Ulrich H Thome1, Orsolya Genzel-Boroviczeny2, Bettina Bohnhorst3, Manuel Schmid4, Hans Fuchs5, Oliver Rohde6, Stefan Avenarius7, Hans-Georg Topf8, Andrea Zimmermann9, Dirk Faas10, Katharina Timme11, Barbara Kleinlein12, Horst Buxmann13, Wilfried Schenk14, Hugo Segerer15, Norbert Teig16, Corinna Gebauer17, Roland Hentschel5, Matthias Heckmann18, Rolf Schlösser13, Jochen Peters12, Rainer Rossi11, Wolfgang Rascher8, Ralf Böttger7, Jürgen Seidenberg6, Gesine Hansen3, Maria Zernickel4, Gerhard Alzen19, Jens Dreyhaupt20, Rainer Muche20, Helmut D Hummler4. 1. Division of Neonatology, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany. Electronic address: uhthome@web.de. 2. Division of Neonatology, Dr. von Hauner University Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany. 3. Division of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany. 4. Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, University of Ulm, Ulm, Germany. 5. Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, Albert Ludwigs University Freiburg, Freiburg, Germany. 6. Division of Neonatology and Pediatric Critical Care, Elisabeth Children's Hospital, Klinikum Oldenburg, Medical Campus, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany. 7. Hospital for General Pediatrics and Neonatology, Otto von Guericke University Magdeburg, Magdeburg, Germany. 8. Division of Neonatology, University Hospital for Children and Adolescents, Friedrich-Alexander University Erlangen, Erlangen, Germany. 9. Mutter-Kind-Zentrum, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 10. University Hospital for General Pediatrics and Neonatology, Justus Liebig University Giessen, Giessen, Germany. 11. Division of Neonatology, Hospital for Children and Adolescents, Vivantes-Hospital Neukölln, Berlin, Berlin, Germany. 12. Hospital for Children and Adolescents, Children's Hospital of the Third Order, Munich, Germany. 13. Division of Neonatology, University Hospital for Children and Adolescents of the J.W. Goethe University Frankfurt am Main, Frankfurt am Main, Germany. 14. Hospital for Children and Adolescents, Central Hospital Augsburg, Augsburg, Germany. 15. St. Hedwig Hospital, University of Regensburg, Regensburg, Germany. 16. Department of Neonatology and Pediatric Intensive Care, Katholisches Klinikum, Ruhr University Bochum, Bochum, Germany. 17. Division of Neonatology, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany. 18. Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, Ernst Moritz Arndt University Greifswald, Greifswald, Germany. 19. Division of Pediatric Radiology, University Hospital of the Justus Liebig University Giessen, Giessen, Germany. 20. Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
Abstract
BACKGROUND: Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS: In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS:Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION: Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING: Deutsche Forschungsgemeinschaft.
RCT Entities:
BACKGROUND: Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS: In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS: Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION: Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING: Deutsche Forschungsgemeinschaft.
Authors: Leeann R Pavlek; Brian K Rivera; Charles V Smith; Joanie Randle; Cory Hanlon; Kristi Small; Edward F Bell; Matthew A Rysavy; Sara Conroy; Carl H Backes Journal: J Pediatr Date: 2021-04-21 Impact factor: 6.314