A5V4d

Feverish illness in children
Two RCTs found a higher proportion of children who were afebrile after they received alternating
ibuprofen and ibuprofen combined compared with children who received only ibuprofen. This finding
was statistically significant. This effect size was large. The evidence was of low to very low quality.
One RCT reported no difference in adverse events in children who received alternating paracetamol
and ibuprofen compared with children who received only paracetamol to treat fever. The evidence
was of low quality.
Paracetamol and ibuprofen combined compared with paracetamol and ibuprofen alternating
No data on quality of life was identified.
One RCT found no difference in temperature reduction in children who received alternating
paracetamol and ibuprofen compared with children who received combined paracetamol and
ibuprofen taken together to treat fever. The evidence was of low quality.
No evidence was found reporting adverse events.
Health economics profile
No cost effectiveness studies were identified for this question and no additional health economics
analysis was undertaken.
Evidence to recommendations
Relative value placed on the outcomes considered
The GDG stated that the overarching aim of the guideline was the early and accurate detection of
serious illness in children with fever. This allows for suitable treatment to begin, which will then reduce
morbidity and mortality.
For this review, the aim was to assess the effectiveness of antipyretics. The GDG stated ‘distress’
was the main concern for parents and carers, and for the majority of children with self-limiting viral
disease the aim of treatment would be to relieve ‘distress’. Therefore, change in a child’s level of
‘distress’ was used as the primary outcome. However, although ‘distress’ was the primary outcome,
the GDG recognised that is was a poorly understood concept and rarely measured in clinical studies,
therefore secondary outcomes of change in temperature and time without fever were also used as
proxies for ‘distress’. Furthermore, both short- and long-term adverse events were assessed.
Consideration of clinical benefits and harms
The GDG members stated that, to their knowledge, all relevant available evidence had been
reviewed.
The GDG emphasised that the evidence shows that both ibuprofen and paracetamol reduce
temperature in febrile children, and that both also improve some aspects of quality of life. Although
there was some evidence that paracetamol was associated with increased risks of asthma,
rhinoconjunctivitis and eczema, the GDG recognised that the evidence from this study did not show a
causal pathway between use of paracetamol and long-term conditions.
Evidence shows that improvement in quality of life and reduction in temperature was greater with
ibuprofen than paracetamol within 4 hours of treatment starting, but that there were no differences
over the longer term. No difference was found in the rate of adverse events reported. The GDG
concluded that these differences were not clinically important in that either agent is likely to be
effective in any individual case. On this basis the GDG concluded that either paracetamol or ibuprofen
could be used.
Evidence showed little difference between paracetamol and ibuprofen given alone or given
simultaneously to reduce temperature. The GDG recognised that some of the evidence showed a
small benefit in reducing temperature when both drugs were given together, but no evidence of a
reduction in distress, which was the primary outcome. The GDG recognised that the simultaneous
administration of paracetamol and ibuprofen is sometime used by healthcare professionals and
carers. However, there is no evidence on effectiveness to support this approach and a lack of data on
safety. Furthermore, each drug is known to be effective as a single agent and the potential for
confusion and drug administration errors is increased by using more than one drug.
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2013 Update