Spotlight on the William L. Young Neuroscience Research Award Interview with Michael Devinney, MD, PhD

Ines Koerner, MD, PhD
Oregon Health Sciences University
Portland, OR

Dr. Koerner
By Ines Koerner, MD, PhD

Dr. Michael Devinney is Assistant Professor of Anesthesiology at Duke University. In 2020, he received the William L. Young Neuroscience Research Award for his project investigating the association of blood-brain barrier breakdown with sleep apnea and postoperative delirium.

Why did you choose a career in Anesthesiology-Critical Care Medicine?
Overall, I was led to anesthesia and critical care by following my interests at each step of my training. As an undergraduate at the University of Pittsburgh, I became fascinated by neurophysiology and began to appreciate how the central nervous system responds to disease and stress. I then sought out an MD, PhD program with a strong foundation in neuroscience research and excellent clinical training and landed at the University of Wisconsin-Madison.

Dr. Devinney
Michael Devinney, MD, PhD

My PhD research there focused on hypoxia-induced neuroplasticity in respiratory control as a means of restoring normal breathing in the face of respiratory disease. I uncovered cellular/molecular mechanisms of this neuroplasticity by recording phrenic nerve signals in anesthetized rats. Doing this work with anesthetized animals led me to appreciate further the complex interactions between our central nervous system and physiological systems and seeded my interest in anesthesiology and critical care.

When I resumed clinical rotations, I found that my experiences in anesthesiology and the intensive care unit were more exciting than others, confirming my interest in the specialty. I loved to learn about the complex interactions between the brain, cardiovascular and respiratory systems that occur in response to insults, such as surgery, anesthesia, and various disease states.

Navigating these complex inter-relationships is the exciting ‘art’ of anesthesiology and critical care and also has important consequences for patient outcomes. The desire to master this ‘art’ and improve patient outcomes led me to pursue training in anesthesiology and critical care medicine. I also think it is important that we recognize how derangements in other physiological systems can negatively impact the brain.

Thus, my research focuses on finding ways to protect the brain in the face of these insults, to potentially prevent delirium and cognitive dysfunction after surgery or during critical illness.

What recommendations do you have for trainees who want to establish themselves as physician-scientists?
Embrace flexibility and adopt a growth mentality. I think everyone's path to becoming a physician-scientist will be different and also full of twists and turns. The twists and turns are part of our training - they prepare us for shifting our mindsets between physician and scientist roles. The ability to shift between these mindsets is a necessary and unique physician-scientist skill because separate mindsets are needed for being a good physician vs. a good scientist.

In the ICU, for example, I rapidly apply knowledge to address problems related to the patient’s unique pathological situation while adhering to accepted standards of practice. In contrast, each decision in my clinical-translational research is meticulously thought out to make our studies impactful and novel, and I strive to question dogma to prioritize discovery.

Growing into the physician-scientist role has required flexibility throughout training, but I also cannot overstate the importance of good mentorship. A good mentor will find ways to support you, help you define your goals, and challenge you in ways that make you grow. Even after formal training, it is no secret that continued growth in our abilities is critical for success as a physician-scientist. I am fortunate that I have found many wonderful mentors in many different welcoming communities along the way, such as academic anesthesiology, critical care medicine, geriatrics, and sleep medicine.

What do you see as the most exciting current topic in perioperative neuroscience?
One of the COVID-19 pandemic horrors is the epidemic of delirium in older adults hospitalized with COVID-19. This brought delirium in focus as an immense clinical problem affecting an enormous number of patients – especially in the ICU and in the wards and postoperative recovery units.

While we know that humanizing care helps prevent delirium, we still know little about the underlying cellular/molecular mechanisms of delirium, and this has really limited the development of specific treatments. Many biomarker studies fail to find a unifying mechanism, likely because the breakdown of normal cognition can occur in multiple ways. Work characterizing how consciousness and cognition break down is currently being done by members of the SNACC community in anesthetic neuroscience and the neuroscience community-at-large.

I think that all of our efforts to discover more about the brain and its connectivity will eventually enable us as a community to unlock the secrets of delirium and hopefully prevent it in our patients. One thing is for sure – we're definitely going to need to work together to discover new prevention strategies and treatment for delirium. In this past year, delirium has become an even more urgent problem with a significant burden on our patients, their families, and our entire healthcare system.

Can you tell us about your research and how the William Young Award supported your success?
My research goal is to understand the mechanisms and risk factors of postoperative delirium and postoperative cognitive dysfunction (POCD). POCD is a disorder of objective thinking/memory deficits that occur 1-12 months after surgery. Most of the defined risk factors for delirium and POCD, such as age, preoperative cognitive impairment, and Alzheimer's disease neuropathology, are unfortunately immutable.

However, one possible modifiable risk factor is undiagnosed sleep apnea. In sleep apnea patients, hypoxia and sleep disruptions might increase the risk for delirium and POCD by causing increased neuroinflammation. To help us understand these relationships, ~100 older surgical patients will undergo sleep apnea testing and pre-and postoperative cognitive testing, delirium assessments, and blood/cerebrospinal fluid (CSF) sampling in our FAER-funded Sleep Apnea, Neuroinflammation, and Cognitive Dysfunction Manifesting After Non-cardiac Surgery (SANDMAN) study. SANDMAN is nearly finished, so we hope to share these results soon.

The William Young Award has enabled us to leverage the SANDMAN cohort to better understand how untreated sleep apnea could give rise to neuroinflammation and delirium. Increased neuroinflammation and delirium in sleep apnea patients might be due to blood-brain barrier (BBB) breakdown since animal models of sleep apnea exhibit significant BBB breakdown. Using various CSF markers of BBB breakdown, we will determine whether sleep apnea patients exhibit increased BBB breakdown before surgery and whether increased BBB breakdown after surgery is associated with postoperative delirium.

The William Young Award funds a portion of these BBB breakdown marker assays. We have used our preliminary findings to apply for larger grants studying multiple BBB breakdown markers in our entire SANDMAN cohort. We are excited about extending this work and hope to be able to share our results soon.

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