Preoperative Exercise to Improve Vagal Tone (PREVENT) Study

With the support of a 2019 IARS Mentored Research Award, John Whittle, MD, was able to combine his undergraduate training in applied physiology with anesthesia research to explore strategies to prevent patient complications after surgery, expanding knowledge and the understanding of the benefits of prehabilitation. His IMRA-funded project, “Preoperative Exercise to Improve Vagal Tone (PREVENT) Study,” initially sought to determine if a high intensity interval training program could improve vagal tone and laboratory markers of inflammation and mitochondrial capacity. When the COVID-19 pandemic threw a wrench in that plan, Dr. Whittle, an Assistant Professor in Anesthesiology at Duke University Medical School at the time, pivoted and designed a study looking at longitudinal metabolism in patients admitted to critical care with COVID. The techniques uncovered in that study have now been applied to a new longitudinal metabolic study in surgical patients, which is currently underway. Today, this initial investigation has spurred even more progress for the study of prehabilitation. Now an Associate Professor in Perioperative Medicine at University College London, Dr. Whittle has set up a nutritional and physical prehabilitation program at the university which is linked to other national programs. He hopes this program will just be the start of developing patient-centered treatment strategies to reduce the risk of undergoing surgery. Below, he discusses how the IMRA helped him progress as an early-career researcher, his dedication to finding strategies to prevent complications after surgery and his hopes for the future of anesthesia research.

1. What is your current position? How long have you been in this position? What was your role when you were first funded by IARS?

I am currently a Consultant in Anaesthesia, Perioperative & Critical Care Medicine at University College London Hospitals in the UK. I am also an Associate Professor at University College London. I joined UCL in 2000. When I was funded by IARS, I was an Assistant Professor in Anesthesiology at Duke University Medical School.

2. What drew you to anesthesiology and to your particular area of research? Has your research subject area evolved since the award?

Like many people, I did not go to medical school with a career in Anesthesiology in mind. I did, however, have a passion for applied physiology (my undergraduate degree was in Aerospace Physiology), and it became clear that Anesthesiology and Critical Care Medicine allowed for a clear correlation where applied sciences from first principles could be used on a daily basis. I also came into contact with anesthesiologists during training, and I was impressed by how calmly they applied first principles to what often seemed to be critical situations, without even ruffling their feathers!

My area of research is focused on understanding why people develop complications after surgery. As a critical care doctor, I have unfortunately often had to care for patients when complications have occurred and as a result have dedicated my professional career to helping prevent this from happening in the first place. Since it was applied physiology that got me into Anesthesiology in the first place, my research has used this approach. I have been using exercise testing as a care modality for testing patients before surgery, and over time I have focused on different aspects of what it means to be fit for surgery.

3. What was the goal of your initial research project? Was it met?

My initial research project looked to extend work I had previously been involved with, looking at parasympathetic autonomic dysfunction (PAD) as a candidate mechanism for the development of postoperative morbidity. PAD is common in aerobically unfit individuals and in older surgical patients. It is associated with an established inflammatory phenotype, mitochondrial dysfunction and an increased risk of intraoperative and perioperative morbidity. Aerobic exercise training can improve parasympathetic function in older and multimorbid patients and is a promising non-invasive intervention to reduce perioperative risk.

We set out to see if a 4-week supervised high intensity interval training program could improve vagal tone and laboratory markers of inflammation and mitochondrial capacity. We were successful in recruiting 10 patients to our program, but unfortunately the COVID-19 pandemic hit which precluded us from undertaking in-person exercise training and testing. During review of the initial 10 patients, and in collaboration with my mentor and exercise scientists, we pivoted our area of interest into metabolic flexibility as a candidate mechanism for the development of postoperative morbidity. We undertook a study looking at longitudinal metabolism in patients admitted to critical care with COVID and used techniques learnt in that study to design a new longitudinal metabolic study in surgical patients which is running now.

In terms of research goals being met, we were able to see changes in mitochondrial function after training, and in a parallel cohort of patients recruited in another study impacted by COVID, as such we were able to identify another promising candidate mechanism for further exploration.

4. How did your findings impact patient care?

We have set up a nutritional and physical prehabilitation program at UCL which is linked to other national programs. We have been able to apply some of the learning from my IARS project alongside other studies to improve preparation of patients for surgery and develop new pathways for exploration.

5. How did your research impact the field of anesthesiology?

Through engagement with this kind of research the concept of prehabilitation (preventative rehabilitation) before surgery has gained increasing traction around the world. National guidance has been issued in the UK recommending this approach and consensus guidelines for specific surgical specialties are under development.

6. How did the award affect your research/professional trajectory?

As a result of this award, I have been able to progress towards independence in research. I moved to UCL in the UK from the USA during the duration of the award where I have been able to set up my own laboratory within the wider Centre for Perioperative Medicine. I am now an Associate Professor and have received funding from the UCL UK National Institute of Health Research Biomedical Research Centre in Critical Care/Perioperative Medicine theme.

7. How do you feel about having received the IARS Mentored Research Award?

I am immensely grateful this scheme exists as it has provided me with the supported boost towards the next stage in my research career.

8. What would you like to convey to our donors, the people who made this award possible?

Your donation is facilitating the development of a new cohort of researchers who will improve the care given to those undergoing surgery, who without this award may have found it difficult to take the next steps towards establishing their own research program. I am personally very thankful for the support of IARS and the kind donors who make this sort of award possible.

9. What is something that someone would be surprised to learn about you?

I picked up Bluegrass Banjo lessons when I worked in North Carolina and still like to pick and strum in the evening when at home in London, England!

10. What do you hope for the future of anesthesia research?

I hope that anesthesiologists continue to reach beyond the OR into perioperative medicine, embracing the focus on basic science at the core of Anesthesiology and applying it to understanding why people develop complications after surgery. My dream is that we leverage this knowledge to develop patient-centered treatment strategies to reduce the risk of undergoing surgery.