Mechanical Ventilation and Bronchopulmonary Dysplasia

Key points

What is ventilator-associated lung injury?

The huge number of articles published since the first description of ventilator-associated lung injury (VALI) highlights its importance and the incomplete understanding of this complex subject. The central role of MV and oxygen exposure in VALI and subsequent development of BPD have been recognized since the early days of neonatal medicine. In 1975, Alistair Philip described the etiology of BPD as “oxygen plus pressure plus time.”⁹ Although fundamentally this concept still holds, it has since

Mitigating ventilator-associated lung injury

Because some degree of impairment of normal pulmonary development is probably inevitable when an extremely preterm fetus is suddenly thrust into a hyperoxic (by fetal standards) environment and must initiate air breathing with lungs that are incompletely developed, it is unlikely that advances in neonatal care, including avoidance of MV, can completely prevent impairment of lung structure and function. Optimal respiratory and general supportive care, however, can minimize the overlay of

Importance of the golden first hour

The time immediately after birth when air breathing is initiated in a structurally immature surfactant deficient lung has been recognized as a critical time that may rapidly and irrevocably initiate the process of lung injury and repair. To achieve a successful transition to extrauterine life, newborn infants must rapidly aerate their lungs, clear lung fluid from the air spaces, and maintain a functional residual capacity (FRC), ultimately facilitating a dramatic increase in pulmonary blood

Positive end-expiratory pressure in the delivery room

The use of positive end-expiratory pressure (PEEP)/continuous positive airway pressure (CPAP) during initial stabilization of preterm infants mitigates the effect of excessively compliant chest wall and surfactant deficiency by stabilizing alveoli during the expiratory phase and has been shown to help establish FRC. Siew and colleagues¹⁸ demonstrated the beneficial effects of PEEP by using phase-contrast radiography in preterm rabbits, showing that virtually no FRC was established after several

Sustained inflation

Because liquid has much greater viscosity than air, resistance to moving liquid through small airways is orders of magnitude higher than that for air, making the time constants required to clear fluid from the airways much longer. Recognition of these factors supports the concept that a prolonged (sustained) inflation applied soon after birth should be more effective than short inflations in clearing lung fluid in the first minutes of life. Theoretically, ensuring effective lung recruitment

Hyperoxic injury

Preterm infants have immature antioxidant defenses, making them more susceptible to oxidative stress from relative or absolute hyperoxia. Several studies of early respiratory management in the delivery room evaluated whether reducing oxygen exposure results in improved respiratory outcomes. A single-center randomized clinical trial (RCT) in infants born at 24 to 28 weeks’ gestation demonstrated less oxidative stress, lower proinflammatory cytokine levels, and a lower incidence of BPD (15.4% vs

Noninvasive respiratory support

There is little doubt that avoiding MV reduces iatrogenic lung injury superimposed on the inevitable arrest of pulmonary development. Although earlier cohort comparisons of CPAP or MV suggested a large reduction in the risk of BPD,³² a series of more recent RCTs showed a much more modest benefit of avoiding MV. A meta-analysis of 4 recent RCTs2, 3, 33, 34 that enrolled nearly 2800 preterm infants showed that BPD rates were not significantly reduced by the use of different types of nasal CPAP

Less invasive surfactant administration

Traditionally, the avoidance of intubation and MV and the use of noninvasive respiratory support have meant a trade-off between the presumed benefits of this approach and the well documented benefits of surfactant replacement therapy. Early surfactant trials suggested that prophylactic surfactant administration was superior to rescue use⁴⁰; thus, some clinicians still intubate very premature infants in the delivery room for the sole purpose of administering surfactant. It must be recognized,

Lung-protective strategies of mechanical ventilation

There are numerous modes and modalities of MV and little high-quality evidence to guide clinicians in selecting the optimal method. A detailed discussion of these techniques is beyond the scope of this article; interested readers are referred to several recent reviews of the topic.47, 48 Key principles of lung-protective strategies, however, are outlined.

Putting it all together

Based on the key concepts discussed previously, certain general guidelines for the use of MV can be formulated. The overarching goal is to support adequate gas exchange with the minimum of adverse effects on the infant’s lungs, hemodynamics, and brain. Longer duration of ventilation is associated with increased likelihood of chronic lung disease, late-onset sepsis, and neurodevelopmental impairment; therefore, successful extubation at the earliest possible time is desirable. Ventilation

Summary

Although even with optimized respiratory care it is likely that some degree of lung injury is inevitable in ELBW infants, the wide variation in the risk-adjusted incidence of BPD among the academic medical centers that comprise the Neonatal Research Network suggests that MV and other clinical practices are potentially modifiable risk factors.82, 83 Although the evidence to guide respiratory support strategies remains incomplete, the key concepts outlined in this review are based on the best