Intervention Review

Anticonvulsants for neonates with seizures

  1. David Booth1,*,
  2. David J Evans2

Editorial Group: Cochrane Neonatal Group

Published Online: 19 JUL 2004

Assessed as up-to-date: 29 MAR 2004

DOI: 10.1002/14651858.CD004218.pub2

How to Cite

Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD004218. DOI: 10.1002/14651858.CD004218.pub2.

Author Information

  1. 1

    Norfolk and Norwich University Hospital, Neonatal Intensive Care Unit, Norwich, Norfolk, UK

  2. 2

    Southmead Hospital, Neonatal Intensive Care Unit, Bristol, UK

*David Booth, Neonatal Intensive Care Unit, Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk, Nr4 7UY, UK. drdbooth@btopenworld.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 JUL 2004

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Neonatal seizures are a common problem and most neonates with seizures are treated with anticonvulsants. There is wide variation in clinical practice in both diagnosis and treatment of such seizures and this reflects the lack of clear evidence of the relative benefit and harm of the anticonvulsants used. The routine use of anticonvulsants to treat seizures in neonates needs to be evaluated.

Objectives

To assess and compare (with respect to benefits and harm) different anticonvulsants administered to neonates for the treatment of established seizures.

Search methods

Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE 1966 - March 2004, EMBASE 1980 - March 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and hand searches. Identification of ongoing or unpublished trials was attempted by contacting prominent authors in the field and searching electronic registers of ongoing trials.

Selection criteria

All randomised or quasi-randomised controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, need for additional anticonvulsants, need for maintenance anticonvulsants at discharge and adverse events (hypotension requiring volume or inotropic support, arrhythmia, respiratory depression, hepatotoxicity) in neonates treated for seizures with systemic anticonvulsants compared to placebo, no drug or alternative anticonvulsants.

Data collection and analysis

Methodological quality and validity were assessed without consideration of the results. The first reviewer screened the title and abstracts of studies identified by the above search strategy. Full text versions of studies of potential relevance were re-screened by both reviewers. Studies meeting the pre-specified inclusion criteria were included. Relevant data were extracted and analysed separately and any disagreements were resolved by discussion.

Main results

Only two randomised controlled trials published in full could be identified. Painter 1999 showed that both of the two most commonly used anticonvulsants (phenobarbital and phenytoin) were similarly effective (RR 1.03 95% CI 0.96 to 1.62), controlling seizures in less than fifty percent of infants. Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004 randomised infants who failed to respond to phenobarbital to receive either lidocaine or midazolam as second-line agents. There was a trend for lidocaine to be more effective in reducing seizure burden (RR 0.40 95% CI 0.14 to 1.17) but both groups had similarly poor long term outcomes assessed at one year.

Authors' conclusions

At present there is little evidence from randomised controlled trials to support the use of any of the anticonvulsants currently used in the neonatal period. In the literature, there remains a body of opinion that seizures should be treated because of the concern that seizures in themselves may be harmful, although this is only supported by relatively low grade evidence (Levene 2002; Massingale 1993).

Development of safe and effective treatment strategies relies on future studies of high quality (randomised controlled trials with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Anticonvulsants for neonates with seizures

Plain language summary will be included with future review update.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

抗癲癇藥物應用於新生兒癲癇發作

新生兒癲癇是一種常見的問題,大多數新生兒癲癇發作時都是用抗癲癇藥物治療。在臨床上的診斷和治療癲癇發作有很大的差異,這反映了缺乏明確證據來提供抗癲癇藥物使用所帶來相對利益和壞處。常規使用抗癲癇藥物治療新生兒癲癇是需要進行評估的。

目標

為了評估和比較(相對於好處和壞處)不同的抗癲癇藥物投以新生兒治療癲癇發作。

搜尋策略

使用電子數據庫檢索(MEDLINE 1966 – 2004年3月,EMBASE資料庫 1980年  2004年3月),Cochrane中心註冊的對照試驗(CENTRAL,Cochrane Library,第1期,2004年)和人工合併搜索相關的隨機對照試驗。另外為了確認進行中或未發表的論文, 我們透過聯繫這方面的有名專家和電腦搜索已進行中有登記的試驗。

選擇標準

所有的隨機或半隨機對照臨床試驗的數據與想要比較的結果如下:比較治療新生兒癲癇發作時全身性抗癲癇藥物使用與安慰劑, 無藥物或替代抗癲癇藥物相比的 : 死亡率,神經發育障礙,需要額外的抗癲癇藥物,出院時需要持續使用抗癲癇藥物,副作用(低血壓且需要體液補充或強心劑,心律不整,呼吸抑制,肝毒性)。

資料收集與分析

在不考慮結果的情況下,對方法學要求的品質和有效性進行評估。第一審閱者透過上述搜索策略篩選出我們研究所要的相關標題和摘要。而相關研究全文版的相關性則是由兩位審閱者一起再篩選一次。當研究符合我們預先指定的入選標準就會被涵括在內。有關數據會分開進行提取,分析,若有任何分歧則透過通過討論釐清。

主要結論

只有兩個隨機對照試驗可確定。Painter 1999年的研究顯示2個最常用的抗癲癇藥(phenobarbital與 phenytoin)對控制嬰兒癲癇發作是同樣的效果(RR 1.03 95%CI為 0.96至1.62),都不到百分之五十的。。Painter 1999年的研究沒有報告死亡率或神經發育的結果。Boylan 2004的研究顯示對phenobarbital沒有用的嬰兒隨機使用lidocaine 或 midazolam作為二線藥物。發現有一個趨勢顯示idocaine能較有效地減少發作(RR 0.40 95%CI為 0.14至1.17),但兩組在長期評估結果(一年後)則都是一樣差。

作者結論

目前,很少隨機對照試驗有證據以支持使用任何目前在新生兒期使用的抗癲癇藥物。在文獻中,仍然存在著一個主要概念認為,癲癇發作是應該被治療, 因為擔心癲癇發作本身可能是有害的,儘管這只是相對較低的支持度證據(Levene 2002; Massingale 1993)。開發安全有效的治療策略依賴於未來高品質(隨機對照試驗, 方法學上保證的效度),並有足夠的規模來證明其有能力臨床降低死亡率和嚴重的神經發育殘疾效果與 減少任何短期癲癇負擔的研究出現

翻譯人

本摘要由臺中榮民總醫院薛榮華翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

待總結概要