Randomized controlled trial of the effect of regular paracetamol on influenza infection


Abstract

Background and objective

Anti-pyretic treatment is recommended in the management of influenza infection. In animal models anti-pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection.

Methods

This is a randomized, double-blind, placebo-controlled trial of adults aged 18–65 years with influenza-like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT-PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log10 viral load from Baseline to Day 5.

Results

A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR-positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log10 viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR.

Conclusion

Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR-confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection.

Severe H1N1 Influenza Infection: Hold the Corticosteroids!


An observational European study shows that corticosteroids increased risk for pneumonia and conferred no mortality benefit in patients with severe H1N1 infection.

Use of corticosteroids to mitigate the cytokine storm that might contribute to poor outcomes in otherwise healthy people with pandemic H1N1 influenza infection is controversial, even in those with acute respiratory distress syndrome (ARDS). In a prospective observational study, investigators evaluated the effect of corticosteroids on outcomes in 220 intensive care unit (ICU) patients who were enrolled in the European Society of Intensive Care Medicine H1N1 registry from June 2009 through February 2010. H1N1 influenza A infection was confirmed in 194 patients, probable in 2, and suspected in 24. All patients received antivirals, and 78% were mechanically ventilated.

The 126 patients (57%) who received corticosteroids on ICU admission (dosages equivalent to >24 mg/day of methylprednisone or >30 mg/day of prednisone), compared to patients who did not, were significantly older, more likely to have comorbid pulmonary conditions, and more likely to be chronic corticosteroid users. Although patients who received corticosteroids on ICU admission were significantly more likely to contract hospital-acquired pneumonia (26% vs. 14%; odds ratio, 2.2) and to die in the ICU (46% vs. 18%; OR, 3.8), the association with mortality was no longer present after adjustment for severity of disease and other confounding variables (age, asthma, chronic obstructive pulmonary disease, chronic corticosteroid use). Results were similar when the analysis was limited to the 74% of patients with ARDS.

Comment: This study is limited by its observational nature, variable dosing of oseltamivir, and that patients who received “rescue” corticosteroids after ICU admission were not considered part of the corticosteroid group. For now, corticosteroids do not seem helpful — and might be harmful — in patients with H1N1 influenza.

Kristi L. Koenig, MD, FACEP

Published in Journal Watch Emergency Medicine February 18, 2011