Intervention Review

Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants

  1. Gautham Suresh1,*,
  2. Jonathan M Davis2,
  3. Roger Soll3

Editorial Group: Cochrane Neonatal Group

Published Online: 22 JAN 2001

Assessed as up-to-date: 20 NOV 2000

DOI: 10.1002/14651858.CD001968


How to Cite

Suresh G, Davis JM, Soll R. Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD001968. DOI: 10.1002/14651858.CD001968.

Author Information

  1. 1

    Dartmouth-Hitchcock Medical Center, Department of Pediatrics, Neonatal Division, Lebanon, NH, USA

  2. 2

    Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York, USA

  3. 3

    University of Vermont, Division of Neonatal-Perinatal Medicine, Burlington, Vermont, USA

*Gautham Suresh, Department of Pediatrics, Neonatal Division, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03576-001, USA. gautham.suresh@hitchcock.org.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 22 JAN 2001

SEARCH

 

Abstract

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

Background

Free oxygen radicals have been implicated in the pathogenesis of chronic lung disease in preterm infants. Superoxide dismutase is a naturally occurring enzyme which provides a defence against such oxidant injury. Exogenously administered superoxide dismutase has been tested in clinical trials to prevent chronic lung disease in preterm infants.

Objectives

To determine if exogenously administered superoxide dismutase is efficacious in the prevention of chronic lung disease in preterm infants who are mechanically ventilated, and efficacious in decreasing the following outcomes: bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus and mortality. To determine the frequency and nature of adverse effects of superoxide dismutase.

Search methods

We searched Medline (1966 - 2000) and the Cochrane Controlled Trials Register (CCTR) using the following keywords: {bronchopulmonary dysplasia OR chronic lung disease} AND superoxide dismutase, limited to human studies in newborn infants (infant, newborn). We hand searched the reference lists of articles located and the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) from 1980 - 2000.

Selection criteria

Randomized controlled trials where subjects were preterm infants who had developed or were at risk of developing respiratory distress syndrome requiring assisted ventilation and who were randomly allocated to receive either superoxide dismutase (in any form, by any route) or placebo or no treatment. We included studies which reported any of the following outcomes: chronic lung disease, bronchopulmonary dysplasia, any intraventricular hemorrhage, intraventricular hemorrhage grades III/IV, patent ductus arteriosus, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, neonatal mortality, death prior to discharge and neurodevelopmental outcome.

Data collection and analysis

We extracted and assessed separately all data for each study and entered final data into RevMan. We did not perform subgroup analyses (which were originally planned) because only two studies were eligible for inclusion. We assessed the methodological quality of the studies by assessing the risk for bias. We pooled the outcomes of infants who had developed bronchopulmonary dysplasia at 28 days with those who had died at 28 days to derive the combined outcome of bronchopulmonary dysplasia or death at 28 days. Similarly we pooled the outcomes of infants who had respiratory problems after discharge with those who had died prior to discharge to derive the combined outcome of respiratory problems after discharge or death. We used the standard method of the Cochrane Neonatal Review Group for statistical analysis, using a fixed effect model.

Main results

Two randomized controlled trials were included for analysis. No differences were found in either study or in the pooled data in death prior to discharge, oxygen dependency at 36 weeks corrected age, oxygen dependency at 28 days of life or in other outcomes. In one study (Rosenfeld 1984), survivors who had been treated with superoxide dismutase had a shorter duration of continuous positive airway pressure (4.9 vs 9.7 days), a lower frequency of respiratory problems after discharge (relative risk 0.33, 95% confidence limits 0.11, 0.96) and a lower frequency of chest radiograph abnormalities (relative risk 0.30, 95% confidence limits 0.11, 0.87) compared to survivors who received placebo. A third study was available only in abstract form and will be evaluated for inclusion after publication.

Authors' conclusions

Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.

 

Plain language summary

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

Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants

Not enough evidence to show the effectiveness of superoxide dismutase in preventing chronic lung disease in premature babies. Chronic lung disease (CLD) is a common problem in preterm babies who are mechanically ventilated (machine assisted breathing). Free oxygen radicals are believed to cause CLD. Superoxide dismutase is an enzyme normally present in the body to provide a defence against free radicals but preterm infants do not have a sufficient supply to provide natural resistance. Giving superoxide dismutase to preterm infants may therefore prevent CLD. The review of trials found there is not enough evidence yet to show if this is effective. More research is needed.

 

摘要

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

背景

對於使用機械式呼吸器的早產兒而言,用超氧化物歧化? (superoxide dismutase) 來預防慢性肺部疾病

已經有過報告指出,在早產兒身上,氧氣自由基為慢性肺部疾病的發病原因。超氧化物歧化?是1種天然的酵素,它可以提供防禦機制來對抗這類氧化性傷害。在某些臨床試驗當中,已經試著在早產兒身上,藉由外部給予超氧化物歧化?的方式,來預防慢性肺部疾病。

目標

對於使用機械式呼吸器的早產兒而言,藉由外部給予超氧化物歧化?的方式來預防慢性肺部疾病,要確定它是否具有這樣的功效,而且還要確認它是否能夠有效地減緩下列的狀況:肺部支氣管發育不良、腦室內出血、周腦室白質軟化症、早產視網膜病變、壞死性腸炎、開放性動脈導管,以及死亡的情況。要確認超氧化物歧化?的所有副作用之頻率與性質。

搜尋策略

這些隨機對照試驗的對象是早產兒,而且他們已經產生了呼吸窘迫症候群,或是正處於產生呼吸窘迫症候群的風險之中,因此需要使用輔助性的呼吸系統,其中他們都被隨機地分配到不同的組別當中,包括了接受超氧化物歧化?(不論是何型式,或透過何路徑來使用)或是安慰劑,或是不採取治療。在我們收集的這些研究當中,都有針對下列結果的至少1項來提出報告:慢性的肺部疾病、肺部支氣管發育不良、任何腦室內出血的狀況、第三/四級的腦室內出血、開放性動脈導管、周腦室白質軟化症、早產視網膜病變、壞死性腸炎、新生兒死亡的情況、在出院前便已死亡,以及神經發展的預後。

選擇標準

我們搜尋Medline (1966年2000) 及Cochrane Controlled Trials Register (CCTR) ,所使用的關鍵字為: {bronchopulmonary dysplasia 或 chronic lung disease} 以及superoxide dismutase, 限制為新生兒之人體研究 (infant, newborn) 。人工搜尋文獻中之參考資料清單以及自1980年至2000年Society for Pediatric Research (美國) (發表於Pediatric Research) 的摘要。

資料收集與分析

對於所有的研究而言,我們分頭擷取出所有的資料,並且加以評估,再將最後的資料輸入到RevMan之中。我們並沒有進行次群組的分析(原本是有這樣的計畫),因為只有2份研究符合了收集的標準。針對這些研究,我們藉由評估誤差上所帶來的風險來評估了研究方法的品質。在28天時已經患有肺部支氣管發育不良的嬰兒們,以及那些在28天時已經死亡的嬰兒們,我們將這些合併起來,推導出在28天時有關於肺部支氣管發育不良或是死亡的綜合結果。同樣地,在出院之後還有呼吸方面之疾病的嬰兒們,以及那些在出院之前就已經死亡的嬰兒們,我們將這些結果合併起來,以用來推導出死亡或出院尚有呼吸疾病的綜合結果。關於統計學的分析方面,我們使用了 Cochrane Neonatal Review Group的標準方法,其中還使用了固定的效果模型。

主要結論

共有2份隨機對照試驗可作為分析。對於在出院前就死亡、在36週的矯正年齡時對於氧氣的依賴程度、在出生28天大時對於氧氣的依賴程度、或是在其他的預後,不論是就單一研究或是合併後的資料來看,當中都沒有發現到任何差異。在其中1份研究(Rosenfeld 1984)中,跟那些接受安慰劑的生還者比較起來,對於接受超氧化物歧化?來進行治療的生還者而言,需要使用持續性呼吸道正壓的時間長度會比較短(4.9天相較於9.7天),在出院之後發生呼吸疾病的頻率比較低(相對風險為0.33,95% 信賴極限為0.11、0.96),而且發生胸部放射線影像異常的頻率也比較低(相對風險為0.30,95% 信賴極限為0.11、0.87)。至於第3份研究,我們能夠取得的只有摘要的型式,將會在其論文發表之後再收集加以評估。

作者結論

根據目前能夠取得的已發表試驗,關於超氧化物歧化?在預防早產所造成的慢性肺部疾病,並沒有足夠的證據能夠歸納出確切的結論。從少數接受過治療的嬰兒身上所得到的資料顯示,早產兒對於它的耐受程度很高,而且它並不會帶來嚴重的副作用。

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

在早產兒使用超氧化物歧化?來預防慢性肺部疾病,並沒有足夠的證據可以說明它的功效。對於早產而且又必須使用機械式呼吸器(機械輔助式呼吸)的嬰兒而言,慢性肺部疾病(CLD)是常見的問題。人們相信,氧氣自由基會引起慢性肺部疾病。超氧化物歧化?是存在於身體裡面的酵素,為對抗自由基的防禦機制,但是早產兒身上並沒有充足的供應量,以致於無法產生天然的抵抗力。因此,在早產兒身上給予超氧化物歧化?,或許能夠預防慢性肺部疾病。本篇的試驗回顧發現,關於這樣的方法是否會有功效,到目前為止還沒有足夠的證據能夠加以顯示。還需要有更多的研究。