European Journal of Pediatrics

, Volume 178, Issue 7, pp 1063–1068 | Cite as

Prediction of prolonged ventilator dependence in preterm infants

  • Kamal Ali
  • Sabena Kagalwalla
  • Iram Cockar
  • Emma E Williams
  • Kentaro Tamura
  • Theodore Dassios
  • Anne GreenoughEmail author
Original Article


Volutrauma is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Our aims were to identify risk factors in the first 24 h for prolonged ventilator dependence and assess volume delivery and carbon dioxide levels in infants with evolving BPD. A retrospective study was undertaken of 41 infants born at less than 32 weeks of gestational age (GA). A higher tidal volume, minute volume and resistance and a lower GA, birth weight and compliance were associated with a significantly higher risk of ventilator dependence at 28 days. The strongest relationships were with birth weight (area under the receiver operating characteristic curve, AUROC = 0.771) and GA (AUROC = 0.813). Tidal volume remained significantly higher after adjusting for GA in those who remained ventilator dependent at 28 days. The 18 who remained ventilator dependent at 28 days had increased mean carbon dioxide (PCO2) levels with increasing age from a mean of 41 mmHg in the first 24 h to 65 mmHg at 28 days PMA (p < 0.001). The increase in PCO2 occurred despite increases in peak inflation pressures (p < 0.001), tidal volumes (p = 0.002) and minute volumes (p < 0.001).

Conclusion: These results suggest that initial volutrauma may contribute to the development of chronic ventilator dependence.

What is Known:

In prematurely born infants, excessive tidal volumes are important in the pathogenesis of bronchopulmonary dysplasia (BPD), but a tidal volume that is too low will increase the risk of atelectasis, work of breathing and energy expenditure.

What is New:

A high tidal volume in the first 24 h was associated with an increased risk of ventilator dependence at 28 days, which remained significant after adjusting for gestational age. Carbon dioxide levels significantly increased over the first month despite increased pressures and volumes in those who remained ventilator dependent.


Tidal volume Compliance Resistance Ventilator dependence Carbon dioxide levels Gestational age 



assist control ventilation


bronchopulmonary dysplasia


compliance of the respiratory system


gestational age


minute volume


peak inflation pressure


pressure limited ventilation


synchronised intermittent mandatory ventilation


vascular endothelial growth factor


tidal volume


Authors’ contributions

KA and AG designed the study. KA, SK and IC collected the data. KA, TD and AG analysed the data. All authors were involved in the preparation of the manuscript, critically reviewed the manuscript and approved the final manuscript as submitted.


The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Compliance and ethical standards

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

Routinely collected data were analysed, hence informed consent was not required.

Conflict of interest

AG has held grants from various manufacturers (Abbot Laboratories, MedImmune) and ventilator manufacturers (SLE). Professor Greenough has received honoraria for giving lectures and advising various manufacturers (Abbot Laboratories, MedImmune) and ventilator manufacturers (SLE). Professor Greenough is currently receiving a non conditional educational grant from SLE.


  1. 1.
    Berger TM, Fontana M, Stocker M (2013) The journey towards lung protective respiratory support in preterm neonates. Neonatology 104:265–274CrossRefGoogle Scholar
  2. 2.
    Bhutani VK, Ritchie WG, Shaffer TH (1986) Acquired tracheomegaly in very preterm neonates. Am J Dis Child 140:449–452Google Scholar
  3. 3.
    Björklund LJ, Ingimarsson J, Curstedt T, John J, Robertson B, Werner O, Vilstrup CT (1997) Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatr Res 42:348–355CrossRefGoogle Scholar
  4. 4.
    Dassios T, Kaltsogianni O, Greenough A (2017) Determinants of pulmonary dead space in ventilated newborn infants. Early Hum Dev 108:29–32CrossRefGoogle Scholar
  5. 5.
    Dassios T, Dixon P, Hicky A, Fouzas S, Greenough A (2018) Physiological and anatomical dead space in mechanically ventilated newborn infants. Pediatr Pulmonol 53:57–63CrossRefGoogle Scholar
  6. 6.
    Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL (2017) Late (>7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 10:CD001145Google Scholar
  7. 7.
    Dreyfuss D, Saumon G (1998) Ventilator induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 157:294–323CrossRefGoogle Scholar
  8. 8.
    Gien J, Kinsella J, Thrasher J, Grenolds A, Abman SH, Baker CD (2017) Retrospective analysis of an interdisciplinary ventilator care program intervention on survival of infants with ventilator-dependent bronchopulmonary dysplasia. Am J Perinatol 34:155–163Google Scholar
  9. 9.
    Harris C, Rushwan S, Wang W, Thorpe S, Thompson C, Peacock J, Knight M, Gooptu B, Greenough A (2017) P07 Interleukin response to cyclical mechanical stretch with models of different neonatal ventilation modes. Arch Dis Child 102:A4. CrossRefGoogle Scholar
  10. 10.
    Harris C, Thorpe SD, Rushwan S, Wang W, Thompson CL, Peacock JL, Knight MM, Gooptu B, Greenough A (2019) An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation. J Biomech 88:186–189. CrossRefGoogle Scholar
  11. 11.
    Hird M, Greenough A, Gamsu HR (1990) Gas trapping during high frequency positive pressure ventilation using conventional ventilators. Early Hum Dev 22:51–56CrossRefGoogle Scholar
  12. 12.
    Hunt K, Dassios T, Ali K, Greenough A (2018) Volume targeting levels and work of breathing in infants with evolving or established bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 104:F46–F49. CrossRefGoogle Scholar
  13. 13.
    Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729CrossRefGoogle Scholar
  14. 14.
    Keszler M, Nassabeh-Montazami S, Abubakar K (2009) Evolution of tidal volume requirement during the first 3 weeks of life in infants <800 g ventilated with volume guarantee. Arch Dis Child Fetal Neonatal Ed 94:F279–F282CrossRefGoogle Scholar
  15. 15.
    Klingenberg C, Wheeler KI, McCallion N, Morley CJ, Davis PG (2017) Volume-targeted versus pressure limited ventilation in neonates. Cochrane Database Syst Rev 10:CD003666Google Scholar
  16. 16.
    Laughon MM, Langer JC, Bose CL, Smith PB, Ambalavanan N, Kennedy KA, Stoll BJ, Buchter S, Laptook AR, Ehrenkranz RA, Cotten CM, Wilson-Costello DE, Shankaran S, Van Meurs KP, Davis AS, Gantz MG, Finer NN, Yoder BA, Faix RG, Carlo WA, Schibler KR, Newman NS, Rich W, Das A, Higgins RD, Walsh MC, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (2011) Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med 183:1715–1722CrossRefGoogle Scholar
  17. 17.
    Morley CJ (2012) Continuous positive airway pressure. In: Donn SM, Sinha SK (eds) Manual of Neonatal Respiratory Care. Springer-Verlag, New YorkGoogle Scholar
  18. 18.
    O’Reilly M, Sozo F, Harding R (2013) Impact of preterm and bronchopulmonary dysplasia on the developing lung: long term consequences for respiratory health. Clin Exp Pharmacol Physiol 40:765–773CrossRefGoogle Scholar
  19. 19.
    Pugin J, Dunn I, Jolliet P, Tassaux D, Magnenat JL, Nicod LP, Chevrolet JC (1998) Activation of human macrophages by mechanical ventilation in vitro. Am J Phys 275:L1040–L1050CrossRefGoogle Scholar
  20. 20.
    Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD (1999) Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Phys 277:L167–L1773Google Scholar
  21. 21.
    Wada K, Jobe AH, Ikegami M (1997) Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs. J Apply Physiol 83:1054–1061CrossRefGoogle Scholar
  22. 22.
    Wenzel U, Wauer RR, Schmalisch G (1999) Comparison of different methods for dead space measurements in ventilated newborns using CO2-volume plot. Intensive Care Med 25:705–713CrossRefGoogle Scholar
  23. 23.
    Zivanovic S, Peacock J, Alcazar-Paris M, Lo JW, Lunt A, Marlow N, Calvert S, Greenough A (2014) Late outcomes of a randomized trial of high-frequency oscillation in neonates. N Engl J Med 370:1121–1130CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neonatal Intensive Care CentreKing’s College Hospital NHS Foundation TrustLondonUK
  2. 2.Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and MedicineKing’s College LondonLondonUK
  3. 3.Division of Neonatology, Maternal and Perinatal CentreToyama University HospitalToyamaJapan
  4. 4.MRC Centre for Allergic Mechanisms of AsthmaKing’s College LondonLondonUK
  5. 5.NIHR Biomedical Centre at Guy’s & St Thomas NHS Foundation TrustKing’s College LondonLondonUK

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