Relation between initial hypothermia, course of the hypothermia and mortality in patients with septic shock: a post-hoc analysis of the SEPSISPAM randomized trial - 12/03/26

Doi : 10.1016/j.aicoj.2026.100051

Louis Bordeau ^a, Valérie Seegers ^b, Julien Demiselle ^c,^d, Frédérique Schortgen ^e, Fabien Grelon ^f, Bruno Mégarbane ^g, Nadia Anguel ^h, Jean-Paul Mira ⁱ, Pierre-François Dequin ^j, Soizic Gergaud ^k, Nicolas Weiss ^l, François Legay ^m, Yves Le Tulzo ⁿ, Marie Conrad ^o, Remi Coudroy ^p, Frédéric Gonzalez ^q, Christophe Guitton ^r, Fabienne Tamion ^s, Jean-Marie Tonnelier ^t, Jean Pierre Bedos ^u, Thierry Van Der Linden ^v, Antoine Vieillard-Baron ^w,^x, Eric Mariotte ^y, Gaël Pradel ^z, Olivier Lesieur ^A, Jean-Damien Ricard ^B, Fabien Hervé ^C, Damien du Cheyron ^D, Claude Guerin ^E, Alain Mercat ^a, Jean-Louis Teboul ^F, Peter Radermacher ^a,^G, Pierre Asfar ^a, Nicolas Fage ^a,^h,^H,⁎

^a Department of Medical Intensive Care, University Hospital of Angers, Angers, France

^b Biometry department Biométrie, Western Cancer Institute, Paul Papin Center, Angers, France

^c Department of Intensive Care (Service de Médecine Intensive – Réanimation), Hôpital de Hautepierre, University Hospital of Strasbourg, Strasbourg, France

^d INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France

^e Intercommunal Hospital Center, Department of Adult Intensive Care, Créteil, France

^f Medical and Surgical Intensive Care Unit, Le Mans Hospital, Le Mans, France

^g Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris University, INSERM UMRS-1144, Paris, France

^h Department of Medical Intensive Care, Bicêtre University Hospital, AP-HP, Paris-Saclay University, Le Kremlin Bicêtre, France

ⁱ Department of Medical Intensive Care, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France – University of Paris Cité, Paris, Franc - Institut Cochin, INSERM U1016, CNRS UMR 8104, University of Paris Cité

^j Department of Medical Intensive Care, Tours University Hospital, Tours, France

^k Department of Surgical Intensive Care, University Hospital of Angers, Angers, France

^l Department of Medical Intensive Care, Georges Pompidou European Hospital, Assistance Publique – Hôpitaux de Paris, University of Paris, Paris, France

^m Medical and Surgical Intensive Care Unit, Saint Brieuc Hospital, Saint Brieuc, France

ⁿ Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital, Rennes, France

^o Department of Medical Intensive Care, Nancy University Hospital, Nancy, France

^p Department of Medical Intensive Care, INSERM CIC-1402, IS-ALIVE research group, University of Poitiers, CHU Poitiers, Poitiers, France

^q Department of Medical and Surgical Intensive Care, Avicenne Teaching Hospital, Bobigny, France

^r Department of Medical Intensive Care, Nantes University Hospital, Nantes, France

^s Univ Rouen Normandie, Inserm, ENVI UMR 1096, Department of Medical Intensive Care, F-76000 Rouen, France

^t Department of Medical Intensive Care, Brest University Hospital, Brest, France

^u Intensive Care Unit, Versailles Hospital, Le Chesnay, France

^v Department of Intensive Care, Hospital Group of the Catholic institute of Lille, FMMS-ETHICS EASaint Philibert Hospital, Catholic University of Lille, Lille, France

^w Department of Medical Intensive Care, University Hospital of Ambroise Paré, Boulogne Billancourt, France

^x Inserm U1018, Center for Research in Epidemiology and Population Health (CESP), Faculty of Paris Saclay, Villejuif, France

^y Department of Intensive Care, Saint Louis Hospital, Paris, France

^z Department of Intensive Care, Avignon Hospital, Avignon, France

^A Department of Medical and Surgical Intensive Care, La Rochelle Saint Louis Hospital, La Rochelle, France

^B University of Paris Cité, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive Réanimation, Colombes, France and Université Paris Cité, INSERM, IAME, UMR1137, Paris, France

^C Department of Medical and Surgical Intensive Care, Quimper Hospital, Quimper, France

^D Department of Medical Intensive Care, Caen University Hospital, Caen, France

^E Department of Medical Intensive Care, Edouard Herriot Hospital, Lyon, France

^F Paris-Saclay Medical School, Paris-Saclay University, Le Kremlin-Bicêtre, France

^G Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, Ulm, Germany

^H MITOVASC Laboratory UMR INSERM (French National Institute of Health and Medical Research), 1083 – CNRS 6015, University of Angers, Angers, France

^⁎ Corresponding author.

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Abstract

Background

In patients with septic shock as well as in the critically ill, the impact of hypothermia and core temperature changes during the first 24 hours on mortality remains uncertain. In this post-hoc analysis of the SEPSISPAM trial, we investigated the association between hypothermia at inclusion, hypothermia trajectories and 90-day mortality in patients with septic shock.

Methods

This post-hoc analysis of the SEPSISPAM trial included patients with septic shock enrolled within 6 hours of vasopressors initiation. Core temperature was assessed every 2 hours during the first 24 hours. Hypothermia was defined by a temperature < 36 °C. Mortality was assessed at day 90.

Results

We included 691 patients from the SEPSISPAM trial, of whom 103 (14.9%) presented with hypothermia at inclusion. After adjustment for confounding factors, as compared with patients without hypothermia at inclusion, patients with hypothermia at inclusion had a higher mortality (HR 1.92, 95% CI [1.38 – 2.67], p < 0.001). Three groups of patients were identified according to the evolution of their core temperature: “without hypothermia” (86.6%), i.e., patients without any hypothermia during the first 24 hours; “transient hypothermia” (10%), i.e., patients with hypothermia at inclusion and becoming normothermic during the first 24 hours, and “persistent hypothermia” (3.4%), i.e., patients with sustained hypothermia both at inclusion and during the first 24 hours. Compared with patients without hypothermia, the “persistent hypothermia” group had the highest mortality rate at day 90 (78.3%, HR 2.83 [1.62-4.95], p < 0.0001). Mortality at day 90 increased according to temperature trajectories, being highest in patients with persistent hypothermia (78%), followed by those with transient hypothermia (49%), and lowest in patients without hypothermia (40%).

Conclusion

In patients with septic shock, hypothermia at inclusion and persistence of hypothermia during the first 24 hours were associated with higher mortality at day 90. Mortality increased according to the course of hypothermia during the first 24 hours, being highest in patients with persistent hypothermia, followed by those with transient hypothermia, and lowest in patients who never developed hypothermia.

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Keywords : evolution of core temperature, hemodynamics, hypothermia, sepsis, septic shock, mortality

Abbreviations : AIC, CI, HR, ICU, MAP, SAPS II, SOFA