Giovanni Vento1, Maria Luisa Ventura2, Roberta Pastorino3, Anton H van Kaam4, Virgilio Carnielli5, Filip Cools6, Carlo Dani7, Fabio Mosca8, Graeme Polglase9, Paolo Tagliabue2, Luca Boni10, Francesco Cota11, Milena Tana11, Chiara Tirone11, Claudia Aurilia11, Alessandra Lio11, Simonetta Costa11, Vito D'Andrea11, Mariella Lucente12, Gabriella Nigro12, Lucio Giordano13, Vincenzina Roma13, Paolo E Villani14, Francesca P Fusco15, Valeria Fasolato14, Maria Rosa Colnaghi8, Piero G Matassa8, Valentina Vendettuoli8, Chiara Poggi7, Antonio Del Vecchio16, Flavia Petrillo16, Pasqua Betta17, Carmine Mattia17, Giampaolo Garani18, Agostina Solinas18, Eloisa Gitto19, Vincenzo Salvo19, Giancarlo Gargano20, Eleonora Balestri20, Fabrizio Sandri21, Giovanna Mescoli21, Stefano Martinelli22, Laura Ilardi22, Elena Ciarmoli2, Sandra Di Fabio23, Eugenia Maranella23, Carolina Grassia24, Gaetano Ausanio24, Vincenzo Rossi24, Angela Motta25, Lucia G Tina25, Kim Maiolo25, Stefano Nobile26, Hubert Messner27, Alex Staffler27, Federica Ferrero28, Ilaria Stasi28, Luisa Pieragostini29, Isabella Mondello30, Cristina Haass31, Chiara Consigli31, Stefania Vedovato32, Alessandra Grison32, Gianfranco Maffei33, Giuseppe Presta34, Roberto Perniola34, Marcello Vitaliti35, Maria P Re35, Mario De Curtis36, Viviana Cardilli36, Paola Lago37, Francesca Tormena37, Luigi Orfeo38, Camilla Gizzi38, Luca Massenzi38, Diego Gazzolo39, Maria Chiara M Strozzi40, Roberto Bottino41, Federica Pontiggia41, Alberto Berardi42, Isotta Guidotti42, Caterina Cacace43, Valerio Meli43, Lorenzo Quartulli44, Antonio Scorrano44, Alessandra Casati45, Lidia Grappone46, J Jane Pillow47. 1. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: giovanni.vento@unicatt.it. 2. Fondazione Monza e Brianza per il Bambino e la sua Mamma, Ospedale San Gerardo Monza, Italy. 3. Department of Woman and Child Health and Public Health, Public Health Area, Fondazione Policlinico Universitario A Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. 4. Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 5. Division of Neonatology, Department of Clinical Sciences, Polytechnic University of Marche and Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. 6. Department of Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium. 7. Department of Mother and Child Health, Division of Neonatology and Neonatal Intensive Care Unit, Careggi University Hospital, Florence, Italy. 8. Department of Clinical Sciences and Community Health, University of Milan, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. 9. The Ritchie Centre Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia. 10. SC Epidemiologia Clinica Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genova, Italy. 11. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy. 12. Azienda Ospedaliera Cosenza, Cosenza, Italy. 13. Ospedale Pineta Grande, Castel Volturno, Italy. 14. Azienda Ospedaliera Carlo Poma, Mantova, Italy. 15. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy; Azienda Ospedaliera Carlo Poma, Mantova, Italy. 16. Dipartimento Materno Infantile ASL Bari, Ospedale Di Venere, Bari, Italy. 17. Azienda Ospedaliera-Universitaria Policlinico Vittorio Emanuele- Presidio Ospedaliero Gaspare Rodolico, Catania, Italy. 18. Azienda Ospedaliera-Universitaria, Ferrara, Italy. 19. Università degli studi, Messina, Italy. 20. Azienda Unità Sanitaria Locale, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy. 21. Ospedale Maggiore, Bologna, Italy. 22. Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy. 23. Ospedale San Salvatore, L'Aquila, Italy. 24. Azienda Ospedaliera S Anna e S Sebastiano, Caserta, Italy. 25. ARNAS Garibaldi, Catania, Italy. 26. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy; Division of Neonatology, Department of Clinical Sciences, Polytechnic University of Marche and Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. 27. Ospedale di Bolzano, Novara, Italy. 28. Ospedale Maggiore, Novara, Italy. 29. Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy; Dipartimento Materno Infantile, Unità Operativa Complessa Neonatologia e Pediatria, Ospedale Augusto Murri, Fermo, Italy. 30. Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. 31. Ospedale Fatebenefratelli-San Pietro, Rome, Italy. 32. Ospedale San Bortolo, Vicenza, Italy. 33. Azienda Ospedaliera-Universitaria Ospedali Riuniti, Foggia, Italy. 34. Azienda Ospedaliera Vito Fazzi, Lecce, Italy. 35. ARNAS Civico, Palermo, Italy. 36. Maternal and Child Health Department, University of Rome La Sapienza, Rome, Italy. 37. Ospedale Cà Foncello, Treviso, Italy. 38. Ospedale "San Giovanni Calibita" Fatebenefratelli, Rome, Italy. 39. Ospedale C Arrigo, Alessandria, Italy; Chieti University, Chieti, Italy. 40. Ospedale C Arrigo, Alessandria, Italy. 41. Fondazione Poliambulanza, Brescia, Italy. 42. Azienda Ospedaliera-Universitaria Policlinico, Modena, Italy. 43. Ospedale Barone Romeo, Patti, Italy. 44. Azienda Ospedaliera "Card G Panico", Tricase, Italy. 45. Ospedale Bel Colle, Viterbo, Italy. 46. Azienda Ospedaliera G Rummo, Benevento, Italy. 47. Centre for Child Health Research and School of Human Sciences, The University of Western Australia, Perth, WA, Australia.
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.
RCT Entities:
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.
Authors: Peter Aaby; Christine Stabell Benn; Katie L Flanagan; Sabra L Klein; Tobias R Kollmann; David J Lynn; Frank Shann Journal: Nat Rev Immunol Date: 2020-05-27 Impact factor: 53.106
Authors: Ömer Erdeve; Emel Okulu; Kari D Roberts; Scott O Guthrie; Prem Fort; H Gözde Kanmaz Kutman; Peter A Dargaville Journal: Turk Arch Pediatr Date: 2021-11