Total liquid ventilation in an ovine model of extreme prematurity: a randomized study.

BACKGROUND: This study aimed at comparing cardiorespiratory stability during total liquid ventilation (TLV)-prior to lung aeration-with conventional mechanical ventilation (CMV) in extremely preterm lambs during the first 6 h of life. METHODS: 23 lambs (11 females) were born by c-section at 118-120 days of gestational age (term = 147 days) to receive 6 h of TLV or CMV from birth. Lung samples were collected for RNA and histology analyses. RESULTS: The lambs under TLV had higher and more stable arterial oxygen saturation (p = 0.001) and cerebral tissue oxygenation (p = 0.02) than the lambs in the CMV group in the first 10 min of transition to extrauterine life. Although histological assessment of the lungs was similar between the groups, a significant upregulation of IL-1a, IL-6 and IL-8 RNA in the lungs was observed after TLV. CONCLUSIONS: Total liquid ventilation allowed for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Refinement of our TLV prototype and ventilation algorithms is underway to address specific challenges in this population, such as minimizing tracheal deformation during the active expiration. IMPACT: Total liquid ventilation allows for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Total liquid ventilation is systematically achievable over the first 6 h of life in the extremely premature lamb model. This study provides additional incentive to pursue further investigation of total liquid ventilation as a transition tool for the most extreme preterm neonates.

Effects of Nasal Respiratory Support on Laryngeal and Esophageal Reflexes in Preterm Lambs.

BACKGROUND: Significant cardiorespiratory events can be triggered in preterm infants as part of laryngeal chemoreflexes (LCRs) and esophageal reflexes (ERs). We previously showed that nasal continuous positive airway pressure (nCPAP) blunted the cardiorespiratory inhibition induced with LCRs. Therefore, we aimed to compare the effects of nCPAP and high-flow nasal cannulas (HFNC) on the cardiorespiratory events induced during LCRs and ERs. The hypothesis is that nCPAP but not HFNC decreases the cardiorespiratory inhibition observed during LCRs and ERs. METHODS: Eleven preterm lambs were instrumented to record respiration, ECG, oxygenation, and states of alertness. LCRs and ERs were induced during non-rapid eye movement sleep in a random order under these conditions: nCPAP 6 cmH2O, HFNC 7 L/min, high-flow nasal cannulas 7 L/min at a tracheal pressure of 6 cmH2O, and no respiratory support. RESULTS: nCPAP 6 cmH2O decreased the cardiorespiratory inhibition induced with LCRs, but not with ERs in preterm lambs. This blunting effect was less marked with HFNC 7 L/min, even when the tracheal pressure was maintained at 6 cmH2O. CONCLUSIONS: nCPAP might be a treatment for cardiorespiratory events related to LCRs in newborns, either in the context of laryngopharyngeal refluxes or swallowing immaturity. Our preclinical results merit to be confirmed through clinical studies. IMPACT: Laryngeal chemoreflexes can be responsible for significant cardiorespiratory inhibition in newborns, especially preterm. Nasal continuous positive airway pressure at 6 cmH2O significantly decreased this cardiorespiratory inhibition. High-flow nasal cannulas at 7 L/min had a lesser effect than nasal continuous positive airway pressure. Esophageal stimulation was responsible for a smaller cardiorespiratory inhibition, which was not significantly modified by nasal continuous positive airway pressure or high-flow nasal cannulas. Nasal continuous positive airway pressure should be tested for its beneficial effect on cardiorespiratory events related to laryngeal chemoreflexes in preterm newborns.

Hemodynamic impacts of apelin-13 in a neonatal lamb model of septic peritonitis.

BACKGROUND: Apelins are potential candidate therapeutic molecules for hemodynamic support. The objective of this study was to assess the hemodynamic impacts of apelin-13 in a neonatal lamb model of septic shock. METHODS: Lambs were randomized to receive apelin-13 or normal saline. Septic shock was induced by injecting a fecal slurry into the peritoneal cavity. Lambs underwent volume repletion (30 mL/kg over 1 h) followed by intravenous administration of 5 incremental doses (D) of apelin-13 (D1 = 0.039 to D5 = 19.5 µg/kg/h) or normal saline. RESULTS: Following fecal injection, mean arterial pressure (MAP) and cardiac index (CI) dropped in both groups (p < 0.05). The MAP decreased non-significantly from D1 to D5 (p = 0.12) in the saline group, while increasing significantly (p = 0.02) in the apelin group (-12 (-17; 12) vs. +15 (6; 23) % (p = 0.012)). Systemic vascular resistances were higher in the apelin-13 group at D5 compared to the saline group (4337 (3239, 5144) vs. 2532 (2286, 3966) mmHg/min/mL, respectively, p = 0.046). The CI increased non-significantly in the apelin-13 group. CONCLUSION: Apelin-13 increased MAP in a neonatal lamb septic shock model. IMPACT: Administration of apelin-13 stabilized hemodynamics during the progression of the sepsis induced in this neonatal lamb model. Systemic vascular resistances were higher in the apelin-13 group than in the placebo group. This suggests ontogenic differences in vascular response to apelin-13 and warrants further investigation. This study suggests that apelin-13 could eventually become a candidate for the treatment of neonatal septic shock.

Cardiorespiratory alterations in a newborn ovine model of systemic viral inflammation.

BACKGROUND: Respiratory viruses can be responsible for severe apneas and bradycardias in newborn infants. The link between systemic inflammation with viral sepsis and cardiorespiratory alterations remains poorly understood. We aimed to characterize these alterations by setting up a full-term newborn lamb model of systemic inflammation using polyinosinic:polycytidylic acid (Poly I:C). METHODS: Two 6-h polysomnographic recordings were carried out in eight lambs on two consecutive days, first after an IV saline injection, then after an IV injection of 300 µg/kg Poly I:C. RESULTS: Poly I:C injection decreased locomotor activity and increased NREM sleep. It also led to a biphasic increase in rectal temperature and heart rate. The latter was associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Lastly, brainstem inflammation was found in the areas of the cardiorespiratory control centers 6 h after Poly I:C injection. CONCLUSIONS: The alterations in heart-rate variability induced by Poly I:C injection may be, at least partly, of central origin. Meanwhile, the absence of alterations in respiratory-rate variability is intriguing and noteworthy. Although further studies are obviously needed, this might be a way to differentiate bacterial from viral sepsis in the neonatal period. IMPACT: Provides unique observations on the cardiorespiratory consequences of injecting Poly I:C in a full-term newborn lamb to mimic a systemic inflammation secondary to a viral sepsis. Poly I:C injection led to a biphasic increase in rectal temperature and heart rate associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Brainstem inflammation was found in the areas of the cardiorespiratory control centers.

Effects of upper airway obstruction or hypoxia on gastroesophageal reflux in newborn lambs.

BACKGROUND: Although it is commonly accepted that upper airway obstruction (UAO) increases gastroesophageal reflux (GER), the link is poorly understood and insufficiently documented. In addition, while hypoxia is often encountered in infants with UAO, its consequences on GER are virtually unknown. The two aims of the present study were to characterize the effects of (1) UAO and (2) hypoxia on GER. METHODS: Seventeen lambs underwent polysomnographic and esophageal impedance/pH-metry monitoring during UAO vs. a control condition (6 h, ten lambs) or 10% hypoxia vs. normoxic condition (3 h, seven other lambs). RESULTS: Moderate-to-severe UAO was maintained throughout monitoring (inspiratory tracheal pressure of -13 (-15, -12) cm H2O vs. -1 (-1, -1) cm H2O in control condition, p = 0.005). While the number of GERs increased with UAO (2 (1, 4) vs. 0 (0, 3) in the control condition, p = 0.03), the increase was less than anticipated and inconsistent among the lambs. Also, sustained 10% hypoxia did not alter the number of GERs (2 (1, 3) vs. 0 (0, 5) in the control condition, p = 0.9). CONCLUSIONS: The presence of an UAO for 6 h mildly increased the number of GERs, whereas hypoxia for 3 h had no significant effect. IMPACT: The effect of upper airway obstruction and hypoxia on gastroesophageal reflux is poorly documented in the neonatal period. A moderate-to-severe upper airway obstruction for 6 h results in a mild, inconsistent increase in the number of gastroesophageal refluxes. Overall, a hypoxia of 10% for 3 h had no significant impact on gastroesophageal reflux. The prescription of an antireflux medication in infants with upper airway obstruction must not be systematic but rely on objective signs of a pathologic gastroesophageal reflux.

Evolution of inspiratory muscle function in children during mechanical ventilation.

BACKGROUND: There is no universally accepted method to assess the pressure-generating capacity of inspiratory muscles in children on mechanical ventilation (MV), and no study describing its evolution over time in this population. METHODS: In this prospective observational study, we have assessed the function of the inspiratory muscles in children on various modes of MV. During brief airway occlusion maneuvers, we simultaneously recorded airway pressure depression at the endotracheal tube (ΔPaw, force generation) and electrical activity of the diaphragm (EAdi, central respiratory drive) over five consecutive inspiratory efforts. The neuro-mechanical efficiency ratio (NME, ΔPaw/EAdimax) was also computed. The evolution over time of these indices in a group of children in the pediatric intensive care unit (PICU) was primarily described. As a secondary objective, we compared these values to those measured in a group of children in the operating room (OR). RESULTS: In the PICU group, although median NMEoccl decreased over time during MV (regression coefficient - 0.016, p = 0.03), maximum ΔPawmax remained unchanged (regression coefficient 0.109, p = 0.50). Median NMEoccl at the first measurement in the PICU group (after 21 h of MV) was significantly lower than at the only measurement in the OR group (1.8 cmH2O/µV, Q1-Q3 1.3-2.4 vs. 3.7 cmH2O/µV, Q1-Q3 3.5-4.2; p = 0.015). Maximum ΔPawmax in the PICU group was, however, not significantly different from the OR group (35.1 cmH2O, Q1-Q3 21-58 vs. 31.3 cmH2O, Q1-Q3 28.5-35.5; p = 0.982). CONCLUSIONS: The function of inspiratory muscles can be monitored at the bedside of children on MV using brief airway occlusions. Inspiratory muscle efficiency was significantly lower in critically ill children than in children undergoing elective surgery, and it decreased over time during MV in critically ill children. This suggests that both critical illness and MV may have an impact on inspiratory muscle efficiency.

Mechanical ventilation causes diaphragm dysfunction in newborn lambs.

BACKGROUND: Diaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VIDD). We investigated the impact of MV (mean duration = 7.65 h), either with or without co-existent respiratory failure caused by surfactant deficiency, on the development of VIDD in newborn lambs. METHODS: Newborn lambs (1-4 days) were assigned to control (CTL, non-ventilated), mechanically ventilated (MV), and MV + experimentally induced surfactant deficiency (MV+SD) groups. Immunoblotting and quantitative PCR assessed inflammatory signaling, the ubiquitin-proteasome system, autophagy, and oxidative stress. Immunostaining for myosin heavy chain (MyHC) isoforms and quantitative morphometry evaluated diaphragm atrophy. Contractile function of the diaphragm was determined in isolated myofibrils ex vivo. RESULTS: Equal decreases (25-30%) in myofibrillar force generation were found in MV and MV+SD diaphragms compared to CTL. In comparison to CTL, both MV and MV+SD diaphragms also demonstrated increased STAT3 transcription factor phosphorylation. Ubiquitin-proteasome system (Atrogin1 and MuRF1) transcripts and autophagy indices (Gabarapl1 transcripts and the ratio of LC3B-II/LC3B-I protein) were greater in MV+SD relative to MV alone, but fiber type atrophy was not observed in any group. Protein carbonylation and 4-hydroxynonenal levels (indices of oxidative stress) also did not differ among groups. CONCLUSIONS: In newborn lambs undergoing controlled MV, there is a rapid onset of diaphragm dysfunction consistent with VIDD. Superimposed lung injury caused by surfactant deficiency did not influence the severity of early diaphragm weakness.

A new ovine model of spine and chest wall deformity at birth with alteration of respiratory system mechanics and lung development: a feasibility study.

PURPOSE: To develop an animal model of spine and chest wall deformity (CWD) at birth and to evaluate its effects on respiratory system mechanics and lung development. METHODS: A spine and CWD was created in utero between 70 and 75 days of gestation in six ovine fetuses by resection of the seventh and eighth left ribs. Two days after birth, respiratory system mechanics was assessed in anesthetized lambs using the flexiVent apparatus, followed by postmortem measurement of lung mechanics as well as histological lung analysis. RESULTS: A range of severity of CWD was found (Cobb angle from 0° to 48°) with a mean decrease in compliance of 47% and in inspiratory capacity of 39% compared to control lambs. Proof-of-concept histological analysis in one lamb showed marked lung hypoplasia. CONCLUSION: Our ovine model represents a pilot proof-of-concept study evaluating the impact of a spine and CWD present at birth on lung respiratory mechanics and development. This study lays down the groundwork for future studies evaluating the impact of these deformities on lung development and potential treatments. These slides can be retrieved under Electronic Supplementary Material.

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.

Effect of ultra-fast mild hypothermia using total liquid ventilation on hemodynamics and respiratory mechanics.

Ultra-fast cooling for mild therapeutic hypothermia (MTH) has several potential applications, including prevention of post-cardiac arrest syndrome. Ultra-fast MTH by total liquid ventilation (TLV) entails the sudden filling of the lungs with a cold perfluorocarbon liquid and its subsequent use to perform TLV. The present physiological study was aimed at assessing whether pulmonary and systemic hemodynamics as well as lung mechanics are significantly altered during this procedure. Pulmonary and systemic arterial pressures, cardiac output as well as airway resistance and respiratory system compliance were measured during ultra-fast MTH by TLV followed by rewarming and normothermia in six healthy juvenile lambs. Results show that none of the studied variables were altered upon varying the perfluorocarbon temperature from 12 to 41 °C. It is concluded that ultra-fast MTH by TLV does not have any deleterious effect on hemodynamics or lung mechanics in healthy juvenile lambs.

Recursive Model Identification for the Evaluation of Baroreflex Sensitivity.

A method for the recursive identification of physiological models of the cardiovascular baroreflex is proposed and applied to the time-varying analysis of vagal and sympathetic activities. The proposed method was evaluated with data from five newborn lambs, which were acquired during injection of vasodilator and vasoconstrictors and the results show a close match between experimental and simulated signals. The model-based estimation of vagal and sympathetic contributions were consistent with physiological knowledge and the obtained estimators of vagal and sympathetic activities were compared to traditional markers associated with baroreflex sensitivity. High correlations were observed between traditional markers and model-based indices.

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.

Ovine model of congenital chest wall and spine deformity: From birth to 3 months follow-up.

Background: The evolution and treatment of lung alterations related to congenital spine and chest wall deformities (CWD) are poorly understood. Most animal models of CWD created postnatally were not evaluated for respiratory function. The goal of our study was to evaluate the effects of a CWD induced in utero on lung growth and function in an ovine model. Methods: A CWD was induced in utero at 70-75 days of gestation in 14 ovine fetuses by resection of the 7th and 8th left ribs. Each non-operated twin fetus was taken as control. Respiratory mechanics was studied postnatally in the first week and at 1, 2, and 3 months. Post-mortem respiratory mechanics and lung histomorphometry were also assessed at 3 months. Results: Eight out of 14 CWD lambs (57%) and 14 control lambs survived the postnatal period. One severe and five mild deformities were induced. At birth, inspiratory capacity (25 vs. 32 mL/kg in controls), and dynamic (1.4 vs. 1.8 mL/cmH2O/kg), and static (2.0 vs. 2.5 mL/cmH2O/kg) respiratory system compliances were decreased in CWD lambs. Apart from a slight decrease in inspiratory capacity at 1 month of life, no other differences were observed in respiratory mechanics measured in vivo thereafter. Postmortem measurements found a significant decrease in lung compliance-for each lung and for both lungs taken together-in CWD lambs. No differences in lung histology were detected at 3 months in CWD animals compared to controls. Conclusions: Our study is the first to assess the effects of a prenatally induced CWD on lung development and function from birth to 3 months in an ovine model. Our results show no significant differences in lung histomorphometry at 3 months in CWD lambs compared to controls. Resolution at 1 month of the alterations in respiratory mechanics present at birth may be related to the challenge in inducing severe deformities.

Effects of vanilla odor on hypoxia-related periodic breathing in premature newborns: A pilot study.

BACKGROUND: Periodic breathing (PB)-related intermittent hypoxia can have long-lasting deleterious consequences in preterm infants. Olfactory stimulation using vanilla odor is beneficial for apnea of prematurity in the first postnatal days/weeks. We aimed to determine for the first time whether vanilla odor can also decrease PB-related intermittent hypoxia. METHOD: This pilot study was a balanced crossover clinical trial including 27 premature infants born between 30 and 33+6 weeks of gestation. We performed 12-h recordings on two nights separated by a 24-h period. All infants were randomly exposed to vanilla odor on the first or second study night. The primary outcome was the desaturation index, defined as the number per hour of pulse oximetry (SpO2) values <90 % for at least 5 s, together with a drop of ≥5 % from the preceding value. Univariate mixed linear models were used for the statistical analysis. RESULTS: Overall, exposure to vanilla odor did not significantly decrease the desaturation index (52 ± 22 events/h [mean ± SD] on the intervention night vs. 57 ± 26, p = 0.2); furthermore, it did not significantly alter any secondary outcome. In a preliminary post hoc subgroup analysis, however, the effect of vanilla odor was statistically significant in infants with a desaturation index of ≥70/h (from 86 ± 12 to 65 ± 23, p = 0.04). CONCLUSION: In this pilot study, vanilla odor overall did not decrease PB-related intermittent hypoxia in infants born at 30-33+6 weeks of gestation, which is when they are close to term. Preliminary results suggesting a beneficial effect in infants with the highest desaturation index, however, justify further studies in the presence of PB-related intermittent hypoxia as well as in infants born more prematurely.

Milk temperature influences esophageal motility in the newborn lamb.

Esophageal dysmotility is common in infants. We aimed to evaluate the influence of milk temperature on esophageal motility using multichannel intraluminal impedance-pH monitoring (MII-pH). Five healthy lambs, ages 2 to 3 days, underwent a MII-pH whereas bottle-fed randomly with 50 mL of ewe milk at 26 °C, 38.5 °C, and 41.5 °C. Impedance motility parameters were studied on 5 swallows at each temperature. At 38.5 °C we noted a higher total propagation velocity and a shorter total bolus transit time (TBTT) (P < 0.05). These unique results suggest a potential role of milk temperature alterations in improving oral feeding in infants with esophageal dysmotility.

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.

Mathematical modeling of respiratory system mechanics in the newborn lamb.

In this paper, a mathematical model of the respiratory mechanics is used to reproduce experimental signal waveforms acquired from three newborn lambs. As the main challenge is to determine specific lamb parameters, a sensitivity analysis has been realized to find the most influent parameters, which are identified using an evolutionary algorithm. Results show a close match between experimental and simulated pressure and flow waveforms obtained during spontaneous ventilation and pleural pressure variations acquired during the application of positive pressure, since root mean square errors equal to 0.0119, 0.0052 and 0.0094. The identified parameters were discussed in light of previous knowledge of respiratory mechanics in the newborn.

Chronic tracheostomy care of ventilator-dependent and -independent children: Clinical practice patterns of pediatric respirologists in a publicly funded (Canadian) healthcare system.

OBJECTIVES: To describe the current clinical practice patterns of Canadian pediatric respirologists at pediatric tertiary care institutions regarding chronic tracheostomy tube care and management of home invasive ventilation. METHODS: A pediatric respirologist/pediatrician with expertise in tracheostomy tube care and home ventilation was identified at each Canadian pediatric tertiary care center to complete a 59-item survey of multiple choice and short answer questions. Domains assessed included tracheostomy tube care, caregiver competency and home monitoring, speaking valves, medical management of tracheostomy complications, decannulation, and long-term follow-up. RESULTS: The response rate was 100% (17/17) with all Canadian tertiary care pediatric centers represented and heterogeneity of practice was observed in all domains assessed. For example, though most centers employ Bivona™ (17/17) and Shiley™ (15/17) tracheostomy tubes, variability was observed around tube change, re-use, and cleaning practices. Most centers require two trained caregivers (14/17) and recommend 24/7 eyes on care and oxygen saturation monitoring. Discharge with an emergency tracheostomy kit was universal (17/17). Considerable heterogeneity was observed in the timing and use of speaking valves and speech-language assessment. Inhaled anti-pseudomonal antibiotics are employed by most centers (16/17) though the indication, agent, and protocol varied by center. Though decannulation practices varied considerably, the requirement of upper airway patency was universally required to proceed with decannulation (17/17) independent of ongoing ventilatory support requirements. CONCLUSION: Considerable variability in pediatric tracheostomy tube care practice exists across Canada. These results will serve as a starting point to standardize and evaluate tracheostomy tube care nationally.

Newborn lamb as a new model for studying gastroesophageal reflux.

We aimed to determine whether the newborn lamb at term is a valid model for studying gastroesophageal reflux. Seven bottle-fed lambs, ages 2 to 3 days, underwent esophageal multichannel intraluminal impedance-pH monitoring (MII-pH). A total of 196 reflux episodes were recorded, including 73% alkaline and 27% weakly acidic. No acid refluxes were observed. Median bolus clearance time was 4  seconds (3; 5.5), and proximal reflux extent was 35% (26). This first report of MII-pH in the newborn mammal sets the foundations for future studies with physiological and clinical relevance to human neonates.

Corrigendum: Safety of Bottle-Feeding Under Nasal Respiratory Support in Preterm Lambs With and Without Tachypnoea.

[This corrects the article DOI: 10.3389/fphys.2021.785086.].