Why does creatine kinase MB (CKMB) increase after injection of Acuphase (generic name)?

Creatine Kinase-MB Elevation After Acuphase Injection

Creatine kinase-MB (CK-MB) elevation after Acuphase (zuclopenthixol acetate) injection is most likely due to intramuscular injection trauma causing skeletal muscle damage, which releases CK-MB into circulation, rather than from cardiac injury.

Mechanism of CK-MB Elevation After Intramuscular Injections

• CK-MB, while primarily associated with cardiac muscle, is also present in small amounts in skeletal muscle, and can be released following trauma to skeletal muscle such as intramuscular injections 1
• Intramuscular injections of medications like Acuphase (zuclopenthixol acetate) can cause local tissue damage at the injection site, leading to release of muscle enzymes including CK and CK-MB 2
• The elevation of CK-MB after intramuscular injections is typically modest (less than 2-3% of total CK) compared to the higher proportions seen in actual myocardial injury (typically >5%) 3, 4

Differentiating from Cardiac Injury

• True myocardial injury typically shows CK-MB levels greater than 5% of total CK, while skeletal muscle trauma (including IM injections) typically shows CK-MB less than 2-3% of total CK 3
• In patients with elevated CK-MB after procedures or interventions, cardiac guidelines recommend evaluating for additional evidence of cardiac injury such as:
  • Ischemic symptoms (chest pain, dyspnea)
  • ECG changes (new ST-segment or T-wave changes)
  • Imaging evidence of new loss of viable myocardium 1
• Troponin measurements are more cardiac-specific than CK-MB and can help differentiate between cardiac and non-cardiac sources of CK-MB elevation 1

Time Course of CK-MB Elevation

• After intramuscular injections, CK and CK-MB typically begin to rise within 2-4 hours, peak at 24-48 hours, and return to normal within 3-5 days 5
• This differs from the pattern seen in acute myocardial infarction, where CK-MB rises more rapidly (especially with reperfusion) and follows a more predictable pattern 5
• The kinetics of CK-MB release from skeletal muscle differ from those of cardiac origin, with skeletal muscle trauma showing a more gradual rise and fall pattern 4

Clinical Implications

• Isolated CK-MB elevation after intramuscular Acuphase injection without other signs of cardiac ischemia should not be misinterpreted as myocardial injury 1
• When evaluating CK-MB elevation after intramuscular injections, clinicians should consider:
  • The timing relative to the injection
  • The proportion of CK-MB to total CK
  • The presence or absence of cardiac symptoms
  • ECG findings
  • More cardiac-specific markers like troponin 1
• False attribution of CK-MB elevation to cardiac injury can lead to unnecessary cardiac evaluations and interventions 1

Recommendations for Clinical Practice

• When CK-MB elevation is detected after Acuphase injection, measure troponin levels to better assess for true cardiac injury 1
• Calculate the ratio of CK-MB to total CK; ratios <5% are more consistent with skeletal muscle origin 3
• Consider alternative injection sites or routes of administration in patients with recurrent elevations or in whom diagnostic confusion might lead to unnecessary interventions 1
• Document the relationship between the injection and enzyme elevation in the medical record to prevent future diagnostic confusion 1