AAP儿童发热与退热药物(中英对照版)
Fever and Antipyretic Use in Children 儿童发热和退热药物应用
Abstract
摘要
Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern.Many parents administer antipyretics even when there is minimal or no fever,because they are concerned that the child must maintain a“normal”temperature.Fever,however,is not the primary illness but is a physiologic mechanism that has bene?cial effects in?ghting infection.There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications. Thus,the primary goal of treating the febrile child should be to improve the child’s overall comfort rather than focus on the normalization of body temperature.When counseling the parents or caregivers of a febrile child,the general well-being of the child,the importance of monitoring activity,observing for signs of serious illness,encouraging appropriate?uid intake, and the safe storage of antipyretics should be emphasized.Current evidence suggests that there is no substantial difference in the safety and effectiveness of acetaminophen and ibuprofen in the care of a generally healthy child with fever.There is evidence that combining these2 products is more effective than the use of a single agent alone;however,there are concerns that combined treatment may be more complicated and contribute to the unsafe use of these drugs. Pediatricians should also promote patient safety by advocating for simpli?ed formulations, dosing instructions,and dosing devices.Pediatrics2011;127:580–587
儿童发热是儿科医生及医护人员常遇见的临床症状，同时也是引发家长焦虑的常见原因。许多患儿家长会在孩子轻微发热甚至无发热的情况下使用退热药，因为他们认为孩子的体温必须正常。发热并非一种疾病，它是机体对抗感染的一种生理机制。目前并无证据显示发热是某种疾病的导因或会导致神经系统并发症。因此，对发热患儿的首要任务并非将体温降至正常水平而是让孩子感到舒服。在给家长或护理人给予建议时，重点强调孩子的正常精神状态表现，观察活动程度的重要性，关注严重疾病的症状，鼓励适当的液体摄入以及退热药物的安全剂量。目前的证据显示，在安全性和效果方面，用于一般发热儿童的护理的对乙酰氨基酚和布洛芬并没有显著差异。有证据显示使用2种药物比单一使用某种更加有效；但是使用两种药物较为复杂同时易引发用药不安全事件的发生。儿科医生同时需要通过单一剂型、严格控制剂量和喂服药物器械上保证患儿安全。
INTRODUCTION
简介
Fever is one of the most common clinical symptoms managed by pediatricians and other health care providers and accounts,by some estimates,for one-third of all presenting conditions in children.1Fever in a child commonly leads to unscheduled physician visits,telephone calls by parents to their child’s physician for advice on fever control,and the wide use of over-the-counter antipyretics.
儿童发热是儿科医生及医护人员常遇见的临床症状，据估算，有将近三分之一的就诊儿童均有此症状。儿童发热通常会导致无预约的就诊，电话咨询关于发热控制的建议以及超剂量的退热药物使用。
Parents are frequently concerned with the need to maintain a“normal”temperature in their ill child.Many parents administer antipyretics even though there is either minimal or no fever.2 Approximately onehalf of parents consider a temperature of less than38°C(100.4°F)to be a fever,and25%of caregivers would give antipyretics for temperatures of less than37.8°C (100°F).1,3Furthermore,85%of parents(n=340)reported awakening their child from sleep to
give antipyretics.1Unfortunately,as many as one-half of parents administer incorrect doses of antipyretics;approximately15%of parents give supratherapeutic doses of acetaminophen or ibuprofen.4Caregivers who understand that dosing should be based on weight rather than age or height of fever are much less likely to give an incorrect dose.4
家长通常都有一种要求——保持患儿的体温“正常”。许多家长在低热甚至无发热状态下给孩子以退热药物。大约有一半的家长认为38℃以下也算发热，同时有25%的护理人会在体温低于37.8℃时给予退热药物。更甚，85%的家长（统计总数为340）有叫醒睡眠中的孩子服用退烧药的经历。不幸的是，有一半以上的家长都给予了孩子不恰当剂量的退热药物；大约15%的家长会给予孩子超剂量的对乙酰氨基酚或布洛芬。了解药物剂量按体重计算优于年龄或发热高低的护理人会更不容易给予错误的剂量。
Physicians and nurses are the primary source of information on fever management for parents and caregivers,although there are some disparities between the views of parents and physicians regarding antipyretic treatment.1The most common indications for initiating antipyretic therapy by pediatricians are a temperature higher than38.3°C(101°F)and improving the child’s overall comfort.5Although only13%of pediatricians speci?cally cite discomfort as the primary indication for antipyretic use,6this intent is generally implied in their recommendations.Most pediatricians(80%)believe that a sleeping ill child should not be awakened solely to be given antipyretics.5
尽管对于退热药物的使用，儿科医生和家长之间存在着些许分歧，但是儿科医生和护士仍为家长和护理人发热患儿获取有关发热的治疗信息的主要来源。儿科医生关于退热药物使用的普遍共识为高于38.3℃可使用退热药物同时提升孩子的整体舒适度。尽管有13%的儿科医生特别强调孩子不舒适为使用退热药物的主要指征，但是这一条目通常都会被纳入标准之中。绝大多数（80%）的儿科医生认为不应在患儿的睡眠过程中唤醒患儿以服用退热药物。
Antipyretic therapy will remain a common practice by parents and is generally encouraged and supported by pediatricians.Thus,pediatricians and health care providers are responsible for the appropriate counseling of parents and other caregivers about fever and the use of antipyretics.7使用退热药物进行退热为家长的常规措施，同时也是儿科医生所推介的处理方式。因此，儿科医生及护士应负责地给予家长和护理人有关发热及退热药物使用的合适建议。PHYSIOLOGY OF FEVER
发热的生理学
It should be emphasized that fever is not an illness but is,in fact,a physiologic mechanism that has bene?cial effects in?ghting infection.8–10Fever retards the growth and reproduction of bacteria and viruses,enhances neutrophil production and T-lymphocyte proliferation,and aids in the body’s acute-phase reaction.11–14The degree of fever does not always correlate with the severity of illness.Most fevers are of short duration,are benign, and may actually protect the host.15Data show bene?cial effects on certain components of the immune system in fever,and limited data have revealed that fever actually helps the body recover more quickly from viral infections,although the fever may result in discomfort in children.11,16–18Evidence is inconclusive as to whether treating with antipyretics, particularly ibuprofen alone or in combination with acetaminophen,increases the risks of complications with certain types of infections.19,20Potential bene?ts of fever reduction include relief of patient discomfort and reduction of insensible water loss,which may decrease the occurrence of dehydration.Risks of lowering fever include delayed identi?cation of the underlying diagnosis and initiation of appropriate treatment and drug toxicity.
值得强调的是，发热并非一种疾病，事实上，它是一种有助于机体对抗感染的正常生理反应。发热可以阻止细菌和病毒的生长繁殖，促进中性粒细胞数的升高及T-淋巴细胞的增殖并辅助急性期反应。发热时体温高低不与病情严重程度成正比，多数发热持续时间较短且为良性，发热还具有保护患儿的作用。数据显示，发热对免疫系统某些特定组分具有促进作用，同时有限的数据先是发热实质上可以帮助机体从病毒感染中恢复，但副作用为引起患儿感觉不适。
There is no evidence that children with fever,as opposed to hyperthermia,are at increased risk of adverse outcomes such as brain damage.7,9,21–23Fever is a common and normal physiologic response that results in an increase in the hypothalamic“set point”in response to endogenous and exogenous pyrogens.9,23In contrast,hyperthermia is a rare and pathophysiologic response with failure of normal homeostasis(no change in the hypothalamic set point)that results in heat production that exceeds the capability to dissipate heat.9,23Characteristics of hyperthermia include hot,dry skin and central nervous system dysfunction that delirium,convulsions,or coma.23Hyperthermia should be addressed promptly,because at temperatures above41°C to42°C,adverse physiologic effects begin to occur.7,9,24Studies of health care workers,including physicians,have revealed that most believe that the risk of heat-related adverse outcomes is increased with temperatures above 40°C(104°F),although this belief is not justi?ed.5,23,25–27A child with a temperature of 40°C(104°F)attributable to a simple febrile illness is quite different from a child with a temperature of40°C(104°F)attributable to heat stroke.Thus,extrapolating similar outcomes from these different illnesses is problematic.
目前并无证据显示发热，而非体温过高，会引发不良后果，例如大脑损伤。发热是一种正常的生理反应，其生理机制为内源性或外源性致热源导致体温调定点上移所致。相比之下，体温过高很罕见，病理生理反应为机体稳态的紊乱（不存在体温调定点变化）这是由于产热量大于散热量导致的。体温过高的特征包括皮肤干燥发烫以及中枢神经系统症状例如谵妄，抽搐和昏迷等。体温过高应及时处理，因为在体温高于41℃到42℃的时候，体内已经开始不良的生理反应。虽然这一说法并未取得共识，但健康工作者（包括儿科医生）的研究显示绝大多数认为当体温高于40℃的时候，与发热相关的不良结局风险将会上升。因单纯发热性疾病所致体温40℃与因中暑所致体温40℃的孩子有显著差别。因此，从相同的症状中去别处不同的疾病是一个难题。
TREATMENT GOALS
治疗目标
A discussion of the use of antipyretics in febrile children must begin with consideration of the therapeutic end points.When counseling families,physicians should emphasize the child’s comfort and signs of serious illness rather than emphasizing normothermia.A primary goal of treating the febrile child should be to improve the child’s overall comfort.Most pediatricians observe,with some supporting data from research,that febrile children have altered activity, sleep,and behavior in addition to decreased oral intake.28Unfortunately,there is a paucity of clinical research addressing the extent to which antipyretics improve discomfort associated with fever or illness.It is not clear whether comfort improves with a normalized temperature,because external cooling measures,such as tepid sponge baths,can lower the body temperature without improving comfort.7,29The use of alcohol baths is not an appropriate cooling method,because there have been reported adverse events associated with systemic absorption of alcohol.30 Furthermore,antipyretics have other clinical outcomes,including analgesia,which may enhance their overall clinical effect.Regardless of the exact mechanism of action,many physicians
continue to encourage the use of antipyretics with the belief that most of the bene?ts are the result of improved comfort and the accompanying improvements in activity and feeding,less irritability,and a more reliable sense of the child’s overall clinical condition.Because these are the most important bene?ts of antipyretic therapy,it is of paramount importance that parental counseling focus on monitoring of activity,observing for signs of serious illness,and appropriate ?uid intake to maintain hydration.
在对发热儿童使用退热药物的讨论中，必须首先考虑治疗目标。当给家庭进行咨询的时候，儿科医生应该重点强调孩子的整体舒适性和危重疾病的症状而非强调正常体温。治疗发热儿童的首要目标是让孩子的整体舒适度提升。根据研究数据，除了进食减少以外，绝大多数儿科医生可以观察到发热儿童具备以下方面的改变：活动、睡眠以及行为。可惜的是，临床上缺乏针对退热药物可改善因发热或疾病引发的不适的程度的相关研究。目前尚未明确舒适度改善是够与体温正常相关，因为物理降温措施，例如温水擦浴可以降低体温但不一定能提高舒适度。酒精擦浴并非适合的降温措施，因为酒精会被吸收。此外，退热药物的使用也会有一些临床后果，包括镇痛作用，这有提升总体临床效果的可能。不管作用机制，许多儿科医生都建议使用退热药物，他们认为退热药物的作用为提升舒适度和加强活动活跃度以及增强食欲，减少烦躁，以及让孩子整体的状况更加好。以上这些都是使用退热药物的重要效应，因此观察孩子的活动活跃度，危重疾病的症状以及恰当的补液以防止脱水非常重要。
The desire to improve the overall comfort of the febrile child must be balanced against the desire to simply lower the body temperature.It is well documented that there are signi?cant concerns on the part of parents,nurses,and physicians about potential adverse effects of fever that have led to a description in the literature of“fever phobia.”31The most consistently identi?ed serious concern of caregivers and health care providers is that high fevers,if left untreated,are associated with seizures,brain damage,and death.1,25,32,33It is argued that by creating undue concern over these presumed risks of fever,for which there is no clearly established relationship, physicians are promoting an exaggerated desire in parents to achieve normothermia by aggressively treating fever in their children.
There is no evidence that reducing fever reduces morbidity or mortality from a febrile illness. Possible exceptions to this could be children with underlying chronic diseases that may result in limited metabolic reserves or children who are critically ill,because these children may not tolerate the increased metabolic demands of fever.34Finally,there is no evidence that antipyretic therapy decreases the recurrence of febrile seizures.22,35,36
提升发热患儿的整体舒适度应与降低患儿体温之间保持平衡。有记载，在部分家长、护士甚至是儿科医生中，存在着对发热的强烈焦虑，这种潜在的效应被称之为“发热恐惧症”。护理人和健康工作者对于发热的最焦虑的是如果高热不治疗，会导致惊厥、大脑损伤甚至死亡。有人认为，儿科医生通过创建对发热的并无明确关系的假定风险的不必要的关注，来向患儿父母传递一种强烈的通过积极治疗发热患儿以达到降温的愿望。目前并没有证据表明，减少发热可以减少发热疾病的发病率或者死亡率。有一些特殊情况就是孩子有慢性疾病而这种疾病会导致有限的代谢储备或者是孩子有严重疾病时，因为这些孩子可能是不能耐受代谢增加所带来的发热。最后，并没有证据表明退热药物可以预防热性惊厥。
Despite insuf?cient evidence,many pediatricians recommend the routine practice of pretreatment with acetaminophen or ibuprofen before a paitient receives immunizations to decrease the discomfort associated with the injections and subsequently at the injection sites
and to minimize the febrile response.9,17,37–39In addition,results of1recent study suggested the possibility of decreased immune response to vaccines in patients treated early with antipyretics.40
尽管证据不足，许多儿科医生推荐在病人接受免疫接种前使用对乙酰氨基酚或布洛芬作为预处理，以减少在注射部位与注射相关的不适，并尽量减少发热反应。此外，最近的一个研究结果表明在早期使用退热药治疗的患者，可降低疫苗的免疫应答的可能性。
Although the available literature is limited on the actual risks of fever and the bene?ts of antipyretic therapy,it is recognized that improvement in patient comfort is a reasonable therapeutic objective.Furthermore,at this time,there is no evidence that temperature reduction, in and of itself,should be the primary goal of antipyretic therapy.
尽管在现有的文献中，关于发热的实际风险和退热药物的优势的文章很有限，但是提升患儿舒适度是公认的合理的治疗目标。此外，就目前而言，并没有证据表明，降温本身应该是服用退热药物的主要目标。
Acetaminophen
对乙酰氨基酚
After suf?cient evidence emerged of an association between salicylates and Reye syndrome, acetaminophen essentially replaced aspirin as the primary treatment of fever.Acetaminophen doses of10to15mg/kg per dose given every4to6hours orally are generally regarded as safe and effective.Typically,the onset of an antipyretic effect is within30to60minutes; approximately80%of children will experience a decreased temperature within that time(Table 1).
在出现水杨酸盐和瑞氏综合征之间关联充分的证据后，对乙酰氨基酚基本上取代阿司匹林作为发烧的主要治疗药物。对乙酰氨基酚的安全及有效剂量为10?15毫克/每公斤，每4?6小时口服。典型地，起效时间为30至60分钟内;约80％的孩子将会在这个时间内降低体温（表1）。
Although alternative dosing regimens have been suggested,41–43no consistent evidence has indicated that the use of an initial loading dose by either the oral(30mg/kg per dose)or rectal (40mg/kg per dose)route improves antipyretic ef?cacy.The higher rectal dose is often used in intraoperative conditions but cannot be recommended for use in routine clinical care.44,45The use of higher loading doses in clinical practice would add potential risks for dosing confusion leading to hepatotoxicity;therefore,such doses are not recommended.
尽管替代的给药方案已经提出，但没有一致的证据表明，无论是口服（30mg/kg）或直肠给药（40mg/kg）的初始剂量会提高退热功效。较高的直肠剂量常用于术中情况，但不能被推荐用于常规临床护理使用。在临床实践中采用较高的剂量会导致给药剂量错误引发肝毒性的潜在风险；因此并不推介这样的剂量。
Although hepatotoxicity with acetaminophen at recommended doses has been reported rarely, hepatoxicity is most commonly seen in the setting of an acute overdose.In addition,there is signi?cant concern over the possibility of acetaminophen-related hepatitis in the setting of a chronic overdose.The most commonly reported scenarios are those of children receiving multiple supratherapeutic doses(ie,>15mg/kg per dose)or frequent administration of appropriate single doses at intervals of less than4hours,which has resulted in doses of more than90mg/kg per day for several days.46,47Giving an adult preparation of acetaminophen to a child may result in supratherapeutic dosing.In1case series,46half of the children with hepatotoxicity had received adult preparations of acetaminophen.
虽然在推荐剂量下对乙酰氨基酚所致的肝损害鲜有报道，肝毒性是最常见的一种急性过量
的状况。此外，有一种慢性过量导致的与对乙酰氨基酚相关的肝炎值得关注。最常见的是那些孩子接受多次超治疗剂量（即>15mg/kg）或4小时内多次安全剂量，这会导致多日的日总剂量超过90mg/kg。给予孩子成年剂量的对乙酰氨基酚可能会导致超治疗剂量。在一系列病例回顾中，半数肝损害的孩子都服用了成人剂量的对乙酰氨基酚。
One safety concern is the effect of acetaminophen on asthma-related symptoms;although asthma has also been associated with acetaminophen use,causality has not been demonstrated.48–51
一个有关安全的关注点是对乙酰氨基酚对哮喘相关的症状的治疗效果;虽然哮喘也与对乙酰氨基酚的使用存在相关性，但其因果关系尚未得到证实。
Ibuprofen
布洛芬
The use of ibuprofen to manage fever has been increasing,because it seems to have a longer clinical effect related to lowering of the body temperature(Table1).Studies in which the effectiveness of ibuprofen and acetaminophen were compared have yielded variable results;the consensus is that both drugs are more effective than placebo in reducing fever and that ibuprofen(10mg/kg per dose)is at least as effective as,and perhaps more effective than, acetaminophen(15mg/kg per dose)in lowering body temperature when either drug is given as a single or repetitive dose.52–57Data also show that the height of the fever and the age of the child(rather than the speci?c medication used)may be the primary determinants of the ef?cacy of antipyretic therapy;those who have a higher fever and are older than6years show decreased ef?cacy or response to antipyretic therapy.54Studies that compare the effect of ibuprofen versus acetaminophen on children’s behavior and comfort are generally lacking.
使用布洛芬来治疗持续升温的发热患儿是因为它似乎具有更加长效的降温效果（见表1）。研究中，布洛芬和对乙酰氨基酚的效果进行了比较，并得出了不同的结果；共识是这两种药物在降温方面比安慰剂组更有效同时布洛芬（10mg/kg）与对乙酰氨基酚
（15mg/kg）相比，在单独使用或者是重复使用时至少一样有效甚至更加有效。数据还表明，发热程度和儿童的年龄（而不是所使用的特定的药物）可能为影响退热药物治疗发热疗效的主要决定因素;对于6岁以上的较高体温的发热儿童而言，他们对于退热药物的治疗效果会有所下降。关于布洛芬与对乙酰氨基酚对儿童的行为和舒适的效果比较普遍缺乏。There is no evidence to indicate that there is a signi?cant difference in the safety of standard doses of ibuprofen versus acetaminophen in generally healthy children between6months and 12years of age with febrile illnesses.58Similar to other nonsteroidal antiin?ammatory drugs (NSAIDs),ibuprofen can potentially cause gastritis,59,60although no data suggest that this is a common occurrence when used on an acute basis,such as during a febrile illness.58However, there have been case reports of bleeding,gastritis,and ulcers of the stomach,duodenum,and esophagus associated with many NSAIDs,including ibuprofen,even when used in typical antipyretic and analgesic doses.59,60Ibuprofen does not seem to worsen asthma symptoms.
没有任何证据表明，对一般状况好的6个月以上，12岁以下发热患儿使用安全剂量的布洛芬或对乙酰氨基酚存在显著差异。虽然没有数据表明，但类似于其它非甾体抗炎药（NSAID）一样，在常见的发生在紧急情况——如发热性疾病中使用时，布洛芬有可能导致胃炎。但是，与许多NSAID类药物一样，包括布洛芬，即便是使用了解热镇痛药的剂量是，也出现了出血的病例报告，包括胃溃疡和胃，十二指肠，食道等部位。同时，布洛芬似乎并没有加重哮喘症状。
Concern has been raised over the nephrotoxicity of ibuprofen.In numerous case reports,
children with febrile illnesses developed renal insuf?ciency when treated with ibuprofen or other NSAIDs.Thus,caution is encouraged when using ibuprofen in children with dehydration or with complex medical illnesses.61–63In children with dehydration,prostaglandin synthesis becomes an increasingly important mechanism for maintaining appropriate renal blood?ow.The use of ibuprofen or any NSAID interferes with the renal effects of prostaglandins,which reduces renal blood?ow and potentially precipitates or worsens renal dysfunction.61,63However,it is not possible to determine the actual incidence of ibuprofen-related renal insuf?ciency after short-term use,because it has not been systematically investigated or reported.64Children who are at greatest risk of ibuprofen-related renal toxicity are those with dehydration,cardiovascular disease,preexisting renal disease,or the concomitant use of other nephrotoxic agents.62 Another potential group at risk is infants younger than6months because of the possibility of differences in ibuprofen pharmacokinetics and developmental differences in renal function.65 Data are inadequate to support a speci?c recommendation for the use of ibuprofen for fever or pain in infants younger than6months(there are dosing data for neonatal closure of patent ductus arteriosus66,67),although the package insert states to“ask a doctor”for guidance on its use in this population.Another potential risk associated with the use of ibuprofen is the possible association between ibuprofen and varicella-related invasive group A streptococcal infection.68,69However,at the time of this report,data were insuf?cient to support a causal relationship between ibuprofen and invasive group A streptococcal disease.
布洛芬的肾毒性已得到广泛关注。在许多病例报告中，使用布洛芬或其他NSAIDs治疗发热性疾病时，儿童易发展肾功能不全。因此，在患儿脱水时或患有复杂的内科疾病时使用布洛芬应更加谨慎。患儿脱水时，前列腺素合成这一机制在保持适当的肾血流量时越来越重要。使用布洛芬或任何NSAID会干扰前列腺素合成，前列腺素可降低肾血流量的肾功能的影响，并可能沉淀或加重的肾功能障碍。但是，短期使用布洛芬所致的肾功能不全的实际发病率无法确定，因为它没有被系统地研究或报道。布洛芬相关的肾毒性的最大风险的孩子是那些有脱水，心血管疾病，先前存在肾脏疾病，或同时使用其他肾毒性药物的孩子。因为布洛芬的药代动力学和肾功能发育的差异，6月龄以下婴儿是另一潜在风险的群体。目前数据不足以支持6月龄以下婴儿（有相关数据为动脉导管未闭的新生儿）使用布洛芬治疗发热或疼痛，虽然包装说明书中声明“咨询医生”为其在这一人群中使用的指导具体建议。与使用布洛芬相关的另一个潜在风险是布洛芬和水痘相关的侵袭性A组链球菌感染之间可能存在的关联。然而，在这个报告的时候，数据不足以支持布洛芬和侵袭性A 组链球菌疾病之间的因果关系。
TABLE1AntipyreticInformation退热药物信息
Variable条目Acetaminophen对乙酰氨基酚Ibuprofen布洛芬Decline in temperature,°C可降体温1–21–2
Time to onset,h起效时间<1<1
Time to peak effect,h药物峰值时间3–43–4
Duration of effect,h维持时间4–66–8
Dose,mg/kg剂量10–15every4h每4小时10~15mg/kg10every6h每6小时10~15mg/kg Maximum daily dose,mg/kg最大剂量90mg/kg a40mg/kg
Maximum daily adult dose,g/d成人每日最大使用次数4 2.4 Alternating or Combination Therapy
替代或联合疗法
A practice frequently used to control fever is the alternating or combined use of acetaminophen and ibuprofen.In a convenience sample survey of256parents or caregivers,67%reported
alternating acetaminophen and ibuprofen for fever control,81%of whom stated that they had followed the advice of their health care provider or pediatrician.70Although4hours was the most frequent interval,parents reported alternating therapy every2,3,4,and6hours,which suggests that there is no consensus on dosing instructions.
交替或联合使用对乙酰氨基酚和布洛芬是经常用来控制发热的做法。在256对父母或护理人中进行便利抽样调查显示，67％的家长会交替使用对乙酰氨基酚和布洛芬，其中81％表示，他们曾参照他们的健康工作者者或儿科医生的意见。虽然4小时为最常见的给药时间间隔，但仍有家长表明每2，3，4，和6小时为给药间隔，这表明对给药说明并没有达成共识。
At the time of this report,5studies had been identi?ed that compared alternating ibuprofen and acetaminophen versus either acetaminophen or ibuprofen as single agents.71–75Initially, changes in temperature were similar for all groups in these studies,regardless of therapy. However,4or more hours after the initiation of treatment,lower temperature was consistently observed in the combinationtreatment groups.For example,6and8hours after the initiation of the study,a greater percentage of children were afebrile in the combination group(83%and81%, respectively)compared with those in the group that received ibuprofen alone(58%and35%, respectively).71Only1study72evaluated issues related to stress and comfort and found lower stress scores and less time missed from child care in the combination-treatment group.Another study73showed a trend toward a normalization of fever-related symptoms by24and48hours after institution of therapy,but these trends disappeared by day5.
在本报告发布之时，已有5项研究是关于布洛芬和对乙酰氨基酚交替使用与对乙酰氨基酚或布洛芬单药治疗的区别。最初，无论任何疗法，在这些研究中，所有组的体温变化都是相似的。然而，在治疗开始4小时或更长时间后，可在联合治疗组中观察到体温降低的更多。例如，在研究开始6小时和8小时后，与那些单一使用布洛芬的组（58％和35％）相比，联合治疗组（83％和81％）有更多孩子达到无发热状态。只有1个研究评估关于压力和舒适性的问题，研究发现联合治疗组有低应力成绩，并得到了更短的时间可以降温的结果。另一项研究显示，对发热相关的症状通过治疗后24和48小时出现正常化的趋势，但这种趋势在5天后消失。
Although the aforementioned studies provide some evidence that combination therapy may be more effective at lowering temperature,questions remain regarding the safety of this practice as well as the effectiveness in improving discomfort,which is the primary treatment end point.The possibility that parents will either not receive or not understand dosing instructions,combined with the wide array of formulations that contain these drugs,increases the potential for inaccurate dosing or overdosing.76,77Finally,this practice may only promote the fever phobia that already exists.
虽然上述的研究提供了一些证据表明，联合治疗可能更有效地降低体温，但这种做法的安全性，以及主要的治疗目标——提升舒适度，仍旧存在问题。家长要么不接受或不明白给药说明，同时使用广泛含有这些成分的药物制剂，这便增加了不准确的剂量或用药过量的危险性。最终，这种做法只能加剧已经存在的发热恐惧症。
Although there is some evidence that combination therapy may result in a lower body temperature for a greater period of time,there is no evidence that combination therapy results
in overall improvement in other clinical outcomes.Also,these studies have not contained adequate numbers of subjects to fully evaluate the safety of this practice.Therefore,there is insuf?cient evidence to support or refute the routine use of combination treatment with both acetaminophen and ibuprofen.Practitioners who choose to follow this practice should counsel
parents carefully regarding proper formulation,dosing,and dosing intervals and emphasize the child’s comfort instead of reduction of fever.
虽然有一些证据表明，联合治疗可以更长效地降温，但没有证据表明，联合治疗的结果相对于其他方法有明显改善。此外，这些研究并没有包含的足够的样本数量以充分评估这种做法的安全性。因此，没有足够的证据来支持或反驳的常规使用联合治疗对乙酰氨基酚和布洛芬。执业医师选择这一方法应该认真告知患儿父母以正确剂型，剂量和给药间隔，并强调孩子的舒适度为首要目标而非退热。
INSTRUCTIONS FOR CAREGIVERS
护理人员患者准备指南
It is critically important for pediatricians to clearly describe the appropriate use(ie,formulation, dose,and dosing interval)of acetaminophen and ibuprofen to caregivers(Table1).Child safety will be further enhanced by clear labeling and the development of simpli?ed dosing methods, standardized drug concentrations,and standardized delivery devices.78–80Coughand-cold products that contain acetaminophen and ibuprofen should not be given to children because of the possibility that parents may unintentionally give their child simultaneous doses of an antipyretic and a coughand-cold medication that contains the same antipyretic.In addition,there is a lack of proven ef?cacy for this class of combination products for children.For children who require liquid preparations,physicians should encourage families to only use1formulation. Acetaminophen is the most common single ingredient implicated in emergency department visits for medication overdoses among children,and more than80%of these emergency visits are a result of unsupervised ingestions81;therefore,proper handling and storage of antipyretics should be encouraged.
对儿科医生而言，向护理人清楚地说明对乙酰氨基酚和布洛芬的使用方法（即剂型，剂量和给药间隔）是极为重要的。儿童安全可通过更清楚的标识和简化服药方法，标准化的药物浓度，标准化的服药设备的发展得到进一步加强。含有对乙酰氨基酚和布洛芬的感冒药不应该给患儿服用因为有可能父母可能会无意中给他们的孩子同时服用退热药物和感冒药，而感冒药中含有相同的对乙酰氨基酚和布洛芬。此外，缺乏一系列证据证明这一类的组合产品对孩子们是有效的。对需要液体制剂的孩子，医生应鼓励家长只使用1种配方。对乙酰氨基酚是急诊科就诊的儿童用药过量中最常见的成分，而超过80％的急诊是无监督误食的结果;因此，应注意妥善处理退热药和贮存。
SUMMARY
总结
Appropriate counseling on the management of fever begins by helping parents understand that fever,in and of itself,is not known to endanger a generally healthy child.In contrast, fever may actually be of bene?t;thus,the real goal of antipyretic therapy is not simply to normalize body temperature but to improve the overall comfort and well-being of the child. Acetaminophen and ibuprofen,when used in appropriate doses,are generally regarded as safe and effective agents in most clinical situations.However,as with all drugs,they should be used judiciously to minimize the risk of adverse drug effects and https://www.wendangku.net/doc/3913241564.html,bination therapy with acetaminophen and ibuprofen may place infants and children at increased risk because of dosing errors and adverse outcomes,and these potential risks must be carefully considered.When counseling a family on the management of fever in a child,pediatricians and other health care providers should minimize fever phobia and emphasize that antipyretic use does not prevent febrile seizures.Pediatricians should focus instead on monitoring for
signs/symptoms of serious illness,improving the child’s comfort by maintaining hydration, and educating parents on the appropriate use,dosing,and safe storage of antipyretics.To promote child safety,pediatricians should advocate for a limited number of formulations of acetaminophen and ibuprofen and for clear labeling of dosing instructions and an included dosing device for antipyretic products.
关于发烧的咨询应从一开始就帮助父母明白，发烧本身，不会危害一般健康的孩子。相比之下，发烧实际上可能是有益的;因此，解热治疗的真正目标不是简单的恢复正常体温，但提高了孩子的整体舒适度。适当剂量的对乙酰氨基酚和布洛芬，在大多数临床情况下通常被认为是安全和有效的。然而，与所有的药物一样，它们应谨慎使用，以尽量减少药物的不良反应和毒性的风险。因为剂量错误和不良后果，联合治疗对乙酰氨基酚和布洛芬可能使婴幼儿和儿童面临更大的风险，而这些潜在的风险，必须仔细考虑。当家庭对发烧的孩子的治疗，儿科医生和其他健康工作者应尽量减少发热恐惧症，并强调退热药物的使用并不能预防热性惊厥。儿科医生应重点监测危重疾病的征兆/症状，通过补液以提高孩子的舒适性，并在教育家长药物正确的使用方法、剂量及安全储存。为促进儿童安全，儿科医生应倡导对乙酰氨基酚和布洛芬的限制剂量及投加详细说明标签和退热药物所包含的剂量装置。