Test Catalog

Test ID: CAFF    
Caffeine, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring caffeine therapy in neonates


Assessing caffeine toxicity in neonates

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Caffeine is used to treat apnea of prematurity that occurs in newborn infants, the most frequent complication seen in the neonatal nursery.


In neonates, caffeine has a half-life that ranges from approximately 3 to 4 days, which is much longer than in adults (typically 4-6 hours) due to the immaturity of the neonatal liver. This requires that small doses be administered at much longer intervals than would be predicted based on adult pharmacokinetics.


The volume of distribution of caffeine is 0.8-0.9 L/kg (infants) or 0.6 L/kg (adults) and the drug is approximately 36% protein bound.


Toxicity observed in neonates is characterized by central nervous system and skeletal muscle stimulation and bradycardia. These symptoms are seen in adults at lower levels than in neonates, suggesting that neonates have much greater tolerance to the drug.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Therapeutic: 8.0-20.0 mcg/mL

Critical value: > or =30.0 mcg/mL

Interpretation Provides information to assist in interpretation of the test results

Optimal pharmacologic response occurs when the serum level is in the range of 8.0 to 20.0 mcg/mL.


Toxicity in neonates and adults may be seen when the serum level is above 20.0 mcg/mL.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay is not intended to detect levels in adults.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Milone MC, Shaw LM: Therapeutic drugs and their management. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier; 2018:800-831

2. Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. McGraw-Hill; 2018

3. Ou CN, Frawley VL: Concurrent measurement of theophylline and caffeine in neonates by an interference-free liquid-chromatographic method. Clin Chem. 1983;29:1934-1936