Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages

Abstract

Caffeine is widely used for the treatment of apnea in premature neonates. 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 aim of this study was to assess the activity of the peripheral chemoreceptors in relation to sleep stages in premature neonates treated (or not) with caffeine for idiopathic apnea. Peripheral chemoreceptor activity was assessed in 22 neonates (postconceptional age of 36 +/- 1 wk with birth weights ranging from 790 to 1,910 g) by performing a 30-s hyperoxic test during active and quiet sleep. Eleven neonates received caffeine treatment (4.0 +/- 0.5 mg.kg(-1).day(-1)) and 11 served as controls. For all neonates, the decrease in minute ventilation observed during hyperoxia 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 (caffeine; -29.7 +/- 12.8% vs. control; -22.0 +/- 7.4%; F(1,15) = 4.6, P = 0.04). We conclude that caffeine administration increases the effectiveness of chemoreceptor activity. Because sleep stage durations were not affected by the treatment, it is likely that the decrease in apneic episodes typically observed with caffeine therapy is only related to respiratory processes and is independent of the sleep stage organization.

Ventilatory Response to a Hyperoxic Test Is Related to the Frequency of Short Apneic Episodes in Late Preterm Neonates

“…Neonates showed a pronounced decline inV E (Ϫ25%) in response to the hyperoxic test, as reported elsewhere (27,28). The ventilation decrease is detected at the RT, allowing measurement of the effectiveness of the peripheral chemoreceptors (22,23).…”

Caffeine at High Altitude: Java at Base Camp

“…Although caffeine had only a small effect on respiratory muscle fatigue at sea level (Lanigan et al, 1993), its effect could be more pronounced at altitude, where ventilation is markedly increased from sea level and muscle fatigue is relatively more important. Caffeine has been used for decades in neonates for treatment of apnea (Comer et al, 2001;Chardon et al, 2004). At 4 mg=kg=day, it apparently works by increasing the effectiveness of chemoreceptor activity.…”

Apneic preterms and methylxanthines: arousal deficits, sleep fragmentation and suppressed spontaneous movements

“…Prematurity, and specifically the 30 to 40 weeks post-menstrual age (PMA), is a critical developmental window for sleep-wake state organization, and the emergence of sustained arousal capacity. [9][10][11][12] Although two laboratories have failed to find effects of methylxanthines on sleep states in the premature, 13,14 behavioral indices of waking and temporal properties of movement were not studied. Thoman et al 12 found increased wake and decreased active sleep 8 weeks after cessation of theophylline treatment in preterm infants.…”