Does caffeine prevent hypoxaemic episodes in premature infants?

Abstract

Fifty spontaneously breathing, preterm infants 48h old, of 32 weeks' gestation or less, were assigned randomly to receive caffeine citrate (loading dose 20 mg/kg, maintenance dose 10 mg/kg per day) or a placebo (NaCl 0.9%). The study hypothesis was that caffeine reduces the proportion of infants with recurrent hypoxaemic episodes (decrease in transcutaneous PO₂ of 20% within 20ss) from 50% to 25%. Transcutaneous oxygen tension (tcPO₂) and heart rate were recorded continuously for 50h and analysed by computer. The two groups were similar in gestational age, birth weight, delivery mode, sex distribution, and Apgar scores. The mean serum concentration (±SD) of caffeine 2h after the second maintenance dose was 96.0 (±34.5) μmol/l in the group receiving caffeine and 9.3 (±12.8) μmol/l in the group receiving a placebo. The mean proportion of infants with more than six hypoxaemic episodes per 12h in the caffeine groups was higher (57%) than in the control group (51%). The mean proportion of infants with more than six episodes of bradycardia per 12h was not statistically different in the caffeine group (79%) from the control group (86%). Our results suggest that prophylactic caffeine has little if any effect on the risk of developing hypoxaemic episodes and bradycardia in small preterm infants and the supposed 50% reduction which was considered clinically important at the start of the trial can be rejected with confidence.