How to deal with fever?
In this video series Dr. David Martin awnsers questions about fever and how to deal whith it.
In this video-series Prof. Dr. David Martin answers questions concerning fever. They are developed in collaboration with Dr. Valentin Wember and the Stratos Verlag. (For a similar series in German please click on above)
Here you can find more articles on the subject:
- In this article, the author asks why so many people are still afraid of fever: Fever phobia 35 years later: did we fail?
- These reviews/guidelines from England and USA state that there are no maximum temperatures from which to lower the fever
- In these articles the author investigates “Fever: Views in Anthroposophic Medicine and Their Scientific Validity” and fever from am anthroposophic perspective „Fieber aus anthroposophischer Sicht“. Author: David.martin(at)med.uni-tuebingen.de
- The article „Fieberkrämpfe: Hilft Wärme im Fieberanstieg?“ provides information on possible alternative treatment in cases of febrile convulsions: in particular, it could help to warm the children during the fever rise.
- This article shows that one cannot avoid febrile convulsions with fever-reducing drugs
- This article compares the current practice with the evidence in dealing with fever
You are welcome to visit our facebook page on the topic.
Advice to parents
Additional advice to parents of children with febrile infections
Disclaimer: The content on this website is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always consult with a qualified and suitable medical care provider, and follow their advice without delay regardless of anything read on this website. You assume full responsibility for using any information on this site, and you understand and agree that the author and his affiliates are not responsible or liable for any claim, loss or damage resulting from its use.
Dear parents, every healthy child gets a feverish illness from time to time. Nevertheless, many parents feel insecure with a febrile child or are frightened. But what exactly is meant by fever, what can you do and what is important?
QUESTION: „My partner obviously grew up with the idea that fever is dangerous and should be lowered – she says her cousin developed meningitis as 1-year old because of high fever and now she has epilepsy as a result, or so she thinks…”
ANSWER: This is a very frequent and understandable cause for “fear of fever” (fever-phobia). This fear is due to a confusion between cause and effect. The fever did not cause the epilepsy. The fever was a healthy reaction against the pathogens that were causing the meningitis. In fact, the child may have been able to deal better with the meningitis and perhaps even avoided developing epilepsy if it had been supported in developing and maintaining fever. Using antipyretics (= medicines that suppress the fever like paracetamol/acetaminophen or ibuprofen) can also suppress the symptoms and thereby delay proper diagnosis and antibiotic treatment (antibiotics are often not necessary in febrile children but need to be given promptly if there are signs of meningitis). Fever enhances the immune defense against bacteria that cause meningitis and antibiotics work better at febrile temperatures (1)(2)(3)(4).
Recommendations and ideas on how to deal with fever:
– Relax. If you are anxious, your child cannot relax and tolerate the fever. Then make sure the child does not have any symptom that requires immediate medical advice (see Q&A: When do I need to see a doctor?”).
– Be near. See febrile illnesses as opportunities to nurture relationships. Candlelight, songs, stories can be helpful, or just your calm presence. Electronic media are not a substitute and should be kept at a minimum, if at all (see Q&A below: “What about Media?”).
– Be positive. Science has proven it: positive people live longer and healthier. Be a good example for your child and be positive and peaceful in the face of any challenge and set-back. Always ask yourself “what could this be good for?” – what may initially seem like a problem turns often out to be the start ofsomething good.
– Welcome the fever. Fever is a friend and can to fight infections and develop the immune system (see scientific facts below).
– First give warmth! Make sure the child is warm when the temperature is rising. The child will thus need less energy to develop fever, have less chills, less discomfort and this may even prevent febrile seizures in some children (see also Q&A: What about febrile seizures?”)
– Some children feel very uncomfortable at the beginning. Offer fluids, preferably warm, comfort, tell very brief self-made stories or rhymes, sing or hum. The discomfort usually does not last long. If you are unable to comfort your child, or if your child seems very unwell, then you need to seek medical advice. In adults, fever often leads to headaches that can be relieved with painkillers, in children this is seldom necessary (see Q&A: When do I need to see a doctor?”).
– Allow the fever to do its work. The temperature itself is not the danger, the potential danger is the underlying disease to which the child reacts with fever. Once you and/or your doctor have made sure that the child does not have anything dangerous, you can concentrate on making the experience as enjoyable as possible for everyone. This does not have to involve giving fever suppressing medicines: in otherwise healthy child, there is no temperature above which fever-lowering medicines must be given. In a quiet and secure setting, most children can have high temperatures without suffering. If the child is suffering you can try to apply natural methods (5) such as thin slices of lemon on the soles of the feet, or thin warm damp cloths on the lower legs (many parents apply cold damp cloths, but cold leads to discomfort and counter-reactions, whereas warmth damp thin cloths are not a shock to the child and nevertheless quickly take away heat by evaporating) (regarding enemas, see Q&A).
– Then allow gentle cooling. Once the child is feels warm all the way to its feet and, after a few hours of fever, starts sweating, you can gently take away some layers of sheets and clothing in order for the child to feel comfortable – but still leaving enough sheets and clothing for the child to feel warm all the way into the hands and feet! In some countries, the patients are kept very warm to sweat at this stage. The author is not sure yet as to when this is beneficial and when it is just strenuous (see also Q&A).
– Drinking and eating. In the initial phase, the phase of fever increase, the body has just one goal: get the temperature up there! So don’t expect your child to want to drink, let alone eat. Just give warmth. Once the fever plateau is reached, you can offer the child small sips – of a preferably warm fluid (e.g. mild thyme, elderflower or chamomile tea (6,7)). Later, when the fever is abating the child will be more ready to drink, and even eat light foods like thin soups.
– Show your doctor you are educated about the positive effects of fever: many doctors prescribe antipyretics (paracetamol and ibuprofen) even though they know that fever itself is not dangerous because they think the parents are afraid of fever (8). Tell your doctor you know fever is a helpful reaction of the body.
QUESTIONS AND ANSWERS (Q&A)
QUESTION: Is fever a disease?
ANSWER: Always remember that fever itself is not the disease, it is there to enable the body to fight the infection. This is why the American Academy of Pediatrics and the UK Nice Guidelines say you do not need to suppress it (8).
QUESTION: What are the Temperature limits of fever?
ANSWER: Fever is defined as an increase in body temperature above 38.5 °C (101.3 °F). Fever rarely goes beyond 41.7 °C (107.1 °F) and temperatures above 42.2 °C (108.0 °F) are extremely rare. Normal fever is actively created and guided by the body and therefore does not increase to levels that would endanger the body (9).
QUESTION: When do we need to see a doctor?
ANSWER: Fever is not dangerous but the underlying disease can be a threat to your child. Here are the signs that let you know that the disease may be dangerous (10):
· all children under the age of 6 months with fever should be seen by a doctor on the same day unless experienced carers can make a well-founded judgement that the child is not in danger
· call a doctor if your child is not reacting as it normally does, or is apathetic, or acting in a very strange way, or if it does not let itself be comforted, does not stop crying or if you are otherwise worried or unsure
· call a doctor if your child is looking very ill or limp, has a stiff neck, is not drinking anything for more than 6 hours (eating is not important at first)
· call a doctor if the fever lasts more than 2 days, just to be on the safe side, unless your child is clearly getting better. In the case of fever lasting more than three days the urine of the child must be examined to exclude a urinary tract infection.
QUESTION: What is fever?
ANSWER: Fever is the reaction of the body towards invading bacteria and viruses. Bacteria and viruses often cause illnesses when the body has not (yet) learnt do deal with them, or when a person is weakened and stressed. It is very important to understand that fever is actively created by the body: suddenly the body acts as if its normal temperature of about 36.5-37 °C (97.3-99,1 °F) is too cold and starts to shiver and retract warmth from the periphery to increase the core temperature.
QUESTION: Do you have some kind of animation showing how fever is a friend to the body, how it works etc.?
ANSWER: I have not found one yet. Maybe you like to help me make one? You can read about the positive effects of fever (here, for example (5,11))
QUESTION: What is a good way of dealing with fever?
ANSWER: The first phase of a fever is associated with cold hands and feet, chills and warmth-seeking, rest-seeking behavior. If you understand this, then you understand that the person needs warmth and you can follow your instincts: put them in a warm bed, cover them well, give them a hot water bottle (a warm cherry-stone pillow is safer for children) and warm drinks until their hands and feet are warm and they do not feel cold anymore. This is usually when they have reached the plateau, the peak of their fever. It usually takes an hour or two for someone to reach their plateau. The fever-plateau can then last for several hours before the temperature begins to decrease. When they start sweating and feeling too hot you can uncover them just enough for them to not feel cold. Usually, the fever increases in the evening and is lower on the next morning, and this cycle of evening fevers may be repeated for several days. (see above for “when to call a doctor”).
QUESTION: You say “Don’t be afraid of high temperatures”, but what if something goes wrong? what should we do? We feel like we need to control the fever…”
ANSWER: Fever is not the disease. The disease can go wrong, though, which is why you need to see a doctor if in doubt. Just “controlling the fever” can hide the symptoms and lead to delayed diagnosis of more serious conditions (12).
QUESTION: What about febrile convulsions?
ANSWER: Randomized trials have shown that conventional antipyretics do not prevent simple febrile convulsions (13)(14)(15). About 5% of all children are prone to febrile convulsions between the ages of 6 months and 6 years. They almost all grow out of it, with no developmental sequels. Febrile convulsions are hardly avoidable, but luckily, simple febrile convulsions are not dangerous, even though they are scary (8). Epilepsia is a different matter: some epileptic fits get better with fever and others get worse.
Question: Does fever need to be treated with antipyretics?
Answer: No. Antipyretics (paracetamol/acetaminophen/Tylenol, ibuprofen) are medicines that induce the brain to suppress the fever reaction. Although many hospitals and practices have not yet translated this into practice (16), there is broad scientific consensus that the potential benefits of the febrile reaction and risks of using antipyretics are to be weighed up against the discomfort or exhaustion experienced by a minority (8)(5). (see below for more scientific facts).
QUESTION: Does fever always need to be treated with antibiotics?
ANSWER: No. Antibiotics are medicines that poison bacteria, either directly killing them or preventing them from replicating. Fever is much more frequently due to viruses than to bacteria, and antibiotics are of no help whatsoever against viruses. Even many bacterial infections can be overcome perfectly well by the immune system without the use of antibiotics. (And this works better if you are allowed to fever, as the following experiemtn in rabbits has shown: Pneumococcus type III bacteria were injected under their skin. They developed high fever and a local abscess that healed within a few days – without antibiotics. When, however, their fever was suppressed, these rabbits could not fight the bacteria sufficiently anymore and died of sepsis (17).
QUESTION: Some doctors have told us to take layers of clothing off when the fever is present so whom should we believe – can you back up your statement that children need warmth at the onset of fever?
ANSWER: Just think: your child’s brain is telling your child’s body to get warmer in order to better fight the viruses or bacteria, and you take your child’s clothes off. Well the brain will tell the body to work harder at getting warmer, the child will start feeling cold, uncomfortable and perhaps even start to shiver. Warming your child, on the other hand will tell the brain: “all is well, the temperature is rising, no need to put on more pressure”. And the child will feel more comfortable. Animal studies show that animals do better in warmer environments when they have a fever (5,18).
QUESTION: When should we give a warm bath? beginning or middle of fever?
ANSWER: A bath is a little tricky when a child has fever. Usually a child is better off just tucked into bed and kept nice and warm.
QUESTION: What about Media? Why should febrile children not watch TV or Youtube cartoons? Most people think it’s fine.
ANSWER: Just watch cartoons yourself when you have a fever and try to feel whether this is really doing you good. In fact, having your eyes closed or at least not straining them with anything is most probably what you will feel like doing. This instinct will be overridden by a fascinating cartoon, but that is not to the benefit or your child. Having to unconsciously process the 8-50 frames per second of a film or comic is not what your brain needs when you have fever.
Aside from the neurosensory strain and the hypnotic nature of screens leading to poor neuromotor development, the content and quality of most cartoons are not helpful for children. This is also the message of the American Academy of Pediatrics (19)(also for children without fever!):
For children younger than 18 months, avoid use of screen media other than video-chatting (e.g. with grandparents who live far away). Parents of children 18 to 24 months of age who want to introduce digital media should choose high-quality programming, and watch it with their children to help them understand what they’re seeing.
For children ages 2 to 5 years, limit screen use to 1 hour per day of high-quality programs. Parents should co-view media with children to help them understand what they are seeing and apply it to the world around them.
For children ages 6 and older, place consistent limits on the time spent using media, and the types of media, and make sure media does not take the place of adequate sleep, physical activity and other behaviors essential to health.
Designate media-free times together, such as dinner or driving, as well as media-free locations at home, such as bedrooms.
Here are some links to information use of media in childhood:
QUESTION: Enemas are used in many countries, like Germany and India, are they recommendable?
ANSWER: Enema can relieve febrile discomfort, constipation, and dehydration. Enemas must be seen critically and are only acceptable in appropriately safe settings, yet families who have learnt to deal with enemas hardly ever have to bring their small children into hospital for intravenous rehydration, making enemas very relevant for third-world and remote areas (20). A warm enema of approx. 35 to 37 °C with water (infants 50-100 ml, toddlers up to 200 ml; alternatively, an electrolyte solution as offered in pharmacies for oral rehydration of children with diarrhea can be used in the enema (e.g. Oralpaedon® neutral)) stabilizes the circulation, especially in small and low-drinking children, and slowly and mildly reduces the temperature. Appropriate 220 ml rubber enema bulbs are available at the pharmacy or over the internet (6,7).
QUESTION: But what if we want the fever to go down?
ANSWER: Infectious diseases usually do not proceed more quickly when the fever is lowered (although you may temporarily feel better). On the contrary, many scientific studies show that infection control is more effective at 39 to 41 °C than at 37 °C. In about 97% of cases, natural remedies are sufficient (6,7,21–25). I do have one patient, however, who was born with a brain defect and always vomits profusely at high temperatures. In this case I do use conventional antipyretics.
Question: How should one use conventional antipyretics (such as paracetamol/acetaminophen or ibuprofen)?
ANSWER: Be aware that in most cases children do not need conventional antipyretics and have not long-term benefit from them. So first try other means to make your child feel safe and comfortable. Conventional antipyretic drugs (paracetamol/acetaminophen or ibuprofen) may be administered restrictively to relieve pain or discomfort (irrespective of fever level). For children, Ibuprofen may be safer than paracetamol. After giving an antipyretic, the child may temporarily sweat, the body temperature should cool down, the child feels temporarily less sick than it is, and after about 6 to 8 hours, fever and worsening of general well-being resumes, provided the fever cause persists. This interruption of the natural course of the disease and the up-and-down of the temperature caused by the administration of the antipyretic may be an extra strain on your child and its immune system. Please be aware that this course is to be expected and accompany your child accordingly (uncover when the temperature is going down and cover again when it is rising).
QUESTION: Can you provide more scientific facts?
ANSWER: Here’s a little science on the subject: Fever is a highly conserved evolutionary host response with survival and salutary benefit. Fever is one component of the acute phase response, which is a complex physiological reaction to disease or injury, and elicits cytokine mediated rise in core temperature, generation of acute phase reactants and activation of a number of physiologic, endocrinologic and immunological effects (26). Even though increasing the body temperature is energy-costly (10-12.5% increase in metabolic rate for 1°C increase in body temperature in warm-blooded animals (27)), it is an established mechanism in response to injury and infection in fish, amphibians, reptiles, birds and mammals and many invertebrates such as insects (28). Even cold-blooded animals seek external ways of increasing their body temperature when they are infected and their mortality increases if they are prevented from doing so (29). Studies point to potentially harmful effects of suppressing fever in mammals and humans (16)(30)(31)(32)(33). The protective effects of fever against invading organisms result from a variable combination of direct thermic effects (34) and humoral (35) and cellular (36) defense enhancement. With few exceptions (34), from the point of view of immunity and survival, fever offers the host an adaptive advantage (37). Human studies on malaria (32), chicken pox (31) and induced rhinovirus (38) infections also suggest that fever suppression delays recovery. Fever was associated with decreased mortality in Gram-negative bacteremia (39). Hospitalized elderly patients with community-acquired pneumonia were seven times more likely to die if they did not display fever and leukocytosis (40).
Although many main-stream hospitals and practices have not yet translated this into practice (16), there is broad scientific consensus that the potential benefits of the febrile reaction are to be weighed up against the discomfort or exhaustion experienced by a minority (8).
Beyond suppressing the benefits of fever, pharmacological antipyresis has its own risks: a review financed by ibuprofen distributors (41) could not convincingly disprove that ibuprofen may increase the risk of necrotising fasciitis caused by Group A Streptococcus (GAS) secondary to varicella or herpes zoster (42) (43) (44) (45) while mice inoculated with (GAS) had increased wound area and mortality when receiving ibuprofen (46). There is increasing evidence that ibuprofen in case of respiratory infections or pneumonia may facilitate empyema and complicated pneumonia in children (47) (48) (12) (49) and adults (50), possibly via modification of neutrophil and alveolar macrophages functionality (chemotaxis, adhesion, aggregation, degranulation (51)) and the inhibition of prostaglandin synthesis as well as via cover-up effects on subjective symptoms, thereby delaying diagnosis and treatment. This may explain the correlation between increased sales of ibuprofen for children and complicated pneumonia in France (48), although reverse causation is also possible. Further risks associated with antipyretic use include systemic reactions, asthma (especially for paracetamol (52)(53)(54)(55)), gastrointestinal complications and anorexia (56), low white blood cell count (ibuprofen) (57), hepatic injury (paracetamol) (58), overdose (paracetamol) (58), and, extremely rarely, anaphylaxis (59)(60) (although sometimes the reaction may be due to other substances such as mannitol (61)).
The suppression of the acute phase reaction symptoms and the slightly euphorizing effect of antipyretics is likely to increase interaction with other people and the rate and duration of viral shedding, as has been shown in human volunteers (62) and ferrets (63). Indeed, recent modeling of available data suggests a significant increase in contagion and mortality risk through antipyretics (64). Considering further that accidental acetaminophen overdose has caused over 100 deaths per year in the USA (58), one wonders how many lives may have been saved had scientists popularized their positive attitude towards fever even earlier. (adapted from (5)). Literature
1. Ostberg JR, Repasky EA. Emerging evidence indicates that physiologically relevant thermal stress regulates dendritic cell function. Cancer Immunol Immunother CII. März 2006;55(3):292–8.
2. Hanson DF. Fever, temperature, and the immune response. Ann N Y Acad Sci. 15. März 1997;813:453–64.
3. Blatteis CM. Endotoxic fever: new concepts of its regulation suggest new approaches to its management. Pharmacol Ther. 2006;111(1):194–223.
4. Hajdu S, Holinka J, Reichmann S, Hirschl AM, Graninger W, Presterl E. Increased temperature enhances the antimicrobial effects of daptomycin, vancomycin, tigecycline, fosfomycin, and cefamandole on staphylococcal biofilms. Antimicrob Agents Chemother. 2010;54(10):4078–4084.
5. Martin DD. Fever: Views in Anthroposophic Medicine and their Scientific Validatidity. Evid Based Complement Alternat Med [Internet]. 2016; Verfügbar unter: https://www.hindawi.com/journals/ec…
6. Goebel MW, Michael MK, Glöckler MM. Kindersprechstunde: ein medizinisch-pädagogischer Ratgeber. Verlag Urachhaus; 2016.
7. Glöckler M, Goebel W. A Guide to Child Health: A Holistic Approach to Raising Healthy Children. Floris Books; 2013.
8. Sullivan JE, Farrar HC, American Academy of Pediatrics, the Section on Clinical Pharmacology and Therapeutics. Clinical Report–Fever and Antipyretic Use in Children. Pediatrics. 28. Februar 2011;peds.2010-3852.
9. Mackowiak PA, Boulant JA. Fever’s glass ceiling. Clin Infect Dis. März 1996;22(3):525–36.
10. Richardson M, Purssell E. Who’s afraid of fever? Arch Dis Child. 2015;100(9):818–820.
11. Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol. 2015;15(6):335–349.
12. Elemraid MA, Thomas MF, Blain AP, Rushton SP, Spencer DA, Gennery AR, u. a. Risk factors for the development of pleural empyema in children. Pediatr Pulmonol. 2015;50(7):721–726.
13. El-Radhi AS, Banajeh S. Effect of fever on recurrence rate of febrile convulsions. Arch Dis Child. 1989;64(6):869–870.
14. El-Radhi A, Barry W. Do antipyretics prevent febrile convulsions? Arch Dis Child. Juli 2003;88(7):641–2.
15. Strengell T, Uhari M, Tarkka R, Uusimaa J, Alen R, Lautala P, u. a. Antipyretic Agents for Preventing Recurrences of Febrile Seizures: Randomized Controlled Trial. Arch Pediatr Adolesc Med. 1. September 2009;163(9):799–804.
16. El-Radhi ASM. Why is the evidence not affecting the practice of fever management? Arch Dis Child. November 2008;93(11):918–20.
17. Small PM, Täuber MG, Hackbarth CJ, Sande MA. Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits. Infect Immun. Mai 1986;52(2):484–7.
18. Kluger MJ. The evolution and adaptive value of fever: Long regarded as a harmful by-product of infection, fever may instead be an ancient ally against disease, enhancing resistance and increasing chances of survival. Am Sci. 1978;66(1):38–43.
19. Hill D, Ameenuddin N, Chassiakos YLR, Cross C, Hutchinson J, Levine A, u. a. Media and young minds. Pediatrics. 2016;e20162591.
20. Ulbricht M. Antipyretische Wirkung eines körperwarmen Einlaufes. Universität Tübingen; 1991.
21. Hamre HJ, Fischer M, Heger M, Riley D, Haidvogl M, Baars E, u. a. Anthroposophic vs. conventional therapy of acute respiratory and ear infections. Wien Klin Wochenschr. 2005;117(7–8):256–268.
22. Jeschke E, Lüke C, Ostermann T, Tabali M, Huebner J, Matthes H. Verordnungsverhalten anthroposophisch orientierter Ärzte bei akuten Infektionen der oberen Atemwege. Forsch KomplementärmedizinResearch Complement Med. 2007;14(4):207–215.
23. Soldner G, Stellman HM. Individuelle Pädiatrie: leibliche, seelische und geistige Aspekte in Diagnostik und Beratung; anthroposophisch-homöopathische Therapie. 4. Auflage. Wiss. Verlag-Ges.; 2011. 984 S.
24. Soldner G, Stellman HM. Individual Paediatrics: Physical, Emotional and Spiritual Aspects of Diagnosis and Counseling – Anthroposophic-homeopathic Therapy, Fourth edition. 4 edition. CRC Press; 2014. 984 S.
25. Girke M. Innere Medizin. Grundlagen und therapeutische Konzepte der Anthroposophischen. Second Edition. Berlin: Salumed; 2012.
26. Mackowiak PA. Concepts of fever. Arch Intern Med. 1998;158(17):1870–81.
27. Kluger MJ. Phylogeny of fever. In: Federation Proceedings [Internet]. 1979 [zitiert 15. Februar 2016]. S. 30–34. Verfügbar unter: http://europepmc.org/abstract/med/7…
28. Blatteis CM. Fever: is it beneficial? Yale J Biol Med. 1986;59(2):107–16.
29. Bernheim HA, Kluger MJ. Fever: effect of drug-induced antipyresis on survival. Science. 16. Juli 1976;193(4249):237–9.
30. Eyers S, Weatherall M, Shirtcliffe P, Perrin K, Beasley R. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analyis. J R Soc Med. 1. Oktober 2010;103(10):403–11.
31. Doran TF, De Angelis C, Baumgardner RA, Mellits ED. Acetaminophen: more harm than good for chickenpox? J Pediatr. Juni 1989;114(6):1045–8.
32. Brandts CH, Ndjave M, Graninger W, Kremsner PG. Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet. 1997;350(9079):704–9.
33. Schulman CI, Namias N, Doherty J, Manning RJ, Li P, Li P, u. a. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect. 2005;6(4):369–75.
34. Mackowiak PA. Direct effects of hyperthermia on pathogenic microorganisms: Teleologic implications with regard to fever. Rev Infect Dis. 1. Januar 1980;3(3):508–20.
35. Mackowiak PA, Marling C. Hyperthermic enhancement of serum antimicrobial activity: mechanism by which fever might exert a beneficial effect on the outcome of gram-negative sepsis. Infect Immun. Januar 1983;39(1):38–42.
36. Appenheimer MM, Chen Q, Girard RA, Wang WC, Evans SS. Impact of fever-range thermal stress on lymphocyte-endothelial adhesion and lymphocyte trafficking. Immunol Invest. 2005;34(3):295–323.
37. Roberts NJ. Temperature and host defense. Microbiol Rev. Juni 1979;43(2):241–59.
38. Plaisance KI, Kudaravalli S, Wasserman SS, Levine MM, Mackowiak PA. Effect of antipyretic therapy on the duration of illness in experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections. Pharmacotherapy. Dezember 2000;20(12):1417–22.
39. Bryant RE, Hood AF, Hood CE, Koenig MG. Factors affecting mortality of gram-negative rod bacteremia. Arch Intern Med. Januar 1971;127(1):120–8.
40. Ahkee S, Srinath L, Ramirez J. Community-acquired pneumonia in the elderly: association of mortality with lack of fever and leukocytosis. South Med J. März 1997;90(3):296–8.
41. Southey ER, Soares-Weiser K, Kleijnen J. Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in paediatric pain and fever. Curr Med Res Opin. 2009;25(9):2207–2222.
42. Souyri C, Olivier P, Grolleau S, Lapeyre-Mestre M. Severe necrotizing soft-tissue infections and nonsteroidal anti-inflammatory drugs. Clin Exp Dermatol. 2008;33(3):249–255.
43. Ford LM, Waksman J. Necrotizing fasciitis during primary varicella. Pediatrics. 2000;105(6):1372–1375.
44. Veenstra RP, Manson WE, van der Werf TS, Fijen J, Tulleken JE, Zijlstra JG, u. a. Fulminant necrotizing fasciitis and nonsteroidal anti-inflammatory drugs. Intensive Care Med. 2001;27(11):1831–1831.
45. Hidalgo-Carballal A, Suárez-Mier MP. Sudden unexpected death in a child with varicella caused by necrotizing fasciitis and streptococcal toxic shock syndrome. Am J Forensic Med Pathol. 2006;27(1):93–96.
46. Weng T-C, Chen C-C, Toh H-S, Tang H-J. Ibuprofen worsens Streptococcus pyogenes soft tissue infections in mice. J Microbiol Immunol Infect. 2011;44(6):418–423.
47. Byington CL, Spencer LY, Johnson TA, Pavia AT, Allen D, Mason EO, u. a. An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations. Clin Infect Dis. 2002;34(4):434–440.
48. François P, Desrumaux A, Cans C, Pin I, Pavese P, Labarère J. Prevalence and risk factors of suppurative complications in children with pneumonia. Acta Paediatr. 2010;99(6):861–866.
49. Le Bourgeois M, Ferroni A, Leruez-Ville M, Varon E, Thumerelle C, Brémont F, u. a. Nonsteroidal anti-inflammatory drug without antibiotics for acute viral infection increases the empyema risk in children: A matched case-control study. J Pediatr. 2016;175:47–53.
50. Voiriot G, Dury S, Parrot A, Mayaud C, Fartoukh M. Nonsteroidal antiinflammatory drugs may affect the presentation and course of community-acquired pneumonia. CHEST J. 2011;139(2):387–394.
51. Mikaeloff Y, Kezouh A, Suissa S. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. Br J Clin Pharmacol. 2008;65(2):203–209.
52. Beasley R, Clayton T, Crane J, von Mutius E, Lai CK., Montefort S, u. a. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme. The Lancet. 2008;372(9643):1039–48.
53. Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, FitzGerald JM. Acetaminophen Use and the Risk of Asthma in Children and Adults. Chest. 2009;136(5):1316.
54. Perzanowski MS, Miller RL, Tang D, Ali D, Garfinkel RS, Chew GL, u. a. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort. Thorax. 2010;65(2):118.
55. Kanabar D, Dale S, Rawat M. A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms. Clin Ther. Dezember 2007;29(12):2716–23.
56. Ludvigsson JF. Epidemiological study of constipation and other gastrointestinal symptoms in 8000 children. Acta Paediatr. 2006;95(5):573–580.
57. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen: a practitioner-based randomized clinical trial. Jama. 1995;273(12):929–933.
58. Nourjah P, Ahmad SR, Karwoski C, Willy M. Estimates of acetaminophen (Paracetomal)-associated overdoses in the United States. Pharmacoepidemiol Drug Saf. Juni 2006;15(6):398–405.
59. Kang LW, Kidon MI, Chin CW, Hoon LS, Hwee CY, Chong NK. Severe anaphylactic reaction to ibuprofen in a child with recurrent urticaria. Pediatrics. 2007;120(3):e742–e744.
60. Bachmeyer C, Vermeulen C, Habki R, Blay F, Leynadier F. Acetaminophen (paracetamol)-induced anaphylactic shock. South Med J. 2002;95(7):759–761.
61. Jain SS, Green S, Rose M. Anaphylaxis following intravenous paracetamol: the problem is the solution. Anaesth Intensive Care. 2015;43(6).
62. Graham NM, Burrell CJ, Douglas RM, Debelle P, Davies L. Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers. J Infect Dis. Dezember 1990;162(6):1277–82.
63. Husseini RH, Sweet C, Collie MH, Smith H. Elevation of nasal viral levels by suppression of fever in ferrets infected with influenza viruses of differing virulence. J Infect Dis. April 1982;145(4):520–4.
64. Earn DJ, Andrews PW, Bolker BM. Population-level effects of suppressing fever. Proc R Soc Lond B Biol Sci. 2014;281(1778):20132570.