This was a prospective multi-center study that enrolled a convenience sample of patients who presented with agitation or ExDS. Patients were enrolled from three academic emergency departments (ED), two in the United States and one in Canada. Three study groups (SG) included SG1 patients brought to the ED with ExDS based on the use of standardized clinical criteria; SG2 emergency department patients with acute agitation who were not in a clinical state of ExDS but required sedation; and SG3 a laboratory control group of subjects exercised to physical exhaustion, restrained, and psychologically stressed with the threat of Conducted Energy Device (CED) activation. Using blood analysis, the study also examined a panel of stress-related biomarkers, including norepinephrine (NE), cortisol, copeptin, orexin A, and dynorphin (Dyn). A total of 82 subjects were enrolled: 31 in the agitation group, 21 in the ExDS group, and 30 in the laboratory control group. Data were analyzed, comparing the findings between ExDS and the two other groups to determine whether specific stress-related biomarkers were associated with ExDS. Biomarker comparisons between subjects identified with ExDS, agitation, and control groups demonstrated that cortisol levels were more elevated in the ExDS group compared with the other groups. Orexin was only significant in ExDs (with Agitated tendency but lot of variability in the group). NE and Dyn increased as response to stress in Agitated and ExDS. The study determined that cortisol levels were more elevated in subjects in the ExDS group compared with the other comparison groups, and orexin was elevated in ExDS compared to controls, a trend that did not reach statistical significance in the agitated group. The clinical or diagnostic significance of these differences have yet to be defined and warrant further study. (publisher abstract modified)
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