Abstract Background: Septic shock (SS) is associated with profound inflammatory, hypoxic, and neurohormonal disturbances and remains a leading cause of mortality in critical care. However, data describing early (first 24 h) biomarker dynamics that distinguish refractory from resolved SS are limited. This study aimed to describe and compare early 24 h temporal trends of inflammatory, hypoxic, and neurohormonal biomarkers in patients with refractory versus resolved SS. Materials and Methods: This prospective, exploratory study was conducted in two teaching hospitals. Patients aged 20–64 years with SS defined by sepsis-3 criteria were consecutively enrolled. Patients were classified post hoc as having refractory SS (norepinephrine requirement >0.2 μg/kg/min for >6 h) or resolved SS (decreasing vasopressor requirement). Plasma concentrations of hypoxia-inducible factor-1 alpha (HIF-1 α ), tumor necrosis factor-alpha (TNF- α ), interleukin-10 (IL-10), and angiotensin II were measured at baseline, 12 h, and 24 h using enzyme-linked immunosorbent assay. Results: We analyzed 25 patients; 16 (64%) had refractory SS, and 9 (36%) had resolved SS. Overall, in-hospital mortality was 76%. In patients with resolved shock, TNF- α concentrations declined significantly over 24 h ( P = 0.028). In contrast, patients with refractory shock demonstrated a significant reduction in IL-10 levels over time ( P = 0.010). No statistically significant temporal changes were observed for HIF-1 α , angiotensin II, or the TNF- α /IL-10 ratio in either group. Conclusion: Early biomarker dynamics during SS differed between refractory and resolved states, particularly for inflammatory mediators. These findings are hypothesis-generating and support the need for larger longitudinal studies to clarify the clinical relevance of early inflammatory, hypoxic, and neurohormonal trajectories in SS.
Andriyanto et al. (2026) studied this question.