Use of the oculocardiac reflex to assess vagal reactivity during quiet sleep in neonates JACQUES DUCROCQ 1 , VIRGINIE CARDOT 1 , PIERRE TOURNEUX 1,2 , KAREN CHARDON 1 , FRE ´ DE ´ RIC TELLIEZ 1 , JEAN-PIERRE LIBERT 1 , ALAIN DE BROCA 2 and V E ´ RONIQUE BACH 1 1 Unite´ de Recherches sur les Dysre´gulations Me´taboliques Acquises et Ge´ne´tiques (EA 3901-INERIS), Faculte´ de Me´decine, Amiens Cedex and 2 Service de Me´decine Ne´onatale et Re´animation Pe´diatrique Polyvalente, Centre Hospitalier Universitaire, Amiens Ce´dex 1, France Accepted in revised form 19 November 2005; received 12 May 2005 SUMMARY Arousal from sleep can be a protective response to life-threatening stimuli. Hence, faults within state-switching processes may lead to fatal events. To investigate the role of the nervous system during cardiac failure triggered by phasic, vagally mediated stimulation, we analysed autonomic and behavioural reactions in 50 premature neonates during quiet sleep (QS) – a sleep state characterized by a preponderance of tonic, parasympathetic activity. Bradycardia was induced with a standardized ocular compression test. Neither awakening nor behavioural escape reactions were observed during or after an episode of bradycardia. Eighty-six per cent of the provoked bradycardic episodes induced central apnoea. During QS, the neonatesÕ respiratory response and arousability were found to be time-dependent: when the test was performed early in the QS episode, apnoea was more frequent (94%), and no sleep state change occurred. When ocular compression was performed in the later part of the QS episode, a transition towards active sleep was observed, together with significantly fewer episodes of apnoea (64%). These results indicate that a progressive decrease in the respiratory system’s responsiveness to phasic, parasympathetic stimulation occurs during QS, whereas arousability increases. Our study suggests that newborns could be more vulnerable to potentially fatal events during the initial portion of a QS episode. keywords arousal, autonomic nervous system, bradycardia, neonate, sleep INTRODUCTION Sleep state changes and awakening from sleep are important protective responses to life-threatening stimuli. Defects in the systems regulating these responses may correspond to an infant’s failure to arouse, and thus may underlie fatal events, such as sudden infant death syndrome (SIDS). An appropriate response to a respiratory or a cardiac challenge during sleep may involve arousal or a state-switching process (Harper and Bandler, 1998; Harper et al., 2000). As neonates show more episodes of bradycardia and apnoea during active sleep (AS) than during quiet sleep (QS) (Curzi-Dascalova and Christova- Gueorguieva, 1983; Curzi-Dascalova et al., 2000; Goto et al., 1999), AS is usually considered to be the most critical sleep state. However, the possibility that QS may be implicated in fatal events cannot be ruled out – notably because this sleep state is characterized by lower arousability when compared with AS and could, therefore, be more vulnerable than AS (see Horne et al., 2004 for a review). Thus, it could be postulated that autonomic challenges (such as bradycardia) during QS may be unable to elicit awakening. Such a defect would limit the ability of the central nervous system (CNS) to overcome a cardiac challenge when the appropriate regulatory responses necessitate a sleep state change or awakening. Several studies have shown that sympathetic heart rate modulation is enhanced in AS, whereas vagal modulation predominates in QS (Harper et al., 1978; Correspondence: Ve´ ronique Bach, Unite´ de Recherches sur les Dysre´ gulations Me´ taboliques Acquises et Ge´ ne´ tiques (EA 3901- INERIS), Faculte´ de Me´decine, 3 rue des Louvels, F-80036 Amiens Cedex, France. Tel.: 33-(0)3-22-82-78-99; fax: 33-(0)3-22-82-78-96; e-mail: veronique.bach@u-picardie.fr J. Sleep Res. (2006) 15, 167–173 Ó 2006 European Sleep Research Society 167