Methylxanthine for apnea of prematurity

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Over the years, multiple interventions have been used to treat apnea of prematurity – ranging from increased oxygen exposures to physical stimulation to pharmacologic interventions. The group in Winnipeg have a distinguished record of studies of respiratory control in infants. Recently, they have explored the potential of increased CO₂ as a stimulant of respiratory drive. They now report a well-designed randomized and controlled trial of increased inspired CO₂ in comparison to theophylline treatments for infants with apnea of prematurity. Both treatments worked, but theophylline was clearly a superior treatment. Given that the trial by Schmidt et al of caffeine demonstrated not only safety, but improved neurodevelopmental outcomes (NEJM 2007;357:1893-1902), and giving a drug is easier than providing a gas containing CO₂ to infants, the practical conclusion from this trial is that methylxanthine therapy is the standard of care for infants with enough apnea of prematurity to need treatment. However, the concept that increasing CO₂ will increase respiratory drive is physiologically sound and should not be forgotten.

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