Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study

Abstract

Objectives: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. “Flow-controlled ventilation”, providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. Design: Preclinical, randomized controlled animal study. Setting: Animal research facility. Subjects: Nineteen German landrace hybrid pigs. Intervention: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. Measurements and Main Results: Pao 2 and Paco 2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated Pao 2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable Paco 2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 µm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039). Conclusions: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.

Individualized flow-controlled ventilation compared to best clinical practice pressure-controlled ventilation: a prospective randomized porcine study.

“…In addition, improved lung aeration with less atelectasis was observed in FCV animals, even though a lower PEEP level was established than with PCV. These ndings agree with those of previous studies, where a recruiting effect due to a linearized expiratory airway pressure decline was supposed for FCV [12,13]. In fact, controlling expiratory ow mimics physiological effects provided by the glottis (acting as a dynamic resistor to the egress of gas) and the diaphragm (slowing down expiratory ow by controlled muscle relaxation).…”

“…We showed that compliance-guided pressure adjustment with FCV did not cause more regional overin ation of lung tissue when compared to evidence-based, low tidal volume PCV even though higher V T s were applied with FCV. Several studies report a signi cant improvement in ventilation e ciency and aeration of lung tissue when FCV is applied [12,13,14,15,16]; however, these studies did not use an individualized ventilation approach. Our study shows that normocapnia was maintained in individualized FCV despite a remarkable reduction of respiratory minute volume by 50% compared to PCV.…”

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

“…Yet, the parenchyma also absorbs some of the potential energy stored at end-inspiration, experiencing additional strains during the early part of de ation as the lung refolds and rearranges into its (proto-inspiratory) position. Experimental and clinical evidence provided by several groups suggests that slowing early expiration and regulating expiratory ow may reduce lung injury [34,35]. While the exact mechanism underlying these intriguing and consistent observations remains obscure, the tacit inference has been that the explanation would center on the magnitude and distribution of the released parenchymal energy.…”

Estimating the Damaging Power of High-Stress Ventilation

“…Although neglected in practice, this deflation energy also may contribute to injury, but to an as yet undetermined degree. 25,26 Nonetheless, Total > P t Area ABCF 2P D + P t -P S 18.45 13.2 2(P D -P t ) -P S + PEEP Area ABF + (PEEP -P t area) 17.0 Dynamic > P t Area ABC P S + P t 9.45 7.2 P S -2P t + PEEP Area AB + (PEEP -P t area) 7.0 Driving > P t Area AB P S + P t -2PEEP 5.0 4.2 P S -PEEP Area AB 5.0 Increment > P t Area AF 2P D -P t -P S 13.05 7.8 2(P D -P t ) -P S + PEEP Area ABCDEFG -(P t area) 17.0 Total Area ABCDEFG 2P D -P S + PEEP 20.0 20.0 2P D -P S + PEEP Area ABCDEFG 20.0…”