Caffeine Drug Monitoring in Newborns

Caffeine, Serum or Plasma 2011603
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Caffeine is used in the treatment of apnea of prematurity in newborns. Therapeutic monitoring is critical to ensure concentration does not become toxic, which may cause tremor, cardiac abnormalities, and seizures. Reference ranges for this test do not apply to adults.

Disease Overview

Physiology

  • Apnea in newborns is defined by apnea that lasts
    • >20 seconds, or
    • >10 seconds when accompanied by bradycardia or oxygen desaturation <80%
  • In newborns with apnea associated with prematurity, caffeine
    • Stimulates central respiratory center
    • Decreases carbon dioxide threshold
    • Increases response to hypercapnea
    • May increase skeletal muscle tone
    • May aid respiratory effort by decreasing fatigue of diaphragm

Drug Profile

  • Chemical name – 1,3,7-trimethylxanthine
  • Antagonist to endogenous adenosine at A1 and A2 receptor subtypes
    • Inhibits cyclic nucleotide phosphodiesterases and leads to increased levels of cyclic AMP
  • Net effects
    • Stimulates central nervous system (CNS) and cardiac muscle
    • Relaxes bronchial smooth muscle
    • Acts as mild diuretic
  • Bioavailability is near 100% with oral administration
  • Caffeine is metabolized in the liver by cytochromes P450 1A2 (CYP1A2), CYP2E1, and CYP3A3/4
  • Toxicity in infants has been associated with serum levels of 24-350 mg/mL

Test Interpretation

Analytical Sensitivity

Limit of quantification 1 mg/mL

Results

  • Concentration is reported
  • Therapeutic range in neonates
    • Age 0-28 days
      • 8-20 mg/mL
    • Age 29 days and older
      • ≤20 mg/mL (not well established)
  • Toxic range – >20 mg/mL
    • Toxic concentrations may cause tremor, cardiac abnormalities, and seizures

Limitations

Therapeutic and toxic ranges for this test are not applicable for adults.

Last Update: April 2019