Skip to main content
Top
Published in: Intensive Care Medicine 4/2019

01-04-2019 | Original

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

Authors: Paul J. Young, Rinaldo Bellomo, Gordon R. Bernard, Daniel J. Niven, Frederique Schortgen, Manoj Saxena, Richard Beasley, Mark Weatherall

Published in: Intensive Care Medicine | Issue 4/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Golding R, Taylor D, Gardner H, Wilkinson JN (2016) Targeted temperature management in intensive care—do we let nature take its course? JICS 17:154–159PubMed Golding R, Taylor D, Gardner H, Wilkinson JN (2016) Targeted temperature management in intensive care—do we let nature take its course? JICS 17:154–159PubMed
2.
go back to reference Manthous CA, Hall JB, Olson D, Singh M, Chatila W, Pohlman A, Kushner R, Schmidt GA, Wood LD (1995) Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med 151:10–14CrossRefPubMed Manthous CA, Hall JB, Olson D, Singh M, Chatila W, Pohlman A, Kushner R, Schmidt GA, Wood LD (1995) Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med 151:10–14CrossRefPubMed
3.
go back to reference Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT (2008) Occurrence and outcome of fever in critically ill adults. Crit Care Med 36:1531–1535CrossRefPubMed Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT (2008) Occurrence and outcome of fever in critically ill adults. Crit Care Med 36:1531–1535CrossRefPubMed
4.
go back to reference Laupland KB, Zahar JR, Adrie C, Schwebel C, Goldgran-Toledano D, Azoulay E, Garrouste-Orgeas M, Cohen Y, Jamali S, Souweine B, Darmon M, Timsit JF (2012) Determinants of temperature abnormalities and influence on outcome of critical illness. Crit Care Med 40:145–151CrossRefPubMed Laupland KB, Zahar JR, Adrie C, Schwebel C, Goldgran-Toledano D, Azoulay E, Garrouste-Orgeas M, Cohen Y, Jamali S, Souweine B, Darmon M, Timsit JF (2012) Determinants of temperature abnormalities and influence on outcome of critical illness. Crit Care Med 40:145–151CrossRefPubMed
5.
go back to reference Niven DJ, Stelfox HT, Shahpori R, Laupland KB (2013) Fever in adult ICUs: an interrupted time series analysis. Crit Care Med 41:1863–1869CrossRefPubMed Niven DJ, Stelfox HT, Shahpori R, Laupland KB (2013) Fever in adult ICUs: an interrupted time series analysis. Crit Care Med 41:1863–1869CrossRefPubMed
6.
go back to reference Young P, Saxena M, Bellomo R, Freebairn R, Hammond N, van Haren F, Holliday M, Henderson S, Mackle D, McArthur C, McGuinness S, Myburgh J, Weatherall M, Webb S, Beasley R (2015) Acetaminophen for fever in critically ill patients with suspected infection. N Engl J Med 373:2215–2224CrossRefPubMed Young P, Saxena M, Bellomo R, Freebairn R, Hammond N, van Haren F, Holliday M, Henderson S, Mackle D, McArthur C, McGuinness S, Myburgh J, Weatherall M, Webb S, Beasley R (2015) Acetaminophen for fever in critically ill patients with suspected infection. N Engl J Med 373:2215–2224CrossRefPubMed
7.
go back to reference Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918CrossRefPubMed Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918CrossRefPubMed
8.
go back to reference Schortgen F, Clabault K, Katsahian S, Devaquet J, Mercat A, Deye N, Dellamonica J, Bouadma L, Cook F, Beji O, Brun-Buisson C, Lemaire F, Brochard L (2012) Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 185:1088–1095CrossRefPubMed Schortgen F, Clabault K, Katsahian S, Devaquet J, Mercat A, Deye N, Dellamonica J, Bouadma L, Cook F, Beji O, Brun-Buisson C, Lemaire F, Brochard L (2012) Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 185:1088–1095CrossRefPubMed
9.
go back to reference Dallimore J, Ebmeier S, Thayabaran D, Bellomo R, Bernard G, Schortgen F, Saxena M, Beasley R, Weatherall M, Young P (2018) Effect of active temperature management on mortality in intensive care unit patients. Crit Care Resusc 20:150–163PubMed Dallimore J, Ebmeier S, Thayabaran D, Bellomo R, Bernard G, Schortgen F, Saxena M, Beasley R, Weatherall M, Young P (2018) Effect of active temperature management on mortality in intensive care unit patients. Crit Care Resusc 20:150–163PubMed
12.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829CrossRefPubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829CrossRefPubMed
13.
go back to reference Metnitz PG, Moreno RP, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR (2005) SAPS 3—from evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description. Intensive Care Med 31:1336–1344CrossRefPubMedPubMedCentral Metnitz PG, Moreno RP, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR (2005) SAPS 3—from evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description. Intensive Care Med 31:1336–1344CrossRefPubMedPubMedCentral
14.
go back to reference Niven DJ, Stelfox HT, Leger C, Kubes P, Laupland KB (2013) Assessment of the safety and feasibility of administering antipyretic therapy in critically ill adults: a pilot randomized clinical trial. J Crit Care 28:296–302CrossRefPubMed Niven DJ, Stelfox HT, Leger C, Kubes P, Laupland KB (2013) Assessment of the safety and feasibility of administering antipyretic therapy in critically ill adults: a pilot randomized clinical trial. J Crit Care 28:296–302CrossRefPubMed
15.
go back to reference Saxena MK, Taylor C, Billot L, Bompoint S, Gowardman J, Roberts JA, Lipman J, Myburgh J (2015) The effect of paracetamol on core body temperature in acute traumatic brain injury: a randomised, controlled clinical trial. PLoS One 10:e0144740CrossRefPubMedPubMedCentral Saxena MK, Taylor C, Billot L, Bompoint S, Gowardman J, Roberts JA, Lipman J, Myburgh J (2015) The effect of paracetamol on core body temperature in acute traumatic brain injury: a randomised, controlled clinical trial. PLoS One 10:e0144740CrossRefPubMedPubMedCentral
16.
go back to reference Drewry AM, Ablordeppey EA, Murray ET, Stoll CRT, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA (2017) Antipyretic therapy in critically ill septic patients: a systematic review and meta-analysis. Crit Care Med 45:806–813CrossRefPubMedPubMedCentral Drewry AM, Ablordeppey EA, Murray ET, Stoll CRT, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA (2017) Antipyretic therapy in critically ill septic patients: a systematic review and meta-analysis. Crit Care Med 45:806–813CrossRefPubMedPubMedCentral
17.
go back to reference Young PJ, Saxena M, Beasley R, Bellomo R, Bailey M, Pilcher D, Finfer S, Harrison D, Myburgh J, Rowan K (2012) Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Med 38:437–444CrossRef Young PJ, Saxena M, Beasley R, Bellomo R, Bailey M, Pilcher D, Finfer S, Harrison D, Myburgh J, Rowan K (2012) Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Med 38:437–444CrossRef
Metadata
Title
Fever control in critically ill adults. An individual patient data meta-analysis of randomised controlled trials
Authors
Paul J. Young
Rinaldo Bellomo
Gordon R. Bernard
Daniel J. Niven
Frederique Schortgen
Manoj Saxena
Richard Beasley
Mark Weatherall
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 4/2019
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-019-05553-w

Other articles of this Issue 4/2019

Intensive Care Medicine 4/2019 Go to the issue