Prophylactic high-frequency oscillatory ventilation in preterm infants

The role of high-frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Several randomized trials, comparing HFOV and conventional ventilation (CV) have been performed and their results suggest that HFOV may reduce the incidence of chronic lung disease (CLD) in preterm infants. However, the trials have several limitations and it remains unclear whether HFOV might increase intracranial pathology in very prematurely born infants. UKOS, a large, UK-based, multicentre trial was conducted to establish conclusively the role of prophylactic HFOV for the prevention of CLD in infants born prior to 29 wk of gestational age. CONCLUSION: There is still a need to fully evaluate prophylactic HFOV with particular emphasis on both short and long term respiratory and neurological outcomes.     

The role of high frequency oscillatory ventilation in very preterm infants

The role of high frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Animal work demonstrates reduced lung injury with HFOV compared to conventional ventilation (CV), and previous human trials suggest that in preterm infants HFOV reduces the incidence of chronic lung disease (CLD). However, the trials themselves have several limitations. In an attempt to conclusively establish the role of HFOV for the prevention of CLD in very preterm infants we conducted a large, UK based, multicentre trial. Preliminary results of this study suggest there are no significant differences between the two modes of ventilation regarding mortality and incidence of CLD.     

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.     

Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years

BACKGROUND: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. OBJECTIVE: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. METHODS: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. RESULTS: Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26-28 weeks. CONCLUSIONS: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.     

高频震荡通气对新生儿呼吸窘迫综合征的治疗作用及其潜在危害性的Meta分析

目的：综合比较高频震荡通气(HFOV)与传统机械通气(CMV)对新生儿呼吸窘迫综合征的治疗作用及其潜在危害性。方法：通过数据库检索出符合纳入分析条件的相关文献12篇,采用Meta分析方法进行定性、定量综合分析,得出合并OR值及其95％的可信区间。结果：与CMV相比,HFOV能明显改善呼吸窘迫综合征患儿的呼吸功能(P<0.05)以及降低慢性肺部疾病的发生率(P<0.01),但增加了新生儿颅内出血的危险性(P<0.05);在HFOV和CMV两种通气方式导致的气漏发生方面,则无明显差异(P>0.05)。结论：经用Meta分析认为应用HFOV治疗新生儿呼吸窘迫综合征的效果优于CMV,并可减少慢性肺部疾病的发生,但应注意新生儿颅内出血的并发症发生。     

Non-invasive respiratory support in preterm infants

Survival of preterm infants has increased steadily over recent decades, primarily due to improved outcomes for those born before 28 weeks of gestation. However, this has not been matched by similar improvements in longer-term morbidity. One of the key long-term sequelae of preterm birth remains bronchopulmonary dysplasia (also called chronic lung disease of prematurity), contributed primarily by the effect of early pulmonary inflammation superimposed on immature lungs. Non-invasive modes of respiratory support have been rapidly introduced providing modest success in reducing the incidence of bronchopulmonary dysplasia when compared with invasive mechanical ventilation, and improved clinical practice has been reported from population-based studies. We present a comprehensive review of the key modes of non-invasive respiratory support currently used in preterm infants, including their mechanisms of action and evidence of benefit from clinical trials.     

High frequency oscillatory ventilation in acute respiratory failure

High frequency oscillatory ventilation (HFOV) has emerged over the past 20 years as a safe and effective means of mechanical ventilatory support in patients with acute respiratory failure. During HFOV, lung recruitment is maintained by application of a relatively high mean airway pressure with superimposed pressure oscillations at a frequency of 3 to 15Hz, creating adequate ventilation using tidal volumes less than or equal to the patient's dead space volume. The physiologic rationale for the application of HFOV in the clinical arena comes from its ability to preserve end-expiratory lung volume while avoiding parenchymal overdistension at end-inspiration and theoretically limiting the potential for ventilator-associated lung injury. Data in the neonatal population suggests significant benefits in pulmonary outcomes when HFOV is applied with a recruitment strategy in preterm infants with respiratory distress syndrome (RDS). Use of HFOV in the paediatric and adult populations has not as yet been associated with significant improvements in clinically important outcome measures.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

早产儿机械通气治疗的研究进展

机械通气在治疗早产儿严重并发症尤其是呼吸系统疾病中起着非常重要的作用.随着产前及新生儿期护理技术和治疗策略的改进,早产儿生存率逐年增加,支气管肺发育不良的发生率也在持续增加,严重影响早产儿的预后.近年新生儿学者在非侵袭性呼吸支持技术对减轻肺损伤、降低早产儿并发症方面进行了许多有益的探索.本文就不同机械通气模式在治疗早产儿呼吸衰竭中的作用及肺保护策略在降低早产儿肺损伤中的应用现状进行综述.     

高频振荡通气治疗新生儿肺透明膜病文献的Meta分析

目的　综合比较高频振荡通气 (HFOV)与传统机械通气 (CMV)对新生儿肺透明膜病的治疗作用及其潜在危害性。方法　通过数据库检索出符合纳入分析条件的相关文献 12篇 ,采用Meta分析方法进行定性、定量综合分析 ,得出合并OR值及其 95 %可信区间。结果　与CMV相比 ,HFOV能明显改善肺透明膜病患儿的呼吸功能 (P <0 0 0 5 )以及降低慢性肺部疾病的发生率 (P <0 0 1) ,但增加新生儿颅内出血的危险性 (P <0 0 5 ) ;在两种通气方式引起的气漏方面 ,无明显差异 (P >0 0 5 )。结论　应用HFOV治疗新生儿肺透明膜病的效果优于CMV ,并可减少慢性肺部疾病的发生 ,但应注意其它并发症的出现。     

Development of chronic lung disease in preterm infants treated with surfactant

BACKGROUND: Chronic lung disease (CLD) is generally known to develop among preterm infants who have severe respiratory distress syndrome (RDS) at birth. Many clinical trials have established the efficacy of surfactant replacement therapy to treat RDS at birth with differing doses. In this study, the preterm infants diagnosed to have RDS at birth and treated with one or two doses of surfactant, depending on the severity of the RDS, were studied to evaluate the effect of surfactant on the later development of CLD. METHODS: A retrospective examination of case records of preterm infants who were born at < or = 28 weeks gestation period were studied. The subjects received a natural surfactant product (survanta) between September 1994 and April 1996 at the Monash Medical Center, Australia. RESULTS: Despite less severe initial lung disease, the subsequent respiratory outcome of infants who received one dose of surfactant, showed a trend towards being poorer compared to those who were diagnosed as having severe RDS at birth and received two doses of surfactant. At the corrected gestational age of 36 weeks, 54% of those infants began with mild RDS required oxygen, while only 44% of those who started with a severe RDS required supplemental O2. CONCLUSION: This study reports the infants with severe RDS at birth had responded slightly better or equally, compared to those with mild RDS, in terms of later development of CLD under surfactant treatment proportional to the severity.     

Antenatal glucocorticoid treatment does not reduce chronic lung disease among surviving preterm infants

BACKGROUND: Antenatal glucocorticoid treatment (AGT) is associated with a number of postnatal benefits to the preterm infant, including reduced risk of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. OBJECTIVe: To evaluate the hypothesis that maternal AGT not only reduces the risk of surfactant deficiency but also reduces the occurrence of chronic lung disease (CLD) among surviving preterm infants. STUDY DESIGN: Case-referent study of 1454 very low birth weight infants born between January 1991 and December 1993 at 4 university medical centers. RESULTS: Rates of AGT varied among the 4 centers (11%-69%), as did rates of CLD (4%-21%), defined as a requirement for supplemental oxygen at 36 weeks' postmenstrual age. CLD rates at each center, however, did not vary with the rate of AGT exposure. In multivariate logistic regression analyses, AGT did not contribute significantly to CLD risk. CONCLUSION: AGT may play a less prominent role in modifying CLD risk than other factors such as biologic immaturity, infection, or neonatal intensive care unit practices, such as mechanical ventilation, continuous positive airway pressure, and surfactant replacement therapy.     

Chronic lung disease of prematurity and respiratory outcome at eight years of age

AIM: The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. METHODS: Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. RESULTS: There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. CONCLUSION: Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.     

早产儿呼吸窘迫综合征高频振荡通气后两种撤机方式的安全性研究：前瞻性随机对照试验

目的 探讨高频振荡通气（HFOV）治疗早产儿呼吸窘迫综合征（RDS）后两种撤机方式的安全性。方法 前瞻性纳入2019年1月1日至2020年6月30日厦门市妇幼保健院新生儿科重症监护病房（NICU）收治的胎龄≤ 32⁺⁶周或体重≤ 1 500 g、首选HFOV治疗的RDS早产儿101例,随机分为HFOV直接撤机组（观察组）50例,HFOV转为常频机械通气撤机组（对照组）51例。比较两组患儿撤机后72 h内的撤机失败率,撤机前2 h、撤机后2 h、撤机后24 h的血气分析各指标,比较两组呼吸支持治疗情况、并发症的发生率及出院时的转归情况。结果 观察组和对照组撤机失败率差异无统计学意义（8% vs 14%,P > 0.05）。观察组有创机械通气时间较对照组缩短[（64±39）h vs（88±69）h,P < 0.05]。两组患儿总机械通气时间、总用氧时间、撤机前后的血气分析各指标、并发症发生率、出院时转归情况差异均无统计学意义（均P > 0.05）。结论 对于RDS早产儿,使用HFOV后采取直接撤机策略是安全可靠的,且可减少有创呼吸机使用时间,值得临床推广应用。     

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.     

Rehospitalization for respiratory syncytial virus infection in infants with extremely low gestational age or birthweight in Denmark

AIM: To determine the risk of rehospitalization for respiratory syncytial virus (RSV) infection during the first 2 y of life in extremely preterm infants. METHODS: Records on all rehospitalizations during the first 2 living years of all infants born with gestational age <28 wk or birthweight <1,000g during 1994 and 1995 in Denmark were retrospectively reviewed. RESULTS: Among 240 eligible infants, 43 (18%) had been rehospitalized 48 times owing to RSV. In infants (n = 210) without CLD the risk of rehospitalization for RSV was 16%, whereas in infants with CLD (n = 30) it was 30% (p = 0.065). Eighteen infants (38%) required respiratory support (supplemental oxygen only 3, continuous positive airway pressure 14, mechanical ventilation 1). Apart from CLD the only factor that could be associated with increased risk of hospitalization for RSV was discharge during autumn (p = 0.05). No infant died from RSV infection. CONCLUSION: The high rate of rehospitalization for RSV in extremely preterm infants in Denmark, especially in infants with CLD, should lead to considerations concerning more widespread use of prophylaxis against RSV in these infants.     

新生儿高频振荡通气的撤机方式探讨

新生儿呼吸衰竭是新生儿重症监护室常见的危重症,尽管临床医生希望最大限度地利用无创呼吸支持,但有些低出生体重早产儿一开始就需要用到有创呼吸支持。高频振荡通气（HFOV）作为治疗呼吸衰竭的重要呼吸管理技术,它允许用小于或等于解剖死腔的潮气量快速输送进行气体交换,利用持续膨胀压使肺均一扩张,但同时对肺组织的反复牵拉作用较小,对肺部有保护作用,从而受到临床医师的青睐,目前临床应用已较为普遍。但对于HFOV后如何拔管撤机目前仍不统一。该文就HFOV的撤机方式进行综述,以期为临床提供帮助。     

Management of infants with chronic lung disease of prematurity in Chile

Despite advances in the prevention and management of respiratory distress syndrome, chronic lung disease of prematurity (CLD) remains a major cause of morbidity and mortality in preterm babies in Chile. Its incidence varies from 10% to 60% in different regions of Chile. Since 1998, the management of CLD after discharge from neonatal unit follows national guidelines. Target oxygen saturation is 85% to 91% in the first 1 week of life, 91% to 94% from 1 to 2 weeks and over 95% after 44 weeks postconceptional age. National home oxygen program has improved outcome in infants with CLD. Other specific treatments are used with caution. Diuretics are used for pulmonary oedema. The adverse neurological outcome in infants treated with postnatal steroids restricts its use to infants who cannot be weaned from mechanical ventilation. Inhaled steroids and bronchodilators may reduce asthma-like symptoms in established CLD. Prevention of RSV infection in CLD babies is paramount. The preterm infant population has been maintained under surveillance nationally since 1998.     

How to ventilate term babies

Infants born at term frequently require mechanical ventilation and suffer significant mortality and morbidity. Yet, there have been few randomised trials (RCTs) exclusively of term born infants and when term born infants have been included in studies, a sub-analysis of their results has rarely been undertaken. The limited evidence demonstrates in term born infants that there are no benefits in using rates > 60 bpm during conventional mechanical ventilation (CMV) or using synchronous intermittent mandatory ventilation. Pressure support ventilation may reduce their work of breathing (WOB). During volume targeted ventilation, a volume targeted (VT) level of 6 mls/kg reduces the WOB compared to a lower level or no VT. High frequency oscillatory ventilation in infants born at or near term with severe respiratory failure does not reduce mortality, oxygen dependency at 28 days or intracranial haemorrhage. RCTs with long term outcome are required to determine the optimum ventilatory modes in term born infants.     

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.