Ventilatory efficiency during high-frequency oscillatory ventilation with volume guarantee in preterm infants

This study aims to evaluate the relationship between ventilator-derived carbon dioxide clearance and arterial CO₂ elimination during high-frequency oscillatory ventilation with volume guarantee (HFOV-VG), and to examine determinants and clinical relevance of ventilatory efficiency. In this cohort study, preterm infants less than 30 weeks of gestation receiving HFOV-VG were studied during the first 72 h after birth. Minute-level ventilator data were paired with arterial blood gases. Ventilatory efficiency was defined as weight-normalised DCO₂ divided by arterial PCO₂. Temporal patterns and determinants were analysed using generalised estimating equations. The clinical outcome was death or moderate-to-severe bronchopulmonary dysplasia (BPD). A total of 185,018 ventilator observations and 595 paired ventilator-blood gas measurements from 60 infants were analysed. Arterial PCO₂ remained stable (50 [43-56] mmHg) despite wide variation in DCO₂ (34.6 [27.1-47.8]). Ventilatory efficiency varied between infants (0.72 [0.55-0.98]) and demonstrated a temporal pattern, decreasing from 0.77 (0.61-0.90) at 0-6 h to 0.65 (0.45-0.80) at 6-12 h and increasing to 0.76 (0.56-1.07) at 24-48 h. Higher efficiency was associated with higher oscillatory frequency (p < 0.001). Death or moderate-to-severe BPD occurred in 85.0%, 70.0%, and 45.0% across low, intermediate-, and high-efficiency tertiles, respectively. Ventilatory efficiency demonstrated moderate discrimination for the composite outcome (AUC 0.69), improving to 0.76 with FiO₂ and mean airway pressure.

During HFOV-VG, ventilator-derived CO₂ clearance showed limited correspondence with arterial PCO₂. Ventilatory efficiency had moderate discrimination for adverse respiratory outcomes.

• During high-frequency oscillatory ventilation, ventilator-derived indices such as oscillatory tidal volume and DCO2 are commonly used to guide carbon dioxide clearance. • The relationship between ventilator-derived carbon dioxide transport and effective arterial CO2 elimination during HFOV with volume guarantee remains incompletely understood.

• Ventilatory efficiency provides a physiological measure integrating ventilator-derived carbon dioxide transport and arterial CO2 elimination during HFOV with volume guarantee, a relationship that is not routinely evaluated in clinical practice. • Ventilatory efficiency demonstrated modest discrimination for death or moderate-to-severe bronchopulmonary dysplasia, with discrimination improving when combined with markers of respiratory support intensity.