Venovenous Extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe ARDS: A systematic review and meta-analysis of the literature

BackgroundA strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS.MethodsMEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 hours of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 hours of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data.ResultsTen studies reporting 421 patients (PaO2:FiO2 141.03mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p<0.001) and a 1.89 ml/kg (95%-CI: 1.75-2.02, p<0.001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy.ConclusionsVenovenous ECCO2R permitted significant reductions in ΔP in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting.Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.Key MessagesWhat is the Key Question?In adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS), can venovenous extracorporeal carbon dioxide removal (ECCO2R) support ultraprotective lung ventilation beyond the current standard for protective ventilation in ARDS?What is the bottom line?Systematic review of available data on venovenous ECCO2R shows that it can reduce driving pressure in ventilated patients with moderate-to-severe ARDS, supporting ultraprotective ventilation. Prospective measurement of mechanical power, and greater emphasis on safety and patient-centred outcomes is needed.Why read on?This is the first systematic review to exclusively address venovenous ECCO2R use in the moderate-to-severe ARDS cohort. We report the degree of lung protection achieved with venovenous ECCO2R devices, along with factors potentially limiting widespread adoption.

The use of extracorporeal CO2 removal in acute respiratory failure

Background Chronic obstructive pulmonary disease (COPD) exacerbation and protective mechanical ventilation of acute respiratory distress syndrome (ARDS) patients induce hypercapnic respiratory acidosis. Main text Extracorporeal carbon dioxide removal (ECCO2R) aims to eliminate blood CO2 to fight against the adverse effects of hypercapnia and related acidosis. Hypercapnia has deleterious extrapulmonary consequences, particularly for the brain. In addition, in the lung, hypercapnia leads to: lower pH, pulmonary vasoconstriction, increases in right ventricular afterload, acute cor pulmonale. Moreover, hypercapnic acidosis may further damage the lungs by increasing both nitric oxide production and inflammation and altering alveolar epithelial cells. During an exacerbation of COPD, relieving the native lungs of at least a portion of the CO2 could potentially reduce the patient's respiratory work, Instead of mechanically increasing alveolar ventilation with MV in an already hyperinflated lung to increase CO2 removal, the use of ECCO2R may allow a decrease in respiratory volume and respiratory rate, resulting in improvement of lung mechanic. Thus, the use of ECCO2R may prevent noninvasive ventilation failure and allow intubated patients to be weaned off mechanical ventilation. In ARDS patients, ECCO2R may be used to promote an ultraprotective ventilation in allowing to lower tidal volume, plateau (Pplat) and driving pressures, parameters that have identified as a major risk factors for mortality. However, although ECCO2R appears to be effective in improving gas exchange and possibly in reducing the rate of endotracheal intubation and allowing more protective ventilation, its use may have pulmonary and hemodynamic consequences and may be associated with complications. Conclusion In selected patients, ECCO2R may be a promising adjunctive therapeutic strategy for the management of patients with severe COPD exacerbation and for the establishment of protective or ultraprotective ventilation in patients with ARDS without prognosis-threatening hypoxemia.

Ultraprotective ventilation allowed by extracorporeal CO2 removal improves the right ventricular function in acute respiratory distress syndrome patients: a quasi-experimental pilot study

Background Right ventricular (RV) failure is a common complication in moderate-to-severe acute respiratory distress syndrome (ARDS). RV failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. Veno-venous extracorporeal CO2 removal (ECCO2R) might allow ultraprotective ventilation with lower tidal volume (VT) and plateau pressure (Pplat). This study investigated whether ECCO2R therapy could affect RV function. Methods This was a quasi-experimental prospective observational pilot study performed in a French medical ICU. Patients with moderate-to-severe ARDS with PaO2/FiO2 ratio between 80 and 150 mmHg were enrolled. An ultraprotective ventilation strategy was used with VT at 4 mL/kg of predicted body weight during the 24 h following the start of a low-flow ECCO2R device. RV function was assessed by transthoracic echocardiography (TTE) during the study protocol. Results The efficacy of ECCO2R facilitated an ultraprotective strategy in all 18 patients included. We observed a significant improvement in RV systolic function parameters. Tricuspid annular plane systolic excursion (TAPSE) increased significantly under ultraprotective ventilation compared to baseline (from 22.8 to 25.4 mm; p < 0.05). Systolic excursion velocity (S’ wave) also increased after the 1-day protocol (from 13.8 m/s to 15.1 m/s; p < 0.05). A significant improvement in the aortic velocity time integral (VTIAo) under ultraprotective ventilation settings was observed (p = 0.05). There were no significant differences in the values of systolic pulmonary arterial pressure (sPAP) and RV preload. Conclusion Low-flow ECCO2R facilitates an ultraprotective ventilation strategy thatwould improve RV function in moderate-to-severe ARDS patients. Improvement in RV contractility appears to be mainly due to a decrease in intrathoracic pressure allowed by ultraprotective ventilation, rather than a reduction of PaCO2.

Efficacy and safety of lower versus higher CO2 extraction devices to allow ultraprotective ventilation: secondary analysis of the SUPERNOVA study

Retrospective analysis of the SUPERNOVA trial exploring the hypothesis that efficacy and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate reduction of tidal volume (VT) to 4 mL/kg in patients with acute respiratory distress syndrome (ARDS) may differ between systems with lower (area of membrane length 0.59 m2; blood flow 300–500 mL/min) and higher (membrane area 1.30 m2; blood flow between 800 and 1000 mL/min) CO2 extraction capacity. Ninety-five patients with moderate ARDS were included (33 patients treated with lower and 62 patients treated with higher CO2 extraction devices). We found that (1) VT of 4 mL/kg was reached by 55% and 64% of patients with the lower extraction versus 90% and 92% of patients with higher extraction devices at 8 and 24 hours from baseline, respectively (p<0.001), and (2) percentage of patients experiencing episodes of ECCO2R-related haemolysis and bleeding was higher with lower than with higher extraction devices (21% vs 6%, p=0.045% and 27% vs 6%, p=0.010, respectively). Although V T of 4 mL/kg could have been obtained with all devices, this was achieved frequently and with a lower rate of adverse events by devices with higher CO2 extraction capacity.

Ultraprotective Ventilation during CPB Protects the Alveolar-Capillary Barrier in Pulmonary Normotensive Congenital Heart Patients

Background: Alveolar-capillary membrane damage develops as a result of the inflammatory effect of cardiopulmonary bypass (CPB). In the presence of a healthy alveolar-capillary barrier, there is little or no surfactant in the blood. The aim of this study was to evaluate the protective effects of ultraprotective ventilation during CPB by measuring serum and bronchoalveolar lavage (BAL) surfactant protein B (SPB) values in congenital heart surgery.Methods: This prospective study was designed for 46 patients with congenital heart defects. Patients were classified into two groups: group 1 comprising pulmonary normotensive patients and group 2 consisting of pulmonary hypertensive (PH) patients. Each group was divided into two sub-groups: (a) those who received ultraprotective ventilation during CPB and (b) those who did not receive ultraprotective ventilation during CPB. Serum SPB (S-SPB) values were measured preoperatively (ST1); at the fourth hour postop (ST2); and at the 24th hour postop (ST3). BAL SPB values were measured preoperatively (BT1); and at the fourth hour postop (BT2). Results: ST1, ST2, and ST3 values of group 1a (pulmonary normotensive ventilated patients) and group 1b (pulmonary normotensive non-ventilated patients) were much lower than those of group 2a (pulmonary hypertensive ventilated patients) and group 2b (pulmonary hypertensive non-ventilated patients) (P < .05). The evaluation of ST1, ST2, and ST3 values between groups 1a and 1b did not show statistically significant differences. When comparing ST1 to ST3, a decrease in value was observed in group 1a (32.28 ± 13.27 ng/mL to 19.38 ± 7.6 ng/mL) (P = .006). In Group 1b, values increased between ST1 and ST2 before decreasing from ST2 to ST3; however, the ST3 values were still higher than their ST1 counterparts. It was recorded that there was no statistically significant difference between the ST1, ST2, and ST3 values of group 2a and group 2b. A comparison of the BT1 and BT2 values in groups also yielded no statistically significant differences. Conclusion: Although pulmonary hypertension is known to result in lung injury, this study is important as it shows that ultraprotective ventilation protects the alveolar-capillary barrier in pulmonary normotensive congenital heart patients.

Intraoperative Management of Hypercapnia with an Extracorporeal Carbon Dioxide Removal Device during Giant Bullectomy

Extracorporeal CO2-removal devices have been introduced in clinical practice to provide protective and ultraprotective ventilation strategies in different settings to avoid retention of carbon dioxide. The need to facilitate lung-protective ventilation is required not only for the treatment of acute respiratory distress syndrome but also in thoracic surgery during complex operations, especially in respiratory compromised patients. This report describes a case of giant bullectomy for vanishing lung syndrome in which intraoperative hypercapnia secondary to protective ventilation was managed with a CO2-removal device (Decap-Hemodec s.r.l., Salerno, Italy). To the best of our knowledge, this is the first report in the literature of the intraoperative use of the Decap system for giant bullectomy.