CO2 Inhalation as a Treatment for Apnea of Prematurity: A Randomized Double-Blind Controlled Trial

Objective To compare the effect of prolonged inhalation of a low concentration of CO 2 with theophylline for the treatment of apnea of prematurity. Study design Prospective, randomized, double-blind controlled trial of 87 preterm infants with apnea of prematurity (27-32 weeks' gestational age) assigned to either theophylline plus 0.5 L/min of room air via nasal prongs or placebo plus 0.5 L/min with CO 2 (about 1% inhaled) by nasal prongs for 3 days. Results Apnea time significantly decreased in the theophylline group from 189±33 s/h (control) to 57±11, 50±9, and 61±13 (days 1-3) ( P =.0001) and in the CO 2 group from 183±44 (control) to 101±26, 105±29, and 94±26 s/h (days 1-3) ( P =.03). Seven infants in the CO 2 group but none in the theophylline group failed to complete the study due to severe apneas ( P =.003). Conclusions Because theophylline was more effective in reducing the number and severity of apneas, inhalation of low concentration of CO 2 , as used in the present study, cannot be considered as an alternative to theophylline in the treatment of apnea of prematurity. The less effectiveness of CO 2 treatment may have been related to the variability of the delivery of CO 2 .