The Antipyretic Effect of High-Dose Paracetamol Versus Mefenamic Acid in the Treatment of Febrile Children: A Randomized Control Trial.

Introduction Fever is the most common presenting symptom in children and causes distress in patients and parents. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as antipyretics, they should be reserved for pain or chronic inflammatory conditions due to safety concerns. If we can safely achieve the same antipyretic effect using a higher dose (20 mg/kg) of paracetamol, NSAIDs may be avoided for treating fever. There is a paucity of literature comparing the antipyretic effect of mefenamic acid and high-dose paracetamol. We hypothesized that there would be no difference in the antipyretic effect of high-dose paracetamol and mefenamic acid. Methods In this randomized control trial, 165 febrile children were randomly allocated to one of the following three groups: standard-dose (15 mg/kg) paracetamol (SDPCM) as the control group and high-dose (20 mg/kg) paracetamol (HDPCM) and mefenamic acid (6 mg/kg) (MFN) as the intervention groups. The temperature was measured using a digital thermometer at the start of drug dosage and every 15 minutes until it reached normal. One-way between-group analysis of variance (ANOVA) was used to compare outcome measures such as time for temperature to reach normal, fall of temperature in 60 minutes, and time for the next fever. Post hoc analysis was performed to compare mean differences. Patients were monitored for adverse effects. Results Out of 165 enrolled patients, 159 were analyzed. The baseline demographic data were comparable among the groups. There was a statistically significant difference in the mean time taken for the temperature to reach normal (F-value (F) (2,156)=3.184, p<0.05) and the mean reduction in temperature at 60 minutes (F (2,156)=23.40, p<0.001) among the groups. The mean time for temperature to reach normal in the SDPCM group (97.50±26.60 minutes) was longer than that in the HDPCM (85.09±31.43 minutes) and MFN (84.90±30.42 minutes) groups. The decrease in temperature over 60 minutes was greater in the HDPCM (0.46°C±0.19°C) and MFN (0.45°C±0.11°C) groups than in the SDPCM (0.33°C±0.10°C) group. The time to the next fever spike was shorter for the SDPCM group (5.07±2.66 hours) than for the HDPCM (7.20±3.08 hours) and MFN (8.82±3.83 hours) groups. Post hoc analysis demonstrated that high-dose paracetamol and mefenamic acid had similar and faster antipyretic effects than standard-dose paracetamol. Although the duration of action was found to be longer in the mefenamic acid group, the difference was not statistically significant. There were negligible adverse effects in the groups. Conclusion  Standard-dose paracetamol (15 mg/kg/dose) had a slower and shorter antipyretic effect than high-dose paracetamol (20 mg/kg/dose) and mefenamic acid (6 mg/kg/dose). A single dose of high-dose paracetamol was safe and had a similar antipyretic effect as mefenamic acid. Mefenamic acid may be avoided as an antipyretic and spared for pain and anti-inflammatory indications. Multicentered double-blind clinical trials with larger sample sizes and comparisons of other NSAIDs will be required to confirm these findings.