对乙酰氨基酚和布洛芬联合及交替治疗发热儿童

Tiffany Wong, Antonia S Stang, Heather Ganshorn, Lisa Hartling, Ian K Maconochie, Anna M Thomsen, David W Johnson
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However, there is uncertainty about whether these regimens are better than the use of single agents, and about the adverse effect profile of combination regimens.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>To assess the effects and side effects of combining paracetamol and ibuprofen, or alternating them on consecutive treatments, compared with monotherapy for treating fever in children.</p>\n </section>\n \n <section>\n \n <h3> Search methods</h3>\n \n <p>In September 2013, we searched Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and International Pharmaceutical Abstracts (2009–2011).</p>\n </section>\n \n <section>\n \n <h3> Selection criteria</h3>\n \n <p>We included randomized controlled trials comparing alternating or combined paracetamol and ibuprofen regimens with monotherapy in children with fever.</p>\n </section>\n \n <section>\n \n <h3> Data collection and analysis</h3>\n \n <p>One review author and two assistants independently screened the searches and applied inclusion criteria. Two authors assessed risk of bias and graded the evidence independently. We conducted separate analyses for different comparison groups (combined therapy versus monotherapy, alternating therapy versus monotherapy, combined therapy versus alternating therapy).</p>\n </section>\n \n <section>\n \n <h3> Main results</h3>\n \n <p>Six studies, enrolling 915 participants, are included. Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children can result in a lower mean temperature at one hour after treatment (MD −0.27 °Celsius, 95% CI −0.45 to −0.08, two trials, 163 participants, <i>moderate quality evidence</i>). If no further antipyretics are given, combined treatment probably also results in a lower mean temperature at four hours (MD −0.70 °Celsius, 95% CI −1.05 to −0.35, two trials, 196 participants, <i>moderate quality evidence</i>), and in fewer children remaining or becoming febrile for at least four hours after treatment (RR 0.08, 95% CI 0.02 to 0.42<i>,</i> two trials, 196 participants, <i>moderate quality evidence</i>). Only one trial assessed a measure of child discomfort (fever associated symptoms at 24 hours and 48 hours), but did not find a significant difference in this measure between the treatment regimens (one trial, 156 participants, <i>evidence quality not graded</i>).</p>\n \n <p>In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child's fever fails to resolve or recurs. 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引用次数: 70

摘要

背景:卫生专业人员经常建议儿童发烧治疗方案,要么联合使用扑热息痛和布洛芬,要么交替使用。然而,这些方案是否比使用单一药物更好,以及联合方案的不良反应概况尚不确定。目的评价对乙酰氨基酚与布洛芬联用或联用连续治疗与单药治疗小儿发热的疗效和副作用。检索方法2013年9月,我们检索Cochrane传染病组专业注册;Cochrane中央对照试验登记册;MEDLINE;EMBASE;紫丁香;《国际药学文摘》(2009-2011)。我们纳入了比较对乙酰氨基酚和布洛芬交替或联合治疗方案与单药治疗发热儿童的随机对照试验。一名综述作者和两名助理独立筛选检索并应用纳入标准。两位作者独立评估了偏倚风险并对证据进行了分级。我们对不同的对照组进行了单独的分析(联合治疗与单一治疗,交替治疗与单一治疗,联合治疗与交替治疗)。主要结果纳入6项研究,共纳入915名受试者。与单独给予退烧药相比,给予发热儿童扑热息痛和布洛芬联合治疗可导致治疗后1小时的平均体温降低(MD为- 0.27℃,95% CI为- 0.45至- 0.08,两项试验,163名受试者,中等质量证据)。如果不给予进一步的退热药物,联合治疗也可能导致4小时平均体温降低(MD - 0.70摄氏度,95% CI - 1.05至- 0.35,2项试验,196名受试者,中等质量证据),并且在治疗后至少4小时仍保持或发热的儿童较少(RR 0.08, 95% CI 0.02至0.42,2项试验,196名受试者,中等质量证据)。只有一项试验评估了儿童不适的测量(24小时和48小时的发烧相关症状),但在治疗方案之间没有发现该测量的显著差异(一项试验,156名参与者,证据质量未分级)。在实践中,护理人员通常被建议最初只给一种药物(扑热息痛或布洛芬),如果孩子的发烧不能消退或复发,再给另一种剂量的药物。以这种方式进行交替治疗可能导致第二次剂量后1小时的平均体温降低(MD - 0.60摄氏度,95% CI - 0.94至- 0.26,两项试验,78名受试者,低质量证据),并且还可能导致在给药后3小时内保持或发热的儿童减少(RR 0.25, 95% CI 0.11至0.55,两项试验,109名受试者,低质量证据)。一项试验评估了儿童不适(24、48和72小时的平均疼痛评分),发现交替治疗的平均评分较低,尽管总体上给予的退烧药剂量较少(一项试验,480名参与者,低质量证据)。只有一项小型试验比较了交替治疗和联合治疗。在1小时、4小时或6小时的平均体温或发热儿童的数量上没有统计学上的显著差异(一项试验,40名参与者,证据质量非常低)。试验中没有直接归因于所使用药物的严重不良事件。有一些证据表明交替和联合退热治疗在降低体温方面可能比单独治疗更有效。然而,改善儿童不适措施的证据仍然没有定论。没有足够的证据表明哪种联合治疗或交替治疗可能更有益。未来的研究需要使用标准化的工具来测量儿童不适,并评估联合和交替退热治疗的安全性。交替或联合退烧药治疗儿童发热当儿童感染疾病时,通常会出现发烧。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combined and alternating paracetamol and ibuprofen therapy for febrile children

Background

Health professionals frequently recommend fever treatment regimens for children that either combine paracetamol and ibuprofen or alternate them. However, there is uncertainty about whether these regimens are better than the use of single agents, and about the adverse effect profile of combination regimens.

Objectives

To assess the effects and side effects of combining paracetamol and ibuprofen, or alternating them on consecutive treatments, compared with monotherapy for treating fever in children.

Search methods

In September 2013, we searched Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and International Pharmaceutical Abstracts (2009–2011).

Selection criteria

We included randomized controlled trials comparing alternating or combined paracetamol and ibuprofen regimens with monotherapy in children with fever.

Data collection and analysis

One review author and two assistants independently screened the searches and applied inclusion criteria. Two authors assessed risk of bias and graded the evidence independently. We conducted separate analyses for different comparison groups (combined therapy versus monotherapy, alternating therapy versus monotherapy, combined therapy versus alternating therapy).

Main results

Six studies, enrolling 915 participants, are included. Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children can result in a lower mean temperature at one hour after treatment (MD −0.27 °Celsius, 95% CI −0.45 to −0.08, two trials, 163 participants, moderate quality evidence). If no further antipyretics are given, combined treatment probably also results in a lower mean temperature at four hours (MD −0.70 °Celsius, 95% CI −1.05 to −0.35, two trials, 196 participants, moderate quality evidence), and in fewer children remaining or becoming febrile for at least four hours after treatment (RR 0.08, 95% CI 0.02 to 0.42, two trials, 196 participants, moderate quality evidence). Only one trial assessed a measure of child discomfort (fever associated symptoms at 24 hours and 48 hours), but did not find a significant difference in this measure between the treatment regimens (one trial, 156 participants, evidence quality not graded).

In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child's fever fails to resolve or recurs. Giving alternating treatment in this way may result in a lower mean temperature at one hour after the second dose (MD −0.60 °Celsius, 95% CI −0.94 to −0.26, two trials, 78 participants, low quality evidence), and may also result in fewer children remaining or becoming febrile for up to three hours after it is given (RR 0.25, 95% CI 0.11 to 0.55, two trials, 109 participants, low quality evidence). One trial assessed child discomfort (mean pain scores at 24, 48 and 72 hours), finding that these mean scores were lower, with alternating therapy, despite fewer doses of antipyretic being given overall (one trial, 480 participants, low quality evidence)

Only one small trial compared alternating therapy with combined therapy. No statistically significant differences were seen in mean temperature, or the number of febrile children at one, four or six hours (one trial, 40 participants, very low quality evidence).

There were no serious adverse events in the trials that were directly attributed to the medications used.

Authors' conclusions

There is some evidence that both alternating and combined antipyretic therapy may be more effective at reducing temperatures than monotherapy alone. However, the evidence for improvements in measures of child discomfort remains inconclusive. There is insufficient evidence to know which of combined or alternating therapy might be more beneficial.Future research needs to measure child discomfort using standardized tools, and assess the safety of combined and alternating antipyretic therapy.

PLAIN LANGUAGE SUMMARY

Alternating and combined antipyretics for treatment of fever in children

When they are ill with infections, children often develop a fever. The fever with common viral illnesses, such as colds, coughs, sore throats and gastrointestinal illness, usually lasts a few days, makes children feel unwell, and is distressing for the children, their parents, or other caregivers.

Paracetamol (also known as acetaminophen) and ibuprofen lower the child's temperature and relieve their discomfort. This review evaluates whether giving both treatments together, or alternating the two treatments, is more effective than giving paracetamol or ibuprofen alone.

In September 2013, we found six studies, involving 915 children, that evaluated combined or alternating paracetamol and ibuprofen to treat fever in children.

Compared to giving ibuprofen or paracetamol alone, giving both medications together is probably more effective at lowering temperature for the first four hours after treatment (moderate quality evidence). However, only one trial assessed whether combined treatment made children less uncomfortable or distressed and found no difference compared to ibuprofen or paracetamol alone.

In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child continues to have a fever. Giving alternating treatment in this way may be more effective at lowering temperature for the first three hours after the second dose (low quality evidence), and may also result in less child discomfort (low quality evidence)

Only one small trial compared alternating therapy with combined therapy and found no advantages between the two (very low quality evidence).

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