Pulmonary Epithelial Permeability

An Animal Study of Inverse Ratio Ventilation and Conventional Mechanical Ventilation

¹ From the Medical ICU, Department of Medicine, Södersjukhuset, Stockholm, Sweden
² From the Department of Hospital Physics, Södersjukhuset, Stockholm, Sweden
³ From the Department of Clinical Pathology, Karolinska Hospital, Solna, Sweden
⁴ From the Department of Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden

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 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.

Key Words: ARDS • intrinsic PEEP • inverse ratio ventilation • lung clearance • PEEP • ventilation • artificial

Submitted on December 6, 1995
Accepted on February 5, 1996

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