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Aeration strategy at birth influences the physiological response to surfactant in preterm lambs
  1. David Gerald Tingay1,2,3,4,
  2. Andrea Togo1,
  3. Prue M Pereira-Fantini2,3,
  4. Martijn Miedema1,5,
  5. Karen E McCall1,2,
  6. Elizabeth J Perkins1,2,
  7. Jessica Thomson2,3,
  8. Georgie Dowse2,3,
  9. Magdy Sourial2,
  10. Raffaele L Dellacà6,
  11. Peter G Davis2,4,7,
  12. Peter Anderson Dargaville2,8,9
  1. 1 Neonatology, Royal Children’s Hospital, Parkville, Victoria, Australia
  2. 2 Neonatal Research, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
  3. 3 Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
  4. 4 Neonatal Research, The Royal Women’s Hospital, Parkville, Victoria, Australia
  5. 5 Neonatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
  6. 6 TBM Lab, Dipartimento di Elettronica, Informazione e BioIngegneria (DEIB), Politecnico di Milano University, Milan, Italy
  7. 7 Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
  8. 8 Neonatal and Paediatric Intensive Care Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia
  9. 9 Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  1. Correspondence to Dr David Gerald Tingay, Neonatal Research, Murdoch Children’s Research Institute, Parkville VIC 3052, Australia; david.tingay{at}


Background The influence of pressure strategies to promote lung aeration at birth on the subsequent physiological response to exogenous surfactant therapy has not been investigated.

Objectives To compare the effect of sustained inflation (SI) and a dynamic positive end-expiratory pressure (PEEP) manoeuvre at birth on the subsequent physiological response to exogenous surfactant therapy in preterm lambs.

Methods Steroid-exposed preterm lambs (124–127 days’ gestation; n=71) were randomly assigned from birth to either (1) positive-pressure ventilation (PPV) with no recruitment manoeuvre; (2) SI until stable aeration; or (3) 3 min dynamic stepwise PEEP strategy (maximum 14–20 cmH2O; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol. Surfactant (200 mg/kg poractant alfa) was administered at 10 min. Dynamic compliance, gas exchange and regional ventilation and aeration characteristics (electrical impedance tomography) were measured throughout and compared between groups, and with a historical group (n=38) managed using the same strategies without surfactant.

Results Compliance increased after surfactant only in the DynPEEP group (p<0.0001, repeated measures analysis of variance), being 0.17 (0.10, 0.23) mL/kg/cmH2O higher at 60 min than the SI group. An SI resulted in the least uniform aeration, and unlike the no-recruitment and DynPEEP groups, the distribution of aeration and tidal ventilation did not improve with surfactant. All groups had similar improvements in oxygenation post-surfactant compared with the corresponding groups not treated with surfactant.

Conclusions A DynPEEP strategy at birth may improve the response to early surfactant therapy, whereas rapid lung inflation with SI creates non-uniform aeration that appears to inhibit surfactant efficacy.

  • animal research
  • neonatology
  • respiratory
  • resuscitation

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  • Contributors DGT, RLD, PGD and PAD developed the concept, designed the experiment and interpreted the data. DGT, PMPF, EJP, KEMcC, MM and MS were involved in lamb experimental work. DGT supervised all aspects of the study and subsequent data analysis. KEMcC, JT, GD and DGT performed the EIT analysis. All authors participated in data interpretation under supervision of DGT, RLD, PGD and PAD. AT and DGT wrote the first draft and all authors contributed to redrafting the manuscript.

  • Funding This study is supported by a National Health and Medical Research Council Project Grant (Grant ID 1009287) and the Victorian Government Operational Infrastructure Support Program (Melbourne, Australia). DGT is supported by a National Health and Medical Research Council Clinical Career Development Fellowship (Grant ID 1053889). PGD is supported by a National Health and Medical Research Council Program Grant (Grant ID 606789) and by a National Health and Medical Research Council Practitioner Fellowship (Grant ID 556600). Chiesi Farmaceutici (Parma, Italy) provided the Curosurf used in this study as part of an unrestricted grant to DGT at the Murdoch Children’s Research Institute. Swisstom (Landquart, Switzerland) manufactured EIT belts custom-built for lambs for this study. All EIT hardware was purchased by Murdoch Children’s Research Institute.

  • Competing interests DGT and RLD have previously received grant funding from Chiesi Farmaceutici unrelated to this study.

  • Ethics approval All techniques and procedures were approved by the Animal Ethics Committee of the Murdoch Children’s Research Institute, Melbourne, Australia, in accordance with the National Health and Medical Research Council guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data, including raw data used for all figures and analysis, are available upon request to the corresponding author or via the Murdoch Children’s Research Institute open access ownCloud server (NeoResMCRI) at

  • Patient consent for publication Not required.