This is not the most recent version of the article. View current version (13 AUG 2013)

Intervention Review

Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants

  1. Andrew Whitelaw*,
  2. David Odd

Editorial Group: Cochrane Neonatal Group

Published Online: 17 OCT 2007

Assessed as up-to-date: 30 MAY 2007

DOI: 10.1002/14651858.CD001691.pub2


How to Cite

Whitelaw A, Odd D. Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD001691. DOI: 10.1002/14651858.CD001691.pub2.

Author Information

  1. University of Bristol Medical School, Neonatal Intensive Care Unit, Bristol, UK

*Andrew Whitelaw, Neonatal Intensive Care Unit, University of Bristol Medical School, Southmead Hospital, Bristol, BS10 5NB, UK. andrew.whitelaw@bristol.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 OCT 2007

SEARCH

This is not the most recent version of the article. View current version (13 AUG 2013)

 

Abstract

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

Background

Intraventricular hemorrhage (IVH) is a major complication of preterm birth. Large hemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals.

Objectives

To determine the effect of postnatal administration of phenobarbital on the risk of intraventricular hemorrhage (IVH), neurodevelopmental impairment or death in preterm infants.

Search methods

See the Search Strategy of the Neonatal Collaborative Review Group. The reviewer has been a active trialist in this area and has personal contact with many groups in this field. Journals handsearched from 1976 (when cranial CT scanning started) to October 2000 include: Pediatrics, J Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European J of Pediatrics, Neuropediatrics, New England J of Medicine, Lancet and British Medical J. The National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) were searched through to April 2007 using the MeSH terms intraventricular hemorrhage, newborn infants, premature infant, intracranial hemorrhage, phenobarbitone, phenobarbital. The searches were not limited to the English language, as long as the article included an English abstract. Promising articles were read in the original language or translated.

Selection criteria

Randomized or quasi-randomized controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g, or respiratory failure were included. Adequate determination of IVH by ultrasound or CT was also required.

Data collection and analysis

In addition to details of patient selection and control of bias, the details of the administration of phenobarbital were extracted. The end-points searched for included: IVH ( with grading), posthemorrhagic ventricular dilatation or hydrocephalus, neurodevelopmental impairment and death. In addition, possible adverse effects of phenobarbitone such as hypotension, mechanical ventilation, pneumothorax, hypercapnia, and acidosis were searched for.

Main results

Ten controlled trials were included with 740 infants recruited. There was heterogeneity between trials for the outcome IVH, with one trial finding a significant decrease in IVH and another trial finding an increase in IVH in the group receiving phenobarbital. Meta-analysis showed no difference between the phenobarbital treated group and the control group in either IVH (typical relative risk 1.04, 95% CI 0.87, 1.25), severe IVH (typical relative risk 0.91, 95% CI 0.66, 1.24), posthemorrhagic ventricular dilatation (typical relative risk 0.89, 95% CI 0.38, 2.08), severe neurodevelopmental impairment (typical relative risk 1.44, 95% CI 0.41, 5.04) or death before hospital discharge (typical relative risk 0.88, 95% CI 0.64, 1.21) There was a consistent trend in the trials towards increased use of mechanical ventilation in the phenobarbital treated group, which was supported by the meta-analysis (typical relative risk 1.18, 95% CI 1.06, 1.32; typical risk difference 0.129, 95% CI 0.045, 0.213), but there was no significant difference in pneumothorax, acidosis or hypercapnia.

Authors' conclusions

Postnatal administration of phenobarbital cannot be recommended as prophylaxis to prevent IVH in preterm infants and is associated with an increased need for mechanical ventilation.

 

Plain language summary

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

Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants

There is not enough evidence that phenobarbital is effective in preventing intraventricular hemorrhage (IVH) in premature babies. Intraventricular hemorrhage (IVH) is a major problem of preterm birth. Large bleeds in the centre of the brain can cause disability or death in the preterm baby. Unstable blood pressure and blood flow to the brain are believed to cause IVH. The drug phenobarbital is believed to stabilise blood pressure and, therefore, potentially help prevent IVH. The review of trials found there was not enough evidence that postnatal phenobarbital is effective in preventing IVH. Furthermore, phenobarbitone suppresses breathing in infants who are breathing spontaneously, causing a need for mechanical ventilation.

 

摘要

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

背景

早產兒在出生之後使用phenobarbital來預防腦室出血

對於早產兒來說,腦室出血(IVH)是種重大的併發症。大量的出血會使得殘疾與水腦的風險升高。血壓不穩與腦內的血流量不穩定被認為是造成 VH之原因。另外1種造成原因的解釋為氧氣自由基所所帶來再灌注之危害。Phenobarbital被認為是1種以用來穩定血壓,或許還能夠保護人體對抗自由基的安全治療方法。

目標

早產兒在出生後,給予phenobarbital這種藥物,要確認它對於腦室出血(IVH)、神經發展異常,或是死亡等方面的風險上,會產生什麼樣的影響。

搜尋策略

搜尋策略請參見 eonatal Collaborative Review Group。本文之文獻回顧者為本領域相當活躍的試驗者,並且與許多本領域之團體有私人聯繫。人工搜尋期刊,時間自197 當時剛開始有腦部電腦斷層掃描之檢查)至2000年10月,包括之期刊有 ediatrics、J Pediatrics、Archives of Disease in Childhood、 ediatric Research、Developmental Medicine以及Child Neurology、Acta Paediatrica、European J of Pediatrics、Neuropediatrics、New England J of Medicine、Lancet以及British Medical J. 另外搜尋The National Library of Medicine (USA) 資料庫(via PubMed) 以及Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library) ,日期直到2007年4月,使用MeSH搜尋之名詞有: ntraventricular hemorrhage、newborn infants、premature infant、 ntracranial hemorrhage、phenobarbitone, phenobarbital。搜尋不限定為英文,只要當中有英文摘要即可。針對合適的文章閱讀其原文或是翻譯。

選擇標準

當中收集的都是隨機或是半隨機的對照試驗,在早產的嬰兒因為被認定為處於腦室出血的風險之中而給予phenobarbital這種藥物,這些嬰兒包含妊娠週數低於34週、出生時體重低於1500克,或是呼吸衰竭。使用超音波或是斷層掃描的方式,以對腦室出血進行適當的判斷也是必要的。

資料收集與分析

除了病患挑選與偏差管控的詳細內容之外,phenobarbital之給藥方式的細節也會記錄。對於收集的內容而言,研究的預後包括了:腦室出血(附帶等級分布)、出血後所造成的腦室擴大或是水腦、神經發展異常,以及死亡。除此之外, 同時也搜尋phenobarbital可能會引起的副作用,例如低血壓、呼吸器的使用、氣胸、高碳酸血症,以及酸中毒。

主要結論

共收集了10份對照試驗,當中包含了740名嬰兒。對於腦室出血而言,不同的試驗之間結果不盡相同,在接受過phenobarbital的那組當中,有1份試驗發現了腦室出血的現象顯著地減少,但另外1份試驗則是發現腦室出血的現象增加了。統合分析顯示,在接受過phenobarbital治療的那組與對照組之間,不論是就腦室出血(典型的相對風險為1.04,95% I 0.87,1.25)、嚴重的腦室出血(典型的相對風險為0.91,95% I 0.66,1.24)、出血後所造成的腦室擴大(典型的相對風險為0.89,95% I 0.38,2.08)、嚴重的神經發展異常(典型的相對風險為1.44,95% I 0.41,5.04),或是住院中死亡(典型的相對風險為0.88,95% I 0.64,1.21)等項目中的哪1項來看,都沒有差異。在這些試驗當中,有某種共同的趨勢顯示,在接受了phenobarbital治療的那組當中,需要使用呼吸器的情形變多了,而且這樣的情況可以從統合分析當中獲得證實(典型的相對風險為1.18,95% I 1.06,1.32;典型的相對風險為0.129,95% I 0.045,0.213),但是在得到氣胸、酸中毒,或是高碳酸血症方面,並沒有顯著的差異。

作者結論

對於早產兒而言,並不建議在出生後給予phenobarbital來預防腦室出血,而且給予phenobarbital還會造成對於呼吸的需求增加。

翻譯人

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

總結

對於早產兒而言,關於 henobarbital在預防腦室出血(IVH)方面的功效,並沒有足夠的證據能夠加以證實。 對於早產兒而言,腦室出血(IVH)是重大的問題。在早產兒身上,若是在腦部中心發生了大量出血的現象,就有可能會引發殘疾或是死亡。不穩定的血壓,以及通往腦部的血流量不固定,被認為是引起腦室出血的原因。 henobarbital這種藥物被認為可以穩定血壓,因此,它就有可能幫助我們預防腦室出血的現象。本篇試驗的回顧發現,並沒有足夠的證據顯示在出生後給予 henobarbital可以帶來預防腦室出血之功效。甚至,對於那些可以自主呼吸的嬰兒而言,phenobarbitone會抑制他們的呼吸,因而造成需要使用到呼吸器。