AUTHOR=Güldner Andreas , Huhle Robert , Beda Alessandro , Kiss Thomas , Bluth Thomas , Rentzsch Ines , Kerber Sarah , Carvalho Nadja C. , Kasper Michael , Pelosi Paolo , de Abreu Marcelo G. 

TITLE=Periodic Fluctuation of Tidal Volumes Further Improves Variable Ventilation in Experimental Acute Respiratory Distress Syndrome

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00905

DOI=10.3389/fphys.2018.00905

ISSN=1664-042X

ABSTRACT=<p>In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (<italic>V</italic><sub><italic>T</italic></sub>) during volume controlled ventilation improves gas exchange and respiratory system mechanics (so-called stochastic resonance hypothesis). It is unknown whether those positive effects may be further enhanced by periodic <italic>V</italic><sub><italic>T</italic></sub> fluctuation at distinct frequencies, also known as deterministic frequency resonance. We hypothesized that the positive effects of variable ventilation on lung function may be further amplified by periodic <italic>V</italic><sub><italic>T</italic></sub> fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious <italic>V</italic><sub><italic>T</italic></sub> (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four <italic>V</italic><sub><italic>T</italic></sub> patterns: (1) random variation of <italic>V</italic><sub><italic>T</italic></sub> (WN); (2) P<sub>04</sub>, main <italic>V</italic><sub><italic>T</italic></sub> frequency of 0.13 Hz; (3) P<sub>10</sub>, main <italic>V</italic><sub><italic>T</italic></sub> frequency of 0.05 Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable <italic>V</italic><sub><italic>T</italic></sub>, the coefficient of variation was identical (30%). We assessed lung mechanics and gas exchange, and determined lung histology and inflammation. Compared to VCV, WN, P<sub>04</sub>, and P<sub>10</sub> resulted in lower respiratory system elastance (63 ± 13 cm H<sub>2</sub>O/L vs. 50 ± 14 cm H<sub>2</sub>O/L, 48.4 ± 21 cm H<sub>2</sub>O/L, and 45.1 ± 5.9 cm H<sub>2</sub>O/L respectively, <italic>P</italic> &lt; 0.05 all), but only P<sub>10</sub> improved PaO<sub>2</sub>/F<sub>I</sub>O<sub>2</sub> after 6 h of ventilation (318 ± 96 vs. 445 ± 110 mm Hg, <italic>P</italic> &lt; 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P<sub>10</sub>. Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic <italic>V</italic><sub><italic>T</italic></sub> fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.</p>