Intensive fever control using a therapeutic normothermia protocol in patients with febrile early septic shock: A randomized feasibility trial and exploration of the immunomodulatory effects

OBJECTIVES: Fever control has been shown to reduce short-term mortality in patients with septic shock. This study aimed to explore the feasibility of early intensive fever control in patients with septic shock and to assess the immunomodulatory effects of this intervention. METHODS: In this single-center, randomized, open-label trial, febrile patients with septic shock presenting to the emergency department were assigned to either a standard fever control or therapeutic normothermia group. Therapeutic normothermia involved intensive fever control in maintaining normothermia below 37°C. The primary outcome was the feasibility of fever control for 24 h. Secondary outcomes included changes in immunomodulatory biomarkers and adverse events. RESULTS: Fifteen patients were enrolled and analyzed. Fever control was comparable in both groups, but significantly more patients in the therapeutic normothermia group experienced shivering (p = 0.007). Both groups demonstrated increased C-reactive protein and unchanged neutrophil chemotaxis and CD11b expression. The therapeutic normothermia group revealed significant decreased IL-6 and IL-10. The standard fever control group significantly expressed increased monocytic human leukocyte antigen. There were no significant differences between the groups in terms of immunomodulation. CONCLUSIONS: Therapeutic normothermia was feasible in patients with febrile septic shock but was not superior to standard fever control in terms of average body temperature and host defense function. Shivering was more frequent in the therapeutic normothermia group. TRIAL REGISTRATION: Thai Clinical Trials Registry number: TCTR20160321001