Impact of Caffeine Boluses and Caffeine Discontinuation on Apnea and Hypoxemia in Preterm Infants

Abstract

Background: Apnea of prematurity often occurs during and following caffeine therapy. We hypothesized that number of apnea events would be impacted by adjustments in caffeine therapy. Materials and Methods: An automated algorithm was used in all infants ≤32 weeks gestation admitted to a level IV Neonatal Intensive Care Unit from 2009 to 2014 to analyze chest impedance, electrocardiogram, and oxygen saturation data around the time of serum caffeine levels, caffeine boluses while on maintenance therapy, and caffeine discontinuation. Episodes of central apnea/bradycardia/desaturation (ABDs), and percent time with SpO₂ <88% and <75% were measured. Results: ABDs were analyzed in 302 preterm infants (mean gestational age 27.6 weeks) around the time of 485 serum caffeine levels, 90 caffeine boluses, and 273 episodes of caffeine discontinuation. Higher serum caffeine levels were not associated with fewer ABDs or higher heart rate. For caffeine boluses given due to clinically recognized spells, hypoxemia and algorithm-detected ABDs decreased day 1-2 after the bolus compared to the day before and day of the bolus (mean 4.4 events/day after vs. 6.6 before, p = 0.004). After caffeine discontinuation, there was no change in hypoxemia and a small increase in ABDs (2 events/day 3-5 days after discontinuation vs. 1 event/day before and >5 days after, p < 0.01). This increase in ABDs occurred irrespective of gestational age, respiratory support, or postmenstrual age at the time caffeine was stopped. Conclusions: In this retrospective analysis, caffeine boluses and caffeine discontinuation were associated with a small change in the number of ABD events in preterm infants.

Keywords: apnea; caffeine; hypoxemia; preterm infant.

FIG. 1.

Serum caffeine levels, ABD events, and heart rate. Serum caffeine levels were obtained during maintenance therapy when clinically indicated (485 levels in 238 infants). We retrospectively analyzed the number of ABD events (A) and mean heart rate (B) on the day of the caffeine level. Linear regression (solid line) and 95% confidence intervals (dotted lines) are shown. ABD, apnea/bradycardia/desaturation; HR, heart rate.

FIG. 2.

Impact of caffeine discontinuation on ABD events and hypoxemia. For 273 infants, ABDs and hypoxemia were analyzed around the time of caffeine discontinuation. (A) PMA at the time of caffeine discontinuation was higher for lower GA infants. (B) For a subset of infants, serum caffeine levels were obtained within 10 days of discontinuing caffeine, and all levels were <8 mcg/mL within 6 days. (C) Mean number of ABD events per day before and after caffeine discontinuation. (D) Mean percent time with SpO₂ <88%. Standard error bars are shown. GA, gestational age; PMA, post-menstrual age.

FIG. 3.

ABD increase after caffeine discontinuation based on respiratory support, GA, and PMA. Mean number of ABD events per day is shown 3–5 days after caffeine discontinuation compared to 0 to 2 days before discontinuation. Infants were analyzed based on whether they were on no respiratory support or CPAP, or nasal cannula (A, filled vs. open circles); whether they were < or ≥28 weeks GA (B, filled vs. open triangles); and whether they were < or ≥33 weeks PMA at the time of caffeine discontinuation (C, filled vs. open squares). Asterisks indicate a significant increase in ABDs after caffeine discontinuation for each of the three groupings (p < 0.01). CPAP, continuous positive airway pressure; NC, nasal cannula; RA, room air.