Thankfully the extreme temperatures seen around the UK and Europe this week have now eased off but many of our patients are still feeling hot – feverish in fact. Whether it’s covid, the common cold, UTI or pneumonia, fever is a common symptom of infection. Unlike the weather, we have the ability to modify fever, most commonly through the use of antipyretics.
Fever occurs due to pyrogens, pyrogenic cytokines released by the body in response to infection or inflammation, causing the body’s temperature set-point to be increased via its thermoregulatory centre in the hypothalamus thus triggering the physical responses that increase temperature such as shivering.
In day-to-day practice most medics would advise patients it’s fine to take some paracetamol or ibuprofen (or both – “yes, it is ok to take them at the same time”, “is staggering them better? I’m not sure there’s any research in that area… but definitely do it if you think it will help and it keeps you busy…”) to help bring down a fever. But could we be giving dangerous advice? Does “controlling” the fever impair the body’s innate defenses and potentially increase the risks from an infection?
Surprisingly this is an area of significant uncertainty but a very recent BMJ paper (BMJ 2022;378:e069620) has helped to take some of the heat out of the debate.
A number of smaller studies have been conducted in this area but due to their size they have been insufficiently powered to answer questions around mortality with antipyretics. To get around this common problem the BMJ undertook a systematic review and meta-analysis of relevant trials and examined 42 studies involving >5k adult patients. They examined adults receiving temperature-lowering treatments for both infective and non-infective disease, those with critical and non-critical illness and looked at anti-pyretics (11 different ones in total, who knew there were more than two? or perhaps three if you’re proper old-school and still recommend aspirin…) and physical cooling methods (cold flannels at the ready).
They found that fever therapy did not affect the risk of death nor the change of serious adverse events. So fever therapy appears safe and we can breathe a sigh of relief that one of the most ingrained pieces of advice given by medics is not harming our patients.
But do antipyretics do any good?
Incredibly only one of the dozens of trials included reported on quality of life and that study failed to show any benefit of using antipyretics. Does this mean we should not recommend antipyretics? Given this result comes from just one study that seems inappropriate. Many of us will have personal experience of feeling better having managed our own fevers, and positive feedback from hundreds of patients saying the same.
So while this data closes one door on the argument against antipyretics, behind that is yet another door marked “does they truly help?” plus a side entrance with a sign saying “and what about kids?”. It might be a while before we have the right key for those.