Minimally invasive extracorporeal CO2 removal in hypercapnic respiratory failure: a prospective observational study.

Extracorporeal Carbon Dioxide Removal (ECCO2R): A Potential Perioperative Tool in End-Stage Lung Disease

Lung-protective ventilation (LPV) with low tidal volumes can significantly increase the survival of patients with acute respiratory distress syndrome (ARDS) by limiting ventilator-induced lung injuries. However, one of the main concerns regarding the use of LPV is the risk of developing hypercapnia and respiratory acidosis, which may limit the clinical application of this strategy. This is the reason why different extracorporeal CO2 removal (ECCO2R) techniques and devices have been developed. They include low-flow or high-flow systems that may be performed with dedicated platforms or, alternatively, combined with continuous renal replacement therapy (CRRT). ECCO2R has demonstrated effectiveness in controlling PaCO2 levels, thus allowing LPV in patients with ARDS from different causes, including those affected by Coronavirus disease 2019 (COVID-19). Similarly, the suitability and safety of combined ECCO2R and CRRT (ECCO2R-CRRT), which provides CO2 removal and kidney support simultaneously, have been reported in both retrospective and prospective studies. However, due to the complexity of ARDS patients and the limitations of current evidence, the actual impact of ECCO2R on patient outcome still remains to be defined. In this review, we discuss the main principles of ECCO2R and its clinical application in ARDS patients, in particular looking at clinical experiences of combined ECCO2R-CRRT treatments.

To assess the safety and efficacy of combining extracorporeal CO2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. Prospective human observational study. Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution. Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. A membrane oxygenator (0.65 m) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal CO2 removal. The primary endpoint was 20% reduction in PaCO2 at 20 minutes after extracorporeal CO2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and PaO2/FIO2 was 135 ± 41. Adding extracorporeal CO2 removal at tidal volume 6 mL/kg decreased PaCO2 by 21% (95% CI, 17-25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised PaCO2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator's blood flow was 410 ± 30 mL/min and the CO2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0.001) and the CO2 removal rate (p = 0.083) were higher when the membrane oxygenator was placed upstream of the hemofilter. There was no safety concern. Combining extracorporeal CO2 removal and continuous venovenous hemofiltration in patients with acute respiratory distress syndrome and acute kidney injury is safe and allows efficient blood purification together with enhanced lung protective ventilation.

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.

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.

Counterpoint: Is Pressure Assist-Control Preferred Over Volume Assist-Control Mode for Lung Protective Ventilation in Patients With ARDS? No

RATIONALE: Acute Respiratory Distress Syndrome (ARDS) carries high morbidity and mortality, often compounded by acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT). While lung-protective ventilation is a priority, limited data link these settings to renal outcomes in ARDS, and few studies consider biological factors like age, sex, race, and ethnicity. This study examines how ventilator parameters influence CRRT needs and ARDS outcomes across these biological variables. METHODS: Using a multi-center ARDS cohort dataset, we analyzed associations between baseline ventilator settings—positive end-expiratory pressure (PEEP), tidal volume (TV), plateau pressure (PPLAT), and driving pressure—and CRRT requirements, as well as ARDS outcomes (ICU-free days, ventilator-free days, and time to death). Logistic and linear regression models, adjusted for age, sex, race, and ethnicity, evaluated the relationships between ventilator parameters, CRRT requirements, and ARDS outcomes. Kaplan-Meier analysis assessed CRRT's impact on mortality, and model coefficients were visualized in a heatmap to illustrate the effects of ventilation parameters on outcomes. RESULTS: Kaplan-Meier analysis showed significantly reduced survival for CRRT users (p&amp;lt;1e-4). Overall, higher baseline PEEP, PPLAT, and driving pressure were associated with an increased likelihood of requiring CRRT, although this trend was reversed among Hispanic patients. CRRT use was linked to fewer ICU- and ventilator-free days, though this association was not significant for Black, Hispanic, and female patients. Outcome prediction models highlighted further divergent trends across biological variables, particularly for PPLAT settings among females. CONCLUSION: Baseline ventilator settings and CRRT status are significant determinants of clinical outcomes in ARDS patients. High baseline PEEP, PPLAT, and driving pressure correlate with increased CRRT needs and reduced ICU- and ventilator-free days, although these associations vary by age, sex, race, and ethnicity. These findings emphasize the need to integrate these variables into future research and individualized management plans. Tailored respiratory strategies could optimize ARDS outcomes across diverse populations.

Extracorporeal CO2 removal (ECCO2R) is intended to facilitate lung protective ventilation in patients with hypercarbia. The combination of continuous renal replacement therapy (CRRT) and minimal-flow ECCO2R offers a promising concept for patients in need of both. We hypothecated that this system is able to remove enough CO2 to facilitate lung protective ventilation in mechanically ventilated patients. In 11 ventilated patients with acute renal failure who received either pre- or postdilution CRRT, minimal-flow ECCO2R was added to the circuit. During 6 h of combined therapy, CO2 removal and its effect on facilitation of lung-protective mechanical ventilation were assessed. Ventilatory settings were kept in assisted or pressure-controlled mode allowing spontaneous breathing. With minimal-flow ECCO2R significant decreases in minute ventilation, tidal volume and paCO2 were found after one and three but not after 6 h of therapy. Nevertheless, no significant reduction in applied force was found at any time during combined therapy. CO2 removal was 20.73ml CO2/min and comparable between pre- and postdilution CRRT. Minimal-flow ECCO2R in combination with CRRT is sufficient to reduce surrogates for lung-protective mechanical ventilation but was not sufficient to significantly reduce force applied to the lung. Causative might be the absolute amount of CO2 removal of only about 10% of resting CO2 production in an adult as we found. The benefit of applying minimal flow ECCO2R in an uncontrolled setting of mechanical ventilation might be limited.

BackgroundLung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS.MethodsWe conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2019. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 h identified ARDS as the value of 1st, and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and parameters related to respiratory dynamics, clinical outcomes as well as daily fluid balance during the first four days after ARDS diagnosed.ResultsThe 1st LUS score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the LUS score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with Cdyn (dynamic lung compliance) (1st: r = − 0.757, 2nd: r = − 0.906, 3rd: r = − 0.885, 4th: r = − 0.834), OI (oxygenation index) (1st: r = 0.678, 2nd: r = 0.689, 3rd: r = 0.486, 4th: r = 0.324) based on 1st to 4th values (all P < 0.05). Only values of the 3rd and 4th LUS score after ARDS diagnosed were correlated with duration of mechanical ventilation [1st: r = 0.167, P = 0.325; 2nd: r = 0.299, P = 0.072; 3rd: r = 0.579, P < 0.001; 4th: r = 0.483, P = 0.002]. LUS score decreased from 22 (18–25) to 15 (13–18) and OI decreased from 15.92 (14.07–17.73) to 9.49 (8.70–10.58) after CRRT for four days (both P < 0.001).ConclusionsLUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score.Trial registration CCTR, ChiCTR-ONC-16009698. Registered 1 November 2016, prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=16535&htm=4. This study adheres to CONSORT guidelines.

Hypercapnic respiratory failure is afrequent problem in critical care and mainly affects patients with acute exacerbation of COPD (AECOPD) and acute respiratory distress syndrome (ARDS). In recent years, the usage of extracorporeal CO2 removal (ECCO2R) has been increasing. Summarizing the state of the art in the management of hypercapnic respiratory failure with special regard to the role of ECCO2R. Review based on aselective literature search and the clinical and scientific experience of the authors. Noninvasive ventilation (NIV) is the therapy of choice in hypercapnic respiratory failure due to AECOPD, enabling stabilization in the majority of cases and generally improving prognosis. Patients in whom NIV fails have an increased mortality. In these patients, ECCO2R may be sufficient to avoid intubation or to shorten time on invasive ventilation; however, corresponding evidence is sparse or even missing when it comes to hard endpoints. Lung-protective ventilation according to the ARDS network is the standard therapy of ARDS. In severe ARDS, low tidal volume ventilation may result in critical hypercapnia. ECCO2R facilitates compensation of respiratory acidosis even under "ultra-protective" ventilator settings. Yet, no positive prognostic effects could be demonstrated so far. Optimized use of NIV and lung-protective ventilation remains standard of care in the management of hypercapnic respiratory failure. Currently, ECCO2R has to be considered an experimental approach, which should only be provided by experienced centers or in the context of clinical trials.

Renal Support for Acute Kidney Injury in the Developing World

Objective To explore the effects of continuous renal replacement therapy (CRRT) on the changes of the respiration and blood circulation as well as peripheral blood cytokines levels in patients with severe acute pancreatitis(SAP) complicated with acute respiratory distress syndrome. Methods 48 SAP patients complicated with acute respiratory distress syndrome were divided into control group and CRRT treatment group according to the parallel control design principle.The control group was treated with routine way, and the CRRT treatment group was treated with CRRT on the basis of routine way.The clinical data and the levels of IL-6, IL-1β, TNF-α were compared between the two groups. Results The levels of IL-6, TNF-α were significantly lower in the CRRT treatment group than those in the control group in 12h[(147.72±22.06)ng/L vs.( 132.27±18.03)ng/L, t=2.315, P 0.05; (34.62±7.36)cmH2O vs.(35.18±4.04)cmH2O, t=0.416, P>0.05; (152.61±31.53)ng/L vs (150.74±30.26)ng/L, t=0.668, P>0.05; (40.06±5.15)ng/L vs.(38.09±10.13 )ng/L, t=0.819, P>0.05; (226.85±37.62)ng/L vs.(225.47±39.02)ng/L, t=0.702, P>0.05]. Conclusion CRRT can effectively reduce the plasma levels of IL-6, IL-1β, TNF-α in SAP patients complicated with acute respiratory distress syndrome, it has therapeutic effect on the respiration through changing the cytokines of SAP patients complicated with acute respiratory distress syndrome. Key words: Pancreatitis; Interleukin-6; interleukin-1β; Tumor necrosis factor-α; Renal replacement therapy; Respiratory distress syndrome, adule

Metabolic aspects of continuous renal replacement therapies

Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.

Introduction: Hypercapnic respiratory failure is associated with high morbidity and mortality. Low-flow extracorporeal CO2 removal (ECCO2R) has been shown to facilitate lung-protective ventilation or spontaneous breathing. However, three multicenter randomized trials have failed to show benefit which could potentially be a result of patient selection. In this study, we aimed to characterize prognostic scores developed for extracorporeal membrane oxygenation therapy which could potentially assist with the selection of patients for ECCO2R. Methods: A total of 70 patients admitted to the intensive care unit at the University Hospital of Zurich between 10/2009 and 02/2017 with hypercapnic respiratory failure were treated with ECCO2R if pH ≤7.25 and/or PaCO2 ≥ 9 kPa experiencing respiratory exhaustion during spontaneous breathing in obstructive lung disease or reaching the limits of lung protective ventilation (n = 22 and n = 48) in patients with restrictive lung pathologies. Data including baseline characteristics and respiratory parameters were collected prospectively. Scores were calculated retrospectively. Results: The underlying diseases were acute respiratory distress syndrome (n = 27), chronic-obstructive pulmonary disease (n = 12), bronchiolitis obliterans syndrome (BOS; n = 9), cystic fibrosis (n = 10), pulmonary fibrosis (n = 8), and other causes (n = 4). The 180-day mortality was 45.7% with the highest rate observed in PF and BOS patients as well as in patients who had been mechanically ventilated >6 days before initiation of ECCO2R. The modified PRedicting dEath for SEvere hypercapnic respiratory failure on vv-ECCO2R (PRESERVE-CO2) score differentiated well between survivors and non-survivors (4.3 ± 2.2 vs. 6.9 ± 2.6, p < 0.01), whereas the modified Respiratory ECMO Survival Prediction (RESP-CO2) score showed no significant distinction. Receiver operating characteristics analysis of the PRESERVE-CO2 score revealed an area under the curve of 0.78, suggesting a cut-off of 7 points. Conclusion: Careful selection of patients for ECCO2R therapy may help to improve outcomes. The proposed PRESERVE-CO2 score may serve as a guide. A score of 7 points or higher is associated with an unfavorable outcome regarding the 180-day mortality in the specific patient cohort of this study, but future studies to externally validate this score are required.