Positron emission tomography study of regional cerebral blood flow and flow–metabolism coupling during general anaesthesia with xenon in humans

Rex, Steffen; Meyer, Philipp T.; Baumert, J.‐H.; Rossaint, Rolf; Fries, Michael; Büll, U; Schaefer, Wolfgang M.

doi:10.1093/bja/aen036

Cited by 35 publications

(18 citation statements)

References 29 publications

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“…Although the mechanism of action of many anaesthetic agents is not fully understood, it is known that neuronal activity is depressed by GA. 24 It is extremely difficult to directly measure cerebral metabolism directly in vivo and studies have used a number of proxy measures, including changes in cerebral uptake of oxygen (CMRO 2 ) and relative glucose metabolic rate (rGMR) to identify changes in cerebral metabolic rate caused by anaesthetic agents. 25,26 Sevoflurane was found to decrease global cerebral GMR by 56% (p < 0.01).…”

Section: Discussionmentioning

confidence: 99%

Purine nucleoside use as surrogate markers of cerebral ischaemia during local and general anaesthetic carotid endarterectomy

et al. 2019

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Objectives: In periods of cerebral ischaemia, adenosine triphosphate is metabolised, leading to accumulation of adenosine inosine and hypoxanthine. These can be measured in real time using peripheral blood samples intraoperatively. The primary aim of this study was to describe changes in purine concentrations in a cohort of patients undergoing carotid endarterectomy under general anaesthetic, and to evaluate correlation between changes in values with major perioperative steps. The secondary aim was to compare changes in concentrations with a previous cohort of patients who had undergone carotid endarterectomy under local anaesthetic. Methods: This was a prospective observational study. Purine concentrations were determined from arterial line samples and measured via an amperometric biosensor at specific time points during carotid endarterectomy. Mean arterial pressure was manipulated to maintain steady cerebral perfusion pressure throughout the procedure. These results were analysed against data from a cohort of patients who underwent carotid endarterectomy under local anaesthetic in previously published work. Results: Valid results were obtained for 37 patients. Purine concentrations at baseline were 3.02 ± 1.11 µM and 3.16 ± 1.85 µM for the unshunted and shunted cohorts, respectively. There was no significant change after 30 min of carotid clamping at 2.07 ± 0.89 and 2.4 ± 3.09 µM, respectively (both p > 0.05). Peak purine during the clamp phase in the loco-regional anaesthetic cohort was 6.70 ± 3.4 µM, which was significantly raised compared to both general anaesthetic cohorts (p = 0.004). There were no perioperative neurological events in either cohort. Conclusion: This small study does not demonstrate conclusive evidence that purine nucleosides can be used as a marker of cerebral ischaemia; the comparisons to the loco-regional anaesthetic data offer information about differences in the cerebral adenosine triphosphate metabolism between general anaesthetic and loco-regional anaesthetic. We hypothesise that the lack of a rise in purine nucleosides under general anaesthetic may be caused by a decrease in the cerebral metabolic rate and loss of metabolic rate-blood flow coupling caused by general anaesthetic agents.

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Section: Discussionmentioning

confidence: 99%

Purine nucleoside use as surrogate markers of cerebral ischaemia during local and general anaesthetic carotid endarterectomy

et al. 2019

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“…Neuroprotection by xenon is most likely achieved by diverse mechanisms including antagonism at the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor [ 13 ], an enhanced synthesis of prosurvival (B-cell lymphoma 2 and extra large) proteins and the suppression of neuronal apoptosis [ 14 , 15 ]. Moreover, xenon preserves cerebral flow-metabolism coupling [ 16 , 17 ] and possesses anti-inflammatory qualities that may directly interfere with the pathogenesis of POD [ 18 ]. Furthermore, the favorable physicochemical properties of xenon result in rapid clearance from the brain, thereby reducing any residual anesthetic effects that may predispose to POD [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial

Tmimi

Velde

Herijgers

et al. 2015

Trials

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BackgroundPostoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass.Methods/DesignOne hundred and ninety patients, older than 65 years, and scheduled for elective cardiac surgery, will be enrolled in this prospective, randomized, controlled trial. Patients will be randomized to receive general anesthesia with either xenon or sevoflurane. Primary outcome parameter will be the incidence of POD in the first 5 postoperative days. The occurrence of POD will be assessed by trained research personnel, blinded to study group, with the validated 3-minute Diagnostic Confusion Assessment Method (3D-CAM) (on the intensive care unit in its version specifically adapted for the ICU), in addition to chart review and the results of delirium screening tools that will be performed by the bedside nurses). Secondary outcome parameters include duration and severity of POD, and postoperative cognitive function as assessed with the Mini-Mental State Examination.DiscussionOlder patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population.Trial registrationEudraCT Identifier: 2014-005370-11 (13 May 2015).

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“…In 18 F-FDG microPET imaging, the brain metabolism in the BrdU/GFAP-positive boundary zone at 7 days recovered in the aLA group. In the previous studies, the majority of 18 F-FDG hyperuptake regions were not recruited in the final infarction, suggesting that the 18 F-FDG uptake may be associated with neuronal survival and activity [ 49 - 51 ]. The increased 18 F-FDG uptake might be through facilitative expressing of GFAP-positive cells [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats

et al. 2015

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The antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no comprehensive studies examining the neurorestorative effects of aLA administration after the onset of ischemia. The middle cerebral artery (MCA) of adult rats was occluded for 2 hours and then reperfused. aLA (20 mg/kg) was administered in 71 animals (aLA group) through the left external jugular vein immediately after reperfusion. An equivalent volume of vehicle was administered to 71 animals (control group). Functional outcome, levels of endogenous neural precursors with neurogenesis, glial cell activation, and brain metabolism were evaluated. Immediate aLA administration after reperfusion resulted in significantly reduced mortality, infarct size, and neurological deficit score (NDS) in the test group compared to the control group. Long-term functional outcomes, measured by the rotarod test, were markedly improved by aLA treatment. There was a significant increase in the number of cells expressing nestin and GFAP in the boundary zone and infarct core regions after aLA treatment. Furthermore, significantly more BrdU/GFAP, BrdU/DCX, and BrdU/NeuN double-labeled cells were observed along the boundary zone of the aLA group on days 7, 14, and 28 days, respectively. And brain metabolism using 18F-FDG microPET imaging was markedly improved in aLA group. The effects of aLA was blocked by insulin receptor inhibitor, HNMPA (AM)3. These results indicate that immediate treatment with aLA after ischemic injury may have significant neurorestorative effects mediated at least partially via insulin receptor activation. Thus, aLA may be useful for the treatment of acute ischemic stroke.

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Positron emission tomography study of regional cerebral blood flow and flow–metabolism coupling during general anaesthesia with xenon in humans

Abstract: Xenon exerted distinct regional effects on CBF: relative decreases in several cortical, subcortical, and cerebellar areas were accompanied by an increase in white matter. Flow-metabolism coupling was not impaired during xenon anaesthesia.

Cited by 35 publications

References 29 publications

Purine nucleoside use as surrogate markers of cerebral ischaemia during local and general anaesthetic carotid endarterectomy

Purine nucleoside use as surrogate markers of cerebral ischaemia during local and general anaesthetic carotid endarterectomy

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial

Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats

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