Fever control in critically ill adults. An individual patient data meta-analysis of randomised controlled trials

Abstract

Purpose

One potential way to protect patients from the physiological demands that are a consequence of fever is to aim to prevent fever and to treat it assiduously when it occurs. Our primary hypothesis was that more active fever management would increase survival among patient subgroups with limited physiological reserves such as older patients, patients with higher illness acuity, and those requiring organ support.

Methods

We conducted an individual-level patient data meta-analysis of randomised controlled trials to compare the outcomes of ICU patients who received more active fever management with the outcomes of patients who received less active fever management. The primary outcome variable of interest was the unadjusted time to death after randomisation.

Results

Of 1413 trial participants, 707 were assigned to more active fever management and 706 were assigned to less active fever management. There was no statistically significant heterogeneity in the effect of more active compared with less active fever management on survival in any of the pre-specified subgroups that were chosen to identify patients with limited physiological reserves. Overall, more active fever management did not result in a statistically significant difference in survival time compared with less active fever management [hazard ratio 0.91; (95% CI 0.75–1.10), P = 0.32].

Conclusions

Our findings do not support the hypothesis that more active fever management increases survival compared with less active fever management overall or in patients with limited physiological reserves.

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Acknowledgements

This research was conducted during the tenure of a Clinical Practitioner Research Fellowship from the Health Research Council of New Zealand held by PY. The Medical Research Institute of New Zealand is supported by independent research organisation funding from the Health Research Council of New Zealand.

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Correspondence to Paul J. Young.

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Conflicts of interest

Dr. Paul Young and Dr. Manoj Saxena report receiving speaker’s fees from Bard Medical Pty. Dr. Gordon Bernard reports having an equity stake and is on the Board of Directors for Cumberland Pharmaceuticals, Nashville, TN, makers of intravenous ibuprofen (Caldolor).

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An approval by an ethics committee was not applicable.

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Young, P.J., Bellomo, R., Bernard, G.R. et al. Fever control in critically ill adults. An individual patient data meta-analysis of randomised controlled trials. Intensive Care Med 45, 468–476 (2019). https://doi.org/10.1007/s00134-019-05553-w

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Keywords

  • Sepsis
  • Fever
  • Septic shock
  • Paracetamol
  • Non-steroidal anti-inflammatory drugs
  • Physical cooling