Respiratory distress syndrome (RDS) is one of the most common consequences of prematurity and a leading cause of neonatal mortality and morbidity as a result of immature lungs. RDS particularly affects neonates born before 32 weeks of gestational age but is also recognised in babies with delayed lung maturation of different aetiology i.e. maternal diabetes. Since its initial recognition there have been vast advances in understating the pathology and management of this complex syndrome. However, in order to understand the pathology behind RDS it is imperative to obtain a good foundation of normal lung maturation and physiological changes that occur in the respiratory system during the transition from fetal to neonatal life.
Physiological Development and Function of the lungs
During intrauterine growth, fetal lung development begins as early as 3 weeks and progresses until 2-3 years. Conventionally it is divided into 5 stages; embryonic, pseudoglandular, canalicular, saccular and finally alveolar1 (Table 1). During the embryonic stage, the lungs develop from the fetal ectoderm to form the trachea, the main bronchi, the five lobes of the lung and the major blood vessels that connect the fetal lungs to the heart; the pulmonary arteries. This is followed by the pseudo glandular stage which results in the formation of the terminal bronchioles and associated primitive alveoli. These then further divide in the Canalicular stage to form the primary alveoli and subsequently the alveolar capillary barrier. This stage also comprises the differentiation of Type 1 and 2 pneumocytes which will later go on to produce surfactant. Thus babies born after 24 weeks, have a chance of survival as the platform for basic gas exchange has begun to develop. During the saccular stage there is further differentiation of type 1 and type 2 pneumocytes and the walls of the airways, in particular the alveoli, thin to enlarge the surface area present for gaseous exchange. This is followed by the alveolar stage which occurs through the transition form fetal to neonatal life up until 2-3 years. The hallmark of this stage is alveolar formation and multiplication to augment the surface area available for gas exchange to meet the increasing respiratory demands as the infant grows.
Trachea, main bronchi and five lobes of the lungs develop from the fetal ectoderm. Pulmonary arteries form and connect to heart.
Formation of terminal bronchioles and alveoli
Formation of alveoli-capillary barrier and differentiation of type I and II pneumocytes
Walls of airway thin for efficacious gas exchange
36 weeks -2 years
Table 1: Stages of Lung Development
Once the pulmonary epithelium develops, it begins to secret fluid into fetal lungs, the volume and rate of which is imperative for normal lung growth. Another important factor essential for normal lung development and function is the production of surfactant.
At about 24 weeks of gestation the enzymes and lamellar bodies required for surfactant production and storage begin to appear 3. Thus a normal fetus age is not ready to be delivered at this stage due to surfactant deficiency. As type II pneumocytes mature between 32-36 weeks, surfactant production increases and it is stored in the lamellar bodies of these cells.
Surfactant is a complex mixture of phospholipids, neutral lipids and proteins 1, 4 that has a fundamental role in maintaining the alveolar-capillary interface and reducing surface tension. It is secreted as a thin film at the liquid-air barriers to facilitate alveolar expansion and prevent end-expiratory collapse of small alveoli, especially at low alveolar volumes.
A key event in the development of the lungs is the establishment of spontaneous breathing post-delivery. Prior to delivery the fetal lungs decrease lung fluid production and as the lungs mature there is simultaneous maturation of the lung lymphatic system. During labour the mechanical compression of the fetal chest forces about 1/3 of this lung fluid thus preparing the fetus for spontaneous ventilation. This will require several stimuli; including hypoxia, hypercrabia and acidosis as a results of labour5 and hypothermia and tactile stimulation. Furthermore the stress of labour stimulates chemo-receptors in the fetal aorta and carotids to trigger the respiratory centre in the medulla to commence breathing. As the fetus emerges from the birthing canal, the fetal chest re-expands creating negative airway pressure which subsequently draws air into the lungs. This again forces the lung fluid out of the alveoli and allows for adequate lung expansion. As the newborn cries there is further expansion and lung aeration generating positive intrathoracic pressure which maintains alveolar patency and forces any remaining fluid into the lymphatic circulation.
As the neonate adapts to extra-uterine life, the normal muscles of respiration work to maintain breathing (Figure 1). In order to inhale, the diaphragm and external intercostals muscles contract to increase the size of the thorax. This generates negative air pressure in the pleura and lowers the air pressure in the lungs so that the gradient between atmospheric air and alveolar air causes air to enter into the lung of the neonate. As the neonate inhales, the elastic recoil force of the lung increases. Once inspiration ceases, the elastic recoil force of the lung causes expiration. The diaphragm and external intercostals muscles relax, the thorax returns to its pre-inspiratory volume resulting in an increase in intra-thoracic pressure. This pressure is now greater than atmospheric pressure and air moves out of the lungs producing exhalation.
Figure 1: The Mechanics of breathing6
For most neonates, this transition from fetal to extra-uterine life is uneventful and completed during the first 24 hours of life. The neonate is able to establish good lung function, maintain cardiac output and thermoregulate. However, for a certain population of neonates, usually those that are born early and thus called preterm, this transition is less smooth and it is these babies that will require the support and care of the whole paediatric department.
Respiratory Distress Syndrome
Respiratory distress syndrome (RDS) is the most prevalent disorder of prematurity and despite a better understanding of its aetiology and pathology, RDS still accounts for significant neonatal mortality and morbidity. The incidence RDS is inversely proportional to gestational age2 such that it decreases with advancing gestational age, from about 60-80% in babies born at 26-28 weeks, to about 15-30% in babies born at 32-36 weeks 1. Risk factors for developing RDS are summarised in Table 2 and include maternal illness, complications during pregnancy and labour and neonatal complications
Table 2: Risk Factors for RDS1
Respiratory distress presents early in post-natal life particularly during the phase of transition from fetal to extra-uterine life. These babies will present with signs of grunting, cyanosis, nasal flaring, intercostal and subcostal recession, increased respiratory effort, and less commonly apnoeic episodes and circulatory failure. The severity of symptoms experienced are related to the pathology of disease and it is important to identify babies at greatest risk and commence management early in order to prevent respiratory complications such as chronic lung disease (previously called bronchopulmonary dysplasia), pulmonary hypertension and in adverse cases respiratory failure and even death.
Identifying normal transition and respiratory distress is largely based on evaluating the risk factors for RDS, assessing the severity of symptoms and close neonatal observation if in doubt. Babies that are born close to term or those via caesarean section may display a difficult albeit a normal transition. These babies present with transient tachypnoea of the newborn in the first few hours with respiratory rates of about 100 breaths per minute and increased oxygen requirements. Symptoms are short lived, self limiting in most cases and usually relived by oxygen. Neonates who suffer from RDS will present with worsening symptoms of longer duration, respiratory rates of 120 and increased respiratory effort with a longer requirement for oxygen. Recovery if plausible usually begins after 72 hours and is associated with decreased oxygen requirements and better functional residual capacity.
Pathophysiology of Respiratory Distress Syndrome
Since its initial recognition, more than 30-40 years ago, much has been elucidated about the pathophysiology of this complex syndrome. In the premature neonate, the structurally immature and surfactant deficient lung is unable to maintain the basic lung mechanics required for adequate ventilation. As aforementioned lung mechanics rely on surfactant production, alveolar multiplication and maturity for effective gas exchange, chest wall elasticity and a functionally developed diaphragm. It is therefore evident that premature neonate who lack surfactant and have structurally immature lungs will develop RDS, atelectasis and abnormal lung function. In these neonates the essential first breaths are followed by a secondary pathological cascade characterised by tissue damage, protein leakage into the alveolar space and inflammation, which may resolve or progress to BDP or chronic lung disease of prematurity (CLD)7.
In neonates with RDS, end-expiration results in the collapse of alveoli due to surfactant deficiency and a subsequent reduction in the functional residual capacity (FRC). The FRC is the volume available for gaseous exchange i.e the volume of gas left in the lungs after exhalation. It is determined by an intricate balance between the collapsing and expanding forces of the chest wall and lungs7. An ideal FRC enables the best possible lung mechanics, efficient ventilation and gaseous exchange.
As the FRC is reduced at end-expiration due to alveolar collapse due to high surface tension, the pressure that will be required to re-inflate the already immature lungs is increased. This in turn increases the respiratory effort needed for adequate gas exchange which presents clinically as increased respiratory rate and subcostal/intercostal recession. Moreover reaching an optimal FRC may be further impeded by both surfactant deficiency and by the preterm infant’s impaired ability to clear fetal lung fluid. Radiographically a chest x-ray will show the characteristic “ground-glass ” appearance with diminished lung volumes and the cardinal features of respiratory stress, tachypnoea, nasal flaring, intercostals recession, subcostal recession, increased breathing effort and grunting will begin to manifest early on.
Despite this effort to breathe, alveolar ventilation remains poor. As these areas are receiving an adequate blood supply this produces a ventilation/perfusion mismatch resulting in right to left intrapulmonary shunting1. The lungs are unable to maintain good gas exchange and blood oxygen saturation and the level of carbon dioxide begins to increase resulting in respiratory acidosis, hypoxaemia and hypercarbia. The neonate further struggles to breath and attempts to generate higher negative pleural pressures to ventilate the lungs. The ensuing acidosis further diminishes surfactant production and neonates deteriorate rapidly as blood oxygen saturations plummet. The natural progression of the disease if left untreated will lead to pulmonary oedema, right-sided heart-failure and ultimately the most devastating outcome, neonatal death.
Therefore the management of these neonates requires an aggressive multi-disciplinary team approach based on the pathology of these aforementioned homeostatic mechanisms. Alongside this the basic principles of neonatology; thermoregulation, nutritional support, efficacious cardiovascular support and infection control, are all fundamental in achieving the best therapeutic goal. Ultimately the aim is to provide adequate ventilatory support, allow the lungs to heal, impede further pulmonary injury, correct hypoxaemia and acidosis and above all to keep the neonate alive.
Management of RDS
As aforementioned the aim of treatment is to promote lung healing and reduce further pulmonary insults. We have already established that with increasing gestational age, particularly post-32 weeks, the infant will require less aid to help it cope with the transition from fetal to neonatal life. However, before 32-weeks there is an increased propensity to develop RDS and as the neonate is unable to cope, some form of respiratory support is required. Over the past 40 years there have been numerous management therapies including ventilatory support, surfactant therapy, nitric oxide therapy and supportive therapeutics strategies amongst others. The mainstay of treatment today remains supportive and involves the use of antenatal steroids, surfactant replacement therapy, continuous positive airway pressure and mechanical ventilation, which all aim to address the pulmonary insufficiency that manifest in these individuals
Glucocorticoid receptors are expressed in the fetal lung at early gestation and as the fetus grows stimulate surfactant production post-32 weeks. Alongside receptor expression there is an increase in fetal cortisol levels at late gestation9, which coincides with lung maturation, type II pneumocyte differentiation, surfactant synthesis as well as alveolar thinning. If birth occurs before this increase in serum cortisol, the pulmonary system has not matured adequately and therefore there is an increased propensity to develop RDS. Thus a single dose of glucocorticoids such as dexamethasone or betamethasone in the antenatal period promotes lung maturation.
One of the first published reviews that showed the efficacy of antenatal steroids in preterm labour was produced by Crowley in 19958. Crowley showed that steroids given in preterm labour were effective in preventing RDS and improving neonatal mortality rates. Since then several randomised controlled clinical trials have evaluated the efficacy of steroids in reducing RDS. A recent Cochrane review of 21 trials assessed the effects of antenatal corticosteroids, given to women expected to go into preterm labour, on fetal/neonatal mortality and morbidity8. The authors concluded that a single dose of antenatal steroids promoted fetal lung maturation thereby reducing the risk of RDS and the need for assisted respiratory management. The mechanisms by which glucocorticoids are thought to exert their efficacy are described below.
Firstly, glucocorticoids stimulate phospholipid production. Phospholipids are a major component of endogenous surfactant and as a result augment surfactant synthesis in the biochemically immature and surfactant deficient lung 9, although the exact mechanisms by which this occurs remains to be elucidated. Secondly glucocorticoids enhance lung maturation and development. As aforementioned, in order to produce surfactant, fetal lungs must produce type II pneumocytes which will then generate lamellar bodies in which surfactant is stored. Glucocorticoids enhance this process, promoting pulmonary epithelial cell maturity and differentiation into type II pneumocytes9. Furthermore glucocorticoids cause a decrease in pulmonary interstitial tissue thereby decreasing alveolar wall thickness. A thin alveolar wall thickness facilitates efficacious gaseous exchange and will therefore assist ventilation and oxygenation of the neonate once born thus decreasing the chances of developing RDS. Another known benefit of antenatal glucocorticoids is found in reducing oxidative stress on the immature lung and prevention of pulmonary oedema9.
This accumulative evidence suggests that glucocorticoids are essential for normal pulmonary development and giving a single dose to mothers at risk of preterm birth may substantially decrease the chances of the infant developing RDS.
As discussed before, endogenous surfactant has a fundamental role in maintaining the alveolar-capillary interface in order to prevent end-expiratory alveolar collapse. This is achieved by thin spread of surfactant around the alveoli which ultimately acts to reduce surface tension. The most important component of surfactant which achieves this fundamental function is a phospholipid called dipalmitoylated phopshatidylcholine (DPPC)11. DPPC also stabilises the alveoli at end expiration, further preventing alveolar collapse. Alongside DPPC the synergistic actions of surfactant proteins (SP) SP-B and SP-C also lower surface tension11. Thus a deficiency in surfactant will cause alveolar collapse, decrease pulmonary compliance, increased pulmonary vascular resistance and produce ventilation-perfusion mismatch. Hence the aim of exogenous surfactant therapy is to reverse this pathological cascade and ultimately prevent alveolar collapse thereby limiting pulmonary damage and improving ventilation.
Since the first clinical trial assessing the use of surfactant in managing neonatal RDS by Fujiwara in the 1980s10, our understanding of the composition, structure and function of surfactant has progressed vastly. In this uncontrolled trial the chest x-rays of 10 babies diagnosed with RDS, both clinically and radiologically, showed significant improvement after exogenous modified bovine surfactant was administered with a decreased requirement for ventilation. Since then several randomised controlled trials12 have shown that surfactant therapy, alongside antenatal steroids and ventilation continues to improve neonatal morbidity and mortality.
Both natural (derived from an animal source) and synthetic (manufactured chemically) surfactants are available to use in managing RDS. Meta-analysis of trials comparing the two types of surfactant have shown that natural surfactants show a more rapid response in improved lung compliance and oxygenation12 thereby reducing neonatal mortality. Furthermore natural surfactants are less sensitive to inhibition by accumulative products of lung injury such as serum proteins.
Surfactants need direct delivery to lungs and usually require intubation with short periods of assisted ventilation. Traditionally two therapeutic approaches have been established in managing RDs with surfactant. The first adopts the use of surfactant prophylactically, with surfactant given immediately after birth to enable the neonate to cope with extra-uterine life. The obvious benefit of this approach is that surfactant is administered to the baby before severe RDS develops resulting in long-term pulmonary sequelae for the neonate. However this technique is invasive, as surfactant administration requires endotracheal intubation, it is expensive and furthermore it may result in the unnecessary treatment of neonates. Moreover poor intubation with failed attempts and prolonged apnoeic episodes may further damage the lungs resulting in CLD. Despite this, there is a strong body of evidence for prophylactic use of surfactant and current guidelines state that all preterm babies born before 27 weeks of gestation, who have not been given antenatal steroids should be intubated and given surfactant at birth7.
The second therapeutic approach evaluates the role of surfactant in rescue treatment used in neonates with an established diagnosis of RDS requiring ventilation and oxygen. The advantages of rescue treatment include that it is reserved for neonates in whom RDS is confirmed and it may decrease the morbidity associated with unnecessary intubation. The obvious disadvantage is that delay in surfactant delivery may allow for irreversible lung injury to develop with decreased efficacy of surfactant administration12.
Several studies have aimed to clarify the issue between prophylactic and rescue surfactant treatment. A randomised trial by Rojas et al. showed the benefits of surfactant delivery within 1h of birth in neonates born between 27-31 weeks14 with an established diagnosis of RDS who were treated with continuous positive airway pressure soon after birth. 279 infants were randomly assigned either to the treatment group (intubation, very early surfactant, extubation, and nasal continuous positive airway pressure) or the control group (nasal continuous airway pressure alone). The results of this study demonstrated that infants in the treatment group i.e. those treated with surfactant, showed a decreased need for mechanical ventilation with a decrease in the incidence of CLD and pneumothoraces. Neonatal mortality rates were similar between both groups.
A meta-analysis by Soll and Morley compared the effects of prophylactic surfactant to surfactant treatment of established respiratory distress syndrome (i.e. rescue treatment) in preterm infants33. The authors analysed eight studies comparing the use of prophylactic and rescue surfactant treatment and concluded that the majority of the evidence demonstrated a decrease in the incidence of RDS when surfactant was given prophylactically. Moreover the meta-analysis showed that infants treated with prophylactic surfactant had a better clinical outcome with a reported decrease in the risk of pneumothorax, pulmonary interstitial emphysema, CLD and mortality33.
As a result of such studies most neonatal units continue to practice delivery of surfactant prophylactically in preterm babies at high risk of RDS. However, some literature still debates whether there are any real advantages of prophylactic surfactant over rescue treatment. What is evident is that surfactant therapy should play a fundamental role in the management of RDS. Future trials will need to further assess the indications for surfactant therapy in treating neonatal RDS and perhaps in the management of other pulmonary insufficiency disorders that affect the neonate. Although much remains to be elucidated about the complex pulmonary surfactant system, since its introduction 25 years ago, surfactant therapy has been at the forefront of reducing RDS and its role in decreasing neonatal mortality and morbidity cannot be disputed.
Mechanical ventilations is one of the cornerstones of neonatal intensive care units and regardless of the modality used, the primary function is to maintain adequate oxygenation and ventilation. The goals of mechanical ventilation are:
to establish efficacious gaseous exchange
to limit pulmonary insult and CLD
to reduce the respiratory effort and work of breathing of the patient
To achieve these basic goals several techniques, devices and therapeutic options are available to the neonatologist that can be either invasive or non-invasive.
Continuous Positive Airway Pressure
The use of CPAP; continuous positive airway pressure, in the treatment of RDS was first described in the 1970’s and has since been identified as a important management strategy. CPAP applies positive end expiratory pressure (PEEP) to the alveoli throughout inspiration and expiration so that the alveoli remain inflated thereby preventing collapse. The pressure required to re-inflate the lungs is reduced as partially inflated alveoli are easily to inflate than completely collapsed ones.
Animal studies with premature lambs have shown the benefits of nasal CPAP over mechanical ventilation. CPAP acts to lower the markers for CLD for example granulocytes, and markers of white cell activation, increases the amount of surfactant available, improves oxygenation and lastly corrects ventilation/perfusion mismatching2, 15. Moreover CPAP produces a more regulated pattern of breathing in neonates by stabilising the chest wall and reducing thoracic distortion16.
Like surfactant therapy there are two ways in which CPAP can be administered. The first method, InSUrE: intubation, surfactant and extubation, adopts a brief intubation to administer surfactant and extubation to CPAP approach and the second is the Columbia method in which babies are started on CPAP in the delivery room and are only mechanically ventilated, and intubated if the need for surfactant is established.
Several studies have shown the benefit of the first approach. A study by Verder et al. randomised 68 neonates with moderate to severe RDS; 35 infants were randomised to surfactant therapy following a short period of intubation and then extubation to CPAP and 33 neonates were randomised to nasal CPAP alone. The results of this study showed that infants in the earlier group had a reduced need for ventilation; 21% in comparison to 63% in the second group16,17. Another similar trial by Haberman et al. assessed the use of surfactant with early extuabtion to CPAP and subsequently the results showed a decreased need and duration for mechanical ventilation12. Furthermore a recent Cochrane review of six studies using the InSuRE method showed that neonates with RDS treated with early surfactant therapy followed by nasal CPAP, were less likely to need mechanical ventilation and develop air leaks in comparison to neonates that were treated with the Columbia approach (i.e. early CPAP therapy followed by surfactant if needed)17, 18. A more recent review by the same authors further confirmed the findings of the initial review and the relative risk for developing CLD was 0.51 (95% CI 0.26-0.99) with early surfactant treatment and nasal CPAP when comparing the two methods18.
The Columbia method requires the stabilisation of neonates with CPAP in the delivery room with intubation and surfactant therapy used as necessitated. This approach was adopted when retrospectives studies done by Avery et al. and later Van Marter et al. evaluated the clinical outcomes in multiple neonatal units across the US2. In both cases a lower incidence of CLD was observed in the Columbia University Hospital which adopted CPAP as a primary treatment strategy as opposed to intubation and mechanical ventilation like other units. Leading on from this Ammari et al.. evaluated the Columbia method recently. The outcomes of 261 neonates with birth weight < 1250g that were managed on respiratory support, either CPAP or ventilators, were reviewed at 72 hours. Their results showed that infants started on CPAP were more mature and weighed heavier at 3 weeks in comparison with those that were ventilator started with a lower mortality rate reported in the CPAP group (9%) than in the ventilator group (66%). The results of this study highlighted that perhaps a large number of very preterm babies (gestation <27w) could benefit from early CPAP treatment.
So far the evidence base for the Columbia method has been derived from retrospective cohort studies with a lacking in RCTS and therefore a lack of stronger evidence. One RCT that had aimed to evaluate the Columbia method was the recent COIN trial by Morley. This study evaluated whether the incidence of death or BPD would be reduced by CPAP rather than intubation and ventilation shortly after birth13. 610 neonates born between 25-28 weeks were randomised to CPAP or intubation and ventilation at 5minutes after birth and surfactant was administered at the neonatologists’ discretion. The results of the study demonstrated that at 28 days of gestation, infants in the CPAP group had a decreased need for supplemental oxygen and fewer deaths2,13. However worrying results from this study were that approximately 46% of babies in the CPAP group went onto require intubation and had a higher rate of pneumothoraces13.
There are few randomised control trials assessing the benefit of CPAP alone in managing RDS and the results of the Columbia Hospital study have been irreproducible in other centres. The mainstream use of CPAP for managing RDS remains to start CPAP in the delivery room, after intubation for surfactant treatment. There is not enough evidence to show that CPAP alone can prevent RDS and associated complications in comparison with invasive ventilation. The evidence does suggest that there is a decrease in complications with surfactant therapy and CPAP but the relationship with CLD is less transparent.
At present there are two RCTs ongoing that may provide further insight into the role of CPAP in RDS when complete. The first trial is the SUPPORT study, which is randomising infants between 24-27 weeks to CPAP beginning in the delivery room with stringent criteria for subsequent intubation, or intubation with surfactant treatment within 1 h of birth with continuing mechanical ventilation2. The second is the trial by the Vermont-Oxford Network in which infants born at 26-29 weeks gestation will be randomised after 6 days into one of three groups; (1) intubation, early prophylactic surfactant, and subsequent stabilisation on mechanical ventilation; (2) intubation, early prophylactic surfactant, and rapid extubation to CPAP; and lastly (3) early stabilisation with nasal CPAP, with selective intubation and surfactant administration according to clinical guidelines2. The immediate management of the RDS neonate with CPAP remains controversial and maybe the results of these ongoing RCTS will provide invaluable answers to the many uncertainties surrounding this device.
Nasal intermittent positive pressure ventilation
Another relatively recent development in non-invasive ventilation that has evolved from NICU ventilator machines and CPAP devices is the use of NIPPV for managing RDS. Sometimes called BiPAP (for bi-level positive airway pressure), this form of non-invasive ventilation is able to provide two levels of airway pressure, without the need for intubation. BiPAP maintains positive pressure throughout respiration but with a slightly higher pressure during inspiration. By doing so BiPAP/NIPPV is able to assist neonatal breathing by:
reducing the work of breathing
improving tidal volume
increasing blood oxygen saturation and increasing removal of CO2 thereby limiting hypoxaemia and respiratory acidosis.
As the neonate inhales, the NIPPV device generates a positive pressure thereby assisting the neonates spontaneous breath and providing ventilatory support. This is at a slightly higher positive pressure. As the neonate begins to exhale, the pressure drops, but a positive airway pressure remains in the lungs to prevent alveolar collapse and thus increase gaseous exchange.
NIPPV may be a potential beneficial treatment for the management of babies with RDS and has been used in NICU’s since the 1980s. Recently multiple studies have aimed to evaluate the efficacy of NIPPV in stabilising neonates. A randomised controlled prospective study by Kulgeman et al.. found that NIPPV was more successful than NCPAP in the initial treatment of RDs in preterm infants19. Kulgeman and his colleagues randomised infants <35 gestational age to either NCAP or NIPPV with 41 infants randomised to NCPAP and 43 to NIPPV. The results established that the failure rate in the NIPPV group was les in comparison to the CPAP group (25.6% vs. 48.8%, respectively, p=0.04).These findings not only documented the beneficial used of NIPPV over CPAP, but also demonstrated that there was a decreased incidence of CLD; 2% in the NIPPV group in comparison to 17% in the NCPAP group, (p-value <0.05)19.
A further study by Sai and colleagues also established the advantages of NIPPV over CPAP in managing RDs and reducing the need for mechanical ventilation and intubation in preterm infants. In their study 76 neonates between 28-34 weeks gestation with RDs at 6h of birth were randomised either to ‘early NIPPV’ (37 neonates) or ‘early CPAP’ (39 neonates) after surfactant use20. Firstly they documented that the failure rate with NIPPV was less in comparison to the CPAP group (p
Cite This Work
To export a reference to this article please select a referencing style below: