Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants—“The OPTTIMMAL-Trial”—Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial
Markus Waitz,
Corinna Engel,
Rolf Schloesser,
Ulrich Rochwalsky,
Sascha Meyer,
Michael Zemlin,
Bettina Bohnhorst,
Corinna Peter,
Marc Hoppenz,
Thomas Pabst,
Klaus-Peter Zimmer,
Axel R. Franz,
Harald Ehrhardt,
Annesuse Schmidt,
Alexander Larsen,
Paul Hoffmann,
Christoph Haertel,
Eric Frieauff,
Julia Sandkötter,
Katja Masjosthusmann,
Philipp Deindl,
Dominique Singer
Affiliations
Markus Waitz
Department of General Pediatrics and Neonatology, Center for Child and Adolescent Medicine, Justus-Liebig-University
Corinna Engel
Center for Pediatric Clinical Studies, University of Tübingen
Rolf Schloesser
Division of Neonatology, University of Frankfurt
Ulrich Rochwalsky
Division of Neonatology, University of Frankfurt
Sascha Meyer
Neonatal Intensive Care Unit, Department of Pediatrics and Neonatology, Saarland University Medical Center
Michael Zemlin
Neonatal Intensive Care Unit, Department of Pediatrics and Neonatology, Saarland University Medical Center
Bettina Bohnhorst
Division of Pediatric Pulmonology, Allergology and Neonatology Hannover Medical School
Corinna Peter
Division of Pediatric Pulmonology, Allergology and Neonatology Hannover Medical School
Marc Hoppenz
Neonatology and Pediatric Intensive Care Medicine, Hospital Cologne
Thomas Pabst
Neonatology and Pediatric Intensive Care Medicine, Hospital Cologne
Klaus-Peter Zimmer
Department of General Pediatrics and Neonatology, Center for Child and Adolescent Medicine, Justus-Liebig-University
Axel R. Franz
Center for Pediatric Clinical Studies, University of Tübingen
Harald Ehrhardt
Department of General Pediatrics and Neonatology, Center for Child and Adolescent Medicine, Justus-Liebig-University
Annesuse Schmidt
Department of General Pediatrics and Neonatology, Center for Child and Adolescent Medicine, Justus-Liebig-University
Alexander Larsen
Neonatal Intensive Care Unit, Department of Pediatrics and Neonatology, Saarland University Medical Center
Paul Hoffmann
Neonatal Intensive Care Unit, Department of Pediatrics and Neonatology, Saarland University Medical Center
Christoph Haertel
University Children’s Hospital, University of Würzburg
Eric Frieauff
University Children’s Hospital, University of Würzburg
Julia Sandkötter
Department of General Pediatrics, University Children’s Hospital Muenster
Katja Masjosthusmann
Department of General Pediatrics, University Children’s Hospital Muenster
Philipp Deindl
Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Medical Center Hamburg-Eppendorf
Dominique Singer
Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Medical Center Hamburg-Eppendorf
Abstract Background Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. Methods In this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH2O) or a lower (3–5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). Discussion Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. Trial registration drks.de DRKS00019940 . Registered on March 13, 2020
