ReviewLung-protective ventilatory strategies in intubated preterm neonates with RDS
Introduction
There is an increasing interest for avoiding endotracheal intubation by increased use of non-invasive ventilation (NIV) [1], [2], [3], [4], including nasal continuous positive airway pressure (NCPAP), nasal intermittent positive airway pressure (NIPPV), nasal high frequency ventilation (nHFO), and high flow nasal cannula (HFNC) for respiratory support in preterm infants. Nevertheless, endotracheal intubation and mechanical ventilation (MV) is a lifesaving therapy and is commonly required, either in the delivery room (DR) or neonatal intensive care unit (NICU). Failure of NIV may be as high as 60%, depending on gestational age, birth weight, disease severity, mode of NIV and other perinatal variables [5], [6]. However, early and even short MV with high intrathoracic airway pressures and tidal volumes (TV) may cause injury to the lungs and other organs like the brain due to hemodynamic disturbances and/or inflammatory mediator-induced systemic responses [7], [8]. Acute and chronic pulmonary ventilator- induced/or associated lung injury (VILI) are pulmonary air leaks such as pneumothorax or pulmonary interstitial emphysema (PIE) and bronchopulmonary dysplasia (BPD), a form of chronic lung disease (CLD). BPD, regardless of diagnostic criteria [either continued oxygen requirement at 28 days of life or at 36 weeks postmenstrual age (BPD 36wks)], is the most common short-term adverse outcome in very preterm infants and may be associated with impairments in respiratory and neurological long-term outcomes [9], [10], [11], [12]. Although the “classical, old” picture of BPD changed in the last decade [9], with the increased survival of infants with extremely low gestational age (< 28 weeks) and birth weight (< 1000 g, ELBWI) the overall BPD incidence has not changed and continues to be a challenging problem in neonatology [1]. Therefore, various lung-protective ventilatory strategies (LPVS) were introduced to minimize lung injury associated with MV. These are the different modes of patient triggered or synchronized ventilation (PTV, High Frequency Positive Pressure Ventilation with short inspiratory times and ventilator rates > 60/min (HFPPV)), volume targeted ventilation (VTV), INSURE strategy (INtube, SURfactant- Extubate to NCPAP), High Frequency Ventilation (HFV) (including High Frequency Oscillatory Ventilation (HFOV) and High Frequency Jet Ventilation (HFJV) and permissive hypercapnia (PH). Furthermore, one may add lung recruitment with the “open lung” concept, and the manual or automatic control of oxygen to facilitate appropriate targeting of peripheral oxygen saturation (SpO2). The main goals of LPVS are avoidance of volutrauma, atelectotrauma, and oxygen toxicity. The aim of this narrative review article is to provide an update of LPVS during MV including the evaluation of long-term effects on pulmonary and neurodevelopmental outcomes in preterm infants with respiratory distress syndrome (RDS). For SpO2 monitoring and the option of automated oxygen control we refer to other recently published articles in the literature [13], [14], [15], [16], [17].
Section snippets
Patient-triggered, synchronized ventilation
Synchronization of spontaneous breathing efforts with inflations provided by the ventilator, either by adjusting ventilator rate and inspiratory time or by using triggered ventilation, has shown to have several benefits compared to non synchronized ventilation including consistent TV, improved oxygenation, less use of sedatives/analgesic drugs, and shorter duration of MV [18]. There are different PTV-techniques available in modern ventilators like “Synchronized Intermittent Mandatory
Volume targeted ventilation
From experimental and clinical studies in the late 1980s and 1990s in adults, it became increasingly evident that not pressure but volume significantly contributes to lung injury during MV [31], [32], [33]. The historical and classical term barotrauma was then shifted to other types of VILI like volutrauma, rheotrauma, atelectotrauma, biotrauma [34], volutrauma being considered to be the key determinant of VILI [34]. For a long period “Time Cycled Pressure Limited” ventilation with TV varying
INSURE-Strategy
The clinical implementation of surfactant as a safe and efficient therapy for preterm infants with RDS during MV in the early 1990s can be considered as a milestone in neonatal intensive care resulting in a significant reduction in neonatal mortality and short-term respiratory morbidity [1], [52], [53]. Nevertheless, the incidence of BPD has not changed. This might be explained by its multifactorial etiology and the invasive nature of intubation, positive pressure ventilation (PPV) and
Lung recruitment and the “open lung” concept
RDS is the most frequent respiratory disease in preterm neonates and it's severity correlates inversely with gestational age. Surfactant deficient lungs of preterm infants with severe RDS are characterized by marked lung opacification, poor lung function with low compliance and functional residual capacity (FRC), high oxygen requirements and poor gas exchange. Despite surfactant replacement therapy being a landmark in the treatment of RDS the basic ventilation concept in atelectatic lungs is
Permissive Hypercapnia
The tolerance of arterial partial pressure of carbon dioxide (pCO2) >45 mmHg by using a minimal ventilatory support strategy is referred to as permissive hypercapnia (PH). PH is common in many NICUs and neonatologists have PH accepted as a way of facilitating weaning from MV with the potential of reducing VILI. Mariani et al [71] first described in 1999 a ventilator strategy of PH in preterm neonates who received assisted ventilation to be feasible, safe and reducing the duration of ventilation.
Conventional versus unconventional mechanical ventilation
CMV is generally referred to as PPV with frequencies and VT in the physiological range of a spontaneously breathing preterm infant and is considered a standard treatment for RDS. Unconventional MV is usually defined as a strategy using supra-physiological ventilator frequencies and VT close to the airway dead space with lower inflation pressures at the alveolar level compared to CMV. There are generally two types of HFV used in the NICU, HFOV and HFJV [77], HFOV being more commonly used. HFOV
Conclusion
Various approaches have been developed and implemented in the respiratory care of preterm infants over recent decades. Techniques and strategies of LPVS aim to accelerate weaning from MV and to protect against VILI. There are different modes of LPVS, with inconsistencies in short- and long-term benefits for respiratory and neurological outcomes. Currently several LPVS may be combined or individually and sequentially applied (Fig. 1), NIV starting in the DR being a potentially important first
Directions for future research
Future studies should examine further improvements of efficiency of NIV and MV applied in the DR and NICU and to evaluate their impact on various gestational ages, and disease severity, focusing on long-term respiratory and neurological outcomes. It will be important to combine LPVS with new modalities and techniques to prevent lung and/or brain injury. Among these are optimization of exogenous surfactant treatment [87], [88], early low-dose hydrocortisone [89] and high-dose oral vitamin A in
Educational Aims
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To get a closer insight into the mechanism of lung injury during mechanical ventilation and the available lung protective ventilatory strategies (LPVS) in intubated preterm neonates with RDS.
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To describe the different LPVS used in the management of RDS.
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To emphasize the importance of monitoring during LPVS.
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To evaluate short-and longterm-outcomes in studies with LPVS.
Practice Points
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A single recommendations on optimal LPVS cannot be made.
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Different modes of LPVS may be may be combined or individually and sequentially applied, early use of non-invasive ventilation being a potential important first step in the prevention of lung injury.
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HFO with an high-lung volume strategy or using a lung-protective concept during CMV seems equally effective.
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There are inconsistencies in short- and long-term benefits for respiratory and neurological outcomes.
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