Dr Agerstrand: When a hospital's calling us for help and we're deploying our ECMO team to that ICU to help a sick patient, they are usually as sick as they ever have been. Hours can be the difference between life and death.
Erin: That's Dr. Cara Agerstrand, director of the Medical ECMO Program at NewYork-Presbyterian and Columbia.
Dr Agerstrand: Whenever we receive a call for somebody who needs ECMO, we need to go now.
Erin: Dr. Agerstrand's team is responsible for managing some of the most critically ill patients in intensive care with ECMO, extracorporeal membrane oxygenation. ECMO is a rare life-saving technology that provides oxygen to blood outside a patient's body. It's a technology that Dr. Agerstrand has been at the forefront of deploying at NewYork-Presbyterian. While ECMO is more commonly used today than ever before, it remains a highly specialized therapy that's not widely available. In fact, it's not uncommon for critical care teams in other hospitals to contact the ECMO team at Columbia when they have patients who need this treatment.
Dr Agerstrand: Many of these patients that we're getting called for are so sick they can't even be turned in their ICU bed, let alone leave the room or the hospital that they're already in. So without ECMO, that patient would be stuck.
Erin: Dr. Agerstrand's team is one of the largest and most experienced ECMO teams in the US. Since the program began, not only have they pioneered methods for treating patients in the NewYork-Presbyterian ICU, they've provided hundreds of transports locally, regionally, and even internationally at any time, day or night.
Dr Agerstrand: Their oxygen might be dropping. They may be in severe shock. They may have had a cardiac arrest. And our team comes in with our surgeons, our paramedics, our perfusionists, and a lot of equipment. We come to the patient's bedside and get to work. It's really our ability to go to these hospitals where a sick patient is and help place them on ECMO there, stabilize them, and then bring them back to our ECMO center that has allowed us to help so many people that would otherwise not have had any option.
Erin: Deploying ECMO care can be challenging even in the most ideal clinical settings. The ability to take life-saving care beyond the walls of a single hospital with ECMO transport is just one of the efforts that makes Dr. Agerstrand's team at NewYork-Presbyterian global leaders in critical care medicine.
Dr Agerstrand: We have been able to provide not only ECMO care to a relatively large number of patients, but also to provide in its most innovative ways in terms of ventilator management, anticoagulation management, transfusion management, physical therapy, all these elements that go into helping that patient have a good outcome.
Erin: And that attention to long-term outcomes doesn't end when a patient leaves the hospital. For Dr. Matthew Baldwin, a critical care specialist and research lead for Columbia's Baldwin Lab, addressing long-term survivorship for ICU patients is just as important as getting them out of critical care. Dr. Baldwin is part of Columbia's ECMO Center of Excellence and has devoted his research to understanding post-intensive care syndrome, or PICS.
Dr Baldwin: The vast majority of my work for the past five to seven years has really focused on what are the molecular mechanisms that really drives persistent physical disability in post-intensive care syndrome?
Erin: Dr. Baldwin's groundbreaking research is laying the foundation of a new standard for post-intensive care by identifying druggable targets that could revolutionize critical care recovery.
Dr Baldwin: Drugs that patients could potentially take after the ICU as they prepare for discharge that could speed their body's recovery from a state of what's been catabolism and breakdown in the ICU to one of anabolism in building up, with the overall goal of restoring them back to their prior health and hopefully over the long-term, having the same longevity as they would've had, had they never become critically ill.
Dr Baldwin: I'm Erin Welsh, and this is Advances in Care, a podcast about groundbreaking developments in modern medicine. In this episode, I speak with Dr. Cara Agerstrand and Dr. Matthew Baldwin about how they have pioneered new treatments for patients with the most severe cardiac and respiratory failure, both during and after their time in the ICU.
Erin: The first successful use of ECMO for an adult with respiratory failure was in 1971, but in the '70s, '80s, and '90s, the technology came with a lot of complications.
Dr Agerstrand: Patients couldn't be successfully supported for that long on ECMO, and even under best-case scenarios, many of them didn't survive. There were too many complications with it. Like the oxygen function worked, yet it came with a lot of bleeding or clotting or hemolysis.
Erin: At the center of an ECMO device is a red diamond box, the oxygenator that takes in lines from the patient's central veins and arteries. When a patient is on the device, their blood runs the ECMO circuit through wide hoses, usually connected through ports in the patient's femoral artery and jugular vein, where they are held carefully in place. Just connecting a patient to the ECMO device is a high-risk procedure, which helps to explain why for a long time ECMO wasn't widely adopted.
Dr Agerstrand: Columbia was a very early adopter of ECMO, and we really saw this technology was working to save the lives of people that otherwise had no options, and that combined with some, you know, really brilliant leadership of our physicians, helped us develop an early adult ECMO program.
Erin: That meant they were in a prime position to save lives in two thousand and nine when the H1N1 pandemic sent a wave of relatively young and healthy people into critical care with severe respiratory failure. As early as twenty eleven, Dr. Agerstrand and Dr. Baldwin were co-publishing on the techniques they were developing for using ECMO, setting a new standard for its use in the ICU. They knew they had developed a playbook for treatment that patients beyond New York City would need, sometimes way beyond. With ECMO transport, the Columbia team traveled to other states across the US and even other countries. By twenty fifteen, the team had already done one hundred life-saving missions, gaining invaluable experience along the way as they pioneered this treatment. As they worked out the techniques that made ECMO a huge critical care asset, they developed world-leading expertise in the processes that make using ECMO successful.
Dr Agerstrand: There aren't a lot of rules for ECMO. These patients who are so critically ill really don't follow kind of algorithmic approaches to medicine in a lot of ways, and it requires people who not only have a deep understanding of physiology, but also an expertise in patient management and the unique issues that come with someone supported with ECMO. Knowing how to initiate ECMO requires a great degree of expertise. An equal amount of expertise is required in how to manage that patient successfully once they're on that machine. It means managing the ventilator in a way that doesn't cause ongoing injury to these already damaged lungs. It means preventing infections, treating infections adequately, reducing complications such as bleeding or thrombosis, and minimizing other very common ICU-related complications. So in changing the way we, uh, manage them as far as anticoagulation, with blood transfusions, the ventilator, all these other elements that are required to help someone have a good outcome.
Erin: Successful deployment of ECMO requires an intense level of attention to the individual patient and constant adaptation to their needs from a team of experts who are prepared to constantly communicate and adapt.
Dr Agerstrand: Our ECMO patients are very special patients, uh, to us. Um, we thought early on to provide a, you know, personalized medicine approach to the care of these patients. So as opposed to really focusing on the device or the ECMO circuit itself, we focus on the patient and their underlying disease. Patients' needs change as time goes on. It could be that somebody has a severe form of combined cardiopulmonary failure, and one day they're needing much more cardiac support on ECMO, and the next day it's much more respiratory support, and it's being able to recognize that dynamic situation and adapt and support the patient in the best way possible.
Erin: Dr. Agerstrand sees ECMO as just part of a patient's overall recovery. Her team delivers incredibly complex care when patients are on ECMO, but Columbia's critical care team continues the same level of dedication to patient health once the patient is disconnected from the machine and begins to recover from their critical illness.
Dr Agerstrand: It's not only the ECMO machine itself that's helping sustain that person and provide them with the necessary oxygen that they are required to stay alive, but it's also in the way these patients are managed in the ICU on a broader level, and having that global expertise is really what can allow someone to have a good outcome.
Dr Baldwin: Twenty days in the ICU can age you forty years.
Erin: That's Dr. Matthew Baldwin again, a specialist in pulmonology and critical care medicine at NewYork-Presbyterian and Columbia. He focuses his care and his research on patients suffering from post-intensive care syndrome, or PICS. As rescue therapies like ECMO become more common, there's a growing number of people who survived a life-threatening illness in the ICU. For a long time, this post-ICU stage of a patient's treatment was considered outside the view of critical care medicine.
Dr Baldwin: There's a new population of patients that's now emerging who are debilitated ICU survivors. After the ICU, when patients leave, historically, we'll follow up with your primary care doc. Primary care doctors are probably the most overextended people in the world, and they got no formal training in how to treat someone who has deficits from receiving prolonged critical care. And so there really is no formal follow-up for these patients.
Erin: Dr. Baldwin knows that the care these patients received post-ICU was just as critical to their long-term health as their care in the ICU itself. He's often caring for patients with critical illnesses that began long before an ICU stay and some that will continue after they walk out.
Dr Baldwin: The patient population that I mostly deal with is many patients who are undergoing lung transplant, heart transplant, kidney transplant, or even fighting cancer. Patients who have had bad pneumonia through an event of ARDS, even some young patients who develop severe pneumonia and ultimately need days to weeks of mechanical ventilation and/or ECMO.
Erin: Today, Dr. Baldwin has established a research lab that aims to improve critical illness survivorship for these medically complex patients. He and his team are developing some eye-opening advancements in this field. His most notable research connects the challenges of recovering from a stay in the ICU with inflammation and aging, studying cells formed during critical illness that trigger a hyperinflammatory state.
Dr Baldwin: What we really found over the years is that critical illness that requires mechanical ventilation is a level of critical illness that really leads to some profound changes in the body. The average patient who's mechanically ventilated in the ICU loses twenty percent of their body's muscle mass in seven days. Now, imagine you're ventilated for two or three weeks. Imagine if you're hospitalized for three or four. So the vast majority of our patients have lost a tremendous amount of weight during a hospitalization which, on average, usually lasts about a month.
Erin: A lot of that weight loss is in muscle mass, and beyond the loss of mass, disuse atrophy also changes the ability of muscles to contract normally, meaning muscle function itself often declines, and that's just the physical impact.
Dr Baldwin: The second part is mental health issues. That's primarily depression, anxiety, and PTSD. We know in the general population that somewhere around 9% of, of adult Americans suffer from depression. Coming out of the ICU, we've seen studies with numbers as high as 30%. PTSD, rather rare in the general population. Some studies out of the US and Europe have shown that it's as high as 13% in ICU survivors. We also see a number of patients that once the endotracheal tube is out and they can start to talk, they'll oftentimes recall terrible memories or even hallucinations, and this could create sometimes that we've observed panic attacks. I've seen professors, lawyers, other physicians literally have panic attacks after their ICU illness, and it's hard for them to even know what's triggering it.
Erin: Finally, there's the issue of cognitive impairment suffered by ICU survivors.
Dr Baldwin: ICU survivors after their critical illness with the extensive neurocognitive testing score on a level of pre-Alzheimer's cognitive impairment, which is quite scary.
Erin: All of this has prompted Dr. Baldwin to examine the ways inflammation is identified and measured because high levels of inflammation lead to muscle breakdown. That's true for patients coming out of the ICU, where ongoing muscle breakdown due to inflammation slows recovery. It's also true that as we age, the levels of inflammation in our bodies increase. That parallel led Dr. Baldwin to wonder how the cognitive impairments and inflammation he's seeing in ICU patients could be related to the cognitive decline and increasing frailty we suffer as we age.
Dr Baldwin: It's the same type of inflammation that leads to muscle wasting with aging. It's the same decrease in anabolic hormones that we see over decades from our 50s to our 80s, and it's the same problems with the muscle mitochondria that we see with aging actually affecting much younger people who have survived critical illness. Has their biology been changed in a fundamental way that perhaps was protective while they were critically ill and the switches have just not turned back in the more anabolic direction to get them back to health?
Erin: Dr. Baldwin and his team set themselves a goal: find a biomarker to measure this inflammation and treat it. That's what they're doing now, measuring anabolic hormones and finding biomarkers that reflect the health of cellular and muscle mitochondria.
Dr Baldwin: Where we seek to make progress and advance science is we're now doing single cell RNA sequencing transcriptomics of the blood in patients at hospital discharge and three months later. I took lung aspirates of cells of people who were the sickest people on the ventilator for seven days or more with COVID ARDS during my clinical rounds, and what we found is that there's a certain type of cell called a monocyte. During critical illness is made in the bone marrow and probably gets released from the bone marrow in an immature hyperinflammatory state, and there's certain chemicals expressed in the lung that attract the monocyte into the lung, and then the monocyte breathes fire, so to speak. It, it releases cytokines which release more damage and prolong the ARDS.
Erin: Dr. Baldwin says the hypothesis he's been testing is that these hyperinflammatory monocytes, which the body keeps making for days or even weeks after the critical illness, may be a cellular source of inflammation in the body tied to the challenges of recovering from a stay in the ICU. Where other therapies look downstream of inflammation and attempt to modulate the body's immune response, that comes with a higher likelihood of further infections. Instead, Dr. Baldwin is looking the other way, upstream of the monocyte release.
Dr Baldwin: To understand the cellular sources of persistent inflammation and then to more specifically target cellular surface proteins to manipulate the future function in phenotyping of those cells. If we understand the cellular source of the inflammation and we can tweak the cell itself to turn it off rather than the inflammatory cytokine that it secretes, we can get them to a normal state rather than just trying to shut off all the cytokines with an antibody and potentially creating immunosuppression, which will only beget perhaps more sepsis, pneumonia, and ARDS.
Erin: If his lab develops a treatment for cutting off the monocyte release and stopping hyperinflammation before it starts, that would be a game changer for ICU patients, not just during their time in critical care, but long after. By leading the field in critical care research, Dr. Baldwin is also blazing a trail for research across fields of medicine. The promise of addressing increasing frailty and supporting cognitive function by targeting inflammation has major implications for other fields from geriatric medicine to recovery from other kinds of serious illness, including cancer.
Dr Baldwin: Great patient care really isn't just providing care, but it's dovetailing it with research because if you wanna give the most outstanding clinical care tomorrow, you have to do the research today.
Erin: Dr. Baldwin is leading a wave of research into critical care at Columbia that will continue improving the way that patients recover from a stay in the ICU and provide models of care for a new generation of physicians. Dr. Agerstrand and Dr. Baldwin are pushing forward the field of critical care with the lives of patients at the very core of their work. Treating the most critically ill patients means they face a challenging day today, but they never lose sight of how important their work is. The survivors who owe their lives to the cutting-edge treatment in the NewYork-Presbyterian ICU make sure of that.
Dr Agerstrand: ECMO patients, by the fact that they need ECMO, are the sickest of the sick patients. We know that means that not all of them are going to survive, but what keeps me going is also remembering that we are giving these patients a chance. We are giving their families a chance to take their loved one home. We'll have patients come back sometimes year after year to visit our ICU and say, "Hey, I was here this year on ECMO. Do you remember me?" Or, "Is this nurse here? Is this nurse practitioner still here?" They come back to visit, and for the whole team, it is incredible to see.
Erin: Many thanks to Dr. Cara Agerstrand and Dr. Matthew Baldwin for taking us inside the incredible work of critical care medicine at NewYork-Presbyterian and Columbia. I'm Erin Welsh. Advances in Care is a production of NewYork-Presbyterian Hospital. As a reminder, the views shared on this podcast solely reflect the expertise and experience of our guests. To listen to more episodes of Advances in Care, be sure to follow and subscribe on Apple Podcasts, Spotify, or wherever you get your podcasts. And to learn more about the latest medical innovations from the pioneering physicians at NewYork-Presbyterian, go to nyp.org/advances.
