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Higher CPAP levels improve functional residual capacity at birth in preterm rabbits

Abstract

Background

Preterm infants are commonly supported with 4–8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC).

Methods

Preterm rabbits delivered at 29/32 days (~26–28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing ~2 cm H2O/min) for up to 10 min after birth.

Results

FRC was lower in the 0 (6.8 (1.0–11.2) mL/kg) and 5 (10.1 (1.1–16.8) mL/kg) compared to the 15 (18.8 (10.9–22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates.

Conclusion

In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O.

Impact

  • Although preterm infants are commonly supported with 4–8 cm H2O CPAP at birth, preclinical studies have shown that higher PEEP levels improve lung aeration.

  • In this study, CPAP levels of 15 cm H2O improved lung aeration and reduced apnoea in preterm rabbit kittens immediately after birth. In all, 15 cm H2O CPAP did not increase the risk of lung over-expansion (indicated by bulging between the ribs), pneumothorax, or CPAP belly.

  • These results can be used when designing future studies on CPAP strategies for preterm infants in the delivery room.

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Fig. 1: Summary of the “Methods” section.
Fig. 2: Phase contrast X-ray imaging.
Fig. 3: Functional residual capacity (FRC).
Fig. 4: Spontaneous breathing.
Fig. 5: CPAP decrease.

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Acknowledgements

The authors thank the support provided by the SPring-8 Japan Synchrotron Radiation Research Institute, which was provided by the SPring-8 Program Review Committee (2016A0132), and gratefully acknowledge the expert assistance of Kentaro Uesugi, Naoto Yagi, Masato Hoshino and Hiroyuki Iwamoto for assistance to conduct our experiments at SPring-8. This experiment was supported by the National Health and Medical Research Council (NHMRC) Program Grant (606789), NHMRC Research Fellowships (SH: APP1058537) and the Victorian Government’s Operational Infrastructure Support Program. A.B.t.P. is recipient of an NWO innovational research incentives scheme (VIDI 91716428). E.V.M. was supported by a Monash University Postdoctoral Fellowship (BPF17-0066) and a NHMRC Peter Doherty Biomedical Early Career Fellowship (APP1138049). M.J.K. is a recipient of ARC Future Fellowship (FT160100454). We acknowledge travel funding provided by the International Synchrotron Access Program (ISAP) managed by the Australian Synchrotron and funded by the Australian Government (AS/IA173/12909 and ISP12221).

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All authors included in this paper fulfil the criteria of authorship. T.M., K.J.C., E.V.M., A.B.t.P. and S.B.H. made substantial contributions to the design of the experiment. All authors were involved in performing the experiment and obtaining data. T.M., M.K.C., M.J.K., A.B.t.P. and S.B.H. were responsible for data analysis and interpretation. T.M., A.B.t.P. and S.B.H. drafted the first version of the manuscript, after which all authors provided feedback and approved the final version.

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Correspondence to Tessa Martherus.

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Martherus, T., Croughan, M.K., Crossley, K.J. et al. Higher CPAP levels improve functional residual capacity at birth in preterm rabbits. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01647-8

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