Re: 아이들 발열 치료 가이드라인 2017

[문형철]

fever-phobia

BMJ Open

. 2017 Jul 31;7(7):e015404. doi: 10.1136/bmjopen-2016-015404

Guidelines for the symptomatic management of fever in children: systematic review of the literature and quality appraisal with AGREE II

Elena Chiappini 1, Barbara Bortone 1, Luisa Galli 1, Maurizio de Martino 1

• Author information
• Article notes
• Copyright and License information

PMCID: PMC5642818  PMID: 28760789

Abstract

Introduction

Several societies have produced and disseminated clinical practice guidelines (CPGs) for the symptomatic management of fever in children. However, to date, the quality of such guidelines has not been appraised.

Objective

To identify and eval‎uate guidelines for the symptomatic management of fever in children.

Methods

The research was conducted using PubMed, guideline websites, and Google (January 2010 to July 2016). The quality of the CPGs was independently assessed by two assessors using the Appraisal of Guidelines for Research & Eval‎uation II (AGREE II) instrument, and specific recommendations in guidelines were summarised and eval‎uated. Domain scores were considered of sufficient quality when >60% and of good quality when >80%.

Results

Seven guidelines were retrieved. The median score for the scope and purpose domain was 85.3% (range 66.6–100%). The median score for the stakeholder involvement domain was 57.5% (range 33.3–83.3%) and four guidelines scored >60%. The median score for the rigour of development domain was 52.0% (range 14.6–98.9%), and only three guidelines scored >60%. The median score for the clarity of presentation domain was 80.9% (range 50.0–94.4%). The median score for the applicability domain was 39.3% (8.3–100%). Only one guideline scored >60%. The median score for the editorial independence domain was 48.84% (0–91.6%); only three guidelines scored >60%.

Conclusion

Most guidelines were recommended for use even if with modification, especially in the methodology, the applicability and the editorial independence domains. Our results could help improve reporting of future guidelines, and affect the selection and use of guidelines in clinical practice.

초록
서론
여러 학회에서는 소아 발열의 증상 관리에 대한 임상 실무 지침(CPGs)을 개발하고 배포해 왔습니다. 그러나 현재까지 이러한 지침의 품질이 평가되지 않았습니다.

목적
소아 발열의 증상 관리에 대한 지침을 식별하고 평가하는 것입니다.

방법
이 연구는 PubMed, 지침 웹사이트, Google(2010년 1월부터 2016년 7월까지)을 통해 수행되었습니다. CPGs의 품질은 두 명의 평가자가 Appraisal of Guidelines for Research & Eval‎uation II(AGREE II) 도구를 사용하여 독립적으로 평가했으며, 지침 내 구체적인 권고사항은 요약 및 평가되었습니다. 도메인 점수는 60% 이상일 경우 충분한 품질, 80% 이상일 경우 우수한 품질로 간주되었습니다.

결과
7개의 지침이 검색되었습니다. 범위 및 목적 도메인의 중간 점수는 85.3% (범위 66.6–100%)였습니다. 이해관계자 참여 도메인의 중간 점수는 57.5% (범위 33.3–83.3%)였으며, 4개의 지침이 60%를 초과했습니다. 개발 엄격성 도메인의 중간 점수는 52.0% (범위 14.6–98.9%)였으며, 3개의 지침만 60%를 초과했습니다. 제시 명확성 도메인의 중간 점수는 80.9% (범위 50.0–94.4%)였습니다. 적용 가능성 도메인의 중간 점수는 39.3% (8.3–100%)였습니다. 단 1개의 지침만 60% 이상을 기록했습니다. 편집 독립성 분야의 중간 점수는 48.84% (0–91.6%)였으며, 60% 이상을 기록한 지침은 3개뿐이었습니다.

결론
대부분의 지침은 수정 사항을 반영하더라도 사용이 권장되었으며, 특히 방법론, 적용 가능성 및 편집 독립성 분야에서 이 점이 두드러졌습니다. 본 연구 결과는 향후 지침 보고를 개선하는 데 기여할 수 있으며, 임상 실무에서 지침의 선택 및 사용에 영향을 미칠 수 있습니다.

Keywords: Children, guidelines, antipyretics, fever

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Strengths and limitation of this study.

• To the best of our knowledge this is the first study to appraise guidelines on the symptomatic management of fever with the AGREE II instrument.

• Moreover, recommendations dealing with symptomatic management of fever have been extracted and resumed in comparative tables, focusing on possible gaps and common messages between the guidelines.

• The AGREE methodology does not provide a threshold for discrimination between high quality and low quality guidelines.

• Searching may not have been exhaustive; therefore, we cannot exclude the possibility that some guidelines may have been omitted from this study.

Introduction

Fever is one of the most common clinical reasons for paediatric consultations, accounting for about one-third of all presenting conditions in children.1–3

Concerns of parents/tutors/caregivers about serious causes of fever (ie, severe bacterial infections) and misconceptions about fever as a sufficient trigger of brain damage have led to the spreading of ‘fever-phobia’.1 4 5 Several studies have reported a high percentage of parents/tutors/caregivers administering antipyretics even when there is minimal or no fever, with wrong dosages or with insufficient intervals between the doses.4–6 Fever is a physiologic mechanism with beneficial effects in fighting infection and it is not associated with long-term neurologic complications.7 The only purpose for treating fever in children must be to relieve the child's discomfort and not to lower the body temperature.8

The inappropriate management of fever may delay the diagnosis and increase the risk of antipyretic overdose. Moreover, other factors may increase drug toxicity such as the alternate/combined use of two antipyretics,9 the use of rectal formulations,10 and the administration of these drugs in the presence of contraindicated underlying diseases.11 Finally, overtreatment may have a significant economic impact in low-middle income and high income countries.

In order to rationalise and standardise the symptomatic management of fever in children, national health agencies and scientific societies have produced and disseminated clinical guidelines. It has been demonstrated that parents/tutors do not fully comply with these recommendations, as they used to employ traditional physical means and administer antipyretics with inappropriate indications and posology.3 12–16 Moreover, important discrepancies have been reported between the practices of healthcare professionals and the recommendations of guidelines.17–19

Several barriers to applying these guidelines in clinical practice have been identified.19–22 Thus, we conducted this study to identify and eval‎uate the quality of the international clinical practice guidelines (CPGs) for the use of antipyretics and physical methods in children with fever, focusing on discrepancies.

이 연구의 장점과 한계.

• 우리의 지식 범위 내에서 이 연구는 AGREE II 도구를 사용하여 발열의 증상 관리 지침을 평가한 첫 번째 연구입니다.
• 또한, 발열의 증상 관리에 관한 권장 사항을 추출하여 비교 표에 정리했으며, 지침 간 가능한 격차와 공통된 메시지에 초점을 맞췄습니다.
• AGREE 방법론은 고품질과 저품질 지침을 구분하기 위한 임계값을 제공하지 않습니다.
• 검색이 완전하지 않을 수 있으므로, 이 연구에서 일부 지침이 누락되었을 가능성을 배제할 수 없습니다.

서론

발열은

소아과 진료의 가장 흔한 임상적 원인 중 하나로,

소아의 전체 진료 사례의 약 1/3을 차지합니다.1–3

부모/보호자/간병인의

발열의 심각한 원인(예: 중증 세균 감염)에 대한 우려와

발열이 뇌 손상의 충분한 유발 요인이라는 오해는

'발열 공포증'의 확산을 초래했습니다.1 4 5

여러 연구에서 부모/보호자/간병인이

발열이 최소하거나 전혀 없는 경우에도 해열제를 투여하거나,

잘못된 용량이나 투여 간격으로 투여하는 경우가 높게 보고되었습니다.4–6

발열은

감염과 싸우는 데 유익한 효과를 가진 생리적 메커니즘이며

장기적인 신경학적 합병증과 관련이 없습니다.7

어린이의 발열을 치료하는 유일한 목적은

어린이의 불편함을 완화하는 것이며

체온을 낮추는 것이 아닙니다.8

발열의 부적절한 관리는

진단 지연을 초래하고

해열제 과다 투여 위험을 증가시킬 수 있습니다.

또한, 두 가지 해열제의 병용 투여,9

직장 투여 제제의 사용,10 또는

금기 질환이 있는 경우 약물을 투여하는 등

다른 요인이 약물 독성을 증가시킬 수 있습니다.11

마지막으로,

과도한 치료는 저소득 및 중소득 국가와 고소득 국가에서

상당한 경제적 영향을 미칠 수 있습니다.

어린이의 발열 증상 관리의 합리화 및 표준화를 위해 국가 보건 기관과 과학 학회는 임상 지침을 작성하고 배포했습니다. 부모/보호자가 이러한 권장 사항을 완전히 준수하지 않는 것으로 나타났으며, 전통적인 물리적 방법 사용, 부적절한 적응증 및 용량으로 해열제를 투여하는 경우가 많았습니다.3 12–16 또한 의료 전문가의 실무와 지침 권장 사항 사이의 중요한 차이에 대한 보고가 있었습니다.17–19

임상 실무에서 이러한 지침을 적용하는 데 여러 장애물이 식별되었습니다.19–22 따라서 본 연구는 발열을 동반한 어린이에서 해열제 및 물리적 방법의 사용에 대한 국제 임상 실무 지침(CPGs)의 품질을 식별하고 평가하기 위해, 특히 불일치에 초점을 맞춰 진행되었습니다.

MethodsPrimary outcomes

The primary outcomes of the study were to encourage the improvement of the quality of guidelines, to reinforce the messages of common recommendations, and to stimulate further research on discordant recommendations and the issues of international guidelines in order to unify medical behaviour.

Guidelines research

The search for guidelines for the symptomatic management of fever in children was carried out using documents issued by national scientific societies or by government organisations between January 2010 and July 2016 in every language, through the use of appropriate keywords and the following search engines: PubMed; National Guideline Clearinghouse (www.guideline.gov); NICE: National Institute for Health and Care Excellence (www.nice.org.uk); Canadian CPG Infobase: Clinical Practice Guidelines Database (www.cma.ca/En/Pages/clinical-practice-guidelines.aspx); Scottish Intercollegiate Guidelines Network (SIGN) (www.sign.ac.uk); Australian Clinical Practice Guidelines (http://www.clinicalguidelines.gov.au/);%20and Guidelines International Network (http://www.g-i-n.net/). Additional research was conducted on Google. In this research we used the following keywords: ‘guideline’, ‘fever’, ‘children’, and ‘antipyretics’, (see ‘Search strategy’ in supplementary material 1). The search was limited to January 2010 and not earlier in order to eval‎uate only the most recent and updated guidelines.

Supplementary file 1

bmjopen-2016-015404supp001.pdf (140KB, pdf)

Exclusion criteria

Guidelines that did not focus on the management of fever as a symptom/sign, or were not original or were issued on a regional level, were excluded, as well as any documents that were not guidelines (such as position papers and reviews).

Quality eval‎uation

Two assessors, one with experience in developing and eval‎uating guidelines (EC) and another assessor (BB), used the online training tools recommended by the AGREE collaboration before conducting appraisals.23 They independently eval‎uated the included guidelines using the AGREE II instrument,23 which consists of a total of 23 items in six domains: ‘Scope and purpose’, ‘Stakeholder involvement’, ‘Rigour of development’, ‘Clarity of presentation’, ‘Applicability’, and ‘Editorial independence’. Each item was rated on a seven-point scale from 1 (strongly disagree) to 7 (strongly agree). A scaled domain percentage score was calculated, according to the AGREE II methodology,23 as follows: (obtained score−minimum possible score)/(maximum possible score−minimum possible), where the ‘obtained score’ is the sum of the appraisers scores per each item, making it possible to consider the natural discrepancies between the two appraisers.

Although the domain scores are useful for comparing guidelines and attest whether a guideline should be recommended for use, the AGREE II instrument does not set minimum domain scores or patterns of scores across domains to differentiate between high quality and poor quality guidelines. These decisions should be made by the users and guided by the context in which AGREE II is being used.23 Then, as reported in previous studies,24 25we considered a value >60% as sufficient quality score and a value >80% as a good quality score.

On completing the 23 items, the appraisers provided the overall assessment of each guideline, and decided which guideline was recommendable, with or without modifications, and which was not recommendable. This choice was the result of the six domains’ scores and of the personal judgement of the appraisers. To resolve discrepancies between the two assessors, a method was used from a previous study: if the scores assigned by the assessors differed by 1 point the lower score was used; if they differed by 2 points they were averaged; and if they varied by ≥3 points a consensus was reached after a discussion.24 25 We decided to recommend without modification the guidelines with an overall score equal to 7, to recommend with modification the guidelines with an overall score ≥4 but <7, and not to recommend the guidelines with an overall score ≤3.

Comparison of recommendations

Recommendations regarding the symptomatic management of fever in children, reported in the selected guidelines, have been extracted and summarised in comparative tables focusing on possible gaps and common messages.

ResultsGuideline selection

A total of 122 records were initially identified, of which, after screening titles and abstracts, 97 were excluded because they were irrelevant or duplicates. The remaining 25 records were retrieved for full text.2 26–49 Among these, 18 documents were excluded because they were not guidelines26 28 29 31–38 40–42 or they were not medical societies’ or health government guidelines39 43 46; one of the guidelines was excluded because the original publication date was before 2010.45 Finally, seven CPGs were selected2 27 30 44 47–49 (figure 1). The characteristics of the included guidelines are presented in table 1.

권고사항 비교
선정된 지침서에 보고된 소아 발열의 증상 관리에 대한 권고사항은 가능한 격차와 공통된 메시지에 초점을 맞춰 비교 표로 추출 및 요약되었습니다.결과지침서 선정초기에는 총 122개의 기록이 식별되었으며, 제목과 초록을 검토한 후 관련성이 없거나 중복된 97개가 제외되었습니다. 남은 25건의 기록은 전체 텍스트를 검색했습니다.2 26–49 이 중 18건은 지침이 아니었기 때문에26 28 29 31–38 40–42 또는 의료 학회나 보건 당국의 지침이 아니었기 때문에39 43 46 제외되었으며, 한 지침은 원본 출판일이 2010년 이전이었기 때문에 제외되었습니다.45 최종적으로 7개의 CPG가 선정되었습니다2 27 30 44 47–49 (그림 1). 포함된 지침의 특성은 표 1에 제시되어 있습니다.

Figure 1.

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Flow chart of searching and selecting guidelines.

Table 1.

Characteristics of the retrieved clinical practice guidelines

Title

Year of publication

Country/region

Level of development

Organisation

Authors number

Number of references

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AGREE II scores

The domain-standardised scores for selected guidelines and overall recommendations are presented in table 2 and figure 2.

Table 2.

Standardised scores of each domain by AGREE II of guidelines

Scope and purpose

Stakeholder involvement

Rigour of development

Clarity of presentation

Applicability

Editorial Independence

Overall assessment

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AAP, American Academy of Pediatrics; NICE, National Institute for Health and Care Excellence; NSW, New South Wales Ministry of Health; SA, South Australian Ministry of Health; SIP, Italian Pediatric Society.

Figure 2.

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Standardised scores of each domain by AGREE II of guidelines—histogram.

The American Academy of Pediatrics (AAP)2 guideline has good scores in clarity of presentation and editorial independence domains, sufficient score in scope and purpose, with low scores in stakeholder involvement, rigour of development and applicability domains.

The Italian Pediatric Society (SIP)27 guideline has good scores in scope and purpose, stakeholder involvement, rigour of development, clarity of presentation and editorial independence domains with a low score in applicability domain.

The South African30 guideline has good scores in scope and purpose and clarity of presentation, sufficient score in stakeholder involvement, but low scores in rigour of development, applicability and editorial independence domains.

The National Institute for Health and Care Excellence (NICE)44 guideline has good scores in scope and purpose, stakeholder involvement, rigour of development, clarity of presentation and applicability domains with a low score in editorial independence.

The New South Wales Ministry of Health (NSW)47 guideline has a sufficient score in the scope and purpose domain, but low scores in all the others.

The South Australian Ministry of Health (SA)48 guideline has a good score in scope and purpose, a sufficient score in clarity of presentation domain, but low scores in the others.

The WHO49 guideline has good scores in scope and purpose, rigour of development, clarity of presentation and sufficient scores in stakeholder involvement, applicability and editorial independence domains.

Scope and purpose

The median score for the scope and purpose domain was 85.28% (range 66.6–100%).

Most guidelines clearly described their overall objectives, health questions and target populations. The NSW guideline has the lowest score.47

Stakeholder involvement

The median score for the stakeholder involvement domain was 57.5% (range 33.30–83.30%). Only the SIP, South African, NICE, and WHO guidelines scored above 60% for this domain,27 30 44 49 whereas the AAP, NSW and SA guidelines did not consider the views and preferences of the target population.2 47 48 No guideline clearly described their members’ roles in the guideline development process. Only the SIP and NICE guidelines had methodology experts included in the guideline development group.27 44 Only in the NICE guideline were there health economists among the guideline authors.44

Rigour of development

The median score for the rigour of development domain was 51.97% (range 14.60–98.90%). Only the SIP, NICE, and WHO guidelines scored >60% because they used systematic methods of searching for evidence and for formulating recommendations27 44 49; only the NICE and WHO CPGs clearly described methods for conducting external reviews44 49; and only the NICE and WHO CPGs described their procedures for updating guidelines.44 49

Clarity of presentation

Most guidelines provided specific, unambiguous and easily identifiable recommendations. The median score for the clarity of presentation domain was 80.9% (range 50–94.4%). Only the NSW guideline scored <60%.47

Applicability

The median score for the applicability domain was 39.3% (8.3–100%). Only the NICE guideline scored >60%.44 Most guidelines did not describe the facilitators and barriers of their applications and did not sufficiently consider the costs of applying their recommendations; only the NICE guideline involved a health economist in finding and analysing cost information.44Only the AAP and SA guidelines did not provide any tool or suggestions for putting the recommendations into practice.2 48

Editorial independence

The median score for the editorial independence domain was 48.84% (0–91.6%); only the AAP, SIP and WHO CPGs scored >60%.2 27 49 The NWS and SA CPGs did not clearly provide financial support information.47 48 Although the WHO guideline reported the funding source, it did not specify the possible funding influence on the CPG content.49 Moreover, only the AAP, SIP and WHO guidelines include a conflict of interest statement by the guideline development group.2 27 49

Overall assessment

Based on the six domain scores and on a personal judgement, the AAP, SIP, South African and WHO guidelines were recommended with modifications,2 27 30 49 only the NICE CPG was recommended without modifications,44 and the NSW and SA CPGs were not recommended.47 48

Summary of recommendations

Specific recommendations have been identified and summarised in table 3, as well as common and discordant messages.

Table 3.

Specific recommendations

Specific recommendations	AAP2	SIP27	South- Africa30	NICE44	NSW47	SA48	WHO49
Age of target population	Not specified	0–18 years	Not specified	<5 years	1 month −5 years	<3 years	<5 years

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✔agree; ✘disagree; nr, not reported; Sup. table: supplementary table.

*Unwrapping an overdressed child is appropriate.47

†Undressing the child t is recommended to reduce the fever.49

‡In children <3 months it can be administered only after medical advice.2

§In children <3 months it can be administered by adapting the dosage and intervals to the gestational age.47 48

¶Insufficient evidence to support or refuse the routine use of combination treatment.2

**Alternating the two drugs is possible if discomfort persists or recurs using only one antipyretic.44 48

††Ibuprofen is contraindicated in known cases of asthma related to non-steroidal anti-inflammatory drugs.27

‡‡Management of paracetamol intoxication is reported in chapter 1: Triage and emergency conditions/common poisoning.49

AAP, American Academy of Pediatrics; NICE, National Institute for Health and Care Excellence; NSW, New South Wales Ministry of Health; SA, South Australian Ministry of Health; SIP, Italian Pediatric Society.

Supplementary file 2

bmjopen-2016-015404supp002.pdf (46.1KB, pdf)

Supplementary file 3

bmjopen-2016-015404supp003.pdf (38.7KB, pdf)

Supplementary file 4

bmjopen-2016-015404supp004.pdf (27.3KB, pdf)

Common messages

1. Antipyretics are indicated only in cases of discomfort associated with fever and not with the sole aim of reducing body temperature.

2. Recommended antipyretics are paracetamol or ibuprofen, according to the child's age, weight and characteristics.

3. The use of antipyretics does not prevent either febrile convulsions or reactions to vaccines.

4. Tepid sponging and alcoholic baths are not recommended for the treatment of fever.

5. The use of cough and cold medicine is discouraged because of the risks of overdoses and interactions.

6. Caution is recommended using antipyretics in chronic diseases such as pre-existing hepatic and renal impairment or in cases of diabetes, cardiac disease and severe malnutrition.

7. In asthmatic children with fever, paracetamol does not seem to worsen asthma symptoms.

일반적인 안내사항

1. 해열제는 발열과 관련된 불편감을 완화하기 위해 사용되며, 체온을 낮추는 것을 유일한 목적으로 사용해서는 안 됩니다.
2. 해열제로는 어린이의 연령, 체중 및 특성에 따라 파라세타몰 또는 이부프로펜이 권장됩니다.
3. 해열제의 사용은 발열성 경련이나 백신 반응을 예방하지 않습니다.
4. 미지근한 스펀지 목욕이나 알코올 목욕은 발열 치료에 권장되지 않습니다.
5. 기침 및 감기 약물의 사용은 과다 복용 및 상호작용의 위험으로 인해 권장되지 않습니다.
6. 만성 질환(기존 간 기능 장애 또는 신장 기능 장애, 당뇨병, 심장 질환, 심각한 영양 결핍 등)이 있는 경우 해열제 사용 시 주의가 필요합니다.
7. 발열이 있는 천식 어린이에서 파라세타몰은 천식 증상을 악화시키지 않는 것으로 보입니다.

Divergent messages

1. The physical method of unwrapping/uncovering children with fever is contraindicated by the SIP, South African and NICE CPGs25 28 42 and indicated by the NWS and WHO CPGs.47 49

2. The alternate use of two antipyretics is discouraged by most of the guidelines with the exception of the NICE and SA CPGs.44 48 These two guidelines permit the alternate use only if the discomfort persists after the administration of one antipyretic.44 48

3. The minimum age for administering paracetamol varies from birth (SIP, NWS, SA27 47 48) to 2 months (WHO49), to 3 months (South African30) (online supplementary file 2).

4. The posology of paracetamol varies in terms of dosage per single administration (10–15 or 15 mg/kg/dose), of intervals between doses (4 hour, 4–6 hour or 6 hour) and of maximum allowable daily dosage that ranges from 60 mg/kg/day to 90 mg/kg/day (online supplementary file 2).

5. The posology of paracetamol in newborns27 48 varies by paracetamol dosage per single administration and maximum daily dosages in newborns (online supplementary file 3).

6. The minimum age for ibuprofen administration ranges from 2 to 3 months (NWS,47 WHO49) to 6 months (AAP2) (online supplementary file 4).

7. The posology of ibuprofen is divergent in terms of dosage per single administration (5–10 or 10 mg/kg/dose), of intervals between doses (6, 6–8 hours) and maximum daily dosage of 40 mg for all guidelines except the SIP CPG that allows up to 30 mg27(online supplementary file 4).

8. The use of ibuprofen in asthmatic patients is contraindicated in the SIP CPG only in patients with asthma related to non-steroidal anti-inflammatory drugs but indicated with caution in all asthmatic patients by the South African and SA CPGs.30 48

9. The use of ibuprofen in children with dehydration is contraindicated by the SIP CPG,27 but recommended with caution by the AAP, South African and SA CPGs.2 30 48

10. The use of ibuprofen in the case of varicella is contraindicated by the SIP CPG27 and advised with caution by the AAP and South African CPGs.2 30

상반된 메시지

1. 발열이 있는 어린이의 옷을 벗기거나 덮개를 벗기는 물리적 방법은 SIP, 남아프리카 공화국 및 NICE 임상 지침(CPGs)25 28 42에서 금기 사항으로 지정되었으며, NWS 및 WHO CPGs에서는 권장됩니다.47 49
2. 대부분의 지침은 두 가지 해열제의 교대 사용을 권장하지 않으며, NICE 및 SA CPGs를 제외합니다.44 48 이 두 지침은 한 가지 해열제 투여 후 불편함이 지속될 경우에만 교대 사용을 허용합니다.44 48
3. 파라세타몰 투여의 최소 연령은 출생 시(SIP, NWS, SA27 47 48)부터 2개월(WHO49), 3개월(남아프리카30)까지 다양합니다(온라인 보충 자료 2).
4. 파라세타몰의 용량은 단일 투여량(10–15 또는 15 mg/kg/dose), 투여 간격(4시간, 4–6시간 또는 6시간), 최대 허용 일일 용량(60 mg/kg/일에서 90 mg/kg/일까지)에 따라 다릅니다(온라인 보충 자료 2).
5. 신생아에서의 파라세타몰 용법 용량은 단일 투여량 및 신생아의 최대 일일 투여량에 따라 다릅니다(온라인 보충 자료 3).
6. 이부프로펜 투여의 최소 연령은 2~3개월(NWS, 47 WHO 49)에서 6개월(AAP 2)까지 다양합니다(온라인 보충 자료 4).
7. 이부프로펜의 용량은 단일 투여량(5–10 또는 10 mg/kg/dose), 투여 간격(6, 6–8 시간), 최대 일일 용량(모든 지침에서 40 mg)에서 차이가 있으며, SIP CPG를 제외하고는 최대 일일 용량이 40 mg입니다. SIP CPG는 최대 30 mg까지 허용합니다27(온라인 보충 자료 4).
8. SIP CPG에서는 비스테로이드성 항염증제 관련 천식 환자에게만 이부프로펜 사용이 금기되지만, 남아프리카공화국 및 SA CPG에서는 모든 천식 환자에게 주의하에 사용을 권장합니다.30 48
9. 탈수 증상이 있는 어린이에서 이부프로펜 사용은 SIP CPG에서 금기 사항으로 지정되어 있습니다.27 그러나 AAP, 남아프리카 공화국 및 SA CPG에서는 주의하여 사용하도록 권장됩니다.2 30 48
10. 수두 환자에게 이부프로펜 사용은 SIP CPG에서 금기 사항으로 지정되어 있습니다.27 그러나 AAP 및 남아프리카 공화국 CPG에서는 주의하여 사용하도록 권장됩니다.2 30

Discussion and conclusions

In the present study a systematic search of the available national guidelines regarding the management of fever in children was performed, and key messages have been summarised. Overall, only seven guidelines were retrieved, which is less than expected considering that fever represents a large part of the practice of healthcare professionals, and how common the use of these drugs is. In particular, only two guidelines (AAP, SIP2 27) focused specifically on the symptomatic management of feverish children, whereas the other five guidelines dealt with the other aspects of fever management, including aetiological diagnosis and therapy.

Considering the impact of the quality of the guidelines in their application, we appraised the quality scores of the CPGs with the AGREE II instrument.

Interestingly, lower quality scores were observed in the domains of methodology, applicability and editorial independence, whereas all the guidelines had moderate to high scores in the purpose and objective and the clarity of the recommendations. The methodology analysis showed acceptable results only for the SIP,27 NICE,44 and WHO guidelines49 whereas the AAP,2 South African,30 NWS47 and SA guidelines48 had insufficient scores because they were not based on a systematic review of the literature and they did not provide recommendations explicitly linked to evidence, or because they did not involve all the required members in the guideline development group.

Regarding the ‘applicability’ item, most guidelines did not describe the facilitators and barriers to their application and did not provide audit criteria. Some CPGs lacked a summary document, and educational tools.2 30 This finding is in contrast with the need for clarity and user friendliness suggested by some authors19–22 and should be taken into consideration when developing new guidelines. Information on editorial independence was also neglected in most guidelines.30 44 47 48 Indeed only AAP, SIP and WHO guidelines reported detailed information on potential conflicts of interest.2 27 49 This is particularly important considering that conflicts of interest are the most common source of bias in guideline development.49 One strength of our study is that we used the AGREE II instrument for the first time to assess the methodological quality of guidelines related to fever in children.

The AGREE II instrument is a tool that assesses the methodological rigour and transparency with which a guideline is developed.23 A potential limitation of this method is that there is no threshold for distinguishing between high quality and low quality CPGs. Thus, the guideline quality would be left to the appraisers to identify and the scores of an AGREE II eval‎uation have to be interpreted with caution and confined to a particular situation. Furthermore, AGREE II does not consider the relative importance of the six domains of quality: rigour of development is considered of equal importance to the other five domains.24 This suggests that the domains of AGREE II should not be weighed equally. If the guideline has a low score on the domain of rigour of development, the corresponding recommendations have a high risk of bias, and the other domains are of little relevance in quality assessment. Another possible limitation of our study is that some guidelines may have been missed by our research.

From a comparison of the recommendations we observe that the guidelines agree on some crucial aspects. In particular, all guidelines agree on prescribing antipyretics only with the aim of relieving the child's discomfort caused by fever and not with the sole aim of reducing body temperature. There is also an agreement on the type of recommended antipyretics which are paracetamol or ibuprofen, according to a child's age, weight and characteristics. Several studies demonstrated the high tolerability of both these drugs with similar efficacy in reducing body temperature.7 9 However, few data are available regarding the impact of antipyretics in reducing the child's discomfort.7 9 The concept of ‘discomfort’ is not easy to define because it varies across different age groups, and may be influenced by the caregiver's perception. Therefore, future research needs to define child discomfort more precisely, and how to measure it using standardised clinical scores.

On the other hand, some messages diverge, either about the use of physical methods or the pharmacological approach. The common physical method to unwrap/uncover children with fever is contraindicated by the SIP, South African and NICE CPGs,27 30 44 but it is considered in the NWS and WHO CPGs.47 49 Furthermore, most guidelines discourage the alternate/combined use of two antipyretics except the NICE and SA CPGs that allow the alternate use of the two drugs, only when distress persists after the administration of one antipyretic.44 48 Alternate use can be associated with better control of body temperature, but no study demonstrated superiority in terms of distress control compared with monotherapy. However, it is certain that alternating two drugs increases the risk of overdose and toxicity.9 A greater consensus from the international scientific community would be desirable on a topic of such wide resonance.

In conclusion, most guidelines issued at national or international levels were of good quality and could be adopted in clinical practice. Nevertheless, the quality of the CPGs could be improved, in particular the methodological, applicability and editorial independence domains. Our study reinforces the messages of concordant recommendations and shines a light on discordant suggestions, and could stimulate the issues of international guidelines in order to unify medical behaviour.

논의 및 결론

본 연구에서는 어린이의 발열 관리에 관한 기존 국가 지침을 체계적으로 검색했으며, 주요 내용을 요약했습니다. 전체적으로 7개의 지침만 확인되었으며, 이는 발열이 의료 전문가의 임상 실무에서 차지하는 비중과 이러한 약물의 사용 빈도를 고려할 때 예상보다 적은 수입니다. 특히, 발열을 보이는 어린이의 증상 관리에 특화되어 있는 지침은 두 개(AAP, SIP2 27)에 불과했으며, 나머지 다섯 개의 지침은 발열 관리의 다른 측면, 즉 원인 진단 및 치료 등에 초점을 맞추었습니다.

지침의 품질이 적용에 미치는 영향을 고려하여, 우리는 AGREE II 도구를 사용하여 CPGs의 품질 점수를 평가했습니다.

흥미롭게도, 방법론, 적용 가능성 및 편집 독립성 분야에서 낮은 품질 점수가 관찰되었으며, 모든 지침은 목적과 목표 및 권고 사항의 명확성 분야에서 중간에서 높은 점수를 받았습니다. 방법론 분석 결과, SIP,27 NICE,44 및 WHO 지침49만 수용 가능한 결과를 보였으며, AAP,2 남아프리카,30 NWS47 및 SA 지침48은 문헌의 체계적 검토에 기반하지 않았거나 증거와 명시적으로 연결된 권고사항을 제공하지 않았거나, 지침 개발 그룹에 필요한 모든 구성원이 참여하지 않았기 때문에 충분한 점수를 얻지 못했습니다.

‘적용 가능성’ 항목과 관련하여 대부분의 지침은 적용의 촉진 요인과 장애물을 설명하지 않았으며 감사 기준을 제공하지 않았습니다. 일부 CPG는 요약 문서나 교육 도구가缺如했습니다.2 30 이 결과는 일부 저자들이 제안한 명확성과 사용자 친화성의 필요성과 대조되며, 새로운 지침을 개발할 때 고려되어야 합니다. 편집 독립성에 대한 정보도 대부분의 지침에서 소홀히 되었습니다.30 44 47 48 실제로 AAP, SIP 및 WHO 지침만 잠재적 이해 충돌에 대한 상세한 정보를 보고했습니다.2 27 49 이는 지침 개발에서 이해 충돌이 편향의 가장 흔한 원천이라는 점을 고려할 때 특히 중요합니다.49 본 연구의 강점 중 하나는 어린이 발열 관련 지침의 방법론적 품질을 평가하기 위해 AGREE II 도구를 처음으로 사용했다는 점입니다.

AGREE II 도구는 지침이 개발되는 과정에서 방법론적 엄격성과 투명성을 평가하는 도구입니다.23 이 방법의 잠재적 한계는 고품질과 저품질 CPG를 구분하는 기준점이 없다는 점입니다. 따라서 지침의 품질은 평가자에게 맡겨지며, AGREE II 평가 점수는 특정 상황에 한정하여 신중하게 해석되어야 합니다. 또한 AGREE II는 품질의 6개 영역의 상대적 중요성을 고려하지 않습니다. 개발의 엄격성은 다른 5개 영역과 동일한 중요성을 갖습니다.24 이는 AGREE II의 영역이 동일하게 가중되어서는 안 된다는 것을 시사합니다. 지침이 개발의 엄격성 영역에서 낮은 점수를 받았다면, 해당 권고 사항은 편향 위험이 높으며, 다른 영역은 품질 평가에서 거의 관련이 없습니다. 우리 연구의 또 다른 가능성 있는 한계는 일부 지침이 연구에서 누락되었을 수 있다는 점입니다.

권고사항을 비교한 결과, 지침들은 일부 중요한 측면에서 일치합니다.

특히 모든 지침은

발열로 인한 어린이의 불편함을 완화하기 위해 해열제를 처방해야 하며,

체온을 낮추는 것을 유일한 목적으로 해열제를 처방해서는 안 된다는 점에 동의합니다.

해열제의 유형에 대해서도

어린이의 연령, 체중 및 특성에 따라 파라세타몰 또는 이부프로펜을

권장한다는 점에서 일치합니다.

여러 연구에서 이 두 약물의 높은 내약성과 체온 감소 효과의 유사성이 입증되었습니다.7 9 그러나 해열제가 어린이의 불편감을 줄이는 데 미치는 영향에 대한 데이터는 부족합니다.7 9 '불편감'이라는 개념은 연령대에 따라 다를 수 있으며, 보호자의 인식에 영향을 받을 수 있어 정의가 어렵습니다. 따라서 향후 연구에서는 어린이의 불편감을 더 정확히 정의하고 표준화된 임상 점수를 사용하여 측정하는 방법을 확립해야 합니다.

한편, 물리적 방법이나 약물적 접근에 대한 일부 메시지는 서로 다릅니다. 발열이 있는 어린이의 옷을 벗기거나 덮개를 벗기는 일반적인 물리적 방법은 SIP, 남아프리카공화국 및 NICE 임상 지침에서 금기 사항으로 지정되어 있습니다.27 30 44 그러나 NWS 및 WHO 임상 지침에서는 고려 대상입니다.47 49 또한 대부분의 지침은 두 가지 해열제의 교대/병용 사용을 권장하지 않지만, NICE 및 SA CPGs는 한 가지 해열제 투여 후 불편함이 지속될 경우 두 약물의 교대 사용을 허용합니다.44 48 교대 사용은 체온 조절에 더 효과적일 수 있지만, 단일 요법과 비교해 불편함 조절 측면에서 우월성을 입증한 연구는 없습니다. 그러나 두 약물을 번갈아 사용하는 것은 과다 투여 및 독성 위험을 증가시킨다는 것은 확실합니다.9 이처럼 광범위한 관심을 받는 주제에는 국제 과학 커뮤니티의 더 큰 합의가 바람직합니다.

결론적으로, 국가나 국제 수준에서 발행된 대부분의 지침은 품질이 우수하며 임상 실무에 적용될 수 있습니다. 그럼에도 불구하고 CPGs의 품질은 특히 방법론적, 적용 가능성 및 편집 독립성 분야에서 개선될 수 있습니다. 본 연구는 일치하는 권고 사항의 메시지를 강화하고 불일치하는 제안에 빛을 비추며, 국제 지침의 문제를 자극하여 의료 행위의 통일성을 도모하는 데 기여할 수 있습니다.

Supplementary Material

Reviewer comments

bmjopen-2016-015404.reviewer_comments.pdf (175.2KB, pdf)

Author's manuscript

bmjopen-2016-015404.draft_revisions.pdf (3.3MB, pdf)

Footnotes

Contributors: EC conceptualised and designed the study, used AGREE II instrument to eval‎uate the retrieved guidelines, drafted the initial manuscript, and approved the final manuscript as submitted. BB carried out the initial analysis, used AGREE II instrument to eval‎uate the retrieved guidelines, drafted the initial manuscript, and approved the final manuscript as submitted. LG critically reviewed the manuscript, and approved the final manuscript as submitted. MdM critically reviewed the manuscript, and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Competing interests: None declared.

Patient consent: The study does not includes patient data.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data sharing statement: No additional data available.

References

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