Keywords

Adult, Cardiac assist, Challenges, Circulatory support, ECMO, Extracorporeal life support, H1N1, Reflection of ELSO registry, Stakeholders

 

Authors

  1. Kurniawati, Eva R. MSc
  2. Weerwind, Patrick W. PhD

Abstract

Extracorporeal life support (ECLS) is an external medical device to treat critically ill patients with cardiovascular and respiratory failure. In a nutshell, ECLS is only a "bridging" mechanism that provides life support while the heart and/or the lungs is recovering either by therapeutic medical interventions, transplantation, or spontaneously. Extracorporeal life support has been developed since 1950s, and many studies were conducted to improve ECLS techniques, but unfortunately, the survival rate was not improved. Because of Dr Bartlett's success in using ECLS to treat neonates with severe respiratory distress in 1975, ECLS is made as a standard lifesaving therapy for neonates with severe respiratory distress. However, its use for adult patients remains debatable. The objectives of this study are to outline and provide a general overview of the use of ECLS especially for adult patients for the past 10 years and to elaborate on the challenges encountered by each stakeholder involved in ECLS. The data used for this study were extracted from the ELSO Registry Report of January 2018. Results of this study revealed that the number of ECLS centers and the use of ECLS are increasing over the year for the past decade. There was also a shift of the patient's age category from neonatal to adult patients. However, the survival rates for adult patients are relatively low especially for cardiac and extracorporeal cardiopulmonary resuscitation cases. To date, the complications are still the major challenge of ECLS. Other challenges encountered by the stakeholders in ECLS are the limited amount of well-trained and experienced ECLS teams and centers, the limited government expenditure on health, and the lack of improvement and development of ECLS techniques and devices. Further studies are needed to evaluate the value of ECLS for adult patients.

 

Article Content

Extracorporeal life support (ECLS), also known as extracorporeal membrane oxygenation, is an external medical device to treat critically ill patients with cardiovascular and/or respiratory failure.1 Extracorporeal life support, with different configurations (veno-venous [VV] or veno-arterial [VA]), is used to manage 3 obstinate medical conditions, namely, respiratory failure,2 cardiac failure,3 and refractory cardiac arrest when conventional cardiopulmonary resuscitation failed.4 The key concept of ECLS is its hemodynamic support while oxygenated blood and carbon dioxide removal are provided via an artificial lung also referred to as a membrane oxygenator.5 Extracorporeal life support is only a "bridging" mechanism that provides life support while the heart and/or the lungs is recovering either by therapeutic medical interventions, transplantation, or spontaneously.6

 

The history of ECLS started in the 1950s when John Gibbon7 developed a device to transport the oxygenated blood through a membrane oxygenator to prolong cardiopulmonary bypass during cardiac surgery. Compared with a conventional cardiopulmonary bypass circuit, ECLS is a less complicated and a far more feasible option to treat cardiovascular and respiratory failure outside the operating room.8 During the 1960s and 1970s, there were vast developments to improve ECLS techniques, but unfortunately, there was still no improvement of the survival rate.9 In 1972, Hill and associates10 successfully saved an adult patient with acute respiratory distress syndrome by using prolonged extracorporeal circulation for the first time. This success was followed by the successful use of ECLS to treat an adult patient with a cardiogenic shock in 1973.11 In 1975, Bartlett and associates12 made a remarkable achievement in the ECLS history when they used ECLS to treat neonates with severe respiratory distress. These successful cases led National Institutes of Health to sponsor a prospective, randomized, multicenter study of the use of ECLS to manage adult patients with acute respiratory distress syndrome between 1975 and 1978. This study, however, showed that 90% of all patients in both the conventional treatment and ECLS groups died.13 In contrast, since Bartlett's success in 1975, the use of ECLS to manage neonatal respiratory failure has grown steadily with an overall survival rate of 84% compared with conventional ventilator management.14 Since then, ECLS is considered as a standard lifesaving therapy for neonates with severe respiratory distress,13 whereas the use of ECLS for adult patients remains debatable because of the outcome and its efficacy in adult patients.1,15-19

 

The purpose of this study is to outline and provide a general overview of the use of ECLS especially for adult patients for the past 10 years and to elaborate on the challenges encountered by each stakeholder involved in ECLS. To do so, this study uses the data primarily from the Extracorporeal Life Support Organization (ELSO) registry report international summary of January 2018.15 The ELSO Registry provides a broad, international overview of current ECLS use and outcomes.

 

REFLECTION OF ELSO REGISTRY FROM 2007 TO 2017

Data from the ELSO international registry of January 2018 showed that there was a steady increase in the number of patients and ECLS centers every year since 2007 (Figure 1). This increase is offset by the growing number of patients, which rose from 2564 patients in 2007 to 9330 patients in 2017. Consequently, the ratio of patients per ECLS centers per year has continuously risen for the past decade and reached its peak in 2016 with 28 (Figure 1). This means that, on average, every ECLS center treated 28 patients with ECLS in 2016. This trend was likely initiated by the global pandemic of H1N1 influenza in 2009. During this outbreak, ECLS was used when the patients failed to respond to conventional treatment, and 79% of the patients recovered and survived.20 In addition, an improvement of ECLS technology in 2008 made the new ECLS device much safer and simpler. This further helped boost the use of ECLS during the H1N1 global pandemic in the later year.21 Ever since, there is a significant growth of ECLS use especially in adult patients with respiratory and/or cardiac failure and as a resuscitation mode (extracorporeal cardiopulmonary resuscitation [ECPR]).15

  
Figure 1 - Click to enlarge in new windowFigure 1. The number of reported extracorporeal life support (ECLS) centers and cases worldwide from 2007 to 2017.

Emerging Practice of ECLS

In the last 10 years, there has been a vast shift in the patient population composition of ECLS use (Figure 2). In 2007, neonatal patients accounted for most of the total ECLS cases (51.4%), whereas pediatric and adult patients held 32.3% and 16.3% of the total ECLS cases, respectively. These numbers began to make a substantial shift in 2010 when the composition of adult patients almost doubled to 30.8% and the neonatal patient population decreased to 38.1%. This shift was slow but steady, and by 2017, adult patients dominated the total ECLS cases with 70.4%, whereas neonatal patients had dropped to 12.6% (Figure 2). Moreover, the development of less invasive medication and techniques such as prone position, high-frequency ventilation, surfactant replacement, and inhaled nitric oxide therapy made ECLS a less attractive option for cardiovascular and pulmonary failure cases for neonatal patients.22-24

  
Figure 2 - Click to enlarge in new windowFigure 2. The number of extracorporeal life support cases based on patient's age population (neonate, infant, and adult) in percentage (%) from 2007 to 2017.

Total cumulative adult ECLS cases in 2017 were 35 617, which consists of 15 677 respiratory cases (44.0%), 15 195 cardiac cases (42.7%), and 4745 ECPR cases (13.3%).15 Moreover, a close examination of the ECLS numbers per year shows that the adult population was dominated by cardiac cases in 2007 (42.3%) and 2008 (48.4%). Subsequently, the adult respiratory ECLS caseload increased (58.2%) in 2009 because of the global H1N1 pandemic. The respiratory cases were still dominating in 2010 (50.8%) and 2011 (47.8%). Since then, respiratory and cardiac cases took a turn in dominating the total adult ECLS caseload (Figure 3).

  
Figure 3 - Click to enlarge in new windowFigure 3. The number of extracorporeal life support case category for adult patients in percentage (%) from 2007 to 2017. ECPR, extracorporeal cardiopulmonary resuscitation.

Notably, the survival rate of respiratory ECLS patients is the highest compared with cardiac and ECPR cases. In 2017, the numbers were 59%, 41%, and 29%,15 respectively. Despite the increase in ECLS cases and centers in the last decade, there has been no significant difference in the survival rates. In general, the survival rate of ECLS patients depends on the patient's age,25 preexisting comorbidities,26,27 reversibility of underlying disease,28 and timely ECLS initiation.29

 

Respiratory Support

Veno-venous ECLS is considered to be a standard therapy for patients with acute respiratory failure,2,16 for patients with primary graft failure after lung transplantation,30 as a "bridge" for patients at the end stage of lung disease to lung transplantation,31 and also to provide patients' cardiopulmonary system a time to "rest" and recover.16

 

In 2017, the total adult respiratory caseload holds 38.6% of the total adult ECLS cases. This number was slightly increasing from 37.1% in 2007. Figure 4 shows that adult respiratory cases were steady until 2009 when it showed a significant increase from 200 cases in 2008 to 495 cases (147.5%) in 2009 during the global H1N1 influenza pandemic during that period. Ever since, the number of adult respiratory cases is still increasing, averaging 37.0% every year. The survival rate of ECLS with respiratory cases was 51% in 2007 and improved to 61% in 2017. This resulting, the average of the survival rate of ECLS with respiratory cases for the past decade was 58%. In the meantime, the most frequent adult respiratory ECLS complications for the past decade were the need for cardiovascular inotropes, kidney replacement therapy, and culture-proven infection.15

  
Figure 4 - Click to enlarge in new windowFigure 4. Annual adult extracorporeal life support respiratory cases from 2007 to 2017.

Cardiac Support

Extracorporeal life support for cardiac support is known as VA ECLS. Veno-arterial ECLS can be applied for cases such as supporting the circulation before or during percutaneous coronary intervention for patients with shock secondary to acute myocardial infarction without mechanical complications,32 patients with postcardiotomy cardiogenic shock,33 patients who failed to wean from cardiopulmonary bypass,33,34 bridging to a ventricular assist device or a heart transplant for patients with end-stage cardiac failure and severe cardiogenic shock,35 and also supplying circulatory support for patients with primary graft dysfunction after heart transplantation.36 Adult cardiac cases have been rising since the 90s. The most significant jump was during the H1N1 global pandemic in 2009 to 2010 when the number was almost doubled from 270 cases in 2009 to 415 cases in 2010. Since then, the numbers are constantly upsurging (Figure 5). Albeit, the biggest leap of the registered cardiac adult caseload was from 601 cases in 2011 to 1082 cases in 2012. The survival rate of cardiac ECLS cases for adult patients was 39% in 2007 and increased to 42% in 2017. In fact, the average survival rate of ECLS cardiac cases for the last decade was 42%. Complications such as the need for cardiovascular inotropes and kidney replacement therapy were also common for adult cardiac ECLS cases for the past 10 years. In addition, bleeding also seemed to be one of the most frequent complications for adult cardiac ECLS cases during the same timeline.15

  
Figure 5 - Click to enlarge in new windowFigure 5. Annual adult extracorporeal life support cardiac cases from 2007 to 2017.

Extracorporeal Cardiopulmonary Resuscitation

Extracorporeal cardiopulmonary resuscitation has not been recommended as standard cardiac arrest management, but it is advisable for patients with a potentially reversible cause.37 In general, adult ECPR cases shared the same trend as other adult ECLS cases within the past decade with the biggest rise in 2013 (84.4%), as depicted in Figure 6. However, the average survival rate of ECPR for the past decade is the lowest (28%) compared with respiratory (58%) and cardiac (42%) cases. Nevertheless, this number is still favorable compared with conventional cardiopulmonary resuscitation, which has a survival rate of 12% to 24.8%.38 Apart from the most prevailing complications for adult ECLS patients during the last decade such as the need for cardiovascular inotropes and kidney replacement therapy, other common complications for adult ECPR cases were acidosis, hyperglycemia, and cardiac arrhythmia.15 Following factors such as correctable arrhythmic cause of cardiac arrest, age, and severity of organ dysfunction should be considered carefully to increase the chance of a successful ECPR intervention.39

  
Figure 6 - Click to enlarge in new windowFigure 6. Annual adult extracorporeal life support extracorporeal cardiopulmonary resuscitation (ECPR) cases from 2007 to 2017.

THE CHALLENGES

The challenges of ECLS are to be divided based on each stakeholder. Stakeholder in this context can be defined as people or groups who have different perspectives and interests in health care decisions and who will be affected by it.40 Each stakeholder has different goals, but the main focus is improving the quality of life for patients.41 The main stakeholders of ECLS and their challenges are discussed hereinafter.

 

Patients

The patient's role is not only to fund the health care system but also, most importantly, to be the end user of health care services.42 It should be noted that patients are not the only stakeholders funding the health care system. The government and insurance companies do so as well.41 As the end user of the health care system, patients get the firsthand experience from the services provided by health care providers. The biggest challenges of ECLS are its potential complications such as renal failure, bacterial pneumonia, bleeding, oxygenator dysfunction, sepsis, hemolysis, liver dysfunction, leg ischemia, venous thrombosis, central nervous system complications, gastrointestinal bleeding, aspiration pneumonia, and disseminated intravascular coagulation.43 Furthermore, bleeding is known to be the most common complication for adult ECLS patients (30%-50%).44,45 In general, patients treated with VA ECLS are prone to have more complications than VV ECLS patients. Furthermore, apart from neurological complications, adult patients are also prone to have more complications than children.34 These complications can cause morbidity and mortality, and even if the patients survive, it might result in a disability and lower their quality of life.46 Hence, patients who are considered suitable for ECLS are those with a high risk of dying even when treated with an excellent conventional treatment.47 Nonetheless, a study by Mirabel et al48 in 2011 found that ECLS survivors have higher risks of experiencing severe anxiety, depression, and/or posttraumatic stress disease symptoms.

 

It should be noted that the patients who need ECLS are in critical condition and unable to participate in decision making to determine their own care. Hence, the patient's family needs to make the decisions. The family needs to be informed about the device's risk and support limitations, benefits, and possible unfavorable outcomes before signing the informed consent. Furthermore, the ECLS team must ensure that the family understands the information delivered.49 The family may feel pressured to make a time-sensitive choice provided with very limited time to review and understand the risks and benefits of such treatment.50

 

Clinicians

The clinician roles are being the patient's advocate, controlling health care costs, and also being the middleman between patients and insurance companies, although the main role of clinicians is to deliver a decent health care service.44 Regarding the success of ECLS cases, clinicians play an essential role because as mentioned before, the success of ECLS relies heavily on their expertise and experience. Previous studies indicated significantly better outcomes for ECLS centers performing more than 20 to 25 cases per year compared with centers treating less patients.51,52 In addition, the risk of complications can be minimized by the use of standard nursing care practice along with meticulous assessments.53 Importantly, selecting the right patient, the right type of ECLS, and the right type of configuration (site, management, and complication anticipation) is also necessary for better outcomes.54,55 However, there are still no well-established criteria for adult patient selection for ECLS, which makes it even more challenging for the clinicians to give the "right" recommendation, as recently elaborated in a respiratory case vignette.56

 

ECLS Centers

Reflecting on the H1N1 global pandemic, there is a potentially greater need for ECLS use, which cannot be accommodated because there are only a limited number of ECLS centers in the world.57 Hospitals that provide ECLS should have an ECLS team consisting of intensive care unit (ICU) physicians, perfusionists, ICU nurses, and surgeons ready 24/7.58 Extracorporeal life support staffs are required to meet the qualifications based on their subspecialty training as set forth by their specific governing board.48 For example, the ECLS coordinator should have a strong ICU background or should be a certified clinical perfusionist with ECLS experience, and the physicians should have completed at least 3 years of postgraduate pediatric, surgical, or adult medical training including a separate ECLS course. In addition, Combes et al59 suggested a nurse-to-ECLS-patient ratio of 1:2. Another recommendation is that ECLS centers should have mobile teams composed of multidisciplinary team members, as mentioned previously, with additional transport specialists to transport the referred patient from another hospital.59,60 Hospitals providing ECLS treatment should also have nutritionists, pharmacists, respiratory therapists, and social workers as part of a multidisciplinary ECLS team.61 In addition, it is advisable for ECLS centers to have a well-defined training and continuing educational program for the ECLS team. The program should include educational lectures, training with ECLS equipment, bedside training, a defined system to evaluate the competency of team members, and also continuous education and emergency training.62 Thus, ECLS is a highly specialized intervention where other essential support services and expert training and continued expertise in caring for ECLS patients are a conditio sine qua non; it is certainly not for everyone.

 

Furthermore, ECLS centers are recommended to join either an international registry (ELSO), a surrogate international registry, or the national registry.58 Finally, short- and long-term follow-up after hospital discharge with customized, patient-oriented, and rehabilitation programs is necessary to improve the long-term quality of life of ECLS survivors.59

 

The Government

In general, the government's roles within the health care system are purchasing health care (social and public goods), providing health care to those who are incapable of providing it by themselves, protecting the health care access for vulnerable groups, creating health care market regulations, developing and evaluating health technologies and practices, monitoring and improving the quality and safety of health care, and uniting other stakeholders.63 According to the World Health Organization, 15.7% of total government expenditure was allocated for health in 2011.64 In addition, on average, the government spends 50% to 80% of total health care spending, and the rest is private financing (out-of-pocket and/or private health insurance).65

 

The median total hospitalization cost for adult ECLS patients is [Euro sign]106.263 per patient,66 and the average adult patients are 51 years old.67 Thus, because of its high cost, the average age of the patients, the survival rate, and the limited financial resources, the government needs to allocate its budget wisely on ECLS.

 

Manufacturers

The key role of ECLS manufacturers is to produce a safe and affordable medical device without ignoring their moral responsibility. As mentioned previously, there are still a limited number of ECLS centers in the world.57 This might be caused by the relatively high price of the ECLS systems. Thus, making these systems more affordable by potentially lowering the production costs will in part increase ECLS availability for more highly specialized hospitals. Furthermore, it is inevitable for the manufacturers to collaborate with clinicians. The clinicians play an important role in the development of new technologies and products.68 Clinicians contribute their knowledge, and as the end user of medical devices, they offer essential knowledge relating to unmet needs, patients' preferences, and feedbacks to improve and refine the medical devices.69 Moreover, the clinicians' role is crucial during the clinical trial, testing, and training to develop effective and safe medical devices.68,69 The improvement and development of ECLS techniques and devices are needed specially to minimize the most common complications for general ECLS cases caused by mechanical issues. Those complications for adult patients in the last decade were circuit component clots and oxygenator failure. In addition, other complications also appeared such as cannula problem for respiratory and ECPR cases and clot formation during cardiac ECLS cases.15 The improvement is hoped not only to minimize the chance of complications and to increase the survival rate but also to broaden its chance to be applied to a wider range of patients with less severe cardiopulmonary issues.70 According to research by MarketsandMarkets,71 the key players of ECLS machines in 2015 were Getinge Group, Medtronic plc, and LivaNova with a total market share of 68.8%.

 

CONCLUSION

Extracorporeal life support has been used for treating patients with respiratory failure and cardiac failure and as a resuscitation mode for the past 4 decades. It is proved to save neonates and pediatrics, but its use for treating adult patients remains controversial because of its high risk and relatively low survival rate. Nonetheless, the new improvement of ECLS technology to a safer and simpler device and the H1N1 pandemic in 2009 have boosted the use of ECLS in adult patients. This led to the increase of ECLS centers in the world and to the significant rise of adult patients treated with ECLS. The challenges nowadays are low survival rate especially for patients with cardiac failure and in ECPR cases due to its complications, the limited amount of well-trained and experienced ECLS teams and centers, the limited government expenditure for health, and the lack of improvement and development of ECLS techniques and devices. In addition, further studies are necessary to examine the value of ECLS for adult patients considering that ECLS is a complex treatment that requires a lot of resources.

 

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