Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial

Giovanni Vento, Maria Luisa Ventura, Roberta Pastorino, Anton H. van Kaam, Virgilio Carnielli, Filip Cools, Carlo Dani, Fabio Mosca, Graeme Polglase, Paolo Tagliabue, Luca Boni, Francesco Cota, Milena Tana, Chiara Tirone, Claudia Aurilia, Alessandra Lio, Simonetta Costa, Vito D'Andrea, Mariella Lucente, Gabriella NigroLucio Giordano, Vincenzina Roma, Paolo E. Villani, Francesca P. Fusco, Valeria Fasolato, Maria Rosa Colnaghi, Piero G. Matassa, Valentina Vendettuoli, Chiara Poggi, Antonio Del Vecchio, Flavia Petrillo, Pasqua Betta, Carmine Mattia, Giampaolo Garani, Agostina Solinas, Eloisa Gitto, Vincenzo Salvo, Giancarlo Gargano, Eleonora Balestri, Fabrizio Sandri, Giovanna Mescoli, Stefano Martinelli, Laura Ilardi, Elena Ciarmoli, Sandra Di Fabio, Eugenia Maranella, Carolina Grassia, Gaetano Ausanio, Vincenzo Rossi, Angela Motta, Lucia G. Tina, Kim Maiolo, Stefano Nobile, Hubert Messner, Alex Staffler, Federica Ferrero, Ilaria Stasi, Luisa Pieragostini, Isabella Mondello, Cristina Haass, Chiara Consigli, Stefania Vedovato, Alessandra Grison, Gianfranco Maffei, Giuseppe Presta, Roberto Perniola, Marcello Vitaliti, Maria P. Re, Mario De Curtis, Viviana Cardilli, Paola Lago, Francesca Tormena, Luigi Orfeo, Camilla Gizzi, Luca Massenzi, Diego Gazzolo, Maria Chiara M. Strozzi, Roberto Bottino, Federica Pontiggia, Alberto Berardi, Isotta Guidotti, Caterina Cacace, Valerio Meli, Lorenzo Quartulli, Antonio Scorrano, Alessandra Casati, Lidia Grappone, J. Jane Pillow

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Abstract

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57–0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7–135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. Funding: None.

Original languageEnglish
Number of pages8
JournalThe Lancet Respiratory Medicine
DOIs
Publication statusAccepted/In press - 17 Jul 2020

Cite this

Vento, G., Ventura, M. L., Pastorino, R., van Kaam, A. H., Carnielli, V., Cools, F., Dani, C., Mosca, F., Polglase, G., Tagliabue, P., Boni, L., Cota, F., Tana, M., Tirone, C., Aurilia, C., Lio, A., Costa, S., D'Andrea, V., Lucente, M., ... Pillow, J. J. (Accepted/In press). Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(20)30179-X