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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Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome (Review)

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Exogenous surfactant replacement is the most effective evidence-based therapy for respiratory distress syndrome in preterm infants. The mode of administration has evolved in the last decade towards less invasive techniques that aim to effectively provide an adequate dose of surfactant, while allowing spontaneous respiration to continue, and with the support of continuous positive airway pressure. Surfactant delivery via aerosolisation, pharyngeal instillation, and laryngeal mask are being actively pursued in research, but have not yet been adopted to any significant degree in clinical practice. Surfactant administration via thin catheter, on the other hand, is becoming more widely used in neonatal intensive care units worldwide and is now an acknowledged alternative to the standard mode of surfactant delivery. Different devices, including nasogastric tubes, vascular catheters, and purpose-built surfactant instillation catheters are used. We present here a contemporary review of surfactant administration via thin catheter, in a practical guide format that reflects the individual and collective scientific opinions of the clinicians who participated in formulating the guide.

Meconium aspiration syndrome (MAS) is a complex respiratory disease of the term and near-term neonate. Inhalation of meconium causes airway obstruction, atelectasis, epithelial injury, surfactant inhibition, and pulmonary hypertension, the chief clinical manifestations of which are hypoxaemia and poor lung compliance. Supplemental oxygen is the mainstay of therapy for MAS, with around one-third of infants requiring intubation and mechanical ventilation. For those ventilated, high ventilator pressures, as well as a relatively long inspiratory time and slow ventilator rate, may be necessary to achieve adequate oxygenation. High-frequency ventilation may offer a benefit in infants with refractory hypoxaemia and/or gas trapping. Inhaled nitric oxide is effective in those with pulmonary hypertension, and other adjunctive therapies, including surfactant administration and lung lavage, should be considered in selected cases. With judicious use of available modes of ventilation and adjunctive therapies, infants with even the most severe MAS can usually be supported through the disease, with an acceptably low risk of short- and long-term morbidities.

To the Editor The OPTIMIST-A trial 1 found that minimally invasive surfactant therapy, compared with sham treatment, did not reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome. However, the incidence of bronchopulmonary dysplasia was significantly lower in the minimally invasive surfactant therapy group (relative risk, 0.83; 95% CI, 0.70-0.98).In addition, although there was no significant difference in death between groups, an exploratory analysis suggested an increased mortality risk associated with minimally invasive surfactant therapy in the gestational age stratum of 25 to 26 weeks. Because any signal of an increased risk of death raises a significant concern, the authors advised caution about the use of minimally invasive surfactant therapy in infants with gestational ages of 25 to 26 weeks.Nevertheless, subgroup analyses should be interpreted cautiously. 2 There was an imbalance in baseline variables between the groups in the 25 to 26 weeks' gestational age strata, which could have influenced the outcome of death. Within the gestational age stratum of 25 to 26 weeks, infants in the minimally invasive surfactant therapy group, compared with those receiving the control treatment, had a higher frequency of male sex (50% vs 37.9%, respectively), multiple birth (47.8% vs 34.5%), and no or incomplete exposure to antenatal corticosteroids (40% vs 26.4%).Although it is unclear why these imbalances occurred when randomization was stratified by gestational age, they may have resulted from premature trial termination. 3 An analysis performed after adjusting for these covariates was not significantly different; however, the event rate was lower and many covariates may not have been included in the regression analysis. In addition, the credibility of subgroup analyses depends on replication in other studies and biological plausibility supporting the subgroup effect. 2 A previous trial 4 and systematic review 5 did not show harm with the use of minimally invasive surfactant therapy in premature infants.Surfactant therapy is lifesaving, and giving it early via a thin catheter would be expected to be lifesaving rather than life-threatening. 4 In addition, this study 1 did not demonstrate any indication that death was directly attributable to the minimally invasive surfactant therapy intervention. Therefore, I believe the association of higher mortality risk in infants with gestational ages of 25 to 26 weeks who received minimally invasive surfactant therapy was likely attributable to chance rather than minimally invasive surfactant therapy itself.

This randomized control trial determines if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures.