Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Symptomatic fever management in children: A systematic review of national and international guidelines

  • Cari Green,

    Roles Data curation

    Affiliation Gerhard Kienle Chair, Health Department, University of Witten/Herdecke, Herdecke, Germany

  • Hanno Krafft,

    Roles Writing – original draft

    Affiliation Gerhard Kienle Chair, Health Department, University of Witten/Herdecke, Herdecke, Germany

  • Gordon Guyatt,

    Roles Formal analysis

    Affiliation Departments of Health Research Methods, Evidence and Impact and Medicine at McMaster University, Hamilton, Canada

  • David Martin

    Roles Conceptualization

    david.martin@uni-wh.de

    Affiliations Gerhard Kienle Chair, Health Department, University of Witten/Herdecke, Herdecke, Germany, University Children’s Hospital, Tübingen University, Tübingen, Germany

Symptomatic fever management in children: A systematic review of national and international guidelines

  • Cari Green, 
  • Hanno Krafft, 
  • Gordon Guyatt, 
  • David Martin
PLOS
x

Abstract

Introduction

Divergent attitudes towards fever have led to a high level of inconsistency in approaches to its management. In an attempt to overcome this, clinical practice guidelines (CPGs) for the symptomatic management of fever in children have been produced by several healthcare organizations. To date, a comprehensive assessment of the evidence level of the recommendations made in these CPGs has not been carried out.

Methods

Searches were conducted on Pubmed, google scholar, pediatric society websites and guideline databases to locate CPGs from each country (with date coverage from January 1995 to September 2020). Rather than assessing overall guideline quality, the level of evidence for each recommendation was evaluated according to criteria of the Oxford Centre for Evidence-Based Medicine (OCEBM). A GRADE assessment was undertaken to assess the body of evidence related to a single question: the threshold for initiating antipyresis. Methods and results are reported according to the PRISMA statement.

Results

74 guidelines were retrieved. Recommendations for antipyretic threshold, type and dose; ambient temperature; dress/covering; activity; fluids; nutrition; proctoclysis; external applications; complementary/herbal recommendations; media; and age-related treatment differences all varied widely. OCEBM evidence levels for most recommendations were low (Level 3–4) or indeterminable. The GRADE assessment revealed a very low level of evidence for a threshold for antipyresis.

Conclusion

There is no recommendation on which all guidelines agree, and many are inconsistent with the evidence–this is true even for recent guidelines. The threshold question is of fundamental importance and has not yet been answered. Guidelines for the most frequent intervention (antipyresis) remain problematic.

Introduction

Clinical observation has shown that fever is a physiologically controlled elevation of temperature with a strongly regulated upper limit (via protective endogenous antipyretics and inactivity of thermosensitive neurons at temperatures above 42˚C). It rarely reaches 41˚C and does not spiral out of control [1] as is feared by many parents and health professionals [24]. Divergent attitudes towards fever have led to a high level of inconsistency in approaches to its management. Many healthcare providers and parents view fever as a dangerous condition or a discomfort to be eliminated [5], despite evidence that fever is an evolutionary resource that aids in overcoming acute infections [6]. Antipyretic treatment can be harmful: in 2006, accidental paracetamol overdose caused 100 deaths in the USA alone [7]. A number of organizations have responded to this situation by developing clinical practice guidelines (CPGs) for management of fever in children with goals of guiding antipyretic treatment, responding to discrepancies between evidence and clinical practice, and diminishing irrational fear of fever and overzealous attempts at its suppression. Nevertheless, a published review addressing the quality of seven such CPGs [8] concluded that even guidelines judged as “high quality” are neither comprehensive in content nor in agreement with each other in their recommendations. Whether these conclusions apply to the full spectrum of guidelines for management of fever in children remains uncertain. Therefore, we have summarized all recommendations made by existing fever management CPGs, and assessed the level of evidence for each recommendation. This systematic review was not registered.

Methods

All methods were structured according to the PRISMA statement (S1 Checklist). Relevant medical guideline databases were identified through a google search for ‘medical guideline databases’ and then searched using the following search terms: ((((((children[MeSH Terms]) OR (pediatric[MeSH Terms])) OR (children[Title/Abstract])) OR (pediatric[Title/Abstract])) AND ((((treatment[MeSH Terms]) OR (therapy[MeSH Terms])) OR (management[Title/Abstract])) OR (intervention[Title/Abstract]))) AND ((((guideline[MeSH Terms]) OR (principles[MeSH Terms])) OR (guideline[Title/Abstract])) OR (principles[Title/Abstract]))) AND (((((fever[MeSH Terms]) OR (pyrexia[MeSH Terms])) OR (fever[Title/Abstract]))) OR (pyrexia[Title/Abstract])). 1. A search for CPGs (defined as documents on symptomatic fever management in children, issued by governmental organizations, pediatric associations or other healthcare groups) was conducted on the medical databases listed below, as well as websites of the above-mentioned organizations. 2. Google searches incorporating the country name in addition to the original search criteria were then carried out for each of the 195 countries in an attempt to identify any documents that had been missed by the previous methods. 3. A list of national pediatric associations was obtained from the International Pediatric Association’s website (http://ipa-world.org/society.php) and the website of each association was searched for relevant documents using the term “fever” in the language of each. All CPGs, whether intended for healthcare workers or parents,between the dates of 1995 and September 1, 2020 in the 57 languages available on Pubmed, were included. Only the latest CPG of each series was included. Articles that did not focus on the symptomatic management of fever, or were exact copies of other guidelines, were excluded. The process of screening the retrieved documents, as well as eligibility determination and inclusion in the review were carried out by one author.

The following databases were included in the search: PubMed, Google Scholar, National Guideline Clearing House (https://www.guideline.gov/), Canadian Medical Association CPG Infobase (https://www.cma.ca/En/Pages/clinical-practice-guidelines.aspx), Danish Health Authority National Clinical Guidelines (https://www.sst.dk/en/national-clinical-guidelines), Haute Autorite de Sante (https://www.has-sante.fr/portail/jcms/fc_1249693/en/piliers), German Agency for Quality in Medicine (http://www.leitlinien.de/nvl/), Dutch Institute for Healthcare Improvement (http://www.cbo.nl/), Scottish Intercollegiate Guidelines Network (http://www.sign.ac.uk/), National Institute for Health and Care Excellence (https://www.nice.org.uk/guidance), Malaysia Ministry of Health (http://www.moh.gov.my/english.php/pages/view/218).

Data

Data from all sources was extracted to an excel table by one reviewer. The table summarized guideline information (country, title, source, date); pharmacologic recommendations (threshold temperature for antipyretic treatment, recommended medications, posology) and non-pharmacologic recommendations (ice/cold/tepid sponge baths, hydration status, nutrition, ambient temperature, dress, covering, compresses, activity level, complementary/herbal recommendations) according to age group (S1 Table).

Quality of evidence assessment

For each recommendation, two authors conducted a search for the highest level of supporting evidence as defined by a modified version of the OCEBM Criteria (Oxford Centre for Evidence Based Medicine) [9]. Systematic reviews of randomized trials provided the highest quality evidence (level 1); systematic reviews of observational and single randomized control trials, the second level of evidence (level 2); individual prospective observational studies and systematic reviews of case reports the third (level 3); individual case reports the fourth (level 4); and mechanistic explanations the fifth (level 5). Our modifications to the OCEBM included assigning systematic reviews of prospective observational studies to Level 2 and systematic reviews of case reports to Level 3, as well as relevant non-human studies of high quality to level 5. We also rated the rigour of systematic reviews using AMSTAR criteria (“A MeaSurement Tool to Assess systematic Reviews”) [10]; if the review met fewer than 7 out of the 11 AMSTAR criteria we rated the quality of evidence down one level (e.g. if a systematic review of randomized trials failed AMSTAR criteria we classified the quality of evidence as level 2 rather than level 1) [10]. Apart from one main question (see below), we did not perform a formal quality assessment of each body of evidence. We created a table categorizing and comparing the CPG statements and the highest level of evidence found in the literature in support of each statement. Two authors independently rated the quality of the evidence and resolved disagreement through discussion.

GRADE assessment of the threshold question

We found conflicting statements and a lack of evidence regarding one fundamental category that affects almost all other recommendations. This concerns the question: “is there a temperature above which antipyresis should be attempted in acute febrile infections in children?”–in short: the threshold question. Since the NICE guidelines [11] have previously been judged to be of high quality [8], and make a recommendation to treat distress rather than body temperature, we thoroughly examined their data for evidence supporting a lack of temperature threshold and determined that the conclusion they came to was unjustified based on the evidence that they provided.

Two authors then independently attempted to address this question using the GRADE method [12]. One author used the search terms: “fever AND temperature threshold AND children AND guideline AND permissive treatment” and identified a pilot RCT trial [13] and 8 papers related to threshold that were surveys and thus deemed ineligible for inclusion in a GRADE analysis. The other author used the terms: ((("acetaminophen"[MeSH Terms] OR "acetaminophen"[All Fields]) OR ("acetaminophen"[MeSH Terms] OR "acetaminophen"[All Fields] OR "paracetamol"[All Fields]) OR antipyresis[All Fields] OR ("ibuprofen"[MeSH Terms] OR "ibuprofen"[All Fields]) OR threshold[All Fields] OR ("antipyretics"[Pharmacological Action] OR "antipyretics"[MeSH Terms] OR "antipyretics"[All Fields] OR "antipyretic"[All Fields])) AND (harm[All Fields] OR benefit[All Fields] OR outcome[All Fields] OR ("mortality"[Subheading] OR "mortality"[All Fields] OR "mortality"[MeSH Terms]) OR ("epidemiology"[Subheading] OR "epidemiology"[All Fields] OR "morbidity"[All Fields] OR "morbidity"[MeSH Terms]) OR ("immune system phenomena"[MeSH Terms] OR ("immune"[All Fields] AND "system"[All Fields] AND "phenomena"[All Fields]) OR "immune system phenomena"[All Fields] OR ("immune"[All Fields] AND "function"[All Fields]) OR "immune function"[All Fields]) OR distress[All Fields])) AND ((peak[All Fields] AND ("body temperature"[MeSH Terms] OR ("body"[All Fields] AND "temperature"[All Fields]) OR "body temperature"[All Fields])) OR ("fever"[MeSH Terms] OR "fever"[All Fields]) OR ("fever"[MeSH Terms] OR "fever"[All Fields] OR "febrile"[All Fields]) OR ("fever"[MeSH Terms] OR "fever"[All Fields] OR ("elevated"[All Fields] AND "temperature"[All Fields]) OR "elevated temperature"[All Fields])) and identified 1704 papers.

Results

Guideline selection

The search procedure identified 586 documents, of which 441 were excluded due to lack of relevance or duplication after screening titles and abstracts. The remaining records (n = 145) were retrieved in full text. After examining the full text version, a further 71 documents were excluded because they were not CPGs.

Finally, 74 guidelines [11, 1486] were included: three international guidelines as well as the national guidelines for 49 countries (multiple guidelines published by different associations exist in some countries) (S1 Table). Six countries follow the recommendations of another national or international guideline. Therefore, our study represents the fever management recommendations of at least 55 countries.

A detailed inventory of the categories and sub-categories of recommendations revealed conflicting advice in all categories. Furthermore, only a few CPGs provided references to substantiate their recommendations. Table 1 and Fig 13 summarize the results; for full details, see S1 Table.

thumbnail
Fig 2. Threshold for antipyresis.

Temperatures indicate the height of the given threshold.

https://doi.org/10.1371/journal.pone.0245815.g002

thumbnail
Fig 3. Summary of recommendations.

Y-axis: numbers of guidelines reporting.

https://doi.org/10.1371/journal.pone.0245815.g003

GRADE assessment.

The search identified several articles addressing the impact of fever management on disease outcome in ICU patients. However, upon closer examination these studies either included a threshold value for rescue therapy and/or specifically excluded children [161]. With the exception of two studies [162, 163] (Table 2), even the placebo arms of antipyretic RCTs operated with a threshold rescue value; and neither study reported outcomes related to temperature and morbidity/mortality. It is likely that permissive management of fever did not result in negative outcomes because this would have been reported but as the outcomes were not measured, the studies could not be included.

Discussion

Main findings

A comparison of worldwide fever management guidelines, revealed striking discrepancies with each other and with scientific literature on all parameters. The heterogeneity of the recommendations and the low quality of evidence on which they are based, point to a need for better data. Our findings are in line with the previous work of other authors and demonstrate, that many discordant suggestions in guidelines at national or international could be improved [8], in particular, our review stated this fact for recommendations for the use of antipyretis, relevant temperature parameters and treatments. In contrast to previous studies of CPGs, which showed what improvements are needed in terms of methodology, the applicability and the editorial independence domains [8], our review complements the previous work by the result of low or indeterminable evidence levels for recommendations and a very low level of evidence for the threshold for antipyresis. Through summarizing and assessing the available evidence, we provide an extensive basis for the development of a consensus and evidence based, interdisciplinary fever guideline.

Temperature threshold for antipyresis: Evidence vs. clinical practice.

The majority of CPGs recommend against treatment of fever itself, regardless of temperature. In the guidelines that give a threshold for antipyresis, there is little agreement about the temperature, with values ranging from 37.5˚C to 40.5˚C and no rationale provided. Our GRADE assessment suggests–with a very low quality of evidence–that there is no need for a threshold for antipyresis below 39.5 ˚C because that was the maximum threshold used in the studies [13, 161]. Whether a threshold is necessary remains unclear because there are no adequate studies. Despite the majority of guidelines recommending against giving antipyretics based on body temperature, studies of health care workers have shown that most believe that the risk of heat-related adverse outcomes is increased with temperatures above 40°C (104°F) and that more than 90% of doctors prescribe antipyretic therapy at temperatures >39˚C [164, 165]. Even in the UK, a country with longstanding guidelines that recommend only treating distress, a large study of pediatric ICUs has shown that the threshold for treatment of fever is still 38˚C and that 58% of care-givers asked, considered a fever of 39˚C unacceptable [166].

Pharmacologic treatment: Choice of drug, dosing, adverse effects.

Paracetamol is the only medication recommended by all guidelines and 17 give it preference over ibuprofen. Although high quality evidence (Level 1) has shown that they are both effective in lowering temperature, the evidence for effectiveness in distress reduction (the more relevant outcome) is lower (Level 3). There is no justification for paracetamol being the sole, or debatably, even the first-choice antipyretic as no systematic review or RCT comparing it with ibuprofen has shown a superior effect or safety profile. 15 out of 30 RCTs comparing paracetamol and ibuprofen concluded that ibuprofen is superior in effect while the remainder found no significant difference in either effect or safety profiles [90]. This raises the question as to whether paracetamol should be relegated to second-line [91, 167] because while the safety profiles of both drugs are equivalent at therapeutic doses, the toxic level of paracetamol is reached much sooner and causes more deaths than supratherapeutic doses of ibuprofen [7, 168]. Adverse effects caused by ibuprofen generally resolve, although there have been deaths due to triggering of asthma as well as long-term complications from toxic epidermal and soft tissue necrolysis [90]. Also, despite high level evidence [132134] that combining/alternating antipyretics leads to little additional benefit in temperature control, is associated with a higher risk of supratherapeutic dosing and has not been shown to reduce discomfort, the rate of alternating antipyretics in medical practice is 67% [169]. Given that parents misdose antipyretics in almost half of cases with 15% using supratherapeutic doses [170], arriving at a consensus regarding medication choice and dose, along with methods of communicating this to parents would be a valuable contribution towards standardization of fever management. For a full discussion of dosage recommendations, see e-Supplement.

Antipyretics for prevention of febrile seizures: No evidence.

Several systematic reviews and RCTs have shown that antipyretics are ineffective in preventing febrile seizures (Level 1 [137139]). Interestingly, one trial found that antipyretics are ineffective in lowering the temperature at all during febrile episodes that are associated with febrile seizure [138]. However, a recent study concluded that rectal paracetamol administration significantly decreased the likelihood of recurrent febrile seizures during the same fever episode [140].

Nonpharmacologic measures: Fluid intake, bath, rubs and compressions.

Many guidelines recommend an adequate/increased intake of fluids in order to avoid dehydration. Caution should be observed in universally recommending increased fluids as it may cause harm [153]. No direct published evidence was found regarding the optimal amount or type of fluid intake during fever. Proctoclysis is only mentioned in one guideline though the literature suggests that it could be helpful in maintaining hydration status (Level 4), resulting in increased well-being and fewer hospitalizations [159, 160, 171178]. Nutrition is mentioned in 25% of the guidelines with a majority in agreement that children should not be forced to eat during fever. We did not identify any studies on this.

In terms of other physical recommendations, several seemingly opinion based, contradictory approaches are mentioned: cool to warm room temperatures, ventilated to unventilated rooms, bundling to undressing the child completely, and bedrest to normal activity. A systematic review that attempted to analyze these factors [150] found that there were no studies investigating physiological interventions or environmental cooling measures as separate interventions.

Given the lack of evidence, one may appeal to knowledge of the fever process to determine that appropriate use of physical measures depends on the fever phase: As the fever is rising, the child should be kept warm or even actively warmed–thus reducing the energy needed to develop fever and thereby discomfort. Once the child is warm all the way to its feet and starts sweating, layers of sheets and clothing can be carefully removed (level 5 [154]).

Despite high level evidence (level 1) that tepid sponging increases discomfort and should be avoided [150, 151], 61% of guidelines are still in favor of its use. Recommendations about compresses show a similar distribution (63% in favor) though fewer guidelines address the topic and little directly applicable research is available. The decrease in temperature that results from external cooling is of short duration. A mismatch between the hypothalamic set point and skin temperature leads to peripheral vasoconstriction and metabolic heat production, which results in shivering and increased discomfort of the child. The initial small reduction in body temperature may not be worth the potential discomfort and the use of these methods indicates a continued focus on the reduction of body temperature rather than distress.

Complementary recommendations.

Recommendations on complementary treatments only appear in three guidelines, despite their widespread use by parents and health professionals. The evidence for the proposed treatments is low (Level 4)–perhaps partially because most forms of alternative medicine do not advocate fever suppression as a treatment goal. With regard to well-being, the scientific literature suggests greater or equal efficacy and satisfaction compared with conventional treatments, with high safety and tolerability [157, 158, 179181].

Other potential issues not yet included in the published guidelines.

Digital media: None of the guidelines mention screen exposure. Most countries are beginning to formulate recommendations on child screen exposure [182]. We point to the need for recommendations on screen use in illness.

Parental care by interaction and empathy and relationship: None of the guidelines mention the quality of parental care during illness, which may be the most important factor for both immediate well-being and long-term health [183]. Finding ways to reduce fever phobia by education or counseling intervention may contribute to relational and empathetic fever management and facilitate a significant reduction of distress [184, 185].

Limitations and strengths

Only 74 guidelines were retrieved which, considering the high frequency of fever, is fewer than expected. We cannot exclude that other documents exist as some may not be online and our attempts to contact these countries’ pediatric societies per email did not yield any additional documents. Out of a responsibility for resource investment, we refrained from duplicate assessment of guideline eligibility, risk of bias for the individual intervention and duplicate data extraction (except for the GRADE assessment, which was duplicate), judging that minor changes would have no effect on the overall guideline assessment results. Due to a lack of information regarding the developmental procedure of most guidelines, an overall assessment of quality (using AGREE II) was not feasible. Therefore, we chose to examine the supporting evidence for each of the recommendations using the OCEBM criteria [9] and discuss the results based on the highest level of evidence. This is a unique strength of this review.

Conclusion

A comparison of worldwide fever management guidelines, revealed some uniform themes and recommendations supported by a high level of evidence, but also striking discrepancies and a low level of evidence supporting most recommendations. So far, we can conclude that some recommendations should be part of all guidelines:

  • Parents and carers should be educated about the benefits of fever, and how to recognize and act on othersigns of danger and judge the condition rather than fever alone.
  • In an otherwise healthy child with an acute febrile infection, treatment should focus on reduction of distress rather than temperature (Level 5). The social and physical environment should be optimized before considering use of antipyretic medications (Level 5).
  • Antipyretics should not be combined (Level 1), or routinely alternated (Level 1), and be used, if at all, only as long as the child appears distressed (Level 5).
  • Antipyretics should not be given with the intention of preventing febrile seizures (Level 1)
  • External cooling may increase discomfort and metabolic strain (Level 1).

None of the CPGs include statements about the potential benefits of fever (level 1). Studies are needed to assess whether educating parents and carers (i.e. about the side effects of antipyretics, the positive immunological effects of fever and how to recognize signs of danger) influences outcomes. The question as to whether or not there should be a threshold for initiating antipyresis must be met with solid evidence.

Acknowledgments

Jana Wachmeister, M.Sc., is thanked for systematic literature searches and data curation.

References

  1. 1. DuBOIS EF. Why are fever temperatures over 106 degrees F. rare? Am J Med Sci. 1949;217: 361–368. pmid:18115151
  2. 2. Karwowska A, Nijssen-Jordan C, Johnson D, Davies HD. Parental and health care provider understanding of childhood fever: a Canadian perspective. CJEM. 2002;4: 394–400. pmid:17637156
  3. 3. Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: have parental misconceptions about fever changed in 20 years? Pediatrics. 2001;107: 1241–1246. pmid:11389237
  4. 4. Elkon-Tamir E, Rimon A, Scolnik D, Glatstein M. Fever Phobia as a Reason for Pediatric Emergency Department Visits: Does the Primary Care Physician Make a Difference? Rambam Maimonides Med J. 2017;8. pmid:28178434
  5. 5. Purssell E, Collin J. Fever phobia: The impact of time and mortality—a systematic review and meta-analysis. Int J Nurs Stud. 2016;56: 81–89. pmid:26643444
  6. 6. Duff GW. Is fever beneficial to the host: a clinical perspective. Yale J Biol Med. 1986;59: 125–130. pmid:3488618
  7. 7. Nourjah P, Ahmad SR, Karwoski C, Willy M. Estimates of acetaminophen (Paracetomal)-associated overdoses in the United States. Pharmacoepidemiol Drug Saf. 2006;15: 398–405. pmid:16294364
  8. 8. Chiappini E, Bortone B, Galli L, de Martino M. Guidelines for the symptomatic management of fever in children: systematic review of the literature and quality appraisal with AGREE II. BMJ Open. 2017;7: e015404. pmid:28760789
  9. 9. OCEBM Levels of Evidence Working Group. The Oxford Levels of Evidence 2. In: Oxford Centre for Evidence-Based Medicine [Internet]. 1 May 2016 [cited 13 Sep 2018]. Available: https://www.cebm.net/index.aspx?o=5653
  10. 10. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358: j4008. pmid:28935701
  11. 11. National Institute for Health and Care Excellence (NICE). Fever in under 5s: assessment and initial management | Guidance and guidelines | NICE. 2017 [cited 23 May 2018]. Available: https://www.nice.org.uk/guidance/cg160
  12. 12. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336: 924–926. pmid:18436948
  13. 13. Peters MJ, Woolfall K, Khan I, Deja E, Mouncey PR, Wulff J, et al. Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: a multicentre randomized clinical pilot trial. Crit Care. 2019;23: 69. pmid:30845977
  14. 14. When the baby has a fever. In: Naver Blog | Yonsei Bärenpädiatrie [Internet]. [cited 24 Sep 2020]. Available: https://blog.naver.com/gomdori4585/221229492288
  15. 15. Ministry of Public Health, General Directorate of Pharmaceutical Affairs. National Standard Treatment Guidelines for the Primary Level. 2013. Available: http://apps.who.int/medicinedocs/documents/s21744en/s21744en.pdf
  16. 16. L’association des pédiatres libéraux d’Alger (APLA). Childhood fever: what to do? In: apla [Internet]. [cited 23 May 2018]. Available: http://www.apla-dz.org/conseils-aux-parents/maladies-infantiles/votre-enfant-a-de-la-fievre/
  17. 17. SAP. Argentine Society of Pediatrics | News | Fever. [cited 24 Sep 2020]. Available: http://www.sap.org.ar/
  18. 18. What to do and what is forbidden if the baby has a fever [cited 24 Sep 2020]. Available: http://arabkirjmc.am/baby-high-temperature/
  19. 19. NSW Department of Health. Children and Infants with Fever—Acute Management. 2010. Available: http://www1.health.nsw.gov.au/pds/ActivePDSDocuments/PD2010_063.pdf
  20. 20. Fever Without Source—Kids Health WA (PMH ED Guidelines). In: Kids Health WA (PMH ED Guidelines) [Internet]. [cited 23 May 2018]. Available: http://kidshealthwa.com/guidelines/fever-without-source/
  21. 21. South Australian Child Health Clinical Network. Management of Fever without Focus in Children (excluding neonates), Clinical Guideline. 2013. Available: http://www.sahealth.sa.gov.au/wps/wcm/connect/812ad70040d041b4972cbf40b897efc8/Fever+without+Focus_Apr2015.pdf?MOD=AJPERES&CACHEID=812ad70040d041b4972cbf40b897efc8
  22. 22. Clinical Practice Guidelines: Febrile child. [cited 24 Sep 2020]. Available: https://www.rch.org.au/clinicalguide/guideline_index/Febrile_child/
  23. 23. Joana Briggs Institute. Management of the Child with Fever. 2004. Available: http://www.babyhintsandtips.com/wp-content/uploads/2013/05/feverhandout.pdf
  24. 24. Österreichische Gesellschaft für Kinder- und Jugendheilkunde. Fieber und Schmerzen: Was tun? Available: http://www.paediatrie.at/home/Spezialbereiche/Infektiologie/fieber_und_schmerzen_bei_kindern_was_tun.php
  25. 25. Fever In Children. [cited 23 May 2018]. Available: http://www.pediatrie.be/fr/xi-la-fievre-chez-l_enfant/251/2
  26. 26. Arteaga Bonilla R. Fever and the use of antipyretics in children. Revista de la Sociedad Boliviana de Pediatría. 2011;50: 27–29.
  27. 27. Fever: Beware of fever phobia. SBP [Internet]. [cited 24 Sep 2020]. Available: https://www.sbp.com.br/especiais/pediatria-para-familias/cuidados-com-a-saude/febre-cuidado-com-a-febrefobia/
  28. 28. The College of Family Physicians Canada. Fever in Infants and Children. 2011 [cited 23 May 2018]. Available: http://www.cfpc.ca/ProjectAssets/Templates/Resource.aspx?id=3596
  29. 29. What you need to know: fever. [Internet]. [cited 24 Sep 2020]. Available: https://www.cheo.on.ca/en/resources-and-support/resources/P5325E.pdf
  30. 30. Government of Manitoba. Healthy Child, Caring for a Child with Fever. 2006. Available: https://www.gov.mb.ca/health/documents/fever.pdf
  31. 31. Canada Pharmacist’s Association. Fever. 2010. Available: http://www.pharmacists.ca/cpha-ca/assets/file/store/PSC-Fever.pdf
  32. 32. Canadian Pediatric Society. Fever and temperature taking—Caring for Kids. 2015 [cited 23 May 2018]. Available: https://www.caringforkids.cps.ca/handouts/fever_and_temperature_taking
  33. 33. SOCHIPE—Soc. Chilena de Pediatría. Fever: Outpatient Treatment. 2013 [cited 23 May 2018]. Available: http://www.sochipe.cl/v3/presenta_dos.php?id=610
  34. 34. Colombian Society of Pediatrics | SCP Colombian Society of Pediatrics. [cited 24 Sep 2020]. Available: https://scp.com.co/
  35. 35. Fever in the child. In: ACOPE C.R. [Internet]. 11 Apr 2018 [cited 24 Sep 2020]. Available: https://acopecr.com/fiebre-en-el-nino/
  36. 36. Nurse performance at a fever in children. [cited 24 Sep 2020]. Available: https://www.revista-portalesmedicos.com/revista-medica/actuacion-enfermera-cuadro-febril/
  37. 37. Fever and fever phobia Cyprus Pediatric Society. [cited 24 Sep 2020]. Available: https://www.child.org.cy/phobia-of-fever/
  38. 38. When the child has a fever. Drug and Therapeutics Bulletin. 2008;46: 17–21. pmid:18337462
  39. 39. Asociación de Pediatría de El Salvador. What you need to know about your child’s fever. In: Asopedes [Internet]. 24 Sep 2015 [cited 23 May 2018]. Available: http://asopedes.org/lo-que-debe-saber-sobre-la-fiebre-de-su-hijo/
  40. 40. Haute Autorite de Sante. Management of fever in children. 2016. Available: https://www.has-sante.fr/portail/upload/docs/application/pdf/2017-03/dir5/guidance_leaflet_management_of_fever_in_children.pdf
  41. 41. Agence française de sécurité sanitaire des produits de santé (Afssaps). Update on the management of fever in children. Available: http://ansm.sante.fr/var/ansm_site/storage/original/application/8a3e72e8fec9c0f68797a73832372321.pdf
  42. 42. Société Française de Pédiatrie. Symptomatic Management of Young Childhood Fever. 2004 [cited 23 May 2018]. Available: http://www.sfpediatrie.com/recommandation/prise-en-charge-symptomatique-de-la-fi%C3%A8vre-du-jeune-enfant
  43. 43. Der Berufsverband der Kinder- und Jugendärzte. Fever. [cited 23 May 2018]. Available: https://www.kinderaerzte-im-netz.de/erste-hilfe/sofortmassnahmen/fieber
  44. 44. Fever in children patient guideline. [cited 23 May 2018]. Available: http://www.patientenleitlinien.de/Fieber_Kindesalter/fieber_kindesalter.html
  45. 45. Niehues T. The febrile child: diagnosis and treatment. Dtsch Arztebl Int. 2013;110: 764–773; quiz 774. pmid:24290365
  46. 46. Parents info fever. In: Deutsche Gesellschaft für Kinder- und Jugendmedizin [Internet]. [cited 24 Sep 2020]. Available: https://www.dgkj.de/eltern/dgkj-elterninformationen/elterninfo-fieber
  47. 47. Ministry of Health, Republic of Ghana. Standard Treatment Guidelines:—Ch 19 Fever. 2010. Available: http://apps.who.int/medicinedocs/documents/s18015en/s18015en.pdf
  48. 48. Indian Academy of Pediatrics (IAP) | Search. [cited 24 Sep 2020]. Available: https://iapindia.org/search.php
  49. 49. Jehangir Apollo hospital. Fever in children. 2013. Available: http://www.jehangirhospital.com/blog/item/2-fever-in-children
  50. 50. Handling Fever in Children. In: IDAI [Internet]. [cited 24 Sep 2020]. Available: https://www.idai.or.id/artikel/klinik/keluhan-anak/penanganan-demam-pada-anak
  51. 51. Irish College of General Practitioners. Antipyretic Prescribing 2013. 2013 [cited 23 May 2018]. Available: https://www.icgp.ie/go/library/catalogue/item/6686EC55-D046-1DCB-B9ED227FA2C07DA6
  52. 52. Chiappini E, Venturini E, Remaschi G, Principi N, Longhi R, Tovo P-A, et al. 2016 Update of the Italian Pediatric Society Guidelines for Management of Fever in Children. J Pediatr. 2017;180: 177–183.e1. pmid:27810155
  53. 53. Kodomo QQ Kids Emergency (ONLINE-QQ)—Go to the hospital by car/taxi. [cited 24 Sep 2020]. Available: http://kodomo-qq.jp/en/?pname=hatsunetsu%2Fr2
  54. 54. Jordan Pediatric Society. Fever in children. [cited 24 Sep 2020]. Available: https://jps.org.jo/
  55. 55. Clinical Guidelines for Diagnosis and Treatment of Common Conditions in Kenya.: 356.
  56. 56. Al Salam Hospital. Fever and Its Treatment. [cited 23 May 2018]. Available: http://www.sih-kw.com/Fever_En.cms?ActiveID=1132
  57. 57. Ministère-Direction de la Santé. Fièvre. 2005 [cited 23 May 2018]. Available: http://www.sante.public.lu/fr/maladies/zone-corps/sang/fievre/index.html
  58. 58. La fièvre chez les enfants | Kannerklinik. [cited 24 Sep 2020]. Available: https://kannerklinik.chl.lu/fr/dossier/la-fievre-chez-les-enfants
  59. 59. Dutch College of General Practitioners. Children with Fever (Page 25). 2016. Available: https://assortiment.bsl.nl/files/e27c6c2f-8fa3-4f91-9c60-39597b8ecf7d/voorbeeldhoofdstuk.pdf
  60. 60. NVK—Document. [cited 24 Sep 2020]. Available: https://www.nvk.nl/themas/kwaliteit/overige-kennisdocumenten/document?documentregistrationid=8257539
  61. 61. Starship Children’s Hospital of New Zealand. Fever Investigation and Management. 2009 [cited 23 May 2018]. Available: https://www.starship.org.nz/for-health-professionals/starship-clinical-guidelines/f/fever-investigation-and-management/
  62. 62. Fever in children. In: Ministry of Health NZ [Internet]. [cited 24 Sep 2020]. Available: https://www.health.govt.nz/your-health/conditions-and-treatments/diseases-and-illnesses/fever/fever-children
  63. 63. The Norwegian Medical Association. [cited 24 Sep 2020]. Available: https://www.legeforeningen.no/
  64. 64. Png Paediatric Society. Standard Treatment forCommon Illnesses of Children in Papua New Guinea (Page 61). 2016. Available: http://pngpaediatricsociety.org/wp-content/uploads/2016/11/PNG-Standard-Treatment-Book-10th-edition-2016.pdf
  65. 65. Isolated fever. In: Issuu [Internet]. [cited 24 Sep 2020]. Available: https://issuu.com/protocoale_pediatrie/docs/45_febra_izolata
  66. 66. Union of Pediatricians of Russia. In: Union of Pediatricians of Russia [Internet]. [cited 24 Sep 2020]. Available: https://www.pediatr-russia.ru/parents_information/soveti-roditelyam/likhoradka.php
  67. 67. Fever: What is it, medication, other measures and when to consult a doctor. | KKH. [cited 24 Sep 2020]. Available: https://www.kkh.com.sg/patient-care/conditions-treatments/fever-childhood-illnesses
  68. 68. Green R, Jeena P, Kotze S, Lewis H, Webb D, Wells M, et al. Management of acute fever in children: guideline for community healthcare providers and pharmacists. S Afr Med J. 2013;103: 948–954. pmid:24300636
  69. 69. Fever: what to do when the child has a fever? In: EnFamilia. [cited 24 Sep 2020]. Available: https://enfamilia.aeped.es/temas-salud/que-hacer-cuando-nino-tiene-fiebre
  70. 70. Sri lanka college of paediatrician. 2019 Standard Treatment Protocols—PAEDIATRICS. [cited 24 Sep 2020]. Available: https://slcp.lk/
  71. 71. Ministry Of Health Government Of Southern Sudan. Prevention & Treatment Guidelines for Primary Healthcare Centers and Hospitals. 2006. Available: http://apps.who.int/medicinedocs/documents/s21010en/s21010en.pdf
  72. 72. Fever in children [cited 23 May 2018]. Available: https://www.1177.se/Other-languages/Engelska/Barn/Feber—vad-kan-man-gora-sjalv/
  73. 73. Swiss Pediatrics Association. When children are ill: some advice for parents. 1995. Available: http://www.swiss-paediatrics.org/sites/default/files/parents/10-16_ans/maladie/pdf/2012.12.31_ryan_kate_e_homepage.pdf
  74. 74. Ministry of Health and Social Welfare. Standard Treatment Guidelines and Essential Medicines List. 2013. Available: http://www.who.int/selection_medicines/country_lists/Tanzania_STG_052013.pdf
  75. 75. Ministry of Health Tuvalu. Standard Treatment Guidelines. 2010. Available: https://srhr.org/abortion-policies/documents/countries/02-Tuvalu-Standard-Treatment-Guidelines-2010.pdf
  76. 76. Asssociation of Ukranian Pediatricians. Fever and Hyperperexia In Children. Available: http://www.uf.ua/wp-content/uploads/2017/05/Georgiyants_Lyhomanka_giperpireksiya_dity_ENG_R_verstka_c.pdf
  77. 77. Mayo Clinic. Fever: First aid. 2015 [cited 23 May 2018]. Available: https://www.mayoclinic.org/first-aid/first-aid-fever/basics/ART-20056685?p=1
  78. 78. American Academy of Pediatrics. Fever. In: HealthyChildren.org [Internet]. 2016 [cited 23 May 2018]. Available: http://www.healthychildren.org/English/health-issues/conditions/fever/Pages/default.aspx
  79. 79. UpToDate. Fever in children (Beyond the Basics). 2017. Available: https://www.uptodate.com/contents/fever-in-children-beyond-the-basics
  80. 80. PubMed Health. Fever in children: How can you reduce a fever? 2016 [cited 23 May 2018]. Available: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072637/
  81. 81. Sullivan J E. Fever and Antipyretic Use in Children | From the American Academy of Pediatrics | Pediatrics. 2011 [cited 23 May 2018]. Available: http://pediatrics.aappublications.org/content/127/3/580 pmid:21357332
  82. 82. Fever in Infants and Children—Pediatrics. In: MSD Manual Professional Edition [Internet]. [cited 24 Sep 2020]. Available: https://www.msdmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children
  83. 83. SVPP. [cited 24 Sep 2020]. Available: http://www.svpediatria.org/
  84. 84. Medecins Sans Frontieres. Clinical Guidelines: Diagnosis and Treatment Manual. 2016. Available: http://refbooks.msf.org/msf_docs/en/clinical_guide/cg_en.pdf
  85. 85. WHO/Unicef. Handbook IMCI: Integrated management of childhood illness. 2007. Available: http://apps.who.int/iris/bitstream/10665/42939/1/9241546441.pdf
  86. 86. World Health Organization. WHO pocketbook of hospital care for children: guidelines for the management of common childhood illness. 2013. Available: http://apps.who.int/iris/bitstream/10665/81170/1/9789241548373_eng.pdf
  87. 87. Mackowiak PA, Boulant JA. Fever’s Glass Ceiling. Clinical Infectious Diseases. 1996;22: 525–536. pmid:8852974
  88. 88. Narayan K, Cooper S, Morphet J, Innes K. Effectiveness of paracetamol versus ibuprofen administration in febrile children: A systematic literature review: Antipyretics in paediatric fever. Journal of Paediatrics and Child Health. 2017;53: 800–807. pmid:28437025
  89. 89. Temple AR, Temple BR, Kuffner EK. Dosing and antipyretic efficacy of oral acetaminophen in children. Clin Ther. 2013;35: 1361–1375.e1–45. pmid:23972576
  90. 90. de Martino M, Chiarugi A, Boner A, Montini G, de’ Angelis GL. Working Towards an Appropriate Use of Ibuprofen in Children: An Evidence-Based Appraisal. Drugs. 2017;77: 1295–1311. pmid:28597358
  91. 91. Perrott DA, Piira T, Goodenough B, Champion GD. Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis. Arch Pediatr Adolesc Med. 2004;158: 521–526. pmid:15184213
  92. 92. George M, Phelps MA, Kitzmiller JP. Acetaminophen pediatric dose selection: caregiver satisfaction regarding the antipyretic efficacy of acetaminophen in children. Clin Pediatr (Phila). 2012;51: 1030–1031. pmid:22890329
  93. 93. de Martino M, Chiarugi A. Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management. Pain Ther. 2015;4: 149–168. pmid:26518691
  94. 94. Shahroor S, Shvil Y, Ohali M, Granot E. [Acetaminophen toxicity in children as a “therapeutic misadventure”]. Harefuah. 2000;138: 654–657, 710. pmid:10883207
  95. 95. Kozer E, Barr J, Bulkowstein M, Avgil M, Greenberg R, Matias A, et al. A prospective study of multiple supratherapeutic acetaminophen doses in febrile children. Vet Hum Toxicol. 2002;44: 106–109. pmid:11931497
  96. 96. Heard K, Bui A, Mlynarchek SL, Green JL, Bond GR, Clark RF, et al. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases. Am J Ther. 2014;21: 174–183. pmid:22407198
  97. 97. Temple AR, Zimmerman B, Gelotte C, Kuffner EK. Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies. J Pediatr Pharmacol Ther. 2017;22: 22–32. pmid:28337078
  98. 98. 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: 2207–2222. pmid:19606950
  99. 99. Purssell E. Treating fever in children: paracetamol or ibuprofen? Br J Community Nurs. 2002;7: 316–320. pmid:12066066
  100. 100. Alvarez-Coca González J, Caballero Mora FJ, Alonso Martín B, Martínez Pérez J. Es aconsejable evitar el ibuprofeno en la enfermedad de Kawasaki? [Is it advisable to avoid ibuprofen in Kawasaki disease?]. An Pediatr (Barc). 2009 Jul;71(1):83–4. Spanish. Epub 2009 May 29. pmid:19481990.
  101. 101. 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. Journal of the Royal Society of Medicine. 2010;103: 403–411. pmid:20929891
  102. 102. Plaisance KI, Mackowiak PA. Antipyretic therapy: physiologic rationale, diagnostic implications, and clinical consequences. Arch Intern Med. 2000;160: 449–456. pmid:10695685
  103. 103. Eyers S, Jefferies S, Shirtcliffe P, Perrin K, Beasley R. Antipyretic therapy for influenza infection—benefit or harm? In: https://www.nzma.org.nz/journal/read-the-journal/all-issues/2010-2019/2011/vol-124-no-1338/letter-eyers. 8 Jul 2011. pmid:21946975
  104. 104. Kellstein D, Fernandes L. Symptomatic treatment of dengue: should the NSAID contraindication be reconsidered? Postgrad Med. 2019;131: 109–116. pmid:30575425
  105. 105. Zoubek ME, Lucena MI, Andrade RJ, Stephens C. Systematic review: ibuprofen-induced liver injury. Aliment Pharmacol Ther. 2020;51: 603–611. pmid:31984540
  106. 106. Shen X, Huang Y, Guo H, Peng H, Yao S, Zhou M, et al. Oral ibuprofen promoted cholestatic liver disease in very low birth weight infants with patent ductus arteriosus. Clin Res Hepatol Gastroenterol. 2020. pmid:32723673
  107. 107. 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: 203–209. pmid:18251759
  108. 108. Fu L-S, Lin C-C, Wei C-Y, Lin C-H, Huang Y-C. Risk of acute exacerbation between acetaminophen and ibuprofen in children with asthma. PeerJ. 2019;7: e6760. pmid:31024768
  109. 109. 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. 2007;29: 2716–2723. pmid:18201589
  110. 110. Sherbash M, Furuya-Kanamori L, Nader JD, Thalib L. Risk of wheezing and asthma exacerbation in children treated with paracetamol versus ibuprofen: a systematic review and meta-analysis of randomised controlled trials. BMC Pulm Med. 2020;20: 72. pmid:32293369
  111. 111. François P, Desrumaux A, Cans C, Pin I, Pavese P, Labarère J. Prevalence and risk factors of suppurative complications in children with pneumonia: Suppurative complications of pneumonia. Acta Paediatrica. 2010;99: 861–866. pmid:20178517
  112. 112. Elemraid MA, Thomas MF, Blain AP, Rushton SP, Spencer DA, Gennery AR, et al. Risk factors for the development of pleural empyema in children. Pediatr Pulmonol. 2015;50: 721–726. pmid:24692118
  113. 113. Voiriot G, Dury S, Parrot A, Mayaud C, Fartoukh M. Nonsteroidal Antiinflammatory Drugs May Affect the Presentation and Course of Community-Acquired Pneumonia. CHEST. 2011;139: 387–394. pmid:20724739
  114. 114. Le Bourgeois M, Ferroni A, Leruez-Ville M, Varon E, Thumerelle C, Brémont F, et al. 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.e3. pmid:27339249
  115. 115. Rainsford KD, Bjarnason I. NSAIDs: take with food or after fasting? Journal of Pharmacy and Pharmacology. 2012;64: 465–469. pmid:22420652
  116. 116. Marriott SC, Stephenson TJ, Hull D, Pownall R, Smith CM, Butler A. A dose ranging study of ibuprofen suspension as an antipyretic. Arch Dis Child. 1991;66: 1037–1042. pmid:1929509
  117. 117. Autret-Leca E. A general overview of the use of ibuprofen in paediatrics. Int J Clin Pract Suppl. 2003; 9–12. pmid:12723740
  118. 118. Walson PD, Galletta G, Chomilo F, Braden NJ, Sawyer LA, Scheinbaum ML. Comparison of Multidose Ibuprofen and Acetaminophen Therapy in Febrile Children. Am J Dis Child. 1992;146: 626–632. pmid:1621669
  119. 119. Diseases C on I, Fulginiti VA, Brunell PA, Cherry JD, Ector WL, Gershon AA, et al. Aspirin and Reye Syndrome. Pediatrics. 1982;69: 810–812. pmid:7079050
  120. 120. Çaksen H, Güler E, Alper M, Üstünbaş HB. A Fatal Case of Reye Syndrome after Varicella and Ingestion of Aspirin. The Journal of Dermatology. 2001;28: 286–287. pmid:11436370
  121. 121. Moroz LA. Increased blood fibrinolytic activity after aspirin ingestion. N Engl J Med. 1977;296: 525–529. pmid:836536
  122. 122. Kokki H, Kokki M. Dose-finding studies of ketoprofen in the management of fever in children: report on two randomized, single-blind, comparator-controlled, single-dose, multicentre, phase II studies. Clin Drug Investig. 2010;30: 251–258. pmid:20225908
  123. 123. Kokki H, Kokki M. Ketoprofen versus paracetamol (acetaminophen) or ibuprofen in the management of fever: results of two randomized, double-blind, double-dummy, parallel-group, repeated-dose, multicentre, phase III studies in children. Clin Drug Investig. 2010;30: 375–386. pmid:20380479
  124. 124. Polman HA, Huijbers WA, Augusteijn R. The use of diclofenac sodium (Voltaren) suppositories as an antipyretic in children with fever due to acute infections: a double-blind, between-patient, placebo-controlled study. J Int Med Res. 1981;9: 343–348. pmid:7028533
  125. 125. Sharif MR, Haji Rezaei M, Aalinezhad M, Sarami G, Rangraz M. Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children. Iran Red Crescent Med J. 2016;18: e27932. pmid:26889398
  126. 126. Khubchandani RP, Ghatikar KN, Keny S, Usgaonkar NG. Choice of antipyretic in children. J Assoc Physicians India. 1995;43: 614–616. pmid:8773063
  127. 127. Kamour A, Crichton S, Cooper G, Lupton DJ, Eddleston M, Vale JA, et al. Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service. Br J Clin Pharmacol. 2017;83: 855–862. pmid:27785820
  128. 128. Prado J, Daza R, Chumbes O, Loayza I, Huicho L. Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial. Sao Paulo Med J. 2006;124: 135–140. pmid:17119689
  129. 129. Wong A, Sibbald A, Ferrero F, Plager M, Santolaya ME, Escobar AM, et al. Antipyretic effects of dipyrone versus ibuprofen versus acetaminophen in children: results of a multinational, randomized, modified double-blind study. Clin Pediatr (Phila). 2001;40: 313–324. pmid:11824173
  130. 130. Giovannini M, Longhi R, Besana R, Michos N, Sarchi C. Clinical experience and results of treatment with suprofen in pediatrics. 5th communication: a single-blind study on antipyretic effect and tolerability of suprofen syrup versus metamizole drops in pediatric patients. Arzneimittelforschung. 1986;36: 959–964. pmid:3527181
  131. 131. Cashman TM, Starns RJ, Johnson J, Oren J. Comparative effects of naproxen and aspirin on fever in children. J Pediatr. 1979;95: 626–629. pmid:480048
  132. 132. Purssell E. Systematic review of studies comparing combined treatment with paracetamol and ibuprofen, with either drug alone. Arch Dis Child. 2011;96: 1175–1179. pmid:21868405
  133. 133. Pereira GL, Dagostini JMC, Pizzol T da SD. Alternating antipyretics in the treatment of fever in children: a systematic review of randomized clinical trials. J Pediatr (Rio J). 2012;88: 289–296. pmid:22915173
  134. 134. Trippella G, Ciarcià M, de Martino M, Chiappini E. Prescribing Controversies: An Updated Review and Meta-Analysis on Combined/Alternating Use of Ibuprofen and Paracetamol in Febrile Children. Front Pediatr. 2019;7. pmid:30778379
  135. 135. Yue Z, Jiang P, Sun H, Wu J. Association between an excess risk of acute kidney injury and concomitant use of ibuprofen and acetaminophen in children, retrospective analysis of a spontaneous reporting system. Eur J Clin Pharmacol. 2014;70: 479–482. pmid:24445686
  136. 136. Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, et al. Cochrane in context: Combined and alternating paracetamol and ibuprofen therapy for febrile children. Evid Based Child Health. 2014;9: 730–732. pmid:25236310
  137. 137. Offringa M, Newton R, Cozijnsen MA, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Epilepsy Group, editor. Cochrane Database of Systematic Reviews. 2017 [cited 9 Apr 2018]. pmid:28225210
  138. 138. Rosenbloom E, Finkelstein Y, Adams-Webber T, Kozer E. Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis. European Journal of Paediatric Neurology. 2013;17: 585–588. pmid:23702315
  139. 139. Mewasingh LD. Febrile seizures. BMJ Clin Evid. 2014;2014. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908738/ pmid:24484859
  140. 140. Murata S, Okasora K, Tanabe T, Ogino M, Yamazaki S, Oba C, et al. Acetaminophen and Febrile Seizure Recurrences During the Same Fever Episode. Pediatrics. 2018;142. pmid:30297499
  141. 141. Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants. Acta Anaesthesiol Scand. 2001;45: 20–29. pmid:11152028
  142. 142. Ziesenitz VC, Zutter A, Erb TO, van den Anker JN. Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months. Pediatric Drugs. 2017;19: 277–290. pmid:28516288
  143. 143. Gupta P, Sachdev HPS. Safety of oral use of nimesulide in children: systematic review of randomized controlled trials. Indian Pediatr. 2003;40: 518–531. pmid:12824661
  144. 144. Aluka TM, Gyuse AN, Udonwa NE, Asibong UE, Meremikwu MM, Oyo-Ita A. Comparison of Cold Water Sponging and Acetaminophen in Control of Fever Among Children Attending a Tertiary Hospital in South Nigeria. J Family Med Prim Care. 2013;2: 153–158. pmid:24479070
  145. 145. Senz EH, Goldfarb DL. Coma in a child following use of isopropyl alcohol in sponging. J Pediatr. 1958;53: 322–323. pmid:13576384
  146. 146. McFadden SW, Haddow JE. Coma produced by topical application of isopropanol. Pediatrics. 1969;43: 622–623. pmid:5777081
  147. 147. Moss MH. Alcohol-induced hypoglycemia and coma caused by alcohol sponging. Pediatrics. 1970;46: 445–447. pmid:5454799
  148. 148. Arditi M, Killner MS. Coma following use of rubbing alcohol for fever control. Am J Dis Child. 1987;141: 237–238. pmid:3812394
  149. 149. Wise JR. Alcohol sponge baths. N Engl J Med. 1969;280: 840. pmid:5773646
  150. 150. Watts R, Robertson J. Non-pharmacological Management of Fever in Otherwise Healthy Children. JBI Libr Syst Rev. 2012;10: 1634–1687. pmid:27820389
  151. 151. Purssell E. Physical treatment of fever. Arch Dis Child. 2000;82: 238–239. pmid:10685930
  152. 152. Thomas S, Vijaykumar C, Naik R, Moses PD, Antonisamy B. Comparative effectiveness of tepid sponging and antipyretic drug versus only antipyretic drug in the management of fever among children: a randomized controlled trial. Indian Pediatr. 2009;46: 133–136. pmid:19242030
  153. 153. Guppy MPB, Mickan SM, Mar CBD. “Drink plenty of fluids”: a systematic review of evidence for this recommendation in acute respiratory infections. BMJ. 2004;328: 499–500. pmid:14988184
  154. 154. Martin DD. Fever: Views in Anthroposophic Medicine and Their Scientific Validity. Evidence-Based Complementary and Alternative Medicine. 2016;2016: 1–13. pmid:27999605
  155. 155. Kinmonth AL, Fulton Y, Campbell MJ. Management of feverish children at home. BMJ. 1992;305: 1134–1136. pmid:1463951
  156. 156. Gibson JP. How much bed rest is necessary for children with fever? The Journal of Pediatrics. 1956;49: 256–261. pmid:13358016
  157. 157. Rabe A, Weiser M, Klein P. Effectiveness and tolerability of a homoeopathic remedy compared with conventional therapy for mild viral infections: Effectiveness and Tolerability of Homoeopathic Remedy. International Journal of Clinical Practice. 2004;58: 827–832. pmid:15529515
  158. 158. van Haselen R, Thinesse-Mallwitz M, Maidannyk V, Buskin SL, Weber S, Keller T, et al. The Effectiveness and Safety of a Homeopathic Medicinal Product in Pediatric Upper Respiratory Tract Infections With Fever. Glob Pediatr Health. 2016;3. pmid:27493984
  159. 159. Lyons N, Nejak D, Lomotan N, Mokszycki R, Jamieson S, McDowell M, et al. An alternative for rapid administration of medication and fluids in the emergency setting using a novel device. The American Journal of Emergency Medicine. 2015;33: 1113.e5–1113.e6. pmid:25662805
  160. 160. Tremayne V. Emergency rectal infusion of fluid in rural or remote settings. 2010 [cited 23 May 2018]. Available: https://web.a.ebscohost.com/abstract?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=13545752&AN=48329032&h=v1IVL0qBvq8mmA4VOif%2fK%2fBLm1kF6DP6ByiDDmGa2AID6nzeeef7mgBWUrUALz7AfXpbQ7hwzyASOebUmheEvg%3d%3d&crl=c&resultNs=AdminWebAuth&resultLocal=ErrCrlNotAuth&crlhashurl=login.aspx%3fdirect%3dtrue%26profile%3dehost%26scope%3dsite%26authtype%3dcrawler%26jrnl%3d13545752%26AN%3d48329032 pmid:20209752
  161. 161. Dallimore J, Ebmeier S, Thayabaran D, Bellomo R, Bernard G, Schortgen F, et al. Effect of active temperature management on mortality in intensive care unit patients. Crit Care Resusc. 2018;20: 150–163. pmid:29852854
  162. 162. van Stuijvenberg M, Derksen-Lubsen G, Steyerberg EW, Habbema JDF, Moll HA. Randomized, Controlled Trial of Ibuprofen Syrup Administered During Febrile Illnesses to Prevent Febrile Seizure Recurrences. Pediatrics. 1998;102: e51–e51. pmid:9794981
  163. 163. Brewer ET. A comparative evaluation of indomethacin, acetaminophen and placebo as antipyretic agents in children. Arthritis & Rheumatism. 1968;11: 645–651. pmid:4878632
  164. 164. Chiappini E, Parretti A, Becherucci P, Pierattelli M, Bonsignori F, Galli L, et al. Parental and medical knowledge and management of fever in Italian pre-school children. BMC Pediatr. 2012;12: 97. pmid:22794080
  165. 165. Bertille N, Fournier-Charrière E, Pons G, Chalumeau M. Managing Fever in Children: A National Survey of Parents’ Knowledge and Practices in France. Esposito S, editor. PLoS ONE. 2013;8: e83469. pmid:24391772
  166. 166. Brick T, Agbeko RS, Davies P, Davis PJ, Deep A, Fortune P-M, et al. Attitudes towards fever amongst UK paediatric intensive care staff. Eur J Pediatr. 2017;176: 423–427. pmid:28097438
  167. 167. Hay A, Redmond N, Costelloe C, Montgomery A, Fletcher M, Hollinghurst S, et al. Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial. Health Technology Assessment. 2009;13. pmid:19846024
  168. 168. van den Anker JN. Optimising the management of fever and pain in children. Int J Clin Pract Suppl. 2013; 26–32. pmid:23163545
  169. 169. Wright AD, Liebelt EL. Alternating antipyretics for fever reduction in children: an unfounded practice passed down to parents from pediatricians. Clin Pediatr (Phila). 2007;46: 146–150. pmid:17325087
  170. 170. Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatric Emergency Care. 2000;16: 394. pmid:11138879
  171. 171. Kearns RD, Conlon KM, Matherly AF, Chung KK, Bebarta VS, Hansen JJ, et al. Guidelines for Burn Care Under Austere Conditions: Introduction to Burn Disaster, Airway and Ventilator Management, and Fluid Resuscitation. J Burn Care Res. 2016;37: e427–439. pmid:27224004
  172. 172. Carassiti M, Pumpo AD, Agrò FE. Fluid Management in Palliative Care. Body Fluid Management. Springer, Milano; 2013. pp. 195–203. https://doi.org/10.1007/978-88-470-2661-2_16
  173. 173. Bruera E, Pruvost M, Schoeller T, Montejo G, Watanabe S. Proctoclysis for Hydration of Terminally Ill Cancer Patients. Journal of Pain and Symptom Management. 1998;15: 216–219. pmid:9601155
  174. 174. Peck M, Jeng J, Moghazy A. Burn Resuscitation in the Austere Environment. Crit Care Clin. 2016;32: 561–565. pmid:27600127
  175. 175. Nelson BD, Collins LB, Pritchard EWJ. Innovations in Low- and Middle-Income Countries for Newborn and Child Health. Innovating for Healthy Urbanization. Springer, Boston, MA; 2015. pp. 19–40. https://doi.org/10.1007/978-1-4899-7597-3_2
  176. 176. Rouhani S, Meloney L, Ahn R, Nelson BD, Burke TF. Alternative Rehydration Methods: A Systematic Literature Review and Lessons for Resource-Limited Care. Pediatrics. 2011; peds.2010-0952. pmid:21321023
  177. 177. Lozynsky OA, Dupuis L, Shandling B, Gilmour RF, Zimmerman B. Anaphylactoid and systemic reactions following saline enema administration. Six case reports. Ann Allergy. 1986;56: 62–66. pmid:3511778
  178. 178. Grocott MPW, McCorkell S, Cox ML. Resuscitation From Hemorrhagic Shock Using Rectally Administered Fluids in a Wilderness Environment. Wilderness & Environmental Medicine. 2005;16: 209–211. pmid:16366202
  179. 179. Hamre HJ, Glockmann A, Fischer M, Riley DS, Baars E, Kiene H. Use and Safety of Anthroposophic Medications for Acute Respiratory and Ear Infections: A Prospective Cohort Study. Drug Target Insights. 2007;2: 209–219. pmid:21901075
  180. 180. Bornhöft G, Matthiessen P. Homeopathy in Healthcare: Effectiveness, Appropriateness, Safety, Costs. Springer Science & Business Media; 2011. pmid:21525600
  181. 181. Hamre HJ, Glockmann A, Heckenbach K, Matthes H. Use and Safety of Anthroposophic Medicinal Products: An Analysis of 44,662 Patients from the EvaMed Pharmacovigilance Network. Drugs—Real World Outcomes. 2017;4: 199–213. pmid:28965336
  182. 182. American Academy of Pediatrics, Council on Communications and Media C on CA. Policy statement: Children, Adolescents, and the Media. Pediatrics. 2013;132: 958–961. pmid:28448255
  183. 183. Andersson MA. Chronic Disease at Midlife: Do Parent-child Bonds Modify the Effect of Childhood SES? Journal of health and social behavior. 2016;57: 373–389. pmid:27601411
  184. 184. Gunduz S, Usak E, Koksal T, Canbal M. Why Fever Phobia Is Still Common? Iran Red Crescent Med J. 2016;18: e23827. pmid:27781110
  185. 185. Bertille N, Purssell E, Corrard F, Chiappini E, Chalumeau M. Fever phobia 35 years later: did we fail? Acta Paediatrica. 2016;105: 9–10. pmid:26725574