What is the role of creatinine kinase (CK) and serum myoglobin in diagnosing and managing malignant hyperthermia in patients with a history of muscle disorders or family history of malignant hyperthermia?

Role of Creatine Kinase and Serum Myoglobin in Malignant Hyperthermia

Creatine kinase (CK) and serum myoglobin are markers of muscle breakdown during an acute malignant hyperthermia (MH) crisis but have no role in diagnosing MH susceptibility and should not be used as screening tests for MH risk.

Diagnostic Role: Acute MH Crisis vs. Susceptibility Testing

During Acute MH Episodes

Elevated CK and myoglobin indicate rhabdomyolysis during an active MH crisis but do not confirm the diagnosis. 1

• CK elevation occurs as a consequence of muscle breakdown during acute MH episodes, with peak levels varying widely depending on severity, succinylcholine use, and the surgical procedure itself 2
• Myoglobinuria develops from severe muscle damage and can lead to acute tubular necrosis and renal failure, requiring aggressive fluid management with urine output maintained >2 ml/kg/h 3, 4
• Approximately 30% of MH-positive patients treated with dantrolene have peak CK values within the normal range expected from the surgical procedure alone, making CK unreliable for distinguishing MH from surgical trauma 2
• Succinylcholine significantly increases peak CK levels in MH-positive patients compared to those not receiving succinylcholine, creating substantial overlap with CK elevations from major surgical procedures 2

Critical Limitation: No Role in Screening or Diagnosis of MH Susceptibility

Serum CK levels do not identify MH-susceptible individuals and should be abandoned as a screening or diagnostic test for MH susceptibility. 5

• In a definitive study of 131 patients undergoing muscle biopsy for in vitro contracture testing (IVCT), all 34 MH-susceptible patients had normal baseline CK levels 5
• All 87 MH-non-susceptible patients also had normal CK levels, demonstrating zero discriminatory value 5
• The European Malignant Hyperthermia Group guidelines identify persistently raised serum CK as a referral criterion only when it represents idiopathic hyperCKemia (after neurological work-up excludes other myopathies), not as a diagnostic marker for MH 1

When to Measure CK and Myoglobin in MH Context

Preoperative Considerations

Preoperative CK measurement is not routinely necessary for known MH-susceptible patients. 6

• Consider measuring CK, potassium, and myoglobin only if there is history of elevated resting CK, muscular symptoms (cramps, myalgia), or rhabdomyolysis to evaluate for underlying myopathy rather than MH susceptibility 6
• Persistently elevated CK (>500 U/L) after neurological work-up warrants referral for MH susceptibility testing via IVCT or genetic testing, not because CK diagnoses MH but because it may indicate an associated myopathy 1, 7

During Suspected Acute MH Crisis

Monitor CK and myoglobin as markers of rhabdomyolysis severity and renal risk, not to confirm MH diagnosis. 3, 4

• Check urinalysis for myoglobinuria (positive for myoglobin, negative for hematuria and bilirubin) to assess risk of acute kidney injury 8, 4
• CK levels can reach extraordinarily high values (>178,000 IU/L documented in pediatric cases) but may also be only moderately elevated (375 IU/L) even with clinical MH features 9, 4
• Moderate CK elevation does not exclude MH, as demonstrated by a case with CK of only 375 IU/L and myoglobin of 114 μg/L presenting with classic MH features (though IVCT was ultimately negative) 9

Gold Standard for MH Susceptibility Diagnosis

The in vitro contracture test (IVCT) remains the gold standard for diagnosing MH susceptibility, with DNA analysis playing an important but less sensitive role. 1

• IVCT has the highest sensitivity for detecting MH susceptibility through pharmacological challenge of fresh skeletal muscle with halothane and caffeine 1
• DNA analysis is less invasive but not as sensitive as IVCT, with major utility in family screening after an index case is identified 1
• Clinical evaluation based on anesthetic history, medical history, and family history guides the decision to pursue IVCT or genetic testing 1

Common Pitfalls to Avoid

Do not use CK or myoglobin levels to screen for MH susceptibility in patients with family history or prior concerning anesthetic events—these markers have zero predictive value for identifying at-risk individuals 5

Do not reassure patients with normal CK that they are not MH-susceptible—all MH-susceptible individuals in validation studies had normal baseline CK 5

Do not delay dantrolene administration during acute MH crisis while waiting for CK or myoglobin results—diagnosis is clinical (unexplained hypercarbia, tachycardia, muscle rigidity, temperature increase), and treatment must be immediate 1, 6

Do not attribute elevated CK solely to MH when it could represent the surgical procedure itself—major vascular and abdominal surgeries produce CK elevations overlapping with MH, requiring clinical context for interpretation 2

Do not overlook myoglobinuria as a marker of severe rhabdomyolysis requiring aggressive fluid resuscitation—this complication can cause acute renal failure and must be managed aggressively regardless of MH diagnosis 3, 4