Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity

Apnea of prematurity is common and none of the treatments being used are fully effective and free of significant adverse side effects. We hypothesized that low concentrations of CO2 (< or = 1.5%) may reduce apnea without causing discomfort from an increase in ventilation. We studied 10 preterm infants at a gestational age of 32+/-1 wk (mean +/- SEM) and birthweight 1.8+/-0.2 kg. After a control period of 1 hour, concentrations of CO2 were given (0.5%, 1%, and 1.5%) for 1 hour each, followed by a recovery period of 1 hour. Apnea number significantly decreased from 2.0+/-0.3 apneas/min during control to 1.0+/-0.1 apneas/min (0.5% CO2; P < .05), 1.1+/-0.2 (1% CO2; P < .05), and to 0.7+/-0.2 (1.5% CO2; P < .01). The apnea time significantly decreased from 14.2+/-2.5 s/min during control to 5.2+/-0.8 (0.5% CO2; P < .01), 5.8+/-0.7 (1% CO2; P < .01), and to 3.7+/-0.9 (1.5% CO2; P < .01). Minute ventilation significantly increased with CO2 without evidence of respiratory discomfort. TcPCO2 did not change and TcPO2 increased slightly. These findings suggest that inhalation of low concentrations of CO2 in preterm infants with apnea 1) decreases the number and time of apneas, 2) improves oxygenation, 3) increases ventilation, and 4) is effective even in such low concentrations as 0.5%. We speculate that inhalation of CO2 (< 1%) is more effective and safer than methylxanthines for the treatment of apnea of prematurity.