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.
Highlights
Brain injury, white matter injury and intracranial hemorrhage, is a major problem in very premature infants and the incidence and severity increases with decreasing gestational age and birth weight [1]
Ventilation and Oxygenation Peak inspiratory pressure was higher in the High VT group during the initial 15 min resuscitation period, as expected, and remained higher for the subsequent 75 min ventilation period (p = 0.002; Figure 1A) compared to the Prot VT group
The mean tidal volume obtained in the High VT group in the first 15 minutes was 12.560.3 mL/kg (Range 10.9–13.4 mL/kg) while in the Prot VT group it was 7.060.2 (Range 6.7–7.2 mL/kg; p,0.001; Figure 1B)
Summary
White matter injury and intracranial hemorrhage, is a major problem in very premature infants and the incidence and severity increases with decreasing gestational age and birth weight [1]. In addition to immaturity of the brain at the time of preterm birth, these babies may be exposed to systemic pathogenic factors such as infection/inflammation (both ante- and post-natal) and disturbed cerebral blood flow [2,3,4]. Recent clinical trials find that many preterm infants are inadvertently exposed to high tidal volumes (VT) during the initial resuscitation in the delivery room [5,6]. The initiation of respiratory support after birth, with high VT, can induce an inflammatory response leading to chronic diseases of the lung such as bronchopulmonary dysplasia [8,9]
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