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Total liquid ventilation in an ovine model of extreme prematurity: a randomized study



This study aimed at comparing cardiorespiratory stability during total liquid ventilation (TLV)—prior to lung aeration—with conventional mechanical ventilation (CMV) in extremely preterm lambs during the first 6 h of life.


23 lambs (11 females) were born by c-section at 118–120 days of gestational age (term = 147 days) to receive 6 h of TLV or CMV from birth. Lung samples were collected for RNA and histology analyses.


The lambs under TLV had higher and more stable arterial oxygen saturation (p = 0.001) and cerebral tissue oxygenation (p = 0.02) than the lambs in the CMV group in the first 10 min of transition to extrauterine life. Although histological assessment of the lungs was similar between the groups, a significant upregulation of IL-1a, IL-6 and IL-8 RNA in the lungs was observed after TLV.


Total liquid ventilation allowed for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Refinement of our TLV prototype and ventilation algorithms is underway to address specific challenges in this population, such as minimizing tracheal deformation during the active expiration.


  • Total liquid ventilation allows for remarkably stable transition to extrauterine life in an extremely preterm lamb model.

  • Total liquid ventilation is systematically achievable over the first 6 h of life in the extremely premature lamb model.

  • This study provides additional incentive to pursue further investigation of total liquid ventilation as a transition tool for the most extreme preterm neonates.

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Fig. 1: Peripheral oxygen saturation, cerebral tissue oxygenation and heart rate throughout the first 10 min following umbilical cord clamping.
Fig. 2: Latent class modeling of the cerebral tissue oxygenation.
Fig. 3: Lung histological inflammation score.
Fig. 4: Relative RNA expression of several inflammatory biomarkers in the lungs.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.


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The authors would like to thank Samuel Lemaire-Paquette from the biostatistics department of the Université de Sherbrooke Hospital Research Center for help with the statistical analysis and review of the manuscript.


This research was funded by the Center de recherche du CHUS, Foundation of Stars, Quebec Respiratory Health Research Network, Fonds de Recherche en Santé du Québec, the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research.

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Authors and Affiliations



Substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data: C.M., É.S., J.P.P., B.C., P.L., W.S., M.S., R.I., C.N., N.S., S.M., S.T., P.M., and E.F.P. Drafting the article or revising it critically for important intellectual content: C.M., E.F.P., J.P.P., and P.M. Final approval of the version to be published: all authors.

Corresponding author

Correspondence to Étienne Fortin-Pellerin.

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Competing interests

P.M. declares to be a co-inventor of patents on liquid ventilation (US patents #7,726,311 B2; US patent 2016/0,271,348 A1; US patent 2021/0,077,759 A1; European patent 21305533.8). P.M. is a shareholder of a start-up company dedicated to the commercialization of a liquid ventilator for ultra-fast hypothermia induction after cardiac arrest (Orixha). The remaining authors declare no conflicts of interest of any sort.

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Morin, C., Simard, É., See, W. et al. Total liquid ventilation in an ovine model of extreme prematurity: a randomized study. Pediatr Res 95, 974–980 (2024).

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