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. 2012;7(6):e39535.
doi: 10.1371/journal.pone.0039535. Epub 2012 Jun 22.

Initiation of resuscitation with high tidal volumes causes cerebral hemodynamic disturbance, brain inflammation and injury in preterm lambs

Graeme R Polglase  1 , Suzanne L Miller, Samantha K Barton, Ana A Baburamani, Flora Y Wong, James D S Aridas, Andrew W Gill, Timothy J M Moss, Mary Tolcos, Martin Kluckow, Stuart B Hooper
Affiliations

Initiation of resuscitation with high tidal volumes causes cerebral hemodynamic disturbance, brain inflammation and injury in preterm lambs

Graeme R Polglase et al. PLoS One. 2012.

Abstract

Aims: Preterm infants can be inadvertently exposed to high tidal volumes (V(T)) 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 V(T) resuscitation strategy to a less injurious resuscitation strategy on cerebral haemodynamics, inflammation and injury.

Methods: Preterm lambs at 126 d gestation were surgically instrumented prior to receiving resuscitation with either: 1) High V(T) targeting 10-12 mL/kg for the first 15 min (n = 6) or 2) a protective resuscitation strategy (Prot V(T)), consisting of prophylactic surfactant, a 20 s sustained inflation and a lower initial V(T) (7 mL/kg; n = 6). Both groups were subsequently ventilated with a V(T) 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.

Results: High V(T) lambs had worse oxygenation and required greater ventilatory support than Prot V(T) lambs. High V(T) 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 V(T) resuscitation significantly amplified the effect (p = 0.014 and p<0.001). Vascular extravasation was evident in the brains of 60% of High V(T) lambs, but not in UVC or Prot V(T) lambs.

Conclusion: High V(T) resulted in greater cerebral haemodynamic instability, increased brain inflammation, oxidative stress and vascular extravasation than a Prot V(T) strategy. The initiation of resuscitation targeting Prot V(T) may reduce the severity of brain injury in preterm neonates.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Peak inspiratory pressure (A), tidal volume (B), dynamic compliance (C) and the fraction of inspired oxygen (FiO2; D) in High VT (open circles) and Prot VT (closed circles) lambs.
*p<0.05 High VT vs. Prot VT.
Figure 2
Figure 2. The partial pressure of arterial (Pa) carbon dioxide (CO2; A), oxygen (O2; B), oxygenation index (C) and the alveolar-arterial difference in oxygen (AaDO2; D) in High VT (open circles) and Prot VT (closed circles) lambs.
*p<0.05 High VT vs. Prot VT.
Figure 3
Figure 3. Left (A) and right (B) carotid blood flow (CABF) and mean arterial pressure (C) in High VT (open circles) and Prot VT (closed circles) lambs.
*p<0.05 High VT vs. Prot VT.
Figure 4
Figure 4. Tissue oxygenation index (TOI; A & B) and cerebral blood volume (C & D) in High VT (open circles) and Prot VT (closed circles) lambs.
Values are derived using spatially resolved near infrared spectroscopy. Note the greater variability in TOI within the first 15 min during High VT lambs (B) compared to Prot VT. Cerebral vascular vasoparalysis is evident in 4 of 5 High VT lambs by the maintenance of near stable cerebral blood volume (D).
Figure 5
Figure 5. Lung pro-inflammatory mRNA cytokine expression of interleukin (IL)-1β, IL-6 and IL-8 in unventilated controls (open bars), Prot VT (shaded bars) and High VT (black bars) lambs.
Values are expressed relative to UVC. Resuscitation, irrespective of the strategy, increased lung inflammation. *p<0.05 vs UVC.
See this image and copyright information in PMC

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