Periodic Fluctuation of Tidal Volumes Further Improves Variable Ventilation in Experimental Acute Respiratory...

In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (V ) 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 V 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 V fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious V (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four V patterns: (1) random variation of V (WN); (2) P₀₄, main V frequency of 0.13 Hz; (3) P₁₀, main V frequency of 0.05 Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable V , the coefficient of variation was identical (30%). We assessed lung mechanics and gas exchange, and determined lung histology and inflammation. Compared to VCV, WN, P₀₄, and P₁₀ resulted in lower respiratory system elastance (63 ± 13 cm H₂O/L vs. 50 ± 14 cm H₂O/L, 48.4 ± 21 cm H₂O/L, and 45.1 ± 5.9 cm H₂O/L respectively, P < 0.05 all), but only P₁₀ improved PaO₂/F_IO₂ after 6 h of ventilation (318 ± 96 vs. 445 ± 110 mm Hg, P < 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P₁₀. Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic V fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.