or after volume resuscitation

Compartment syndrome can occur at any stage of rhabdomyolysis and is an orthopedic emergency. ^[4][12]

We list the most important complications. The selection is not exhaustive.