CK

Background

• Creatine kinase (CK, also called CPK) is an enzyme found predominantly in skeletal muscle, cardiac muscle, and brain.
• When these tissues are damaged, CK leaks into the bloodstream.
• In the ED, CK is most commonly used in the evaluation of rhabdomyolysis and as an adjunct in certain cardiac and neuromuscular presentations.

• CK catalyzes the conversion of creatine + ATP → phosphocreatine + ADP, providing energy to tissues with high metabolic demand
• Three isoenzymes based on tissue of origin:
  • CK-MM: Skeletal muscle (~98% of skeletal muscle CK) — the predominant source of elevated total CK in the ED
  • CK-MB: Cardiac muscle (~20–30% of cardiac CK) — largely supplanted by troponin for MI diagnosis
  • CK-BB: Brain — rarely measured clinically
• Kinetics: CK rises within 2–12 hours of muscle injury, peaks at 24–36 hours, and declines at ~30–40% per day (half-life ~36 hours). Levels typically normalize within 3–5 days if injury resolves
• Normal range: ~22–198 U/L (varies by lab, sex, race, and muscle mass; higher in males, African Americans, and those with greater muscle mass)

Clinical Features

CK is ordered as an adjunct to clinical evaluation. Consider checking CK in the following ED presentations:

• Muscle pain, weakness, or dark urine — rhabdomyolysis evaluation
• Prolonged immobilization, found down, crush injury — occult rhabdomyolysis
• Drug/toxin ingestion — cocaine, amphetamines, MDMA, ethanol, heroin, NMS, serotonin syndrome, statins
• Seizures, agitation, physical restraint — rhabdomyolysis screening
• Exertional heat illness — heat stroke workup
• Chest pain — CK-MB historically used for MI; now supplanted by troponin (CK-MB may still add value in detecting reinfarction or periprocedural MI)
• Suspected compartment syndrome — CK elevation supports diagnosis but does not replace pressure measurement

Differential Diagnosis

Causes of Elevated CK

• Rhabdomyolysis (most common ED-relevant cause): Trauma/crush injury, prolonged immobilization ("found down"), cocaine/amphetamines/MDMA, seizures, extreme exertion, heat stroke, neuroleptic malignant syndrome, serotonin syndrome, malignant hyperthermia, statins + fibrates, hypokalemia, hypothyroidism
• Cardiac: Acute coronary syndrome (CK-MB fraction), myocarditis, cardiac surgery
• Inflammatory myopathy: Polymyositis, dermatomyositis
• Muscular dystrophy: Duchenne, Becker (can be markedly elevated)
• Other: Hypothyroidism, sickle cell disease, intramuscular injections, recent surgery, intense exercise (benign exertional), statin myopathy, viral myositis, compartment syndrome
• Mild elevations (2–10× normal): Common after vigorous exercise, IM injections, minor trauma — often clinically insignificant

Causes of Low CK

• Low muscle mass (cachexia, elderly, sedentary)
• Connective tissue disease (e.g., rheumatoid arthritis — some patients)
• Liver disease, alcoholism

Evaluation

Workup

• Total CK is the primary test ordered in the ED
• When evaluating for rhabdomyolysis, also order:
  • BMP/CMP (creatinine, potassium, calcium, phosphorus, bicarbonate)
  • Urinalysis — heme-positive on dipstick with few/no RBCs on microscopy suggests myoglobinuria
  • LDH, AST (both elevated in rhabdomyolysis; AST from muscle, not necessarily liver)
  • Uric acid (often elevated)
  • Coagulation studies if DIC concern
• Consider checking urine myoglobin if available, though it has a very short half-life (~2–4 hours) and may be negative by the time CK peaks
• Serial CK every 6–12 hours to establish peak and trend — failure to decline suggests ongoing injury (consider compartment syndrome or persistent cause)
• CK-MB and CK-MB index are rarely needed in the troponin era but may help distinguish cardiac vs. skeletal muscle source if total CK is very high and troponin is borderline

Diagnosis

• Rhabdomyolysis: CK >5× upper limit of normal (~1,000 U/L) is the consensus threshold; CK ≥5,000 U/L increases risk of acute kidney injury; CK >15,000 U/L is a significant predictor of renal failure
• Mild CK elevation (200–1,000 U/L): Common after exercise, IM injections, seizures, minor trauma — usually clinically insignificant without symptoms or renal dysfunction
• Dipstick heme-positive urine without RBCs = myoglobinuria until proven otherwise — assume rhabdomyolysis
• Elevated AST out of proportion to ALT with elevated CK suggests muscle (not liver) as the source of the transaminase elevation — do not reflexively attribute elevated AST to hepatic injury in rhabdomyolysis

Management

• Management is directed at the underlying cause and prevention of acute kidney injury
• Rhabdomyolysis with CK >5,000 U/L or AKI:
  • Aggressive IV crystalloid resuscitation (target urine output 200–300 mL/hr in adults)
  • Monitor and correct hyperkalemia (immediate life threat), hypocalcemia, hyperphosphatemia
  • Serial CK, BMP, and urine output monitoring
  • Avoid nephrotoxins (NSAIDs, contrast if possible)
  • Bicarbonate for urine alkalinization is controversial and not routinely recommended
• Mild CK elevation without symptoms or renal dysfunction: Oral hydration, outpatient follow-up, repeat CK if persistent concern
• Statin-associated myopathy: Hold statin; discuss with PCP regarding rechallenge vs. alternative agent

Disposition

• Admit if: CK >5,000 U/L with rising trend, AKI, hyperkalemia, significant electrolyte derangements, ongoing muscle injury (e.g., compartment syndrome), or unable to maintain adequate oral hydration
• Consider admission or observation for: CK 1,000–5,000 U/L with renal risk factors (dehydration, CKD, diabetes, NSAID use, cocaine use, multiple etiologies)
• Discharge with follow-up if: Mild CK elevation (<1,000 U/L), normal renal function, no electrolyte abnormalities, able to hydrate orally, and clear benign etiology (e.g., post-exercise)
• McMahon score may help risk-stratify patients with rhabdomyolysis for AKI and need for dialysis (validated score using age, sex, initial CK, creatinine, calcium, phosphate, bicarbonate, and etiology)

See Also

• Rhabdomyolysis
• Acute kidney injury
• Hyperkalemia
• Compartment syndrome
• Neuroleptic malignant syndrome
• Heat stroke
• Crush injury

External Links

• EMCrit IBCC: Rhabdomyolysis