Higher Frequency Ventilation Attenuates Lung Injury during High-frequency Oscillatory Ventilation in Sheep Models of Acute Respiratory Distress Syndrome

Abstract

Background: High-frequency oscillatory ventilation (HFOV) at higher frequencies minimizes the tidal volume. However, whether increased frequencies during HFOV can reduce ventilator-induced lung injury remains unknown. Methods: After the induction of acute respiratory distress syndrome in the model by repeated lavages, 24 adult sheep were randomly divided into four groups (n = 6): three HFOV groups (3, 6, and 9 Hz) and one conventional mechanical ventilation (CMV) group. Standard lung recruitments were performed in all groups until optimal alveolar recruitment was reached. After lung recruitment, the optimal mean airway pressure or positive end-expiratory pressure was determined with decremental pressure titration, 2 cm H 2 O every 10 min. Animals were ventilated for 4 h. Results: After lung recruitment, sustained improvements in gas exchange and compliance were observed in all groups. Compared with the HFOV-3 Hz and CMV groups, the transpulmonary pressure and tidal volumes were statistically significantly lower in the HFOV-9 Hz group. The lung injury scores and wet/dry weight ratios were significantly reduced in the HFOV-9 Hz group compared with the HFOV-3 Hz and CMV groups. Expression of interleukin-1β and interleukin-6 in the lung tissue, decreased significantly in the HFOV-9 Hz group compared with the HFOV-3 Hz and CMV groups. Malondialdehyde expression and myeloperoxidase activity in lung tissues in the HFOV-9 Hz group decreased significantly, compared with the HFOV-3 Hz and CMV groups. Conclusion: The use of HFOV at 9 Hz minimizes lung stress and tidal volumes, resulting in less lung injury and reduced levels of inflammatory mediators compared with the HFOV-3 Hz and CMV conditions. A CUTE respiratory distress syndrome (ARDS) is the most severe manifestation of acute lung injury caused by various direct and indirect factors. Inflammatory pulmonary edema, severe hypoxemia, and diffuse endothelial and epithelial injury are key characteristics of ARDS, which can often lead to multiple organ failure.1,2 Despite being the most widely used approach to treat ARDS, conventional mechanical ventilation (CMV) can induce ventilatorinduced lung injury (VILI) due to alveolar overdistension and the cyclic collapse/reopening of lung units, eliciting inflammatory responses, and worsening the damage. 3,4 Recently, protective CMV has been shown to decrease lung and systemic inflammatory responses and improve What We Already Know about This Topic• High-frequency oscillatory ventilation provides efficient gas exchange using very high frequencies and low tidal volumes, while maintaining a constant mean airway pressure • The effects of frequency in high-frequency oscillatory ventilation on ventilation-induced lung injury are yet to be evaluated What This Article Tells Us That Is New• This study suggests that high-frequency oscillatory ventilation at higher frequencies minimizes lung stress and tidal volume, resulting in less lung injury and reduced local lung inflammation

High-Frequency Oscillatory Ventilation in Pediatric Acute Lung Injury

“…This change in practice is likely related to evolution of our understanding of the lung protective effects of HFOV. Meyer et al (20) and Liu et al (6) used an animal model to demonstrate less lung injury and reduced levels of inflammatory mediators using a higher Hertz strategy. Hager et al (21) examined factors determining Vt during HFOV in both a test lung model and patients using a hot wire anemometer placed in series with a Sensormedics 3100B high-frequency ventilator.…”

“…In several models of lung injury, HFOV has been associated with lower concentrations of inflammatory cytokines than CMV (6,7).…”

Bias flow rate and ventilation efficiency during adult high-frequency oscillatory ventilation: a lung model study

“…If the BF rate is inadequate, the resultant higher aSV might tend to impair the benefit of HFOV. In the animal study which showed the superiority of higher frequency for lung protection, the aSV was lower with higher frequency [ 10 ]. In their study, it was unclear whether the higher frequency or the lower aSV was more important.…”

Efficacy and adverse events of high-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis

“…Both are potentially detrimental to the patients. Additionally, we should utilize the highest possible frequency of HFOV in ARDS because the higher frequencies, the more easily a collapsed lung could be opened, leading to more homogeneous distribution of volumes and reduction in lung injury [34-36]. Finally, the resonance phenomenon may take place during HFOV [37], and some study found that the delivered gas volume actually exceeded the stroke volume at certain frequencies [37].…”