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We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO 2 R) to facilitate ultra-protective ventilation (V T 4 mL/kg and P PLAT ≤ 25 cmH 2 O) in patients with moderate acute respiratory distress syndrome (ARDS). Methods: Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO 2 not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO 2 R-related adverse events (ECCO 2 R-AE) were reported to an independent data and safety monitoring board. We used lower CO 2 extraction and higher CO 2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m 2 ; flow 300-500 mL/min vs. 800-1000 mL/min, respectively). Results: Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68-89%) and 82% (78 out of 95 patients; 95% confidence interval 76-88%), respectively. ECCO 2 R was maintained for 5 [3-8] days. Six SAEs were reported; two of them were attributed to ECCO 2 R (brain hemorrhage and pneumothorax). ECCO 2 R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge.

Shape of the Paw-t curve detects tidal recruitment and tidal hyperinflation.

These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

BackgroundMechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R).MethodsIn fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected.ResultsDuring the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking).ConclusionsThe low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

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Mechanical stretch can induce an epithelial-mesenchymal transition phenotype mediated by the MK-Notch2-angiotensin-converting enzyme signaling pathway, contributing to lung remodeling. The MK pathway is a potential therapeutic target in the context of ARDS-associated lung fibrosis.

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 +/- 2 cm H2O) and higher (16 +/- 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 +/- 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 +/- 36 to 396 +/- 138), and reduction in static lung elastance (from 23 +/- 3 to 20 +/- 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 +/- 5 to 28 +/- 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume-pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.