Every morning, millions of adults consume voluminous cups of coffee, seeking the jolting effect of caffeine. As these adults consume their coffee, they do so unaware that some of the youngest Americans are also getting a treatment of caffeine - not to stay awake, but to assist in treating a major sleep disorder found in some neonates.
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 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.
Only one study has dealt with sleeping neonates: it showed that increased oxygen in the tissues and organs induces a greater decrease in ventilation after ingestion of aminophylline (10 mg/kg). This study was performed in infants who did not suffer from ventilatory problems, and so each infant served as his or her own control, i.e., before and after administration of aminophylline. The apnea frequency and the different sleep stages were not, however, scored.
Now a team of French physiologists has conducted a study to (1) assess whether caffeine treatment in premature neonates stimulates ventilation through peripheral chemoreceptors and (2) determine the potential influence of sleep states. The mechanism of caffeine’s action on the peripheral chemoreflex was assessed by monitoring immediate changes in the respiratory pattern in response to a 30-s hyperoxic test performed during active sleep or quiet sleep.
The authors of the study, entitled “Effect of Caffeine on Peripheral Chemoreceptor Activity in Premature Neonates: Interaction with Sleep Stages,” are Karen Chardon, Ve´ronique Bach, Fre´de´ric Telliez, Virginie Cardot, Jean-Pierre Libert, and Pierre Tourneux, all with the Laboratoire d’Environnement Toxique Pe´rinatal et Adaptations Physiologiques et Comportementales (EA2088), Faculte´ de Me´decine, Universite´ de Picardie Jules Verne, Amiens; and Andre´ Leke, at the Me´decine Ne´onatale et Re´animation Pe´diatrique, University Hospital Center Nord, Amiens, France. Their findings appear in the June 2004 edition of the Journal of Applied Physiology.