Does the use of antipyretics in children prolong febrile illness?

David KingClinical Research Fellow05/09/2013

Clinical scenario• A 13 month old is admitted with a temperature of

39.6ᵒC with no obvious focus

• Currently sleeping

• Nurse asks for regular antipyretics to be prescribed “to keep the child comfortable”.

• You wonder if there is any evidence that regular antipyretics can be harmful in this situation

Clinical question

In children with an acute febrile illness (population)

does the use of antipyretics (intervention)

compared to no antipyretics (comparison) prolong

the time to resolution of the fever (outcome)?

Search strategy• Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)

searched with the terms “antipyretic AND prolong AND illness”

– 5 results– 1 systematic review

The Journal of Pediatrics, Volume 163, Issue 3, September 2013, Pages 822–827.e2

Background to the study• Fever is an important part of the response to

infection

• Animal studies show that fever associated with an increase in survival

• Fever is an evolutionarily conserved trait ?beneficial

• Some studies indicate illnesses can be prolonged by antipyretics

“Fever phobia”• Term coined in the 1980s

• Parents and healthcare professionals rush to treat fever and are not satisfied until apyrexial

– “They can go home if their temperature stays down”– “We’ll do bloods if they spike again”– “Their temperature is still raised; can you prescribe

ibuprofen?”– “When you go home give paracetamol and ibuprofen

regularly for a couple of days”

Studies eligible for inclusion• Randomised or quasirandomised controlled trial in which

the authors compared one antipyretic drug with another

– Primary outcome method was time to resolution of fever

– Secondary outcomes were infection-specific indications of disease resolution

Search strategy• Medline/Embase/Google scholar searched

– Freetext and MeSH filter

• “freetext and MeSH term (ie, Medical Subject Headings; where applicable): child, children; temperature, fever, acetaminophen, antipyretic, ibuprofen, NSAID, paracetamol, antibodies; and behavioral symptoms or symptoms, fever clearance, healing, recovery

• RCT filter applied

• Reference lists checked by hand – no additional studies found

Results

Details of the included studies• Three studies in children with malaria

– Paracetamol compared with placebo– Naproxen compared with placebo– Ibuprofen compared with placebo

• One study in children with varicella– Paracetamol compared to placebo– Excluded as no information on time to fever resolution

• Two studies in children with presumed viral illnesses/fever of unknown origin– Paracetamol compared with placebo

Primary outcome

Slightly shorter duration of fever with antipyretics

Did they use the right data...?

Secondary outcomes

No difference in any of the other signs/symptoms of infection

Discussion• No evidence that antipyretics prolong febrile illness in the

trials studied (in terms of time to fever resolution)

• Authors also state that data on other outcomes such as malaria parasite clearance and time to symptom resolution shows no effect of antipyretics

Critical analysis

Critical analysis (2)

Critical analysis (3)• Was it reasonable to combine the results of the

studies?

– Several illnesses studied– Malaria, varicella, viral illnesses– Different antipyretics– Although statistical heterogeneity low, still very

different illnesses and treatments – are they equivalent?

– Quality of the studies variable

Critical analysis (4)• What are the results of the review and how

precise are they?

– No difference in time to resolution of fever when antipyretics used

– Some of the results look statistically suspect

Critical analysis (5)• Can the results be applied to the local population?

– Majority of studies examined children with malaria

– Only two looked at children with viral illness or fever of unknown origin

– Results may be applicable but different populations and illnesses

– None of the studies examine combining antipyretics

Critical analysis (6)• Were all important outcomes considered?

– No– The results of two studies were not acknowledged in the

discussion• Brandt et al – time to clearance of malaria parasites

significantly prolonged in patients taking paracetamol• Doran et al – time to scabbing of varicella lesions

significantly prolonged in children taking paracetamol

• Discussed with authors via email– Not felt to be “clinically significant” but discussion could be

clearer – writing follow-up letter to clarify

Summary• Available evidence does not indicate that antipyretics

prolongs febrile illnesses

• However, majority of studies conducted in children overseas with malaria

• Is this applicable to our population?

• Is this true when paracetamol/ibuprofen combined?

• Further research required