The paracorporeal artificial lung improves 5-day outcomes from lethal smoke/burn-induced acute respiratory distress syndrome in sheep

Abstract

Background Our low-impedence, paracorporeal artificial lung (PAL) prototype is well-tolerated in-series with the normal sheep pulmonary circulation. Using our lethal dose 80% to 100% smoke/burn acute respiratory distress syndrome (ARDS) sheep model, we compared PAL to volume-controlled mechanical ventilation (VCMV) in a prospective, randomized, controlled, unblinded, 5-day outcome study. Methods Fourteen sheep were randomized to PAL (n = 8) versus VCMV (n = 6) to assess outcome. For PAL, arterial cannulas were anastomosed to the proximal and distal main pulmonary artery with an interposing snare diverting full flow through a paracorporeal loop. Acute respiratory distress syndrome was induced in both groups (48 breaths smoke insufflation, third degree burn on 40% of total body surface area). When acute respiratory distress syndrome criteria were met (24 to 30 hours after injury), the PAL was interposed in the paracorporeal loop. Both groups were managed with a VCMV algorithm minimizing tidal volume, ventilator rate, and fractional inspired concentration of oxygen (FiO 2). Results Six of eight PAL versus 1 of 6 VCMV sheep survived the 5-day study. In PAL, cardiac output, mean arterial pressure, pulmonary artery pressure, left atrial pressure, and central venous pressure remained stable. Average PAL gas transfer was 218.6 ± 17.7 mL/min O 2 and 183.0 ± 27.8 mL/min CO 2. Ventilator settings 48 hours after lung injury in PAL were significantly lower ( p < 0.05) than VCMV (TV 210 versus 425 mL; respiratory rate 6 versus 29 breaths/min; minute ventilation 1.2 versus 10.8 L/min; FiO 2 21 versus 100%). Likewise, PaO 2/FiO 2 ratio was normalized in PAL and still met acute respiratory distress syndrome criteria in VCMV. The PAL wet/dry ratio was significantly lower than VCMV (6.36 ± 0.63 versus 11.85 ± 1.54; p = 0.008). Conclusions In a prospective, randomized, controlled, unblinded, outcomes study, PAL decreased ventilator-induced lung injury in a lethal dose 80% to 100% ARDS model to improve 5-day survival.