Randomized trial of the effect of intravenous paracetamol on inflammatory biomarkers and outcome in febrile critically ill adults

BACKGROUND AND THE PURPOSE OF THE STUDY: The febrile reaction is a complex response involving immunologic and other physiologic systems. Antipyretics are commonly used in critically ill patients with fever. We investigated the inflammatory responses following application of antipyretic therapy in febrile critically ill patients with Systemic Inflammatory Response Syndrome (SIRS). PATIENTS AND METHODS: In a prospective, randomized controlled study, critically ill patients with fever (T ≥ 38.3°C), SIRS diagnosed within 24 hours of Intensive Care Unit (ICU) admission and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥10 were randomized into two groups. Upon appearance of fever, one group received intravenous paracetamol 650 mg every 6 hours for 10 days and other group received no treatment unless temperature reached 40°C. Body temperature, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality and infectious complications were recorded. Levels of Interleukin-1 alpha (IL-1(α)), IL-6, IL-10, Tumour Necrosis Factor alpha (TNF(α)) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention. RESULTS AND DISCUSSION: During a period of 15-month screening, 20 patients met the criteria and randomized to the control or paracetamol group. Body temperature decreased significantly in the paracetamol group (p = 0.004) and control group (p = 0.001) after 24 hours, but there was no significant difference between two groups at this time point (p = 0.649). Levels of IL-6 and IL-10 decreased significantly (p = 0.025 and p = 0.047, respectively) in the paracetamol group at 24 hours but this was not of statistical significance in control group. No patterns over time in each group or differences across two groups were found for HS-CRP, TNF(α), and IL-1(α) (p > 0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups. CONCLUSION: These results suggest that antipyretic therapy may not be indicated in all ICU patients. Allowing fever to take its natural course does not appear to have detrimental effects on critically ill patients with SIRS and may avoid unnecessary expenses.