Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients

Abstract

Background: Perflubron is a perfluorocarbon with unique physical characteristics. It has twice the density of water, allows free diffusion of O2 and CO2, is easily dispersed, and is insoluble. Thus, it can act as "liquid positive end-expiratory pressure" to recruit collapsed alveoli and improve oxygenation. Results of laboratory studies suggest that perflubron exerts an anti-inflammatory effect on alveolar cells. Limited clinical data in neonates and adults with severe acute respiratory distress syndrome are promising. We present a single institution's experience with partial liquid ventilation (PLV) in trauma patients compared with conventional mechanical ventilation (CMV) with particular attention to the alveolar inflammatory response.

Methods: Ventilated patients with bilateral lung injury and PaO2/FIO2 < 300 were eligible in this prospective multicenter trial. Perflubron was administered by means of the endotracheal tube to fill up to functional residual capacity (approximately 30 mL/kg), followed by supplemental doses up to 96 hours. At this institution, bronchoscopy with bronchoalveolar lavage was performed serially for white blood cell count, protein, interleukin (IL)-1, IL-6, IL-8, and IL-10, and analyzed as early (< 48 hours) and late (48-96 hours). Clinical response was defined as a sustained 10% increase in PaO2/FIO2 at 48 hours.

Results: 16 patients were enrolled: 12 PLV patients and 4 CMV patients. There were no differences between groups relative to sex, Injury Severity Score, or initial PaO2/FIO2. There were no major outcome differences between groups in this pilot study relative to pneumonia (50% PLV and 75% CMV), deaths (one death in each group caused by multiple organ failure), or for oxygenation after 5 days. Eight PLV patients were responders (PLV-R) compared with four patients who did not (PLV-NR). The main differences between these subgroups was time from injury to study (1.8 days for PLV-R vs. 5.8 for PLV-NR, p < 0.02) and age (30 years for PLV-R vs. 42 years for PLV-NR, p < 0.04). Both white blood cell count and protein were higher in CMV, suggesting a greater inflammatory response. Neutrophils were significantly higher in CMV, despite equal IL-8 levels in both PLV and CMV. The inflammatory cytokines IL-1 and IL-6 were greater in CMV, and the anti-inflammatory IL-10 was lower in PLV.

Conclusion: Early institution of partial liquid ventilation is effective at reducing the alveolar inflammatory response. Perflubron exhibits an anti-inflammatory effect in the alveolar environment with reduction of proinflammatory IL-1 and IL-6 (possibly removing a stimulus for IL-10), white blood cell count, and protein capillary leak. PLV also reduces alveolar neutrophils independent of IL-8. Further characterization of this altered inflammatory response is necessary.