早产儿出生时和生后早期呼吸支持指南解读

对于存在呼吸窘迫综合征(RDS)的早产儿,现有指南多推荐在出生时或出生后不久进行气管插管和预防性使用肺表面活性物质(PS)。然而,近期发表的几篇多中心随机对照研究(RCT)认为超早产儿生后早期使用持续气道正压通气(CPAP),必要时选择性使用PS的方法较预防性使用PS,可减少肺支气管发育不良(BPD)的发生率及病死率。最近,美国儿科学会制定新的指南,推荐这种新的早产儿生后早期呼吸支持策略。     

肺表面活性物质预防早产儿呼吸窘迫综合征疗效观察

目的 探讨肺表面活性物质(PS)预防早产儿呼吸窘迫综合征(RDS)的疗效。方法2001年3月～2002年6月我院产科出生早产儿22例；胎龄29～32周；体重1050～1720g。将其分为预防组10例，治疗组12例。预防组于生后30min内即从气管插管内滴入PS(Curosurf，120mg)，用药后应用鼻塞持续气道正压(CPAP)辅助呼吸；治疗组于确诊RDS后应用PS，方法同预防组。结果预防组CPAP辅助呼吸时间、鼻管法氧疗时间明显缩短；PaO2、PaCO2、pH与治疗组比较有显著差异；预防组均存活，不用机械通气，无肺出血、支气管肺发育不良等并发症。结论应用PS预防早产儿RDS，可减轻病情，避免机械通气、缩短氧疗时间，减少早期及后期并发症。     

鼻塞双水平正压通气用于呼吸窘迫综合征早产儿拔管的临床研究

目的评价鼻塞双水平正压通气（nBiPAP）作为预防新生儿呼吸窘迫综合征（RDS）撤机失败措施的临床效应。方法采用前瞻性随机对照研究方法,选择2011年1月至2012年6月收入新生儿重症监护病房且临床诊断RDS的≤32周早产儿,经气管插管及呼吸机辅助呼吸并达到撤机标准,且于初次拔管后仍有呼吸困难而需无创通气者56例作为研究对象。研究对象随机分为nBiPAP组（27例）和鼻塞持续正压通气（nCPAP）组（29例）,比较两组改用无创通气前、后的血气分析、无创通气7 d内失败率及各种并发症的发生率。结果拔管后第一次的血气分析,nBiPAP组氧分压[（58.7±6.3）mmHg]高于nCPAP组[（55.1±5.9）mmHg],二氧化碳分压[（46.4±4.9）mm Hg]低于nCPAP组[（49.9±5.0）mmHg],差异均有统计学意义（P<0.05）。nBiPAP组无创通气7 d内的失败率为7.4%,低于nCPAP组的31.0%,差异有统计学意义（P=0.042）。两组并发症发生率差异无统计学意义。结论 nBiPAP作为预防胎龄≤32周合并RDS的早产儿撤机失败的效应优于nCPAP,且安全。     

两种无创呼吸支持治疗极低出生体重儿呼吸窘迫综合征疗效分析

目的 探讨早期应用经鼻间歇正压通气（NIPPV）与加温湿化经鼻导管高流量通气（HHHFNC）治疗极低出生体重呼吸窘迫综合征（RDS）早产儿的临床疗效。方法 89例极低出生体重RDS早产儿依据初始呼吸支持治疗方式随机分为NIPPV组（46例）和HHHFNC组（43例）。分析两组患儿初始治疗失败率、肺表面活性物质（PS）使用率、呼吸支持治疗相关数据及各种并发症的发生率。结果 NIPPV组治疗72 h内气管插管率、PS使用率、有创辅助通气时间、无创辅助通气时间及总用氧时间、严重呼吸暂停发生率、肺炎发生率与HHHFNC组的差异无统计学意义（P > 0.05）;NIPPV组支气管肺发育不良、颅内出血、早产儿视网膜病、坏死性小肠结肠炎、动脉导管未闭、气漏的发生率与HHHFNC组的差异均无统计学意义（P > 0.05）;NIPPV组鼻损伤的发生率高于HHHFNC组（P < 0.05）。结论 对于极低出生体重RDS早产儿的初始呼吸支持治疗,HHHFNC与NIPPV疗效相当,是可供临床选择的另一种安全和有效的无创辅助通气治疗方式。     

双水平正压通气和持续气道正压通气在早产儿呼吸窘迫综合征中应用的比较

目的：对患有新生儿呼吸窘迫综合征（RDS）的早产儿早期使用双水平正压通气（DuoPAP）和经鼻持续气道正压通气（NCPAP）模式在降低有创呼吸支持率和支气管肺发育不良（BPD）发生率方面进行比较分析。方法：该试验为单中心随机对照试验,将胎龄30~35 周患有RDS生后6 h内的早产儿随机分为早期使用DuoPAP组（n=34）和早期使用 NCPAP组（n=33）,若这两种方式不能维持则使用气管内插管、呼吸机辅助呼吸,肺表面活性物质作为急救药物。观察患儿生后24 h、48 h及72 h内的总插管有创呼吸支持率、支气管肺发育不良（BPD）发生率及使用无创呼吸支持后1、12、24、48、72 h 二氧化碳分压（PaCO2）、氧分压（PaO2）及氧合指数（OI）。结果：DuoPAP组48 h内、72 h内总插管有创呼吸支持率明显低于NCPAP组（P0.05）。DuoPAP组OI无创呼吸支持后1、12、24、48、72 h均高于NCPAP组（均P<0.05）。DuoPAP组PaCO2在无创呼吸支持后1、12、24 h明显小于NCPAP组（P<0.05）;DuoPAP组PaO2在无创呼吸支持后1、12 h 明显大于NCPAP组（P<0.05）。结论：早期使用DuoPAP与NCPAP相比,可明显降低RDS患儿插管有创呼吸支持率,值得推广。     

早产儿支气管肺发育不良防治环节中早期呼吸支持的策略

虽然呼吸窘迫综合征( RDS)仍然是导致极早和超早早产儿呼吸衰竭最常见疾病,但由于NICU呼吸技术的进步,其已经不再是死亡的主要病因。伴随着 RDS的发生,支气管肺发育不良( BPD)这一成熟依赖性肺疾病的发生和发展成为现代NICU防治的核心疾病之一。在早期呼吸支持策略环节中有以下共识与建议：(1)最大可能的使具有高风险RDS或RDS的极早和超早早产儿期避免气管插管,接受无创通气(nCPAP);(2)早期选择合适的方式接受肺表面活性物质(PS)治疗;(3)个体化的制定nCPAP或其他无创通气失败的标准,尽早接受PS救治和适宜的有创通气模式;(4)缩短通气时间,应用无创通气方式辅以咖啡因治疗降低拔管失败率。这些临床研究成果仍需要不断在实践中改进与完善,BPD的发生是多因素作用的结果,需要多维度的管理的进步才能真正实现有效的防治。     

早产儿经鼻间歇正压通气的专家共识

经鼻间歇正压通气（nasal intermittent positive pressure ventilation,NIPPV）是在经鼻持续气道正压通气（nasal continuous positive airway pressure,n CPAP）的基础上给予间歇正压的一种呼吸支持模式,由于其具有避免气管插管等无创呼吸支持的优点,在早产儿领域的应用越来越多,已经成为早产儿的重要辅助通气方式[1,2]。     

新生儿无创辅助呼吸支持介绍

随着新生儿微创辅助通气时代的到来及“开肺策略”的提出,新生儿的无创通气技术理念在世界范围内的NICU得到普及。该文复习了近年来新生儿无创通气技术的有关文献并作简要综述。持续气道正压通气（CPAP）主要原理为在呼气末予以压力支持的一种通气模式,又称之为持续扩张压或呼气末正压通气,经过世界范围内多年的临床实践,CPAP已被证实是一种有效的对患有呼吸系统疾病的新生儿实施呼吸支持的辅助通气模式。由于CPAP价格相对便宜,且易于在临床应用,因此更适合于在发展中国家推广。CPAP辅助通气,除可显著地改善患儿机体的氧合外,对有不同程度气道阻塞的患儿,它可以减轻气道塌陷,因此有助于减少患儿呼吸暂停的发生。文献研究表明,对于32周以下的早产儿,早期应用CPAP可减少患儿气管插管机械通气的机率。该文将试图介绍几种不同的CPAP应用装置和几种不同的CPAP应用方法。虽然对于早期应用CPAP是否能够降低新生儿死亡率及患病率目前尚不十分清楚,但临床实践已经表明,与有创通气比较,CPAP对患儿的损伤小,是一种较为舒适的通气模式,早期应用CPAP还可减少肺泡表面活性物质的使用频率。另外,该文还介绍CPAP的应用指征、优点及其局限性,CPAP的衍生模式如经鼻间歇正压辅助通气以及infant flow CPAP装置等。     

改良气管插管-肺表面活性物质-拔管后鼻塞呼吸道正压通气方法治疗早产儿呼吸窘迫综合征的疗效北大核心CSCD

目的 探讨改良INSURE[气管插管-肺表面活性物质（PS）-拔管后鼻塞呼吸道正压通气]方法治疗早产儿呼吸窘迫综合征（RDS）的疗效及并发症.方法 分析2010年1月至2013年2月淮安市妇幼保健院新生儿科INSURE方法治疗的51例RDS早产儿临床资料.按治疗方法不同分为研究组23例（改良INSURE方法即拔管后经鼻间歇正压通气）,对照组28例（传统INSURE方法即拔管后经鼻持续正压通气）,比较2组治疗前及治疗后24h动脉血氧分压[pa（O2）]、二氧化碳分压[pa（CO2）]、动脉氧分压/吸入氧体积分数[pa（O2）/FiO2]、无创通气和氧疗时间、住院时间、并发症、第2剂PS、氨茶碱应用等情况.结果 治疗后24h,研究组pa（O2）、Pa（CO2）、PH、pa（O2）/FiO2均比对照组改善明显（t=2.196、2.702、4.255、3.706、0.000、0.000,P均＜0.05）.研究组无创通气、氧疗和住院时间均明显短于对照组（t=2.638、2.254、2.620,P均＜0.05）.研究组气管插管机械通气比例、需药物关闭的动脉导管开放、第2剂PS及氨茶碱应用均低于对照组（x2=5.123、4.366、5.123、4.791,P均＜0.05）.在气漏、支气管肺发育不良、坏死性小肠结肠炎、Ⅲ～Ⅳ级颅内出血等方面,2组差异均无统计学意义（x2=0.000、0.032、0.000、0.000,P均＞0.05）.结论 改良INSURE方法治疗RDS疗效优于传统INSURE方法,可减少RDS早产儿气管插管机械通气、第2剂PS及氨茶碱的需要,缩短无创通气、氧疗和住院时间.     

肺表面活性物质预防早产儿呼吸窘迫综合征的临床观察及护理

目的探讨肺表面活性物质（PS）预防呼吸窘迫综合征（RDS）的有效性及临床价值。方法对我院2004年5月～2005年5月收治的87例高危早产儿在生后6h内均行气管内一次性滴注预防剂量PS（120mg／kg）。结果87例高危早产儿均痊愈出院，未发生RDS。结论PS预防用药可降低早产儿RDS发生率，减少呼吸机的应用。     

RDS--CPAP or surfactant or both

There is mounting evidence that early continuous positive airway pressure (CPAP) from birth is feasible and safe even in very preterm infants. However, many infants will develop respiratory distress syndrome (RDS) and require surfactant treatment. Combining a non-invasive ventilation approach with a strategy for surfactant administration is important, but questions remain about the optimal timing, mode of delivery and the value of predictive tests for surfactant deficiency. CONCLUSION: Early CPAP in very preterm infants is as safe as routine intubation in the delivery room. However, a strategy for surfactant administration should be part of a non-invasive ventilation approach for those infants at risk of developing significant RDS.     

系统评价胎龄小于32周早产儿预防性经鼻持续气道正压通气的作用

目的 评价早产儿早期应用经鼻持续气道正压通气（NCPAP）预防呼吸窘迫综合征（RDS）,减少呼吸机应用、病死率和并发症的发生。方法 以（prophylactic nasal CPAP OR early nasal CPAP）AND （preterm infants OR low birth weight infants） ,经鼻持续气道正压通气AND（早产儿OR低出生体重儿）为英中文关键词,检索PubMed、EMBASE、Cochrane临床对照试验库、维普中文科技期刊数据库、中国知网和万方数据库,检索时间均从建库至2011年12月,并辅以手工检索。应用RevMan 5.0软件进行Meta分析,根据异质性结果选择相应的效应模型分析;无法进行Meta分析时采用描述性分析。结果 8篇RCT文献进入分析。Meta分析结果显示： NCPAP组未能显著降低早产儿气管插管呼吸机应用率（RR＝-0.09,95%CI：-0.19~0.02,P=0.09）、RDS发生率（RR＝0.81,95%CI：0.59~1.1, P =0.18）和病死率（RR＝0.88,95%CI：0.72~1.09,P=0.25）;NCPAP组能显著减少早产儿肺表面活性物质应用率（RR＝0.72,95%CI：0.64~0.80,P﹤0.000 01）。NCPAP组未能显著减少气管插管呼吸机通气时间（MD= -1.91 d,95%CI：-6.47~4.45 d,P= 0.72）及氧气应用时间(MD=-0.46 d,95%CI：-6.55~5.63 d,P= 0.88）。NCPAP组除增加气胸的发生率外,并未明显增加支气管肺发育不良、颅内出血、早产儿视网膜病、败血症、新生儿坏死性小肠结肠炎和动脉导管未闭等并发症的发生率。结论 目前的证据表明早期应用NCPAP可减少肺表面活性物质应用,但增加了气胸的发生率;未能减少早产儿呼吸机应用、RDS发生率和病死率,未增加除气胸外的其他并发症发生率。     

不同肺表面活性物质治疗新生儿呼吸窘迫综合征疗效比较

目的 比较猪肺表面活性物质与牛肺表面活性物质治疗早产儿呼吸窘迫综合征（RDS）的疗效.方法 选择本院新生儿科2011年1月至2012年6月收治、应用肺表面活性物质和持续气道正压通气（CPAP）的RDS患儿进行回顾性分析,根据用药情况分为猪肺表面活性物质组（固尔苏组）和牛肺表面活性物质组（珂立苏组）,两组诊断RDS后均予以气管插管给药.比较两组应用肺表面活性物质前后血气指标、CPAP时间、氧疗时间、住院时间、并发症及死亡情况.结果 固尔苏组36例,珂立苏组32例,两组患儿应用肺表面活性物质后6h、24 h的PaO2、PaCO2和pH值与用药前相比均明显改善（P＜0.05）,两组间各时间点比较差异无统计学意义（P＞0.05）.固尔苏组应用CPAP时间短于珂立苏组[（98.8±15.2）h比（113.6±13.0）h,P＜0.05].两组患儿用氧时间、住院时间、并发症（颅内出血、肺气漏、呼吸机相关肺炎、支气管肺发育不良、动脉导管未闭、早产儿视网膜病、新生儿坏死性小肠结肠炎）发生率及死亡率差异均无统计学意义（P＞0.05）.结论 猪肺表面活性物质与牛肺表面活性物质治疗早产儿RDS疗效及安全性相似,使用猪肺表面活性物质的患儿CPAP时间缩短,临床上可综合考虑酌情选用.     

Continuous Positive Airway Pressure for Spontaneously Breathing Premature Infants with Respiratory Distress Syndrome

Objective

To analyze the outcome of inborn preterm neonates with respiratory-distress-syndrome(RDS), using the approach of administering nasal-continuous-positive-airway-pressure(CPAP) alone and administering surfactant only if they require mechanical ventilation(MV).

Methods

All preterm neonates diagnosed as RDS from 01-May-2006 to 10-July-2010 were prospectively enrolled for the study at a referral centre in India. Nasal-CPAP alone was administered to all spontaneously breathing neonates. Surfactant was administered in babies <28 wk gestational age if the baby was intubated for resuscitation at birth. For the remaining babies, surfactant was administered if the baby required ventilation for RDS in first 72 h. The primary outcome assessed was survival to discharge.

Results

Of the 83 babies with RDS, 33(39.76%) neonates needed MV of which one baby was transferred due to non-availability of ventilator. Of the remaining 32 babies administered MV, 31 were administered surfactant. Fifty (61.24%) babies were managed with CPAP alone. Overall, 72/82(87.8%) babies managed at the authors’ center survived the neonatal period, and 71/82(86.8%) babies were discharged to home. Among the neonates who were ventilated, 26/32(81.25%) survived the neonatal period, and 25/32(78.12%) were discharged home. Among the babies receiving CPAP, 46/50 (92%) survived and were discharged to home.

Conclusions

Institution of CPAP alone in all spontaneously breathing preterm babies with RDS and administration of surfactant to only those needing MV reduces the need for intubations and surfactant administration without affecting the outcome adversely. Extreme preterms with RDS, however, may be given surfactant if they happen to be intubated for resuscitation at birth.

     

Early surfactant for neonates with mild to moderate respiratory distress syndrome: a multicenter, randomized trial

OBJECTIVE: We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation. STUDY DESIGN: A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight >or=1250 grams, gestational age or=40% for >or=1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation. RESULTS: Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes). CONCLUSIONS: Routine elective intubation for administration of surfactant to preterm infants >or=1250 grams with mild to moderate RDS is not recommended.     

Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome

Aim:  To determine whether early nasal intermittent positive pressure ventilation (NIPPV), in comparison to early continuous positive airway pressure (CPAP), can reduce the need for intubation and mechanical ventilation in preterm neonates with suspected respiratory distress syndrome (RDS).
Methods:  In this stratified open-label randomized controlled trial, neonates (28–34 weeks gestation) with respiratory distress within 6 h of birth and Downe's score ≥ 4 were eligible. Subjects were randomly allocated to 'early-NIPPV' or 'early-CPAP' after stratifying for gestation (28–30 weeks, 31–34 weeks) and surfactant use. Primary outcome was failure of the allocated mode within 48 h.
Results:  Seventy-six neonates were enrolled (37 in 'early-NIPPV' and 39 in 'early-CPAP' groups). Failure rate was less with 'early-NIPPV' versus 'early-CPAP'[13.5% vs. 35.9%, respectively, RR 0.38 (95% CI 0.15–0.89), p = 0.024]. Similarly, need for intubation and mechanical ventilation by 7 days (18.9% vs. 41%, p = 0.036) was less with NIPPV. Failure rate with NIPPV was less in the subgroups of subjects born at 28–30 weeks (p = 0.023) and who did not receive surfactant (p = 0.018).
Conclusion:  Among preterm infants with suspected RDS, early use of NIPPV reduces the need for intubation and mechanical ventilation compared to CPAP.     

双水平正压通气和经鼻持续气道正压通气在早产儿呼吸窘迫综合征撤机后应用的比较

目的探讨重度新生儿呼吸窘迫综合征（RDS）早产儿撤机后使用双水平正压通气（DuoPAP）和持续气道正压通气（NCPAP）模式相比,是否可以降低撤机失败率。方法选择2012年1—12月入住本院早产儿重症监护病房、胎龄29—34周、需要有创呼吸、并且在生后4周内撤机的重度RDS早产儿,撤机后随机分为DuoPAP组和NCPAP组,若应用这两种方式不能维持则再次气管插管呼吸机辅助呼吸。主要观察指标为撤机失败率、失败原因以及使用无创呼吸支持后1、12、24、48、72h二氧化碳分压（PaCO2）、氧分压（PaO2）和氧合指数（OI）。结果共入选69例RDS早产儿,DuoPAP组35例,NCPAP组34例。DuoPAP组与NCPA组比较,撤机失败率降低（11．4％比35．3％）;12、24hOI升高[12h：（228．1±44．4）比（204．2±44．6）,24h：（254．6±39．5）比（230．4±44．4）],PaCO2（mmHg）降低[12h：（35．1±8．3）比（40．5士8．9）,24h：（36．8±8．4）比（42．1±8．8）];12hPaO2（mmHg）升高[（89．0±12．5）比（74．5±13．8）],P均〈0．05。两组总用氧时间、有创呼吸支持时间、气胸、坏死性小肠结肠炎和重度脑室内出血发生率差异均无统计学意义（P〉0．05）。结论与使用NCPAP相比,撤机后使用DuoPAP可明显降低重度RDS患儿撤机失败率,值得推广。     

The role of surfactant and non-invasive mechanical ventilation in early management of respiratory distress syndrome in premature infants

Background

Surfactant replacement therapy has been used for few decades for the treatment of respiratory distress syndrome (RDS) and has significantly improved morbidity and mortality in premature infants. Non-invasive respiratory support has recently emerged as a strategy in the early management of RDS. In this review, we discuss the different strategies of early management of RDS.

Data sources

A literature search of PubMed database was conducted to review the subject. The quality of evidence of key clinical studies was graded according to a modified grading system of the international GRADE group.

Results

Continuous positive airway pressure (CPAP) with selective surfactant is a safe alternative to routine intubation, surfactant and mechanical ventilation in preterm infants with spontaneous breathing, and such an approach has been associated with decreased risk of death and bronchopulmonary dysplasia. There is a risk of pneumothorax when using a high pressure of CPAP (≥8 cm of H₂O), a high partial pressure of carbon dioxide (PCO₂ >75 mm of Hg), and a high fraction of inspired oxygen (FiO₂ >0.6) as a threshold for intubation while on CPAP.

Conclusion

Not all preterm infants need surfactant treatment, and non-invasive respiratory support is a safe and effective approach.     

CPAP review

Continuous positive airway pressure (CPAP) is widely used in neonatal units both as a primary mode of respiratory support and following extubation from mechanical ventilation. In this review, the evidence for CPAP use particularly in prematurely born infants is considered. Studies comparing methods of CPAP generation have yielded conflicting results, but meta-analysis of randomised trials has demonstrated that delivering CPAP via short nasal prongs is most effective in preventing re-intubation. At present, there is insufficient evidence to establish the safety or efficacy of high flow nasal cannulae for prematurely born infants. Observational studies highlighted that early CPAP use rather than intubation and ventilation was associated with a lower incidence of bronchopulmonary dysplasia (BPD), but this has not been confirmed in three large randomised trials. Meta-analysis of the results of randomised trials has demonstrated that use of CPAP reduces extubation failure, particularly if a CPAP level of 5?cm H2O or more is used. Nasal injury can occur and is related to the length of time CPAP is used; weaning CPAP by pressure rather than by "time-cycling" reduces the weaning time and may reduce BPD. In conclusion, further studies are required to identify the optimum mode of CPAP generation and it is important that prematurely born infants are weaned from CPAP as soon as possible.