Introduction
The biology of fever
Regulation of normal body temperature
The cellular and molecular basis of the febrile response
Heat shock proteins and the febrile response
The physiological consequences of fever
The immunological consequences of fever
The effects of fever on the viability of microbial pathogens
The significance of fever in animals with infections
The significance of fever in humans with infection
Fever, hyperthermia, and antipyresis in non-ICU patients with infections
Viral infections
Bacterial infections
Fever in ICU patients with infections
Observational studies of fever and fever management in ICU patients
Design, setting, and participants | Key findings | |
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Laupland et al. 2008 [30] | Retrospective cohort study of patients admitted to four ICUs in Calgary between 2000 and 2006; n = 24,204 ICU admissions in 20,466 patients | •Fever of ≥ 38.3 °C developed during 44 % of ICU admissions and high fever ≥ 39.3 °C during 8 % of admissions • Fever was not associated with increased ICU mortality but high fever was associated with a significantly increased risk of death |
Young et al. 2011 [31] | Inception cohort study in three tertiary ICUs in Australia and New Zealand over six weeks in 2010 identifying patients with fever > 38 °C and known or suspected infection; n = 565 | 9 % of patients admitted to ICU had or developed a fever and known or suspected infection |
Selladurai et al. 2011 [32] | Retrospective cohort study of patients admitted to a single tertiary ICU in Australia with sepsis between December 2009 and August 2010; n = 106 | • 69 % of septic patients received paracetamol at least once during their first seven days in ICU • 88 % of septic patients with a fever > 38 °C received paracetamol during their first seven days in ICU • Septic patients with a fever > 38 °C were 6.8 times (95 % CI 1.9-24.7) more likely to receive paracetamol than septic patients who were not febrile |
Lee et al. 2012 [33] | Inception cohort study of consecutive patients admitted to 25 ICUs in Japan and Korea for more than 48 hours over three months in 2009; n = 1,425 | • NSAID use independently associated with increased 28-day mortality in patients with sepsis (adjusted OR 2.61; 95 % CI 1.11-6.11; p = 0.03) but with a trend towards a decreased 28-day mortality in patients without sepsis (adjusted OR 0.22; 95 % 0.031.74; p = 0.15) • Paracetamol use independently associated with increased 28-day mortality in patients with sepsis (adjusted OR 2.05; 95 % CI 1.19-3.55; p = 0.01) but with a trend towards a decreased 28-day mortality in patients without sepsis (adjusted OR 0.58; 95 % 0.06-5.26; p = 0.63) |
Laupland et al. 2012 [34] | Inception cohort study of patients admitted to French ICUs contributing to the Outcomerea database between April 2000 and November 2010; n = 10,962 | • 25.7 % of patients had a fever of ≥ 38.3 °C at ICU presentation •Fever was not associated with increased mortality but hypothermia was an independent predictor of death in medical patients |
Young et al. 2012 [35] | Retrospective cohort study of 636,051 patients in Australia, New Zealand and the UK admitted to the ICU between 2005 until 2009 | • Elevated body temperature in the first 24 hours in ICU was associated with an increased risk of mortality in patients without infections and a decreased risk of mortality in patients with infections |
Niven et al. 2012 [36] | Interrupted time series analysis of cumulative fever incidence in ICUs in Calgary from 2004-2009 | • The cumulative incidence of fever ≥ 38.3 during ICU admission decreased from 50.1 % to 25.5 % over the 5.5 years of the study |
Interventional studies of fever management in ICU patients
Design, setting, and participants | Key findings | |
---|---|---|
Bernard et al. 1991 [42] | Double blind placebo-controlled trial of ibuprofen in patients with severe sepsis; n = 30 | • Ibuprofen significantly reduced temperature, heart rate, and peak airway pressure • There was no significant difference between ibuprofen and placebo in terms of in-hospital mortality rate (18.8 % ibuprofen-treated group vs. 42.9 % placebo-treated group) |
Bernard et al. 1997 [43] | Double blind placebo-controlled trial of ibuprofen in patients with severe sepsis in seven centers in North America; n = 455 | • Ibuprofen significantly reduced temperature, heart rate, oxygen consumption, and lactic acidosis in patients with severe sepsis • Ibuprofen did not alter the incidence or duration of shock or ARDS and had no significant effect on 30-day mortality (37 % ibuprofen-treated group vs. 40 % placebo-treated group) |
Memis et al. 2004 [44] | Double blind placebo-controlled trial of lornoxicam in patients with severe sepsis in one center in Turkey; n = 40 | • No significant difference between lornoxicam and placebo was demonstrated in terms of hemodynamic parameters, biochemical parameters, cytokine levels, or ICU mortality (35 % lornoxicam-treated group vs. 40 % placebo-treated group) |
Morris et al. 2011 [45] | Multicenter, randomized trial comparing the antipyretic efficacy of a single dose of placebo,100 mg, 200 mg, or 400 mg of i. v. ibuprofen in hospitalized patients of whom > 90 % had infections; n = 120 (53 critically ill) | • All doses of ibuprofen tested were effective in lowering temperature • There were no significant difference between treatment groups with respect to ventilation requirements, length of stay or in-hospital mortality (4 % placebo, 3 % 100 mg ibuprofen, 7 % 200 mg ibuprofen, 6 % 400 mg ibuprofen) |
Haupt et al. 1991 [46] | Multicenter, placebo-controlled randomized trial of ibuprofen in patients with severe sepsis; n = 29 | • Ibuprofen significantly reduced body temperature • There was no significant difference between the treatment groups in terms of in-hospital mortality (30.8 % in the placebo group vs. 56.3 % in the ibuprofen group) |
Schulman et al. 2006 [47] | Single center, unblinded, randomized trial of aggressive vs. permissive temperature management in febrile patients in a trauma ICU; n = 82 | • There was no significant difference between the treatment arms in terms of the number of new infections • The in-hospital mortality was 15.9 % in the aggressive treatment group and 2.6 % in the permissive treatment group (p = 0.06) |
Niven et al. 2012 [48] | Multicenter, unblinded randomized trial of aggressive vs. permissive temperature management in febrile ICU patients; n = 26 | • The mean daily temperature was lower in the patients assigned to aggressive fever management • The in-hospital mortality was 21 % in the aggressive treatment group and 17 % in the permissive treatment group (p = 1.0) |
Schortgen et al. 2012 [49] | Multicenter, randomized controlled trial of external cooling in patients with fever and septic shock receiving mechanical ventilation in seven centers in France; n = 200 | • External cooling significantly reduced body temperature • External cooling did not alter the proportion of patients who had a 50 % reduction in vasopressor dose after 48 hours • Day-14 mortality was significantly lower in the patients assigned to external cooling but there was no significant difference between the groups in terms of ICU or in-hospital mortality |