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Three Part Question

In [patients with fever], is [oral paracetamol(acetaminophen) or rectal paracetamol] more effective [in lowering the body temperature]?

Clinical Scenario

A 1-year-old boy presented to emergency department with fever. History and Physical examination suggested upper respiratory tract infection. You want to prescribe paracetamol(acetaminophen) for the fever, but the boy kept on crying and oral route was not possible. You wonder if oral route is more effective than rectal administration.

Search Strategy

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1950 to Present
Date of Search: 17-Dec-2008
#1 : Acetaminophen.mp. or exp Acetaminophen/
#2 : paracetamol.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
#3 : 1 or 2
#4 : exp Administration, Oral/ or oral.mp.
#5 : exp Tablets/
#6 : exp Administration, Rectal/
#7 : rect*.mp.
#8 : exp Suppositories/
#9 : (4 or 5) and (6 or 7 or 8)
#10 : exp Body Temperature/ or exp Temperature/
#11 : exp Fever/
#12 : antipyretic.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
#13 : 10 or 11 or 12
#14 : 3 and 9 and 13
#15 : limit 14 to (english language and humans)
A recent meta-analysis(See Below) addressed the clinical question but was not included in the search as it had not been indexed by the date of searching and could not be found in Ovid Medline.
Meta-analysis: Goldstein LH, Berlin M, Berkovitch M, Kozer E. Effectiveness of Oral vs Rectal Acetaminophen. A Meta-analysis. Archives of Pediatrics & Adolescent Medicine NOV 2008, VOL 162 (NO. 11)

Search Outcome

30 papers were found and 5 papers were relevant. Four were clinical trials and the remaining one was a cohort study.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Nabulsi M. Tamim H. Sabra R. Mahfoud Z. Malaeb S. Fakih H. Mikati M. 2005 Lebanon	51 febrile children aged 6 months to 13 years old	This is a randomized, double-dummy, double-blind study.	Time to maximum antipyresis	No significant difference among the three groups	Sample size is 51 only.
			Tme to fever reduction by 1 degrees C	No significant difference among the three groups
Keinanen S. Hietula M. Simila S. Kouvalainen K. 1977 Aug GERMANY, WEST	30 children between the age of 4 months and 12 years, who had infections and a rectal temperature above 38.5 degrees C	Cohort study	Maximum fall of temperature	Oral form is more effective(maximum fall of temperature 1.58 degrees C) then rectal(maximum fall of temperature 1.24 degrees C)	The study is not randomized. the sample size is small
Scolnik D. Kozer E. Jacobson S. Diamond S. Young NL. 2002 Sep Canada	70 patients aged 6 months to 6 years with fever > or =39 degrees C	A randomized, controlled trial.	Temperature change at 3 hours	No significant difference between the two groups	Sample size is small. Study period is only 3 hour.
			Maximum drop in temperature or final temperature	No significant difference between the two groups
Vernon S, Bacon C, Weightman D 1979 Jun	37 febrile children aged between 3 months and 6 years	Randomized Controlled Trial	Antipyretic effect	Oral route and rectal route have the same effect.	Sample size is small. the results are not in details.
Maron JJ, Ickes AC 1976 Jul	83 patients with age 23 to 96 years old	Randomized, double-dummy, controlled trial	Decline in temperature at 1 hour	No difference between two groups	The age range of subjects are too wide.
			Decline in temperature at 3 hours	No difference between two groups

Comment(s)

Four out of 5 study suggested that the effectiveness of rectal paracetamol is comparable with oral route with respect to temperature reduction. A recent meta-analysis which included the four randomized trials(1. Goldstein LH, Berlin M, Berkovitch M, Kozer E. Effectiveness of Oral vs Rectal Acetaminophen. A Meta-analysis Archives of Pediatrics & Adolescent Medicine NOV 2008, VOL 162 (NO. 11)) also showed the same result. The only study which showed opposite result was not randomized and had a small sample size. Further studies are needed to evaluate the toxicity between the two routes of paracetamol administration.

Clinical Bottom Line

Rectal paracetamol have same anti-pyretic effect as oral form and can be given as an alternative in patients who are not able to take oral form.

References

1. Nabulsi M. Tamim H. Sabra R. Mahfoud Z. Malaeb S. Fakih H. Mikati M. Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial BMC Pediatrics 5:35, 2005
2. Keinanen S. Hietula M. Simila S. Kouvalainen K. Antipyretic therapy. Comparison of rectal and oral paracetamol. European Journal of Clinical Pharmacology 12(1):77-80, 1977 Aug 17.
3. Scolnik D. Kozer E. Jacobson S. Diamond S. Young NL. Comparison of oral versus normal and high-dose rectal acetaminophen in the treatment of febrile children. Scolnik D. Kozer E. Jacobson S. Diamond S. Young NL. 110(3):553-6
4. Vernon S, Bacon C, Weightman D Rectal paracetamol in small children with fever. Archives of disease in childhood 54(6):469-70
5. Maron JJ, Ickes AC The antipyretic effectiveness of acetaminophen suppositories versus tablets: a double-blind study. Current therapeutic research, clinical and experimental 20(1):45-52,