does the use of antipyretics in children prolong febrile illness? david king clinical research...
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Does the use of antipyretics in children prolong febrile illness?
David King
Clinical Research Fellow
05/09/2013
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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
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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)?
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Search strategy• Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)
searched with the terms “antipyretic AND prolong AND illness”
– 5 results– 1 systematic review
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The Journal of Pediatrics, Volume 163, Issue 3, September 2013, Pages 822–827.e2
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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
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“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”
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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
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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
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Results
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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
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Primary outcome
Slightly shorter duration of fever with antipyretics
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Did they use the right data...?
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Secondary outcomes
No difference in any of the other signs/symptoms of infection
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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
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Critical analysis
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Critical analysis (2)
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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
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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
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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
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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
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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