Stopping caffeine in premature neonates: how long does it take for the level of caffeine to fall below the therapeutic range?

Background: Caffeine is routinely used in preterm infants for apnea of prematurity. Preterm infants are usually monitored for 5 days after discontinuation of caffeine to assess for possible recurrence of apnea. Our objective was to determine if the serum concentration of caffeine decreases to a subtherapeutic level 5 days after its discontinuation.

Methods: This is a retrospective analysis of caffeine levels after the drug was discontinued in preterm neonates (birth weight ≤1500 g) born between January 2010 and June 2017. The primary outcome was the proportion of infants with therapeutic levels of caffeine 5 days after the drug was stopped.

Results: Caffeine levels were measured in 353 samples from 280 infants (birth weight 1246 ± 390 g and gestational age 29.2 ± 2.4 weeks) after discontinuation of the drug. Five and more days after discontinuation of caffeine, 29.3% (82/280) of the infants had caffeine levels ≥5 mg/L. Approximately 41% (75/181) of the caffeine levels measured between 5 and 7 days and 18% (17/95) between 8 and 10 days were ≥5 mg/L. A caffeine dose of >5 mg/kg/day when discontinued was associated with the caffeine level of ≥5 mg/L (OR 2.3, 95% CI 1.28-4.13,  = .005).

Conclusions: Preterm infants treated with caffeine frequently had therapeutic levels of caffeine 5-10 days after discontinuation of the drug. The infants receiving higher doses were more likely to have a therapeutic level of caffeine 5 days after stopping the medication. Preterm infants should be monitored for recurrence of apnea for more than 5 days after stopping caffeine or levels should be monitored prior to discharge.