**3. ECCO2R technical aspects and principle**

ECCO2R is designed to remove carbon dioxide (CO2) and, unlike extracorporeal membrane oxygen (ECMO), does not provide significant oxygenation.

The device consists of a drainage cannula placed in a large central vein or artery, a membrane lung, and a return cannula into the venous system (**Figure 1**). Blood is pumped through the membrane lung, and CO2 is removed by diffusion. A flowing gas known as "sweep gas" containing little or no CO2 runs along the other side of the membrane, ensuring a diffusion gradient from blood to another side, allowing CO2 removal.

In contrast to ECMO, where the need for oxygenation requires high blood flow rates, ECCO2R allows much lower blood flow rates, a result of significant differences in CO2 and oxygen (O2) kinetics. Almost all the O2 in blood is carried by hemoglobin, which displays sigmoidal saturation kinetics. Assuming normal hemoglobin and venous O2, each liter of venous blood can only carry an extra 40–60 ml of O2 before the hemoglobin is fully saturated. Blood flows of 5–7 L/min are therefore required to supply enough O2 for an average adult. Conversely, most CO2 is transported as dissolved bicarbonate, displaying linear kinetics without saturation. Considering that 1 L of blood is transported around 500 mL of CO2, a perfectly efficient system flow of 0.5 L/min would be enough to remove all of the CO2 produced [1, 15, 16]. Also, CO2 diffuses more readily than O2 across extracorporeal membranes because of higher solubility. However, in practice, ECCO2R is usually able to remove up to 25% of carbon dioxide production given the limitations of blood flow, blood CO2 content, hemoglobin, and membrane efficiency [17].

#### **3.1 VV-ECCO2R**

In the veno-venous configuration, blood is drawn from a central vein by a draining cannula, using a centrifugal or roller pump to generate flow across the membrane. CO2 diffuses into the "sweep gas" and is returned into the venous circulation (**Figure 1A**). Single site cannulation is possible using a double lumen cannula. This approach allows low flow through the use of smaller cannulas (15–19F), commonly introduced via the right internal jugular vein. The setup is very similar to renal

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

Blood flow High extracorporeal flow

Membrane oxygenator

Heparin requirements

*ECMO and ECCO2R differences.*

**Table 1.**

(0.4–1 L/min). With ECCO2R the patient's PaCO2 is principally determined by the rate of fresh gas flow through the membrane lung [2]. These devices are now comparable to renal dialysis equipment, which is routinely used safely as standard care in ICU.

**ECMO ECCO2R**

Large membrane oxygenator Medium size oxygenator

High Higher than ECMO

Low flow, respiratory dialysis (250–1000 ml/min)

Cannulas Large cannulas Double lumen catheter

Oxygenation Full blood oxygenation No blood oxygenation CO2 removal Full blood decarboxylation Partial blood decarboxylation

Setting High technicity, ECMO center Regular ICU

(2000–>5000 ml/min)

Both in asthma and COPD exacerbations, diffuse narrowing of the airways results in profound physiologic consequences. Airway narrowing prevents the lungs from completely emptying ("air trapping") due to resistance to expiratory flow and bronchial closure at higher than average lung volumes. Air trapping results in dynamic hyperinflation (DHI) [7] which is the excessive increase in end-expiratory lung volume above the relaxation volume of the respiratory system, generating intrinsic positive end-expiratory pressure (auto-PEEP) [8]. As a result, the patient breathes at higher total lung volumes, depending on increased residual volume [9] which reduces tidal ventilation. The net effect is that the work of breathing increases significantly. The diaphragm, intercostal muscles, and even the abdominal

series demonstrating improved arterial CO2 and work of breathing [3–6].

muscles are overloaded causing respiratory muscle fatigue and dyspnea.

to pneumothorax and further hemodynamic deterioration [12].

contributing to the long-term cognitive sequelae of critical illness [14].

Pharmacotherapy with bronchodilators and systemic corticosteroids are the cornerstones of medical therapy, designed to reduce this pathophysiological airflow

Patients suffering from a combination of persistent or worsening hypercapnia, respiratory muscle fatigue, and a decline in mental status require mechanical ventilation (MV) along with lung-protective ventilator strategies (e.g., low-tidal-volume ventilation, relatively short inspiratory time and longer expiratory times) [10, 11]. The goal of mechanical ventilation is to provide adequate gas exchange while waiting for airflow obstruction to respond to bronchodilator therapy. However, mechanical ventilation may aggravate alveolar hyperinflation by worsening DHI, which may lead to worsened hypercapnia, barotrauma, and alveolar rupture leading

Furthermore, during mechanical ventilation, these patients receive sedatives or neuromuscular blockade to facilitate ventilatory support [13]. Sedation and paralysis preclude mobilization, promoting muscular deconditioning and potentially

**2. Pathophysiological rationale for ECCO2R**

obstruction and improve symptoms.

This approach has been the subject of many animal experiments and human case

**92**

#### **Figure 1.**

*ECCO2R common configurations. (A) Minimally invasive veno-venous ECCO2R system with a single venous vascular access through a double lumen cannula that can be inserted in the internal jugular or femoral vein (B) Pumpless arteriovenous ECCO2R system with the placement of the membrane in the circuit connecting the femoral artery with the contralateral vein.*

replacement therapy, and in fact, some systems are trying to combine the two in one [18, 19] (NCT02590575). One of the advantages of VV-ECCO2R compared to the AV approach is the less invasiveness by the omission of the arterial cannulation and facilitates early mobilization of patients. It is also possible to set up an ECCO2R system through cannulation of two central veins, one for drainage and the other for reinfusion (femoral-femoral configuration).

### **3.2 AV-ECCO2R**

One ECCO2R configuration is through percutaneous cannulation of the femoral artery to the contralateral femoral vein and creating an arteriovenous (AV) bypass, equipped with an artificial gas exchanger membrane across the AV shunt which acts as a "sweep gas" to remove CO2 that has diffused out of the patient's blood (**Figure 1B**). In this configuration, pumpless systems require an arteriovenous pressure gradient ≥60 mmHg and a cardiac index >3 L/min/m<sup>2</sup> , which is unsuitable for hemodynamically unstable patients [16, 20]. Further, cannulation of a major artery can result in distal ischemia [21], although measuring the artery diameter with ultrasound and selecting a cannula that occupies no more than 70% of the lumen reduce this risk [22].

#### **4. Indications and evidence**

#### **4.1 Chronic obstructive pulmonary disease**

Chronic obstructive pulmonary disease (COPD) is a significant worldwide health burden. Currently, it is the fourth leading cause of death worldwide, is the only leading cause of death that is rising, and will likely become the third cause of

**95**

*Extracorporeal Carbon Dioxide Removal for the Exacerbation of Chronic Hypercapnic…*

death by 2020 [23, 24]. COPD is characterized by progressive destruction in the

Acute exacerbations of COPD (aeCOPD) constitute a significant cause of morbidity and mortality among these patients. Patients with moderate to severe acute exacerbations develop alveolar hyperinflation that may lead to increased work of breathing, muscle fatigue, and hypercapnia, creating a vicious loop refractory to medical treatment [25–27]. The standard respiratory support in this setting in order to break this cycle is noninvasive ventilation (NIV). However, despite the significantly decreased mortality with the emergence of NIV, up to 30% of patients with aeCOPD will "fail" and require intubation and invasive mechanical ventilation (IMV) [28–30]. For patients requiring respiratory support with IMV, in-hospital mortality in recent meta-analysis and observational studies has been reported to be

Patients with COPD requiring IMV develop a considerable reduction in respiratory muscle strength, having a higher risk of prolonged weaning and failure to wean compared to other causes of acute hypercapnic respiratory failure. Up to 60% of the ventilatory time is devoted to these patients to the process of weaning [35], and they are very likely to require a tracheotomy. Having a prolonged time spent under IMV is not surprising an increase in the incidence of ventilatorassociated pneumonia and complications associated with the use of invasive mechanical ventilation such ventilator-induced lung injury (VILI), ventilatorassociated pneumonia (VAP), ventilator-associated diaphragmatic dysfunction (VIDD), and a range of neurological disorders associated with prolonged sedation

One of the first reports on the application of ECCO2R to support respiratory function of a COPD patient was published in 1990 by Pesenti et al. [36]. However,

As the medical community regained interest in ECCO2R, investigators began applying the technique to prevent intubation or to assist weaning from the ventilator in patients with hypercapnic aeCOPD. Several studies in both VV and AV

Brederlau et al. [37] described their experience in three patients that failed NIV for severe aeCOPD. They applied a pumpless AV ECCO2R device with the goal of avoiding endotracheal intubation. Shortly after beginning ECCO2R, PaCO2 fell significantly (from 91, 109, and 142 mmHg to 52, 59, and 83 mmHg, respectively), while pH rose (from 7.2, 7.19, and 7.06 to 7.41, 7.43, and 7.34, respectively). Simultaneously, the respiratory rate dropped from 38, 45, and 37 breaths/min to 15, 25, and 18 breaths/min, respectively. The ECCO2R flow ranged between 1.1 and

Kluge et al. [5] in the same year evaluated the safety and efficacy of using AV pumpless extracorporeal lung assist (PECLA) in 21 COPD patients who did not respond to NIV compared to 21 matched controls. The use of PECLA was associated with a decrease in PaCO2 levels and improved pH after 24 h and obviated the need for intubation and IMV in 90% of the experimental arm. Although the experimental group demonstrated a shorter length of stay, a retrospective analysis with the control group showed no significant difference in mortality at 28 days (19% with

*DOI: http://dx.doi.org/10.5772/intechopen.84936*

as high as 25–39% [31–34].

and immobilization.

*4.1.2 ECCO2R to avoid IMV*

elastic tissue within the lung, causing respiratory failure.

*4.1.1 Evidence and clinical trials of ECCO2R in aeCOPD to date*

the technique was abandoned due to technical complications.

configurations were published, including a meta-analysis (**Table 2**).

1.6 L/min, with the sweep gas flow varying from 3 to 10 L/min.

ECCO2R vs. 24% without ECCO2R) or 6 months (both groups 33%).

#### *Extracorporeal Carbon Dioxide Removal for the Exacerbation of Chronic Hypercapnic… DOI: http://dx.doi.org/10.5772/intechopen.84936*

death by 2020 [23, 24]. COPD is characterized by progressive destruction in the elastic tissue within the lung, causing respiratory failure.

Acute exacerbations of COPD (aeCOPD) constitute a significant cause of morbidity and mortality among these patients. Patients with moderate to severe acute exacerbations develop alveolar hyperinflation that may lead to increased work of breathing, muscle fatigue, and hypercapnia, creating a vicious loop refractory to medical treatment [25–27]. The standard respiratory support in this setting in order to break this cycle is noninvasive ventilation (NIV). However, despite the significantly decreased mortality with the emergence of NIV, up to 30% of patients with aeCOPD will "fail" and require intubation and invasive mechanical ventilation (IMV) [28–30]. For patients requiring respiratory support with IMV, in-hospital mortality in recent meta-analysis and observational studies has been reported to be as high as 25–39% [31–34].

Patients with COPD requiring IMV develop a considerable reduction in respiratory muscle strength, having a higher risk of prolonged weaning and failure to wean compared to other causes of acute hypercapnic respiratory failure. Up to 60% of the ventilatory time is devoted to these patients to the process of weaning [35], and they are very likely to require a tracheotomy. Having a prolonged time spent under IMV is not surprising an increase in the incidence of ventilatorassociated pneumonia and complications associated with the use of invasive mechanical ventilation such ventilator-induced lung injury (VILI), ventilatorassociated pneumonia (VAP), ventilator-associated diaphragmatic dysfunction (VIDD), and a range of neurological disorders associated with prolonged sedation and immobilization.
