Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

Abstract

Background: Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.

Methods: We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia.

Results: With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever.

Conclusions: Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011.

Keywords: Blood cultures; Body temperature; Fever; Lactate; Mortality; Outcome; PCT; Prognosis; Sepsis.

Fig. 1

Frequency distribution of body temperature (°C) in 6542 patients with new onset of severe sepsis

Fig. 2

Lactate concentrations (mmol/ml, a) and procalcitonin concentrations (ng/ml, b), median and interquartile range, associated with body temperature intervals (°C); p value for overall difference, each white letter denotes a homogenous subgroup with increasing values from a to d, categories not sharing a common letter are significantly different from each other. Kruskal–Wallis test with stepwise post hoc comparison

Fig. 3

Frequency of body temperature groups depending on mean outside temperature quartiles up to two days before sepsis onset. p = 0.002 for overall difference, superscript *denote cells significantly different from the expected frequencies (*p < 0.01, **p < 0.001) assessed by adjusted standardized residuals

Fig. 4

Odds ratios for 28-day mortality from a logistic regression model without and with adjustment for other predictors of mortality (see Additional file 2: aT1&aT2)