Use Of Extracorporeal CO2 Removal Research Articles

Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting

BackgroundBy controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial.ResultsThe group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion.ConclusionsECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion.

Extracorporeal membrane oxygenation (ECMO) and beyond in near fatal asthma: A comprehensive review

The treatment of choice in severe asthma exacerbations with respiratory failure includes ventilatory support, both invasive and/or non-invasive, along with different kinds of asthma medication. Of note, the rate of mortality of patients with asthma has decreased substantially in recent years mainly due to significant advances in pharmacological treatment and other management strategies. However, the risk of death in patients with severe asthma who require invasive mechanical ventilation has been estimated between 6.5% and 10.3%. When conventional measures fail, rescue strategies, such as extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) may need to be implemented. While ECMO does not constitute a definitive treatment per se, it can minimize further ventilator associated lung injury (VALI) and can enable diagnostic-therapeutic maneuvers that cannot be performed without ECMO such as bronchoscopy and transfer for diagnostic imaging. Asthma is one of the diseases that is associated with excellent outcomes for patients with refractory respiratory failure requiring ECMO support, as shown by the Extracorporeal Life Support Organization (ELSO) registry. Moreover, in such situations, the use of ECCO2R for rescue has been described and utilized in both children and adults and is more widely spread in different hospitals than ECMO. In this article, we aim to review the evidence for the usefulness of extracorporeal respiratory support measures in the management of severe asthma exacerbations that lead to respiratory failure.

Respiratory Care Management of COPD Exacerbations.

A COPD exacerbation is characterized by an increase in symptoms such as dyspnea, cough, and sputum production that worsens over a period of 2 weeks. Exacerbations are common. Respiratory therapists and physicians in an acute care setting often treat these patients. Targeted O2 therapy improves outcomes and should be titrated to an SpO2 of 88-92%. Arterial blood gases remain the standard approach to assessing gas exchange in patients with COPD exacerbation. The limitations of arterial blood gas surrogates (pulse oximetry, capnography, transcutaneous monitoring, peripheral venous blood gases) should be appreciated so that they can be used wisely. Inhaled short-acting bronchodilators can be provided by nebulizer (jet or mesh), pressurized metered-dose inhaler (pMDI), pMDI with spacer or valved holding chamber, soft mist inhaler, or dry powder inhaler. The available evidence for the use of heliox for COPD exacerbation is weak. Noninvasive ventilation (NIV) is standard therapy for patients who present with COPD exacerbation and is supported by clinical practice guidelines. Robust high-level evidence with patient important outcomes is lacking for the use of high-flow nasal cannula in patients with COPD exacerbation. Management of auto-PEEP is the priority in mechanically ventilated patients with COPD. This is achieved by reducing airway resistance and decreasing minute ventilation. Trigger asynchrony and cycle asynchrony are addressed to improve patient-ventilator interaction. Patients with COPD should be extubated to NIV. Additional high-level evidence is needed before widespread use of extracorporeal CO2 removal. Care coordination can improve the effectiveness of care for patients with COPD exacerbation. Evidence-based practices improve outcomes in patients with COPD exacerbation.

Intraoperative use of extracorporeal CO2 removal (ECCO2R) and emergency ECMO requirement in patients undergoing lung transplant: a case-matched cohort retrospective study

BackgroundThe use of extracorporeal carbon dioxide removal (ECCO2R) is less invasive than extracorporeal membrane oxygenation (ECMO), and intraoperative control of gas exchange could be feasible. The aim of this study in intermediate intraoperative severity patients undergoing LT was to assess the role of intraoperative ECCO2R on emergency ECMO requirement in patients.MethodsThirty-eight consecutive patients undergoing lung transplantation (LT) with “intermediate” intraoperative severity in the intervals 2007 to 2010 or 2011 to 2014 were analyzed as historical comparison of case-matched cohort retrospective study. The “intermediate” intraoperative severity was defined as the development of intraoperative severe respiratory acidosis with maintained oxygenation function (i.e., pH <7.25, PaCO2 >60 mmHg, and PaO2/FiO2 >150), not associated with hemodynamic instability. Of these 38 patients, twenty-three patients were treated in the 2007–2010 interval by receiving “standard intraoperative treatment,” while 15 patients were treated in the 2011–2014 interval by receiving “standard intraoperative treatment + ECCO2R.”ResultsECMO requirement was more frequent among patients that received “standard intraoperative treatment” alone than in those treated with “standard intraoperative treatment + ECCO2R” (17/23 vs. 3/15; p = 0.004). The use of ECCO2R improved pH and PaCO2 while mean pulmonary artery pressure (mPAP) decreased.ConclusionIn intermediate intraoperative severity patients, the use of ECCO2R reduces the ECMO requirement.

Evaluation of a New Extracorporeal CO2 Removal Device in an Experimental Setting.

Background: Ultra-protective lung ventilation in acute respiratory distress syndrome or early weaning and/or avoidance of mechanical ventilation in decompensated chronic obstructive pulmonary disease may be facilitated by the use of extracorporeal CO2 removal (ECCO2R). We tested the CO2 removal performance of a new ECCO2R (CO2RESET) device in an experimental animal model. Methods: Three healthy pigs were mechanically ventilated and connected to the CO2RESET device (surface area = 1.8 m2, EUROSETS S.r.l., Medolla, Italy). Respiratory settings were adjusted to induce respiratory acidosis with the adjunct of an external source of pure CO2 (target pre membrane lung venous PCO2 (PpreCO2): 80–120 mmHg). The amount of CO2 removed (VCO2, mL/min) by the membrane lung was assessed directly by the ECCO2R device. Results: Before the initiation of ECCO2R, the median PpreCO2 was 102.50 (95.30–118.20) mmHg. Using fixed incremental steps of the sweep gas flow and maintaining a fixed blood flow of 600 mL/min, VCO2 progressively increased from 0 mL/min (gas flow of 0 mL/min) to 170.00 (160.00–200.00) mL/min at a gas flow of 10 L/min. In particular, a high increase of VCO2 was observed increasing the gas flow from 0 to 2 L/min, then, VCO2 tended to progressively achieve a steady-state for higher gas flows. No animal or pump complications were observed. Conclusions: Medium-flow ECCO2R devices with a blood flow of 600 mL/min and a high surface membrane lung (1.8 m2) provided a high VCO2 using moderate sweep gas flows (i.e., >2 L/min) in an experimental swine models with healthy lungs.

Daily use of extracorporeal CO2 removal in a critical care unit: indications and results

BackgroundWhile outcome improvement with extracorporeal CO2 removal (ECCO2R) is not demonstrated, a strong pathophysiological rational supports its use in the setting of acute respiratory distress syndrome (ARDS) and COPD exacerbation. We aimed to describe our single-center experience of ECCO2R indications and outcome.MethodsPatients treated with ECCO2R in our medial ICU, from March 2014 to November 2017, were retrospectively enrolled. Primary end point was evolution of ventilator settings during the two first days following ECCO2R start.ResultsThirty-three patients received ECCO2R. Seventeen were managed with Hemolung®, 10 with Prismalung®, 4 with ILA®, and 2 with Cardiohelp®. Indications for ECCO2R were mild or moderate ARDS (n = 16), COPD exacerbation (n = 11), or uncontrolled hypercapnia due to other causes (n = 6). Four patients were not intubated at the time of ECCO2R start. Median duration of ECCO2R treatment was 7 days [5–10]. In ARDS patients, between baseline and day 2, median tidal volume and driving pressure decreased from 5.3 [4.4–5.9] mL/kg and 10 [8–15] to 3.8 [3.3–4.1] mL/kg and 9 [8–11], respectively. Prone positioning was performed in 10 of the 16 patients, without serious adverse event. In COPD patients, between baseline and day 2, median ventilation minute and PaCO2 decreased significantly from respectively 7.6 [6.6–8.7] L/min and 9.4 [8.4–10.1] kPa to 5.8 [4.9–6.2] L/min and 6 [5.3–6.8] kPa. Four out of 11 COPD patients were extubated while on ECCO2R. Device thrombosis occurred in 5 patients (15%). Hemolysis was documented in 16 patients (48%). One patient died of intracranial hemorrhage, while on ECCO2R. Twenty-four patients were discharged from ICU alive. Twenty-eight day mortality was 31% in ARDS, 9% in COPD patients, and 50% in other causes of refractory hypercapnic respiratory failure.ConclusionECCO2R was useful to apply ultra-protective ventilation among ARDS patients and improved PaCO2, pH, and minute ventilation in COPD patients.

Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO2 Removal for Acute Respiratory Distress Syndrome.

In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultraprotective ventilation in ARDS. ECCO2R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO2R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO2R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.

Extracorporeal CO2 removal in critically ill patients: a systematic review.

The use of extracorporeal CO2 removal (ECCO2R) is increasingly employed in critically ill patients. However, the clinical evidence supporting its efficacy remains currently poor. A systematic review using MEDLINE via PubMed was performed to identify eligible studies (until 30th September 2016). The amount of CO2 reduction, the effect on the duration of mechanical ventilation and weaning, the impact on patients' outcome and the occurrence of complications were evaluated. The quality of evidence was evaluated according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Six studies were included (three evaluating patients with chronic obstructive pulmonary disease [COPD]; three evaluating patients with acute respiratory distress syndrome [ARDS]), involving 279 adult patients; 142 treated with ECCO2R and 137 controls. No study on pediatric population met the inclusion criteria for analysis. The overall quality of evidence of the two randomized trials and four case-control studies varied from moderate to very low. PaCO2 was generally reduced by 25-33% within a few hours following ECCO2R initiation. One ARDS study showed a significant decrease in the duration of mechanical ventilation, although this result was only found by post-hoc analysis. The three studies on COPD demonstrated that some patients supported by ECCO2R devices could avoid endotracheal intubation, however the ICU-LOS and survival was not influenced by ECCO2R when compared to controls. In COPD patients, a significantly reduced need for endotracheal intubation was reported. However, the use of ECCO2R has not shown significant improvement on the outcome of critically ill patients in the reviewed studies. Therefore appropriately powered, randomized, controlled studies are urgently needed.

Use of Extracorporeal CO2 Removal to Avoid Invasive Mechanical Ventilation in Hypercapnic Coma and Failure of Noninvasive Ventilation

Invasive mechanical ventilation is known to be detrimental to patients with respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD). If hypercapnic respiratory failure and acidosis cannot be controlled by noninvasive mechanical ventilation, extracorporeal carbon dioxide removal (ECCO2 R) serves as an alternative option. Currently applied systems like extracorporeal membrane oxygenation (ECMO) or pumpless extracorporeal lung assist (PECLA) are associated with potentially significant bleeding complications and require a very high nursing standard. We report a case of AECOPD with hypercapnic coma and failure of noninvasive ventilation for which we used a novel low-flow ECCO2 R device, called the Hemolung Respiratory Assist System. This device requires only a single 15.5 French double-lumen venous catheter and operates at blood flows of 350 mL/min to 550 mL/min. Use of this device enabled the patient to avoid general anesthesia and invasive mechanical ventilation without adverse events. In addition, weaning from noninvasive mechanical ventilation, early mobilization, communication and nutrition were facilitated. CO2 removal with low extracorporeal blood flow avoided intubation in the treatment of hypercapnic coma with failure of non-invasive ventilation.

First experience with a new miniaturized pump-driven venovenous extracorporeal CO2 removal system (iLA Activve): a retrospective data analysis.

iLA Activve is a new minimally invasive device for extracorporeal CO2 removal (ECCO2-R) using a miniaturized pump, a special gas exchange membrane, and a double-lumen cannula. We retrospectively analyzed our experiences in 12 patients with hypercapnic respiratory failure undergoing ECCO2-R. Indication for ECCO2-R was hypercapnia due to terminal lung failure during bridging to lung transplantation, pneumonia, and chronic obstructive lung disease or asthma. The median duration of ECCO2-R was 8 days (range 2-30). Seven patients were successfully weaned and five died. Patients with primarily hypoxic lung failure were significantly longer ventilated before ECCO2-R and had a higher mortality rate. Complications were retroperitoneal hematoma after cannulation in one patient and repeated system changes because of clotting in two patients. We observed effective CO2 removal in all patients, with significant reduction in ventilation pressures and minute volumes at median blood flow rates of 1.2-1.4 L/min. The iLA Activve system using venous double-lumen cannulas proved to be an effective method for ECCO2-R. Invasiveness of ventilation could be reduced. Additional severe impairment of oxygenation and prolonged mechanical ventilation before ECCO2-R are factors of adverse prognosis. The use of ECCO2-R should be thoroughly reconsidered in these cases.

Extracorporeal lung assist: more than kicking a dead horse?

Up to now, the history of extracorporeal lung support has been a tale of great expectations and even greater disappointments. In 1972, Hill et al. 1 published the first case report on the use of extracorporeal membrane oxygenation (ECMO) in a young patient who suffered from acute respiratory distress syndrome (ARDS) after trauma. At that time, mortality rates from ARDS were extremely high and thus this report was embraced with great enthusiasm. However, only 2 yrs later reality caught up when the results of a randomised controlled trial using ECMO in ARDS were published showing mortality rates of >90% in both treatment arms 2. Despite these sobering results, several groups of investigators continued to work on extracorporeal devices. Gattinoni and co-workers 3, 4 were the first to introduce the use of extracorporeal CO2 removal to support protective ventilation strategies, now with survival rates of ∼50% among patients with ARDS. However, once again a randomised controlled trial failed to show a survival benefit in ARDS patients treated with extracorporeal CO2 removal 5 although the survival rates (33% in the extracorporeal group versus 42% in the conventional ventilation group) were now substantially better than in the 1970s. The reasons for the failure to demonstrate a survival benefit with extracorporeal lung support were certainly manifold. The study by Morris et al. 5 included only 40 patients and was gravely underpowered (for comparison, the ARDS Network trial on low tidal volumes recruited >800 patients before a survival difference of 22% became statistically significant 6). More importantly, the …