Lung volume determines airway stability during total liquid ventilation: evidence from neonatal piglets

Total liquid ventilation (TLV) has been proposed as an alternative to gas ventilation in extreme preterm babies. Airway collapse has been described during expiration in TLV. We investigated the impact of varying lung volume on airway deformation and its effects on hemodynamic stability and gas exchange.

Nine piglets (5-7 days old, 2 kg, 5 females) were ventilated with TLV. Perfluorooctyl bromide was added when tracheobronchial collapse was observed, restoring normal expiratory pressure considered as baseline ventilation level (V0). Perfluorooctyl bromide was administered at increments of +1 mL/kg (V1), +3 mL/kg (V3), and +5 mL/kg (V5) in randomized order. Static CT scans were used to measure end-expiratory lung volume (EELV), and dynamic CT scans to assess tracheal cross-sectional area during expiration.

At V0 (EELV of 37 [32;40] mL/kg, median [Q1;Q3]), tracheal area varied by 35% [31;63] from the beginning to the end of expiration. At V3 (EELV 42 [39:51] mL/kg), tracheal deformation decreased to 18% [9;22] (p < 0.005). Mean arterial pressure (MAP) decreased between V0 and V5 (p = 0.02). Blood gases remained unchanged.

There is a narrow therapeutic window for end-expiratory lung volume during TLV in the neonatal-subject in order to stabilize the airway while avoiding hemodynamic impacts.

During total liquid ventilation, severe expiratory tracheobronchial deformation can occur without any detectable drop in airway opening pressure, challenging current safety markers. This is the first in vivo study using dynamic CT imaging to quantify occult airway deformation during TLV in a neonatal model and to link it directly to end-expiratory lung volume. The findings redefine ventilatory safety during TLV, identify a narrow therapeutic window for lung volume optimization, and provide essential mechanistic data to guide safer translational development toward human neonatal application.