Wednesday, August 14, 2013

Does a Failure to Respond to Antipyretics Predict Serious Illness in Children With a Fever?

Arch Dis Child. 2013;98(8):644-646. 
Fever in children is a common reason for parents to seek medical advice. Around 25% of emergency department assessments in children are because of high temperature.
Many of these children have trivial self-limiting viral infections but a significant minority will have a serious bacterial illness requiring prompt treatment with appropriate antibiotics. Despite the introduction of national guidelines, there is still considerable controversy on how to manage these children. One method commonly used by both clinicians and parents to identify whether they think a febrile child requires further evaluation is the response of the temperature to antipyretics. There is a general belief that a fever of benign aetiology responds better to antipyretics compared with a fever due to a serious bacterial illness.
A review of the literature revealed eight studies that test this hypothesis. All the studies were heterogeneous and had a number of different methodological weaknesses. They were also quite old, with the most recent being published nearly 20 years ago. 
In general, the published literature suggests that response to antipyretics in febrile children cannot be used to accurately predict the likelihood of serious bacterial illness. There are three prospective cohort studies that showed that there was no difference in temperature response to antipyretics in children with a bacteraemia compared with children with no bacteraemia.Two further prospective studies examined the response to antipyretics in children with bacterial illnesses compared with viral illnesses, and in children according to the severity of underlying illness. Again, temperature response to antipyretics was not significantly less in children with bacterial illnesses. Indeed, in one of these studies, febrile children with either a bacteraemia, pneumonia or group A streptococcus infection actually had a better response to paracetamol compared with children with other illnesses. A case-control study that compared children with a non-bacterial febrile illness with those with meningitis or an isolated bacteraemia also concluded that response to antipyretics cannot predict serious illness.
Two of the identified studies did suggest that a poor response to antipyretics predicted serious illness in febrile children. However, both these studies were by the same authors and were based on exactly the same cohort of patients. There were also significant methodological limitations that would be expected to affect the results of these studies. These include their retrospective nature that patients were not enrolled consecutively, that a standard dose of paracetamol was not used and that the time at which the temperature was rechecked after receiving paracetamol was variable. In addition, in Mazur et al, the temperature decrease in bacteraemic children compared with non-bacteraemic children following paracetamol is unlikely to be clinically useful (1.0°C vs 1.2°C), even though it reached statistical significance.
It is interesting to note that all the studies published on this topic examined temperature response to either paracetamol or aspirin. Aspirin is no longer prescribed to children due to the risk of Reye's syndrome while the use of ibuprofen as an antipyretic in children is now widespread. There are currently no studies that examine whether temperature response to ibuprofen predicts serious illness in children. As the results of studies using paracetamol or aspirin are not necessarily generalisable to ibuprofen, this remains an area for future research.
In conclusion, the majority of published evidence indicates that clinicians cannot rely on response to antipyretics to predict serious illness in febrile children. Further research should aim to discover whether this finding applies to ibuprofen. In the meantime, assessment by an experienced examiner together with judicious use of laboratory tests and/or a period of observation probably remains the best way to decide on the management of febrile children.

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