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 CO2 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 CO2 (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 CO2 group from 183 +/- 44 (control) to 101 +/- 26, 105 +/- 29, and 94 +/- 26 s/h (days 1-3) (P = .03). Seven infants in the CO2 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 CO2, 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 CO2 treatment may have been related to the variability of the delivery of CO2. (J Pediatr 2012;160:252-7).