How does paracetamol help reduce viral fever

Give ibuprofen and paracetamol alternately?

A recently published British study enrolled 156 children between the ages of six months and six years who were acutely ill with a fever between 37.8 and 41 ° C and were treated at home. The children were randomized to receive either paracetamol (15 mg / kg body weight) or ibuprofen (10 mg / kg body weight) or a combination of both substances to reduce fever. The primary study goal was the fever-free time in the first five hours after the first medication. The goal was achieved fastest with ibuprofen: after 42.2 minutes the children were free of fever. It took slightly longer under the combination treatment: a temperature of 37.2 ° C was measured after 45.5 minutes, while under the paracetamol monotherapy 71 minutes were required.

As a conclusion from these results, the authors recommend that ibuprofen be used first if a rapid reduction in fever is desired. The effect of ibuprofen seems to wane as the disease progresses, because in the study, the children taking the combination of paracetamol and ibuprofen were free of fever by an average of 2.5 hours longer than those taking ibuprofen therapy in the first 24 hours. Compared to paracetamol monotherapy, they were 4.4 hours longer without a fever with the combination.

The authors therefore recommend giving ibuprofen first, if no fever is achieved, ibuprofen and paracetamol should not be administered in combination - as investigated in the study - but alternately. In order to avoid overdosing, it is important that parents carefully note when they gave which drug and in which dosage (for current recommendations, see tables).

The National Institute for Health and Clinical Excellence (NICE), on the other hand, still recommends monotherapy with either ibuprofen or paracetamol.

"Study only marginally relevant!"

The pediatrician and pediatric pharmacologist Prof. Dr. Hannsjörg Seyberth, Berlin, is skeptical of both the British study and the alternating administration of ibuprofen and paracetamol. In his opinion, the exclusion criteria were too broad in the study, only one "ideal" patient was included. The reality is often different. For example, children with a fever are often more or less dehydrated. He also criticizes the method used to determine the fever in the study. Measurements were taken in the Axel cave, a procedure that Seyberth is too imprecise. In infants and young children, body temperature should be measured rectally because it is much more accurate. But there is an Anglo-Saxon aversion to this. The initially faster lowering of fever by ibuprofen appears to Seyberth only marginally clinically relevant. If a very rapid reduction in fever is really necessary in Germany, one would have the much more potent metamizole (Novalgin®) at hand, which is still available in all child-friendly dosage forms. Paracetamol is also said to be dosed twice as high for the first dose in the clinics and at the anesthesiologists for treating fever and pain. H. given at 30 mg / kg body weight. More recent clinical-pharmacological studies would have justified this approach. The approval for this is still pending. The combined and alternating use of ibuprofen and paracetamol should only be used in exceptional cases (e.g. in a clinic). Seyberth does not expect a therapy with fewer side effects. On the contrary: the resulting confusion with regard to dosage and dosage interval can quickly lead to overdoses of both analgesics and should be avoided in any case. In the British study, intellectual demands were made on parents that are not always the case in practice.

Expert tip

Avoid dehydration!

If the fever rises above 39 ° C in children, either paracetamol or ibuprofen can lower the fever. The interval between the individual antipyretic doses should be at least two hours. It is important to ensure that the children drink a lot. Children, reports Prof. Dr. Hannsjörg Seyberth, Berlin, would dehydrate very quickly with a high fever. If the fever does not go down, it could also be a so-called thirst fever, which can be reduced by drinking sufficient fluids. With regard to the side effects of antipyretics, it is important to avoid dehydration in children or to correct them as quickly as possible. Because when dehydrated children are treated with ibuprofen, there is a very fast risk of kidney dysfunction.

"Cheating past maximum limits"

Prof. Dr. Dr. Kay Brune, Erlangen, sees such an alternating therapy as being overwhelming for the parents. In his opinion, the combination of paracetamol and ibuprofen also makes no pharmacological sense. Both drugs intervene in the cyclooxygenase system. According to the latest findings, paracetamol does not only work on a central level. Similar to ibuprofen, it inhibits cyclooxygenase 2. This has been shown by experiments in male test persons in which the COX-2 of monocytes was measured ex vivo after exposure to endotoxins in whole blood. If this interesting finding is confirmed in children with febrile inflammatory diseases and with the help of the in vivo recording of the prostanoid profile in spontaneous urine, it is possible that no other mechanism of action can be used through the additional administration of ibuprofen.

According to Brunes, the alternating administration only serves to cheat the respective maximum dosage limits. In principle, there is a risk that the gastrointestinal toxicity of ibuprofen will be increased by paracetamol. However, these risks are rather low in children. They would have proven to be very robust in this regard in the past.

Brune clearly prefers ibuprofen when it comes to treating fever and pain in children. There is no painful situation in which paracetamol is preferable to ibuprofen. Paracetamol is said to be less effective in fever. When it comes to prolonging the effects of ibuprofen, naproxen would be a rational alternative. Naproxen, however, is only approved for ages twelve and up.

Recommendations are updated

According to information from your chairman Seyberth, the Commission for Drug Safety in Childhood of the German Society for Child and Adolescent Medicine will deal with this topic in the near future. Against the background of the new findings and discussions, she will update corresponding recommendations for pain and fever treatment for common diseases in childhood.

source Hay A et al .: Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomized controlled trial. Br Med J 2008; 337; a1 302. Doi: 10.1136 / bmj.a1302
Doris Uhl

Paracetamol dosage recommendations

Ibuprofen dosage recommendations for pain and fever