Apnea, the absence of breathing, is the most frequently reported disorder of breathing control in premature infants, and neonatal care units habitually use methylxanthine derivatives such as caffeine to treat these patients who are less than a month old. 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. Peripheral chemoreceptors, found in the carotid and aortic bodies and stimulated by chemical changes in blood composition, provide feed-forward control of respiration, which can thus terminate apnea and initiate normal breathing. These receptors are believed to be an important target for caffeine action in premature neonates.
Peripheral chemoreceptor activity is typically assessed by monitoring the rapid decline in minute ventilation (in the first minute) after inhalation of pure O2 . This drop in ventilation involves an acute reduction in peripheral chemoreceptor inputs (i.e., physiological chemodenervation) and thus reflects the strength of the peripheral chemoreceptor drive. The decrease is ultimately followed by an increase in ventilation that is centrally mediated.
However, the localization of caffeine's target site (central nervous system and/or peripheral chemoreceptors) is not well defined, especially for sleeping neonates whose sleep stages interact with respiratory control. The question of an increase in peripheral chemoreceptor responsiveness (associated or n