Can intramuscular (IM) injection cause creatine kinase (CK) elevation?

Intramuscular Injections Can Cause Creatine Kinase Elevation

Yes, intramuscular (IM) injections can cause elevations in creatine kinase (CK) levels due to muscle damage from the injection procedure. This is an important consideration when interpreting laboratory results in patients who have recently received IM injections.

Mechanism of CK Elevation After IM Injections

• Intramuscular injections cause direct trauma to muscle tissue, leading to sarcomeric damage and release of creatine kinase into the bloodstream 1
• CK is an enzyme found primarily in skeletal muscle, cardiac muscle, and brain tissue, and serves as a marker of muscle damage when elevated in serum 1
• When the needle penetrates muscle tissue during an IM injection, it causes local muscle fiber disruption, resulting in CK release 2

Factors Affecting CK Elevation Risk with IM Injections

Injection Technique and Needle Length

• Longer needles (≥8 mm) significantly increase the risk of inadvertent intramuscular injection, particularly in limbs rather than truncal sites 3, 4
• The 4-mm needle is recommended as the safest option for subcutaneous injections as it minimizes the risk of reaching muscle tissue 3
• When using needles ≥6 mm in length, a proper skinfold technique should be used to minimize the risk of IM injection 3

Anatomical Considerations

• The risk of inadvertent IM injection varies by injection site, with highest risk in the thigh and lowest in the buttocks 4
• Subcutaneous fat thickness varies widely between individuals, with women having approximately 5 mm greater subcutaneous fat thickness than men at the same BMI 3, 5
• Truncal sites (abdomen and buttocks) have thicker subcutaneous fat layers than limbs (thighs and arms), making them safer for injections 3

Patient Characteristics

• Slimmer patients, younger patients, and males are at higher risk for inadvertent IM injections due to thinner subcutaneous tissue 3, 5
• BMI directly correlates with subcutaneous fat thickness - for every 10 kg/m² increase in BMI, subcutaneous tissue increases by approximately 4 mm 5

Clinical Implications

• CK elevation following IM injection typically peaks within 24 hours and gradually returns to baseline with rest 1
• Certain injectable medications, particularly local anesthetics and NSAIDs, have demonstrated myotoxic effects that can further increase CK levels when administered intramuscularly 2
• Unexplained glycemic variability and hypoglycemic episodes in diabetic patients may suggest inadvertent IM insulin injection 3
• When interpreting elevated CK levels, recent history of IM injections should be considered as a potential cause 1

Recommendations to Minimize Risk

• Use the shortest appropriate needle length (4-5 mm) for subcutaneous injections to minimize risk of reaching muscle 3, 4
• For insulin administration, the 4-mm pen needle is considered the safest option for all patients regardless of BMI 3
• When using longer needles, employ proper technique including skinfold lifting and 45° insertion angle to reduce IM risk 3
• Choose injection sites with greater subcutaneous tissue thickness (abdomen and buttocks) over limbs when possible 3, 5
• Be particularly cautious in thin patients, children, and males who have less subcutaneous tissue and higher risk of IM injection 3

Monitoring and Assessment

• Consider recent IM injections when interpreting elevated CK levels in clinical practice 1
• In patients with persistently elevated CK without clear cause, evaluate for underlying myopathies that may be exacerbated by IM injections 1
• Monitor patients with diabetes for signs of unexpected hypoglycemia after insulin administration, which may indicate inadvertent IM injection 3