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Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome

  • Review
  • Intervention

Authors

  • Roger Soll,

    Corresponding author
    1. University of Vermont, Division of Neonatal-Perinatal Medicine, Burlington, Vermont, USA
    • Roger Soll, Division of Neonatal-Perinatal Medicine, University of Vermont, Fletcher Allen Health Care, Smith 552A, 111 Colchester Avenue, Burlington, Vermont, 05401, USA. Roger.Soll@vtmednet.org.

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  • Eren Özek

    1. Maramara University Medical Center, Pediatrics / Division of Neonatology, Istanbul, Turkey
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Abstract

Background

Randomized controlled trials have demonstrated the efficacy of surfactant therapy in the treatment of infants at risk for or having respiratory distress syndrome (RDS). Due to surfactant inactivation, multiple doses of surfactant may lead to improved outcome.

Objectives

To determine the effect of multiple doses of exogenous surfactant compared to single doses of exogenous surfactant on mortality and complications of prematurity in premature infants at risk for or having respiratory distress syndrome.

Search methods

For the initial search in 1999, searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infant; publication type, clinical trials), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language.

In June 2008, the searches were updated including Medline, Cinhal and Embase using similar terms as the original search.

Selection criteria

Randomized controlled trials comparing a policy of multiple doses of surfactant to a policy of single doses of surfactant extract in premature infants at risk for or having respiratory distress syndrome were considered for this review.

Data collection and analysis

Data on clinical outcomes including pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and severe intraventricular hemorrhage), bronchopulmonary dysplasia, retinopathy of prematurity, and mortality were excerpted by the both reviewers (R. Soll; E. Özek). For this update additional data were sought on pulmonary hemorrhage, periventricular leukomalacia, neurodevelopmental follow-up, rehospitalization for pulmonary reasons,and reactive airway disease. Data were analyzed according to the standards of the Cochrane Neonatal Review Group.

Main results

Three trials were identified that met study criteria. Two studies were randomized controlled trials of multiple vs. single dose animal derived surfactant extract in infants with established respiratory distress syndrome. Meta-analysis of these trials suggests a reduction in the risk of pneumothorax (typical relative risk 0.51, 95% CI 0.30, 0.88; typical risk difference-0.09, 95% CI -0.15, -0.02) and a trend towards a reduction in the risk of mortality (typical relative risk 0.63, 95% CI 0.39, 1.02; typical risk difference -0.07, 95% CI -0.14, 00.00).

One study of multiple vs. single dose synthetic surfactant in infants at high risk of respiratory distress syndrome was identified. This study reported a decrease in NEC (relative risk 0.20, 95% CI 0.08, 0.51; risk difference-0.05, 95% CI -0.07, -0.02) and mortality (relative risk 0.56, 95% CI 0.39, 0.81; risk difference-0.07, 95% CI -0.12, -0.03)

No data on long-term neurological or pulmonary outcome were reported.

No complications associated with multiple dose treatment were reported in the identified trials.

Authors' conclusions

In infants with established respiratory distress, a policy of multiple doses of animal derived surfactant extract resulted in greater improvements regarding oxygenation and ventilatory requirements, a decreased risk of pneumothorax and a trend toward improved survival.

In infants at high risk of respiratory distress, a policy of multiple doses of synthetic surfactant resulted in greater improvements regarding oxygenation and ventilatory requirements, a decreased risk of NEC and decreased mortality.

The ability to give multiple doses of surfactant to infants with ongoing respiratory insufficiency leads to improved clinical outcome and appears to be the most effective treatment policy.

摘要

背景

比較多次與單次給予外生性的表面張力素來治療新生兒呼吸窘迫症候群

隨機控制試驗 (Randomized controlled trial) 已經證明了在治療有呼吸窘迫症候群或有其風險之嬰兒,表面張力素療法有其功效。由於表面張力素的不活化性,多劑的表面張力素可能致使預後改善。

目標

為確定多劑外生的表面張力素功效跟單劑外生的表面張力素功效在有呼吸窘迫症候群或有其風險之早產兒的早產死亡率和合併症的比較。

搜尋策略

在1999年的首次搜尋中,搜尋了Oxford Database of Perinatal Trials及Medline (關鍵詞: pulmonary surfactant; 限制: age groups, newborn infant; publication type, clinical trials) ,先前的檢閱包含了以英語發表的交叉參考文獻、摘要、會議及討論會記錄、專家建言、及期刊搜尋。在2008年六月,以首次搜尋的相類似詞更新搜尋以下資料庫Medline, Cinhal及Embase。

選擇標準

對照表面張力素的多劑量策略與單一劑量策略在有呼吸窘迫症候群或有其風險之早產兒的隨機控制試驗會被這篇評論所採用。

資料收集與分析

臨床結果的資料包含了氣胸 (pneumothorax) 、開放性動脈導管 (patent ductus arteriosus) 、壞死性腸炎 (NEC, necrotizing enterocolitis) 、腦室內出血 (intraventricular hemorrhage) (所有的腦室內出血及嚴重的腦室內出血) 、肺支氣管發育不全 (bronchopulmonary dysplasia) 、早產兒視網膜病變 (retinopathy of prematurity) 、及死亡率被這兩位評論家 (R. Soll; E. ek) 所摘錄。更新的額外資料搜索肺出血 (pulmonary hemorrhage) ,周腦室白質軟化 (periventricular leukomalacia) ,神經發展追蹤,肺部疾病因素導致再住院及反應性呼吸道疾病。資料分析根據Cochrane Neonatal Review Group的標準。

主要結論

三個試驗被鑑定為吻合研究標準。兩個研究為動物衍生表面張力素在已確立有呼吸窘迫症候群的嬰兒之多劑與單劑比較的隨機控制試驗。統計分析這些試驗顯示降低了氣胸的風險 (typical relative risk 0.51, 95% CI 0.30, 0.88; typical risk difference −0.09,95% CI −0.15, −0.02) 及有降低死亡率的趨勢 (typical relative risk 0.63, 95% CI 0.39, 1.02; typical risk difference −0.07, 95% CI −0.14, 00.00) 。一個多劑與單劑的合成表面張力素在有呼吸窘迫症候群高風險的嬰兒之比較的研究被搜尋到。這項研究報告了壞死性腸炎發生率降低 (relative risk 0.20, 95% CI 0.08, 0.51; risk difference −0.05,95% CI −0.07, −0.02) 及死亡率降低 (relative risk 0.56, 95% CI 0.39, 0.81; risk difference −0.07, 95% CI −0.12, −0.03) 。沒有長期神經或肺部的癒後的資料被發表。在這些試驗中,沒有關於多劑療法的合併症被報告。

作者結論

多劑動物衍生表面張力素的策略在確立有呼吸窘迫的嬰兒身上產生顯著改善氧合與呼吸器需求的結果,降低氣胸的風險以及改善存活率的趨勢。多劑合成表面張力素的策略在有呼吸窘迫高風險的嬰兒身上產生顯著改善氧合與呼吸器需求的結果,降低壞死性腸炎的風險以及降低死亡率。給予多劑表面張力素予持續進展呼吸功能不足的嬰兒可使臨床結果得到改善且似乎是最有效的治療策略。

翻譯人

本摘要由馬偕醫院林佳瑩翻譯。

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

總結

多劑表面張力素比單劑表面張力素帶來較多的好處。表面張力素對嬰兒的正常肺功能是必要的。呼吸窘迫症候群導因於表面張力素的缺乏或功能異常。許多種表面張力素的製劑 (合成的或動物衍生的) 已經被製造並且被用於有呼吸窘迫症候群或有其風險之嬰兒。這篇試驗的檢閱發現多劑比單劑更能改善嬰兒的癒後。多劑降低了呼吸器的需求。在有呼吸窘迫的嬰兒身上使用動物衍生表面張力素的試驗,多劑療法降低肺合併症的風險並且也有降低死亡風險的趨勢。在有呼吸窘迫高風險的嬰兒身上,多劑合成表面張力素的策略導致關於氧合與呼吸器需求較大的改善,降低腸道傷害(壞死性腸炎)的風險以及降低死亡率。

Plain language summary

Multiple vs. single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome

Multiple doses of surfactant have more benefit than a single dose.

Surfactant is essential to normal lung function in babies. Respiratory distress syndrome (RDS) is caused by a lack of, or dysfunction in, surfactant. A variety of surfactants (ranging for synthetic to animal derived) have been manufactured and are given to babies at risk for or having RDS. This review of trials found that multiple doses, rather than a single dose, further improved babies' outcomes. Multiple doses decreased the need for mechanical ventilation (machine-assisted breathing). In trials using animal derived surfactant in babies with RDS, multiple dose treatment lowered the risk of lung complications and there was a trend towards lowering the risk of death as well. In infants at high risk of respiratory distress, a policy of multiple doses of synthetic surfactant resulted in greater improvements regarding oxygenation and ventilatory requirements, a decreased risk of intestinal injury (necrotizing enterocolitis) and decreased mortality.