Survey of neonatal respiratory support strategies

AIM: To survey current practice regarding neonatal respiratory support strategies to determine whether it reflected evidence from randomised trials. METHODS: A questionnaire (in Supplementary Material online) survey of all U.K. neonatal units was undertaken to determine what modes of ventilation, types of endotracheal tube, lung function monitoring and oxygen saturation levels were used. RESULTS: There was an 80% response rate. Most (73%) units used in prematurely born infants (in the first 24 h) the intermittent positive pressure ventilation, and other respiratory modes included: CPAP (2%), triggered ventilation with or without volume guarantee (22%) and high frequency oscillation (2%). Only 15% of units used assist control mode for weaning; the preferred weaning mode was synchronous intermittent mandatory ventilation (73%). Few units used shouldered endotracheal tubes (3%) or lung function measurements (25%) to aid choice of ventilator settings. Oxygen saturation levels from 80% to 98% were used, levels greater or equal to 95% were used by 11% of units for infants with acute respiratory disease but by 34% of units for BPD infants (p < 0.001). CONCLUSION: Many practitioners do not base their choice of neonatal respiratory support strategies on the results of large randomised trials; more effective methods are required to ensure evidence-based practice.     

Optimal strategies for newborn ventilation--a synthesis of the evidence

A variety of ventilation modes are available for the newborn. Although, there have been randomised trials assessing certain modes, these have generally only included prematurely born infants with RDS or infants with severe respiratory failure. Meta-analysis of the results of those trials has demonstrated that neither patient triggered nor high frequency oscillatory ventilation is advantageous for the prematurely born infant with RDS, but extracorporeal membrane oxygenation increases survival in infants with severe respiratory failure. Appropriately designed studies are required to determine the role of newer ventilation modes and whether forms of respiratory support avoiding intubation are less injurious to the lungs. Research should also focus on infants with other respiratory disorders, particularly BPD. Prior to further randomised trials being undertaken, it is essential that the optimum method of applying each ventilator mode is identified and it is clearly understood whether differences in ventilator/oscillator performance influence outcome.     

两种不同通气模式在呼吸窘迫综合征早产儿撤机阶段的应用对比

目的 比较同步间歇指令通气（SIMV）与压力支持加容量保证通气（PSV+VG）两种模式在呼吸窘迫综合征（RDS）早产儿撤机阶段的应用效果。方法 选择2016年3月至2017年5月入住新生儿重症监护室、胎龄小于32周,且需要机械通气的40例RDS早产儿作为研究对象。40例患儿从进入撤机阶段开始被随机分为SIMV组和PSV+VG组,每组各20例。比较两组间呼吸机参数、动脉血气、撤机时间（从进入撤机阶段到拔管时间）、拔管后经鼻持续气道正压通气（NCPAP）使用时间以及拔管失败率;比较两组病死率及气胸、动脉导管未闭（PDA）、支气管肺发育不良（BPD）的发生率。结果 与SIMV组比较,PSV+VG组的平均气道压、撤机时间、撤机后NCPAP使用时间、拔管失败率均明显降低,差异有统计学意义（P < 0.05）。而两组在动脉血气、病死率及气胸、PDA、BPD发生率等方面的比较差异均无统计学意义（P > 0.05）。结论 在RDS早产儿撤机阶段,PSV+VG模式可能是一种相对安全有效的通气方式,但仍需要大样本、多中心的临床试验来证实。     

Review of use of postnatal corticosteroids in evolving or established bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a condition that affects a significant proportion of infants born prematurely. Whilst there have been advances in many aspects of neonatal respiratory care the rates of BPD remain relatively static. Much effort has been put into exploring the role of corticosteroids in potentially reducing inflammation in the developing lung; however, research has been hindered by concerns regarding adverse side–effect profiles and difficulties recruiting adequate numbers to power the results. Currently, two strategies are gaining popularity: low-dose dexamethasone after 7 days of age to facilitate ventilator weaning and prophylactic physiological hydrocortisone use from the first day of life. However, use in practice is limited whilst awaiting full-powered randomised trials. This article briefly discusses the evidence for each approach.     

Clinical practice

The most important goal of introducing noninvasive ventilation (NIV) has been to decrease the need for intubation and, therefore, mechanical ventilation in newborns. As a result, this technique may reduce the incidence of bronchopulmonary dysplasia (BPD). In addition to nasal CPAP, improvements in sensors and flow delivery systems have resulted in the introduction of a variety of other types of NIV. For the optimal application of these novelties, a thorough physiological knowledge of mechanics of the respiratory system is necessary. In this overview, the modern insights of noninvasive respiratory therapy in newborns are discussed. These aspects include respiratory support in the delivery room; conventional and modern nCPAP; humidified, heated, and high-flow nasal cannula ventilation; and nasal intermittent positive pressure ventilation. Finally, an algorithm is presented describing common practice in taking care of respiratory distress in prematurely born infants.     

A randomised controlled trial of two methods of delivering nasal continuous positive airway pressure after extubation to infants weighing less than 1000 g: binasal (Hudson) versus single nasal prongs

OBJECTIVES: Primary: to determine whether nasal continuous positive airway pressure (CPAP) delivered through binasal prongs results in a greater proportion of extremely low birthweight infants being successfully extubated, after a period of intermittent positive pressure ventilation, than nasal CPAP delivered by a single nasal prong. Secondary: to evaluate the effect of mode of delivery of nasal CPAP after extubation on the need for endotracheal reintubation, weight gain, rates of feeding intolerance, sepsis, suspected sepsis, cranial ultrasound abnormalities, retinopathy of prematurity, chronic lung disease, and the duration of assisted ventilation and care in the tertiary neonatal unit. DESIGN AND SETTING: Randomised, controlled, clinical trial conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, Australia. PATIENTS: Infants of birth weight less than 1000 g, ventilated, requiring < 50% oxygen and ventilator rate less than or equal to 20/minute, and considered by the clinical management team to be ready for extubation. INTERVENTION: Infants were randomly allocated to receive nasal CPAP delivered through binasal (Hudson) prongs or a single nasal prong. PRIMARY OUTCOME MEASURE: Failure of extubation as defined by the following criteria: (a) apnoea (more than one episode/hour over a six hour period or one episode requiring bag and mask ventilation); (b) absolute increase in oxygen requirement greater than 15% above that required before extubation; (c) respiratory acidosis (pH < 7.25 with PCO(2) > 6.67 kPa). RESULTS: Ten of the 41 (24%) infants randomised to binasal prongs reached predetermined failure criteria compared with 26 of the 46 (57%) infants randomised to a single nasal prong (p = 0.005). Four of 17 (24%) infants of birth weight less than 800 g extubated to binasal prongs reached failure criteria compared with 14 of 16 (88%) extubated to a single nasal prong (p < 0.001). There were no significant differences in any of the secondary outcomes. CONCLUSIONS: For extremely low birthweight infants ventilated using an endotracheal tube, nasal CPAP delivered through binasal (Hudson) prongs is more effective in preventing failure of extubation than that delivered through a single nasal prong.     

Neonatal ventilation strategies and long-term respiratory outcomes

Long-term respiratory morbidity is common, particularly in those born very prematurely and who have developed bronchopulmonary dysplasia (BPD), but it does occur in those without BPD and in infants born at term. A variety of neonatal strategies have been developed, all with short-term advantages, but meta-analyses of randomized controlled trials (RCTs) have demonstrated that only volume-targeted ventilation and prophylactic high-frequency oscillatory ventilation (HFOV) may reduce BPD. Few RCTs have incorporated long-term follow-up, but one has demonstrated that prophylactic HFOV improves respiratory and functional outcomes at school age, despite not reducing BPD. Results from other neonatal interventions have demonstrated that any impact on BPD may not translate into changes in long-term outcomes. All future neonatal ventilation RCTs should have long-term outcomes rather than BPD as their primary outcome if they are to impact on clinical practice.     

Current methods of non-invasive ventilatory support for neonates

Non-invasive ventilatory support can reduce the adverse effects associated with intubation and mechanical ventilation, such as bronchopulmonary dysplasia, sepsis, and trauma to the upper airways. In the last 4 decades, nasal continuous positive airway pressure (CPAP) has been used to wean preterm infants off mechanical ventilation and, more recently, as a primary mode of respiratory support for preterm infants with respiratory insufficiency. Moreover, new methods of respiratory support have been developed, and the devices used to provide non-invasive ventilation (NIV) have improved technically. Use of NIV is increasing, and a variety of equipment is available in different clinical settings. There is evidence that NIV improves gas exchange and reduces extubation failure after mechanical ventilation in infants. However, more research is needed to identify the most suitable devices for particular conditions; the NIV settings that should be used; and whether to employ synchronized or non-synchronized NIV. Furthermore, the optimal treatment strategy and the best time for initiation of NIV remain to be identified. This article provides an overview of the use of non-invasive ventilation (NIV) in newborn infants, and the clinical applications of NIV.     

Does nasal CPAP reduce bronchopulmonary dysplasia (BPD)?

Abstract Early nasal continuous positive airway pressure (nCPAP) or early surfactant therapy with early extubation onto nCPAP rather than continued mechanical ventilation has been adopted by many centres, particularly in Scandinavia, as part of the treatment of newborns with respiratory distress syndrome. It has been suggested that bronchopulmonary dysplasia is less of a problem in centres adopting such a policy. Results from randomized trials suggest prophylactic or early nCPAP may reduce bronchopulmonary dysplasia (BPD), but further studies are required to determine the relative contributions of an early lung recruitment policy, early surfactant administration and nCPAP in reducing BPD. In addition, the optimum method of generating and delivering CPAP needs to be determined. Conclusion: The efficacy of nCPAP in improving long-term respiratory outcomes needs to be compared with the newer ventilator techniques with the optimum and timing of delivery of surfactant administration.     

Patient-triggered ventilation

During patient triggered ventilation, the infant's inspiratory efforts should occur synchronously with ventilator inflations. Such an optimal interaction, however, is dependent on the performance of the triggering device and the ventilator and the infant's lung function. Triggered ventilation (assist control, A/C), synchronous intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV), volume targeted ventilation (VTV) with A/C, SIMV, PSV or proportional assist ventilation (PAV) can be delivered via the endotracheal tube or via nasal prongs. Meta-analysis of randomised trials demonstrated that the only advantage of A/C/SIMV over non-triggered positive pressure ventilation was a shorter duration of ventilation, in particular there was no significant effect on the incidence of chronic lung disease. The reduction in ventilation duration, however, was only seen if triggered ventilation is started in the recovery stage rather than in the acute phase of respiratory distress syndrome. Results from small randomised trials have suggested that A/C rather than SIMV is a better weaning mode, as reduction of the SIMV rate below 20 breaths per minute increases the work of breathing. Other small trials have highlighted triggered ventilation delivered by nasal prongs may reduce extubation failure rate. Physiological studies have demonstrated some advantages of PSV with and without VTV and PAV, whether these translate into improvements in long term clinical outcomes remains to be tested in appropriately designed randomised trials.     

What is new in ventilation strategies for the neonate?

A large number of ventilation strategies are now available for the neonate. This review has focused on new information, that is, studies published since 2000 and the implication of their results for current clinical practice. Meta-analysis of randomised trials has demonstrated that assist control and synchronous intermittent mandatory ventilation (SIMV) shortens the duration of ventilation only if started in the recovery rather than the early stage of respiratory disease. A recent randomised trial demonstrated pressure-regulated volume control ventilation may also have no advantages if started early. Weaning by SIMV with pressure support is better (reducing oxygen dependency) than SIMV alone. Meta-analysis of volume-targeted ventilation demonstrated significant reductions in the duration of ventilation and pneumothorax, but the trials were small and of different designs. Volume guarantee may provide more consistent blood gas control. The level of volume targeting appears to be crucial to the success of this technique. Meta-analysis of randomised trials of prophylactic high-frequency oscillation trials has shown a modest reduction in bronchopulmonary dysplasia. Randomised trials have failed to confirm the advantages of nasal continuous positive airway pressure (NCPAP) seen in various non-randomised studies; however, the randomised trials reported to date have been small. Inhaled nitric oxide (NO) does not improve the outcome of prematurely born infants with severe respiratory failure, but early low-dose prolonged iNO appears to have benefits that merit further testing. More randomised trials with long-term outcomes are required to identify the optimal ventilation strategy(ies) for the neonate. Source of funding and grants: Atul Sharma is supported by the WellChild Trust.     

Difficult extubation in low birthweight infants

Randomised trials have demonstrated that ventilation techniques which support every spontaneous breath are the most efficacious weaning modes. Nasal continuous positive airway pressure after extubation reduces the likelihood of incidents leading to the need for reintubation in very low birthweight infants; further work is needed to determine if there are advantages of particular delivery techniques. Both methylxanthines and dexamethasone facilitate weaning and extubation; the efficacy of low-dose dexamethasone merits further investigation. Assessments of the efficacy of respiratory efforts and hence the balance of respiratory drive, muscle performance and respiratory load appear to best predict weaning and extubation success. Essential to the success of weaning and extubation are dedicated staff, whether this will be assisted by computerised decision-making tools requires testing. The above approaches are not mutually exclusive and those indicated by this review as appropriately evidence based should be considered by practitioners for current use to reduce difficult/unsuccessful extubation.     

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。     

Elective use of nasal continuous positive airways pressure following extubation of preterm infants

The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24–34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required re-intubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43–0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68–1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia. Conclusion Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support. Received: 12 August 1999 / Accepted: 15 December 1999     

早产儿呼吸窘迫综合征经鼻间歇正压通气治疗的Meta分析

目的 评价经鼻间歇正压通气(nasal intermittent positive pressure ventilation,NIPPV)治疗早产儿呼吸窘迫综合征(respiratory distress syndrome,RDS)的临床疗效.方法 2008年1月至6月,检索PubMed、荷兰医学文摘(Embase)、OVID全文数据库、Cochrane图书馆、中国学术期刊网全文数据库(CNKI)、中国牛物医学文献数据库(CBMdisc),收集NIPPV治疗早产儿RDS的临床试验,进行质量分析,并对符合纳入标准的研究应用Revman4.2软件进行Meta分析.结果 纳入随机对照研究5篇,共284例RDS早产儿,其中在撤除气管插管呼吸机后阶段应用NIPPV与鼻塞持续正压通气(nasal continuous positive airway pressure,NCPAP)的疗效比较共3篇,Meta分析显示NIPPV组拔管失败率低于NCPAP组(8.34%vs 40.79%),差异有统计学意义[RR 0.21(95%CI:0.10～0.45;P<0.001)];3篇研究中2篇进行了支气管肺发育不良(bronchopulmonary dysplasia,BPD)的分析,Meta分析显示NIPPV组BPD患病率较低(39.34%vs 54.39%),但差异无统计学意义[RR 0.73(95%CI:0.49～1.07;P=0.11)];以NIPPV作为初始通气模式2篇,其中与气管插管常规通气(conventional ventilation,cv)模式比较1篇,NIPPV组比CV组BPD患病率低(10%vs 33.33%,P=0.04);与NCPAP比较1篇,NIPPV组比NCPAP组BPD患病率低(2.33%vs 17.07%,P=0.03).结论 NIPPV作为初始通气模式治疗早产儿RDS是可行的,NIPPV组具有较低的BPD患病率.在气管插管呼吸机拔管后阶段应用NIPPV可降低拔管失败率.     

早产儿呼吸窘迫综合征的呼吸支持策略及研究进展

新生儿呼吸窘迫综合征（respiratory distress syndrome,RDS）多见于早产儿,胎龄越小,发病率越高。近年的大规模随机对照研究突出了产房内开始的持续气道正压通气（continuous positive airway pressure,CPAP）在RDS防治中的重要作用,对于生后有自主呼吸的早产儿,产房内应用CPAP优于气管插管,而顶防性应用肺表面活性物质（pulmonary surfactant,PS）不再具有优势。2013版欧洲新生儿RDS防治指南推荐有患RDS风险的早产儿生后均应立即接受CPAP支持,初设呼气末正压至少6cmH2O（1cmn20=0．098kPa）;对于患RDS的早产儿,最理想的处理是生后CPAP以及早期解救性PS应用。而需要气管插管的早产儿应尽早接受PS替代治疗。不能耐受CPAP的患儿更换通气模式为无创正压通气可能降低拔管失败率。目前有多种策略来缩短机械通气时间并增加无创通气的成功率。患RDS的极早产儿应常规接受咖啡因治疗以提高撤机成功率,并降低支气管肺发育不良的发生率。生后1～2周后仍不能脱离呼吸机者,需接受小剂量递减地塞米松治疗,但应避免生后1周内应用地塞米松以及较大剂量应用。     

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。     

Neonatal nasal intermittent positive pressure ventilation: what do we know in 2007?

Although neonatal nasal intermittent positive pressure ventilation (NIPPV) is widely used today, its place in neonatal respiratory support is yet to be fully defined. Current evidence indicates that NIPPV after extubation of very premature infants reduces the rate of reintubation. However, much is still not known about NIPPV including its mechanisms of action. It may improve pulmonary mechanisms, tidal volume and minute ventilation but more studies are required to confirm these findings. There is some evidence that NIPPV marginally improves gas exchange. More research is needed to establish which device is best, what settings to use or whether to use synchronised rather than non-synchronised NIPPV, and about the way to wean NIPPV. Future studies should enrol sufficient infants to detect uncommon serious complications and include long-term follow up to determine important neurodevelopment and pulmonary outcomes.     

Nasal CPAP has become an indispensable part of the primary treatment of newborns with respiratory distress syndrome

Prenatal steroids, early nasal CPAP combined with early surfactant treatment followed by extubation to nasal CPAP, and if necessary mechanical ventilation is a very effective treatment of respiratory distress syndrome. This treatment package is part of the 'Scandinavian model' for treatment of very-low-birthweight infants which also comprises gentle ventilation at birth; minimal handling; 'neonatal individualized development care and assessment program'; high priority of breast feeding; and use of kangaroo method and which facilitates observation and nursing of sick premature infants and optimizes the possibility for early mother–child contact.
The incidence of bronchopulmonary dysplasia seems to be less of a problem in centres preferring nasal CPAP as the primary treatment for respiratory distress syndrome.     

无创高频振荡通气与经鼻间歇正压通气作为早产儿拔管后呼吸支持疗效比较的Meta分析

目的 系统评估无创高频振荡通气(non-invasive high-frequency oscillatory ventilation,NHFOV)与经鼻间歇正压通气(nasal intermittent positive pressure ventilation,NIPPV)作为早产儿拔管后呼吸支持的有效性及安全性。方法 全面检索中国知网、万方数据库、中国期刊全文数据库、中国生物医学文献数据库、PubMed、Web of Science、Cochrane Library等数据库中关于NHFOV与NIPPV作为早产儿拔管后呼吸支持的文献,检索时间从建库至2022年8月31日。采用RevMan 5.4软件及Stata 17.0软件进行Meta分析,比较NHFOV组和NIPPV组拔管后72 h内再插管率、改无创辅助通气后6～24 h的二氧化碳分压(partial pressure of carbon dioxide,PCO₂)及支气管肺发育不良(bronchopulmonary dysplasia,BPD)、气漏、鼻损伤、脑室周围白质软化(periventricula...