Indian Pediatrics 2002; 39:473-477
Comparison of Antipyretic Effect of Nimesulide and Paracetamol in Children Attending a Secondary Level Hospital
Nimesulide is a new non-steroidal anti-inflammatory (NSAID) drug which has been found to be useful in the treatment of fever. In children, owing to the concern of safety, paracetamol continues to be used. However, with the availability of nimesulide as suspension, its utility in treating fever cases in children needs to be assessed under different Indian settings. We could locate only one such study from India. This was from a children’s hospital in Delhi(1). However, the clinical profile of the patients attending such a center are different and are not representative of the morbidity pattern commonly occurring in the community. Most of the fever cases do not require admission. If the utility of nimesulide has to be tested in real life situation, the children will have to be recruited from the outpatients of primary and secondary level hospitals.
Therefore, we conducted a study in a secondary level hospital at Ballabgarh to assess the suitability of nimesulide in treating children with fever. The objective was to compare the effectiveness of nimesulide and paracetamol suspension in the treatment of children with pyrexia attending pediatric out patients at a secondary level hospital at Ballabgarh.
Subjects and Methods
This was a double blinded randomized controlled clinical trial among pediatric out/in-patients of Civil Hospital, Ballabgarh. This hospital is run as a part of the collaborative project between All India Institute of Medical Sciences (AIIMS), New Delhi and the State Government of Haryana. The study subjects were children between the age of 2 months to 12 years who were admitted with pyrexia. The primary outcome variable was number of hours to reach the normal temperature. The secondary outcome variables were; the number of fever cycles in the illness episode, the time elapsed between dosing and the lowest temperature; and extent of temperature decrease. Patients with known allergy to NSAIDs, pre-diagnosed liver disease, renal disease, gastric ulcer, G6PD deficiency and haematological disorders were excluded. Children with temperature more than 40ºC at the time of enrolment were excluded from the study.
A total of 100 children with 50 children in each group were to be recruited. All consecutive children attending pediatric OPD/emergency, who fulfilled the inclusion criteria, and whose parents consented to participate were enrolled. If a child had history of high fever but was afebrile at the time of examination, the child was kept under observation in the ward and enrolled after he became febrile. Informed written consent was taken from all the participants. The drugs were supplied by the manufacturers (Panacea Biotec) in similar colored syrup. The drug bottles were numbered 1 to 100 in a random sequence of nimesulide and paracetamol. The child was given the drug from the bottle numbered as per the sequence of enrolment. Nimesulide (Nimulid) suspension (1.5 mg/kg/dose) thrice daily and paracetamol suspension (10 mg/kg/dose) thrice daily were given in divided doses. The concentration of the drugs were so adjusted that a similar volume of the syrup gave the above doses.
The children were kept in the ward for at least 24 hours or till clinical cure whichever was later. Their temperature was measured using digital thermometer one hourly in the initial 8 hours and every four hours subsequently. All the children were given the treatment for the diagnosed cause of fever as decided by the treating physician based on the investigations done. If the children needed any other rescue therapy substituting these antipyretics it was given. However, they were still included for analysis. Number of patients needing rescue therapy was noted. Side effects of the drug were monitored clinically (renal-urine output, hematuria, edema. liver function - jaundice, bleeding from any site, rash) and as and when felt necessary, further investiga-tions were performed at Ballabgarh hospital itself.
The data was entered in Fox base. SPSS (version 4.0) was used for analysis. Two tailed unpaired t-test was applied to compare the means of the two groups at 0.05 level of significance. The codes were opened at the end of the study after the data analysis for the primary outcome variable was completed. Intention to treat analysis was performed.
A total of 97 children were enrolled. Forty seven children were in the nimesulide group and 50 in the paracetamol group. The base line characteristics of both the groups are shown in Table I. The mean age and weight were similar in both the groups. There were more females in the nimesulide group. However, this was not statistically significant. The mean temperature of children in both the groups at the time of enrolment was similar.Table I-Baseline Characteristics of the Nimesulide and Paracetamol Group
The common causes of fever were respiratory infection in the nimesulide group and unspecified fever in the paracetamol group. In the nimesulide group, 30 children (63.8%) needed admission based on their clinical conditions (others were admitted only for the study) compared to 26 (52%) children in the paracetamol group.
In the children receiving nimesulide, it took 8.6 h to reach normal temperature as compared to 13.4 h in the paracetamol group (Table II and Fig 1). The difference was statistically significant. There were two cases in each group who did not respond to the antipyretics and needed "rescue" therapy. If these cases are excluded from analysis, the difference in number of hours to reach normal temperature is 7.8 h for nimesulide group and 12.5 h for the paracetamol group (not shown). This was significant at 0.003 level.
Table II-Comparison of Outcome Variables in the Two Groups
The antipyretic effect was compared in two subgroups. First, among those who needed admission and those who did not. Among those who needed admission, the mean interval to reach normal temperature was 8.7 h (7.3) in the nimesulide group, compared to 13.9 h (11.7) in the paracetamol group (p = 0.07). In the children who were admitted only for this study, the mean interval in the two groups was 6.0 h (7.8) and 12.5 h (7.9), respectively (p = 0.02). In the unspecified fever group, temperature reached normal level in 9.8 h (10.1) in the nimesulide group, compared to 13.6 h (7.1) in the paracetamol group (p = 0.3). In children with pneumonia, the temperature reached normal faster in paracetamol group (9.9 h ± 7.6) compared to the nimesulide group (13.1 h ± 14.5). This difference was not statistically significant (p = 0.57).
The children were discharged if the fever and the underlying cause was under control after at least 24 hours of admission after monitoring. The number of fever cycles during the period of admission was 2.0 for the nimesulide group. This was significantly higher for the paracetamol group (2.9). The mean number of hours between dosing and the lowest temperature recorded in a cycle was also significantly higher for the paracetamol group (4.5) as compared to the nimesulide group (3.3). The rate of fall of temperature per hour was significantly (p <0.03) faster for the nimesulide group (0.64ºC ± 0.39ºC) as compared to the paracetamol group (0.48ºC ± 0.30ºC). The mean decrease in temperature for each cycle was slightly higher for the nimesulide group. However, this was not statistically significant. The proportion of children who did not attain normal tempera-ture despite the first antipyretic dose was 16 (34%) in nimesulide group and 20 (40%) in the paracetamol group. This was not statistically significant. The differences were not significant for subsequent doses as well.
The drugs were well tolerated by the children. No side effects were reported in any child. One child in the nimesulide group expired. The child was suffering from post measles bronchopneumonia. Four children in the nimesulide and five children in the paracetamol group needed referral.
This was a double blind randomized controlled trial to assess the efficacy of nimesulide and paracetamol in the treatment of fever in children seen at a secondary level hospital in Faridabad District of Haryana. The study setting was reflective of the typical clinical setting in such situations rather than a more controlled experimental setting.
The result showed that nimesulide acted more rapidly than paracetamol in bringing down the temperature to normal. The number of fever cycles before the child could be discharged was lower in nimesulide group again indicating a faster reversion to normal status. The difference in temperature between the start of cycle and the lowest temperature in the cycle was higher for nimesulide group, though not statistically significant. The subgroup analysis had shown that nimesulide performed better than paracetamol in all subgroups except pneumonia. However, the sample size was small for any meaningful subgroup analysis.
Paracetamol was given in eight hourly doses rather than six hourly doses for the purposes of blinding. This could have resulted in underestimation of the antipyretic effective-ness of paracetamol. However, we also studied the fall in temperature within a fever cycle and it was slower in the paracetamol group. The temperature was monitored only on an hourly basis. A preferable method would have been a continuous monitoring. Therefore all the time measures in the study would have been over-estimated. However, as this limitation was equally applicable to both the groups, it is unlikely to have affected the result.
Other studies have also found that the antipyretic and anti-inflammatory effect of nimesulide is better than paracetamol(1-4). Most of these studies have focussed on respiratory infections only. Our study had included a more broader spectrum of patients usually seen at a secondary level hospital. Some studies have reported that their antipyretic effect was similar(5-6).
Our study did not report any major side effect of nimesulide. The safety of nimesulide has been reported before as well. This study did not have enough sample size for assessing the frequency of rarer side effects. In conclu-sion, nimesulide has better antipyretic effect than paracetamol in children in the doses used in the study and appears to be safe for use in them.
Contributors: SKK designed and supervised the trial; he will act as the guarantor of the paper. BB and JS enrolled the children, treated and supervised the temperature monitoring by nursing staff; EP reviewed the literature and did the data management and analysis; KA was responsible for design, execution, analysis and writing of the draft; DS conceived the idea, managed the logistics and helped in drafting.
Funding: Ms. Panacea Biotec
Competing interests: DS is an employee of Ms. Panacea Biotec, a pharmaceutical company that manufactures nimesulide (Nimulid).