title: Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.
abstract: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria.
  
  
  
  In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation.
  
  
  
  From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge.
  
  
  
  ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.
authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy. giovanni.vento@unicatt.it.
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authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
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authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
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authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
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authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
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authors.affiliation: Division of Neonatology, Department for the Protection of Women's Health and the Nascent Life, Child and Adolescent, Policlinico A. Gemelli - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
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authors.affiliation: Ospedale Barone Romeo, Patti (ME), Italy.
authors.forename: Caterina
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authors.affiliation: Ospedale San Bortolo, Vicenza, Italy.
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authors.affiliation: Azienda Ospedaliera-Universitaria di Modena, Modena, Italy.
authors.forename: Alberto
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authors.affiliation: Azienda Ospedaliera-Universitaria di Modena, Modena, Italy.
authors.forename: Francesco
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authors.affiliation: Azienda Ospedaliera-Universitaria di Modena, Modena, Italy.
authors.forename: Isotta
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authors.affiliation: Ospedale San Salvatore, L'Aquila, Italy.
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authors.lastname: di Fabio
authors.affiliation: Ospedale San Salvatore, L'Aquila, Italy.
authors.forename: Eugenia
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authors.lastname: Maranella
authors.affiliation: Azienda ospedaliera "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.
authors.forename: Isabella
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authors.lastname: Mondello
authors.affiliation: Ospedale Santa Maria di Ca' Foncello di Treviso, Treviso, Italy.
authors.forename: Stefano
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authors.lastname: Visentin
authors.affiliation: Ospedale Santa Maria di Ca' Foncello di Treviso, Treviso, Italy.
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mesh_terms: D060666:Airway Extubation / Q000379:methods*; D001688:Biological Products / Q000008:administration & dosage*; D002110:Caffeine / Q000008:administration & dosage; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D002951:Citrates / Q000008:administration & dosage; D045422:Continuous Positive Airway Pressure; D005260:Female; D006612:High-Frequency Ventilation / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007442:Intubation, Intratracheal / Q000379:methods*; D008297:Male; D010743:Phospholipids / Q000008:administration & dosage*; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D000697:Central Nervous System Stimulants; D002951:Citrates; D010743:Phospholipids; D011663:Pulmonary Surfactants; D002110:Caffeine; C068291:poractant alfa; C026189:caffeine citrate
keywords: HFOV; INSURE; Lung recruitment; Preterm infants