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Table 1 Main RCTs comparing antipyretics with no treatment in adult critically ill patients

From: Should we treat pyrexia? And how do we do it?

  Study Patients Number Temperature criteria at inclusion Baseline temperature in the treatment group Antipyretic method Duration of treatment Primary end point Main results
SIRS and Sepsis Gozolli et al. [41] SIRS 38 ≥38.5 °C 39 (SD 0.3) Surface cooling Up to fever resolution (≤37.5 °C) Temperature difference Similar temperature and comfort evolution
Bernard et al. [15] Severe sepsis 455 Nonea 37.9 (SE 0.2) NSAID: IV ibuprofen 10 mg/kg/6 h 48 h 30-day mortality Lower temperature in the treatment group
No difference in mortality
Memis et al. [50] Severe sepsis 40 Nonea 37.8 (SD 0.75) NSAID: IV lornoxicam 8 mg/12 h 72 h Anti-inflammatory effects Similar temperature evolution
Schortgen et al. [27] Septic shock 200 ≥38.3 °C 38.8 (IQR 38.6–39.2) TTM 36.5–37 °C with surface cooling 48 h Dose of vasopressor Less vasopressor requirement and 14-day mortality in the treatment group
Janz [48] Severe sepsis 40 Nonea 37.7 (IQR 37–38.5) IV paracetamol 1 g/6 h 3 days Antioxidant effect Lower maximal temperature in the treatment group
Young et al. [29] Suspected infection 700 ≥38 °C 38.5 (SD 0.5) IV paracetamol 1 g/ 6 h Up to fever resolution (<37.5 °C, 24 h) or day 28 ICU-free days up to day 28. Lower temperature in the treatment group
No difference in ICU-free days
Acute brain injury den Hertog et al. [35] Stroke 1400 Between 36 and 39 °C 36.9 (SD 0.6) Enteral paracetamol 1 g/4 h 72 h Modified Rankin scale at 3 months Lower temperature in the treatment group
No difference in neurological outcome
Saxena et al. [46] TBI 41 Between 36 and 39 °C 37.3 (SD 0.8) IV paracetamol 1 g/4 h 72 h Temperature difference No difference in temperature
  1. aAntipyretics were given with the aim of testing the anti-inflammatory effects of NSAIDs
  2. IQR 25th–75th interquartile range, IV intravenous, NSAID non-steroidal anti-inflammatory drug, SD standard deviation, SE standard error, SIRS systemic inflammatory response syndrome, TBI traumatic brain injury