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

In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (V(T)) 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(T) 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(T) fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious V(T) (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four V(T) patterns: (1) random variation of V(T) (WN); (2) P(04), main V(T) frequency of 0.13 Hz; (3) P(10), main V(T) frequency of 0.05 Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable V(T), 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(04), and P(10) resulted in lower respiratory system elastance (63 ± 13 cm H(2)O/L vs. 50 ± 14 cm H(2)O/L, 48.4 ± 21 cm H(2)O/L, and 45.1 ± 5.9 cm H(2)O/L respectively, P < 0.05 all), but only P(10) improved PaO(2)/F(I)O(2) 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 P(10). Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic V(T) fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.