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Roman Kula
University Hospital Ostrava: Fakultni Nemocnice Ostrava
Corresponding Author
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Background: Fever is a defence against infection. However, its benefit might be masked by cardiorespiratory maladaptation to thermal stress. The aim of this study was to evaluate the effect of fever control on the outcomes of septic patients who were presumed to have a sufficient cardiorespiratory reserve.
Methods: Septic patients with a presumed sufficient cardiorespiratory reserve and fever (>38.3°C) of infectious etiology were randomised to one of the two study arms. In the aggressive arm, the antipyretic intervention was started immediately when the body temperature rose above 38.3°C, in the conservative arm only when it exceeded 39.5°C. Both pharmacological (ibuprofen) and physical antipyretic methods were used. The total SOFA score on day 7 was selected as the primary endpoint. Non-parametric tests were used for statistics when comparing variables between the study arms.
Results: A total of 5998 patients were screened for fever of infectious etiology. 609 patients met inclusion criteria, of whom 154 patients were randomised. A significantly higher body temperature and longer duration of febrile episode was reached in the conservative arm. The SOFA score was significantly lower on day 7 when the conservative approach was applied. In-hospital mortality did not differ between the arms. When analysing a subgroup of patients with ICU stay < 4 days, a significantly lower SOFA score on day 3 and a tendency for lower in-hospital mortality was observed in the aggressive arm. In contrast, among patients with ICU stay ≥ 6 days, a significantly lower SOFA score on day 7 and significantly lower in-hospital mortality was found in the conservative arm.
Conclusions: The conservative approach to the treatment of fever in septic patients with sufficient cardiorespiratory reserve was associated with a lower total SOFA score on day 7 compared to the aggressive approach. However, both approaches may positively influence outcome of septic patients: the aggressive approach seems to be beneficial in the early stage of sepsis, and the conservative approach in the stage of sepsis remission.
Trial registration: The study was retrospectively registered at http://www.clinicaltrials.gov (Ref. No. NCT04227652).
Keywords
Fever, Sepsis, Physiological reserve, Nosocomial infection, Ibuprofen
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This is a list of supplementary files associated with this preprint. Click to download.
- ADDITIONALFILE1.pdf
Table 1. Characteristics of the patients at the baseline in a subgroup of patients with a length of ICU stay < 4 days from randomisation. Table 2. Description of the first septic episode in a subgroup of patients with a length of ICU stay < 4 days from randomisation. Table 3. Study endpoints in subgroup of patients with a length of ICU stay < 4 days from randomisation. Figure 1. The total SOFA score, lactate, PCT, IL-6 and ScvO2 levels during the study period in a subgroup of patients with a length of ICU stay < 4 days from randomisation.
- ADDITIONALFILE2.pdf
Table 1. Characteristics of the patients at the baseline in a subgroup of patients with a length of ICU stay ≥ 4 days from randomisation. Table 2. Description of the first septic episode in a subgroup of patients with a length of ICU stay ≥ 4 days from randomisation. Table 3. Study endpoints in subgroup of patients with a length of ICU stay ≥ 4 days from randomisation. Figure 1. The total SOFA score, lactate, PCT, IL-6 and ScvO2 levels during the study period in a subgroup of patients with a length of ICU stay ≥ 4 days from randomisation.
- ADDITIONALFILE3.pdf
Table 1. Characteristics of the patients at the baseline in a subgroup of patients with a length of ICU stay ≥ 6 days from randomisation. Table 2. Description of the first septic episode in a subgroup of patients with a length of ICU stay ≥ 6 days from randomisation. Table 3. Study endpoints in subgroup of patients with a length of ICU stay ≥ 6 days from randomisation. Figure 1. The total SOFA score, lactate, PCT, IL-6 and ScvO2 levels during the study period in a subgroup of patients with a length of ICU stay ≥ 6 days from randomisation.
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CURRENT STATUS: Under Review
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This preprint is under consideration at Critical Care. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Roman Kula
University Hospital Ostrava: Fakultni Nemocnice Ostrava
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 15 Mar, 2021
Submission checks complete
On 13 Mar, 2021
Editor invited
On 10 Mar, 2021
Editor assigned
On 09 Mar, 2021
First submitted
On 09 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Fever is a defence against infection. However, its benefit might be masked by cardiorespiratory maladaptation to thermal stress. The aim of this study was to evaluate the effect of fever control on the outcomes of septic patients who were presumed to have a sufficient cardiorespiratory reserve.
Methods: Septic patients with a presumed sufficient cardiorespiratory reserve and fever (>38.3°C) of infectious etiology were randomised to one of the two study arms. In the aggressive arm, the antipyretic intervention was started immediately when the body temperature rose above 38.3°C, in the conservative arm only when it exceeded 39.5°C. Both pharmacological (ibuprofen) and physical antipyretic methods were used. The total SOFA score on day 7 was selected as the primary endpoint. Non-parametric tests were used for statistics when comparing variables between the study arms.
Results: A total of 5998 patients were screened for fever of infectious etiology. 609 patients met inclusion criteria, of whom 154 patients were randomised. A significantly higher body temperature and longer duration of febrile episode was reached in the conservative arm. The SOFA score was significantly lower on day 7 when the conservative approach was applied. In-hospital mortality did not differ between the arms. When analysing a subgroup of patients with ICU stay < 4 days, a significantly lower SOFA score on day 3 and a tendency for lower in-hospital mortality was observed in the aggressive arm. In contrast, among patients with ICU stay ≥ 6 days, a significantly lower SOFA score on day 7 and significantly lower in-hospital mortality was found in the conservative arm.
Conclusions: The conservative approach to the treatment of fever in septic patients with sufficient cardiorespiratory reserve was associated with a lower total SOFA score on day 7 compared to the aggressive approach. However, both approaches may positively influence outcome of septic patients: the aggressive approach seems to be beneficial in the early stage of sepsis, and the conservative approach in the stage of sepsis remission.
Trial registration: The study was retrospectively registered at http://www.clinicaltrials.gov (Ref. No. NCT04227652).
Figure 1
Figure 2
Figure 3
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