Written by Jonathan Brewer
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Dual therapy with both ibuprofen and acetaminophen or in alternating regimens may be superior to monotherapy for treating fever in children. Ibuprofen also appears superior to acetaminophen at 4 hours when both are used as monotherapy but similar at 6 hours.
Let’s take a chill pill
There have been multiple trials regarding antipyretics in children. However, there has never been a review to summarize all the existing data. This is a systematic review with network meta-analysis of 31 trials (5009 children) that analyzed both monotherapy with ibuprofen vs acetaminophen but also different protocols of alternating and combined therapy as well. Primary outcomes of this study were the child’s discomfort, fever clearance, and the proportion of afebrile children at 4 hours and 6 hours.
4314 references were initially assessed but after exclusions, 31 were included. After pairwise and network meta-analysis with the random-effects model and independent reviews of the existing trials, the authors found that combined (OR 0.19, 95%CI 0.09-0.42) and alternating therapies (OR 0.20, 0.06-0.63) may be superior to acetaminophen (10-15 mg/kg) alone. In addition, higher dose ibuprofen (closer to 10 mg/kg) was superior at the fourth hour recheck but similar to acetaminophen at the sixth hour. There was no difference in all these analyses (low vs high-dose ibuprofen, alternating regimens, or dual therapy in comparison to acetaminophen alone) in terms of adverse events, which has long been a point of concern. Mean ages ranged between 1.4-5.9 years and in all trials of alternating therapy, acetaminophen was administered first, followed by ibuprofen 2-4 hours later. In addition, fever threshold varied in the studies between ≥ 37.8 ºC and ≥ 38.5 ºC, which differs from the American Academy of Pediatrics (AAP) definition of ≥ 38 C. Finally, there was no discussion between low vs high dose acetaminophen.
How will this change my practice?
Even though I’ve listed some limitations above, this is a strong meta-analysis that further solidifies what we’ve long believed. Even though fever itself does not worsen the course of an illness, it is a large cause of discomfort in children and treating a fever can improve a child’s overall comfort. What I take from this is to consider dual therapy with ibuprofen + acetaminophen (as long as there are no contraindications) instead of monotherapy in my practice.
Source
Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis. Pediatrics. 2024 Oct 1;154(4):e2023065390. doi: 10.1542/peds.2023-065390. PMID: 39318339.
Caution with ibuprofren in dehydrated kids as it can cause AKI
Ibuprofen can inhibit white cell migration and can thus mask SBI.
I want to emphasize your point about making kids feel a little better could also affect their outcomes. For example if they feel so bad they won’t drink they might get dehdrated and this could spiral into a dangerous situation.
I use 10 mg/kg, but cautiously and we need to be aware of these issues. I really don’t need the kid to be running around and playful while they’re sick, just aim for not feeling terrible. I also tell parents they will often fall asleep once they feel better, so 45 min to an hour after they are given the meds is not the time to let them sleep, but rather this is the time to get them to eat/drink, and then they can let them sleep.
Hope this is helpful to younger clinicians.