Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome

  • Review
  • Intervention




Both prophylactic and early surfactant replacement therapy reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS) compared with later selective surfactant administration. However, continued post-surfactant intubation and ventilation are risk factors for bronchopulmonary dysplasia (BPD). The purpose of this review was to compare outcomes between two strategies of surfactant administration in infants with RDS; prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation.


To compare two treatment strategies in preterm infants with or at risk for RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation vs. later selective surfactant administration, continued mechanical ventilation, and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (who receive surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (who receive prophylactic surfactant administration within 15 minutes after birth).

Search methods

Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2006), CINAHL (1982 to December Week 2, 2006), EMBASE (1980 - December 2006), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006), Pediatric Research (1990 - 2006), abstracts, expert informants and hand searching. No language restrictions were applied.

Selection criteria

Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation vs. selective surfactant administration continued mechanical ventilation, and extubation from low respiratory support.

Data collection and analysis

Data were sought regarding effects on the incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, duration of oxygen therapy, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Stratified analysis was performed according to inspired oxygen threshold for early intubation and surfactant administration in the treatment group: inspired oxygen within lower (FiO2 < 0.45) or higher (FiO2 > 0.45) range at study entry. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables.

Main results

Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2 < 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13].

Authors' conclusions

Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2 < 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2 < 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.




針對患有呼吸窘迫症候群且使用呼吸器之嬰兒,給予預防性或早期的表面張力素補充療法皆能比晚期而選擇性的給予表面張力素減少死亡率和肺併發症。但持續的在使用表面張力素後插管並使用呼吸器會增加支氣管肺發育不全(bronchopulmonary dysplasia)之風險。此回顧文章的目的在比較兩種不同給予表面張力素之方法對患有呼吸窘迫症候群之嬰兒之預後:預防性或早期的表面張力素治療後立即拔管或晚期而選擇性的給予表面張力素後持續使用呼吸器。


比較兩種不同方法治療已有或高危險發生呼吸窘迫症候群之早產兒:早期給予表面張力素使用短暫的呼吸器(小於1小時)後即拔管,或晚期選擇性的給予表面張力素後持續使用呼吸器在呼吸器設定條件很低時才拔管。兩群接受早期表面張力素的嬰兒為研究對象:一組為自發性呼吸的嬰兒具有呼吸窘迫症候群徵象(在呼吸窘迫症候群演變為呼吸衰竭而需插管前即給予表面張力素治療),一組為呼吸窘迫症候群之高危險群(在出生後15 分鐘內及預防性的給予表面張力素)。


搜索Oxford Database of Perinatal Trials、MEDLINE (1966  December 2006)、CINAHL (1982 to December Week 2,2006)、EMBASE (1980  December 2006)、Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006)、Pediatric Research (1990 – 2006)、摘要、專家意見及人工搜尋,無語言限制。




收集有關人工呼吸器使用的發生率(在給予表面張力素後1小時持續使用或開始使用呼吸器)、肺支氣管發育不良、慢性肺疾病、死亡的發生率、使用人工呼吸器的時間、住院的時間、使用氧氣的時間、使用呼吸支持(包括連續式正壓呼吸輔助(CPAP)和鼻導管)的時間、使用表面張力素的病人數、每一病人使用表面張力素的劑量數、肺氣漏(包括肺間質氣腫、氣胸)、需治療之開放性動脈導管、肺出血及其它早產兒併發症之資料。治療族群依據在早期插管並使用表面張力素時之氧氣使用之條件加以分層分析:分為較低(給氧濃度(FiO2)< 0.45)或較高(給氧濃度>0.45)之給氧濃度。治療效果類別變項是以相對風險(relative risk (RR))及風險差(risk difference (RD))來表示,連續變項以加權平均差(weighted mean difference (WMD))來表示。


共6篇隨機對照試驗達到本回顧文章之篩選標準而被納入,在有呼吸窘迫症候群症狀的嬰兒,早期插管並給予表面張力素治療後即拔管改用經鼻連續式正壓呼吸輔助(NCPAP)比晚期選擇性的給予表面張力素能減少人工呼吸器的使用[typical RR 0.67, 95% CI 0.57, 0.79]、肺氣漏[typical RR 0.52, 95% CI 0.28, 0.96]及肺支氣管發育不良[typical RR 0.51, 95% CI 0.26, 0.99]之機率。早期使用表面張力素之族群和晚期選擇性的給予表面張力素之族群相比有較高之比率使用表面張力素[typical RR 1.62, 95% CI 1.41, 1.86],每一病人使用表面張力素的劑量數在早期使用表面張力素之族群顯著較高[WMD 0.57 劑/每一病人, 95% CI 0.44, 0.69]。在依據給氧濃度(FIO2)之分層分析,較低之治療門檻(給氧濃度< 0.45)有較低之肺氣漏[typical RR 0.46,95% CI 0.23, 0.93]和肺支氣管發育不良[typical RR 0.43, 95% CI 0.20, 0.92]之機率。較高之治療門檻(給氧濃度>0.45)有較高的需治療之開放性動脈導管[typical RR 2.15, 95% CI 1.09, 4.13]的比率。





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


呼吸窘迫症候群是造成早產兒疾病或死亡的最重要主因,較常用來治療呼吸窘迫症候群的方法包括氧氣和經鼻連續式正壓呼吸輔助(NCPAP),對於嚴重的呼吸窘迫症候群會在使用人工呼吸器的同時給予表面張力素治療。雖然給予表面張力素治療呼吸窘迫症候群群能改善臨床預後,但人工呼吸器的使用會造成肺部傷害並可能導致慢性肺疾病(在週數36週時需要氧氣治療)和肺支氣管發育不良(在出生後第28天時需要氧氣治療)。重要的問題是早期給予表面張力素併計劃性的短暫使用呼吸器後立即拔管(改成使用NCPAP)或在晚期呼吸窘迫症候群惡化造成呼吸功能不足(respiratory insufficiency)而需使用呼吸器時才選擇性的給予表面張力素何者較好?本回顧文章之作者挑選出6 篇於1994年到2006年發表符合本回顧篩選條件之隨機試驗文章,發現對患呼吸窘迫症候群之嬰兒早期給予表面張力素後立即拔管改成使用NCPAP和晚期選擇性的給予表面張力素並持續使用呼吸器相比能顯著的減少呼吸器之使用、肺氣漏(如氣胸等)和肺支氣管發育不良發生之機率。此結果顯示較低之治療門檻(給氧濃度小於0.45)和較高之治療門檻(給氧濃度大於0.45)相比有較多好處。早期給予表面張力素之治療策略會造成更多嬰兒需要使用表面張力素,同時也有更多嬰兒暴露在氣管插管和表面張力素治療之可能的風險下,雖然在本篇回顧文章並無發現使用表面張力素所發生的併發症,早期給予表面張力素之治療策略似乎會增加嬰兒患開放性動脈導管的機率。有兩篇試驗因在計劃性的期中分析時發現使用呼吸器已達顯著差別,而在達成預期收案個數前即終止試驗,另有兩篇試驗收案過慢造成病人數較預期少。

Plain language summary

Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome

Respiratory distress syndrome (RDS) is the single most important cause of illness and death in preterm infants. Common treatments for RDS include supplemental oxygen and nasal continuous positive airway pressure (NCPAP). For severe RDS, surfactant administration during mechanical ventilation is used. Although treating RDS with surfactant improves clinical outcomes, mechanical ventilation can cause lung injury in preterm infants with RDS and contribute to the development of chronic lung disease (oxygen requirements at 36 weeks) and bronchopulmonary dysplasia (requirement for supplementary oxygen at 28 days, BPD). An important question is whether giving early surfactant with planned brief mechanical ventilation followed by prompt extubation (to NCPAP) is better than selectively giving surfactant when RDS has worsened causing respiratory insufficiency necessitating mechanical ventilation. The review authors identified six randomized trials reported between 1994 and 2006 that met the selection criteria for this review. A strategy of early surfactant administration with extubation to NCPAP was associated with significant reductions in the need for mechanical ventilation, fewer air leak syndromes (such as pneumothorax) and lower incidence of BPD compared with a strategy of later selective surfactant administration and continued mechanical ventilation in infants with RDS. The findings suggest that a lower treatment threshold (oxygen requirement < 0.45) confers greater advantage than does a higher treatment threshold (oxygen requirement > 0.45).

An early surfactant therapy strategy results in a greater number of infants receiving surfactant and so more infants being exposed to the potential risks of intubation and surfactant administration. Although no complications of surfactant administration were reported in the studies reviewed, infants treated with an early surfactant therapy strategy tended to have a higher prevalence of patent ductus arteriosus (PDA). Two trials were terminated prior to achieving the targeted enrollment when the need for mechanical ventilation was found to be significantly different between groups at a scheduled interim analysis. Two other trials experienced slow enrollment leading to reduced numbers.