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Table 2 Summary of randomized controlled trials investigating the management of fever in critically ill adults

From: Fever management in intensive care patients with infections

 

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

  1. ARDS: acute respiratory distress syndrome; ICU: intensive care unit.