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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 1-7

Lung-protective ventilation in neonatal intensive care unit


Department of Neonatology, School of Medicine, Celal Bayar University, Manisa, Turkey

Date of Submission25-Sep-2019
Date of Decision11-Dec-2019
Date of Acceptance26-Dec-2019
Date of Web Publication29-Jan-2020

Correspondence Address:
Prof. Esra Arun Ozer
Department of Neonatology, School of Medicine, Celal Bayar University, Manisa 45030
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_96_19

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  Abstract 


Despite the technological advances in the mechanical ventilation in neonatal intensive care units (NICUs), the lungs of preterm infants are still susceptible particularly to ventilator-induced lung injury. The purposes of lung-protective strategy in preterm infants are to prevent atelectrauma, limit tidal volume to avoid overdistension, and minimize oxygen toxicity. Available data suggest that these goals can be successfully achieved by different modes of respiratory support including ideal ventilation. It is important that ventilation with large tidal volumes should be avoided. Lung-protective ventilation in the newborn infants has been a recent trend as a primary mode of ventilation support for early management of respiratory distress syndrome. To reduce the risk of ventilator-induced oxygen toxicity, supplemental oxygen should be guided by pulse oximetry. In this study, current lung-protective ventilation methods in NICU are reviewed.

Keywords: Lung injury, newborn, noninvasive ventilation, ventilation modes, volutrauma


How to cite this article:
Ozer EA. Lung-protective ventilation in neonatal intensive care unit. J Clin Neonatol 2020;9:1-7

How to cite this URL:
Ozer EA. Lung-protective ventilation in neonatal intensive care unit. J Clin Neonatol [serial online] 2020 [cited 2020 Aug 8];9:1-7. Available from: http://www.jcnonweb.com/text.asp?2020/9/1/1/277236




  Introduction Top


The advances in the field of neonatal intensive care unit (NICU) in the past 40 years have yielded a decrease in the mortality and morbidity associated with neonatal lung disease, especially with the use of more sophisticated ventilators, antenatal corticosteroid therapy, and exogenously surfactant treatment.

The goals of ideal mechanical ventilation are to achieve and maintain adequate pulmonary gas exchange, minimize the risk of lung injury, reduce respiratory workload, and provide patient comfort. However, it may carry a risk of secondary lung injury defined as ventilator-induced lung injury (VILI).[1]

Despite the application of new lung-protective ventilation techniques accompanying with surfactant therapy in the acute phase of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) is still an important problem for preterm infants.[2] Expiratory grunting is an important sign of RDS, indicating that the baby has a low lung volume or functional residual capacity (FRC). Infants with RDS are observed to close the glottis during expiration in an attempt to maintain FRC and prevent alveolar atelectasis. An optimal protocol for respiratory support to reduce the incidence of BPD in these patients has not been established. Avoiding invasive mechanical ventilation may be the most effective method to reduce the risk of BPD.

The main factors playing a role in the lung injury during mechanical ventilation are atelectrauma, volutrauma, biotrauma, and barotrauma. The optimal lung volume is the key issue to provide a lung protection regardless of what the ventilation mode is used.[3],[4] High tidal volume status during mechanical ventilation may cause overdistension of small airways and alveoli.[5] Ventilation with insufficient positive end-expiratory pressure (PEEP) causes repetitive opening and collapse of unstable lung units; therefore, it is injurious for alveolar–capillary integrity.[6] In addition, high fractions of inspired oxygen may lead to oxidative stress and subsequent lung injury.[7] As a result, the airways and alveolar spaces filled with fluid, protein, and blood may cause pulmonary inflammation leading to biotrauma. A few large breaths (35–40 mL/kg) given at birth to immature lung are sufficient to cause lung injury and inhibit the effect of surfactant.[8] Therefore, the lung protection during mechanical ventilation in preterm infants should be initiated in the delivery room.

The major principles of lung-protective ventilation in preterm babies are to avoid use of high tidal volumes, minimize the presence of atelectasis, and avoid high oxygen exposure leading to oxidative stress. The ventilation strategy based on these three principles is called as optimal lung volume.[9] Open-lung ventilation strategies can reduce VILI and may be an important adjunct to limiting tidal volume and applying adequate PEEP.[10],[11]


  Noninvasive Ventilation Methods Top


Noninvasive ventilation (NIV) in the newborn infants has been a recent trend as a primary mode of ventilation support for early management of RDS. Five different methods are described in this category.

Nasal continuous positive airway pressure

Although the first continuous positive airway pressure (CPAP) device was designed approximately one century ago, using CPAP in the treatment of RDS was first performed in 1971.[12] In the early 1970s, nasal CPAP (NCPAP) application with binasal prongs was common, but it resulted in more air leaks and gastric distension and also the hard nasal prongs were not well tolerated by the newborn infants. For these reasons, intermittent mandatory ventilation (IMV) became the standard ventilation method for newborn infants in neonates with RDS. However, for the past 20 years, due to the disadvantages resulting from invasive mechanical ventilation, there has been an increased interest on CPAP because it provides a gentle way of maintaining patency of alveoli and allowing sufficient gas exchange. CPAP is now one of the most effective methods to provide respiratory support and superior to invasive mechanical ventilation. The basic mechanisms playing a role in the biological effects of CPAP use are shown in [Table 1].
Table 1: The basic mechanisms playing a role in the biological effects of continuous positive airway pressure

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Today, the most common use of NCPAP is to provide respiratory support for infants with RDS, postextubation, and apnea of prematurity. Besides these three indications, NCPAP is commonly used for the management of transient tachypnea of the newborn. Although there are limited data, it can also be used in some conditions such as patent ductus arteriosus, pulmonary edema, and congestive heart failure. [Table 2] demonstrates the list of common clinical conditions where NCPAP use is an optional strategy.
Table 2: Clinical indications of nasal continuous positive airway pressure use

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Application of CPAP in the early phase of RDS before occurrence of alveolar collapse reduces the need for invasive mechanical ventilation.[13] Recent studies have shown that early NCPAP in the delivery room reduces the need for invasive mechanical ventilation and surfactant administration.[14],[15] The rise of early NCPAP use leads to discuss and reevaluate the indications and timing of surfactant replacement therapy.

It has been reported that prophylactic surfactant treatment has no superiority in terms of air leak syndrome and mortality compared to selective surfactant treatment.[16] Moreover, BPD or mortality rate was decreased with early NCPAP use compared to prophylactic surfactant administration.[14],[15] The American Academy of Pediatrics emphasizes that early initiation of CPAP with subsequent selective surfactant administration in extremely preterm infants provides some benefits such as lower rates of BPD or death in comparison with treatment of prophylactic surfactant therapy.[17] More recently, the European Consensus Guidelines on the Management of Respiratory Distress Syndrome has recommended that CPAP use with early rescue surfactant treatment should be considered as the optimal therapy for babies with RDS.[18] Initiation of CPAP use at birth rather than routine intubation for stabilization or prophylactic surfactant treatment is better for preventing lung injury, although it is important to determine when CPAP administration cannot be effective alone.[16] Whether or not methodology of CPAP use can make a difference in achieving effective outcomes remains still unknown. Although variable-flow CPAP use has been shown to result in more stable level of CPAP and lower work of breathing compared to ventilator-generated CPAP, these theoretical advantages were not supported with large randomized clinical trials.[19],[20],[21]

Nasal intermittent positive pressure ventilation

The preterm infants treated with early NCPAP may experience respiratory failure due to progression of underlying lung disease, apnea of prematurity, and progressive atelectasis. Nasal intermittent positive pressure ventilation (NIPPV) has been proposed as an alternative method to NCPAP in preterm infants to avoid invasive mechanical ventilation and stabilize respiration. The outcomes of NIPPV use are not yet understood completely. It has been observed that pulmonary inflammation is reduced when NIPPV is administered to surfactant-deficient newborn piglets.[22] In human studies, when it is used in the synchronized mode, it reduces the work of breathing, increases mean airway pressure allowing recruitment of alveoli and tidal and minute volumes, and improves gas exchange and FRC and pulmonary mechanics.[23],[24]

Addition of peak inspiratory pressure above PEEP to NIPPV use was shown to increase flow delivery in the upper airway.[25] Because the incidence of gastrointestinal perforation was found to be higher in early studies of NIPPV, the use of synchronized NIPPV (SNIPPV) has become more common.[26] Special devices are needed for SNIPPV to detect the patient's inspiratory effort, whereas NIPPV can be applied with any device to provide intermittent positive inspiratory pressure. The use of NIPPV is classified as primary and secondary. It can be used as primary mode within the first 2 h after birth for ensuring noninvasive respiratory support. The secondary mode refers to its use because it increases the success of extubation after a longer period of intubation.[27]

There are a number of studies comparing the use of NIPPV at the primary mode and NCPAP in the early phase of RDS. In a recent study, the rate of intubation and invasive mechanical ventilation was decreased whereas the complication rate of NIPPV was increased.[28] This finding was more evident, particularly in infants administered with surfactant. However, there was no difference in the rate of BPD occurrence or mortality. The use of NIPPV following a very-early surfactant was shown to decrease the need for intubation and invasive mechanical ventilation. However, we think that further randomized controlled trials are needed to compare the evidence-based effects of NIPPV with or without surfactant therapy.

Previous clinical studies in preterm infants revealed that SNIPPV was more effective than NCPAP in preventing failure of extubation.[29] Non-SNIPPV resulted in a better effect than NCPAP after extubation of preterm infants on mechanical ventilation with respect to reducing the prevalence of postextubation atelectasis and reintubation.[30] However, a recent meta-analysis including ten clinical trials addressed that using SNIPPV in infants by a ventilator yielded positive outcome and benefits more consistently.[31]

Bilevel continuous positive airway pressure

Bilevel CPAP (BiPAP) is a special method providing two levels of PEEP during the respiratory cycle of the newborn. The upper pressure setting is usually at 3–5 cm H2O above the base pressure and it is delivered for an inspiratory time at a set rate. One of the expected benefits of BiPAP is to provide a higher mean airway pressure without exposing its side effects of continuous high distension pressures. Another benefit is the increase in tidal volume and reduction in the effort required for breathing.

Synchronization is provided using either Graseby capsule on the infant's abdomen or a flow trigger. Owen et al.[32] demonstrated that the spontaneous breathing of the patient was supported by synchronization, but without corresponding to tidal volume. Literature data showed that BiPAP was more successful than NCPAP when used as a primary mode of respiratory support for RDS. There was no significant difference between SNIPPV and BiPAP in terms of duration of ventilation and failure in the treatment of preterm infants with RDS.[33]

Nasal high-frequency oscillatory ventilation

Nasal high-frequency oscillatory (NHFO) ventilation is another NIV method that applies an oscillatory pressure waveform to the airways via a nasal cannula or prong. Unlike NIPPV, NHFO does not require synchronization. Although there are very limited studies conducted in newborn infants, animal models have shown that it increases tidal volume and improves gas exchange.[34] The clinical crossover studies comparing NCPAP and NHFO in very low birth weight infants have demonstrated that NHFO has less respiratory distress and better CO2 elimination.[35]

A questionnaire-based survey performed in five European countries revealed that the most common interfaces were binasal prongs in the use of NHFO in clinical settings.[36] The mean airway pressure and the frequency used between units showed large variety of levels. Upper airway obstruction due to viscous secretions and abdominal distension were the most frequent side effects of NHFO. Although NHFO promises as a new NIV method, there are no well-established protocols to be recommended so far. Further clinical trials evaluating short- and long-term reliability and effectiveness are needed.

Heated, humidified, high-flow nasal cannula

Heated, humidified, high-flow nasal cannula (HHFNC) is a new noninvasive respiratory support method in preterm infants. HHFNC application is defined as the use of heated and humidified gas flows at a rate of 2–8 L/min via nasal cannulae. A recent meta-analysis including 19 clinical trials revealed that HHFNC systems may show effectiveness comparable to NCPAP use in improving significant clinical and pulmonary parameters in preterm infants.[37] However, as the authors have also emphasized, larger randomized trials are in need to investigate the efficacy and safety of HHFNC in preterm infants.


  Invasive Mechanical Ventilation Top


Although smaller infants have been sustained successfully without the use of invasive respiratory support, invasive mechanical ventilation application is still an often-used method in NICU. There are many different ventilation modes and invasive ventilation strategies available to optimize mechanical ventilation and prevent VILI. Invasive mechanical ventilation used in the NICU can be divided into two main categories as conventional and high-frequency ventilation (HFV).

Conventional invasive mechanical ventilation

Because there is a consensus that conventional ventilation leads to lung injury, neonatologists prefer more gentle ventilation strategies in which alveolar distension is minimized. Conventional mechanical ventilation is a form of assisted ventilation in which the delivered gas volumes approach to physiologic tidal volumes and it mimics physiologic breathing.

Delivery of conventional ventilation varies by how the breath is initiated, how the tidal volume is regulated, and how the breath is terminated. The most commonly used ventilator in neonates for IMV is the time-cycled, pressure-limited ventilator. However, IMV methods have almost been never used currently in NICU. Therefore, patient-triggered ventilation modes also known as synchronized or assist/control (A/C) ventilation have been developed to optimize compliance between the infant and the ventilator, increase patient comfort, shorten the duration of ventilation, and minimize cardiovascular side effects. The prospective randomized controlled trials comparing the effectiveness of synchronized versus ventilator-triggered ventilation revealed that synchronization facilitated weaning and shorter duration of ventilation.[38],[39] Therefore, synchronized ventilation is now accepted as the standard ventilation method in NICU.

Synchronized intermittent mandatory ventilation (SIMV) is one of the most commonly used patient-triggered ventilation methods. In SIMV, mechanical breaths are initiated simultaneously in response to the onset of the baby's own respiratory effort. The patient may breathe spontaneously between set ventilator's mechanical breaths. In small preterm infants, this leads to inequable tidal volumes and high work of breathing due to high airway resistance.

The A/C ventilation is also called synchronized intermittent positive pressure ventilation or patient-triggered ventilation. In A/C ventilation, the ventilator supports every spontaneous breath; therefore, this leads to more uniform tidal volume and lower work of breathing than SIMV. In case of apnea, the mechanical breaths are provided by preset backup rate.

Pressure support ventilation (PSV) is similar to A/C mode. PSV is a pressure-limited, flow-cycled ventilation mode. The rate and pattern of breathing depend on patient's performance. As a ventilation method, it can be used alone or in combination with SIMV. PSV can be also used with volume-targeted ventilation method. When it is used in this combination, the breath is terminated by volume.

All these volume-targeted ventilation methods allow controlling the volume of gas delivered to the newborn's lung. There are, however, different modes which deliver and maintain the volume in different ways. These modes are volume guarantee (VG), pressure-regulated volume control (PRVC), and volume-assured pressure support (VAPS). However, there is no consensus yet on which modality is better.

There are a few clinical trials comparing the use of PRVC to other modes in newborn infants. In a small study, it was demonstrated that PRVC application resulted in remaining shorter time for extubation in extremely low birth weight infants in comparison with the time-cycled pressure-limited ventilation.[40]

VAPS is a hybrid mode that combines the advantages of pressure and volume ventilation. VAPS can be used with both A/C and SIMV or by itself in infants with reliable respiratory drive. It may be described as “variable-flow volume ventilation."[41] There are no published data comparing VAPS to another mode of ventilation in newborn infants.

VG is the most frequently used mode of volume-targeted ventilation and can be combined with SIMV, A/C, and PSV. The clinician choses a target tidal volume and selects a pressure limit. The ventilator adjusts the inspiratory pressure based on the exhaled tidal volume of the previous breath to deliver the tidal volume that has been set. The pressure required to deliver the tidal volume will automatically decrease as the patient's lung compliance improves automated weaning.

VG allows appropriate use of tidal volume aiming to reduce lung damage.[42] Lista et al.[43] demonstrated the level of proinflammatory cytokines playing a role in the development of BPD and a trend toward shorter duration of mechanical ventilation with VG than pressure-limited ventilation. They also showed that PSV plus VG mode was a better ventilation mode at the weaning phase of very low birth weight infants on mechanical ventilation support for RDS, because it reduced the frequency of postextubation atelectasis and used less positive inspiratory pressure.[44] The tidal volume was more stable when VG was combined with A/C or PSV than SIMV. In a randomized clinical trial involving 34 very low birth weight infants, it was demonstrated that pulmonary mechanics was not different between the uses of PSV plus VG and SIMV plus VG whereas reintubation rate was significantly common in the latter combination.[45] Finally, in a recent meta-analysis including 20 studies and comparing volume-targeted ventilation and pressure-limited ventilation, using volume-targeted ventilation modes was shown to yield better outcome as reducing rate of mortality and incidences of BPD, pneumothoraces, hypocarbia and severe cranial ultrasound pathologies, and duration of ventilation.[46] However, there is no study comparing VG with different modes of volume-targeted ventilation so far.

High-frequency ventilation

The rationale and clinical application of HFV is quite different from the conventional mechanical ventilation methods. The high-frequency ventilator devices are applied as “high-frequency jet ventilation,” “high-frequency flow interrupter,” “high-frequency oscillatory ventilation,” or hybrid forms. The most common approach to HFV use is high-frequency oscillation.

The common point of HFV modes is nontidal volume. HFV devices use small tidal volumes less than anatomical dead space with supraphysiological respiratory rates. The rationale for the application results from its ability to preserve end-expiratory lung volume when avoiding overdistension at end-inspiration and limiting the potential for ventilator-associated lung injury. HFV produces vibrations that facilitate gas exchange and prevent obstruction by activating secretions in the lungs.

The limitation of HFV is that the lung mechanics and the delivered gas volume cannot be monitored as it is in conventional ventilation methods. This problem has been overcome with the emerging technologies. The randomized clinical trials comparing elective HFV with conventional ventilation modes have shown conflicting results.[47],[48] Although it was shown that HFV slightly reduced the risk of chronic lung disease, no significant result has been yet achieved.[49]


  Conclusion Top


In addition to lung-protective ventilation techniques, optimal intensive care support, early rescue surfactant treatment, and early caffeine treatment can be an option in treating preterm infants with RDS to increase survival and reduce the incidence of BPD.[18],[50] Lung-protective strategies in newborn infants with RDS are summarized in [Figure 1]. Nowadays, it is also recommended to use animal-derived surfactant preparations via less invasive surfactant administration method.[51]
Figure 1: Lung-protective strategies in newborn infants with respiratory distress syndrome

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Lung-protective ventilation in the newborn infants has been a recent trend as a primary mode of ventilation support for early management of RDS. However, there is currently no ideal ventilation technique for the prevention of preterm infants from lung injury. NIV techniques seem to be superior to invasive ventilation. Further randomized controlled trials involving large numbers of patients are needed for a well-established protocol.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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