Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401]

Abstract

BackgroundThe antipyretic effectiveness of rectal versus oral acetaminophen is not well established. This study is designed to compare the antipyretic effectiveness of two rectal acetaminophen doses (15 mg/kg) and (35 mg/kg), to the standard oral dose of 15 mg/kg.MethodsThis is a randomized, double-dummy, double-blind study of 51 febrile children, receiving one of three regimens of a single acetaminophen dose: 15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally. Rectal temperature was monitored at baseline and hourly for a total of six hours. The primary outcome of the study, time to maximum antipyresis, and the secondary outcome of time to temperature reduction by at least 1°C were analyzed by one-way ANOVA. Two-way ANOVA with repeated measures over time was used to compare the secondary outcome: change in temperature from baseline at times1, 2, 3, 4, 5, and 6 hours among the three groups. Intent-to-treat analysis was planned.ResultsNo significant differences were found among the three groups in the time to maximum antipyresis (overall mean = 3.6 hours; 95% CI: 3.2–4.0), time to fever reduction by 1°C or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature < 36.5°C) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group.ConclusionStandard (15 mg/kg) oral, (15 mg/kg) rectal, and high-dose (35 mg/kg) rectal acetaminophen have similar antipyretic effectiveness.

Acetaminophen in Children: Which Dosage, Which Route?

“…About 50% of rectal acetaminophen shortcut the liver. The absorption of acetaminophen suppositories is variable and erratic, and depends on the size of the suppository, its composition, its rate of dissolution, its location on the rectum and the contents of the rectum [6,7]. Rectal acetaminophen undergoes variable hepatic first pass metabolism.…”

“…They recommended that acetaminophen be administered orally to control fever in children [9][10][11]. Scolnik et al [9] showed no significant difference between the temperatures decrement (the maximum drop in temperature or final temperature or in temperature change during the 3 hours after administration) in children 6 months to 6 years of age treated with 15 mg/kg oral acetaminophen and the same or double dose rectally [7][8][9]. Similarly, in a study by Vernon et al on 37 children aged 3 months to 6 years, no difference in antipyretic effects of oral and rectal acetaminophen at a dose of 15 mg/kg was observed.…”

“…On average, about 50% of rectal acetaminophen will bypass the liver [8]. Because of reduced efficacy due to poor absorption and the risk of cumulative toxicity due to high or frequent doses, even American Academy of Paediatrics (AAP) has recommended that suppository be used only for oral intolerance cases like as vomiting [7][8][9]. In a meta-analysis, published by Goldstein et al [10] in 2008, it was found that there was no difference in oral and rectal acetaminophen antipyretic effects [8][9][10].…”

“…They concluded that rectal acetaminophen is an acceptable alternative to control fever in children who cannot take it orally [10][11][12]. In a study by Nabulsi et al [7] on 51 children with fever no significant differences were found among the three groups (15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally) in the time to maximum antipyresis, time to fever reduction by 1ºC or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature <36.5ºC) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group.…”

“…Hypothermia (temperature <36.5ºC) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group. They suggested that the usual dose (15 mg/kg) of rectal acetaminophen should be used in cases where oral administration is not possible such as vomiting and, considering the probability of hypothermia, administration of high doses of rectal acetaminophen should be prescribed with caution [6,7]. In our triple blind randomized clinical trial study on 76 children aged 6 months to 6 years with a high rectal temperature of 39 degrees Celsius, we compared antipyretic effects of rectal acetaminophen with two different doses of 15 mg/kg and 30 mg/kg after 1 and 3 hours after administration.…”