Temperature control in sepsis

Summary of Temperature Control in Sepsis


Abstract: This mini-review explores the complex role of temperature control in sepsis. While fever can serve as an adaptive immune response, extreme temperatures—either hyperthermia or hypothermia—may lead to harmful outcomes. Evidence on managing temperature in septic patients remains inconclusive, with limited support for the use of antipyretics or cooling to improve mortality. Hypothermia is consistently associated with worse outcomes, while therapeutic hypothermia has shown no survival benefits. The authors call for a more individualized approach based on recent findings, including the influence of the gut microbiota on temperature variability.


Key Points

  1. Fever Physiology and Immune Response: Fever results from a hypothalamic reset, promoting enhanced immune function including improved neutrophil activity and microbial clearance, although it can also induce metabolic strain and tissue damage at higher levels.

  2. Impact of Temperature on Pathogens and Antibiotic Efficacy: Elevated temperatures (>38.5°C) inhibit bacterial growth, enhance susceptibility to antibiotics, and improve antibiotic effectiveness on bacterial biofilms, thus aiding in microbial eradication.

  3. Negative Effects of Hyperthermia: Despite immunological advantages, high fever increases cardiac oxygen consumption, promotes vasodilation, and may accelerate coagulopathy via neutrophil extracellular traps and tissue factor expression.

  4. Role of Gut Microbiota: Patient temperature trajectories during sepsis correlate with intestinal microbiota composition, suggesting microbial communities may influence thermoregulation and sepsis outcomes.

  5. Fever as a Prognostic Indicator: Higher body temperatures in sepsis are associated with lower mortality, while hypothermia significantly increases the risk of death, possibly due to delayed recognition and inadequate treatment responses.

  6. Temperature Control Methods: Interventions include paracetamol, NSAIDs, and physical cooling. However, clinical trials (e.g., HEAT, CASS) show no clear survival benefit, and some therapies may provoke discomfort or increased metabolic demands.

  7. No Mortality Benefit of Antipyretics: Meta-analyses and randomized controlled trials have failed to demonstrate significant reductions in mortality with either pharmacological or external cooling strategies in septic patients.

  8. Rewarming Hypothermic Patients: While hypothermia correlates with higher mortality, limited data support the routine practice of active rewarming, although some pilot trials suggest potential survival benefits in afebrile or hypothermic septic patients.

  9. Recommendations for Bedside Practice: Temperature control should be conservative. Treat only very high fever (>39.5°C) with paracetamol and cooling if necessary, and consider gradual rewarming in hypothermic patients, avoiding shivering and associated complications.

  10. Conclusion and Future Directions: Despite a strong physiological rationale for temperature management, current evidence does not support aggressive temperature control for survival benefits in sepsis. Further research is required, particularly on the potential value of controlled hyperthermia in hypothermic or normothermic sepsis.

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Mechanisms of fever. Comments: PGE2 is a major component of fever production. PGE2 induces a higher hypothalamus set point and promotes peripheral heat production. PGE2 is synthesized by two pathways: direct stimulation of Kuppfer cells by exotoxins, or stimulation of leukocytes via the Pathogen Associated Molecular Patterns /toll like receptor (PAMPs/TLR) pathway, leading to the production of endogenous pyrogens. Fever has multiple molecular consequences, Heat shock protein is a key response to fever is represented. Legends: HSP, heat shock protein; IFN, interferon; IL, interleukin; LPS, lipopolysaccharide; NF-KB, nuclear factor-kappa B; OVLT, organum vasculosum of the lamina terminalis; PAMPs, Pathogen Associated Molecular Patterns; PGE2, prostaglandin E2; POA, pre-optic area; TNF, tumor necrosis factor.

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Temperature control in sepsis

Copyright © 2023 Doman, Thy, Dessajan, Dlela, Do Rego, Cariou, Ejzenberg, Bouadma, de Montmollin and Timsit. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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