Evaluation of CO2 removal rate of ECCO2R for a renal replacement therapy platform in an experimental setting.

BACKGROUND: A critical parameter of extracorporeal CO2 removal (ECCO2R) applications is the CO2 removal rate (VCO2). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO2 of a low-flow ECCO2R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model. METHODS: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO2R-CRRT system (surface area = 1.8 m2; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO2 was recorded under different combinations of PaCO2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min). RESULTS: VCO2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO2 at two ECBF. VCO2 increased with PaCO2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO2 levels were similar for different levels of premembrane lung PCO2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO2 only at a high ECBF of 350 mL/min (p < 0.05). CONCLUSIONS: Low-flow venovenous extracorporeal ECCO2R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia.

Outcomes of Extracorporeal Life Support (ECLS) in Acute Severe Asthma: A Narrative Review.

BACKGROUND: In this narrative review we aimed to explore outcomes of extracorporeal life support (extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)) as rescue therapy in patients with status asthmaticus requiring mechanical ventilation. METHODS: Multiple databases were searched for studies fulfilling inclusion criteria. Articles reporting mortality and complications of ECMO and ECCO2R in mechanically ventilated patients with acute severe asthma (ASA) were included. Pooled estimates of mortality and complications were obtained by fitting Poisson's normal modeling. RESULTS: Six retrospective studies fulfilled inclusion criteria thus yielding a pooled mortality rate of 17% (13-20%), pooled risk of bleeding of 22% (7-37%), mechanical complications in 26% (21-31%), infection in 8% (0-21%) and pneumothorax rate 4% (2-6%). CONCLUSION: Our review identified a variation between institutions in the initiation of ECMO and ECCO2R in patients with status asthmaticus and discrepancy in the severity of illness at the time of cannulation. Despite that, mortality in these studies was relatively low with some studies reporting no mortality which could be attributed to selection bias. While ECMO and ECCO2R use in severe asthma patients is associated with complication risks, further studies exploring the use of ECMO and ECCO2R with mechanical ventilation are required to identify patients with favorable risk benefit ratio.

Efficacy and Safety of a Low-Flow Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Failure, a Pilot Study in China.

BACKGROUND: Low-flow extracorporeal carbon dioxide removal (LF-ECCO2R) has the potential to play an important role in the management of adults with acute respiratory failure. However, it has never been tested in China. The study aimed at exploring the safety and efficacy on LF-ECCO2R for acute respiratory failure in a Chinese tertiary intensive care unit (ICU). MATERIALS AND METHODS: We performed a retrospective case note review of patients admitted to our tertiary regional ICU and commenced on LF-ECCO2R from June 2020 to September 2021. The LF-ECCO2R device we used was ProLUNG® system (Estor S.p.A., Milan, Italy). The device employed a nonporous poly-4-methyl-1-pentene membrane lung with a surface area of 1.81 m2 and run at an extracorporeal blood flow between 100 and 450 mL/min. Demographic and physiologic data (including ventilation parameters and arterial blood gases) as well as the outcome of LF-ECCO2R treatment were recorded. RESULTS: A total of 12 cases were included. A statistically significant reduction in respiratory rate, driving pressure, PaCO2, and blood lactate was observed. In addition, there was a statistically significant improvement in pH and PaO2/FiO2. Six out of 12 patients (50%) were discharged alive from ICU. Three complications related to LF-ECCO2R were reported, none resulting in serious adverse outcomes. CONCLUSION: Our clinical series indicated that LF-ECCO2R seemed to be safely applied in patients with acute respiratory failure. The efficacy of CO2 removal as well as the improved respiratory parameters was also observed. However, large-scale randomized clinical trials are needed to confirm the effects.

Extracorporeal Carbon Dioxide Removal in Patients with Acute Respiratory Distress Syndrome or Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) was used to prevent invasive mechanical ventilation and associated mechanical damage in patients with acute respiratory distress syndrome (ARDS). OBJECTIVES: This study aimed to investigate the efficacy and safety of ECCO2R treatment in patients with ARDS or chronic obstructive pulmonary disease (COPD). METHODS: MEDLINE, EMBASE, and the Cochrane Library were systematically searched for relevant studies that reported patient prognosis, blood gas parameters, and ECCO2R-related adverse events (AEs) published as of September 2020. Odds ratios (ORs), weighted mean differences (WMDs), and their corresponding 95% confidence intervals (CIs) were used to compare the outcomes. RESULTS: Fifteen studies involving 532 ARDS or COPD patients were included. Compared with controls, ECCO2R did not influence the 28-day mortality (OR = 0.73, 95% CI: 0.28-1.87, p = 0.51), the length of hospital stay (WMD = 3.34, 95% CI: -5.22 to 11.90, p = 0.444), and the length of intensive care unit stay (WMD = -0.39, 95% CI: -8.76 to 7.99, p = 0.928). Compared with baseline values, partial pressure of carbon dioxide (PaCO2) in the ECCO2R group was significantly reduced, while the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and pH increased. The overall rate of ECCO2R-related AEs was 35% (95% CI: 17-53%, p < 0.001), and bleeding was the most common AE with a rate of 22% (95% CI: 13-31%, p = 0.002). The rate of ECCO2R-related deaths was low. CONCLUSIONS: In conclusion, there was no statistically significant difference in the prognosis of patients with and without ECCO2R treatment. ECCO2R significantly reduced PaCO2 and improved PaO2/FiO2 and pH values in patients with ARDS or COPD. Bleeding was the most common ECCO2R-related AE.

Risks and Benefits of Ultra-Lung-Protective Invasive Mechanical Ventilation Strategies with a Focus on Extracorporeal Support.

Lung-protective ventilation strategies are the current standard of care for patients with acute respiratory distress syndrome in an effort to provide adequate ventilatory requirements while minimizing ventilator-induced lung injury. Some patients may benefit from ultra-lung-protective ventilation, a strategy that achieves lower airway pressures and Vt than the current standard. Specific physiological parameters beyond severity of hypoxemia, such as driving pressure and respiratory system elastance, may be predictive of those most likely to benefit. Because application of ultra-lung-protective ventilation is often limited by respiratory acidosis, extracorporeal membrane oxygenation or extracorporeal carbon dioxide removal, which remove carbon dioxide from blood, is an attractive option. These strategies are associated with hematological complications, especially when applied at low blood-flow rates with devices designed for higher blood flows, and a recent large randomized controlled trial failed to show a benefit from an extracorporeal carbon dioxide removal-facilitated ultra-lung-protective ventilation strategy. Only in patients with very severe forms of acute respiratory distress syndrome has the use of an ultra-lung-protective ventilation strategy-accomplished with extracorporeal membrane oxygenation-been suggested to have a favorable risk-to-benefit profile. In this critical care perspective, we address key areas of controversy related to ultra-lung-protective ventilation, including the trade-offs between minimizing ventilator-induced lung injury and the risks from strategies to achieve this added protection. In addition, we suggest which patients might benefit most from an ultra-lung-protective strategy and propose areas of future research.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: A 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. METHODS: MEDLINE 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 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. RESULTS: Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) 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 < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .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. CONCLUSIONS: Venovenous ECCO2R permitted significant reductions in ∆P 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.

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Extracorporeal carbon dioxide removal is an artificial lung auxiliary technique based on extrapulmonary gas exchange and can effectively remove carbon dioxide and provide oxygenation to a certain extent, and it is one of the effective treatment techniques for hypercapnia developed after mechanical ventilation and extracorporeal membrane oxygenation in recent years and has wide application prospect. This article elaborates on the development, working principle, advantages, classification, complications, and clinical application of extracorporeal carbon dioxide removal, so as to provide a new choice for extracorporeal carbon dioxide removal in clinical practice.

Effect of extracorporeal carbon dioxide removal on respiratory quotient measured by indirect calorimetry: Unravelling the mystery.

NEW FINDINGS: What is the main observation in this case? Several studies have reported progressive hypoxaemia once extracorporeal carbon dioxide removal is started in patients with hypercapnic respiratory failure, possibly attributable to an altered respiratory quotient. What insights does it reveal? In this quality control report, we show that the respiratory quotient exhibits only minimal alteration when extracorporeal carbon dioxide removal is started and assume that the progressive hypoxaemia is attributable to an increase in intrapulmonary shunt. ABSTRACT: The use of extracorporeal carbon dioxide removal (ECCO2 R) has been proposed in patients with acute respiratory distress syndrome to achieve lung-protective ventilation and in patients with selective hypercapnic respiratory failure. However, several studies have reported progressive hypoxaemia, as expressed by a need to increase the inspired oxygen fraction (Fi O2 ) to maintain adequate oxygenation or by a decrease in the ratio of arterial oxygen tension (Pa O2 ) to Fi O2 once ECCO2 R is started. We present the case of a patient who was admitted to the intensive care unit for a coronavirus disease 2019 pneumonia and who was intubated because of hypercapnic respiratory insufficiency. Extracorporeal carbon dioxide removal was started, and the patient subsequently developed progressive hypoxaemia. To test whether the hypoxaemia was attributable to the ECCO2 R, blood samples were taken in different settings: (1) 'no ECCO2 R', blood flow 150 ml/min with a ECCO2 R gas flow of 0 L/min; and (2) 'with ECCO2 R', blood flow 400 ml/min with gas flow 12 L/min. We measured Pa O2 , alveolar oxygen tension, Pa O2 /Fi O2 , alveolar-arterial oxygen tension difference, arterial carbon dioxide tension and the respiratory quotient (RQ) by indirect calorimetry in each setting. The RQ was 0.60 without ECCO2 R and 0.57 with ECCO2 R. The alveolar oxygen tension was 220.4 mmHg without ECCO2 R and increased to 240.3 mmHg with ECCO2 R, whereas Pa O2 /Fi O2 decreased from 177 to 171. Our study showed only a minimal change in RQ when ECCO2 R was started. We were the first to measure the RQ directly, before and after the initiation of ECCO2 R, in a patient with hypercapnic respiratory failure.

Annual hospital procedural volume and outcome in extracorporeal membrane oxygenation for respiratory failure.

BACKGROUND: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume. METHODS: Data on all V-V ECMO and ECCO2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality. RESULTS: A total of 25 096 V-V ECMO and 3607 ECCO2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914). CONCLUSION: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO2 R volume and hospital mortality.

Utilization and outcomes of extracorporeal CO2 removal (ECCO2 R): Systematic review and meta-analysis of arterio-venous and veno-venous ECCO2 R approaches.

INTRODUCTION: Extracorporeal carbon dioxide removal (ECCO2 R) provides respiratory support to patients suffering from hypercapnic respiratory failure by utilizing an extracorporeal shunt and gas exchange membrane to remove CO2 from either the venous (VV-ECCO2 R) or arterial (AV-ECCO2 R) system before return into the venous site. AV-ECCO2 R relies on the patient's native cardiac function to generate pressures needed to deliver blood through the extracorporeal circuit. VV-ECCO2 R utilizes a mechanical pump and can be used to treat patients with inadequate native cardiac function. We sought to evaluate the existing evidence comparing the subgroups of patients supported on VV and AV-ECCO2 R devices. METHODS: A literature search was performed to identify all relevant studies published between 2000 and 2019. Demographic information, medical indications, perioperative variables, and clinical outcomes were extracted for systematic review and meta-analysis. RESULTS: Twenty-five studies including 826 patients were reviewed. 60% of patients (497/826) were supported on VV-ECCO2 R. The most frequent indications were acute respiratory distress syndrome (ARDS) [69%, (95%CI: 53%-82%)] and chronic obstructive pulmonary disease (COPD) [49%, (95%CI: 37%-60%)]. ICU length of stay was significantly shorter in patients supported on VV-ECCO2 R compared to AV-ECCO2 R [15 (95%CI: 7-23) vs. 42 (95%CI: 17-67) days, p = 0.05]. In-hospital mortality was not significantly different [27% (95%CI: 18%-38%) vs. 36% (95%CI: 24%-51%), p = 0.26]. CONCLUSION: Both VV and AV-ECCO2 R provided clinically meaningful CO2 removal with comparable mortality.

Combined Renal-Pulmonary Extracorporeal Support with Low Blood Flow Techniques: A Retrospective Observational Study (CICERO Study).

BACKGROUND: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (<400 mL/min). OBJECTIVES: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit. METHODS: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded. RESULTS: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded. CONCLUSION: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI.

Very low blood flow carbon dioxide removal system is not effective in a chronic obstructive pulmonary disease exacerbation setting.

Extracorporeal carbon dioxide removal (ECCO2 R) is a low blood flow veno-venous extracorporeal membrane oxygenation technique that provides artificial blood CO2 removal. Recently, a new ECCO2 R system (PrismaLung), providing very low blood flow has been commercialized. The aim of this study is to report its use in severe chronic obstructive pulmonary disease (COPD) patients needing an ECCO2 R therapy. Six severe COPD patients with acute exacerbation leading to refractory hypercapnic respiratory acidosis were treated with ECCO2 R therapy. Two different systems were used: a PrismaLung system and a conventional ECCO2 R device. The maximum blood flow provided by PrismaLung was significantly lower than that with the conventional ECCO2 R system. In three patients initially treated with PrismaLung, there were no improvements in pH, PaCO2 , or RR. Thus, the therapy was switched to a conventional ECCO2 R system in these three patients, and three others were treated from the outset by the conventional ECCO2 R system, providing significant improvement in pH, PaCO2 , and RR. The present retrospective study describes the first use of PrismaLung in severe COPD patients with acute exacerbation. When compared with a higher blood flow ECCO2 R system, our results show that this novel, very low-flow device is not able to remove sufficient CO2 , normalize pH or decrease respiratory rate.

Mechanical Ventilation for Acute Respiratory Distress Syndrome during Extracorporeal Life Support. Research and Practice.

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post hoc analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

Extracorporeal carbon dioxide removal (ECCO2R) in COPD and ARDS patients with severe hypercapnic respiratory failure. A retrospective case-control study

Background/aim: Treatment of severe hypercapnic respiratory failure (HRF) has some challenges in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS), especially when lung protective ventilation (LPV) strategies are required. Extracorporeal CO2 removal (ECCO2R) therapy is an emerging option to manage hypercapnia while allowing LPV in these cases. However, further data on ECCO2R use is still needed to make clear recommendations. Materials and methods: This study was conducted on patients admitted to intensive care unit (ICU) between January 1st, 2016 to December 31st, 2019. The medical records were retrospectively scanned in institutional software database. Patients who received invasive mechanic ventilation (iMV) support due to severe HRF related to COPD or ARDS were included in the analyses. Patients were grouped according to treatment approaches as that ECCO2R therapy in addition to conventional treatments and conventional treatments alone (controls). Groups were compared for 28-day survival, iMV duration, and length of stay (LOS). Results: ECCO2R therapy was noted in 75 of the cases among included 395 patients (COPD n = 256, ARDS n = 139) out of scanned 1715 medical records. The survival rate of ECCO2R patients was 68% and significantly higher than 58% survival rate of controls (p = 0.025), with relative risk reduction (RRR) = 0.16, absolute risk reduction (ARR)= 0.10, number need to treat (NNT) = 10, and odds ratio (OR) = 1.5. In addition, iMV duration (12.8 ± 2.6 vs. 17.1 ± 4.9 days, p = 0.007) and LOS (16.9 ± 4.1 vs. 18.9 ± 5.5 days, p = 0.032) were significantly shorter than controls. Repeated measure analyses showed that LPV settings were successfully provided by 72 h of ECCO2R therapy. Subgroup analyses according to diagnoses of COPD and ARDS also favored ECCO2R. Conclusion: ECCO2R therapy significantly improved survival, iMV duration and LOS in patients with severe HRF due to COPD or ARDS, and successfully provided LPV approaches. Further studies are needed to assess promising benefits of ECCO2R therapy.

Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA).

BACKGROUND: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. METHODS: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. RESULTS: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of PaCO2, and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus - 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67-0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70-0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53-0.79, p < 0.05) for SOFA score. CONCLUSIONS: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal.

Update on extracorporeal carbon dioxide removal: a comprehensive review on principles, indications, efficiency, and complications.

TECHNOLOGY: Extracorporeal carbon dioxide removal means the removal of carbon dioxide from the blood across a gas exchange membrane without substantially improving oxygenation. Carbon dioxide removal is possible with substantially less extracorporeal blood flow than needed for oxygenation. Techniques for extracorporeal carbon dioxide removal include (1) pumpless arterio-venous circuits, (2) low-flow venovenous circuits based on the technology of continuous renal replacement therapy, and (3) venovenous circuits based on extracorporeal membrane oxygenation technology. INDICATIONS: Extracorporeal carbon dioxide removal has been shown to enable more protective ventilation in acute respiratory distress syndrome patients, even beyond the so-called "protective" level. Although experimental data suggest a benefit on ventilator induced lung injury, no hard clinical evidence with respect to improved outcome exists. In addition, extracorporeal carbon dioxide removal is a tool to avoid intubation and mechanical ventilation in patients with acute exacerbated chronic obstructive pulmonary disease failing non-invasive ventilation. This concept has been shown to be effective in 56-90% of patients. Extracorporeal carbon dioxide removal has also been used in ventilated patients with hypercapnic respiratory failure to correct acidosis, unload respiratory muscle burden, and facilitate weaning. In patients suffering from terminal fibrosis awaiting lung transplantation, extracorporeal carbon dioxide removal is able to correct acidosis and enable spontaneous breathing during bridging. Keeping these patients awake, ambulatory, and breathing spontaneously is associated with favorable outcome. COMPLICATIONS: Complications of extracorporeal carbon dioxide removal are mostly associated with vascular access and deranged hemostasis leading to bleeding. Although the spectrum of complications may differ, no technology offers advantages with respect to rate and severity of complications. So called "high-extraction systems" working with higher blood flows and larger membranes may be more effective with respect to clinical goals.

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.

Control of respiratory drive by extracorporeal CO2 removal in acute exacerbation of COPD breathing on non-invasive NAVA.

BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. METHODS: A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. RESULTS: Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO2R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO2R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO2R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 µV vs. 56 ± 20 µV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO2 and pH values stable. Edi was the best predictor for vv-ECCO2R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. CONCLUSIONS: This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO2R and NIV-NAVA. The Edi during vv-ECCO2R weaning was found to be the best predictor of tolerance to removing vv-ECCO2R.

Carbon dioxide removal using low bicarbonate dialysis in rodents.

BACKGROUND: Extracorporeal carbon dioxide removal may be used to manage hypercapnia, but compared to dialysis, it's not widely available. A recent in vitro study showed that dialysis with low bicarbonate dialysates removes CO2. OBJECTIVE: To show that bicarbonate dialysis removes CO2 in an animal model to validate in-vitro findings and quantify the effect on arterial pH. METHODS: Male Sprague-Dawley hypercapnic rats were dialyzed with either a conventional dialysate (PrismasolTM) or a bicarbonate-free dialysate (Bicarb0). The effect of dialysis on standard blood gases and electrolytes was measured. RESULTS: Partial pressure of CO2 and bicarbonate concentration in blood decreased significantly after exposure to Bicarb0 compared to PrismasolTM (filter outflow values 12.8 vs 81.1 mmHg; p < 0.01 for CO2 and 3.5 vs 22.0 mmol/L; p < 0.01 for bicarbonate). Total CO2 content of blood was reduced by 459 mL/L during dialysis with Bicarb0 (filter inflow 546 ± 91 vs filter outflow 87 ± 52 mL/L; p < 0.01), but was not significantly reduced with PrismasolTM. CONCLUSIONS: Bicarbonate dialysis removes CO2 at rates comparable to existing low-flow ECCO2R.

Feasibility and safety of low-flow extracorporeal CO2 removal managed with a renal replacement platform to enhance lung-protective ventilation of patients with mild-to-moderate ARDS.

BACKGROUND: Extracorporeal carbon-dioxide removal (ECCO2R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) (< 6 ml/kg predicted body weight), plateau pressure (Pplat) (< 30 cmH2O), and driving pressure to limit ventilator-induced lung injury. This study was undertaken to assess the feasibility and safety of ECCO2R managed with a renal replacement therapy (RRT) platform to enable very low tidal volume ventilation of patients with mild-to-moderate acute respiratory distress syndrome (ARDS). METHODS: Twenty patients with mild (n = 8) or moderate (n = 12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP adjusted to reach 23 ≤ Pplat ≤ 25 cmH2O. Standalone ECCO2R (no hemofilter associated with the RRT platform) was initiated when arterial PaCO2 increased by > 20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, Pplat and driving pressure, arterial blood gases, and ECCO2R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO2R and mechanical ventilation were also recorded. RESULTS: While VT was reduced from 6 to 4 ml/kg and Pplat kept < 25 cmH2O, PEEP was significantly increased from 13.4 ± 3.6 cmH2O at baseline to 15.0 ± 3.4 cmH2O, and the driving pressure was significantly reduced from 13.0 ± 4.8 to 7.9 ± 3.2 cmH2O (both p < 0.05). The PaO2/FiO2 ratio and respiratory-system compliance were not modified after VT reduction. Mild respiratory acidosis occurred, with mean PaCO2 increasing from 43 ± 8 to 53 ± 9 mmHg and mean pH decreasing from 7.39 ± 0.1 to 7.32 ± 0.10 from baseline to 4 ml/kg VT, while the respiratory rate was not altered. Mean extracorporeal blood flow, sweep-gas flow, and CO2 removal were 421 ± 40 ml/min, 10 ± 0.3 L/min, and 51 ± 26 ml/min, respectively. Mean treatment duration was 31 ± 22 h. Day-28 mortality was 15%. CONCLUSIONS: A low-flow ECCO2R device managed with an RRT platform easily and safely enabled very low tidal volume ventilation with moderate increase in PaCO2 in patients with mild-to-moderate ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02606240. Registered on 17 November 2015.