Caterina Silvia Barbàra

Current strategies for treating infants with severe bronchopulmonary dysplasia.

Advances in neonatal intensive care have markedly improved survival rates for infants born at a very early lung development stage (<26 weeks gestation). In these premature infants, even low inspired oxygen concentrations and gentle ventilatory methods may disrupt distal lung growth, a condition described as “new” bronchopulmonary dysplasia (BPD). BPD usually develops into a mild form, with only few infants requiring ventilator support and oxygen supplementation at 36 weeks post-conception. No magic bullets exist for treating infants with established severe BPD. Current management of the disease aims at maintaining an adequate gas exchange while promoting optimal lung growth. Prolonged oxygen therapy and ventilator support through nasal cannulae or a tracheotomy are often required to maintain blood gases. Short-course, low-dose corticosteroids may improve lung function and accelerate weaning from oxygen and mechanical ventilation. Pulmonary hypertension is a major complication in infants with severe BPD. Pulmonary vasodilators, such as sildenafil followed by bosentan, may improve the oxygenation and pulmonary outcome.

Old and new uses of surfactant

Exogenous surfactant has been the primary life-saving therapy for respiratory distress syndrome (RDS) of preterm infants for many years. More recently, early surfactant treatment administered less invasively by transient endotracheal intubation and combined to nasal ventilation has been shown to further improve neonatal outcome by reducing the need of mechanical ventilation. In addition to RDS, other neonatal and pediatric respiratory disorders characterized by surfactant inactivation or dysfunction, such as pulmonary hemorrhage, aspiration pneumonia, and viral lower respiratory tract infection, might also be amenable to surfactant replacement therapy. However, the nature of lung injury and the influence of co-morbidities may reduce the efficacy of surfactant in these conditions. Currently under investigation are new syntethic surfactant formulations which may be more effective and resistant to inactivation than natural ones and could be produced at a lower cost. The use of surfactants to deliver drugs directly to the lung also seems to be a promising technique worthy of study.

Synchronized Nasal Intermittent Positive Pressure Ventilation of the Newborn: Technical Issues and Clinical Results

Although mechanical ventilation via an endotracheal tube has undoubtedly led to improvement in neonatal survival in the last 40 years, the prolonged use of this technique may predispose the infant to development of many possible complications including bronchopulmonary dysplasia. Avoiding mechanical ventilation is thought to be a critical goal, and different modes of noninvasive respiratory support beyond nasal continuous positive airway pressure, such as nasal intermittent positive pressure ventilation and synchronized nasal intermittent positive pressure ventilation, are also available and may reduce intubation rate. Several trials have demonstrated that the newer modes of noninvasive ventilation are more effective than nasal continuous positive airway pressure in reducing extubation failure and may also be more helpful as modes of primary support to treat respiratory distress syndrome after surfactant and for treatment of apnea of prematurity. With synchronized noninvasive ventilation, these benefits are more consistent, and different modes of synchronization have been reported. Although flow-triggering is the most common mode of synchronization, this technique is not reliable for noninvasive ventilation in neonates because it is affected by variable leaks at the mouth and nose. This review discusses the mechanisms of action, benefits and limitations of noninvasive ventilation, describes the different modes of synchronization and analyzes the technical characteristics, properties and clinical results of a flow-sensor expressly developed for synchronized noninvasive ventilation.

Control of breathing

The control system of breathing can be considered as a closed loop system, consisting of two subsystems: the controlling system and the controlled system. Both systems are defined by their input-output relationships. The controlling system is defined by the Respiratory Centers that are responsible for two separate, but overlapping, patterns: the automatic control pattern and the behavioral or voluntary control. In the controlling system the input is the blood gas value and the output is some parameters of ventilation. The controlled system is characterized by an input of ventilation and an output of blood gas values. In this closed loop system breathing is normally regulated by two anatomically distinct but functionally integrated elements, referred to as the metabolic and behavioral respiratory control systems. The metabolic control is concerned with blood gas homeostasis and the voluntary control relates with activities such as phonation and singing that use the ventilatory apparatus for purposes other than gas exchange.

Hospital management of severe bronchopulmonary dysplasia

Despite early surfactant therapy, betterventilator strategies and greater use of noninvasive positive pressure ventilation, bronchopulmonary dysplasia (BPD)continues to be a complication of premature births. The mainstay of supportive care for infants with severe BPD is mechanical ventilation with an endotracheal tube, however treatmentcan last for a long time and have many complications. When safe extubation is not possible because of multiple failed attempts, tracheostomy is sometimes recommended [1-5]. In all age groups outside the neonatal period, placement of a tracheostomy is considered after a few weeks of mechanicalventilation [6,7]. By contrast, the optimum time and safety procedures have not yet been determined for the placement of a tracheostomy in infants with BPD who need protracted ventilation. Reasons for not performing a tracheostomy in these patientsinclude technical concerns associatedwith small patient size or the need for high ventilator settings. On the other hand the placement of a tracheostomy early in the course of severe BPD could have positive effects such as improved comfort, decreased need for sedation, lower systemic corticosteroid exposure, and enhanced nutrition and growth. Recent data [8] suggest that a reasonable approach is that chronically ventilated infants should be assessed at 3 months of age, that is around or shortly after 40 weeks corrected gestational age. If the respiratory support remains high and has been so for 2 months with no evidence of improvement and after multiple attempts to wean the baby off positive pressure ventilation, then infants should be considered for a tracheostomy placement. Another important point highlighted by this report is that tracheostomies should be considered a safe procedure even in infants on high pressures and high concentrations of supplemental oxygen. Other results [9] suggest a potential association between earlier (<120 days) tracheostomy and better neurodevelopmental outcomes. Actually, while an infant awaits a tracheostomy, the medical focus is often on strategies to allow weaning and limit ventilator-associated lung injury. Following a tracheostomy, the focus may shift to maximizing parent–child interaction and developmental improvement. Furthermore, after tracheostomy, there is often an opportunity to wean the baby off sedating medications, which are frequently associated with increased risk of neurodevelopmental impairment. In conclusion tracheostomy does not mitigate the significant risk for adverse neurodevelopment that is associated with the many complications of prematurity; however, if tracheostomy is to be performed, earlier surgery may allow opportunities for enhanced neurodevelopmental outcomes.

High-Flow Nasal Cannula to Prevent Desaturation in Endotracheal Intubation: A Word of Caution.

Critical Care Medicine www.ccmjournal.org e327 The second point supporting our assertion comes from our preliminary experience in using HFNC to oxygenate infants undergoing endotracheal intubation, despite a high alveolar ventilation/functional residual lung capacity ratio and a high oxygen uptake with a consequently short desaturation time. We used HFNC in 20 infants younger than 3 months old undergoing endotracheal intubation and found that the benefit differed remarkably between those with healthy or injured lungs. Our study protocol consisted in giving 1–2 L/kg/min HFNC oxygen therapy 2 minutes before patients received sedation with fentanyl and propofol and then continuing HFNC during laryngoscopy and between attempts at intubation. If desaturation episodes less than 96% developed at any time, the mouth was gently closed to increase pharyngeal pressure, and when Sao 2 reached 100%, the procedure was resumed. If Sao 2 dropped to less than 86%, HFNC was suspended and the infant was bag ventilated. The results are shown in Table 1. We believe that despite physiologic differences between children and adults, these conflicting data underscore the need for randomized controlled trials to test the effect of HFNC before and during endotracheal intubation in patients stratified according to lung disease. The authors have disclosed that they do not have any potential conflicts of interest.

Management of acute lung injury and acute respiratory distress syndrome in infants

Acute lung injury and acute respiratory distress (ALI/ARDS) is a clinical syndrome caused primarily by increased permeability to proteins across the endothelial and epithelial barriers of the lungs. It is characterized as restrictive disease with reduced lung compliance caused by loss of surfactant function, atelectatic lung regions and accumulation of interstitial/alveolar plasma leakage. Patients usually develop acute respiratory failure rapidly because of arterial hypoxemia as well as impaired carbon dioxide excretion and elevated work of breathing. The American–European Consensus Conference (AECC) in 1994 defined ARDS as respiratory failure of acute onset with a PaO2/FiO2 ratio ≤200 mm Hg (regardless of the level of positive end expiratory pressure, PEEP) and bilateral infiltrates on a frontal chest radiograph. ALI is defined identically except for a higher PaO2/FiO2 limit of <300 mm Hg. A large prospective trial from Spain demonstrated that 1.4% of all patients admitted to the paediatric intensive care unit and 8.3% of all those mechanically ventilated met ARDS criteria [1]. Overall mortality in children suffering from ALI/ARDS ranges from 18 to 27%, but increases to 29–50% when considering only the ARDS group and is only 3–11% in those who do not develop ARDS [2]. It is essential, however, to distinguish between ALI/ARDS associated with direct pulmonary causes compared to systemic (indirect, extra-pulmonary) causes. In infants, as well as in children and adults, the most frequent direct cause of either ALI or ARDS is viral or bacterial pneumonia, followed by aspiration (e.g., gastric aspiration, meconium aspiration in newborns) and, less frequently, near-drowning and inhalation of toxicants. Indirect (systemic) causes of ALI/ARDS are primarily systemic infections followed by burn injury, hypovolemic shock, generalized trauma, multiple transfusions and other primary extra-pulmonary injuries. Indirect forms of ALI/ARDS have substantial multi-organ pathologies that