Pulmonary epithelial permeability and gas exchange - A comparison of inverse ratio ventilation and conventional mechanical ventilation in oleic acid-induced lung injury in rabbits

Study objective: (1) To explore the interaction between mechanical ventilation and oleic acid (OA)-induced lung injury on indexes of pulmonary gas exchange and epithelial permeability, and (2) to compare this interaction using two different modes of ventilation: pressure-controlled Inverse ratio ventilation (PCIRV) and volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP). Design: Randomized animal study. Setting: Experimental laboratory investigation at Sodersjukhuset, Stockholm, Sweden. Animals: Twenty-four New Zealand white rabbits. Interventions: (1) Ventilation with PCIRV (n=6) or VCV PEEP (n=6) for 6 h at equal end-expiratory alveolar pressure levels of 5 cm H2O followed by induction of lung injury (IV injection of OA 0.15 mL/kg). (2) Induction of lung injury followed by 6 h of ventilation with either PCIRV (n=6) or VCV PEEP (n=6) as described above. Measurements and results: Lung mechanics, heart rate, BP, and gas exchange results were equal at baseline. In group A, after 1 h of ventilation, mean airway pressure was 11.9+/-4.4 with PCIRV and 8.3+/-1.0 cm H2O with VCV PEEP (p<0.05). Forty minutes after OA injection, PaO2/fraction of inspired oxygen (FIo(2)) was 24+/-10 kPa with PCIRV and 44+/-15 kPa with VCV PEEP (p<0.05). Mean airway pressure was higher and peak airway pressure was lower with PCIRV. In group B, after 6 h of ventilation, PaO2/FIo(2) was 17+/-5 kPa with PCIRV and 43+/-8 kPa with VCV PEEP (p<0.01). Systemic BP was lower with PCIRV and mean airway pressure was higher. Technetium-99m diethylene triamine penta-acetic acid lung clearance: In group A, curves were monoexponential with both PCIRV (half-life time [T 1/2], 21+/-8 min) and VCV PEEP (T 1/2, 126+/-59 min, p<0.005) until injection of OA. In the VCV PEEP-treated animals, a marked increase in clearance rate was observed within 60 s of OA injection (T 1/2, 13+/-9 min, p<0.001). Fifteen minutes after OA injections, T 1/2 had decreased to 38+/-17 min with VCV PEEP. In the animals treated with PCIRV, OA injection did not lead to a significant change in clearance rate, although the elimination pattern was observed to change from multicompartment type. In group B, clearance curves were monoexponential with both ventilatory modes, There was no significant difference in clearance rate between PCIRV (T 1/2, 25+/-9 min) and VCV PEEP (T 1/2, 36+/-16 min, not significant). Conclusions: The observation that PaO2 was lower in the PCIRV-treated groups must be interpreted with caution in this animal study with relatively few observations. The finding may reflect differences in the effect of OA injection in the two ventilatory modes, It is also possible that externally applied PEEP is more effective than PCIRV in increasing oxygen tension, either because of a less inhomogenous distribution of ventilation and perfusion or for other reasons. The clearance results imply that PCIRV causes an alteration in lung epithelial or membrane function in co functional difference is most likely caused by the large time-weighted pressure control in combination with a prolonged inspiration. Induction of injury with OA eliminates the difference between PCIRV and VCV PEEP. It remains to be established whether these findings are relevant with regard to ventilator-associated structural lung injury in man.