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

Abstract

Background and the purpose of the studyThe 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 methodsIn 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-1α), IL-6, IL-10, Tumour Necrosis Factor alpha (TNFα) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention.Results and discussionDuring 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, TNFα, and IL-1α (p > 0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups.ConclusionThese 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.

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

“…In the second study, 10 critically ill patients were administered 650 mg paracetamol intravenously every 6 h for 10 days; they were compared with 10 patients not administered any antipyretic unless core temperature reached 40°C. Circulating concentrations of interleukin 6 were significantly decreased from baseline in the paracetamol group but not in the control group, which was in agreement with our previous observations . However, two other prospective studies found that aggressive antipyretic treatment was not of benefit for critically ill patients with sepsis .…”

The efficacy of magnesium sulfate loading on microalbuminuria following SIRS: One step forward in dosing

“…Although, management of patients in ICU is somehow complicated and dependent of the status of each patient [24], it was decided to use an established protocol as a base amount for moderate dose of magnesium that was safe over the years in ICU [25]. Two fold of that dose has been assumed as high dose of magnesium for this study.…”

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

“…Data from critically ill patients in general are available. We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160][161][162][163][164][165][166][167][168][169][170][171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81-1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70-0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29). Given the safety of acetaminophen and lack of harm in the body of evidence, increasing patient comfort through fever management maybe important.…”