Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs

Abstract

Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR.

Nasal Continuous Positive Airway Pressure Inhibits Gastroesophageal Reflux in Newborn Lambs

“…Of note, the laryngeal chemoreflexes have been involved in some cases of apnea of prematurity, apparent life-threatening events in infancy and sudden infant death syndrome [20]–[22]. Of particular interest, we previously showed that nCPAP significantly decreases the cardiorespiratory inhibition observed during experimentally-induced laryngeal chemoreflexes in preterm lambs [23]. The present results fittingly complement the findings of the former study, showing that nCPAP not only decreases the number of GER reaching the proximal esophagus (and thus potentially the laryngeal mucosa), but also prevents the potentially dramatic cardiorespiratory consequences of laryngeal chemoreflexes in newborns.…”

Nasal continuous positive airway pressure influences bottle-feeding in preterm lambs

“…The experiments were conducted on 17 preterm lambs (8 control and 9 nCPAP of 6 cmH 2 O) born 14 days prematurely as previously described (8). Briefly, premature labor was induced by mifepristone (8 mg/kg; Sigma-Aldrich, Oakville, Canada), after stimulation of lung surfactant maturation by intramuscular betamethasone (12 mg × 2; Schering-Plough Canada, Kirland, Canada).…”

The contribution of ovine models to perinatal respiratory physiology

“…This enhanced LCR-related cardiorespiratory inhibition in preterm lambs largely decreased with postnatal maturation (84), whereas the autonomic activity following LCR decreased (103). In addition, while application of nasal continuous positive airway pressure was found to consistently blunt the LCRrelated cardiorespiratory inhibition in preterm lambs, the overall effect of caffeine was found to be nonsignificant (85).…”

“…Lambs require continuous care during the first 48h of life to prevent and treat hypothermia, hypoxia and hypoglycemia. In addition, high-flow nasal cannula is occasionally used in lambs with mild to moderate respiratory distress syndrome (85). Overall, our preterm lambs constitute a model of late preterm infant born at about 34 weeks of gestation.…”