Tuesday, 9 April 2019

What is the deal with fever?

Fever scares parents.  The internet is full of scaremongery about what fever can do to you.  For the uninformed parent, fever not only suggests the possibility of serious infection, it is the enemy.  It must be stopped before it harms the child.

Fever confuses clinicians.  For the clinician, fever indicates an infection (most of the time).  Can it tell me what kind of infection and where it is though?  Fever is sometimes associated with raised heart rate, cool peripheries and general malaise.  This picture can be very difficult to discern from sepsis.  Fever therefore presents a dilemma.  If the tachycardia and lethargy could be simply associated with a febrile moment, do I wait to see if the red flags resolve when the fever settles?  If that resolution happens (by far the most likely outcome), I have avoided unnecessary treatment and admission, both of which are at best unpleasant and inconvenient (at worst they both carry their own small risk of morbidity and mortality).  If it later turns out that the child was septic (unlikely but always possible), then the delay, intended to remove the confounder of fever, may have caused harm.
So if fever causes confusion and anxiety, it’s probably a good thing to be clear about a few things to do with fever.   Let’s work through some common questions.

Is fever helpful or necessary in fighting infections?

This is something that is frequently posed: that fever is a normal feature of an immunological process.   It is then suggested that we should not interfere with it.  I’m afraid that this argument holds little water.  Unless there is good evidence that the height of the fever correlates with better outcome (and unsurprisingly this is not the case) then we can’t attribute the death of the microbes to a thermal effect.  Yes, fever may be a part of a process but that doesn’t make it necessary or desirable.  Are fumes a normal outcome from an engine running?  Yes.  Would it be great if we could get the same performance from our engines with less or no fumes?  Yes.  Fever is a sign that the immune system is doing something but there is no good evidence that reducing fever is harmful to the body’s business of fighting the infection.

Is fever harmful to the brain?

The simple answer is that no, fever itself is not harmful as long as it is due to a functional immune response.  That doesn’t mean that the infection couldn’t be harmful, but a fever is not harmful in itself as far as we know.
(There is such a thing as malignant pyrexia which has a high morbidity and mortality rate.  Malignant pyrexia is not a normal physiological response, fever during an infection is.)

Is fever always significant?

Not always.  Sometimes a raised temperature is not even a fever.  It can be environmental.  Babies in particular are prone to getting hot if overdressed or in a hot room.

If a raised temperature is due to infection, the issue of how determined we should be when we look for a focus is a complicated one.  Different circumstances will require different approaches.  The history and examination are important but so is the age of the child.  Babies have a much higher incidence of sepsis and serious bacterial infections.  The threshold for investigation is far lower in a three week old than a three year old.

Consider these two scenarios:

  • A three year old presents with the parent saying that they were really hot at home that morning.  They now have a normal temperature.  Examination is completely normal and the child looks well.  Heart rate and other parameters are all normal.
  • A three week old presents with the parent saying that they were really hot at home that morning.  They now have a normal temperature.  Examination is completely normal and the child looks well.  Heart rate and other parameters are all normal.

In the first scenario the pre-test probability of significant infection is low as long as there are no special circumstances (returning traveller etc.) but in the second they are far higher.

Does fever cause febrile convulsions?

Probably not.  A review article (1) previously reported that the available evidence showed that antipyretic use was not associated with a reduced rate of febrile convulsions.  This is entirely plausible as two events which repeatedly occur together do not have to be one causing the other.  It makes perfect sense that both the fever and the fit could be caused by biochemical changes brought about by either the infection or the body’s response to it.

There was a new paper (2) published in 2018 in which the authors claimed to have clearly demonstrated that antipyretics reduced the recurrence rate of febrile convulsion in children who had already had a fit.  The recurrence rate of fits during the same illness was so high in this study as to suggest that either the data was skewed or that the population was so different to normal as to make the results difficult to apply to practice.  Although this latest publication did challenge the accepted view that lack of fever control is not to be blamed for febrile convulsion, many have seen it as a blip rather than a reason to change their practice.  I remain open minded but still in the “fever does not directly cause the fit” camp.

Does the height of the fever indicate a more serious infection?

The answer to this is, “not really.”  A fever of 40C is slightly more likely to indicate a serious bacterial infection (SBI) than a temperature of 38C in an unwell child.  Despite this weak correlation, height of fever is an unreliable indicator of SBI.  Ultimately the decisions and diagnosis should be made based on other findings.  A child with a fever of 40C, a red throat, red ears and no signs of SBI probably has a viral URTI.  A child with a temperature of 38C with cough, grunting and focal reduced air entry and coarse crepitation in the chest is presumed to have pneumonia.  The number of the temperature itself is of little use in making those decisions.  Undoubtedly, a high fever might act as a speed bump to a clinician, making them look twice and think carefully.  That’s no bad thing.  However a higher temperature shouldn’t mandate a different diagnosis or course of action.
Should we be treating fever in children?

Fever, it seems, is neither harmful nor beneficial.  The medicines that we give to children should in theory be administered with the aim of reducing pain and general malaise.  In practice, children who are febrile usually display signs of feeling unwell.  This means that we end up giving them medication anyway.  The reason may be different but the end result is the same.

If a child is febrile but seems to feel entirely well and demonstrates no evidence of pain, it seems entirely reasonable to not treat the fever for the fever’s sake.  That scenario does happen but is reasonably uncommon.

We should probably de-emphasise the role of fever in the clinical assessment.  The presence of fever is an important piece of information in the acute assessment of a child but only to trigger a search for a focus.  Once it is known that the child has an infection, the focus should be on useful discriminators such as appearance, behaviour, duration and pattern of the illness.
Fever is an important feature of history and examination.  The significance and cause of the fever is the question which then occupies the clinician’s mind.  If the cause and effect of the symptoms are found to be benign, the fever becomes a detail, not a task.  We treat the child not the fever.

1 comment:

  1. Hello Edward, thank you for highlighting the lack of effect of antipyretics in preventing febrile convulsions. There is a woeful lack of understanding on this topic, particularly in A&E departments where the discredited "paracetamol perk-up test" is in widespread use. And in babies under six months, the use of paracetamol may mask a very useful clinical sign.

    The very important question of whether artificially lowering fever impairs the immune response is one that has intrigued me for the last 20+ years. As a GP and educator, I have looked into the research evidence in adults, children, and animals. The replication rates of meningococci, spirochaetes and influenza virus all decrease at higher temperatures; the story of Julius Wagner-Jauregg and his Nobel prize resonates here. Prophylactic antipyretics reduce the immunogenic effect of vaccines (DH Green Book, Saleh, 2016 www.ncbi.nlm.nih.gov/pmc/articles/PMC5027726) and there is evidence from a meta-analysis of animal studies that antipyretics significantly increase mortality in influenza (Eyers, 2010; doi: 10.1258/jrsm.2010.090441). In the recent Yamamoto study (www.ncbi.nlm.nih.gov/pmc/articles/PMC4902348/), setting aside the group with a temperature below 36 degrees on admission, there was a very convincing correlation between high temperature and low mortality in adults hospitalised with bacterial infection. Admittedly sepsis trials have shown conflicting results, but I remain convinced that there is a significant risk that antipyretics may impair the immune response.

    With my best wishes,
    Gina
    Dr Gina Johnson
    National Minor Illness Centre

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