ECMO as circulatory support is indicated in situations of refractory cardiogenic shock with the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1) scale and always as a bridge to a goal: recovery; heart transplant; until a therapeutic decision has been made or until a different long-term assist device has been implemented.

The use of ECMO as circulatory support should be part of a therapeutic strategy and have a clear-cut target in mind. As a bridge to recovery in potentially reversible diseases, as a bridge to heart transplant or other types of long-term or definitive assist device, or until a decision is made on whether more tests are needed before considering the patient eligible for the heart transplant.4–6

The refractoriness of the state of shock is defined as the persistence of hypotension and/or tissue hypoperfusion due to low cardiac output (<2.2l/min/m2) yet despite optimal volemia, the use of inotropic and/or vasoactive drugs at high doses. High doses of these drugs are associated with high mortality rates and, after the initiation of ECMO, they can be titrated or withdrawn. The following ones are considered elevated doses of inotropic or vasoactive drugs: dopamine >10μg/kg/min, noradrenaline >0.5μg/kg/min, adrenaline >0.1μg/kg/min, dobutamine >10μg/kg/min, milrinone >0.5μg/kg/min.7

Hypoperfusion is defined as oliguria (<30ml/h or <0.5ml/kg/h); cold limbs; mental disorders and/or high levels of serum lactate (>2.0mmol/l).

The cardiac output should be measured using calibrated and reliable methods (a catheter through the pulmonary artery or transpulmonary thermodilution) and/or through echocardiography.8

The indications for circulatory ECMO should be well-defined to avoid implants in pre-mortem situations, in futile cases or patients in whom this technique is contraindicated.

The ECMO technique is not a technique to be used as a last therapeutical resort in pre-mortem situations or terminally ill patients, since in these cases the mortality rate is 100%. To avoid inadequate uses of this technique, we should know what indications and contraindications the ECMO technique has2,9 (Tables 1 and 2).

ECMO should not be the first-line therapy for the management of cardiogenic shock, but it has been confirmed that if implanted early it improves the results.

Before the ECMO, the optimal medical and/or surgical therapy should have already been used, since the ECMO technique is no stranger to complications.11–13

It is hard to tell what the optimal time to implant the ECMO really is, but as a rule of thumb we can say that it should happen before an established multiple organ failure. This means that an accurate monitoring and follow-up of certain clinical and analytical variables should be essential for its early implementation.14

The SAVE scale (www.save-score.com) recommended by the ELSO assigns scores to different parameters to predict mortality once the ECMO has been implanted. It may be useful in the decision-making process.15

The pre-ECMO parameters associated with poor prognosis are:

• •

  Weight (<65kg or >90kg).

• •

  Age (>53 years, above all, patients over 63).

• •

  Hemodynamic: pulse pressure (≤20mmHg), diastolic blood pressure (>40mmHg), cardiac arrest.

• •

  Respiratory: peak inspiratory pressure (>20mmHg), mechanical ventilation (with more h less survival).

• •

  Renal: acute renal failure, chronic renal failure, HCO3 (<15mmol/l).

• •

  Other organ failure: central nervous system dysfunction, renal failure, liver failure.

ECMO as circulatory support should be implanted in tertiary referral centers to secure the results. These should be centers experienced in the use of this technique and other medical-surgical and laboratory specialties to handle whatever complications may occur following the use of circulatory support systems or cardiogenic shock.

The ECMO consists of an extracorporeal mechanical circulation that is no stranger to complications, meaning that the personnel in charge needs to be fully experienced in the management of the patients who undergo this technique.16 Knowledge, training and experience are required at all time: to establish the indication; the optimal time to start the therapy; choose the right optimal cannulation17; the daily management of the technique; the prevention and early detection of complications and the most appropriate resolution. ECMO systems require one multidisciplinary team from different medical specialties led by specialists in the management of critically ill patients; one trained nursing team; techniques and services available at the centers 24/7 all year round. This team should also be in charge for the continuing medical education (CME) programs of the personnel, the protocols, the checklists and a registry of all the cases with further review and analysis.

Once implanted, one individualized and multidisciplinary therapeutical strategy should be used with every patient: how and when should ECMO be disconnected when the myocardial function has been recovered; indicate whether the patient should be in the heart transplant waiting list or contraindicate it on a temporal or definitive basis; indicate the need for a long-term assist system (as a bridge both to recovery and the transplant) or a definitive assist device when the transplant is contraindicated. Choosing the best option for every patient requires training and experience from the entire team. This is something we have learned from the large number of cases where ECMO systems have been used.

The ELSO recommends that ECMO centers should be tertiary referral centers with a minimum amount of annual cases so that the technique can be considered coste-effective.16 The number of ECMO/center/year has not been determined precisely, but according to the latest expert recommendations it should be over thirty procedures (including veno-venous ECMOs, but with a significant amount of veno-arterial ECMOs).18,19

The transfers from the ECMO-free center to the tertiary referral center will occur after evaluating the patient's clinical stability on whether to implant the ECMO prior to the transfer. The transfers from ECMO-capable tertiary referral centers to heart transplant centers will occur with transplant-eligible patients only and after clinical stabilization with circulatory support systems.

Inter-hospital transfer programs are necessary to guarantee the accessibility of this technique to all individuals and provide optimal therapy regardless of the treating hospital. The possibility of accessing these ECMO programs should be seen as a guarantee of the principle of equality, however, given the characteristics of this technique, it needs to be conducted in a specialized center and with a series of requirements and services to improve the patients’ prognosis.20

If a patient in cardiogenic shock is ECMO-eligible and there are no contraindications, he should be transferred early to his tertiary referral center to undergo this technique.21 Then the clinical and hemodynamic state of the patient should be evaluated to decide whether he can be transferred without any assist device. Once at the tertiary referral center, he will be re-evaluated before deciding whether to finally implant the ECMO. In the presence of clinical instability, the assist device should be placed beforehand for a safe transfer, which is why the ECMO team will travel with both the equipment and the personnel required to the center where the patient remains hospitalized.

Once the ECMO has been initiated and the patient has been stabilized, he will be transferred to the tertiary referral center to move on with the therapy and other critical care. When it comes to choosing the means of transportation that we will use with patients on ECMO (ground or aerial transportation are the most common ones, sea transportation if necessary) we need to be aware of the availability of out-of-hospital emergency resources; distance; weather conditions; the existence of a heliport at the referring hospital and certain characteristics of the patient such as his height, weight and clinical situation). Once at the target center, the indication will be re-evaluated, and a decision will be made on whether to implant bedside ECMO.

It has been confirmed that ECMO transfers with experienced teams are safe and possible and have minimal complications. Also, survival is similar to the group of patients at the tertiary referral center.22

ECMO-capable centers without a heart transplant program as required by the patient will need to come to terms with the transplant-capable center what is the optimal moment to perform the transfer and proceed to enter the patient in the transplant waiting list.

It is necessary that each region or autonomous community creates a program establishing the flow of circulatory support-eligible patients for ECMO-capable centers and/or transplant centers. Also, there should be consensus on the management of these patients (pre- and post-ECMO) among the different centers involved in this process (local, ECMO centers and ECMO-transplant centers).

Support from healthcare institutions is required here if we want Spain to have mobile ECMO programs available for all individuals, so access to healthcare can be the same for everyone.23

Veno-venous ECMO is one complex high-flow technique that should be considered early in critically ill patients with respiratory failure refractory to other therapies.

VV-ECMO is one extracorporeal system for oxygenation purposes, CO2 purification and to facilitate protective or ultra-protective mechanical ventilation (MV) using two thick venous cannulae22–30 to allow the necessary blood flow. Double lumen cannulae can be used here but their use in the hypoxemic respiratory failure is limited by the flow. These flows go from 3 to 5l/min, but lower flows are needed to purify the CO2 and perform protective or ultra-protective ventilation, and up to 5–7l/min in cases of hypoxemia refractory to other therapies.24 The VV-ECMO can associate multiple complications being hemorrhages the most common of all and reported in up to 60% of the patients (less common and serious with the use of new systems) followed by infections.1,3

To this day, it is considered a “bailout therapy” for the management of refractory respiratory failure and only when other therapies have failed that, by the way, should always include the use of protective MV: tidal volume (TV): 4–8ml/kg of ideal weight; plateau pressure (Pplat) ≤30cmH2O) and at least a change to the decubitus prone (DP) position unless contraindication25 and the use of neuromuscular blockers for at least 48h.26 There should be a predictable recovery of the disease that triggers respiratory failure, or the VV-ECMO should be established as a bridge to lung transplant.

The optimal time to implant ECMO is still controversial and has not been established yet, but we know that implanting it before multiple organ failure improves the pronosis.27

The results from the recently published EOLIA study28 show that the early use of ECMO for the management of severe cases of acute respiratory distress syndrome (ARDS) reduces 60-day mortality, although not significantly compared to conventional approaches that include ECMO as a bailout therapy (35% versus 46%; p=0.09). Both groups were homogeneous when it comes to severity (SOFA 10.8±3.9 ECMO group; 10.6±3.5 in the control group); randomized, on average, after 34h on MV and with a PaO2/FiO2 ratio of 73±30 and 72±24 respectively). However, 28% of the patients from the control group ended up receiving ECMO due to refractory hypoxemia, and 57% of the patients died. This subgroup of more critically ill patients had a lower PaO2/FiO2 ratio, higher lactate levels; greater cardiac damage and pre-ECMO cardiac arrest in 9 cases.

The ELSO indicates ECMO for the management of hypoxemic respiratory failure with a PaO2/FiO2 ratio <100 with FiO2 >0.9 and/or Murray scale scores ≥3, oxygenation index >80 despite the use of optimal therapy for 6 or less hours.29 Other groups establish PaO2/FiO2 ratios <50 with FiO2 1 despite the use of protective MV and, at least, a change to the DP position for 3h.25 In cases of hypercapnic respiratory failure, one PaCO2 ratio >80mmHg or the impossibility to ventilate keeping Pplat >30cmH2O25 or CO2 retention despite Pplat >30cmH2O25 would be other indications proposed by the ELSO.

Once the ECMO support has been initiated, it is recommended to maintain protective or ultra-protective mechanical ventilation (TV 3–4ml/kg; Pplat <25cmH2O).30

The indications and contraindications of ECMO as respiratory support are shown in Table 3 being most of them relative contraindications.

The VV-ECMO is recommended as part of a global management algorithm that must include the use of protective MV and, at least, a change to the decubitus prone position.

The use of VV-ECMO for the management of acute respiratory distress syndrome in adult patients should be considered as a bailout therapy and indicated in each case. The technological advances made on this technique have made it a safer easy-to-use technique and allowed a more liberal use. However, the implantation of the VV-ECMO should happen methodically and in a very organized way according to several organizations. Also, and in the light of the present data, its use should be evaluated in advance because it is a risky procedure and any wrong indications should be prevented.31,32

All studies – published and ongoing include patients with severe ARDS and certain clinical characteristics as shown in Table 4.

Also, patients who have received an adequate protective mechanical ventilation have been included in these studies and recruitment maneuvers have been conducted among patients in the decubitus prone position before implanting the VV-ECMO.34

The potential indications for the VV-ECMO as a bailout therapy include the severe hypoxemic and/or hypercapnic acute respiratory failure with predictable recovery of the lung function.

The VV-ECMO can be used in patients with severe acute respiratory failure in whom mechanical ventilation cannot maintain oxygenation or with an acceptable and maintained CO2 washout (Table 3). This clinical situation can be seen in the ARDS or status asthmaticus.35–37 The VV-ECMO can also be used in patients in whom the effort to maintain an adequate oxygenation has a high risk of ventilator-induced pulmonary lesion. In this case, the use of VV-ECMO leaves the “lung at rest” reducing pressure on the airway and tidal volume.38 Due to the complications associated with this technique and the lack of studies confirming its effectiveness, patients need to be selected with care.

The absolute contraindications are: dying patients with established multiple organ failure; patients with poor shot-term prognosis or serious comorbidities; or advanced neurological disease. The relative contraindications are: mechanical ventilation of seven-day duration with high pressure on the airways; elderly patients; difficulty managing vascular accesses and contraindications for anticoagulation.39 Also, there are scales to measure risk assessment and predict mortality risk in these patients.40,41

It is advisable to transfer these patients to tertiary referral centers or centers where the VV-ECMO is an essential part of the global management of patients with respiratory failure.

The management of patients on ECMO in tertiary referral centers has lower mortality rates,33,42–44 which is why the transfer of ECMO-eligible patients to tertiary referral centers or centers experienced on the use of this technique should be taken into consideration. Transfers to these centers should be conducted following top safety measures and evaluating the possibility of clinical deterioration if the transfer is done with conventional ventilation. In this case, the ECMO transfer should be kept in mind.45

ECMO transfers are always safe as long as they performed by expert medical teams.46–48 The percentage of complications and mortality rates are similar between patients transferred on ECMO support and those in whom the ECMO system was implanted at the ECMO-capable center.49

The criteria for immediate consultation for transfers to tertiary referral center in the management of respiratory failure include: severe hypoxemia with a PaO2/FiO2 ratio <60mmHg or a PaO2/FiO2 ratio <100mmHg and/or PaCO2 >100mmHg for more than 1h after the administration of the optimal therapy and further failure of other therapies.50 Other criteria have been established as well for transfer-eligibility to ECMO-capable centers51: pH <7.2; Murray scale scores >2.5, FiO2 not higher than 0.8 for 8 days and Pplat not higher than 30cmH2O for 7 days.

The ECCO2R systems (CO2purification systems) are low-flow devices capable of purifying CO2effectively. They should have very precise indications such as to facilitate protective ventilation, but there is still no evidence to establish its indications.

ECCO2R systems (CO2 purification systems) are one extracorporeal life support technique with low-flow devices for the purification of PaCO2 effectively. They should have very accurate indications such as to facilitate protective ventilation, but there is still no evidence to establish its indications. The ECCO2R systems are easier devices to use compared to ECMO and they are considered partial respiratory support techniques. Compared to ECMO, these systems require lower blood flows between 250ml/min and 1.5–2l/min, have a smaller membrane area and require systemic anticoagulation.52,53 They can be arteriovenous systems without pump or veno-venous systems, although the actual tendency are veno-venous systems with single double-lumen cannula since they associate fewer vascular complications.54,55 They allow the effective purification of CO2 and do not contribute directly to oxygenation.56 In patients with chronic obstructive pulmonary disease these devices could be used for the management of hypercapnic respiratory failure to avoid invasive mechanical ventilation, facilitate its withdrawal, in unresponsive patients to non-invasive mechanical ventilation and to facilitate ventilation per se,56,57 although they are no stranger to complications.58 Evidence is more limited for the management of ARDS and its use is more oriented toward controlling hypercapnia during the use of protective or ultra-protective MV (TV 3–4ml/kg; Pplat <25cmH2O) for the management of moderate57 and moderate-to-severe ARDS although we are still waiting for the results from experimental clinical trials.59,60

In conclusion, ECCO2R systems are one promising adjuvant therapeutic strategy for the management of patients with severe exacerbations of chronic obstructive pulmonary disease and for the application of protective or ultra-protective mechanical ventilation in patients with ARDS without potentially fatal hypoxemia. However, given the observational methodology of most clinical trials available and the differences seen in both the technical characteristics and performance of the actual devices, the benefit-risk ratio for and against ECCO2R systems in these populations of patients is still controversial.

Normothermal abdominal perfusion with ECMO (NAP-ECMO) should be considered as an in situ preservation technique in donors of abdominal organs in controlled asystole.

The use of normothermal abdominal perfusion with ECMO as a method to preserve donors’ abdominal organs in controlled asystole has been gaining momentum in our country61 following the excellent findings published about international62,63 and national64 experiences alike. Its use is compatible with lung donation where ultrafast surgery with cold perfusion65 is commonly used and, in recent experiences, even with heart preservation and extraction.66 This technique allows us to recover abdominal organs from ischemic damage – especially the liver.67 Also, it reduces the urgency of the surgical procedure and the iatrogenia sometimes caused by ultrafast surgery.68 The logistics associated with the entire process is easier and it allows us to easily assess suspicious or marginal organs, since it facilitates active interventions on the organ preservation environment and gives us the capacity to determine viability and quality markers during maintenance. Also, it allows us to perform biopsies and analyze intraoperative findings (nodules, steatosis, etc.).

If this technology is not available, agreements should be reached with hospitals that have this technology in its mobile version.

In the intensive care setting, the use of the extracorporeal membrane oxygenation has grown exponentially during the last few years following the advances made on ECMO circuits and due to the experience accumulated in special circumstances such as in the H1N1 pandemics.33,69 It is still a complex procedure that should be conducted in tertiary referral centers according to the recommendations made by the Extracorporeal Life Support Organization.16

On the other hand, according to data from the National Transplant Organization, to this day, our country has 91 hospitals with donation programs in controlled asystole.70 Obviously, very few of these hospitals have ECMO programs available in their intensive care units or for normothermal abdominal perfusion purposes in controlled asystole donors.

The experience accumulated from inter-hospital transfers of mobile support teams for abdominal organ preservation in Andalucía71 and the creation of a mobile team from the Madrid Healthcare Administration72 confirms the benefits of having transplant coordinator intensivists experienced in the management of ECMO systems and controlled asystole donation and the utility of promoting inter-hospital alliances to increase the donation potential of our ICUs.

Before initiating ECMO after the donor's death and while the procedure is being performed, the perfect closure of the thoracic aorta needs to be secured.

The possibility of recovering the donor's pulse after death has been declared when normothermal abdominal perfusion with ECMO is being used can be disturbing from the ethical point of view.73 This situation can only occur when the closure of the thoracic aorta has not been secured.

The adequate inflation of the balloon and the correct placing of the aortic occlusion catheter is essential not only to avoid any hypothetical pulse recoveries but also to secure the adequate perfusion of the organs and restrict preservation to the abdominal territory (Fig. 1).74,75

Figure 1.

Scheme suggested to confirm the correct position of the balloon for aortic occlusion purposes.

(0.2MB).

The following steps need to be observed here.76

• •

  Before limiting life support therapy, one left radial artery should be catheterized together with the arterial and venous cannulae and the aortic occlusion catheter.

• •

  Fill the occlusion balloon catheter and keep it for a few seconds while monitoring the radial and femoral pressures. The femoral pulse wave should disappear, and the radial pulse wave should be present. The filling volume should be written down as the minimal volume of aortic occlusion to be used during normothermal abdominal perfusion.

• •

  Afterwards, check the right position of the occlusion catheter at the level of thoracic aorta and fix it adequately.

• •

  After death has been declared, fill up the occlusion balloon and initiate ECMO.

• •

  During normothermal abdominal perfusion both the radial and the femoral pressures should be monitored. The femoral line should measure the nonpulsatile pressure achieved with the ECMO flow and the radial line should focus on the post-cardiac arrest baseline values.

• •

  If pressure on the radial artery goes up parallel to the femoral pressure increase or in the presence of electrical activity, ECMO should be immediately terminated, the right position of the occlusion catheter checked and normothermal abdominal perfusion resumed after a 5-min observation period.

Hypovolemia, anemia, acidosis or any other alteration of the internal environment and preservation of the donor as we would do with any critically ill patient.

The following preservation parameters should be observed:

• 1.

  Circuit temperature: 37°C.

• 2.

  pH: 7.35–7.45.

• 3.

  PaO2: 100–150mmHg.

• 4.

  Hematocrit levels >20%.

• 5.

  Sodium, potassium, glucose, lactate within lab normal range.77

It is advisable to use charts to register all these variables tested and make the right corrections when it comes to repositioning volume, blood, bicarbonate and keeping normalcy in other parameters such as sodium, potassium, glucose, or lactate to have as much information as possible on the quality of preservation.74

NAP-ECMO should be kept as long as necessary to allow the recovery of the liver after ischemic stress and an adequate viability assessment should be conducted prior to the transplant.

How long should the preservation of normothermal recirculation be is a fundamental though still controversial issue. There is not such thing as an established useful minimal time to achieve the desired cell recovery and the question on for how long should donors be preserved has been decided empirically by different groups. Very short times would lead to incomplete cell recovery after ischemic stress and to a possible inadequate assessment of the graft. On the contrary, very long times would lead to destabilize the system and prolonged recirculation of harmful elements.74

The average time recorded according to national and international experiences is close to 90–120min.77