PRACA POGLĄDOWA

REVIEW ARTICLE

Extracorporeal membrane oxygenation (ECMO) – in the treatment of severe, life-threatening respiratory failure

Krystian Ślusarz1, Paulina Kurdyś1, Paul Armatowicz2, Piotr Knapik3, Ewa Trejnowska3

1STUDENTS’ SCIENTIFIC SOCIETY, DEPARTMENT OF CARDIAC ANESTHESIA AND INTENSIVE THERAPY, SILESIAN CENTRE FOR HEART DISEASES, MEDICAL UNIVERSITY OF SILESIA, ZABRZE, POLAND

2DEPARTMENT OF GENERAL, ENDOCRINE AND VASCULAR SURGERY, MEDICAL UNIVERSITY OF WARSAW, WARSAW, POLAND

3DEPARTMENT OF CARDIAC ANESTHESIA AND INTENSIVE THERAPY, SILESIAN CENTRE FOR HEART DISEASES, MEDICAL UNIVERSITY OF SILESIA, ZABRZE, POLAND

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is a technique involving oxygenation of blood and elimination of carbon dioxide in patients with life-threatening, but potentially reversible conditions. Thanks to the modification of extracorporeal circulation used during cardiac surgeries, this technique can be used in intensive care units. Venovenous ECMO is used as a respiratory support, while venoarterial ECMO as a cardiac and/or respiratory support. ECMO does not cure the heart and/or lungs, but it gives the patient a chance to survive a period when these organs are inefficient. In addition, extracorporeal membrane oxygenation reduces or eliminates the risk of lung damage associated with invasive mechanical ventilation in patients with severe ARDS (acute respiratory distress syndrome). ECMO is a very invasive therapy, therefore it should only be used in patients with extremely severe respiratory failure, who failed to respond to conventional therapies. According to the Extracorporeal Life Support Organization (ELSO) Guidelines, inclusion criteria are: PaO2 / FiO2 < 80 for at least 3 hours or pH < 7.25 for at least 3 hours. Proper ECMO management requires advanced medical care. This article discusses the history of ECMO development, clinical indications, contraindications, clinical complications and treatment outcomes.

Key words: acute respiratory distress syndrome, extracorporeal membrane oxygenation, acute respiratory failure, acute cardiac failure, critical care

Wiad Lek 2019, 72, 9 cz II, 1822-1828

INTRODUCTION

Severe respiratory failure and cardiac failure are the result of many diseases. They can also be a direct threat to the patient’s life. All procedures that temporarily support the respiratory and/or cardiac system, which failed to respond to conventional therapies and treatment, are included under the term extracorporeal life support (ECLS). When ECLS is implemented in intensive care units among critically ill patients to improve respiratory and/or cardiovascular efficiency, it is referred to as extracorporeal membrane oxygenation (ECMO) [1]. Currently accepted indications for the use of ECMO are: acute respiratory distress syndrome (ARDS), cardiogenic shock, pulmonary embolism, myocarditis, and in cardiac surgeries (as a bridge for heart transplantation). Recently, the widespread use of ECMO in people after sudden cardiac arrest is also postulated [2, 3].

ECMO can keep the patient alive, substituting the function of the heart and/or lungs for up to several weeks. However, it is essential to note, that ECMO does not cure an inefficient or damaged organ, but gives the time needed for regeneration and recovery. ECMO should only be considered in the exhaustion of other conventional methods, as it is a very invasive technique. Conventional methods include advanced respiratory therapies, drugs improving respiratory and cardiac efficiency, gases affecting the pulmonary circulation, and prone position used to improve the ventilation in patients with ARDS.

In fact, the implementation criteria illustrate how severe the patient’s condition must be in order to start this support. The basic one is meeting the criteria for the Berlin Definition of severe ARDS [4] and at least one of the following: (a) PaO2 / FiO2 < 80 for at least 3 hours despite VT 6 ml/kg with PEEP ≥ 5 cm H2O and the use of alveolar recruitment; (b) pH <7.25 for at least 3 hours [5]. Chest radiographies of patients with severe ARDS often reveal diffuse ground glass opacities that result from partial loss of pulmonary alveolation (Fig. 1).

This review focuses primarily on ECMO – one modality of ECLS. It concerns the history of development, the types of ECMO, clinical indications, contraindications, clinical complications, predictive scales and treatment outcomes.

HISTORY OF ECMO

The originator and first doctor operating with the use of ECMO prototype was Dr. John Gibbon. His idea was to create a device that would take deoxygenated blood from the body, oxygenate it, and return it to the body. In 1934, together with his wife, he began work on creating such a device. Initially, it was used for cat operations and because they ended successfully, 16 years later, he received support and started to build a more advanced machine. In 1953, he performed his first successful surgery with the use of extracorporeal circulation. The patient was an 18-year-old woman with congenital heart defects [6]. A few years later, the first prototype for bypass therapy was developed [7]. In the 1970s several cases were reported showing successful use of ECMO. In 1972 by Hill et al. for the treatment of ARDS with venoarterial ECMO and in 1977 by Barlett et al. for the treatment of cardiopulmonary failure [8-10]. In this decade, the use of ECMO began to increase significantly and further studies were conducted in order to use it not only in adults but also in neonates and children.

WHAT IS ECMO?

ECMO is a technique of extracorporeal support that involves draining deoxygenated blood from the venous system, pumping it through an oxygenator, and reinfusing warm, oxygenated blood to the patient [11]. The dimensions of ECMO devices have been significantly reduced over the last years that they are now smaller than devices for renal replacement therapy.

The first component of the ECMO circuit is a venous cannula through which blood leaves the body. Then the blood goes to the pump, which gives the adequate pressure in the circulatory system. After passing through the pump, blood runs to the oxygenator, which acts as the lungs. The oxygenator is a device made of tiny tubes between which blood flows. The wall of the tubes is a semipermeable membrane through which oxygen and carbon dioxide can penetrate. Inside the tubes there is a space filled with gases, the concentration of which can be changed depending on the patient’s condition. In modern oxygenators it is also possible to change the temperature of the patient’s body thanks to built-in thermoregulators. The drains connect all ECMO elements into one closed system. The patient’s body is connected to ECMO through cannulas. Blood leaves the body through the venous cannula and returns to it via the arterial cannula or the venous cannula. The type of return cannula determines the type of ECMO [12, 13].

ECMO TYPES

There are two basic types of ECMO: venoarterial ECMO (VA ECMO) and venovenous ECMO (VV ECMO), however the combination of both types is also sometimes used. Schemes of both types of ECMO are shown in Fig. 2 and Fig. 3.

VA ECMO can be carried out using cannulas located peripherally or centrally. In the case of peripheral cannulation, blood is drained from a large vein (femoral vein or jugular vein) and returned to the aorta via access to the axillary, carotid or femoral artery. With central cannulation, blood is drained directly from the right atrium and reinfused to the ascending aorta [14]. It can also be used as a bridge for implantation of a device or heart transplantation. Pagani et al. reported that patients with ECMO as a bridge to implantable left ventricular assist device had a higher survival rate compared to patients without ECMO support [15].

The operating principle of the VV ECMO is similar to the one above, with the difference that oxygen-rich blood returns through the venous circulation (generally to the femoral or internal jugular vein) [16]. In the context of functions, extracorporeal carbon dioxide removal (ECCO2R) is similar to VV ECMO, however ECCO2R only removes carbon dioxide without oxygenation of blood [17].

WHEN TO USE ECMO SUPPORT?

Indications for ECMO support are cardiac and/or respiratory failure where despite the use of respiratory therapy and high oxygen concentrations, persistent hypoxemia and hypercapnia pose a threat to further deterioration of the patient’s condition, with the possibility of death [5].

It is essential that ECMO should be considered only in cases where the cause responsible for respiratory and/or cardiac failure is potentially reversible [18]. Currently, most cases requiring ECMO support are for patients with cardiac failure and this population continues to rise compared to respiratory failure. In 2018, cardiac indications accounted for 44,5% of all cases (4636 out of 10 423 cases), respiratory indications were 39% (4068 out of 10 423 cases) and extracorporeal cardiopulmonary resuscitation (ECPR) was 16,5% (1719 out of 10 423 cases) (Fig. 4) [18]. ECPR might be a life-saving method in patients with cardiac rupture, in-hospital cardiac arrest or out-of-hospital cardiac arrest [19, 20].

VV ECMO

VV ECMO provides only gas exchange without cardiac support. According to the Extracorporeal Life Support Organization (ELSO) Guidelines for Adult Respiratory Failure [21], the indications are listed below:

In hypoxic respiratory failure due to any cause (primary or secondary) ECLS should be considered when the risk of mortality is 50% or greater, and is indicated when the risk of mortality is 80% or greater;

50% mortality risk is associated with a PaO2/FiO2 < 150 on FiO2 > 90% and/or Murray score 2-3, AOI score 60, or APSS score;

80% mortality risk is associated with a PaO2/FiO2 < 100 on FiO2 > 90% and/or Murray score 3-4, AOI > 80, APSS 8 despite optimal care for 6 hours or less; the best outcome in ECMO for adult respiratory failure occurs when ECMO is instituted early after onset (1-2 days);

CO2 retention on invasive mechanical ventilation despite high plateau pressure (>30 cm H2O);

Severe air leak syndromes;

Need for intubation in a patient on lung transplant list;

Immediate cardiac or respiratory collapse – pulmonary embolism (PE), blocked airway, unresponsive to optimal care.

The Polish recommendations for the use of VV ECMO have been published by venovenous ECMO Expert Panel in Anaesthesiology Intensive Therapy in 2017 [5].

Certain causes of respiratory failure typically have a short acute phase and are associated with good recovery of pulmonary function. Therefore, the probability of a good response to ECMO therapy is high. Examples of these diseases are aspiration pneumonitis, asthma, near drowning, and granulomatosis with polyangiitis [22].

In the vast majority of cases, respiratory causes for the implementation of ECMO in the adult population between 2014 and 2018 have not been accurately classified in the ELSO report and are collectively described as “other” (7 203 cases; 58%). Among the classified causes, the most frequent are: ARDS (1 927 cases; 15%), acute respiratory failure (1 504 cases; 12%) and bacterial pneumonia (960 cases; 8%) [18].

VA ECMO

Indications for cardiac failure are not as well defined as for respiratory failure. Cardiac indications for ECMO include failure to wean from cardiopulmonary bypass, life-threatening heart failure secondary to myocardial infarction or fulminant myocarditis, and as an adjuvant to conventional cardiopulmonary resuscitation [22].

The following indications are also relevant: support after cardiac surgery or cardiac transplant, acute myocarditis, myocardial infarction, non-ischaemic cardiogenic shock, cardiomyopathy, drug overdose, short-term bridge for heart transplantation or ventricular assist device insertion, support for cardiac catheterisation procedures in high risk patients, catecholamine crisis and circulatory collapse in pheochromocytoma [14, 16].

As in the case of respiratory causes, most of the cardiac causes for the implementation of ECMO in the adult population between 2014 and 2018 have not been accurately classified in the ELSO report and are collectively described as “other” (8 387 cases; 64%). Among the classified causes, the most common cause was cardiogenic shock (3 753 cases; 29%) [18].

CONTRAINDICATIONS TO ECMO SUPPORT

With the introduction of ECMO therapy, it has raised questions of the ethical nature regarding the exact standards of use.

Contraindications for respiratory and cardiac patients are the same. The benefits and risks of such an invasive method should be considered. Absolute contraindications are severe systemic disease, use of immunosuppressants, intracranial bleeding and other absolute contraindications to anticoagulation. ECMO therapy cannot be used if the respiratory or cardiac disease process is irreversible. In addition, age above 65 is also a reason for disqualification for ECMO support [5, 21].

MANAGEMENT OF ECMO

Treatment with ECMO support should be used with the close cooperation of anesthesiologists and cardiac surgeons with intensive care nurses and perfusionists [5, 23]. After cannulation and obtaining the appropriate range of anticoagulation, ECMO is commenced by unclamping the circuit and slowly increasing flows to the target range [24].

The basic parameters that need to be monitored during ECMO treatment are [5]:

pulse oximetry;

acid-base balance of arterial blood (at least every 3 hours);

invasive blood pressure measurement;

parameters of renal function: creatinine, urea;

ventilation parameters including ventilatory threshold (VT), respiratory rate (f), fraction of inspired oxygen (FiO2), peak inspiratory pressure (PIP), static compliance, positive end-expiratory pressure (PEEP) – at least twice daily;

lactate concentration;

activated clotting time (ACT) or activated partial thromboplastin time (APTT) – no less than every 6 hours; heparin is a standard anticoagulant;

International Normalized Ratio (INR), partial thromboplastin time (PTT), D-dimers, fibrinogen concentration, antithrombin concentration, number of platelets – once a day;

chest X-ray – no less than every 3 days, and

parameters related to the operation of the device should be recorded every hour.

ECMO therapy is interrupted in the following cases [5]: extensive ischemic focus in the central nervous system, massive intracranial bleeding, diagnosis during treatment of another progressive disease preventing the return of respiratory function, and no ability to improve the function of the respiratory system despite long-term therapy or brain death.

COMPLICATIONS

Treatment outcomes are also linked to therapeutic complications that may occur during the course of ECMO. The most common complications are bleeding (29.3% V-V, 42.9% V-A), requiring transfusion of large amounts of blood products. The bleeding may occur from places where cannulas are inserted and from postoperative wounds. There are frequent internal bleeds to the lungs, digestive tract, mediastinum and abdominal cavity. However, the most dangerous is the bleeding to the central nervous system [25−27].

Infections are another very important complication. Most often they relate to the lower respiratory tract, blood and urinary tract infections. Infections increase the risk of death by 38-63%. They also prolong the stay in the intensive care unit and duration of ECMO therapy. The main causative pathogen is coagulase-negative staphylococci [28]. VA EMCO may result in hypoxia of the upper half of the body. Hypoxemia or electrolyte imbalances sometimes are the reason for arrhythmias. It should also be remembered that there is a risk of air embolism caused by a pump defect or cavitation [14]. In addition, there may be ischemia of the lower limb leading to amputation, the need for renal replacement therapy or neurological complications [25].

PREDICTIVE SCALES

To reduce the probability of severe and life-threatening complications in patients, various predictive scales have been developed. Based on specific parameters, they help to assess whether the use of ECMO will result in a significant improvement in outcomes. The most common predictive scales used for VV ECMO are ECMOnet score, PRESERVE score, RESP score and PRESERT-Score [21]. All predictive models were developed retrospectively, without the participation of a control group. The research groups were small and varied. Therefore, they should not be taken as a determinant in deciding whether a patient qualifies for ECMO therapy. Predictive scales should be used to assess the effects of treatment and risk of death. It has been proved that scales such as SAPS II, APACHE and SOFA, used daily in intensive care units, are not useful in the assessment of patients with VA ECMO to assess the severity of the patient’s condition [29]. Therefore, there is a need to create a risk assessment model for this therapy. The most important scale is the SAVE score, which is based, like the RESP score, on the ELSO Registry [21].

CURRENT DATA ON THE FREQUENCY OF USE AND CLINICAL TRIALS

According to the data from the international Extracorporeal Life Support Organization (ELSO) Registry Report, 112 231 patients received ECLS globally (up to January 2019). The majority of patients 40,3% were adults, 37,2% were neonates and 22,5% were paediatric [18]. The most commonly used type of ECLS was respiratory support 54% followed by cardiac support 35% and ECPR 11%.

In the following years, there was a significant increase in the use of ECMO support in adults due to improved equipment and growth of ECMO teams [30]. The global pandemic of the novel influenza A virus was also an important factor because of a higher incidence of ARDS [31, 32]. With the development and spreading of more detailed knowledge about ECMO, within several years in many countries the use of this therapy has increased several times. The number of ECMO centers and ECMO cases in the following years is shown in Fig. 5.

Multi-center randomized CESAR trial published in the Lancet in 2009 compared the use of conventional mechanical ventilation vs ECMO therapy as a treatment for acute respiratory failure. Patients were divided into two groups, the first was ventilated by conventional methods, the second was treated with ECMO therapy. In both cases, data about ICU stay, duration of hospitalization, ventilation parameters, prone position, administration of nitric oxide and steroids were collected. The results of the study showed that in the ECMO group, 6-month survival with good quality of life was higher (63%) compared to the control group (51%) [33].

The latest EOLIA trial, published in 2018, also examined the effectiveness of ECMO venovenous therapy compared to traditional ventilation methods in ARDS [34]. The main cause of acute respiratory failure was bacterial pneumonia (48%) and viral pneumonia (18%). 78% of patients had sepsis or septic shock. The primary end point of the study was mortality at 60 days. In this trial, 149 patients were randomized: 124 in the ECMO group and 125 in the control group. 35 patients in the control group crossed over to the ECMO group because of refractory hypoxemia. In both groups serious complications such as pneumothorax, pneumonia caused by ventilation and severe bleeding occurred. However, patients in the ECMO group had a significantly higher risk of thrombocytopenia and bleeding due to transfusion of packed red blood cells. The most important reasons for the death of patients in both groups were respiratory failure, multi-organ failure and septic shock. Demographic data, severity of ARDS and the center in which patients were treated did not affect mortality. In patients with very severe ARDS who received ECMO therapy early, there was no reduction in mortality within 60 days compared to the conventional mechanical ventilation group. In the ECMO group there was a lower frequency of therapy failure compared to the control group [34].

CONCLUSIONS

Extracorporeal membrane oxygenation (ECMO) is a method for treating severe but potentially reversible states of cardiac and/or respiratory failure.

Therapy with the use of ECMO does not cure the pathogenic cause of the disease, but it gives the time necessary for the regeneration of inefficient organs. In addition, ECMO reduces or eliminates the risk of lung damage associated with mechanical ventilation in patients with severe ARDS (acute respiratory distress syndrome). ECMO is a very invasive therapy, therefore it should only be used in patients with extremely severe respiratory failure, who failed to respond to conventional therapies.

Initiation of ECMO should be performed in centers with the appropriate experience and requires an organized, coordinated effort.

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ORCID:

Krystian Ślusarz – 0000-0002-7829-530X

Paulina Kurdyś – 0000-0001-8154-404X

Paul Armatowicz – 0000-0001-5793-0311

Piotr Knapik – 0000-0002-1058-1502

Ewa Trejnowska – 0000-0003-0279-4935

Conflict of interest:

All authors declare no conflict of interest.

Corresponding author

Krystian Ślusarz

Students’ Scientific Society,

Department of Cardiac Anesthesia and Intensive Therapy,

Silesian Centre For Heart Diseases,

Medical University Of Silesia, Zabrze, Poland

e-mail: slusarzkrystian@gmail.com

Received: 14.05.2019

Accepted: 16.08.2019

Fig. 1. Chest X-ray in a patient with severe ARDS – ground glass opacities. ECMO cannulas are inserted (black arrows) [authors’ material].

Fig. 2. Scheme of the VA ECMO circuit [Modified with the permission of www.ecmo.pl].

Fig. 3. Scheme of the VV ECMO circuit [Modified with the permission of www.ecmo.pl].

Fig. 4. The use of ECMO support in 2018. Based on ECLS Registry Report [18].