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Antipyretic drugs for children
- Charlotte J Mendes da Costa (1 July 2006)
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What is the alternative?
- Rafeeq Muhammed (1 July 2006)
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Why bother?
- ANDREW MONTGOMERY (3 July 2006)
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antipyretic drugs use in children
- dr sudarshan kumari, phase 3 delhi 110052, india (4 July 2006)
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An idea for further research from a personal experience
- Mostafa H Abdel-Hafiz (4 July 2006)
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Antipyretic drugs for children: Which drug is used first-line?
- Tessa L Lewis (4 July 2006)
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Antipyretic drugs for chrildren
- Alan W Fowler (7 July 2006)
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Keep it Simple...
- Gary J Nicholls (7 July 2006)
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Why antipyretics
- simon j moore (8 July 2006)
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Re: Antipyretic drugs for children
- June Thompson (8 July 2006)
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NSAIDs may be more harmful than paracetamol: based on the best evidence available
- Rokuro Hama (13 July 2006)
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Antipyretic drugs for children: education of parents and health care professionals may be more beneficial.
- Francine Verhoeff (14 July 2006)
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What has become of EBM?
- nicholas D. moore (14 July 2006)
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Could "desires" be evidence of higher level than a case-control study?
- Rokuro Hama (19 July 2006)
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Charlotte J Mendes da Costa, FCS GP Bedford Park Surgery, London W4
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The authors did not discuss the physiological uses of fever in infectious diseases, that fever has a use in hastening the immune response to viruses and bacteria. The reverse would also be true that suppressing fever with paracetamol or ibuprofen can impair the immune response. It is my personal experience as a GP that fever suppression with antipyretics can prolong an illness e.g. a viral upper respiratory tract infection with longer lasting sequelae e.g. cough. It is also my experience that parents commonly give regular doses of paracetamol and then send their child who is feeling a little better to school or nursery thus not allowing an unwell child proper time to rest at home and also facilitating transmission of infectious diseases. More work should be done by GPs to allay parent's "fever phobia", that fever should be seen as a healthy response to infection and that physical methods for relieving the distress of fever are perfectly acceptable. Yours sincerely, Charlotte Mendes da Costa. MRCGP DCH MFHom Competing interests: None declared |
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Rafeeq Muhammed, Specialist Registrar in Paediatrics University Hospital of North durham, Durham DH1 5TW
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What is the alternative? In an otherwise comprehensive article by Hay et al (1) about fever management in children, authors did not mention about the complementary and alternative medicine options for fever control in children. Study done by Lee et al in Boston had shown that many patients using alternative therapies including homeopathy and naturopathy are children (2). Armishaw et al had shown that a substantial proportion of children hospitalised with acute medical illnesses had received complementary treatment and alternative health care was used as an adjunct rather than an alternative to conventional health care (3). Receipt of complementary treatment had no significant effect on clinical outcomes for children hospitalised with common acute medical illnesses. Derasse et al had compared the effect of a complex homeopathic medicine (Viburcol, Heel Belgium, Gent, Belgium) with that of Paracetamol in children less than 12 years with infectious fever (4). They have found that Viburcol is an effective alternative treatment to Paracetamol for fever control and it was significantly better tolerated. Parents and practitioners should remember that complementary and alternative treatment is not without its own side effects (5). Finally whatever be the method used for fever control, practitioners and parents should be aware that response to antipyretics does not rule out serious bacterial illnesses. Competing interests to declare: none Dr.Rafeeq Muhammed Paediatric registrar, University Hospital of North Durham, Durham email drrafeeq@rediffmail.com References 1. Alastair D Hay, Niamh Redmond, Margaret Fletcher. Antipyretic drugs for children BMJ 2006; 333; 4-5 2. Lee AC, Kemper KJHomeopathy and naturopathy: practice characteristics and pediatric care. Arch Pediatr Adolesc Med. 2000 Jan; 154(1):75-80. 3. Armishaw J, Grant CC Use of complementary treatment by those hospitalised with acute illness. Arch Dis Child. 1999 Aug; 81(2):133-7. 4. Derasse M, Klein P, Weiser M The effects of a complex homeopathic medicine compared with acetaminophen in the symptomatic treatment of acute febrile infections in children: an observational study. Explore (NY). 2005 Jan; 1(1):33-9. 5. Chowdhury AD, Oda M, Markus AF, Kirita T, Choudhury CR Herbal medicine induced Stevens-Johnson syndrome: a case report. Int J Paediatr Dent. 2004 May; 14(3):204-7 Competing interests: None declared |
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ANDREW MONTGOMERY, locum Auckland
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After 16 years in medical practice I still do not understand the obsession with regard to reducing fever. While I understand that it may be useful in order to prevent febrile convulsions in the 3% of children prone to these and also be useful with respect to improving well being and hydration in an unwell child it appears to have no other function. It may well be that the aggressive control of fever is counterproductive in the longterm. It would be virtually impossible to construct an experiment to confirm this hypothesis. Therefore it is necessary to consider a teleological perspective - that being that it would be better to leave matters to nature -with its potential benefits - rather than medical superstition. Primum non nocere. Competing interests: None declared |
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dr sudarshan kumari, pediatric consultant sunderlal jain hospital, ashok vihar, phase 3 delhi 110052, india
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Use of antipyretics for fever in children has a definite place. All types of fever , viral and bacterial are more frequent in infants than older children.While children at school age can tolerate fever better than infants it is infants who need drugs early to bring down fevers.Use of one or more antipyretics depends on child,s response to fever. Most children respond to either paracetamol or brufen ,often second drug have to be given to bring down the fever. With high fever,infants who are symptomatic(irritability,lethargic,refusal to eat or drink etc)besides being at risk for febrile convulsions, should be given drugs to bring down the fever.Infants can not be put to same practise as older children as they tolerate fevers less. As soon as fever is down a child starts playing and oral intake increases. Even neonates in nicu with rise of temperature of >99 dgerees become symptomatic (increase of o2 requirement, poor perfusion, irritability ,tachycardia etc)and they respond well to paracetamol given orally or as rectal suppository.Only parents know the agony of a febrile infant with pyrexia , hence efforts shold be made for containing temperature by drugs, environmental change etc, of course which drug to choose is personal preferance sudrshan@hotmail.com Competing interests: None declared |
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Mostafa H Abdel-Hafiz, Specialaist Registrar Anaesthetic Department, Great Ormond Street For Children,London,WC1N 3JH
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I do agree with the authors regarding the weakness in the studies they looked at. I was interested in the duration of action ( antipyretic time ) of either paracetamol or brufen. I would like to share a personal experience which could be an idea for further research. I wonder if using paracetamol and brufen at alternative time could lead to better control of child's pyrexia. From my experience as a parent,it does work. My son,who is now 12 years old,used to suffer from pyrexia very often in the fist 2 years of his life including one episode of febrile convulsion .His GP advice was to alternate paracetamol with brufen every three hours and it did work. Needless to say that was before we came to UK Competing interests: None declared |
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Tessa L Lewis, GP Carreg Wen Surgery , Church Road, Blaenavon NP4 9AF
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Further to the issues raised by Hay et al1 regarding combination antipyretic therapy, there appear to be growing concerns about first line treatment of pyrexia and pain in children. The All Wales Prescribing Advisory Group2 recently discussed the observation that both parents and doctors may be using ibuprofen not only in combination, but increasingly as the first line antipyretic/analgesic. Prescribing data3 suggests that the number of prescribed items of paracetamol 120mg/5mls have stayed constant between 2004 and 2006 (based on January-April Welsh data) whereas ibuprofen 100mg/5mls items have increased by approximately 30% over the same period. Dr Hay1 notes that Evidence on safety is also limited [paracetamol and ibuprofen in combination]. Renal failure is associated with the use of ibuprofen in dehydrated children The cBNF states that in children gastro-intestinal symptoms are rare in those taking NSAIDs for short periods. However the adverse effect profile of non-steroidals in adults is well documented: Adverse drug reactions have been shown to account for 6% of hospital admissions and nonsteroidal anti-inflammatory drugs were amongst the drugs most commonly implicated 4. Doctors have been advised that paracetamol is a suitable first choice simple analgesic for most patients with mild to moderate pain, as it is generally well tolerated and effective.5 Both primary and secondary care physicians appear to have concerns regarding the current treatment of pain and pyrexia in children. References 1 Hay A et al, Antipyretic drugs for children. BMJ 2006;333:4-5 2 http://www.wales.nhs.uk/sites3/docmetadata.cfm?orgid=371&id=57962&pid=14033 3. Prescribing Services NHS Wales 4 Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329: 15-19 5 MeReC bulletin vol16 no4 http://www.npc.co.uk/MeReC_Bulletins/2006Volumes/Vol16_No4.pdf Competing interests: None declared |
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Alan W Fowler, Retired orthopaedic surgeon CF31 1QJ
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Antipyretic drugs for children I was surprised to read an editorial on antipyretic drugs for children that expressed no reservations regaring the need for such medication.1 Thomas Sydenham, the famous seventeenth century physician wrote:. Fever is natures engine which she brings into the field to remove her enemy.2 How is it that, more than 300 years later, physicians are still treating fever as a disorder rather than a defence mechanism? Do we still believe that Molly Malone died of a fever, rather than from the typhoid bugs in her cockles and musssels?! The authors end their review with a warning that by prescribing two drugs instead of one for the treatment of pyrexia, we may be encouraging fever phobia. This is ironic. By prescribing drugs instead of recommending equally effective environmental measures to prevent hyperpyrexia, the medical profession is increasing fever phobia and failing to educate the public on the significance of fever.3 1.Hay AD, Redmond N, Fletcher M. Antipyretic drugs for children. BMJ 2006;333:4-5 2. Sydenham T. Methodus curandi fibres 1666 3. Fowler AW. Fever-friend or foe, in Modern Medicine and the Bible, Ortho Books, 2003 Alan W Fowler FRCS High View, Litchard Rise, Bridgend, CF31 1QJ Competing interests: None declared |
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Gary J Nicholls, Clinical Pharmacology Fellow St Vincents Hospital, Sydney, Australia
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Some of my thoughts for you... Most importantly, no child should have to endure 'Pain' and if pain is being treated, then paracetamol should be used first, but Ibuprofen can be added in. Paracetamol is always first line treatment for kids that need to be treated - BUT there is no evidence base that giving antipyretic drugs 'prevents' febrile convulsions - only benzodiazepines have been shown to perhaps do this. Studies done comparing Ibuprofen and Paracetamol used a smaller dose of paracetamol than is normally given and so the results are skewed. Fevers of below 38.5 centigrade are helpful in the body's immune response - and thus treating them is actually not beneficial. Simple regimens are best for parents and prevent confusion. The use of one agent - a single bottle with one syringe/measuring spoon prevents the wrong dose being given, and telling them to get the child reviewed if concerned, and in any case within 24 hours unless they are well again - allows for appropriate review. The use of alternate doses of drugs can cause error. Recommend tepid sponging, and offer an icy-block or ice-lolly/icecream - it usually helps at least build some rappor with the child! Competing interests: None declared |
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simon j moore, GP reg Crouch End, London N8
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Children with fevers are often miserable and appear unwell, worrying doctor and parent, especially if the focus is not immediately obvious. When the fever is controlled, the kid usually perks up dramatically. In a more seriously ill child, this probably wouldnt happen. So response to antipyretics is a useful way of triaging serious causes of fever from non-serious. A response is reassuring to parents and doctor and the child feels better. If I have a fever, I feel lousy. A couple of ibuprofen later, I feel better. Having spent 6 months in childrens A+E, I cant imagine not treating febrile children. Competing interests: None declared |
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June Thompson, Health Visitor London
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As a health visitor I read with interest and some confusion the Editorial and responses to this subject. Gary Nicholls suggests tepid sponging but research is conflicting on whether or not it is effective in lowering temperatures. Also, according to other recent research giving paracetamol and ibuprofen alternatively is the best method for lowering childrens temperature (Sarrell E. Michael et al. Antipyretic Treatment in Young Children With Fever: Acetaminophen, Ibuprofen, or Both Alternating in a Randomised, Double blind Study. Pediatrics & Adolescent Medicine 2006; 160:197-202.) In my experience many mothers become afraid when their young child has a fever or a temperature and may not be susceptible to the advice that it's OK for the child to be 'burning up' as some of them say. We must remember too that NHS immunisations fact sheets advise parents to give paracetamol or ibuprofen to treat a 'fever' if this occurs after babies are given their primary immunisations, or MMR. I always try to make a point of advising parents that at some time their baby is bound to be unwell and to advise them if he has a temperature not to wrap the baby up as is often the instinct of some parents but to undress the baby and keep him cool. Also to offer extra clear fluids or extra breastfeeds. Perhaps in future however,rather than advise that a child with a fever is also given paracetamol or ibuprofen if necessary I should simply tell parents to check with their GP first! June Thompson Health visitor, London Competing interests: None declared |
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Rokuro Hama, Chairman: Japan Institute of Pharmacovigilance, Editor: Kusuri-no-Check (a drug bulletin) #402 Osaka 2-3-2, Tennoji-ku Osaka, Japan 543-0062@
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I was also surprised to read the editorial on antipyretic drugs for children that did not mention the causal relation of salicylate to Reye's syndrome in human and higher mortality in infected animals treated with non-steroidal anti-inflammatory drugs (NSAIDs) compared with vehicle control. I have collected nine papers which reported 15 animal experiments to investigate the effects of NSAIDs on mortality in infected animals. Various NSAIDs were used including ibuprofen, flurubiprofen, mefenamic acid, indomethacin, salicylate and so on. Mantel-Haenztel pooled odds ratio for NSAIDs use on mortality was 10.00 (95% confidence interval (CI): 6.12-30.06, p<0.00000001) [1]. Another evidence available is a case-controlled study reported in the Japanese Task Force's case control study on factors related to onset and severity of influenza-related encephalopathy [2]. Strong relation between the NSAIDs use and fatal influenza-related encephalopathy was observed: crude odd ratio was 47.4 (95%CI; 3.29-1458, p=0.0019)[1,2], though the task force reported that the study could not demonstrate any definite relation of NSAIDs to occurrence of influenza-related encephalopathy. Odd ratio for paracetamol was not significant (OR 2.25; 95%CI; 0.19-58.6) [1,2]. After the warnings against and restriction on use of salicylates, Reye's syndrome disappeared in the U.S [3]. Also, restriction on use of NSAIDs as antipyretics in Japan in 2001 led to dramatic decrease not only in proportion of NSAIDs users (about 30 % to less than 7 %) in treating fever but also in proportion of fatal cases (about 30 % to about 10 %) among Reye's syndrome and/or post-viral infection encephalopathy (including influenza-related encephalopathy) [4]. Many cases of neurological complication in previously healthy children with influenza were reported in the United States recently [5]. I am very much concerned that increasing use of ibuprofen not only in the US but also in Europe might contribute to the complicated morbidity and mortality in flu children instead of salicylates for Reye's syndrome in 1960s to 1980s worldwide or other NSAIDs antipyretics as a cause of epidemics of post-viral infection-encephalopathy (including influenza-related encephalopathy) before 2001 in Japan. I am also concerned about the sudden deaths during sleep and accidental deaths after abnormal behavior after taking oseltamivir. Oseltamivir phosphate may decrease body temperature for it acts as central nervous system suppressants like barbiturates [6]. These two drugs (ibuprofen and oseltamivir) should be closely monitored but should not be confused in epidemiological studies because the spectra of the adverse effects caused by each drug are different: ibuprofen may exacerbate infection and inflammatory responses (indicated by the study [7]: paracetamol-ibuprofen combination was less effective from 10 hours to 24 hours), inducing multi-organ failure including brain, liver and so on in worst cases because they enhance induction of cytokines[8]; on the other hand oseltamivir phosphate could suppress central nervous system leading to sudden deaths from respiratory suppression during sleep or accidental deaths after abnormal behavior [6]. References 1.Hama R. The Informed Prescriber. 2005 ; 20(12); 147-151 (in Japanese, preliminary report) 2.Japanese Task Force. A case control study on factors related to onset and severity of influenza-related encephalopathy: Result: Report of the 2002 study. March 2003 (in Japanese) 3.Belay ED, Bresee JS, Holman RC et al. Reye's syndrome in the United States from 1981 through 1997. N Engl J Med. 1999 May 6;340(18):1377-82. 4.Hama R. unpublished data. 5.Shay D. Surveillance among U.S. Children for Influenza-Related Mortality and Encephalopathy. http://www.fda.gov/ohrms/dockets/ac/05/slides/2005-4180s_06_shay.ppt 6.Hama R. Limited benefit and potential harm of oseltamivir including sudden death and death from abnormal behavior: Rapid response on 26 November 2005 http://bmj.bmjjournals.com/cgi/eletters/331/7526/1203- b#122513 7.Lal A, Gomber S, Talukdar B. Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol. Indian J Pediatr 2000;67: 865- 70.[Medline] 8.Larrick JW, Kunkel SL. Is Reye's syndrome caused by augmented release of tumour necrosis factor? Lancet. 1986 Jul 19;2(8499):132-3. Competing interests: None declared |
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Francine Verhoeff, consultant paediatrician Royal Liverpool Children's NHS Trust, Alder Hey Hospital, L12 2AP
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Editor - Hay et al (1) address in their editorial on antipyretics in children a very important topic including the lack of evidence that two drugs are more advantageous than monotherapy and absence of evidence of effectiveness for drug therapies compared with physical methods in reducing fever. I disagree though with their statement that given the desire from parents and clinicians to do something when faced with febrile children it is churlish to withhold combined drug treatment even when lacking evidence. Benefits of mild to moderate fever have been well described and in a very comprehensive review Walsh and Edwards (2) describe the lack of parents knowledge about normal body temperature, correct dosage or role of antipyretics. This has resulted in a nearly trebling of overdosing in the last 20 years and increase in unnecessary use of healthcare services. The results of the randomised controlled trial Hay and colleagues are currently conducting (http://www.controlled- trials.com/isrctn/trial/|/0/26362730.html) into drugs therapy of fever are desperately needed but clearly, fever management is more than assessing drug effectiveness and should include education of parents and health care professionals about the benefits of mild to moderate fever and the role antipyretics may play. 1 Hay et al. Antipyretic drugs for children. BMJ 2006; 333:4-5 2 Walsh A, Edwards H. Management of childhood fever by parents: literature review. J Adv Nurs. 2006 Apr;54(2):217-27. Competing interests: None declared |
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nicholas D. moore, Professor of clinical pharmacology Universit Victor Segalen, 33076 Bordeaux
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The initial paper concerning the use of paraceetamol and ibuprofen in children is a well thought out and balanced paper stating there is really no indication for simultaneous or alternate use of ibuprofen and paracetamol in children with fever. Whether fever needs to be treated is still debated, and it probably only needs to be treated when it becomes pathological. In the recurrent desire to treat fever, there may be remnants of the times when fever in children often closely preceded death from infectious disease... That being said, some of the responses to this topic concerning relative risks from paracetamol or ibuprofen (NSAIDs) are very strange: they rely on case - control studies, results of irrelevant usage (high-dose, long term risks in adults) and animal experiments to try to state that NSAIDs are more dangerous than paracetamol (which may be true in the absolute, but not in this specific case). For some strange reason I had always thought that the double-blind randomised controlled trial was the referecne methodology to answer medical questions. In this field there is a major clinical trial that shows equal tolerability of ibuprofen and paracetamol in children with fever (1), including in those below 2 years of age (2), but is somehow not cited. Concerning observational studies, since ibuprofen is generally more effective than paracetamol, it will be used when paracetamol fails, i.e., in more severe infections, often when high fever is a harbinger of complications which may then be attributed to ibuprofen (something called the protopathic bias: blaming the messenger for the message) (3). When protopathic bias is likely, good clinical trials will give answers. Recent history in many fields (eg, HRT) should help us not forget this. That being said, of course, the first treatment of fever in children, if needed, is rehydration and cooling, which will reduce the risk of renal failure, which does exist with ibuprofen, even if it is rare (4). Reducing the use of paracetamol will also reduce therisk of inadvertent overdosing, still the first cause of liver failure in small children (5). 1. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. Jama 1995;273(12):929-33. 2. Lesko SM, Mitchell AA. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics 1999;104(4):e39. 3. Lesko SM, O'Brien KL, Schwartz B, Vezina R, Mitchell AA. Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella. Pediatrics 2001;107(5):1108-15. 4. Lesko SM, Mitchell AA. Renal function after short-term ibuprofen use in infants and children. Pediatrics 1997;100(6):954-7. 5. Mahadevan SB, McKiernan PJ, Davies P, Kelly DA. Paracetamol induced hepatotoxicity. Arch Dis Child 2006;91(7):598-603. Competing interests: None declared |
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Rokuro Hama, Chairman: Japan Institute of Pharmacovigilance, Editor: Kusuri-no-Check (a drug bulletin) #402 Osaka 2-3-2, Tennoji-ku Osaka, Japan 543-0062@
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One of the reasons why I thought the editorial's conclusion [1] was strange is that it did not deny the rationale of the combined treatment based on the desires among parents and clinicians to do something when faced with febrile children in the absence of evidence from controlled trials. Could desires be evidence in evidence-based medicine (EBM)? If ever so, are they of higher levels than a case-control study with outcome of mortality and/or systematic review of animal experiments with outcome of mortality when RCT with outcome of mortality or sever morbidity has never been available? ISDB manual [2] stresses the importance of evidence level ranked by the strength of endpoints. The manual was written by modifying a hierarchy introduced by the US National Cancer Institute [3]: overall survival is the strongest endpoint. A large scale randomized controlled trial (RCT) comparing three arms (paracetamol and two different doses of ibuprofen but without placebo-only arm) was conducted [4]. It was a non-placebo-controlled trial and still not large enough for comparison of mortality risks: mortality was not included in the main outcome and no death case was observed. However low white blood cell count was significantly more common and acute gastrointestinal bleeding was more common but not significant in ibuprofen groups than paracetamol group. The reason may be short of power to detect significant difference in acute gastrointestinal bleeding, Reye's syndrome or death. I found another RCT comparing ibuprofen with placebo for severe sepsis [5]. No difference was reported in mortality (40 % with placebo and 37% with ibuprofen) at 30 days, but baseline renal failure was significantly more prevalent in placebo group than ibuprofen group (67 % vs. 53 %). The on-going randomised controlled trial by Hay and colleagues [6] surprisingly does not have placebo-only arm though they say that there is absence of evidence of effectiveness for mono-therapies compared with physical methods of reducing fever or placebo [1]. I would like to add an excellent decision making by Meune et al on the use of NSAIDs for the treatment of viral myocarditis[7]. In view of animal studies and in the absence of controlled studies of aspirin and NSAIDs they did not recommend indiscriminate treatment with NSAIDs or high -dose aspirin in patients with myocarditis where there is no or minimal associated pericarditis. Is there any difference for other viral infections? References 1.Hay AD, Redmond N, Fletcher M. Antipyretic drugs for children. BMJ 2006;333:4-5 2.International Society of Drug Bulletin(ISDB): http://66.71.191.169/isdbweb/pag/documents/12reviewing.pdf) 3. US National Cancer Institute. A hierarchy of strength of endpoints: http://www.cancer.gov/cancertopics/pdq/levels-evidence-adult- treatment/) 4. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA. 1995 Mar 22-29;273(12):929-33. 5. Bernard GR, Wheeler AP et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med. 1997 Mar 27; 336(13):912-8. 6. Hay AD et al. http://www.controlled- trials.com/isrctn/trial/|/0/26362730.html 7. Meune C, Spaulding C. et al. Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies. Drug Saf. 2003;26(13):975-81. Competing interests: None declared |
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