Effectiveness of individualized lung recruitment strategies at birth: an experimental study in preterm lambs

Abstract

Background: In translational animal studies both a sustained inflation (SI) and PEEP have been associated with better lung aeration at birth, but the role of each on lung injury is inconclusive. We aimed to determine the effect of different PEEP and SI strategies at birth on early development of lung injury pathways. Method: 70 antenatal-steroid exposed lambs (125d AE 1d) were instrumented during caesarean section. Lambs were randomly assigned to either 1) Positive Pressure Ventilation (PPV; n = 20) using volume targeted ventilation at PEEP 8 cmH 2 O (maximum PIP 35 cmH 2 O, V T 7 ml/kg), 2) Volumetric Sustained Inflation 1 at 35 cmH 2 O until full aeration was visualised using electrical impedance tomography (SI; n = 23), or 3) 3-min Dynamic PEEP strategy 1 guided by breath-to-breath compliance (n = 27). All lambs were treated at 10 min with surfactant 200 mg/kg, and then received PPV for 90 min, with measurement of mechanics and gas exchange throughout. Standardised samples from the gravity-dependent and non-dependent lung were analysed for early injury mRNA markers (EGR1, CYR61, CTGF, IL-6,-8,-1B) and histology. Results: All groups expressed injury in the non-dependent lung compared to unventilated fetal controls across all injury parameters (p < 0.0001 ANOVA). In the dependent lung, only SI resulted in higher EGR1, CYR61, CTGF, IL-6,-1B expression compared to PPV and dynamic PEEP (p < 0.0001 ANOVA), and both were not different from fetal controls. Dynamic PEEP had better oxygenation throughout (p < 0.0001, two-way ANOVA) Conclusions: This large preterm lamb study is the first to show significant injury differences between SI and PEEP starte-gies. Early lung injury was heterogeneous and greater in the dependent lung following a SI. This suggests that achieving aeration slowly using tidal inflations maybe more beneficial than a SI. Reference: 1. Tingay DG et al. Background: Volume targeted ventilation (VTV) is widely used and may reduce lung injury, but this assumes the clinically set V T (V Tset) is accurately delivered. The aims of this prospective observational study were to determine the relationship between V Tset , expiratory V T (V Te) and endotracheal tube leak in a modern neonatal VTV ventilator, and the resultant PaCO 2 relationship with and without VTV. Method: Continuous inflations were recorded for 24 hours in 100 infants receiving synchronised mechanical ventilation (SLE5000, SLE Ltd, UK) with VTV (n = 77 infants) or without, and either the manufacturer's V4 (n = 50) or newer V5 (n = 50) VTV algorithm. For every inflation the set V Tset , V Te and leak were determined (maximum 90000 inflations/infant). If PaCO 2 was sampled (maximum 2/infant), this was compared with the average V T data from the preceeding 15 minutes. Results: A total of 7,917,020 inflations were analysed. Using VTV the V Tset-V Te bias (95% CI) was 0.3 (−0.12, 0.19) mL/kg. Leak influenced V Tset-V Te bias with V4 algorithm (r 2 = −0.64, p < 0.0001; linear regression) but not V5 (r 2 = 0.04, p = 0.21). Overall 80% of V Te were AE...

Time to lung aeration during a sustained inflation at birth is influenced by gestation in lambs

“…Increasingly, clinicians are using individualized ventilation strategies, such as open-lung ventilation and volume-targeting, in an effort to avoid harmful lung volume states and achieve regional homogeneity (7,32). Previous work from our group, limited to a single GA, demonstrated great heterogeneity in the time constants of the respiratory system at birth, which influenced SI aeration outcomes (2,14,16). We have now demonstrated that GA independently influences aeration during an SI.…”

“…Recent advances in electrical impedance tomography (EIT) have enabled monitoring of the aeration response of the lung from birth, allowing individual titration of the SI duration to the aeration response experimentally, with improved gas exchange and lung mechanics compared with a fixed 30-s SI (2,16). Although this approach offers more favorable lung aeration, it is currently a research tool only.…”

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

“…The vectorial transport of NaCl generates an osmotic gradient, which contributes to fetal lung fluid formation, which fills the bronchial and alveolar spaces. Shortly before birth, Cl Ϫ secretion ceases, and Na ϩ absorption is initiated through the upregulated amiloride-sensitive ENaCs (68,78,101) (Fig. 1).…”

Feasibility of combining two individualized lung recruitment maneuvers at birth for very low gestational age infants: a retrospective cohort study

“…However, studies in the premature lamb have shown better oxygenation, lung mechanics, and end-expiratory global lung volume after a dynamic PEEP strategy based on a step-by-step PEEP increase far beyond 5 cmH2O compared with a nonoptimized SI strategy [4,6]. However, none of these differences were observed when the dynamic PEEP strategy was compared with a SI strategy optimized by real time electrical impedance tomography for the duration of the inflation [5]. We hypothesized that individualized LR maneuvers combining dynamic PEEP and gradually extended SI, as needed, would lower the incidence of mechanical ventilation (MV) in the first 72 h, without increasing neonatal complications.…”

“…Resuscitating premature infants at birth aims to stimulate spontaneous breathing and establish an optimal functional residual capacity without harming the lungs [1]. To this end, lung recruitment maneuvers have been under investigation over the past two decades [2][3][4][5][6]. To date, despite numerous studies, no clear definition of the optimal inflation duration, nor of positive end-expiratory pressure (PEEP) optimal level exists.…”