2021 IARS Mentored Research Award Recipient and Abstract Presenter Interview: Jessica Spence, MD, PhD

The Effect of Restricting Intraoperative Benzodiazepines on the Number of Positive Delirium Assessments After Cardiac Surgery: A Post Hoc Analysis of the 20,000 B-Free Cluster Crossover Trial

Abstract Presentation:

Poster #55: Poster Presentation E, May 19, 2024, 10:00 am – 11:00 am, Columbia AB, Hyatt Regency Seattle

As a resident, Jessica Spence, MD, PhD was initially drawn to the design and conduct of pragmatic clinical trials based on a desire to answer important questions to guide and improve everyday practice as an anesthesiologist. Now an assistant professor at McMaster University and scientist at Population Health Research Institute, Dr. Spence is still determined to unravel some of these important questions and has sharpened her focus to researching whether benzodiazepines should be administered during cardiac surgery. This curiosity led her to her current research project, the B-Free trial, which also inspired research that was awarded the 2021 IARS Mentored Research Award. In the B-Free trial, she sought to determine whether systematically restricting intraoperative benzodiazepines at the institution level could reduce the incidence of delirium in the ICU. During a poster presentation on Sunday, May 19, at the 2024 Annual Meeting, presented by IARS and SOCCA, Dr. Spence will share the results of this vital trial and reveal how these data are informing the design of a large prospective biomarker study. Below, she reveals what drew her to this area of research, the impact of the B-Free trial, and how the IARS meeting offers an important opportunity for knowledge translation of this study.

1. For this research, you are…

Principal Investigator

2. What drew you to this area of research? Has it evolved since your initial research project?

I became interested in the design and conduct of pragmatic clinical trials because they address the questions that anesthesiologists want to know the answers to guide their everyday practice. I remember being a resident and going room to room and seeing how much variation there was in routine, everyday practice. Pragmatic trials address these questions, and help us to understand what really is the best thing to do for patients.

With experience, I’ve developed an appreciation of the strengths and limitations of pragmatic trials. Explanatory trials inform pragmatic trials, and vice versa. In B-Free, some of the data we obtained has informed the design of a large prospective biomarker study.

3. What are the goals you most want to accomplish in your work with this research project?

With the B-Free trial, I wanted to address the question of whether we should be using benzodiazepines during cardiac surgery. Very low-quality evidence has suggested that benzodiazepine administration before and after cardiac surgery is associated with delirium, such that guidelines recommend that these medications not be used. However, intraoperative benzodiazepines continue to be given to approximately 90% of patients undergoing cardiac surgery in North America. In B-Free, we sought to determine whether systematically restricting intraoperative benzodiazepines at the level of an institution could reduce the incidence of delirium in the ICU. 

4. What is the potential impact of your research on the field of anesthesia and patient care?

In B-Free, we found that restricting intraoperative significantly decreased the number of positive delirium assessments after cardiac surgery. When considering the 92% of patients managed according to randomized intraoperative policy (i.e., restrictive arm patients who did not receive intraoperative benzodiazepines and liberal arm patients who did receive intraoperative benzodiazepines), restricting intraoperative benzodiazepines decreased the incidence of postoperative delirium by 10%. In sensitivity analyses examining other populations, the more that benzodiazepine exposure was eliminated, the more that delirium was reduced.

5. What are the benefits of presenting your research at the IARS Annual Meeting?

In my opinion, the IARS meeting is a seminal forum for knowledge translation. It provides the opportunity to exchange information with both international anesthesia researchers and clinicians looking for information to guide their daily practice. The message about benzodiazepines is an important one that affects all practitioners. IARS is the ideal place to disseminate this message.

6. How did the 2021 IMRA affect your research and professional trajectory?

The IMRA provided a massive boost in many different ways. Firstly, it allowed me to join a research community that, as a Canadian, I had not previously been a part of. Secondly, it facilitated my learning how to conduct research relating to the clinical application of proteomic and genomic markers to predict and diagnose postoperative complications. By pairing me with a mentor with whom I would not have otherwise worked, the award broadened the scope of the research that I’m conducting.

7. How is your current research project influenced by your initial 2021 IMRA research project?

My current project (which was under way at the time of application) actually inspired my IMRA project. In reviewing the interim analysis of the B-Free data, it became clear that the diagnosis of delirium in routine clinical care was widely variable. Given that even the gold standard for delirium diagnosis – a formal neuropsychological exam – is subjective, it helped me to appreciate the importance of more objective means of predicting and diagnosing delirium, through the use of polygenic risk scores and proteomic markers.

8. Is there anyone else you wish to acknowledge as part of this research team?

I was very lucky to receive mentorship and guidance from a huge group of senior researchers, including Drs. Eric Jacobsohn, Stuart Connolly, Michael Avidan, and PJ Devereaux. All four have different strengths, experiences, and insights, and were instrumental in helping me to complete this work. Beyond my mentors, it’s also important that I recognize the massive group of B-Free Investigators from across North America who, despite our limited funding, were dedicated to answering this important question. Finally, I have to acknowledge all of the cardiac anesthesiologists working at the hospitals that took part in the trial, who were willing to set aside their personal beliefs and randomly change their default practice in the interests of science and optimizing patient care on a broader scale.

9. Outside of your research, what might someone be surprised to learn about you?

Prior to medicine, I was actually a professional cyclist, and was the 2006 Canadian Women’s Individual Pursuit Champion on the track.