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

Abstract

Objective: To determine if apneic preterm infants currently treated with methylxanthines develop evidence of sleep deprivation from cumulative arousal and motor activational effects.Study Design: Sleep, wake, arousal and actigraphic movements were monitored in extubated clinically stable premature infants (N ¼ 37). Neonates were free of other medications for >72 h and were grouped based on methylxanthine exposure: >5 days with caffeine (n ¼ 14), >5 days theophylline (n ¼ 13) or no prior exposure (n ¼ 10).Result: Duration of methylxanthine treatment predicted increased arousals, wakefulness and actigraphic movements, and decreased active sleep. Recording from 1200 to 0500 hours, methylxanthine-treated groups showed reductions in all arousal parameters: waking state, number of wake epochs, brief arousals and composite arousal index, and shorter fast-burst, sleep-related motility than untreated controls. Conclusion:In apneic preterms, chronic methylxanthine treatment appears to produce sleep deprivation secondary to the stimulatory action of methylxanthines on arousal and motor systems.

Unobtrusive sleep state measurements in preterm infants – A review

“…A wide range of motor activity can be detected (38). Motor activity is sporadic and appears in bursts of 5-60 s (41), but muscle tone is low between the movements (13,41).…”

“…QS: The eyes are closed (5,40,41). Little or no motor activity is detectable (38), only appearing as occasional startles, sighs or other brief discharges.…”

“…AS: The eyes are closed (5,40,41) or slightly opening and closing (22). They might open during REM in AS (41).…”

Long-Term Effects of Caffeine Therapy for Apnea of Prematurity on Sleep at School Age

“…Studies across the age spectrum have shown that methylxanthines result in decreased sleep time and fragmented sleep (8,9), and can also lead to decreased rapid eye movement/ active sleep in neonates (10). This may have important clinical consequences, as sleep, and in particular rapid eye movement sleep, is thought to be important for memory and learning (11).…”

Caffeine Reduces Apnea Frequency and Enhances Ventilatory Long-Term Facilitation in Rat Pups Raised in Chronic Intermittent Hypoxia

“…Another limitation in our experimental design is that we did not take into consideration the sleep-wake state during recordings and we have no data whether n-IH per se affects sleep organization. Sleep/wake cycles are very brief during the first postnatal week in newborn rats (31) and contradictory effects of caffeine are reported in premature infants with either no effects (32) or sleep deprivation (33). Although caffeine may have reduced sleep time in rat pups, it is unlikely that this would interfere with ventilatory LTF expression.…”