Objective Response of Saliva Biomarkers After High-Stress and Mass Casualty Scenarios: A Pilot Study.

Introduction: Surgeons and military personnel are subjected to high-stress scenarios, which leads to greater rates of burnout. There is room to optimize performance and longevity in these careers by better understanding the body's stress response and applying it to stress management training. This study aims to understand the physiological response in those engaged in trauma scenarios by examining 6 hormones and 42 cytokines during the Intensive Surgical and Trauma Skills Course held at Strategic Operations Inc in San Diego, CA.

Methods: Thirty-seven military medical students participated in full immersion, hyper-realistic, and experiential mass casualty high-stress scenarios. Participants were exposed to both operating and emergency room scenarios. Saliva samples were taken after stress inoculation (postinoculation) and again 1 hr after each scenario (recovery). Saliva samples were analyzed using plex assays from Eve Technologies. Data were grouped and analyzed by location and timing using mixed effect nonlinear models. Distributions were compared by location and were analyzed with respect to biomarker levels over the 4-day training period.

Results: For emergency room scenarios, there was a decrease in the following cytokines from postinoculation to recovery: epidermal growth factor (EGF), granulocyte colony stimulating factor (G-CSF), epidermal growth factor, granulocyte colony stimulating factor, interleukin 1alpha (IL-1α), interleukin 1beta (IL-1 β), IL-1RA, IL-4, IL-8, IL-10, IL-18, monocyte chemotactic protein (MCP) 1, macrophage colony stimulating factor (M-CSF), macrophage derived chemokine (MDC), CXC motif ligand 9 (MIG/CXCL9), regulated upon activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (P < 0.05, t > 3.0). For operating room scenarios, there was a decrease in the following cytokines: EGF, G-CSF, IL-1α, IL-1 β, IL-1RA, IL-6, IL-8, IL-10, IL-18, M-CSF, MDC, MIG/CXCL9, RANTES, and tumor necrosis factor alpha. In operating room scenarios, an increase in the hormone levels of progesterone and triodothyronine were observed. The cytokines observed in both groups included EGF, IL-1α, RANTES, MDC, EGF, G-CSF, IL-1RA, IL-18, MIG/CXCL9, IL-8, IL-1β, M-CSF, and IL-10. These significant biomarkers were also graphed and visualized as variable throughout the week.

Conclusions: These preliminary data narrow a wide array of stress biomarkers to a smaller, significant group. Surgeons and military personnel are subjected to extraordinary levels of stress with narrow margins for error. To optimize performance and outcomes, it is pertinent to understand the physiological stress response. Future investigation and pairing of cytokine measurements with neuropsychological and performance-based testing will target opportunities to direct training and identify profiles of individuals well suited for stressful environments.