Low-flow Extracorporeal Carbon Dioxide Research Articles

Combined Use of Alkaline Agents With Low-Flow Extracorporeal Carbon Dioxide Removal in Carbon Dioxide Inhalation Models Preserving Inspiratory Efforts.

Low-flow extracorporeal CO 2 removal (ECCO 2 R), managed using a renal replacement platform, is useful in achieving lung-protective ventilation with low tidal volume. However, its capacity for CO 2 elimination is limited. Whether this system is valuable in reducing strong inspiratory efforts in respiratory failure is unclear. The combined use of alkaline agents with low-flow ECCO 2 R might be useful in hypercapnic subjects preserving inspiratory efforts. This study examined the effects of low-flow ECCO 2 R on respiratory status and investigated the effects of NaHCO 3 , trometamol, and saline on respiratory status during low-flow ECCO 2 R in CO 2 inhalation models. Although low-flow ECCO 2 R did not significantly change the respiratory rate (92.2% ± 24.3% [mean ± standard deviation] of that before ECCO 2 R), it reduced minute ventilation (MV) (78.9% ± 13.5% of that before ECCO 2 R). The addition of NaHCO 3 improved acidemia but did not change MV compared with that of the saline group (0.451 ± 0.026 L/min/kg body weight [BW] vs. 0.556 ± 0.138 L/min/kg BW, respectively). The addition of trometamol improved acidemia and reduced MV compared with that of the saline group (0.381 ± 0.050 L/min/kg BW vs. 0.556 ± 0.138 L/min/kg BW, respectively). The total amounts of CO 2 removed during ECCO 2 R in the NaHCO 3 group were lower than those in the saline and trometamol groups. The low-flow ECCO 2 R reduced MV in subjects preserving spontaneous breathing efforts with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV, whereas the addition of trometamol improved acidemia and reduced MV.

Long term feasibility of ultraprotective lung ventilation with low-flow extracorporeal carbon dioxide removal in ARDS patients.

To explore the feasibility of long-term application of ultraprotective ventilation with low flow ECCO2R support in moderate-severe ARDS patients and the reduction of mechanical power (MP) compared to lung protective ventilation. ARDS patients with PaO2/FiO2 < 200, PEEP of 10 cmH2O, tidal volume 6 ml/Kg of predicted body weight (PBW), plateau pressure > 24 cmH2O, MP > 17 J/min were prospectively enrolled. After 2 h tidal volume was reduced to 4-5 ml/kg, respiratory rate (RR) and PEEP were changed to maintain similar minute ventilation and mean airway pressure (MAP) to those obtained at baseline. After 2 h, ECCO2R support was started, RR was decreased and PEEP was increased to maintain similar PaCO2 and MAP, respectively. The only reduction of tidal volume with the increase in RR did not decrease MP. The application of low flow ECCO2R support allowed a reduction of RR from 25 [24-30] to 11 [9-14] bpm and MP from 18 [13-23] to 8 [7-11] J/min. During the following 5 days no changes in mechanics variables and gas exchange occurred. The application of low flow ECCO2R support with ultraprotective ventilation was feasible minimizing the MP without deterioration in oxygenation in ARDS patients.

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.

Mechanical Ventilation during ECMO: Lessons from Clinical Trials and Future Prospects.

Acute Respiratory Distress Syndrome (ARDS) accounts for 10% of ICU admissions and affects 3 million patients each year. Despite decades of research, it is still associated with one of the highest mortality rates in the critically ill. Advances in supportive care, innovations in technologies and insights from recent clinical trials have contributed to improved outcomes and a renewed interest in the scope and use of Extracorporeal life support (ECLS) as a treatment for severe ARDS, including high flow veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) and low flow Extracorporeal Carbon Dioxide Removal (ECCO2R). The rationale being that extracorporeal gas exchange allows the use of lung protective ventilator settings, thereby minimizing ventilator-induced lung injury (VILI). Ventilation strategies are adapted to the patient's condition during the different stages of ECMO support. Several areas in the management of mechanical ventilation in patients on ECMO, such as the best ventilator mode, extubation-decannulation sequence and tracheostomy timing, are tailored to the patients' recovery. Reduction in sedation allowing mobilization, nutrition and early rehabilitation are subsequent therapeutic goals after lung rest has been achieved.

A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease

BackgroundPatients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials.MethodsOpen-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival.ResultsEighteen patients (median age 67.5, IQR (61.5–71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO2R (7:00 (6:18–8:30) vs 24:30 (18:15–49:45) h, p = 0.004). Arterial pH was higher with ECCO2R at 4 h post-randomisation (7.35 (7.31–7.37) vs 7.25 (7.21–7.26), p < 0.001). Partial pressure of arterial CO2 (PaCO2) was significantly lower with ECCO2R at 4 h (6.8 (6.2–7.15) vs 8.3 (7.74–9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO2R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO2R, and there was no difference in 90-day mortality or functional outcomes at follow-up.InterpretationThere is evidence of benefit associated with ECCO2R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO2R. In addition, there was minimal clinically significant adverse events associated with ECCO2R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO2R for similar outcomes.Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8

Preclinical Evaluation of a New ECCO2R Setup.

Low flow extracorporeal carbon dioxide removal (ECCO2R) is a promising approach to correct hypercapnic lung failure, facilitate lung protective ventilation in acute respiratory distress syndrome and to possibly prevent the application of invasive ventilation. However, the predominant availability of adult membrane lungs (MLs) at most intensive care units are burdens for low flow ECCO2R that intends to reduce cannula size and promote the mobility of the patients. Herein, in a mock setup, we combine the idea of a low flow ECCO2R and the use of adult MLs by installing a recirculation channel into the circuit and comparing the new setup to an already clinically established setup, "the Homburg lung." Furthermore, to make stronger reference to hypercapnic respiratory failure, we investigate the influence of CO2 partial pressure in blood on CO2 removal of both setups. A linear association between CO2 partial pressure in blood and CO2 removal of the ML in the physiologically relevant range was observed. To understand this linear dependence, a simplified mathematical model was proposed. Our new ECCO2R mock setup combines the idea of a low flow ECCO2R and an adult size ML. It shows a reasonable alternative to the current available low flow setups based on pediatric MLs.

ECCO2R in 12 COVID-19 ARDS Patients With Extremely Low Compliance and Refractory Hypercapnia.

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed.Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected.Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons.Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance.Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT04340414.

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

BackgroundRESP 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.MethodsIn 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.ResultsPumpless 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.ConclusionsRESP 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.

In vivo carbon dioxide clearance of a low-flow extracorporeal carbon dioxide removal circuit in patients with acute exacerbations of chronic obstructive pulmonary disease.

Veno-venous extracorporeal carbon dioxide removal allows clearance of CO2 from the blood and is becoming popular to enhance protective mechanical ventilation and assist in the management of acute exacerbations of chronic obstructive pulmonary disease, including the prevention of intubation. The main factor determining CO2 transfer across a membrane lung for any given blood flow rate and venous CO2 content is the sweep gas flow rate. The in vivo characteristics of CO2 clearance using ultra-low blood flow devices in patients with acute exacerbations of chronic obstructive pulmonary disease has not been previously described. Patients commenced on extracorporeal carbon dioxide removal for acute exacerbations of chronic obstructive pulmonary disease recruited to a randomized controlled trial of non-invasive ventilation versus extracorporeal carbon dioxide removal had pre- and post-membrane circuit gases measured after each increment of sweep gas flow to allow calculation of the transmembrane CO2 clearance. This was compared with the clearance reported by the device and also corrected to inlet PCO2 to allow characterization of the CO2 clearance of the device at different sweep gas flow rates. CO2 clearance was calculated using both the transmembrane CO2 whole-blood content difference and CO2 clearance reported by the device. The two methods demonstrated a linear relationship and agreement with a bias of 14 mL/minute (SD = ±10) and an R2 of 0.92. The membrane CO2 clearance was non-linear with nearly two thirds of total clearance achieved with sweep gas flow below 2 L/minute (VCO2 of 40 ± 16.7 mL/minute) and a plateau above 5 L/minute sweep gas flow (VCO2 64 ± 1 2.4 mL/minute). The extracorporeal carbon dioxide removal device used in the study provides efficient clearance of CO2 at low sweep flow rates which then plateaus. This has implications for how the device may be used in clinical practice, particularly during the weaning phase where the final discontinuation of the device may take longer than anticipated. (ClinicalTrials.gov: NCT02086084, registered 13 March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084 ).

In-vitro performance of a low flow extracorporeal carbon dioxide removal circuit.

Extracorporeal gas exchange requires the passage of oxygen and carbon dioxide (CO2) across an artificial membrane. Current European Union regulations do not require the transfer to be assessed in models using clinically relevant haemoglobin, making it difficult for clinicians to understand the CO2 clearance of a membrane, and how it changes in relation to sweep gas flow through the membrane. The characteristics of membrane CO2 clearance are described using a single membrane at different sweep gas flows in an in vitro model with clinically relevant haemoglobin concentrations using three separate methods of calculating CO2 clearance. To define the CO2 removal characteristics of the extra-corporeal CO2 removal (ECCO2R) device, we devised an in-vitro gas exchange circuit formed by a dedicated ECCO2R circuit (ALung, Pittsburgh, USA) in series with two membrane oxygenators. The system was primed with donated expired human red cells provided by the local blood bank. The experimental set-up allowed constant CO2 input (via one membrane oxygenator) with variable removal from a portion of the blood in a manner which was analogous to that seen in vivo. Blood gases were measured from different ports in the circuit in order to measure the experimental membrane CO2 clearance (VCO2). Results demonstrate that the relationship between VCO2 and gas flow at a constant blood flow of 0.4 L/minute with a haemoglobin of 7 g/dL increases sharply from a gas flow of 0 to 2 L/min but plateaus at gas flows >4 L/minute. VCO2, calculated using three different methods, showed a strong linear correlation with minimal bias. The CO2 clearance of the membrane used in this bench test is non-linear. This has implications for clinical practice, especially during the weaning phase of the device.

Practical Clinical Application of an Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Distress Syndrome and Acute on Chronic Respiratory Failure.

We retrospectively reviewed the medical records of 11 patients supported with a veno-venous low-flow extracorporeal carbon dioxide (CO2) removal (ECCO2R) device featuring a large gas exchange surface membrane lung (ML) (i.e., 1.8 m). Seven patients suffered from exacerbation of a chronic pulmonary disease, while four subjects were affected by acute respiratory distress syndrome (ARDS). Twenty-four hours of ECCO2R treatment reduced arterial PCO2 from 63 ± 12 to 54 ± 11 mm Hg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). Extracorporeal blood flow and CO2 removal were 333 ± 37 and 94 ± 18 ml/min, respectively. The median duration of ECCO2R treatment was 7 days (6.5-9.5). All four ARDS patients were invasively ventilated at the time of treatment start, no one was extubated and they all died. Among the seven patients with exacerbation of chronic pulmonary diseases, four were managed with noninvasive ventilation at ECCO2R institution, while three were extubated after starting the extracorporeal treatment. No one of these seven patients was intubated or re-intubated after ECCO2R institution and five (71%) survived to hospital discharge. A low-flow ECCO2R device with a large surface ML removes a relevant amount of CO2 resulting in a decreased arterial PCO2, an increased arterial pH, and in a reduced ventilatory load.

Mechanical ventilation during low-flow extracorporeal carbon dioxide removal and outcome in patients with acute respiratory distress syndrome: A pooled individual patient data analysis of 5 studies

Linalool and geraniol are the primary components of rose oil, palmarosa oil, and citronella oil and many other essential oils, and two important compounds used in the flavour and fragrance, cosmetic or pharmaceutical industries. Phase equilibria (LLE, VLE, solubility, etc.) and related thermodynamic properties of a mixture are essential in the processes design and control of mass transfer process. In this work, experimental (liquid + liquid) equilibria data of the systems (water + 1-propanl + linalool) and (water + 1-propanl + geraniol) are presented. The (liquid + liquid) equilibria of both systems were determined with a tie-line method at T = (283.15, 298.15 and 313.15) K under atmospheric pressure. The well-known Hand, Bachman and Othmer–Tobias equations were used to test the reliability of the experimental values. The influence of the temperature on the (liquid + liquid) phase equilibria of the mixtures, the binodal curves and distribution ratios of 1-propanl are shown and discussed. Moreover, the NRTL and UNIQUAC models were applied to fit the data for both ternary systems. The interaction parameters obtained from both models successfully correlated the equilibrium compositions. Furthermore, the ternary systems could be represented using the binary parameters of the thermodynamic model with a function of temperature.

Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

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.

Management of Severe Hypercapnia Post Cardiac Arrest with Extracorporeal Carbon Dioxide Removal

Normocapnia is recommended in intensive care management of patients after out-of-hospital cardiac arrest. While normocapnia is usually achievable, it may be therapeutically challenging, particularly in patients with airflow obstruction. Conventional mechanical ventilation may not be adequate to provide optimal ventilation in such patients. One of the recent advances in critical care management of hypercapnia is the advent of newer, low-flow extracorporeal carbon dioxide clearance devices. These are simpler and less invasive than conventional extracorporeal devices. We report the first case of using a novel, extracorporeal carbon dioxide removal device in Australia on a patient with out-of-hospital cardiac arrest where mechanical ventilation failed to achieve normocapnia.

Respiratory Dialysis for Avoidance of Intubation in Acute Exacerbation of COPD

Noninvasive ventilatory support has become the standard of care for patients with chronic obstructive pulmonary disease (COPD) experiencing exacerbations leading to acute hypercapnic respiratory failure. Despite advances in the use of noninvasive ventilation and the associated improvement in survival, as many as 26% of these patients fail noninvasive support and have a higher subsequent risk of mortality than patients treated initially with invasive mechanical ventilation. We report the use of a novel device to avoid invasive mechanical ventilation in two patients who were experiencing acute hypercapnic respiratory failure because of an exacerbation of COPD and were deteriorating, despite support with noninvasive ventilation. This device provided partial extracorporeal carbon dioxide removal at dialysis-like settings through a single 15.5 Fr venovenous cannula inserted percutaneously through the right femoral vein. The primary results were rapid reduction in arterial carbon dioxide and correction of pH. Neither patient required intubation, despite imminent failure of noninvasive ventilation before initiation of extracorporeal support. Both patients were weaned from noninvasive and extracorporeal support within 3 days. We concluded that low-flow extracorporeal carbon dioxide removal, or respiratory dialysis, is a viable option for avoiding intubation and invasive mechanical ventilation in patients with COPD experiencing an exacerbation who are failing noninvasive ventilatory support.