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

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.; Nigro, G.; Giordano, L.; Roma, V.; Villani, P. E.; Fusco, F. P.; Fasolato, V.; Colnaghi, M. R.; Matassa, P. G.; Vendettuoli, V.; Poggi, C.; Del Vecchio, A.; Petrillo, F.; Betta, P.; Mattia, C.; Garani, G.; Solinas, A.; Gitto, E.; Salvo, V.; Gargano, G.; Balestri, E.; Sandri, F.; Mescoli, G.; Martinelli, S.; Ilardi, L.; Ciarmoli, E.; Di Fabio, S.; Maranella, E.; Grassia, C.; Ausanio, G.; Rossi, V.; Motta, A.; Tina, L. G.; Maiolo, K.; Nobile, S.; Messner, H.; Staffler, A.; Ferrero, F.; Stasi, I.; Pieragostini, L.; Mondello, I.; Haass, C.; Consigli, C.; Vedovato, S.; Grison, A.; Maffei, G.; Presta, G.; Perniola, R.; Vitaliti, M.; M. P., Re; De Curtis, M.; Cardilli, V.; Lago, P.; Tormena, F.; Orfeo, L.; Gizzi, C.; Massenzi, L.; Gazzolo, D.; Strozzi, M. C. M.; Bottino, R.; Pontiggia, F.; Berardi, A.; Guidotti, I.; Cacace, C.; Meli, V.; Quartulli, L.; Scorrano, A.; Casati, A.; Grappone, L.; Pillow, J. J.

doi:10.1016/S2213-2600(20)30179-X

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.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial / 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.; Nigro, G.; Giordano, L.; Roma, V.; Villani, P. E.; Fusco, F. P.; Fasolato, V.; Colnaghi, M. R.; Matassa, P. G.; Vendettuoli, V.; Poggi, C.; Del Vecchio, A.; Petrillo, F.; Betta, P.; Mattia, C.; Garani, G.; Solinas, A.; Gitto, E.; Salvo, V.; Gargano, G.; Balestri, E.; Sandri, F.; Mescoli, G.; Martinelli, S.; Ilardi, L.; Ciarmoli, E.; Di Fabio, S.; Maranella, E.; Grassia, C.; Ausanio, G.; Rossi, V.; Motta, A.; Tina, L. G.; Maiolo, K.; Nobile, S.; Messner, H.; Staffler, A.; Ferrero, F.; Stasi, I.; Pieragostini, L.; Mondello, I.; Haass, C.; Consigli, C.; Vedovato, S.; Grison, A.; Maffei, G.; Presta, G.; Perniola, R.; Vitaliti, M.; Re, M. P.; De Curtis, M.; Cardilli, V.; Lago, P.; Tormena, F.; Orfeo, L.; Gizzi, C.; Massenzi, L.; Gazzolo, D.; Strozzi, M. C. M.; Bottino, R.; Pontiggia, F.; Berardi, A.; Guidotti, I.; Cacace, C.; Meli, V.; Quartulli, L.; Scorrano, A.; Casati, A.; Grappone, L.; Pillow, J. J.. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - STAMPA. - 9:2(2021), pp. 159-166. [10.1016/S2213-2600(20)30179-X]