Unraveling the Links Between the Initiation of Ventilation and Brain Injury in Preterm Infants

Abstract

The initiation of ventilation in the delivery room is one of the most important but least controlled interventions a preterm infant will face. Tidal volumes (V T) used in the neonatal intensive care unit are carefully measured and adjusted. However, the V Ts that an infant receives during resuscitation are usually unmonitored and highly variable. Inappropriate V Ts delivered to preterm infants during respiratory support substantially increase the risk of injury and inflammation to the lungs and brain. These may cause cerebral blood flow instability and initiate a cerebral inflammatory cascade. The two pathways increase the risk of brain injury and potential life-long adverse neurodevelopmental outcomes. The employment of new technologies, including respiratory function monitors, can improve and guide the optimal delivery of V Ts and reduce confounders, such as leak. Better respiratory support in the delivery room has the potential to improve both respiratory and neurological outcomes in this vulnerable population.

Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room

“…Initiation of ventilation causes brain pathology through the same two mechanistic pathways, which are key to perinatal brain injury: haemodynamic instability and a localised cerebral inflammatory response 44. In the delivery room, pressure-limited ventilation is predominately used resulting in large variable V T deliveries 3–6.…”

“…This alters pulmonary venous return and cardiac output, which results in large swings in cerebral blood flow 45–47. Furthermore, PPV and PEEP induce variability in intrathoracic pressure, which affects preload, afterload and myocardial contractility causing changes in cerebral hemodynamics 44. Preterm infants <1500 g have impaired autoregulation due to their cerebral immaturity, which can cause hypoxia/ischaemia (if cerebral blood flow is low) or cerebral haemorrhage (if cerebral blood flow is high or rapidly fluctuating between low and high flows) 48.…”

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs

“…Preterm neonates exposed to inadvertently injurious ventilation at birth are at increased risk of brain injury [21] . We previously demonstrated that early administration of 5,000 IU/kg EPO worsened lung and brain inflammation and injury caused by the initiation of injurious ventilation [18,19] .…”

Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies

“…However, despite the reduction in the number of infants requiring intubation and/or IPPV, this has not translated into improved neurological outcomes [12]. Mechanisms responsible for brain injury arising from IPPV have been identified via animal experimentation and reviewed in detail previously [13], and hence this review will focus on IPPV. Mechanistic investigations of brain injury associated with non-invasive ventilation strategies are lacking, but we anticipate that the underlying causes are similar to those elicited by IPPV.…”