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Treatment and outcome data of very low birth weight infants treated with less invasive surfactant administration in comparison to intubation and mechanical ventilation in the clinical setting of a cross-sectional observational multicenter study

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Abstract

The aim of this study was to contribute further to existing randomized controlled trials and meta-analyses showing advantages in the outcome of less invasive surfactant administration (LISA)-treated infants and add new aspects concerning treatment and outcome data collected in the routine clinical setting. Four hundred seven very low birth weight infants who received surfactant via either LISA or intubation methods were enrolled in the observational cross-sectional multicenter study. To compare infants in terms of surfactant administration, we used an exact matching procedure (the same gestational age, severe perinatal depression (pH < 7.10), birth weight < 10th percentile, antenatal steroid treatment, and the same gender). To check for robustness, we performed repeated matching. LISA-treated infants required significantly less mechanical ventilation during hospital stay (p < 0.001) and days with supplemental oxygen (p = 0.03). Analgesics and sedatives were used less often during the stay (p < 0.001). Infants treated with LISA had significantly lower rates of bronchopulmonary dysplasia (p = 0.003). LISA failure infants were identified as more likely to be small for gestational age and more immature.

Conclusion: Our study complements former results with advantages for LISA-treated infants in mechanical ventilation and bronchopulmonary dysplasia in the clinical routine.

Trial registration: DRKS00004589

What is Known:

• According to existing literature, LISA-treated infants seem to have some favors in terms of treatment and outcome data. Observational studies in routine clinical setting are missing.

What is New:

• Data of 407 VLBW infants collected in routine clinical setting showed that LISA-treated infants needed less mechanical ventilation and fewer days with supplemental oxygen and less analgesics and sedatives. A reduced risk of BPD could be showed. SGA infants seem to have higher risks of LISA failure.

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Abbreviations

BPD:

Bronchopulmonary dysplasia

bpm:

Beats per minute

n-CPAP:

Nasal continuous positive airway pressure

InSurE:

Intubate, surfactant, extubate

IVH:

Intraventricular hemorrhage

LISA:

Less invasive surfactant administration

MV:

Mechanical ventilation

NICU:

Neonatal intensive care unit

PIE:

Pulmonary interstitial emphysema

PVL:

Periventricular leukomalacia

RCT:

Randomized controlled trial

ROP:

Retinopathy of prematurity

RDS:

Respiratory distress syndrome

SIRS:

Systemic inflammatory response syndrome

VLBW:

Very low birth weight

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Acknowledgements

The study was funded by the Federal Ministry of Education and Research (01GY1152). The authors indicate that they have no financial relationships to disclose that are relevant to this article. No conflict of interest has been declared by the authors. The trial has been registered at the German clinical trials register, DRKS00004589.

The following hospitals and investigators participated in the study (in alphabetical order):

Department of Neonatology, Klinikum Frankfurt (Oder): Cornelia Ast, MD; Department of Neonatology, Children’s Hospital, Marienhospital Bottrop gGmbH: Sezgin Ata, MD; Children’s Hospital, St. Vincenz-Krankenhaus GmbH: Björn Beckers, MD; Department of Neonatology and Pediatric Intensive Care, University Medical Centre Greifswald: Anke Beyersdorff, MD; Department of Neonatology, Charité University Medical Centre Berlin: Christoph Bührer, MD; Children’s Hospital, Klinikum Oberberg GmbH: Salem El-Hamid, MD; Children’s University Hospital, Johannes Wesling Klinikum Minden: Bernhard Erdlenbruch, MD; Department of Neonatology, GFO Kliniken Bonn: St. Marien Hospital: Werner Garbe, MD; Department of Neonatology, Dr. von Hauner Kinderspital, Klinikum der Universität München: O. Genzel-Boroviczény, MD; Department of Neonatology, Christophorus-Kliniken Coesfeld: Hubert Gerleve, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, Marienhospital Witten: Baham Gharavi, MD; Department of Neonatology, Children’s Hospital Lübeck, University Hospital Schleswig-Holstein: Wolfgang Göpel, MD; Department of Neonatology, St. Marien- und St. Annastiftskrankenhaus: Birgit Görtz, MD; Department of Neonatology and Pediatric Intensive Care, University Hospital Halle, Martin-Luther University Halle: Roland Haase, MD; Department of Neonatology, Children’s Hospital, Diakoniekrankenhaus Bad Kreuznach: Edmondo Hammond, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, Helios Klinikum Krefeld: Peter Heister, MD; Department of Neonatology, Children’s Hospital, University of Witten/Herdecke, HELIOS University Hospital Wuppertal: Michael Heldmann, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, University Hospital of Freiburg: Roland Hentschel, MD; Department of Neonatology, Children’s Hospital St. Marien, Landshut: Reinhard Herterich, MD; Department of Neonatology, Children’s Hospital, Krankenhaus St. Elisabeth und St. Barbara Halle (Saale) GmbH: Claudia Heß, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, Klinikum Itzehoe: Georg Hillebrand, MD; Children’s Hospital, Gesundheitszentrum Rheine, Mathias-Spital: Hans-Georg Hofmann, MD; Children’s Hospital, Evangelisches Krankenhaus Lippstadt: Thomas Hofmann, MD; Department of Neonatology, Heinrich-Heine-University Düsseldorf: Thomas Höhn, MD; Children’s Hospital, Klinikum Leverkusen gGmbH: Peter Jahn, MD; Children’s Hospital, Evangelisches Waldkrankenhaus Spandau, Berlin: Frank Jochum, MD; Children’s Hospital, OVGU-University Magdeburg: Gerhard Jorch, MD; Department of Neonatology Ostbayern, Children’s Hospital, Kliniken Dritter Orden gGmbh Passau: Matthias Keller, MD; Children’s Hospital, Bethlehem Gesundheitszentrum Stolberg gGmbH: Heiner Kentrup, MD; Department of Neonatology, University of Regensburg, Klinik St. Hedwig, Krankenhaus Barmherzige Brüder: Jochen Kittel, MD; Children’s Hospital, HELIOS Dr. Horst Schmidt Kliniken Wiesbaden: Markus Knuf, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, Klinikum Links der Weser gGmbH: Hans Thorsten Körner, MD; Department of Neonatology, Städtisches Klinikum Karlsruhe gGmbH: Alexander Krauth, MD; Department of Neonatology, Children’s Hospital, University Hospital of Cologne: Angela Kribs, MD; Department of Neonatology, University Childrens Hospital Göttingen: Helmut Küster, MD; Department of Neonatology, Children’s Hospital, DRK Kliniken Berlin Westend: Arpad von Moers, MD; Department of Neonatology and Pediatric Intensive Care, University Hospital of Bonn: Andreas Müller, MD; Children’s Hospital, Klinikum Kassel: Dirk Müller, MD; Department of Neonatology, Children’s Hospital, Klinikum Memmingen: Ralf Pallacks, MD; Department of Neonatology and Pediatric Intensive Care, DRK Kinderklinik Siegen: Markus Pingel, MD; Department of Neonatology, Children’s Hospital, Klinikum Fulda: Reinald Repp, MD; Children’s Hospital, Vivantes Klinikum Neukölln: Rainer Rossi, MD; Department of Neonatology, Children’s Hospital, Katholisches Karl-Leisner-Klinikum gGmbH, St.-Antonius-Hospital, Kleve: Jochen Rübo, MD; Children’s University Hospital, Paracelsius Medizinische Privatuniversität, Klinikum Nürnberg Süd: Stefan Schäfer, MD; Children’s Hospital, St. Joseph-KH Berlin: Antje Schlesinger, MD; Department of Neonatology, Children’s Hospital, University Hospital of Frankfurt: Rolf L. Schlößer, MD; Children’s Hospital, Städtisches Klinikum Dresden/Neustadt: Stefan Schmidt, MD; Department of Neonatology, Children’s Hospital, Klinikum Esslingen GmbH: Christian von Schnakenburg, MD; Department of Neonatology Nordostbayern, St. Marien, Amberg: Alexander Schnelke, MD; Children’s Hospital, Stauferklinikum Schwäbisch Gmünd: Birgit Schwander, MD; Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, Klinikum Worms gGmbH: Heino Skopnik, MD; Children’s Hospital, Harzklinikum Dorothea Christiane Erxleben: Dieter Sontheimer, MD; Department of Neonatology, Children’s Hospital, Klinikum Herford: Uwe Spille, MD; Children’s Hospital, Klinikum Mutterhaus der Borromäerinnen: Wolfgang Thomas, MD; Children’s Hospital, University of Erlangen-Nürnberg: Hans Georg Topf, MD; Department of Neonatology, Children’s Hospital, Klinikum Singen: Andreas Trotter, MD; Department of Neonatology and Pediatric Intensive Care Medicine, Asklepios Klinik Sankt Augustin: Beatrix Wiebe, MD; Department of Neonatology and Pediatric Intensive Care Medicine, Klinikum Aschaffenburg: Christian Wieg, MD; Children’s Hospital, Caritas Hospital Bad Mergentheim: Christian Willaschek, MD; Department of Neonatology, DONAUISAR Klinikum Deggendorf: Michael Welsch, MD; Department of Neonatology and Pediatric Intensive Care, Altonaer Kinderkrankenhaus gGmbH: Axel von der Wense, MD; Department of Neonatology, Children’s Hospital, Carl-Thiem-Klinikum Cottbus gGmbH: Ulrike Wetzel, MD; Department of Neonatology, Main-Kinzig-Kliniken: Manuel Wilhelm, MD; Department of Neonatology, Children’s Hospital Bamberg: Alfons Wolf, MD; Department of General Pediatrics and Neonatology, University Hospital Saarland: Caroline Wollny.

Funding

All phases of this study were supported by the BMBF (Bundesministerium für Bildung und Forschung) (01GY1152).

Author information

Authors and Affiliations

  1. Department of Neonatology, Children’s Hospital of the University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany

    Kristina Langhammer, Bernhard Roth & Angela Kribs

  2. Department of Pediatrics, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Wolfgang Göpel

  3. Department of Business Administration and Health Care Management, University of Cologne, Dürener Str. 56-60, 50931, Cologne, Germany

    Ludwig Kuntz & Felix Miedaner

Authors
  1. Kristina Langhammer
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  2. Bernhard Roth
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  3. Angela Kribs
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  4. Wolfgang Göpel
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  5. Ludwig Kuntz
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Contributions

Dr. Langhammer contributed to the acquisition and interpretation of data and analysis, was responsible for drafting the article, and approved the final manuscript as submitted.

Prof Dr. Roth conceptualized and designed the study, critically reviewed the manuscript, and approved the final manuscript as submitted.

Dr. Kribs was responsible for revising the article critically for content and approved the final manuscript as submitted.

Prof Dr. Göpel provided data from the German Neonatal Network (GNN). He was responsible for revising the article critically for content and approved the final manuscript as submitted.

Prof Dr. Kuntz provided advice on methods and logic, reviewed the drafts critically and approved the final manuscript as submitted.

M. Sc. Miedaner carried out the initial analyses, reviewed and added the manuscript, and approved the final manuscript as submitted.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Kristina Langhammer.

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Financial disclosure

The authors indicate that they have no financial relationships to disclose that are relevant to this article.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study (represented by their parents).

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Communicated by Patrick Van Reempts

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Langhammer, K., Roth, B., Kribs, A. et al. Treatment and outcome data of very low birth weight infants treated with less invasive surfactant administration in comparison to intubation and mechanical ventilation in the clinical setting of a cross-sectional observational multicenter study. Eur J Pediatr 177, 1207–1217 (2018). https://doi.org/10.1007/s00431-018-3179-x

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