Control of Fever in Septic Patients: the Results of a Randomised Controlled Trial

Abstract Background: Fever is a defence against infection. However, its benefit might be masked by cardiorespiratory maladaptation to thermal stress. The aim of this study was to evaluate the effect of fever control on the outcomes of septic patients who were presumed to have a sufficient cardiorespiratory reserve.Methods: Septic patients with a presumed sufficient cardiorespiratory reserve and fever (>38.3°C) of infectious etiology were randomised to one of the two study arms. In the aggressive arm, the antipyretic intervention was started immediately when the body temperature rose above 38.3°C, in the conservative arm only when it exceeded 39.5°C. Both pharmacological (ibuprofen) and physical antipyretic methods were used. The total SOFA score on day 7 was selected as the primary endpoint. Non-parametric tests were used for statistics when comparing variables between the study arms.Results: A total of 5998 patients were screened for fever of infectious etiology. 609 patients met inclusion criteria, of whom 154 patients were randomised. A significantly higher body temperature and longer duration of febrile episode was reached in the conservative arm. The SOFA score was significantly lower on day 7 when the conservative approach was applied. In-hospital mortality did not differ between the arms. When analysing a subgroup of patients with ICU stay < 4 days, a significantly lower SOFA score on day 3 and a tendency for lower in-hospital mortality was observed in the aggressive arm. In contrast, among patients with ICU stay ≥ 6 days, a significantly lower SOFA score on day 7 and significantly lower in-hospital mortality was found in the conservative arm.Conclusions: The conservative approach to the treatment of fever in septic patients with sufficient cardiorespiratory reserve was associated with a lower total SOFA score on day 7 compared to the aggressive approach. However, both approaches may positively influence outcome of septic patients: the aggressive approach seems to be beneficial in the early stage of sepsis, and the conservative approach in the stage of sepsis remission.Trial registration: The study was retrospectively registered at http://www.clinicaltrials.gov (Ref. No. NCT04227652).