Arteriovenous CO2 Removal Improves Survival Compared to High Frequency Percussive and Low Tidal Volume Ventilation in a Smoke/Burn Sheep Acute Respiratory Distress Syndrome Model

Objectives and Summary Background: Low tidal volume ventilation (LTV) has improved survival with acute respiratory distress syndrome (ARDS) by reducing lung stretch associated with volutrauma and barotrauma. Additional strategies to reduce lung stretch include arteriovenous carbon dioxide removal (AVCO 2 R), and high frequency percussive ventilation (HFPV). We performed a prospective, randomized study comparing these techniques in our clinically relevant LD 100 sheep model of ARDS to compare survival, pathology, and inflammation between the 3 ventilator methods. Methods: Adult sheep (n = 61) received smoke inhalation (48 breaths) and a 40% third-degree burn. After ARDS developed (Pao 2 /FiO 2 <200), animals were randomized. In experiment 1, animals were killed at 48 hours after randomization. Hemodynamics, pulmonary function, injury scores, myeloperoxidase (MPO) in lung tissues and neutrophils, IL-8 in lung tissues, and apoptosis were evaluated. In experiment 2, the end point was survival to 72 hours after onset of ARDS or end-of-life criteria with extension of the same studies performed in experiment 1. Results: There were no differences in hemodynamics, but minute ventilation was lower in the AVCO 2 R group and Paco 2 for the HFPV and AVCO 2 R animals remained lower than LTV. Airway obstruction and injury scores were not different among the 3 ventilation strategies. In experiment 1, lung tissue MPO and IL-8 were not different among the ventilation strategies. However, in experiment 2, lung tissue MPO was significantly lower for AVCO 2 R-treated animals (AVCO 2 R < HFPV < LTV). TUNEL staining showed little DNA breakage in neutrophils from experiment 1, but significantly increased breakage in all 3 ventilator strategies in experiment 2. In contrast, AVCO 2 R tissue neutrophils showed significant apoptosis at 72 hours post-ARDS criteria as measured by nuclear condensation (P < 0.001). Survival 72 hours post-ARDS criteria was highest for AVCO 2 R (71%) compared with HFPV (55%) and LTV (33%) (AVCO 2 R vs. LTV, P = 0.05). Conclusions: Significantly more animals survived AVCO 2 R than LTV. In experiment 2, Lung MPO was significantly lower for AVCO 2 R, compared with LTV (P < 0.05). This finding taken together with the TUNEL and neutrophil apoptosis results, suggested that disposition of neutrophils 72 hours post-ARDS criteria was different among the ventilatory strategies with neutrophils from AVCO 2 R-treated animals removed chiefly through apoptosis, but in the cases of HFPV and LTV, dying by necrosis in lung tissue.