Shuanghong Luo1, Mengdong Ran2, Qiuhong Luo1, Min Shu1, Qin Guo1, Yu Zhu1, Xiaoping Xie3, Chongfan Zhang4, Chaomin Wan5. 1. Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17 Section Three, Ren Min Nan Lu Avenue, Chengdu, 610041, Sichuan, China. 2. Department of Epidemiology and Health Statistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China. 3. Department of Pediatrics, Dujiangyan Medical Center, Chengdu, Sichuan, China. 4. Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai, China. 5. Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17 Section Three, Ren Min Nan Lu Avenue, Chengdu, 610041, Sichuan, China. wanchaomin@scu.edu.cn.
Abstract
BACKGROUND: No evidence can be found in the medical literature about the efficacy of alternating acetaminophen and ibuprofen treatment in children with refractory fever. OBJECTIVE: Our objective was to assess the effect of alternating acetaminophen and ibuprofen therapy on distress and refractory fever compared with acetaminophen or ibuprofen as monotherapy in febrile children. METHODS: A total of 474 febrile children with axillary temperature ≥38.5°C and fever history ≤3 days in a tertiary hospital were randomly assigned to receive either (1) alternating acetaminophen and ibuprofen (acetaminophen 10 mg/kg per dose with shortest interval of 4 h and ibuprofen 10 mg/kg per dose with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen ≥2 h; n = 158), (2) acetaminophen monotherapy (10 mg/kg per dose with shortest interval of 4 h; n = 158), or (3) ibuprofen monotherapy (10 mg/kg per dose with shortest interval of 6 h; n = 158). The mean Non-Communicating Children's Pain Checklist (NCCPC) score was measured every 4 h, and axillary temperatures were measured every 2 h. RESULTS: In total, 471 children were included in an intention-to-treat analysis. No significant clinical or statistical difference was found in mean NCCPC score or temperature during the 24-h treatment period in all febrile children across the three groups. Although the proportion of children with refractory fever for 4 h and 6 h was significantly lower in the alternating group than in the monotherapy groups (4 h: 11.54% vs. 26.58% vs. 21.66%, respectively [p = 0.003]; 6 h: 3.85% vs. 10.13% vs. 17.83%, respectively [p < 0.001]), the mean NCCPC score of children with refractory fever for 4 or 6 h was not lower than those in either of the monotherapy groups. The number of patients who developed persistent high body temperature was consistent across all study groups. CONCLUSIONS: Alternating acetaminophen and ibuprofen can reduce the proportion of children with refractory fever, but if one cycle of alternating therapy cannot reduce febrile distress as defined by NCCPC score, two or more cycles of alternating therapy may have minimal to no clinical efficacy in some cases. The trial was registered with the Chinese Clinical Trial Registry as ChiCTR-TRC-13003440 and the WHO Registry Network as U1111-1146-6714.
RCT Entities:
BACKGROUND: No evidence can be found in the medical literature about the efficacy of alternating acetaminophen and ibuprofen treatment in children with refractory fever. OBJECTIVE: Our objective was to assess the effect of alternating acetaminophen and ibuprofen therapy on distress and refractory fever compared with acetaminophen or ibuprofen as monotherapy in febrile children. METHODS: A total of 474 febrile children with axillary temperature ≥38.5 °C and fever history ≤3 days in a tertiary hospital were randomly assigned to receive either (1) alternating acetaminophen and ibuprofen (acetaminophen 10 mg/kg per dose with shortest interval of 4 h and ibuprofen 10 mg/kg per dose with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen ≥2 h; n = 158), (2) acetaminophen monotherapy (10 mg/kg per dose with shortest interval of 4 h; n = 158), or (3) ibuprofen monotherapy (10 mg/kg per dose with shortest interval of 6 h; n = 158). The mean Non-Communicating Children's Pain Checklist (NCCPC) score was measured every 4 h, and axillary temperatures were measured every 2 h. RESULTS: In total, 471 children were included in an intention-to-treat analysis. No significant clinical or statistical difference was found in mean NCCPC score or temperature during the 24-h treatment period in all febrile children across the three groups. Although the proportion of children with refractory fever for 4 h and 6 h was significantly lower in the alternating group than in the monotherapy groups (4 h: 11.54% vs. 26.58% vs. 21.66%, respectively [p = 0.003]; 6 h: 3.85% vs. 10.13% vs. 17.83%, respectively [p < 0.001]), the mean NCCPC score of children with refractory fever for 4 or 6 h was not lower than those in either of the monotherapy groups. The number of patients who developed persistent high body temperature was consistent across all study groups. CONCLUSIONS: Alternating acetaminophen and ibuprofen can reduce the proportion of children with refractory fever, but if one cycle of alternating therapy cannot reduce febrile distress as defined by NCCPC score, two or more cycles of alternating therapy may have minimal to no clinical efficacy in some cases. The trial was registered with the Chinese Clinical Trial Registry as ChiCTR-TRC-13003440 and the WHO Registry Network as U1111-1146-6714.
Entities:
Keywords:
Acetaminophen; Axillary Temperature; Febrile Seizure; Ibuprofen; Monotherapy Group
Authors: Tiffany Wong; Antonia S Stang; Heather Ganshorn; Lisa Hartling; Ian K Maconochie; Anna M Thomsen; David W Johnson Journal: Cochrane Database Syst Rev Date: 2013-10-30
Authors: Katarzyna Rycerz; Krzysztof Adam Stepien; Marta Czapiewska; Basel T Arafat; Rober Habashy; Abdullah Isreb; Matthew Peak; Mohamed A Alhnan Journal: Pharmaceutics Date: 2019-11-26 Impact factor: 6.321