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Pulmonary epithelial permeability. An animal study of inverse ratio ventilation and conventional mechanical ventilation.

STUDY OBJECTIVE
To compare pressure-controlled inverse ratio ventilation (PCIRV) with volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP) at equal levels of end-expiratory alveolar pressure. The primary focus of the study was on pulmonary epithelial permeability. Histologic and gravimetric indicators of lung injury were also studied.


DESIGN
Randomized animal study.


SETTING
Experimental investigation at Södersjukhuset, Stockholm, Sweden.


ANIMALS
Thirty-two New Zealand white rabbits.


INTERVENTIONS
Ventilation with PCIRV or VCV PEEP for 6 h at an end-expiratory pressure level of 5 cm H2O.


MEASUREMENTS AND RESULTS
Lung mechanics, heart rate, BP, and gas exchange. Measurement of pulmonary epithelial permeability by 99mTc-DTPA lung clearance. Extravascular lung water by gravimetric analysis. Morphology by light microscopy after a perfusion fixation procedure. Mean and peak airway pressures were 12.4 +/- 4.3 and 15.9 +/- 4.5 cm H2O with PCIRV and 8.6 +/- 0.8 (p < 0.001) and 19.9 +/- 4.1 cm H2O (p < 0.03) with VCV PEEP at 6 h. Mean systemic BP was lower with PCIRV (58 +/- 9 mm Hg) than with VCV PEEP (68 +/- 7 mm Hg) at 6 h (p < 0.003). At 6 h, PaCO2 was lower with PCIRV (3.2 +/- 0.6 kPa) than with VCV PEEP (4.1 +/- 0.8 kPa) (p < 0.02). There was no difference in blood oxygenation between PCIRV and VCV PEEP. 99mTc-DTPA lung clearance curves were monoexponential with both PCIRV and VCV PEEP. Mean lung clearance expressed as T 1/2 was 16 +/- 9 min with PCIRV and 107 +/- 74 min with VCV PEEP (p < 0.001). Morphologic examination revealed no differences between the groups and no evidence of significant lung injury.


CONCLUSIONS
The observations reported in this article imply that PCIRV causes an alteration in lung epithelial or membrane function in comparison to VCV PEEP. This functional difference is most likely caused by the large time-adjusted lung volume produced by pressure control in combination with a prolonged inspiration. It remains to be established whether this early functional effect of PCIRV is relevant with regard to structural lung injury in mechanically ventilated subjects.