High-frequency nasal ventilation for 21 d maintains gas exchange with lower respiratory pressures and promotes alveolarization in preterm lambs

Abstract

Background: Short-term high-frequency nasal ventilation (HFNV) of preterm neonates provides acceptable gas exchange compared to endotracheal intubation and intermittent mandatory ventilation (IMV). Whether long-term HFNV will provide acceptable gas exchange is unknown. We hypothesized that HFNV for up to 21 d would lead to acceptable gas exchange at lower inspired oxygen (O2) levels and airway pressures compared to intubation and IMV.

Methods: Preterm lambs were exposed to antenatal steroids and treated with perinatal surfactant and postnatal caffeine. Lambs were intubated and resuscitated by IMV. At ~3 h of age, half of the lambs were switched to noninvasive HFNV. Support was for 3 or 21 d. By design, Pao2 and Paco2 were not different between groups.

Results: At 3 d (n = 5) and 21 d (n = 4) of HFNV, fractional inspired O2 (FiO2), peak inspiratory pressure (PIP), mean airway, intratracheal, and positive end-expiratory pressures, oxygenation index, and alveolar-arterial gradient were significantly lower than matched periods of intubation and IMV. Pao2/FiO2 ratio was significantly higher at 3 and 21 d of HFNV compared to matched intubation and IMV. HFNV led to better alveolarization at 3 and 21 d.

Conclusion: Long-term HFNV provides acceptable gas exchange at lower inspired O2 levels and respiratory pressures compared to intubation and IMV.

Figure 1

HFNV support preparation and airway pressure tracings. Panel a: Head radiograph of a preterm lamb supported by HFNV for 3d (posterior-anterior view; L, left). Black arrows highlight the uncuffed tube in the nasal cavity. The vertical black arrow identifies the tube’s tip, which is ~5 cm along the length of the nose (~10 cm). Panel b: View of the display panel of the Percussionaire VDR4 ventilator, showing phasic trace of intra-tracheal pressure and numeric data for respiratory values. The intra-tracheal pressure trace has continuous high-frequency percussions (jagged contours), including through ‘conventional inspiration’. The convective rate is 26, PIP is 17 cmH₂O, and PEEP is 8 cmH₂O. High-frequency rate is ~7 Hz (445 cycles/min) and mean pressure is 7 cmH₂O.

Figure 2

Chest radiographic and histologic appearance of lungs. Invasive support is endotracheal intubation and IMV (left column). Non-invasive support is HFNV (right column). The top two rows juxtapose radiographic and histologic images for the 3d groups. The bottom two rows juxtapose radiographic and histologic images for the 21d groups. Panels a versus b; and e versus f: Chest radiographs show better aeration and larger lung volume in the HFNV groups compared to the corresponding intubation and IMV groups (posterior-anterior view; L, left). Panels c versus d; and g versus h: Terminal respiratory units (TRU) have more uniform distal airspaces, thinner distal airspace walls (arrowheads), and more and thinner alveolar secondary septa (arrows) in the HFNV groups compared to corresponding intubation and IMV groups (the scale bar is 100 μm in length).

Figure 3

Summary of morphometric measurements (mean ± SD) made in lung tissue sections from preterm lambs managed by intermittent mandatory ventilation (IMV; white bars) or high-frequency nasal ventilation (HFNV; black bars) (n=4/group). Radial alveolar count (panel a) and volume density of secondary septa (panel b) were significantly greater, whereas distal airspace wall thickness (panel c) was significantly narrower, in the HFNV group than in the IMV group. * different from the corresponding IMV group by unpaired t-test (p<0.05).