Presented at the Neonatal Society 2009 Spring Meeting.
Chakkarapani E1, Liu X1, Aquilina K1, Hoque N1, Dingley J2, Thoresen M1
1 Science at South Bristol, University of Bristol, Bristol, UK
2 School of Medicine, University of Wales, Swansea, UK
Background & Aim: Cerebral Autoregulation (CA) is impaired in hypoxic ischaemic encephalopathy (HIE) (1). Cerebrovascular pressure reactivity, the ability of cerebral vessels to respond to transmural pressure changes, is a key component of CA. PRx is a surrogate measure of cerebrovascular pressure reactivity and is calculated as a moving correlation coefficient between mean Intra-Cranial Pressure (ICP) and Mean Arterial Blood Pressure (MABP). Negative and positive PRx values denote normal and abnormal cerebrovascular pressure reactivity respectively (2). As PRx correlates with other measures of CA and a global estimate of cerebrovascular pressure reactivity, we hypothesised that in our global pig HIE model (3).
1) PRx will be normal in HIE associated with favourable neuropathology outcomes and abnormal where these outcomes are adverse.
2) 18h Xenon combined with 12h Hypothermia (XeHT) will improve the PRx score post-HIE as compared to 12h HT alone or normothermia (NT).
Methods & Statistics: All procedures were conducted under UK Home office licence. In 35 newborn piglets (mean age (16.8h), weight (1597g), the inspired oxygen was reduced to ~5%, depressing the EEG to 7µv for 45 min giving a global HI insult (3). The pigs were randomised to NT =12 (T rec 38.5°C); HT12h =9 and XeHT = 14, and had PRx assessment during the insult and subsequent management. PRx was calculated as a correlation coefficient of mean ICP and mean ABP over 5 minute periods. All groups had HI insults of similar severity. After HI, they were ventilated under iv anaesthesia. HT and XeHT animals were cooled immediately after HI to a 33.5°C rectal temperature for 12h and rewarmed over a further 6h. XeHT animals received 18h of 50% Xe, 30%O2 and 20%N2 using a closed-circuit breathing system to conserve xenon (4). At 72h, the pigs underwent autopsy with terminal perfusion fixation of the brain by cannulating common carotid arteries using 10% formaldehyde followed by histopathological examination. ‘Favourable’ outcome was defined as the mean global neuropathology score < 1.75 (mean global neuropathology score range 0.0 to 4.0) and adverse outcome was defined as the mean global neuropathology score > 1.76 (3). Median PRx was calculated from the start of HI insult until 32 h into the recovery period. Results were analysed by students ‘t’ and Kruskal Wallis tests.
Results: Median PRx was negative in the favourable neuropathology outcome (mean (sem)) (-0.048(0.02)) and positive in the adverse outcome group (0.036(0.03)) (p = 0.04, t test). Median PRx over 32h was lowest in the XeHT group (-0.032 (-0.43, 0.07) followed by HT (-0.002(-0.55, 0.12)) and NT (0.028(-0.10, 0.15). (p < 0.0001, KW test).
Conclusion: PRx results from brain trauma patients were reproduced in this neonatal HIE model, good outcomes correlating with low PRX values (ie normal vasoreactivity). HIE pigs with favourable neuropathology had significantly more normal cerebrovascular pressure reactivity. Combined XeHT treatment following HI maintained the cerebrovascular reactivity in the normal range and was better than hypothermia or normothermia. Adding Xe to HT normalised the cerebral autoregulation after HIE as compared to HT.
References
1. Paulson OB Cerebrovasc Brain Metab Rev 1990;2:161-192
2. Zweifel C Neurosurgical focus 2008;25:E2.
3. Thoresen M Pediatr Res 1996;40:738-748.
4. Chakkarapani E Anesthesia & Analgesia (2009 in press)