Initiation of Resuscitation with High Tidal Volumes Causes Cerebral Hemodynamic Disturbance, Brain Inflammation and Injury in Preterm Lambs

Abstract

AimsPreterm infants can be inadvertently exposed to high tidal volumes (VT) in the delivery room, causing lung inflammation and injury, but little is known about their effects on the brain. The aim of this study was to compare an initial 15 min of high VT resuscitation strategy to a less injurious resuscitation strategy on cerebral haemodynamics, inflammation and injury.MethodsPreterm lambs at 126 d gestation were surgically instrumented prior to receiving resuscitation with either: 1) High VT targeting 10–12 mL/kg for the first 15 min (n = 6) or 2) a protective resuscitation strategy (Prot VT), consisting of prophylactic surfactant, a 20 s sustained inflation and a lower initial VT (7 mL/kg; n = 6). Both groups were subsequently ventilated with a VT 7 mL/kg. Blood gases, arterial pressures and carotid blood flows were recorded. Cerebral blood volume and oxygenation were assessed using near infrared spectroscopy. The brain was collected for biochemical and histologic assessment of inflammation, injury, vascular extravasation, hemorrhage and oxidative injury. Unventilated controls (UVC; n = 6) were used for comparison.ResultsHigh VT lambs had worse oxygenation and required greater ventilatory support than Prot VT lambs. High VT resulted in cerebral haemodynamic instability during the initial 15 min, adverse cerebral tissue oxygenation index and cerebral vasoparalysis. While both resuscitation strategies increased lung and brain inflammation and oxidative stress, High VT resuscitation significantly amplified the effect (p = 0.014 and p<0.001). Vascular extravasation was evident in the brains of 60% of High VT lambs, but not in UVC or Prot VT lambs.ConclusionHigh VT resulted in greater cerebral haemodynamic instability, increased brain inflammation, oxidative stress and vascular extravasation than a Prot VT strategy. The initiation of resuscitation targeting Prot VT may reduce the severity of brain injury in preterm neonates.

Hypoxic–ischemic brain damage induces distant inflammatory lung injury in newborn piglets

“…Although much less studied, lung injury can also induce inflammatory brain damage. In this regard, a recent experimental study demonstrates that ventilation with excessive tidal volume during resuscitation at birth induces lung injury and triggers brain inflammation (34). Characteristically, the lung, whose epithelial surface area is so vast that its cross-sectional area is approximately the size of a tennis court, receives most of the systemic blood flow (35).…”

Respiratory support for premature neonates in the delivery room: effects on cardiovascular function and the development of brain injury

“…Review apart from reduced vascular permeability (Figure 4) (4,48), suggesting that simply improving the initial respiratory care in the delivery room may reduce brain injury.…”

“…Considering that systemic proinflammatory cytokines can readily cross the blood-brain barrier (45,57), the circulating cytokines can elicit and exacerbate an inflammatory response within the brain. This can result in increased number of infiltrating inflammatory cells, activation of resident microglia (which causes local amplification of proinflammatory cytokines), increased oxidative stress, and subsequent diffuse white matter gliosis within the periventricular white matter, subcortical white matter, and corpus callosum (Figure 4) (4,58,59). This brain inflammatory environment, notably an increase in activated microglial cells, is a prominent feature of neuropathologies and can be correlated with brain cell death (60).…”

“…Thus, we suggest a progressive series of events that begins with initiation of suboptimal ventilation, which in turn stimulates a systemic proinflammatory cascade and may then directly result in inflammation-induced white matter injury or indirectly cause white matter injury through initiation of hemodynamic instability. Importantly, a recent study demonstrated that optimizing the initial respiratory support at birth in preterm lambs reduced the initiation of a systemic inflammatory cascade and improved the subsequent brain inflammation and injury (4). This indicates that it is not ventilation per se that is injurious but the poorly controlled use of PPV in the delivery room that can significantly increase the risk of brain injury.…”

Sustained inflation at birth did not protect preterm fetal sheep from lung injury

“…The combination of surfactant deficiency and increased lung fluid in the airways leads to increased sheer force injury to the airways during the initiation of ventilation at birth in preterm lambs (10). Large V T ventilation at birth also causes systemic inflammation and brain injury (12,33). These systemic effects are less pronounced with moderate V T (33).…”