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

Daniel O Thomas-Rüddel, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, Philipp Simon, Sven-Olaf Kuhn, Reinhard Wetzker, Michael Bauer, Konrad Reinhart, Frank Bloos, MEDUSA study group, Gernot Marx, Achim Schindler, Tobias Schürholz, Heike Schlegel-Höfner, Gunther Lehmann, Annett Sander, Steffen Friese, Christian Scholz, Pia Fischer, Christina Fuchs, Lutz Becher, Norbert Salewsky, Torsten Schreiber, Anton Goldmann, Didier Keh, Katrin Schmid, Winfried Menning, Renate Steuckart, Robert Barz, Karin Dey, Meike Fahrenholz, Martin Müller, Herwig Gerlach, Susanne Toussaint, Jörg Brederlau, Friedhelm Bach, Dirk Buschmann, Ingo Gummelt, J Hoeschen, Marion Klaproth, Ina Vedder, Ulrike Bachmann-Holdau, Jürgen Eiche, Rolf Hauschild, Martina Lange, Davia Herrmann-Karbaum, Annette Lubasch, Marcus Rücker, Christian Icke, Alexander Lucht, Andreas Meier-Hellmann, Jan Wagner, Olaf Arnold, Steffen Kästner, Tobias Clausen, Michael Sternkopf, Robert Voswinckel, T Benndorf, Christel Eiserloh, Gerhard Kuhnle, Mathias Koch, Manuela Gerber, Matthias Gründling, Liane Guderian, Sven-Olaf Kuhn, Christian Scheer, Gerd Scheiber, Frank Bloos, Susann Christink, Martina Kortegast, Claudia Matthäus-Krämer, Marcel Mücke, Bernhard Poidinger, Hendrik Rüddel, Ulrike Redlich, Daniel Schwarzkopf, Daniel Thomas-Rüddel, Christel Volkmer, Stefanie D'Aria, Thees Lemke, Birgit Michaelsen, Dirk Schädler, Nina Schulz-Ruhtenberg, Norbert Weiler, Martin Anetseder, Zoran Textor, Udo Kaisers, Philipp Simon, Georg Braun, Nicole Jensen, Werner Gegenfurtner, Alexander Meinhardt, Robert Schmitt, Andrea Teichert, Klaus-Dieter Becker, Anja Diers, Florian Jelschen, Andreas Weyland, Frieder Knebel, Thomas Kupfer, Rüdinger Sinz, Petra Bautz, Annemarie Fischer, Armin Seibel, Christoph Fleischhacker, Helene Häberle, Philipp Henn, Friederike Mezger, Peter Rosenberger, Reimer Riessen, Silvia Ziegler, Eberhard Barth, Hendrik Bracht, I Heymann, A Hinder, R Sens, Manfred Weiss, Christof Lascho, Henriette Micke, Falk Schmidt, Stefanie Schilling, Gabriele Wöbker, Daniel O Thomas-Rüddel, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, Philipp Simon, Sven-Olaf Kuhn, Reinhard Wetzker, Michael Bauer, Konrad Reinhart, Frank Bloos, MEDUSA study group, Gernot Marx, Achim Schindler, Tobias Schürholz, Heike Schlegel-Höfner, Gunther Lehmann, Annett Sander, Steffen Friese, Christian Scholz, Pia Fischer, Christina Fuchs, Lutz Becher, Norbert Salewsky, Torsten Schreiber, Anton Goldmann, Didier Keh, Katrin Schmid, Winfried Menning, Renate Steuckart, Robert Barz, Karin Dey, Meike Fahrenholz, Martin Müller, Herwig Gerlach, Susanne Toussaint, Jörg Brederlau, Friedhelm Bach, Dirk Buschmann, Ingo Gummelt, J Hoeschen, Marion Klaproth, Ina Vedder, Ulrike Bachmann-Holdau, Jürgen Eiche, Rolf Hauschild, Martina Lange, Davia Herrmann-Karbaum, Annette Lubasch, Marcus Rücker, Christian Icke, Alexander Lucht, Andreas Meier-Hellmann, Jan Wagner, Olaf Arnold, Steffen Kästner, Tobias Clausen, Michael Sternkopf, Robert Voswinckel, T Benndorf, Christel Eiserloh, Gerhard Kuhnle, Mathias Koch, Manuela Gerber, Matthias Gründling, Liane Guderian, Sven-Olaf Kuhn, Christian Scheer, Gerd Scheiber, Frank Bloos, Susann Christink, Martina Kortegast, Claudia Matthäus-Krämer, Marcel Mücke, Bernhard Poidinger, Hendrik Rüddel, Ulrike Redlich, Daniel Schwarzkopf, Daniel Thomas-Rüddel, Christel Volkmer, Stefanie D'Aria, Thees Lemke, Birgit Michaelsen, Dirk Schädler, Nina Schulz-Ruhtenberg, Norbert Weiler, Martin Anetseder, Zoran Textor, Udo Kaisers, Philipp Simon, Georg Braun, Nicole Jensen, Werner Gegenfurtner, Alexander Meinhardt, Robert Schmitt, Andrea Teichert, Klaus-Dieter Becker, Anja Diers, Florian Jelschen, Andreas Weyland, Frieder Knebel, Thomas Kupfer, Rüdinger Sinz, Petra Bautz, Annemarie Fischer, Armin Seibel, Christoph Fleischhacker, Helene Häberle, Philipp Henn, Friederike Mezger, Peter Rosenberger, Reimer Riessen, Silvia Ziegler, Eberhard Barth, Hendrik Bracht, I Heymann, A Hinder, R Sens, Manfred Weiss, Christof Lascho, Henriette Micke, Falk Schmidt, Stefanie Schilling, Gabriele Wöbker

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.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Frequency distribution of body temperature (°C) in 6542 patients with new onset of severe sepsis
Fig. 2
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
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
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)

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