The Daily Dose • Friday, May 24, 2024

Early-Career Investigators Rapid-Fire Showcase: A Peek into the Future of Anesthesia Research

Young May Cha, MD

Michael J. Devinney, MD, PhD, assistant professor of anesthesiology at Duke University, moderated the “Early-Career Investigators Rapid-Fire Showcase,” co-sponsored by the Early-Stage Anesthesiology Scholars (eSAS), on Sunday, May 19 at the 2024 Annual Meeting, presented by IARS and SOCCA. Showcase presenters were early-career investigators engaged in research ranging from basic science to clinical to qualitative to large-scale data analysis. The presenters show great promise and it will be exciting to see how their stories will develop in the years to come.

Alexander R. Perez, MD, PhD, resident physician in anesthesiology at University of California-San Francisco, presented “High Fidelity CRISPR Libraries to Interrogate Anesthetic Genetic Susceptibilities in Cancer Metastasis.” The CRISPR gene-editing system can sometimes result in off-target toxicity due to mismatches with the endonuclease and the target DNA. Dr. Perez leverages the nonspecificity of CRISPR to intentionally cause off-target toxicity to kill tumor cells. The specificity for the tumor cell comes instead through virus delivery. In a mouse with human-derived glioblastoma cells, injections of CRISPR resulted in a survival benefit without tumor resection. Next steps are to increase the specificity of CRISPR delivery to tumor cells, which has the potential to be effective irrespective of the tumor’s resistance to chemotherapy. Another potential therapeutic application is to induce antigen development in tumor cells that would make them more susceptible to treatment with immunotherapy.

E. Railey White, MD, PhD, assistant professor of anesthesiology and critical care at University of Pennsylvania, presented “A Novel Application of Non-Anesthetic Propofol Analogues.” PropoFLUOR is a fluorinated analogue of propofol originally hypothesized to be an anesthetic but instead antagonizes the effects of propofol in zebrafish. By modifying the position of the alkyl arms around propofol’s benzene ring, the lab has uncovered additional propofol analogues. Some of these analogues function synergistically, suggesting they are likely functioning via separate mechanisms. Other modifications can also be done, such as modifying the halogens or adding nitrogen. These changes have resulted in molecules that are more sedating than propofol and some that are more antagonizing to propofol. These chemical derivatives could provide insight into the mechanism of anesthetics.

Li Li, MD, PhD, assistant professor of anesthesiology at Seattle Children’s Research Institute/University of Washington, presented “Noradrenergic System in Arousal: From Synapses to Circuits.” There is sequential reactivation of the central nervous system during anesthetic emergence, and the locus coeruleus is hypothesized to be the main component of the noradrenergic system that modulates arousal. Using optogenetics, which is a biological technique to activate neurons with a light stimulus, and in vivo recordings in a mouse model, they have revealed that activity from the locus coeruleus to the basal forebrain is a strong sympathetic activator but a weak cortical promoter of arousal. This difference suggests there could be a division of labor in neuromodulatory circuits and that the locus coeruleus could perhaps preferentially activate sympathetic arousal during emergence.

Sydney Brown, MD, PhD, assistant professor of anesthesiology at University of Michigan, presented “Identifying, Measuring, and Operationalizing Patient Reported Outcomes After Outpatient Surgery Among Adolescents.” Nearly 25% of adolescents develop chronic postsurgical pain. This qualitative study reviewed comments from adolescents and their caregivers after different types of surgeries, including both painful and less painful surgeries. Some adolescents endorsed pain out of proportion to surgery invasiveness. Some reported significant debilitating fatigue that was unrelated to pain, anxiety, or sleep. Caregivers also reported challenges, such as the physical labor to care for an adolescent and the distress by adolescents over their loss of independence postoperatively. Caregivers seemed interested and receptive to interventions that could be delivered through a mobile health application, such as resilience building, breathing techniques, and music therapy activities.

Joseph Scarpa, MD, PhD, instructor in anesthesiology at Weill Cornell Medical College, presented “Multi-Omics for Precision Anesthesia.” Machine learning models can integrate multi-omics data, which include DNA, RNA, proteins, and other molecules, to map out molecular networks for various physiological states. Opioids can downregulate and suppress T-cell function, and so, are hypothesized to counteract the therapeutic effects of immunotherapy. By comparing breast cancer patients who were responders or nonresponders to immunotherapy, they were able to map out a network demonstrating how opioids and immunotherapy have opposing effects on cancer networks. This work is being corroborated by clinical epidemiological studies. Next steps are to use organoid models to model the interactions between opioids and T-cells.

Christina Boncyk, MD, assistant professor of anesthesiology critical care medicine at Vanderbilt University, presented “The Drug Burden Index Throughout Critical Illness and its Association with Patient Outcomes.” There is a negative impact of increased prescribing on survivors from the intensive care unit (ICU). The drug burden index (DBI) quantitatively measures exposure to anticholinergic and sedative medications, and an increase in 1 DBI in older adults is thought to be comparable to adding three comorbidities, such as hypertension, diabetes, and smoking. This prospective study looked at the increase in DBI from preadmission to the ICU. They saw a trend towards worsening cognitive impairment and physical disability with increased DBI. There was no correlation with mortality, suggesting that DBI may not be the best tool to assess this measure in this patient cohort.

Alexander Nagrebetsky, MD, MSc, assistant professor of anaesthesia at Harvard Medical School, presented “Perioperative Oxygen Toxicity: The Evidence.” Oxygen is used to help prevent perioperative pulmonary complications, but high doses of oxygen are known to cause harm. One hundred percent oxygen can cause acute respiratory distress syndrome in mouse models, and high-oxygen delivery in hyperbaric chambers can cause seizures. Other negative sequelae of high oxygen use include atelectasis and oxidative stress. Postoperative pulmonary complications are doubled in patients who receive higher intraoperative-inspired oxygen. Their data (unpublished) suggest that higher inspired oxygen during lung resection increased the likelihood of impaired postoperative oxygenation within seven days after surgery. The Oxygen-ICU randomized control trial supports the use of a conservative protocol for oxygen therapy.