fever , defined as a rectal temperature higher than 38c , is the most common complaint 
 among children admitted to emergency departments ( 1 ) .
infectious and noninfectious triggers cause a release of pyrogenic cytokine 
 such as interleukin-1 , interleukin-6 , tumor necrosis factor - alpha ( tnf- ) and 
 interferon - gamma ( ifn- ) .
these cytokines in turn act on the thermoregulatory center 
 of the hypothalamus , which leads to an increase in temperature set point , thus causing fever 
 ( 2 , 3 ) .
fever , as a part of an effective immune system , improves the immunological 
 response and slows growth and replication of viral and bacterial pathogens ( 4 ) .
increased metabolic reactions , increased oxygen 
 consumption , and increased heart and lung function are some effects of fever , which may lead 
 to dangerous outcomes , especially in children with underlying diseases ( 5 ) .
although fever is mostly self - limited in 
 children and usually the underlying cause of fever should be treated , yet antipyretic 
 therapy is also indicated when there is fever higher than 39c , an underlying disease 
 ( such as any cardiac , pulmonary or neurologic problems ) , discomfort or hemodynamic and 
 electrolyte imbalance ( 3 , 6 , 7 ) .
paracetamol ( acetaminophen ) is an antipyretic and analgesic medication , most frequently 
 used in pediatrics for both outpatient and admitted patients .
the mechanism of action of 
 this drug is not fully understood , yet it is postulated that the acetaminophen - induced 
 antipyresis occurs via central inhibition of the enzyme cyclooxygenase ( cox ) . acetaminophen 
 does not inhibit cox in peripheral tissues and , thus , has no peripheral anti - inflammatory 
 effects and is not classified as a member of the non - steroidal anti - inflammatory drugs 
 ( nsaids ) ( 2 , 8) . despite its favorable effects , poisoning , kidney failure and 
 hepatotoxicity are the most serious adverse effects of paracetamol , which may occur due to 
 acute exposure ( 9 ) .
diclofenac is a non - steroidal anti - inflammatory drug ( nsaid ) , which has analgesic and 
 antipyretic activities .
this drug is readily absorbed from the alimentary tract , and its 
 half time is about one to two hours , and it will quickly dissolve in an environment with a 
 ph higher than five .
diclofenac as one of the most potent nsaid has a few side effects when 
 administered rectally ( 10 ) .
antipyretic effects 
 of this drug have received less attention in comparison with its analgesic effects ( 11 , 12 ) .
considering the importance of fever and unknown antipyretic properties of diclofenac in the 
 pediatric population , this clinical trial was designed and implemented in order to compare 
 the antipyretic effectiveness of paracetamol and diclofenac , administered rectally .
this double - blind controlled clinical trial comprised of 80 children aged one to six 
 years , and was conducted from october 2012 to november 2013 , at shahid beheshti hospital 
 of kashan , iran .
shahid beheshti hospital has 393 active beds in 16 different specialist 
 units including pediatric , internal medicine , obstetrics and gynecology , infectious 
 diseases , dermatology , cardiology and intensive care .
this specialty and subspecialty 
 hospital is a public hospital and is considered a regional referral center .
children whose rectal temperatures were higher than 38c and those who had fevers of 
 less than four days were entered in the study .
convenience sampling was used and all 
 patients meeting the least required criteria , who had visited our health center since the 
 beginning of the study until completion of the required sample size , were selected .
those 
 who had received other antipyretic agents , had undergone non pharmacological interventions 
 to control the fever , had diarrhea , had a history of allergic reactions to paracetamol 
 and/or diclofenac , had any anomalies of the gastrointestinal tract , had been affected by 
 chronic diseases and those whose parents refused to participate , were excluded from the 
 study .
however , due to diarrhea ( four cases ) , 
 having had received oral paracetamol prior to the visit ( two cases ) and having had a 
 history of imperforate anus ( one case ) seven cases were excluded , thus the final sample 
 size was 80 . after being informed of the study objectives ,
then a questionnaire , 
 which asked for the child s age , gender , weight and possible diagnosis , was 
 completed .
patients were randomly allocated to two groups of paracetamol and diclofenac using a 
 permuted - block randomization scheme . for this purpose , 20 blocks with a block size of four 
 were used and the blocks were classified in order of numbers .
one of them was responsible for sampling , completing the 
 questionnaires , allocating the patients to different treatment groups and preparation and 
 administration of the drugs .
the other one was responsibility for simply measuring the 
 rectal temperature of the child under study before and after the intervention .
the parents did not 
 know the type of treatment , either ( figure 
 1 ) .
all ethical principles were respected in accordance with resolution 196/96 on research 
 involving human subjects .
the ethics committee of kashan university of medical sciences 
 ( approval code : 29/5/1/2742/p ) approved the study and supervised all stages .
this study 
 was also recorded in the iran center of clinical trials registration database 
 ( irct2012101711145n1 ) . however , since the antipyretic effects of rectal forms of paracetamol and diclofenac have 
 not been compared so far , to determine the required sample size we used the same 
 methodology as was performed in a previous evaluation to compare the analgesic effects of 
 rectal forms of these two drugs . in their study , the mean pain score one hour after the 
 surgery was 7.8  2.25 in the paracetamol group and 6.4  0.8 in the diclofenac 
 group ( 11 ) . with a power of 90% and 
 z1-/2 = 1.28 , and using the equation following equation , the minimum 
 sample size required in each group was calculated to be 31 cases ( equation 1 ) .
taking into account our medical facilities and to allow for losses , we finally estimated 
 a sample size of 40 cases in each group .
the mt 19f1 digital thermometer , manufactured by microlife company , was used for 
 measuring temperature .
this thermometer registers the rectal temperature in degrees celsius within 10 seconds 
 and displays it digitally .
the equipment was calibrated by the manufacturing company , and 
 to evaluate the reliability of the measurements , all recordings were compared with the 
 results obtained with a glass mercury thermometer before the study .
. supervised by the researcher , the tip of thermometer was gently inserted about 2 
 cm into the child s rectum by the parents , and then the registration key was 
 pressed .
rectal temperatures greater than or equal to 38c were labeled as a fever . the rate 
 of temperature change after treatment in each group was calculated and recorded .
three classes of 
 successful treatment were low recovery rate from 0.5 to 0.1 , average recovery rate from 1 
 to 0.6 , and high recovery rate of more than 1c temperature decrease .
paracetamol and diclofenac suppositories were administered per rectum at 15 mg / kg and 1 
 mg / kg dose , respectively .
one hundred and twenty - five milligrams and 325 mg paracetamol 
 suppositories , and 100 mg and 50 mg diclofenac suppository of aboureihan company ( iran ) 
 were used for this purpose . to determine the amount of medication required per dose , the 
 suppositories were scraped - off using a very sharp surgical blade , sectioned 
 longitudinally , and weighed by and digital scale ( made in japan ) with accuracy of 
 0.001 g. the drug
all stages of drug preparation 
 were done by an expert pharmacist . after instructing the parents ,
the drug was inserted 
 into the child s rectum slowly by the parents under supervision of the 
 researcher .
baseline variables , fever 
 reduction grade and fever after treatment were analyzed by the chi - square and 
 fisher s exact tests .
the results of the quantitative data analysis were expressed 
 as mean  standard deviation .
kolmogorov - smirnov was applied to assess the data 
 distribution . according to the normal distribution of age ,
weight and primary and 
 secondary temperature data , independent t test and paired t test were used to compare the 
 averages .
mann - whitney u test was used for comparison of average temperature decrease due 
 to abnormal data distribution .
repeated measure analysis of variance ( anova ) was also used 
 to compare the average body temperature at different study times .
this double - blind controlled clinical trial comprised of 80 children aged one to six 
 years , and was conducted from october 2012 to november 2013 , at shahid beheshti hospital 
 of kashan , iran .
shahid beheshti hospital has 393 active beds in 16 different specialist 
 units including pediatric , internal medicine , obstetrics and gynecology , infectious 
 diseases , dermatology , cardiology and intensive care .
this specialty and subspecialty 
 hospital is a public hospital and is considered a regional referral center .
children whose rectal temperatures were higher than 38c and those who had fevers of 
 less than four days were entered in the study .
convenience sampling was used and all 
 patients meeting the least required criteria , who had visited our health center since the 
 beginning of the study until completion of the required sample size , were selected .
those 
 who had received other antipyretic agents , had undergone non pharmacological interventions 
 to control the fever , had diarrhea , had a history of allergic reactions to paracetamol 
 and/or diclofenac , had any anomalies of the gastrointestinal tract , had been affected by 
 chronic diseases and those whose parents refused to participate , were excluded from the 
 study .
however , due to diarrhea ( four cases ) , 
 having had received oral paracetamol prior to the visit ( two cases ) and having had a 
 history of imperforate anus ( one case ) seven cases were excluded , thus the final sample 
 size was 80 . after being informed of the study objectives ,
then a questionnaire , 
 which asked for the child s age , gender , weight and possible diagnosis , was 
 completed .
patients were randomly allocated to two groups of paracetamol and diclofenac using a 
 permuted - block randomization scheme . for this purpose , 20 blocks with a block size of four 
 were used and the blocks were classified in order of numbers .
one of them was responsible for sampling , completing the 
 questionnaires , allocating the patients to different treatment groups and preparation and 
 administration of the drugs .
the other one was responsibility for simply measuring the 
 rectal temperature of the child under study before and after the intervention .
the parents did not 
 know the type of treatment , either ( figure 
 1 ) .
all ethical principles were respected in accordance with resolution 196/96 on research 
 involving human subjects .
the ethics committee of kashan university of medical sciences 
 ( approval code : 29/5/1/2742/p ) approved the study and supervised all stages .
this study 
 was also recorded in the iran center of clinical trials registration database 
 ( irct2012101711145n1 ) . however , since the antipyretic effects of rectal forms of paracetamol and diclofenac have 
 not been compared so far , to determine the required sample size we used the same 
 methodology as was performed in a previous evaluation to compare the analgesic effects of 
 rectal forms of these two drugs . in their study , the mean pain score one hour after the 
 surgery was 7.8  2.25 in the paracetamol group and 6.4  0.8 in the diclofenac 
 group ( 11 ) . with a power of 90% and 
 z1-/2 = 1.28 , and using the equation following equation , the minimum 
 sample size required in each group was calculated to be 31 cases ( equation 1 ) .
taking into account our medical facilities and to allow for losses , we finally estimated 
 a sample size of 40 cases in each group .
the mt 19f1 digital thermometer , manufactured by microlife company , was used for 
 measuring temperature .
this thermometer registers the rectal temperature in degrees celsius within 10 seconds 
 and displays it digitally .
the equipment was calibrated by the manufacturing company , and 
 to evaluate the reliability of the measurements , all recordings were compared with the 
 results obtained with a glass mercury thermometer before the study .
. supervised by the researcher , the tip of thermometer was gently inserted about 2 
 cm into the child s rectum by the parents , and then the registration key was 
 pressed .
rectal temperatures greater than or equal to 38c were labeled as a fever . the rate 
 of temperature change after treatment in each group was calculated and recorded .
three classes of 
 successful treatment were low recovery rate from 0.5 to 0.1 , average recovery rate from 1 
 to 0.6 , and high recovery rate of more than 1c temperature decrease .
paracetamol and diclofenac suppositories were administered per rectum at 15 mg / kg and 1 
 mg / kg dose , respectively .
one hundred and twenty - five milligrams and 325 mg paracetamol 
 suppositories , and 100 mg and 50 mg diclofenac suppository of aboureihan company ( iran ) 
 were used for this purpose . to determine the amount of medication required per dose
, the 
 suppositories were scraped - off using a very sharp surgical blade , sectioned 
 longitudinally , and weighed by and digital scale ( made in japan ) with accuracy of 
 0.001 g. the drug was then converted into the usable form .
all stages of drug preparation 
 were done by an expert pharmacist . after instructing the parents ,
the drug was inserted 
 into the child s rectum slowly by the parents under supervision of the 
 researcher .
baseline variables , fever 
 reduction grade and fever after treatment were analyzed by the chi - square and 
 fisher s exact tests .
the results of the quantitative data analysis were expressed 
 as mean  standard deviation .
kolmogorov - smirnov was applied to assess the data 
 distribution . according to the normal distribution of age ,
weight and primary and 
 secondary temperature data , independent t test and paired t test were used to compare the 
 averages .
mann - whitney u test was used for comparison of average temperature decrease due 
 to abnormal data distribution .
repeated measure analysis of variance ( anova ) was also used 
 to compare the average body temperature at different study times .
a total of eighty children were examined in two treatment groups of paracetamol and 
 diclofenac .
all patients completed the study and no drug - related allergic reactions were 
 observed .
abbreviations : lrti , lower respiratory tract infection ; uti , urinary tract infection ; 
 urti , upper respiratory tract infection .
( % ) . reduced temperature of at least 0.1c was detected in all patients in both groups . the 
 average temperature one hour after the procedure was 38.39  0.89c in the 
 diclofenac group , which was significantly reduced compared to the initial temperature ( p 
 < 0.001 ) .
the mean temperature was 38.95  1.09c for the paracetamol group , 
 which had also significantly decreased compared to the initial temperature ( p < 
 0.001 ) .
the average temperatures of patients before and after the intervention were compared using 
 the repeated measures anova . despite the significant decrease in the measured temperatures , 
 there were no significant differences between the two groups ( p = 0.47 ) ( figure 2 ) .
this study was conducted to compare the antipyretic effectiveness of the suppository form 
 of paracetamol versus diclofenac .
both diclofenac and paracetamol proved to be successful in 
 reducing temperature , yet diclofenac had a greater antipyretic effect than paracetamol .
oral and rectal forms of paracetamol are among the most popular and widely used 
 over - the - counter drugs for the treatment of pain and fever , especially in the pediatric 
 population ( 13 , 14 ) . in previous studies ,
the antipyretic effect of rectal 
 paracetamol has been well established , yet the antipyretic effect after one hour of 
 administration has not been clarified ( 15 - 17 ) .
to best of our knowledge , only one study has 
 reported a decrease in body temperature one hour following the administration of paracetamol 
 with an average of 1.07  0.16c , which is significantly more than what we 
 detected in our survey ( 0.65  0.17 c ) ( 17 ) .
these differences are hard to explain as the same drugs , dose and methods had 
 been used .
however the initial body temperature ( 39c in the study of karbasi et al . 

( 17 ) and 38c in our study ) could be the 
 cause of these differences . unlike paracetamol , antipyretic properties of nsaids , especially diclofenac , are somewhat 
 unknown and only a few studies have examined these effects ( 18 - 22 ) . in one study , 
 that examined the effect of different doses of oral diclofenac in reducing fever and pain , 
 resulting from acute febrile sore throat , diclofenac significantly reduced fever and throat 
 pain .
the overall efficacy of all doses of diclofenac ( 6.25 , 12.5 and 25 mg ) was rated 
 significantly higher than that of the placebo . also , paracetamol was only slightly better 
 than diclofenac 6.25 mg dose , and the other doses of diclofenac proved to be more effective 
 as compared to paracetamol ( 22 ) .
the study of polman et al . on the antipyretic effect of suppository diclofenac showed that 
 it significantly decreases fever during the first two hours after administration and the 
 body temperature returns to normal values after two hours in all patients receiving 
 diclofenac ( 18 ) .
litalien et al . studied the 
 efficacy of nsaids including suppository diclofenac in reduction of fever and pain in 
 children and reported it to be more effective than oral acetaminophen . also , suppository 
 diclofenac was more effective in relieving pain compared to acetaminophen ( 19 ) .
we believe that this is the first attempt that compares the antipyretic effectiveness of 
 the rectal forms of paracetamol and diclofenac .
diclofenac is rapidly absorbed in those 
 parts of the gastrointestinal tract that have ph values higher than five ( 23 ) .
paracetamol is also highly absorbed under 
 alkaline conditions ; however , its absorption is less dependent on the environmental ph 
 ( 24 , 25 ) .
the alkaline environment of the rectum has a relatively similar impact on the 
 absorption of both drugs ( 26 ) .
so what makes 
 diclofenac more efficient in reducing fever is the variability of the time when maximum 
 concentrations of the drugs are reached , which is one hour for diclofenac and more than two 
 hours for paracetamol ( 27 - 29 ) .
the antipyretic effect during the following hours was not 
 evaluated in this study yet considering the half - life of diclofenac ( which is about 80 to 
 120 minutes ) and paracetamol ( which is about six to eight hours ) , it is postulated that over 
 the following hours the degree of reduction in fever becomes similar in both groups ( 27 ) .
the ability of diclofenac to quickly reduce the body temperature makes this drug a suitable 
 choice for children s fever treatment especially in those patients with poor or 
 critical conditions ; however , its short half - life may increase the likelihood of recurrent 
 fever .
conducting trials , which simultaneously assess antipyretic and analgesic effect of 
 paracetamol and diclofenac may help identify the advantages of each .
as previously stated , to best of our knowledge , this study is the first completed clinical 
 trial comparing the antipyretic properties of rectal forms of diclofenac and paracetamol . 

one of the strengths of the present study is that the drug administration was based on the 
 patients total body weight achieved through accurate measurement and converting the 
 drugs .
this study had some limitations , one of which was the impossibility of assessing the 
 adverse effects of the studied drugs as they were used with other drugs and at a single 
 dose .
not measuring the serum levels of the drugs in studied subjects is considered the 
 other limitation , which prevented the evaluation of the inter - individual differences in 
 absorbing the drugs and the time of maximum serum concentrations .
the last limitation 
 involves non - cooperative parents , who refused to check the rectal temperature frequently 
 during the following hours . in conclusion , this study showed that suppository diclofenac could significantly decrease 
 rectal temperature as compared with suppository paracetamol during the first hour , yet 
 overall both drugs were found to be equally effective for stopping fever .
finally , a similar 
 study with a larger population is warranted to investigate the extent of temperature control 
 at different elapsed times after medication administration in order to better compare the 
 efficacy of these two drugs .
 backgroundfever is the most common complaint in pediatric medicine and its treatment is 
 recommended in some situations . 
 paracetamol is the most common antipyretic drug , which 
 has serious side effects such as toxicity along with its positive effects . 
 diclofenac is 
 one of the strongest non - steroidal anti - inflammatory ( nsaid ) drugs , which has received 
 little attention as an antipyretic drug.objectivesthis study was designed to compare the antipyretic effectiveness of the rectal form of 
 paracetamol and diclofenac.patients and methodsthis double - blind controlled clinical trial was conducted on 80 children aged six 
 months to six years old . 
 one group was treated with rectal paracetamol suppositories at 
 15 mg / kg dose and the other group received diclofenac at 1 mg / kg by rectal 
 administration ( n = 40 ) . 
 rectal temperature was measured before and one hour after the 
 intervention . 
 temperature changes in the two groups were compared.resultsthe average rectal temperature in the paracetamol group was 39.6  1.13c , 
 and 39.82  1.07c in the diclofenac group ( p = 0.37 ) . 
 the average rectal 
 temperature , one hour after the intervention , in the paracetamol and the diclofenac 
 group was 38.39  0.89c and 38.95  1.09c , respectively ( p = 
 0.02 ) . 
 average temperature changes were 0.65  0.17c in the paracetamol group 
 and 1.73  0.69c in the diclofenac group ( p < 0.001).conclusionsin the first one hour , diclofenac suppository is able to control the fever more 
 efficient than paracetamol suppositories . 
1. Background
2. Objectives
3. Patients and Methods
3.1. Study Participants
3.2. Body Temperature Measurement
3.3. Medications
3.4. Statistical Analysis
4. Results
5. Discussion