Effects of Late Surfactant Treatment Delivered After a Recruitment Maneuver on Respiratory Outcomes in Extremely Low Gestational Age Newborns: A Randomized Controlled Pilot Trial – LATE-REC-SURF Trial.

Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

Performance of a capnodynamic method estimating cardiac output during respiratory failure - before and after lung recruitment

Respiratory failure may cause hemodynamic instability with strain on the right ventricle. The capnodynamic method continuously calculates cardiac output (CO) based on effective pulmonary blood flow (COEPBF) and could provide CO monitoring complementary to mechanical ventilation during surgery and intensive care. The aim of the current study was to evaluate the ability of a revised capnodynamic method, based on short expiratory holds (COEPBFexp), to estimate CO during acute respiratory failure (LI) with high shunt fractions before and after compliance-based lung recruitment. Ten pigs were submitted to lung lavage and subsequent ventilator-induced lung injury. COEPBFexp, without any shunt correction, was compared to a reference method for CO, an ultrasonic flow probe placed around the pulmonary artery trunk (COTS) at (1) baseline in healthy lungs with PEEP 5 cmH2O (HLP5), (2) LI with PEEP 5 cmH2O (LIP5) and (3) LI after lung recruitment and PEEP adjustment (LIPadj). CO changes were enforced during LIP5 and LIPadj to estimate trending. LI resulted in changes in shunt fraction from 0.1 (0.03) to 0.36 (0.1) and restored to 0.09 (0.04) after recruitment manoeuvre. Bias (levels of agreement) and percentage error between COEPBFexp and COTS changed from 0.5 (− 0.5 to 1.5) L/min and 30% at HLP5 to − 0.6 (− 2.3 to 1.1) L/min and 39% during LIP5 and finally 1.1 (− 0.3 to 2.5) L/min and 38% at LIPadj. Concordance during CO changes improved from 87 to 100% after lung recruitment and PEEP adjustment. COEPBFexp could possibly be used for continuous CO monitoring and trending in hemodynamically unstable patients with increased shunt and after recruitment manoeuvre.