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Fever is a common symptom in children and probably the most common reason for a child to be taken to the doctor.1 It is a cause of anxiety for carers, bringing to the surface many fears, most of which are unfounded.2,–,5 The reaction of the health professional may reinforce these concerns, particularly if the nature of fever and its significance is not properly communicated and fever is managed as an illness rather than a symptom.3
Antipyretic use is widespread both in prehospital and hospital settings. When temperature reduction is seen as the end point, it is not surprising that various drugs and combinations of drugs have been used. The systematic review of studies comparing combined treatment of the commonly used antipyretics—paracetamol and ibuprofen—concludes that there is little benefit from a polypharmaceutical approach.6 It is also a reminder of how intensely research studies have pursued temperature reduction as the primary end point, perhaps at the expense of more important end points and of thinking of fever as a physiological response.
What is fever?
All forms of life have a range of preferred environmental temperatures and seem to have thermoregulatory mechanisms. As homeotherms, humans regulate and maintain core temperature within very narrow limits, despite much larger variations in ambient temperature.
Fever is not simply an elevated body temperature but a controlled elevation of body temperature above the normal range.7 8 The rise in body temperature results from an elevation of the hypothalamic thermoregulatory set point. Important in this process is interleukin 1, a potent endogenous pyrogen and modulator of the immune response, working through mediators like prostaglandins. Thermoregulatory mechanisms operate to defend this new set point. A commonly used analogy is that the thermostat has been turned up. When the new body temperature is achieved, the thermoregulatory mechanisms still operate and respond to thermal stimuli but they aim to maintain the core temperature at a higher preset level. This distinguishes it from hyperthermia where elevation of temperature is because either heat gain exceeds the capacity of heating losing mechanisms, for example, sitting in a sauna or because there is failure of regulatory mechanisms, for example, malignant hyperthermia.
Should we treat fever?
Physical methods of lowering temperature such as tepid sponging may be uncomfortable for the child and do not reset the ‘central thermostat’ that determines the body temperature. They are not part of current recommendations.9 Antipyretic agents have become an established part of managing febrile children. During fever, paracetamol and ibuprofen do effectively reset the ‘central thermostat’. Whether used alone or in combination, they usually result in a prompt reduction in body temperature.10 Measuring the change in body temperature is an easy end point to determine and may explain why there are so many studies that report on this end point. However, it does not mean it is the only end point worth considering. If drugs are to be so widely used, it is crucial that their side effects and adverse outcomes are well understood and balanced against the potential risks and benefits of fever.11
So, how do we weigh up the risks and benefits of fever and its treatment? Fever is such a highly preserved response to infection throughout the animal kingdom that it has long been argued it must be beneficial and have a potential survival advantage.7 Indeed fever has been regarded a potential therapy for some illnesses in the preantibiotic era.12 Current evidence suggests that fever can enhance immune functioning.
Could suppression of fever be detrimental? There is some evidence that use of antipyretics increases the length of viral shedding and length of illness.13 14 It may also have a negative impact on bacterial illnesses. Furthermore, antipyretics are known to reduce vaccine antibody response, although the exact mechanism for this is not clear and may well be independent of fever.15
By contrast, despite the many fears, there is no evidence to say that fever in itself has any harmful effects. Many of the parental anxieties, often termed fever phobia, are unfounded and may originate because fever is confused with hyperthermia, a condition that although rare undoubtedly does have serious adverse outcomes. The outcome of a febrile illness is dependent on the underlying condition and there is no evidence to suggest that reducing fever reduces mortality or morbidity.10 Similarly, despite understandable concerns about febrile convulsions, there is no evidence that routine antipyretic use prevents them from recurring.16
So why do we give antipyretics? The overall well-being and comfort of a child is often seen to improve after antipyretics and the benefit is often attributed, rightly or wrongly, to the reduction in body temperature. However, antipyretics will also be effective analgesics and many of the benefits may well result from the analgesia effect. There may also be some potential additional benefits to reducing body temperatures such as reducing insensible fluid loss and reducing metabolic demand, although these may well be overstated in the majority of febrile children. The mechanism by which improvements in the overall well-being occur may be uncertain but the benefits that carers and clinicians see in the child's condition strongly reinforce the practice of giving antipyretics. Indeed this improvement in patient comfort is a reasonable therapeutic objective.10
In achieving this objective it is important to avoid harm, particularly given how widespread antipyretic use is. Both paracetamol and ibuprofen are effective antipyretics. There are no substantial differences in temperature reduction or data to indicate that other outcomes of clinical importance are substantially different.1 10 Adverse outcomes with standard doses of either ibuprofen or paracetamol in the context of managing fever are rare, but still need to be considered. Side effects of non-steroidal drugs on the gastrointestinal system such as gastritis are well described; in accidental overdose there can be acute effects on renal function.17 18 Paracetamol is generally regarded safe at standard doses, but inadvertent overdose and accumulation from unrecognised intake can have serious consequences on liver function.19 20 Current guidance supports the use of either paracetamol or ibuprofen and caution against alternating/combination regimes.1 10 The current systematic review does not find evidence to support a combination approach (“polypharmaceutical”) when effective monotherapies exist.6
The American Academy of Pediatrics, in their report on antipyretic use in children, point out that the primary goal of treating febrile children should be to improve the child's overall comfort rather than focus on the normalisation of body temperature.10 Similarly, in the UK the NICE clinical guidelines on feverish illness in children state that antipyretic agents should not be routinely used with the sole aim of reducing body temperature in children with fever who are otherwise well.1 We have drugs that can lower temperature in fever, but just because they are available does not mean it is always the right thing to do. There is still a gap between practice in fever management and what current evidence would support.21 There needs to be better shared understanding between professionals and carers of what fever is and why it is there. With this in place, a more rationale management approach is achievable, in which the use of antipyretics focuses on the comfort of the child, minimising harm and improving the overall outcome.
The author wishes to thank Emma Ingleby for help in preparing the manuscript.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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