Aeration strategy at birth influences the physiological response to surfactant in preterm lambs

Tingay, David G.; Togo, Andrea; Pereira‐Fantini, Prue M.; Miedema, Martijn; McCall, Karen; Perkins, Elizabeth; Thomson, Jessica; Dowse, Georgie; Sourial, Magdy; Dellacà, Raffaele L.; Davis, Peter G; Dargaville, Peter A.

doi:10.1136/archdischild-2018-316240

Cited by 23 publications

(43 citation statements)

References 35 publications

(116 reference statements)

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“…Aeration of the gasless fluid-filled lung is the critical event at birth, triggering the rapid changes in the respiratory and vascular systems necessary to adapt to extrauterine life. Aeration is a complex process dependent on several factors, including developmental and disease state of the lung (15), spontaneous breathing activity (24), expiratory braking (24), effective lung fluid reabsorption (1), effectiveness of positive pressure ventilatory support (15, 25b, 25c, 27, 28, 32), and/or pharma-cological treatments (2,30,33,34). Phase contrast X-ray imaging has shown that this process is initially driven by the transpulmonary pressure that first moves the fluid from the central airways to the lung periphery (10).…”

Section: Introductionmentioning

confidence: 99%

Respiratory mechanics during initial lung aeration at birth in the preterm lamb

Veneroni

Tingay

McCall

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Despite recent insights into the dynamic processes during lung aeration at birth, several aspects remain poorly understood. We aimed to characterize changes in lung mechanics during the first inflation at birth and their relationship to changes in lung volume. Intubated preterm lambs (gestational age, 124–127 days; n = 17) were studied at birth. Lung volume changes were measured by electrical impedance tomography (VL EIT). Respiratory system resistance (R5) and oscillatory compliance (Cx5) were monitored with the forced oscillation technique at 5 Hz. Lambs received 3–7 s of 8 cmH2O of continuous distending pressure (CDP) before delivery of a sustained inflation (SI) of 40 cmH2O. The SI was then applied until either Cx5 or the VL EIT or the airway opening volume was stable. CDP was resumed for 3–7 s before commencement of mechanical ventilation. The exponential increases with time of Cx5 and VL EIT from commencement of the SI were characterized by estimating their time constants (τCx5 and τVL EIT, respectively). During SI, a fast decrease in R5 and an exponential increase in Cx5 and VL EIT were observed. Cx5 and VL EIT provided comparable information on the dynamics of lung aeration in all lambs, with τCx5 and τVL EIT being highly linearly correlated ( r2 = 0.87, P < 0.001). Cx5 and VL EIT decreased immediately after SI. Despite the standardization of the animal model, changes in Cx5 and R5 both during and after SI were highly variable. Lung aeration at birth is characterized by a fast reduction in resistance and a slower increase in oscillatory compliance, the latter being a direct reflection of the amount of lung aeration.

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Section: Introductionmentioning

confidence: 99%

Respiratory mechanics during initial lung aeration at birth in the preterm lamb

Veneroni

Tingay

McCall

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The specific aims of this study were to determine the independent effect of PEEP, tidal ventilation, and SI at birth on: 1) the volumetric conditions of the lung; and 2) subsequent early development of regional lung injury in the preterm lamb lung. Some of the results of these studies have been previously reported in abstract form (25), and some of the lambs have been used across other studies (26).…”

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confidence: 99%

Gradual Aeration at Birth Is More Lung Protective Than a Sustained Inflation in Preterm Lambs

Tingay

Pereira‐Fantini

Oakley

et al. 2019

Am J Respir Crit Care Med

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Rationale: The preterm lung is susceptible to injury during transition to air breathing at birth. It remains unclear whether rapid or gradual lung aeration at birth causes less lung injury. Objectives: To examine the effect of gradual and rapid aeration at birth on: 1) the spatiotemporal volume conditions of the lung; and 2) resultant regional lung injury. Methods: Preterm lambs (125 6 1 d gestation) were randomized at birth to receive: 1) tidal ventilation without an intentional recruitment (no-recruitment maneuver [No-RM]; n = 19); 2) sustained inflation (SI) until full aeration (n = 26); or 3) tidal ventilation with an initial escalating/de-escalating (dynamic) positive end-expiratory pressure (DynPEEP; n = 26). Ventilation thereafter continued for 90 minutes at standardized settings, including PEEP of 8 cm H 2 O. Lung mechanics and regional aeration and ventilation (electrical impedance tomography) were measured throughout and correlated with histological and gene markers of early lung injury. Measurements and Main Results: DynPEEP significantly improved dynamic compliance (P , 0.0001). An SI, but not DynPEEP or NoRM , resulted in preferential nondependent lung aeration that became less uniform with time (P = 0.0006). The nondependent lung was preferential ventilated by 5 minutes in all groups, with ventilation only becoming uniform with time in the NoRM and DynPEEP groups. All strategies generated similar nondependent lung injury patterns. Only an SI caused greater upregulation of dependent lung gene markers compared with unventilated fetal controls (P , 0.05). Conclusions: Rapidly aerating the preterm lung at birth creates heterogeneous volume states, producing distinct regional injury patterns that affect subsequent tidal ventilation. Gradual aeration with tidal ventilation and PEEP produced the least lung injury.

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“…The hypothesis that early application of "higher" PEEP levels could be beneficial is supported by animal data where higher PEEP levels (8-12 cmH 2 O) were more effective than lower levels in terms of gas exchange [12,13]. More recently, a dynamic increase of PEEP in preterm lambs (up to 14-20 cmH 2 O for 3 min) improved response to surfactant treatment and created a more uniform lung aeration, compared to positive pressure ventilation or SLI maneuvers [24]. Further evidence that higher pressure levels may decrease the need for invasive mechanical ventilation derives from studies using NIPPV as a mode of non-invasive respiratory support.…”

Section: Discussionmentioning

confidence: 95%

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants—“The OPTTIMMAL-Trial”—Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial

Waitz

Engel

Schloesser

et al. 2020

Trials

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Background Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. Methods In this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH2O) or a lower (3–5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). Discussion Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. Trial registration drks.de DRKS00019940. Registered on March 13, 2020

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Aeration strategy at birth influences the physiological response to surfactant in preterm lambs

Cited by 23 publications

References 35 publications

Respiratory mechanics during initial lung aeration at birth in the preterm lamb

Respiratory mechanics during initial lung aeration at birth in the preterm lamb

Gradual Aeration at Birth Is More Lung Protective Than a Sustained Inflation in Preterm Lambs

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants—“The OPTTIMMAL-Trial”—Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial

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