Sepsis in the absence of fever: Determining the criteria for and feasibility of future therapeutic temperature management trials

Objective: The purpose of this study is to examine the occurrence, characteristics, and outcomes of intensive care unit (ICU) patients with sepsis and the absence of fever. Design: Multicentre, retrospective cohort study. Setting: Twelve ICUs in Queensland, Australia. Participants: Adults (≥18 years) admitted to the ICU with sepsis between 1 January 2015 and 31 December 2021 were eligible for inclusion. Patients admitted with seizures, traumatic brain injury, postcardiac arrest, end-of-life care, and elective surgery were excluded, as were readmissions. Main outcome measures: The primary outcome was fever deficit (defined as degree-hours under 38.3°C) during the first 72 h of ICU admission, and all-cause 30-day mortality was the key secondary outcome. Results: Of 89,117 admissions, 15,612 were included. Admission temperatures were ≥38.3°C in 1026 (6.6%), 37.5-38.2°C in 2096 (13.4%), 36-37.4°C in 9216 (59.0%), and <36°C in 3274 (21.0%). Temperatures changed rapidly over the first 12 h and, by 24 h, approached reasonably stable levels. For the admission temperature groups of ≥38.3°C, 37.5-38.2°C, 36-37.4°C, and <36°C, fever deficits were a median of 47 (interquartile range (IQR), 24 to 72), 53 (IQR, 29 to 83), 69 (IQR, 40 to 100), and 85 (IQR, 52 to 123) degree-hours, respectively, and 147 (14%), 248 (12%), 1,104 (12%), and 549 (17%) died by day 30. After controlling for confounders, a high fever deficit, defined as a fever deficit above the median, during the first 24 h of ICU admission, was not associated with all-cause 30-day mortality (OR 1.02, 95% CI, 0.93-1.13; p = 0.7). Conclusion: Fever deficits were large, particularly when the initial body temperature was not febrile. Only 1 in 15 ICU patients with sepsis had an initial body temperature ≥38.3°C. Approximately 2000 adults a year with sepsis and an initial body temperature <37.5°C would potentially be eligible for a trial of therapeutic hyperthermia in our 12 ICUs.