Respiratory activity of the cricopharyngeus muscle in the neonatal period.

While phasic electrical activity of the cricopharyngeus muscle (EAcp)-the main component of the upper esophageal sphincter-occurs with inspiration and forceful expiration in adults, no such data is available for newborns. In addition, the effect of nasal respiratory support commonly used in newborns is unknown. We aimed to describe the phasic respiratory EAcp and to assess the potential effect of nasal CPAP (nCPAP, 6 cmH2O) or high-flow nasal cannula (HFNC, 7 L/min) in newborn lambs during 6-h recordings. Phasic EAcp was present in 11/17 lambs, including in 32 % (25, 81) [(median (Q1, Q3)] of respiratory cycles in wakefulness, 40 % (27, 70) in NREM sleep, and 10 % (0, 23) in REM sleep. In addition, EAcp was observed only during post-inspiration and/or expiration. Nasal CPAP or HFNC assessed in 7 of the 17 lambs did not have any effect. We conclude that phasic respiratory EAcp occurs in post-inspiration and expiration in newborn lambs.

Nasal high-frequency oscillatory ventilation inhibits gastroesophageal reflux in the neonatal period.

Nasal high-frequency oscillatory ventilation (nHFOV) in neonates is increasingly considered due to enhanced alveolar ventilation, absence of patient-ventilator asynchrony and lessened ventilator-induced lung injury. Although any type of non-invasive respiratory support can lead to gastric distension via esophageal air passage and thus promote gastroesophageal refluxes (GERs), we have shown that nasal continuous positive airway pressure (CPAP; 6 cmH2O) and intermittent positive pressure ventilation (15/4 cmH2O) conversely inhibit GERs in lambs. The current objective was to test the hypothesis that nHFOV also inhibits GERs compared to spontaneous ventilation without respiratory support. Eight lambs underwent five hours of polysomnographic and esophageal multichannel intraluminal impedance pHmetry recordings to assess GERs and air passage into the esophagus, with and without nHFOV (mean airway pressure = 8 cmH2O, oscillation frequency = 8 Hz, amplitude ≈ 20 cmH2O and I:E = 1:2). Results revealed that GERs were decreased with nHFOV (p = .03), despite an increase in gas-containing swallows (p = .01). In conclusion, similarly to nasal CPAP and intermittent positive pressure ventilation, nHFOV inhibits GERs in newborn lambs.

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

BackgroundIn preterm infants, the time from initiation to full oral feeding can take weeks, which represents a very worrisome problem in neonatal medicine. Although current knowledge suggests that oral feeding should be introduced early, this is often delayed due to the need for prolonged nasal continuous positive airway pressure (nCPAP). Indeed, most caregivers fear that nCPAP could disrupt sucking-swallowing-breathing coordination and induce tracheal aspiration. The goal of the present study was to assess the impact of nCPAP delivered by the Infant Flow System on the physiology of sucking-swallowing-breathing coordination during bottle-feeding in preterm lambs over 24 h.MethodsSeventeen lambs (8 control, 9 nCPAP of 6 cmH2O) born 14 days prematurely were instrumented to record sucking, swallowing, respiration, ECG, and oxygenation. They were fed via a nasogastric tube for the first 5 days of life until introduction of bottle-feeding every 4 h for 24 h.ResultsnCPAP increased the feeding efficiency while maintaining higher oxygenation without any deleterious cardiorespiratory events. However, coughs were observed in lambs under nCPAP immediately following bottle-feeding and may be related to the high milk flow in preterm lambs.ConclusionFurther studies documenting tracheal aspirations are needed, especially in preterm lambs under nCPAP for moderate respiratory difficulties, to further inform future clinical studies.

Effects of Nasal Continuous Positive Airway Pressure and High-Flow Nasal Cannula on Sucking, Swallowing, and Breathing during Bottle-Feeding in Lambs.

The use of prolonged respiratory support under the form of high-flow nasal cannula (HFNC) or nasal continuous positive airway pressure (nCPAP) is frequent in newborn infants. Introduction of oral feeding under such nasal respiratory support is, however, highly controversial among neonatologists, due to the fear that it could disrupt sucking, swallowing, and breathing coordination and in turn induce cardiorespiratory events. The recent observation of tracheal aspirations during bottle-feeding in preterm infants under nCPAP justifies the use of animal models to perform more comprehensive physiological studies on the subject, in order to gain further insights for clinical studies. The objective of this study was to assess and compare the impact of HFNC and nCPAP on bottle-feeding in newborn lambs, in terms of bottle-feeding efficiency and safety as well as sucking-swallowing-breathing coordination. Eight full-term lambs were instrumented to record sucking, swallowing, and respiration as well as electrocardiogram and oxygenation. Lambs were bottle-fed in a standardized manner during three randomly ordered conditions, namely nCPAP 6 cmH2O, HFNC 7 L/min, and no respiratory support. Results revealed that nCPAP decreased feeding duration [25 vs. 31 s (control) vs. 57 s (HFNC), p = 0.03] and increased the rate of milk transfer [2.4 vs. 1.9 mL/s (control) vs.1.1 mL/s (HFNC), p = 0.03]. No other indices of bottle-feeding safety or sucking-swallowing-breathing coordination were significantly altered by HFNC or nCPAP. In conclusion, our results obtained in full-term newborn lambs suggest that: (i) nCPAP 6 cmH2O, but not HFNC 7 L/min, increases bottle-feeding efficiency; (ii) bottle-feeding is safe under nCPAP 6 cmH2O and HFNC 7 L/min, with no significant alteration in sucking-swallowing-breathing coordination. The present informative and reassuring data in full-term healthy lambs must be complemented by similar studies in preterm lambs, including mild-to-moderate respiratory distress alleviated by respiratory support in order to mimic preterm infants with bronchopulmonary dysplasia and pave the way for clinical studies.

Inhibitory Effect of Nasal Intermittent Positive Pressure Ventilation on Gastroesophageal Reflux.

Non-invasive intermittent positive pressure ventilation can lead to esophageal insufflations and in turn to gastric distension. The fact that the latter induces transient relaxation of the lower esophageal sphincter implies that it may increase gastroesophageal refluxes. We previously reported that nasal Pressure Support Ventilation (nPSV), contrary to nasal Neurally-Adjusted Ventilatory Assist (nNAVA), triggers active inspiratory laryngeal closure. This suggests that esophageal insufflations are more frequent in nPSV than in nNAVA. The objectives of the present study were to test the hypotheses that: i) gastroesophageal refluxes are increased during nPSV compared to both control condition and nNAVA; ii) esophageal insufflations occur more frequently during nPSV than nNAVA. Polysomnographic recordings and esophageal multichannel intraluminal impedance pHmetry were performed in nine chronically instrumented newborn lambs to study gastroesophageal refluxes, esophageal insufflations, states of alertness, laryngeal closure and respiration. Recordings were repeated without sedation in control condition, nPSV (15/4 cmH2O) and nNAVA (~ 15/4 cmH2O). The number of gastroesophageal refluxes recorded over six hours, expressed as median (interquartile range), decreased during both nPSV (1 (0, 3)) and nNAVA [1 (0, 3)] compared to control condition (5 (3, 10)), (p < 0.05). Meanwhile, the esophageal insufflation index did not differ between nPSV (40 (11, 61) h-1) and nNAVA (10 (9, 56) h-1) (p = 0.8). In conclusion, nPSV and nNAVA similarly inhibit gastroesophageal refluxes in healthy newborn lambs at pressures that do not lead to gastric distension. In addition, the occurrence of esophageal insufflations is not significantly different between nPSV and nNAVA. The strong inhibitory effect of nIPPV on gastroesophageal refluxes appears identical to that reported with nasal continuous positive airway pressure.

Effects of Inspiratory Pressure Rise Time and Hypoxic or Hypercapnic Breathing on Inspiratory Laryngeal Constrictor Muscle Activity During Nasal Pressure Support Ventilation.

OBJECTIVE: We previously reported the development of an active inspiratory laryngeal narrowing against ventilator insufflations when inspiratory pressure is increased during nasal pressure support ventilation in lambs. The present study aimed to further understand the factors involved in this inspiratory laryngeal narrowing. More specifically, we tested the hypothesis that a short inspiratory pressure rise time or a low PaCO2 level promotes inspiratory laryngeal narrowing observed in nasal pressure support ventilation. The effect of hypoxia was also assessed. DESIGN: Prospective, randomized, interventional study. SETTING: Animal research laboratory at the Faculty of Medicine and Health Sciences, Université de Sherbrooke, Canada. SUBJECTS: Thirteen lambs aged 4-5 days. INTERVENTIONS: Polysomnographic recordings were performed in chronically instrumented lambs to study states of alertness, glottal muscle electrical activity, tracheal pressure, SpO2, and respiratory movements. Lambs were ventilated with progressively increasing levels of nasal pressure support ventilation (10/4, 15/4, and 20/4 cm H2O), using a broad range of inspiratory rise times from 0.05 to 0.4 s. Thereafter, either CO2 (PaCO2 = baseline value + 10 mm Hg) or N2 (PaO2 = 45-55 mm Hg) was added to the inspiratory line. MEASUREMENTS AND MAIN RESULTS: The percentage of respiratory cycles with phasic inspiratory activity of glottal constrictor muscle was measured and compared between the various experimental conditions. The different inspiratory pressure rise times tested did not alter the phasic inspiratory activity of glottal constrictor muscle during nasal pressure support ventilation. By contrast, this activity was virtually abolished by increasing PaCO2 in all lambs. Finally, no alterations in the phasic inspiratory activity of glottal constrictor muscle during nasal pressure support ventilation were observed during hypoxia. CONCLUSIONS: Active inspiratory laryngeal narrowing during nasal pressure support ventilation is not altered by inspiratory rise times ranging from 0.05 to 0.4 s or by moderate hypoxia, whereas a moderate increase in PaCO2 abolishes this activity.

Nasal continuous positive airway pressure inhibits gastroesophageal reflux in newborn lambs.

BACKGROUND: Using esophageal pHmetry, nasal CPAP (nCPAP) has been shown to decrease acid gastroesophageal reflux (GER) in adult humans. Although both GER (mainly non-acid) and nCPAP use are very frequent in newborns, the effect of nCPAP on GER in early life is unknown. Having recently shown that the newborn lamb is a unique model for studying neonatal GER, our main objective was to assess the effect of nCPAP on GER in newborn lambs. METHODS: Eight newborn lambs, aged 2-3 days, were studied. Continuous esophageal pH-Impedance monitoring and polysomnography were performed for six hours during both spontaneous breathing and nCPAP application at 6 cmH2O (nCPAP(6)), in a randomized order. Results were compared in the two experimental conditions, as well as without CPAP during the following 6 hours. RESULTS: i) nCPAP(6) virtually abolished GER [mean ± SD reflux number for 6 h = 9.1 ± 8.6 without nCPAP(6) vs. 0.6 ± 1 with nCPAP(6), P<0.05]; ii) GER number was also reduced during the 6 h-period following nCPAP(6) application (18 ± 16 without nCPAP(6) vs. 7 ± 8.1 with nCPAP(6), P<0.05); iii) nCPAP(6) decreased the depth and duration of lower esophageal sphincter relaxation. CONCLUSIONS: nCPAP inhibits GER in the newborn lamb. Further clinical studies using different levels of nasal CPAP are needed to confirm this result in human infants.

Absence of effect of nasal continuous positive airway pressure on the esophageal phase of nutritive swallowing in newborn lambs.

OBJECTIVES: It is presently recommended that oral feeding be started in premature infants as soon as possible, often at an age at which nasal continuous positive airway pressure (nCPAP) is still required for ventilatory support. Our previous data showed that application of nCPAP up to 10 cmH2O in full-term lambs had no deleterious effect on cardiorespiratory safety, feeding efficiency, or on nutritive swallowing-breathing coordination. Besides fear of swallowing-breathing coordination disturbances, esophageal motility disruption by nCPAP could be a reason to delay oral feeding. To our knowledge, no study has focused on the effects of nCPAP on esophageal motility in the neonatal period. The aim of the present study was therefore to further assess the effects of nCPAP on oral feeding by assessing its effects on the esophageal phase of nutritive swallowing (nutritive esophagodeglutition). METHODS: Six full-term lambs, ages 2 to 3 days, underwent esophageal multichannel intraluminal impedance-pH monitoring. Lambs were bottle-fed under 2 randomized conditions, namely spontaneous breathing and nCPAP 6 cmH(2)O. RESULTS: Beyond confirmation of unaltered feeding efficiency, analysis of multiple variables measured by impedance monitoring revealed that nCPAP 6 does not alter nutritive esophagodeglutition in any way (nCPAP vs spontaneous breathing, P > 0.1 for all variables). CONCLUSIONS: offering further support to neonatologists pleading for initiation of oral feeding in infants still on nCPAP, the present results set the foundations for similar clinical studies in preterm human infants to confirm the absence of effects of nCPAP on nutritive swallowing.