SCCM Resource Library-VV ECMO in the Current and Future Era

Video Transcription

Hello, and welcome to SCCM's 51st Critical Care Congress. My name is Craig Javely. I'm an Associate Professor of Anesthesiology at the Emory University School of Medicine  in Atlanta, Georgia. For the next 15 to 20 minutes, it'll be my pleasure to talk to you about venovenous ECMO in the current and future era.  I have no relevant financial disclosures or other conflicts of interest. This is a talk about ECMO, so I will be discussing the off-label use of medications and medical devices.  We have three objectives for the talk. The first is to summarize the current venovenous ECMO landscape. The second is to juxtapose areas of progress with ongoing challenges.  And the third is to anticipate future areas of development as it relates to venovenous ECMO. I'm going to organize the presentation as follows.  First, we're going to talk about access. After that, we're going to spend some time talking about support, support of the patient,  support of the patient's family, and support of each other. Finally, we're going to talk about liberation from ECMO and what might be coming down the pipeline in the future.  So first up is access. Whenever we're talking about ECMO, it's always good to be clear. We're not talking about vascular access.  We're talking specifically about patient access to ECMO services. So why is access important?  We know from EOLIA that patients with severe respiratory failure benefit from timely access to ECMO.  This was evidenced both by crossover within the study itself and in subsequent Bayesian analysis, which I've highlighted here.  When examining the probability of mortality risk reduction as a function of EOLIA weighting in the Bayesian analysis, there is a near 100% confidence that early access to ECMO  affords some degree of mortality risk reduction up to 10%. And similarly, the likelihood that this reduction is between 10% and 20% is fairly high.  Looking at the same problem another way, consider some recently published data available ahead of print in the Blue Journal.  In Vanderbilt's single-center experience with COVID-19 patients, those who were referred for ECMO and for whom capacity existed had an approximate 60-day mortality of about 40%.  In stark contrast, those who were referred for ECMO and for whom no capacity could be made had about a 90% 60-day mortality, which is a very striking finding.  So all of this is to say, access to ECMO is important. Some of the best data we have to conceptualize how access to ECMO has changed over time comes from the ELSO registry.  ELSO maintains an international registry, and owing to the wide variability in ECMO practice around the world, it becomes a little bit difficult to summarize how access has  changed over time. So for the sake of convenience here, I'm going to talk about the North American experience.  We're going to look at ELSO registry data for venovenous ECMO through 2020. I'm going to present this data in a way that you may not have seen it previously.  If we look at the number of runs and centers as a proportion relative to their 2020 totals, you can see how both total ECMO runs and the number of centers has changed relative to  one another over time. What you see is that these have grown over time, not necessarily in concert, but in relatively  close parity when examining them as a proportion, which is to say that more ECMO centers have opened over time in the United States, and more patients have been afforded access to  ECMO as a result of that. There's no doubt that one of the reasons for the increasing number of venovenous ECMO runs  around the world is due to a sequential reappraisal of what we previously thought to be contraindications to ECMO, either relative indications or absolute contraindications.  Although time here is limited to talk about any one of these in great detail, it should suffice to say that if you were to go to the primary literature, you could find at least  one decent study examining the outcomes of ECMO for any of these types of patients. Patients who are obese, patients who are at the extremes of age, patients who may have  received mechanical ventilation for longer periods of time before the initiation of ECMO, patients with severe comorbid disease, patients with superimposed shock, those with trauma,  those at high bleeding risk, or those with CNS injury, demonstrating that outcomes from venovenous ECMO in each of these potentially challenging patient populations is better  than we previously thought. This has a lot to do with clinical practice development over the years and increasing safety of the technology in ECMO itself.  The majority of ECMO across the United States and worldwide is done in referral centers with moderate to high caseloads.  And to emphasize this point, I'm going to present here the findings of two studies examining U.S. centers via the National Inpatient Sample.  The first by McCarthy and colleagues examined data from 2002 to 2011 and demonstrated that mid and high volume centers accounted for the vast majority of total ECMO runs.  The second by Bailey and colleagues likewise examined data from the National Inpatient Sample between 2008 to 2014 and had similar findings.  Interestingly, however, Bailey and colleagues also demonstrated some degree of volume outcome  decoupling, which is to say that higher volume centers did not necessarily have more favorable patient outcomes.  Also interestingly, the association between higher volumes and better outcomes reemerged after controlling for patients transferred to higher volume centers.  So what are we to make of this outcome volume decoupling? At first, it may have something to do around risk appraisal, which is to say that high  volume centers may apply ECMO more liberally. There are a number of different reasons for that. They may have more expertise, they may feel comfortable taking on riskier patients as  a result of that, or they may have excess capacity and ergo be willing to take on additional patients that other centers may turn down.  Around this, we see that there may be need for more rigorous eligibility criteria and we see that there's need for more research to develop such criteria.  On the other hand, some of this outcome volume decoupling may be due to problems around coordination,  which is that riskier patients may be shunted preferentially to high volume centers. While this is not necessarily a bad thing, and indeed it may be entirely appropriate  for low volume centers to send high risk patients to higher volume centers, it perhaps explains  the observation that controlling for such patients yields better coupling in the types of investigations that we just reviewed and also highlights the need for better coordination.  Again, recognizing that ECMO practice around the world is heterogeneous, not every country in the world and not every region of the United States, for example, enjoys the same  degree of coordination, for example, in a hub and spoke type of model. At present, the financial realities of ECMO may be an important barrier to expansion of access.  In the United States, for example, high treatment costs are offset by high reimbursement.  So clinically and financially, ECMO is a low volume, high complexity service and is incentivized as such.  In the future, however, we might hope that we can offer ECMO to more patients to avoid injurious mechanical ventilation as the lungs become sicker.  However, that would mean that ECMO would need to become much more commonplace than it is now with a pivot to ECMO being a high volume, low complexity service, which is an entirely  different financial and clinical paradigm than the current state. We're going to shift now to talk about the support of patients receiving ECMO therapy  to include the support of their bodies, minds, their families, and ourselves. At present, we are doing things during ECMO that we previously thought were not possible.  Going back to the primary literature, just five or 10 years, and you'll see case reports of patients being awake while supported with ECMO, being supplanted with reports of patients  awake and doing limited physical therapy, being supplanted by reports of patients awake and ambulating while on ECMO.  At high volume centers around the country, ambulatory ECMO is now the common standard of practice.  And although it is relatively labor intensive, the positive impact of this practice on patients'  physical recovery, mental well-being, and the overall spirit of the team really cannot be overemphasized.  These two pictures here I've shared with permission from two of our patients locally. While we've certainly made strides in our treatment of patients while on ECMO therapy,  we certainly have many, many unanswered questions. These relate to the domains, broadly speaking, of anticoagulation, how best to mechanically  ventilate these patients, when these patients should receive steroids and how much they  should receive, how to best surveil for infection and how best to treat it when it does occur,  the extent to which we need to push for early physical therapy versus liberation from ECMO  when it's possible, the timing of the initiation of ECMO support, and the use of adjunctive  therapy, by which I mean the application of interventions primarily studied in adults with severe respiratory failure that have not been as widely studied in patients during  ECMO support. Those include, for example, neuromuscular blockade, pronation, and inhaled pulmonary vasodilators.  Because it's so relevant to this patient population, we're going to spend some additional time talking in particular about anticoagulation.  Nunez and colleagues recently published in Intensive Care Medicine an analysis of the ELSO registry for adults supported with VV ECMO from 2010 to 2017.  Among almost 8,000 VV ECMO patients, about 40% experienced either a bleeding or a thrombotic event during their ECMO run.  The balance between bleeding and thrombotic complications was relatively balanced with about a 50-50 split.  Typically, when we think about bleeding on ECMO, we think about bleeding either from a surgical site or from a cannulation site.  And indeed, that kind of clinical gestalt was paralleled by the findings of this study. Likewise, when we think about thrombosis during ECMO, we typically think about thrombosis  occurring somewhere in the oxygenator or the pump or along the circuit. And again, those findings were confirmed in this study.  Beyond just confirming our clinical gestalt, this study also examined an important question,  namely, what is the impact of these bleeding and thrombotic complications on patient-centered outcomes? They're happening, but do they impact the outcomes of our patients?  The answer is, it depends. When we consider bleeding, bleeding that manifested as intracranial hemorrhage, pulmonary bleeding,  or GI bleeding was clearly associated with heightened mortality, whereas bleeding that was confined to a surgical site or a cannulation access point was not.  I think this mirrors our clinical experience. When it comes to thrombosis, thrombotic complications that manifested as an ischemic stroke were  clearly associated with heightened mortality. It was a bit of a mixed bag when it comes to circuit thrombosis.  Circuit thrombosis that manifested as hemolysis or failure of the oxygenator or pump was associated with mortality, whereas other forms of circuit thrombosis were not.  On the whole, what we can take away from this study is that we remain in desperate need  of additional diagnostic options and therapeutic options for managing the balance between bleeding and thrombosis in patients who are supported with ECMO.  While we could easily spend an hour or more talking about the management of ECMO circuits and the myriad impacts of ECMO on end-organ function, I'd be remiss not to mention that  the support of these patients extends beyond those domains and into the support of the patient's mind, spirit, and eventual recovery.  In contrast to other forms of critical illness, patients who receive ECMO support may experience a more rapid deterioration in their health with resultant crisis.  Additionally, they have extremely prolonged ICU and hospital length of stay with multiple exposures to difficult and traumatic experiences.  Additionally, they have to contend with all of the myriad complications that can result from the circuit and the cannulas themselves, such as infection and the manifestations of  coagulopathy. These and other challenges were highlighted in a really excellent publication out of Australia recently that I want to spotlight here.  Search your mobile device at that QR code and please take a minute to go and read it.  It's a fascinating qualitative study, including interviews with ECMO survivors and their families, and some of the quotes in there are really moving.  The publication also offers an extremely balanced discussion about how best to support these patients through challenging times, so please take a minute to go and review it.  There's no doubt that the patient and family experience during ECMO is extremely challenging, and it's also true that running an ECMO service itself is very challenging.  I borrowed this slide from my local ECMO program medical director, and it highlights some of the difficulties in running an ECMO service and in the day-to-day clinical management  of these patients. ECMO, like critical care in general, is a multidisciplinary and multi-professional endeavor,  and as members of an ECMO team, you have probably felt some or all of these stressors over the past year.  In the same way that we're talking about ways to mitigate the deleterious impact of ECMO support on patients and families, we likely need to spend more time talking about ways  to mitigate some of the deleterious impacts of these stressors on ourselves and on our team members. Let's shift now to talk about liberation from ECMO.  Historically, in talking about liberation, we've thought about ECMO as either a bridge to recovery or a bridge to transplantation, but I'm going to talk about some other options  that may be coming down the pipeline in the future. The basic principles of VV-ECMO are that we use it to facilitate gas exchange.  It supplants the function of the culprit organs, namely the lungs, and supports the other organs.  It helps to avoid injurious mechanical ventilation, and it helps to facilitate rehabilitation.  The reason historically that we've undertaken VV-ECMO is that we should have avenues for liberation, which could be either recovery with or without prolonged mechanical ventilation  or transplantation. In the absence of avenues for liberation, we sometimes find ourselves on the so-called bridge to nowhere.  I want to take a moment to highlight the ability of ECMO to bridge patients to recovery, even during challenging times.  Although the past two years contending with COVID-19 has put an enormous amount of stress and strain on the delivery of critical care services worldwide, ECMO among them, it is  possible to achieve favorable patient outcomes. In this ELSO registry study published in The Lancet, what we see is that the outcomes of  patients with COVID-19 supported with VV-ECMO are similar to those quoted in the literature, with approximately 60% survival stretching out to 90 days.  You'll also note here that mortality starts to taper off around day 30 or 40 of ECMO support.  Of the 380 patients who died in this registry study, support was withdrawn an 85%, owing to a perceived poor prognosis.  And the vast majority of in-hospital deaths occurred within 24 hours of stopping ECMO.  Having said that, of the hospitalized patients on or after day 40, in-hospital 90-day mortality was only 14.1%.  This to me highlights the potential utility for prolonged ECMO support, even in the face of challenging circumstances. The question then becomes, what do we mean by prolonged ECMO?  And historically, we've taken that to mean a run extending past 28 days. In this very nicely presented summary, a relatively small case series looking at prolonged ECMO  runs, reported survival ranges between 21 and 87% for veno-venous ECMO. Clinical ECMO services around the world have been saturated for the past two years owing  to the pandemic. One of the good things to come from this may be an opportunity to reappraise the outcomes  in prolonged ECMO, as we may need to reconsider the historical practice of automatically reconsidering goals of care at four weeks, as this may prove to be too soon.  VEV ECMO can of course also be used as a bridge to transplantation. During 2021, we transplanted 2,500 lungs in comparison to 25,000 kidneys.  And while that comparison is not entirely fair, we did transplant 3,800 hearts during the same time.  Over time, bridging outcomes have gradually approached all cover outcomes in lung transplantation, which is a very favorable development.  Having said that, multiple barriers remain to the expansion of lung transplantation, not the least of which is that only 15 to 25% of eligible donors are ultimately deemed suitable.  To remedy that shortfall, we're using extended criteria donors, donation after circulatory death, and now ex vivo lung perfusion, which can extend the amount of time that the lungs  remain suitable for transplantation after harvest. In the future, we might hope to imagine a third option in addition to bridge to recovery  and bridge to transplantation, which is durable ambulatory outpatient ECMO. Although it goes without saying that such a system would need to be portable, there  are myriad other considerations as well. It would need to be durable, or at least relatively durable, meaning that the patient would not  have to return to an inpatient or a surgical setting frequently. It would need to be biocompatible, at least in the current state of artificial lungs such  as membrane oxygenators, it would need to be monitored. And such a solution may even be pumpless.  It could be truly pumpless, it could use the patient's native pump, that is their heart, and it could even be implanted, removing the extra corporeal part of membrane oxygenation.  In summary, more patients are receiving ECMO at more centers, and in the United States, for example, access is gradually expanding.  However, clinical and logistical considerations appear to be driving outcome volume decoupling, and these instances highlight opportunities for improvement.  For access to ECMO to truly expand, it will have to evolve into a high volume, low complexity modality.  While we are certainly supporting ECMO patients in ways never previously thought possible,  some problems remain in need of better solutions, such as balancing the risks of bleeding and  thrombosis during ECMO support, and its potentially high toll on patients, families, and clinicians requires further mitigation.  Better ECMO support is translating into better patient-centered outcomes, even during prolonged ECMO support.  While the mainstays of liberation remain bridge to recovery and bridge to transplantation, we might envision a future where durable, ambulatory outpatient lung support, such as  a true artificial lung, is able to offer patients a third option. I hope you enjoyed this presentation.  If you have questions or would like to contact me about any of the content, please feel free to reach out either by email or on Twitter. Thanks again.

Video Summary

In this presentation, Dr. Craig Javely discusses the current landscape of venovenous ECMO (extracorporeal membrane oxygenation) and its future developments. He emphasizes the importance of timely access to ECMO for patients with severe respiratory failure, as it has been shown to reduce mortality. The number of ECMO centers and runs has been increasing over time, allowing more patients to have access to ECMO services. Dr. Javely also discusses the challenges and advances in ECMO support, including the importance of ambulatory ECMO for physical and mental recovery of patients. He highlights the need for additional research in various aspects of ECMO management, such as anticoagulation and monitoring for complications. Dr. Javely also discusses the impact of ECMO support on patients and their families, as well as the challenges faced by ECMO teams. He concludes by discussing the potential future of ECMO, including the possibility of long-term ambulatory outpatient support.

Asset Subtitle

Quality and Patient Safety, Cardiovascular, Procedures, 2022

Asset Caption

This session will combine the most popular learning methods for extracorporeal support, combining didactic information on the most up-to-date research and clinical outcomes, case-based presentations that will be used to incorporate the didactic portion, and audience participation by Q&A with the expert faculty panel. Topics covered are: 1. New technology, what's here, why it's important, what's coming 2. Expanding populations, criteria and outcomes (extracorporeal CPR, COVID-19, transplant, cardiac) 3. What's new in anticoagulation? Maybe the answer is to do nothing! 4. How we handle the lung during venovenous extracorporeal membrane oxygenation (ECMO), the heart during venoarterial ECMO, sedation, when and how to unload the left ventricle, whether I need to change from venovenous to another mode for hypoxia (and why) This sessions will focus on adult and pediatric patients but not much on neonatal ECMO. Didactic talks will be incorporated into case-based presentations. Time for Q&A with the speakers will be a major focus.

Meta Tag

Content Type Presentation

Knowledge Area Quality and Patient Safety

Knowledge Area Cardiovascular

Knowledge Area Procedures

Knowledge Level Advanced

Learning Pathway Cardiothoracic Critical Care

Membership Level Select

Tag Evidence Based Medicine

Tag Extracorporeal Life Support

Tag Extracorporeal Membrane Oxygenation ECMO

Tag Cardiothoracic Critical Care

Year 2022

Keywords

venovenous ECMO

respiratory failure

mortality reduction

ambulatory ECMO

ECMO support

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