High- versus Low-Flow Extracorporeal Respiratory Support in Experimental Hypoxemic Acute Lung Injury.

Rationale: In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO2 removal (ECCO2R), provided oxygenation remains acceptable. Objectives: To compare the effects of ECCO2R and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury. Methods: Twenty-four pigs with moderate to severe hypoxemia (PaO2:FiO2 ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50-60 ml/kg/min), ECCO2R (0.4 L/min), or mechanical ventilation alone. Measurements and Main Results: [Formula: see text]o2, [Formula: see text]co2, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; P < 0.001), worse oxygenation (PaO2:FiO2 = 125 ± 14 vs. 151 ± 11 mm Hg; P < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm H2O; P = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCO2R (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; P = 0.003). [Formula: see text]o2 and [Formula: see text]co2, irrespective of lung injury model, were lower during ECMO, resulting in lower PaCO2 and [Formula: see text]e but worse respiratory elastance compared with ECCO2R (64 ± 27 vs. 40 ± 8 cm H2O/L; P < 0.001). Conclusions: ECMO was associated with better oxygenation, lower [Formula: see text]o2, and better hemodynamics. ECCO2R may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.

Increased Longevity of a Novel Gas Exchanger System for Low-Flow Veno-Venous Extracorporeal CO2 Removal in Acute Hypercapnic Respiratory Failure.

INTRODUCTION: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. METHODS: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. RESULTS: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). CONCLUSION: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure.

Mobilizing Carbon Dioxide Stores. An Experimental Study.

Rationale: Understanding the physiology of CO2 stores mobilization is a prerequisite for intermittent extracorporeal CO2 removal (ECCO2R) in patients with chronic hypercapnia.Objectives: To describe the dynamics of CO2 stores.Methods: Fifteen pigs (61.7 ± 4.3 kg) were randomized to 48 hours of hyperventilation (group "Hyper," n = 4); 48 hours of hypoventilation (group "Hypo," n = 4); 24 hours of hypoventilation plus 24 hours of normoventilation (group "Hypo-Baseline," n = 4); or 24 hours of hypoventilation plus 24 hours of hypoventilation plus ECCO2R (group "Hypo-ECCO2R," n = 3). Forty-eight hours after randomization, the current [Formula: see text]e was reduced by 50% in every pig.Measurements and Main Results: We evaluated [Formula: see text]co2, [Formula: see text]o2, and metabolic [Formula: see text]co2 ([Formula: see text]o2 times the metabolic respiratory quotient). Changes in the CO2 stores were calculated as [Formula: see text]co2 - metabolic V̇co2. After 48 hours, the CO2 stores decreased by 0.77 ± 0.17 l kg-1 in group Hyper and increased by 0.32 ± 0.27 l kg-1 in group Hypo (P = 0.030). In group Hypo-Baseline, they increased by 0.08 ± 0.19 l kg-1, whereas in group Hypo-ECCO2R, they decreased by 0.32 ± 0.24 l kg-1 (P = 0.197). In the second 24-hour period, in groups Hypo-Baseline and Hypo-ECCO2R, the CO2 stores decreased by 0.15 ± 0.09 l kg-1 and 0.51 ± 0.06 l kg-1, respectively (P = 0.002). At the end of the experiment, the 50% reduction of [Formula: see text]e caused a PaCO2 rise of 9.3 ± 1.1, 32.0 ± 5.0, 16.9 ± 1.2, and 11.7 ± 2.0 mm Hg h-1 in groups Hyper, Hypo, Hypo-Baseline, and Hypo-ECCO2R, respectively (P < 0.001). The PaCO2 rise was inversely related to the previous CO2 stores mobilization (P < 0.001).Conclusions: CO2 from body stores can be mobilized over 48 hours without reaching a steady state. This provides a physiological rationale for intermittent ECCO2R in patients with chronic hypercapnia.

A bi-centric experience of extracorporeal carbon dioxide removal (ECCO2 R) for acute hypercapnic respiratory failure following allogeneic hematopoietic stem cell transplantation.

Acute respiratory failure (ARF) is the main reason for ICU admission following allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal CO2 removal (ECCO2 R) can be used as an adjunct to mechanical ventilation in patients with severe hypercapnia but has not been assessed in HSCT recipients. Retrospective analysis of all allogeneic HSCT recipients ≥18 years treated with ECCO2 R at two HSCT centers. 11 patients (m:f = 4:7, median age: 45 [IQR: 32-58] years) were analyzed. Acute leukemia was the underlying hematologic malignancy in all patients. The time from HSCT to ICU admission was 37 [8-79] months, and 9/11 (82%) suffered from chronic graft-versus-host disease (GVHD) with lung involvement. Pneumonia was the most frequent reason for ventilatory decompensation (n = 9). ECCO2 R was initiated for severe hypercapnia (Pa CO2 : 96 [84-115] mm Hg; pH: 7.13 [7.09-7.27]) despite aggressive mechanical ventilation (invasive, n = 9; non-invasive, n = 2). ECCO2 R effectively resolved blood gas disturbances in all patients, but only 2/11 (18%) could be weaned off ventilatory support, and one (9%) patient survived hospital discharge. Progressive respiratory and multiorgan dysfunction were the main reasons for treatment failure. ECCO2 R was technically feasible but resulted in a low survival rate in our cohort. A better understanding of the prognosis of ARF in patients with chronic GVHD and lung involvement is necessary before its use can be reconsidered in this setting.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

A novel escalation from veno-venous bypass to veno-venous ECMO during orthotopic liver transplantation. A case report.

We describe the challenging perioperative course of a 55-year-old patient with hepatic failure requiring liver transplantation (LT). Different modalities of the extracorporeal device were successfully used, ranging from veno-veno bypass to partial and full veno-veno extracorporeal membrane oxygenation (ECMO) in order to optimize preload, reduce bleeding from the collateral circulation, optimize acid base balance and/or improve oxygenation. The case highlights the potential use of the device as a rescue method in challenging cases. Furthermore this is the first documented case that extracorporeal CO2 removal (ECCO2R) is used to optimize the biochemistry profile intraoperatively during a LT. The patient was weaned off the device at the end of the case and has been discharged home.

Fifty Years of Research in ARDS. Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high FiO2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3-4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.

Mechanical ventilation in patients subjected to extracorporeal membrane oxygenation (ECMO). / Ventilación mecánica en pacientes tratados con membrana de oxigenación extracorpórea (ECMO).

Mechanical ventilation (MV) is a crucial element in the management of acute respiratory distress syndrome (ARDS), because there is high level evidence that a low tidal volume of 6ml/kg (protective ventilation) improves survival. In these patients with refractory respiratory insufficiency, venovenous extracorporeal membrane oxygenation (ECMO) can be used. This salvage technique improves oxygenation, promotes CO2 clearance, and facilitates protective and ultraprotective MV, potentially minimizing ventilation-induced lung injury. Although numerous trials have investigated different ventilation strategies in patients with ARDS, consensus is lacking on the optimal MV settings during venovenous ECMO. Although the concept of "lung rest" was introduced years ago, there are no evidence-based guidelines on its use in application to MV in patients supported by ECMO. How MV in ECMO patients can promote lung recovery and weaning from ventilation is not clear. The purpose of this review is to describe the ventilation strategies used during venovenous ECMO in clinical practice.

Applying a low-flow CO2 removal device in severe acute hypercapnic respiratory failure.

A novel and portable extracorporeal CO2-removal device was evaluated to provide additional gas transfer, auxiliary to standard therapy in severe acute hypercapnic respiratory failure. A dual-lumen catheter was inserted percutaneously in five subjects (mean age 55 ± 0.4 years) and, subsequently, connected to the CO2-removal device. The median duration on support was 45 hours (interquartile range 26-156), with a blood flow rate of approximately 500 mL/min. The mean PaCO2 decreased from 95.8 ± 21.9 mmHg to 63.9 ± 19.6 mmHg with the pH improving from 7.11 ± 0.1 to 7.26 ± 0.1 in the initial 4 hours of support. Three subjects were directly weaned from the CO2-removal device and mechanical ventilation, one subject was converted to ECMO and one subject died following withdrawal of support. No systemic bleeding or device complications were observed. Low-flow CO2 removal adjuvant to standard therapy was effective in steadily removing CO2, limiting the progression of acidosis in subjects with severe acute hypercapnic respiratory failure.

Effect of extracorporeal CO2 removal on right ventricular and hemodynamic parameters in a patient with acute respiratory distress syndrome.

We present a female patient with severe acute respiratory distress syndrome (ARDS) necessitating intubation and mechanical ventilation on the intensive care unit (ICU). High ventilatory pressures were needed because of hypoxia and severe hypercapnia with respiratory acidosis, resulting in right ventricular dysfunction with impaired haemodynamic stability. A veno-venous extracorporeal CO2 removal (ECCO2R) circuit was initiated, effectively eliminating carbon dioxide while improving oxygenation and enabling a reduction in applied ventilatory pressures. We noted a marked improvement of right ventricular function with restoration of haemodynamic stability. Within one week, the patient was weaned from both ECCO2R and mechanical ventilation. Besides providing adequate gas exchange, extracorporeal assist devices may be helpful in ameliorating right ventricular dysfunction during ARDS.