Combining drugs ‘sees off child fevers sooner’, says The Times today. It reported on a study that compared the effectiveness of ibuprofen to paracetamol and the two drugs combined. Several newspapers covered the story and gave different interpretations of the study’s implications. The Times focused on the success of combining the drugs, while BBC News takes the view that ibuprofen may be best, and the Daily Mail reports that the advice to use both drugs is confusing and contradicts NICE guidelines.
This study provides reliable evidence that ibuprofen is more effective than paracetamol at reducing fever quickly, and reducing the overall time spent with a fever, especially within the first four hours. Combining the two drugs appeared to have a similar effect to ibuprofen alone. There was no difference in the number of adverse events (side effects) between the treatment groups. Although the authors state the current guidance is overly cautious, and that the drugs can be combined to reduce the time children have a fever, this is a single, short-term study. Further evidence of safety will probably be needed before the guidance, mainly aimed at identifying high-risk symptoms in children with fever, is changed.
Where did the story come from?
Dr Alastair D. Hay and colleagues from the Academic Unit of Primary Health Care, at the University of Bristol and the Faculty of Health and Social Care, at the University of West England carried out the research. The study was funded by the National Institute for Health Research’s health technology assessment programme. The study was published in the peer-reviewed British Medical Journal.
What kind of scientific study was this?
This was a three-arm blinded, individually randomised controlled trial. It aimed to investigate if combining paracetamol and ibuprofen is more effective than each drug alone at increasing the time that young children spend without fever and relieving their discomfort.
The target group was sick children aged six months to six years, who had a temperature of between 37.8°C and 41.0°C as a result of illnesses that could be managed at home. The children were recruited and followed up between January 2005 and May 2007 from 35 primary care sites in Bristol that agreed to take part in the study. Of the 4,515 children that visited the primary care sites with a fever, 3,477 were excluded, mostly because they did not have a sufficient fever. This left 1,038 children who could potentially take part in the study. This number was reduced further to 156 by parents not wanting to commit to the study, having concerns about the drugs or children seeing a GP but not the researchers. None of those who took part required hospital admission, appeared dehydrated to a clinician, had recently participated in another trial or if they had a known intolerance, allergy, or contraindication to paracetamol or ibuprofen. Children who had long-term nerve, heart, kidney, liver or lung conditions (except asthma) were also excluded, as were those with parents who could not read or write in English.
The 156 children were split into the three treatment groups, 52 in each group. All three groups received advice on physical measures to reduce temperature (such as fanning and tepid sponging) and the parents were then given paracetamol plus ibuprofen, paracetamol alone or ibuprofen alone.
The researchers measured the time without fever (defined as temperature of less than 37.2°C) in the first four hours after the first dose was given and the proportion of children reported as being normal on the discomfort scale after 48 hours. They also recorded the time to first occurrence of normal temperature (known as fever clearance), the time without fever over 24 hours, any fever-associated symptoms and adverse effects.
What were the results of the study?
The researchers report that the children given paracetamol plus ibuprofen spent significantly less time with fever in the first four hours than the children given paracetamol alone (an adjusted difference of 55 minutes). The combination of drugs also proved more effective than ibuprofen alone, but this was not significant (an adjusted difference of 16 minutes with P=0.2).
Children given paracetamol plus ibuprofen also spent significantly less time with fever over 24 hours compared to those given paracetamol (4.4 hours) or those given ibuprofen (2.5 hours). Combined therapy cleared fever 23 minutes faster than paracetamol alone but no faster than ibuprofen alone.
No benefit was found for discomfort or other symptoms, although the researchers note that there was an insufficient number of patients enrolled in the trial to be certain of this. Adverse effects did not differ between groups.
What interpretations did the researchers draw from these results?
The researchers say that “parents, nurses, pharmacists, and doctors wanting to use medicines to supplement physical measures to maximise the time that children spend without fever should use ibuprofen first and consider the relative benefits and risks of using paracetamol plus ibuprofen over 24 hours”.
What does the NHS Knowledge Service make of this study?
This randomised trial appears reliable and seems most relevant to the treatment of fever in the first four hours. It is important to note that:
- The trial was conducted in children over six months of age and the recommendation to avoid drugs in children younger than three months still applies.
- Although the researchers advise that treatment should start with ibuprofen first for a more rapid resolution of fever, the study did not test this. However, the results do appear to support this recommendation.
- Care is needed to avoid overdose, and as the authors point out, between 6% and 13% of parents exceeded the maximum number of recommended doses in the first 24 hours. Confusion about the recommended doses may be more likely with multiple drugs.
This research further informs the debate about which drug is best and whether both can be safely given together, However, a change in guidance is only likely when all the evidence has been reviewed in line with planned updates to the NICE guideline. Further analysis of the costs of each strategy is expected from these same researchers at a later date.
Sir Muir Gray adds...
This is important, but it is only a single study. We need to see how this is combined with the results of other studies.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 3 September 2008
BBC News, 3 September 2008
The Times, 3 September 2008
Daily Mail, 3 September 2008
Links to the science
Cochrane Database of Systematic Reviews 2003, Issue 2
Cochrane Database of Systematic Reviews 2002, Issue 2
BMJ 2008; 337: Published 2 September