Mechanisms of Neonatal Lung Injury

Introduction

At birth, the term newborn lung is at the alveolar phase of lung development, with a smaller number of alveoli normalized to body weight than an adult has. The lung must make the rapid transition from a fluid-filled structure with low stretch frequency and low strain, to an air-filled structure subjected to high strain at variable frequency to support gas exchange. Spontaneous breathing efforts just after delivery at 40 weeks gestation can generate high transpleural or transpulmonic pressures during the first few breaths. Failure to reabsorb amniotic fluid can lead to uneven gas distribution during spontaneous breathing or positive pressure ventilation, generating stress points that contribute to strain, injury, alveolar rupture, and pneumothorax ( Fig. 69.1 ). The prevalence of spontaneous pneumothorax is undoubtedly higher than recognized because many are clinically insignificant. Pneumothorax is associated with meconium-stained amniotic fluid and elective repeat cesarean deliveries. In babies born very prematurely, at less than 26 weeks, the fetal lung is completing the transition from the canalicular stage to the saccular stage of development. Air sacs are relatively thick walled, and pulmonary capillaries are incompletely branched and do not extend to the ends of the alveolar septa. Surfactant synthesis and secretion are decreased. Enzymatic antioxidants, superoxide dismutase, catalase, and glutathione peroxidase are relatively low and less inducible than at term. Nutritional antioxidants such as vitamin E and retinoids are also relatively low. To support ventilation, the extremely premature newborn lung with these liabilities is often subjected to supplemental oxygen, endotracheal intubation, and positive pressure ventilation, all of which can injure a developing lung, leading to impaired alveolar development and chronic lung disease of prematurity, or bronchopulmonary dysplasia (BPD) ( Fig. 69.2 ). Neonatal lung injury likely impairs normal progenitor cell function during development and diminishes the capacity for repair following later insults.

Newer analyses of clinical approaches that avoid intubation, allowing for more gradual recruitment, appear to decrease the risk for BPD.

Mechanical Mechanisms of Lung Injury

Vulnerability to mechanical lung injury is significant immediately after birth. Present methods of mechanical ventilation unavoidably deliver nonuniform distending forces, which worsen ventilation-perfusion matching and induce cellular injury. Animal studies have shown that structural damage and inflammatory response can be generated after only a few overdistending breaths. Significant lung injury can take place after brief periods of mechanical ventilation of the incompletely recruited lung. Forced “recruitment” maneuvers may be harmful. Despite the promise suggested by prolonged sigh maneuvers in some animal models, preterm newborns requiring intubation at birth did not benefit. In preterm, surfactant-treated lambs, initial recruitment maneuvers with tidal volumes varying from 8 to 30 mL/kg had no benefit, and caused “dose-dependent” histologic damage with increasing tidal volumes. Lung volumes at less than optimal functional residual capacity (FRC) require higher than optimal peak pressures in later breaths to fully re-recruit alveoli. To minimize lung injury, strategies are aimed at identifying adaptive and proper goals of gas exchange which can decrease excessive administration of mechanical support to minimize harm and maximize benefit. These strategies include avoiding atelectrauma by promoting alveolar stability and minimizing de-recruitment, and the use of a broader range of acceptable target pulse oximetry (SpO ₂ ) in the delivery room to minimize the need for positive-pressure ventilation during stabilization after delivery. Maneuvers designed to avoid de-recruitment, such as use of continuous positive airway pressure (CPAP), have decreased injury markers in experimental models of prematurity and respiratory distress syndrome (RDS). To minimize volutrauma during the delivery room resuscitation, some recommend that the positive inspiratory pressure should be adjusted to deliver a tidal volume of 4 to 5 mL/kg. Choosing and delivering the appropriate tidal volume during delivery room resuscitation remain important, but as yet unrealized, goals in the quest to minimize lung injury, particularly in the extremely premature newborn at high risk for developing BPD.

Lung De-Recruitment

Trauma to delicate airways can easily result if the lung is de-recruited to volumes at less than FRC ( Fig. 69.3 ), resulting in alveolar collapse (atelectasis). Higher airway pressures are then required during subsequent mechanical breaths to re-recruit alveoli, leading to stretch injuries in terminal airways. The spontaneously breathing patient must generate greater negative pressures to achieve the same goal, also leading to the same stretch injury, higher work of breathing, and fatigued muscles of respiration. Considerations for mechanical ventilation strategies designed to avoid lung injury due to de-recruitment and atelectasis are discussed in Chapter 159 .