The quality of evidence is downgraded by imprecise results (few patients).
In children with fever that causes significant discomfort, combined or alternating paracetamol and ibuprofen is suggested for rapid and more effective temperature lowering over a single antipyretic alone.
A Cochrane review [Abstract] 1 included 6 studies with a total of 915 children evaluating combined or alternating paracetamol and ibuprofen to treat fever in children.Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children resulted in a lower mean temperature and proportion of febrile children (table T1). Only one study (n=156) assessed a measure of child discomfort (fever associated symptoms at 24 hours and 48 hours), but did not find a significant difference in this measure between the treatment regimens.
| Outcome | Timepoint from baseline | Participants (studies) | Single agent | Combined regimen | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Mean temperature | 1 hour | 163 (2) | The mean temperature in the control groups ranged from37.6 °C to 37.9 °C | The mean temperature in the intervention groups was0.27 °C lower(0.45 °C to 0.08 °C lower) | |
| 4 hours | 173 (2) | The mean temperature in the control groups ranged from36.5 °C to 37.5 °C | The mean temperature in the intervention groups was 0.7 °C lower (1.05 °C to 0.35 °C lower) | ||
| 6 hours | 40 (1) | The mean temperature in the control group was38.5 °C | The mean temperature in the intervention groups was1.30 °C lower(2.01 °C to 0.59 °C lower) | ||
| Proportion febrile | 1 hour | 40 (1) | 20 per 100 | 10 per 100(2 to 49) | RR 0.5 (0.1 to 2.43) |
| 4 hours | 196 (2) | 23 per 100 | 2 per 100(1 to 10) | RR 0.08 (0.02 to 0.43) | |
| 6 hours | 40 (1) | 50 per 100 | 5 per 100(1 to 35) | RR 0.10 (0.01 to 0.71) |
In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child's fever fails to resolve or recurs. Three studies evaluated the benefits of administering a second antipyretic 3 to 4 hours after the first dose of a single agent, and one additional three-arm study compared alternating paracetamol and ibuprofen every four hours with paracetamol alone (every 6 hours) and ibuprofen alone (every 8 hours). Alternating treatment resulted in a lower mean temperature at one hour after the second dose, and in fewer children remaining or becoming febrile for up to 3 hours after it is given (table T2). One study (n=480) assessed child discomfort (mean pain scores at 24, 48 and 72 hours), and found that these mean scores were lower with alternating therapy, despite fewer doses of antipyretic being given overall.
| Outcome | Timepoint from baseline | Participants (studies) | Single agent | Alternating regimen | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Mean temperature | 1 hour after administration of first agent to both groups | 40 (1) | The mean temperature in the control group was37.6 °C | The mean temperature in the intervention groups was0 °C higher (0.28 °C lower to 0.28 °C higher) | |
| 4 hours (one hour after administration of the alternative agent to the intervention group) | 78 (2) | The mean temperature in the control groups ranged from37.5 °C to 38.0 °C | The mean temperature in the intervention groups was0.60 °C lower(0.94 °C to 0.26 °C lower) | ||
| 6 hours | 40 (1) | The mean temperature in the control group was38.5 °C | The mean temperature in the intervention groups was1.60°C lower(2.27 °C to 0.93 °C lower) | ||
| Proportion febrile | 1 hour | 40 (1) | 20 per 100 | 20 per 100(6 to 69) | RR 1 (0.29 to 3.45) |
| 4 hours | 40 (1) | 30 per 100 | 2 per 100(0 to 39) | RR 0.08 (0.00 to 1.29) | |
| 6 hours | 109 (2) | 45 per 100 | 11 per 100(5 to 25) | RR 0.25 (0.11 to 0.55) |
Only one small study (n=40) compared alternating therapy with combined therapy. No statistically significant differences were seen in mean temperature, or the number of febrile children at one, four or six hours.
No serious adverse events that were directly attributed to the medications used were reported.
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