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Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study

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Abstract

Objective

To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation.

Design

Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO2/FIO2 at 48 h, secondary endpoints: PaO2/FIO2 at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant

Setting

Multicenter study in 19 reference centers for ARDS.

Patients

Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12–120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study.

Interventions

Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO2/FIO2 ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO2/FIO2 did not increase by 20%). A second equivalent dose within 48 h was permitted.

Results

In the pilot study the PaO2/FIO2 increased by a mean of 100 at 48 h (n=19). A higher PaO2/FIO2 ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO2/FIO2 in favor of surfactant at 48 h was found in the subgroup with an initial PaO2/FIO2 ratio higher than 65 and in patients without pneumonia.

Conclusions

Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO2/FIO2 ratio higher than 65

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Acknowledgements

This study was funded by Boehringer Ingelheim Pharma KG, Ingelheim, Germany. The ARDS Surfactant Study Group includes the following: Departments of Pediatrics/PICU: University of Aachen: H. Hörnchen MD, PhD, U. Merz MD PhD; Humboldt University of Berlin, PICU: V. Varnholt MD; University of Bonn: L. Bindl MD, S. Buderus MD; University of Erlangen: J. Scharf MD; University of Essen: C. Roll MD, L. Hanssler MD, PhD, University of Freiburg: R. Hentschel MD, T. Höhn MD; University of Giessen: S. Demirakca MD, I. Reiss MD, L. Gortner MD, PhD; University of Göttingen: H. Schiffmann MD, E. Herting MD, PhD; University of Graz: S. Rödl MD, G. Zobel MD, PhD; Medical College of Hanover: T. Paul MD, PhD, M. Sasse MD; University of Innsbruck: B. Simma MD, PhD, R. Trawöger; University of Cologne: B. Roth MD, PhD, A. Vierzig MD; Central Hospital Cologne: P. Groneck MD, PhD; Medical University of Lübeck: J.C. Möller, MD, PhD, FCCM, M. Kohl MD; University of Mainz: R.G. Huth MD, C.F. Wippermann MD; Central Hospital Mannheim/University of Heidelberg: P. Lasch MD, T. Schaible MD; University of Ulm: S. Voßbeck MD, F. Pohlandt MD, PhD; University of Würzburg: L. Schrod MD, PhD, G. Hofmann MD, Medical Sciendes Department, Boehringer Ingelheim Pharma KG: P. Schmidt PhD, H Schumacher PhD, H. von Seefeld PhD.

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Correspondence to Jens Christian Möller.

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Möller, J.C., Schaible, T., Roll, C. et al. Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study. Intensive Care Med 29, 437–446 (2003). https://doi.org/10.1007/s00134-003-1650-1

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Keywords

  • Acute respiratory distress syndrome
  • Surfactant
  • Children
  • Ventilation
  • Oxygenation
  • Pneumonia