Abstract
It's a common scene in the community pharmacy. A parent with a bottle of Tempra or Tylenol or Motrin — maybe all 3 in hand — with questions about their feverish baby. Despite the view by some health care professionals that fever is not necessarily a bad thing, it's an alarming sign for a parent when their child is ill. The fever is often accompanied by discomfort and parents want to know what's best to bring the fever down and help their infant or child feel better. Is it acetaminophen or ibuprofen or both?
In an attempt to help answer this common question, Hay and colleagues conducted a 3-arm, blinded, randomized controlled trial of paracetamol (acetaminophen), ibuprofen and the combination of the 2 drugs in 156 children with fever aged 6 months to 6 years. 1 The children were recruited from UK primary care practices and the community and were admitted in the study with temperatures ranging from 37.8°C to 41.0°C.
The study had 2 primary outcomes: the number of minutes without fever in the first 4 hours and discomfort associated with fever at 48 hours. Due to difficulty in recruitment, the study did not have sufficient power to detect differences for the latter outcome.
The secondary outcomes of the study were the time to the temperature first falling below 37.2°C, time spent without fever over 24 hours and the proportion of children without fever-associated symptoms at 24 and 48 hours and on day 5.
What were the results of this study?
With respect to the primary outcomes, more time was spent without fever in the first 4 hours for the children in the paracetamol plus ibuprofen group (171.1 minutes) as compared to the ibuprofen group (156.0 minutes) and the paracetamol group (116.2 minutes). Only the difference between combination and paracetamol groups reached statistical significance. No difference was found in fever-associated discomfort between the 3 groups at 48 hours.
Looking at the secondary outcomes, the combination group had a faster onset to temperature below 37.2°C than the paracetamol group (–23.5 minutes, p = 0.025) as did ibuprofen vs paracetamol (–26.3 minutes, p = 0.015), but no significant difference was detected between the combination and ibuprofen alone. In addition, the combination treatment was associated with more time without fever in 24 hours than paracetamol (4.4 hours, p < 0.001) and than ibuprofen (2.5 hours, p = 0.008), but no significant difference was detected between ibuprofen and paracetamol. The authors also state that no consistent evidence of effect for fever-associated symptoms from 24 hours to day 5 was seen and they do not include this data in their report.
How do these results apply to practice?
The results of this study need to be interpreted with caution. The trial did not include a placebo arm (the inclusion of which might have further limited ability to recruit). The temperature recorded was the axillary and a temperature of 37.8°C was classified as fever, which is not always agreed upon as a cutoff for treatment. As the authors also recognize, the sample size does not allow for detection of difference in fever-associated discomfort, which could be argued is the more important of the 2 primary outcomes, while the time without fever in the first 4 hours may be a more important outcome for the parents.
Although for some outcomes the combination group appears superior, factors such as the potential for overdose, especially when complicating the dosing regimen, need to be considered before this recommendation is made. Even in this controlled clinical trial, cases of overdose were reported. From the results of this study, it would seem reasonable to suggest that those parents who would like to achieve faster relief of fever in the first 4 hours and have more time without fever in the first 24 hours should choose ibuprofen over paracetamol (acetaminophen). The study does not provide compelling evidence that the combination is worth the potential risks.