Apnea, the absence of breathing, is the most frequently reported disorder of breathing control in premature infants, and neonatal care units often use methylxanthine derivatives such as caffeine to treat these patients who are less than a month old.
Scientists claim that caffeine treatment for premature infants is supposed to increase breathing frequency, decrease the number of apneic spells, and reduce partial tension of carbon dioxide (PCO2) and the need for (and duration of) mechanical ventilation.
But up until recently the localisation of caffeine's target site - central nervous system and/or peripheral chemoreceptors - was not well defined.
"The question of an increase in peripheral chemoreceptor responsiveness (associated or not with a direct, central action of caffeine) remains debatable, particularly in human neonates. Past studies were performed in animal models for which chemical loss of nerve supply can alter respiratory behavior and can lead to sudden death," reports the American Physiological Society.
In the June 2004 edition of the society's bulletin, the Journal of Applied Physiology French researchers report on a new study that for the first time investigated whether caffeine treatment in premature babies stimulates ventilation through peripheral chemoreceptors and also to determine the potential influence of sleep states.
The authors of the study at Picardy University in Amiens and the University Hospital Center Nord in Amiens, France, assessed the mechanism of caffeine's action on the peripheral chemoreflex by monitoring immediate changes in the respiratory pattern in 22 premature babies in response to a 30-s hyperoxic test performed during active sleep or quiet sleep.
The caffeine group consisted of 11 newly borns receiving an oral caffeine citrate treatment for apnea caused by unknown reasons and delivered to those who had shown more than one significant apneic episode per hour during the first hours of life. (A significant apneic episode was defined as a respiratory arrest of seven seconds or more, associated with either a fall of heart rate below 100 beats/min or a fall in blood oxygen level of at least 10 percent relative to the previous baseline.)
After three weeks of treatment, this group was compared with a control group (11 premature babies not undergoing caffeine therapy) matched for age and body mass.
"Two important findings were observed in this study," reports the American Physiological Society. "First, for all neonates, the decrease in minute ventilation observed during increased oxygen was greater during active than during quiet sleep. Neonates receiving caffeine showed a significantly greater decrease in ventilation during hyperoxia in both sleep stages, compared with controls."
Secondly, the data obtained "strongly suggests that the effectiveness of chemoreceptor activity is enhanced during caffeine administration, because the drug amplifies the drop in ventilation compared with controls".
The report adds that, unfortunately, the mechanism of action by which caffeine acts on chemoreceptor activity is unknown. "However, in the present study the researchers cannot rule out a direct effect of caffeine increasing the responsiveness of the central nervous structures that control ventilation."
In addition, the findings validate previous beliefs that the anti-apneic effect of caffeine is not related to sleep state disturbances but rather to a direct action on processes controlling the infant's respiration.