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Three Part Question

In [a febrile child under the age of 12] are [Paracetamol and Ibuprofen together more effective than either drug used on its own] in [reducing a child's temperature]?

Clinical Scenario

A 6 year old child arrives in A and E with a temperature of 39°c. In order to reduce the child's fever and distress you would like to prescribe an antipyretic but are unsure which is better Ibuprofen or Paracetamol.

Search Strategy

OVID Medline <1966-June week 3 2006>
EMBASE < 1980 to 2006 week 26>
CINAHL <1982 to June week 5 2006>
Paediatric filter applied
([(high adj temperature).mp OR (high adj fever).mp. OR fever.mp OR exp FEVER/ OR febrile.mp OR temperature.mp OR exp TEMPERATURE/ OR exp HIGH TEMPERATURE/ OR exp TEMPERATURE/ OR exp BODY TEMPERATURE/ OR exp CORE TEMPERATURE/ or hot.mp]) AND (antipyretic.mp OR Antipyretic Agent/ OR acetaminophen.mp OR exp Paracetamol/ OR exp IBUPROFEN/ OR ibuprofen.mp. OR nurofen.mp. OR exp Ibuprofen/) Limit to (human and english language)

Search Outcome

Medline: 502 papers found
EMBAE: 859 papers found
CINAHL: 110 papers found
Cochrane Library: 1 paper found- not relevant
5 relevant articles found 1 medline 3 EMBASE one article unable to obtain in time.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Carson, S.M. 2003	1 article	Systematic review of which only 1 article found by Mayoral.	Survey on fever management strategies and basis for use of the two drugs	Lack of evidence to support the use of combined therapy.	Lack of evidence available to enter into the review.
Sarrell, M. Wielunsky, E. Avner Cohen, H 2006 Israel	480 patients from 3 primary paediatric community centres consecutive children 6 to 36 months with a rectal temperature of at least 38°c.	Randomised Double Blind Study- parallel group trial.	Mean fever of infants	P<0.001 Results statistically significant between combined and ibuprofen only also statistically significant between combined and paracetamol on days 1, 2,and 3.	Given different medication as loading dose. Parents took the temperatures. Only done over a period of 3 days. It says the temperatures were measured for the next 10 days but only given results for days 1-3. Temp took 3 times daily does't say if took at same time each day and what time of day they took it.-circadian rhythm can affect temp.
Erlewyn-Lajeunesse, M.D.S. Coppens, K. Hunt, L.P. Chinnick, P.J. and Davies, P 2006 UK	Childrens Emergency Department 6months to 10 years attending with a fever 38.0°c or more. 123 children	RCT	Mean fall in temp T0 to T1 - Paracetamol	0.95	Don't know how long they had a fever before they came in. Small sample size Only short measurement period Investigator not blinded
			Mean fall in temp T0 to T1 - Ibuprofen	0.92
			Mean fall in temp T0 to T1 - both	1.22
				no statistical significance
Nabulsi, M.M. Tamim, H. Manfoud, Z. Itani, M. Sabra, R. Chamseddine, F. and Mikat, M. 2006 Beirut	69 patients paediatric inpatient services of 2 hospitals febrile inpatients between 6mths and 14yrs rectal temp greater than or equal to 38.8°c.	Randomised double blind placebo controlled trial	% afebrile intervention group (combined therapy)	83.3%	Small sample size
			% afebrile ibuprofen monotherapy	57.6%
				p= 0.018 significant
			max decline in temp (combined therapy)	2.2 +/- 0.7°c
			max decline in temp (Ibuprofen monotherapy)	2.11 +/- 0.2°c
			Time to recurrence of fever (combined therapy)	7.4 hours
			Time to recurrence of fever (Ibuprofen monotherapy)	5.7hrs
				p<0.001 significant

Comment(s)

In the emergency setting when rapid fever reduction is required combined therapy does not seem to have a role. Only one study found combined therapy to be more effective than monotherapy with statistical significance. Combined treatment appears to have a role in prevention of fever recurrence. All of the studies use different outcomes as a measure of effectiveness of the treatment it would make comparison of results easier if a single outcome measure was used such as average time spent below a certain temperature or mean reduction in temperature.

Clinical Bottom Line

More studies with larger sample sizes and conducted over longer time periods are required in order to judge the safety and efficacy (any long term adverse effects) of combined therapy.

References

1. Carson, S.M. Alternating Acetaminophen and Ibuprofen in the Febrile Child: Examination of the Evidence Regarding Efficacy and Safety Pediatric Nursing. 29 (5) Oct 2003, p379-382.
2. Sarrell, M. Wielunsky, E. Avner Cohen, H Antipyretic Treatment in Young Children With Fever. Acetaminophen, Ibuprofen or both Alternating in a Randomised, Double-blind study Arch Pediatr Adolesc Med. Vol 160 Feb 2006, p197-202.
3. Erlewyn-Lajeunesse, M.D.S. Coppens, K. Hunt, L.P. Chinnick, P.J. and Davies, P Randomised controlled trial of combined paracetamol and ibuprofen for fever. Arch Dis Child. Vol 91 2006, p414-416.
4. Nabulsi, M.M. Tamim, H. Mahfoud, Z. Itani, M. Sabra, R. Chamsddine, F. & Mikati,M. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study. BMC Medicine. 4 (4) 2006, p1-8.