Increased peak end-expiratory pressure in ventilated preterm lambs changes cerebral microvascular perfusion: direct synchrotron microangiography assessment

Abstract

Positive end expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondary to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral haemodynamics in the preterm brain is unknown. We aimed to assess the effect of PEEP on microvessels in the preterm brain using synchrotron radiation (SR) microangiography which, enables in vivo real-time high-resolution imaging of the cerebral vasculature. Preterm lambs (0.8 gestation, n=4) were delivered via caesarean section, anaesthetised and ventilated. SR microangiography of the right cerebral hemisphere was performed with iodine contrast administered into the right carotid artery, during PEEP ventilation of 5 and 10 cmH2O respectively. Carotid blood flow was measured using an ultrasonic flow probe placed around the left carotid artery. An increase of PEEP from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm), but decreased diameter of larger cerebral vessels (>500 µm) in all 4 lambs. Additionally, the higher PEEP increased the cerebral contrast transit time in 3 of the 4 lambs. Carotid blood flow increased in 2 lambs which, also had increased carbon dioxide levels during PEEP 10. Our results suggest that PEEP of 10 cmH2O alters the preterm cerebral haemodynamics, with prolonged cerebral blood flow transit and engorgement of small cerebral microvessels likely due to the increased intrathoracic pressure. These microvascular changes are generally not reflected in global assessment of cerebral blood flow or oxygenation.

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

“…We have previously utilised synchrotron microangiography to investigate cerebral haemodynamics in the preterm newborn lamb which has a brain size comparable to that of the human newborn. 21 The current study has explored and extended the use of synchrotron microangiography in functional brain imaging for the first time and has characterised the functional haemodynamic response based on changes in microvessels in the immature brain. We found that in response to somatosensory stimulation of increasing durations in the 7-10-day old term lambs, more cerebral microvessels were recruited as indicated by vessel contrast transit and visualisation, but there was no overall change in the vessel diameters of the visibly perfused vessels at different durations of stimulation.…”

“…The ewe was intubated, placed in a prone position and anaesthesia was maintained via inhaled 1-2.5% isoflurane with mechanical ventilation and fractional inspired oxygen to keep peripheral arterial oxygen saturation (SpO 2 ) >95%. Preterm lambs were partially exteriorized via a maternal midline abdominal incision and hysterotomy for fetal instrumentation as described previously, 21 whilst maintaining the placental-umbilical circulation. Briefly, a nonocclusive polyvinyl catheter was inserted into the fetal right carotid artery with the catheter tip at the level of the mandibular angle, before the carotid bifurcation, for administration of iodine contrast agent.…”

“…SR cerebral microangiography in the lambs was performed as previously described. 21 In brief, the lamb was put in the prone position, facing and in line with the horizontal path of the X-ray beam. The lamb's head was then rotated anti-clockwise in the horizontal plane with the nose pointing at the 10-11 o'clock position (Figure 1(a)).…”

“…Analysis of vessel counts and vessel diameter measurements were performed as described previously. 21 Briefly, image analysis was performed using ImageJ software (version 2.0.0-rc-69/1.52p, National Institutes of Health). Images were processed by first enhancing image contrast achieved using temporal subtraction.…”

Aeration Strategy at Birth Does Not Impact Carotid Haemodynamics in Preterm Lambs

“…(11) The impact of higher PEEP levels at birth is less clear, with a recent pilot lamb study suggesting engorgement of micro-vessels and an increase in CeBF. (12) . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”