NEW YORK (Reuters Health) – In a randomized trial, prolonged inhalation of low-concentration carbon dioxide for treating apnea in premature infants did not have the same benefit as was seen in a previous short-term trial, and was not as effective as treatment with theophylline.

“The findings suggest that inhalation of small concentrations of CO2, although it may be more tolerable than theophylline, cannot be considered an alternative to methylxanthines for the treatment of apnea of prematurity,” conclude the researchers in their report in the Journal of Pediatrics online September 12.

Dr. Ruben E. Alvaro and colleagues at the University of Manitoba in Winnipeg, Canada, explain that methylxanthines have been the mainstay of treatment for apnea in premature infants for 30 years, but this strategy blocks alpha-adenosine receptors with potential long-term adverse effects. On the other hand, carbon dioxide is the natural breathing stimulus, they note.

The team previously found that inhalation of a low concentration of carbon dioxide for up to 2 hours was as effective as theophylline in small infants with mild apnea of prematurity, prompting them to conduct a longer, prospective trial over 3 days.

The investigators randomized 87 infants born at 27-32 weeks’ gestation and exhibiting apnea to treatment with oral theophylline plus room air via nasal cannula or to oral saline placebo plus 0.5 L/min carbon dioxide (about 1% inhaled) via nasal prongs.

Apnea time decreased in the theophylline group from 189 seconds/hour at baseline to 57 on day 1, 50 on day 2, and 61 on day 3 (p=0.0001), the authors report. The decrease in apnea time was less in the CO2 group (although still significant at p =0.03), declining from 183 s/h to 11360, 105, and 94 on days 1-3.

“Although both treatments seemingly reduced the number and severity of apneas in most infants, theophylline was more effective than CO2,” Dr. Alvaro and colleagues conclude.

In discussing the results, they point out that maintaining a constant inhaled carbon dioxide concentration via nasal prongs would have been impractical, requiring continuous adjustments to match continually changing minute ventilation. Therefore, many infants may have received suboptimal levels of carbon dioxide, they believe.

While carbon dioxide cannot be recommended in place of theophylline, the authors suggest it could have an add-on role. “Further studies should investigate the effect of different concentrations of CO2 in preterm infants with significant apneas despite treatment with methylxanthines,” they conclude.

Reference:
CO2 Inhalation as a Treatment for Apnea of Prematurity: A Randomized Double-Blind Controlled Trial
J Pediatr 2011.