Hyperoxia results in increased aerobic metabolism following acute brain injury

Acute brain injury is associated with depressed aerobic metabolism. Below a critical mitochondrial pO2 cytochrome c oxidase, the terminal electron acceptor in the mitochondrial respiratory chain, fails to sustain oxidative phosphorylation. After acute brain injury, this ischaemic threshold might be shifted into apparently normal levels of tissue oxygenation. We investigated the oxygen dependency of aerobic metabolism in 16 acutely brain-injured patients using a 120-min normobaric hyperoxia challenge in the acute phase (24–72 h) post-injury and multimodal neuromonitoring, including transcranial Doppler ultrasound-measured cerebral blood flow velocity, cerebral microdialysis-derived lactate-pyruvate ratio (LPR), brain tissue pO2 (pbrO2), and tissue oxygenation index and cytochrome c oxidase oxidation state (oxCCO) measured using broadband spectroscopy. Increased inspired oxygen resulted in increased pbrO2 [ΔpbrO2 30.9 mmHg p < 0.001], reduced LPR [ΔLPR −3.07 p = 0.015], and increased cytochrome c oxidase (CCO) oxidation (Δ[oxCCO] + 0.32 µM p < 0.001) which persisted on return-to-baseline (Δ[oxCCO] + 0.22 µM, p < 0.01), accompanied by a 7.5% increase in estimated cerebral metabolic rate for oxygen (p = 0.038). Our results are consistent with an improvement in cellular redox state, suggesting oxygen-limited metabolism above recognised ischaemic pbrO2 thresholds. Diffusion limitation or mitochondrial inhibition might explain these findings. Further investigation is warranted to establish optimal oxygenation to sustain aerobic metabolism after acute brain injury

Care of elderly patients: a prospective audit of the prevalence of hypotension and the use of BIS intraoperatively in 25 hospitals in London

BACKGROUND: Anaesthesia is frequently complicated by intraoperative hypotension (IOH) in the elderly, and this is associated with adverse outcome. The definition of IOH is controversial, and although management guidelines for IOH in the elderly exist, the frequency of IOH and typical clinically applied treatment thresholds are largely unknown in the UK. METHODS: We audited frequency of intraoperative blood pressure against national guidelines in elderly patients undergoing surgery. Depth of anaesthesia (DOA) monitoring was also audited due to the association between low DOA values and IOH with increased mortality (as part of "double" and "triple low" phenomena) and because it is a suggested management strategy to reduce IOH. RESULTS: Twenty-five hospitals submitted data on 481 patients. Hypotension varied depending on the definition, but affected 400 patients (83.3 %) using the AAGBI standard. Furthermore, 2.9, 13.5, and 24.6 % had mean arterial blood pressures <50, <60, and <70 mmHg for 20 min, respectively, and 136 (28.4 %) had systolic blood pressure decrease by 20 % for 20 min. DOA monitors were used for 45 (9.4 %) patients. CONCLUSIONS: IOH is common and use of DOA monitors is less than implied by guidelines. Improved management of IOH may be a simple intervention with real potential to reduce morbidity in this vulnerable group

BrainSignals Revisited: Simplifying a Computational Model of Cerebral Physiology

Multimodal monitoring of brain state is important both for the investigation of healthy cerebral physiology and to inform clinical decision making in conditions of injury and disease. Near-infrared spectroscopy is an instrument modality that allows non-invasive measurement of several physiological variables of clinical interest, notably haemoglobin oxygenation and the redox state of the metabolic enzyme cytochrome c oxidase. Interpreting such measurements requires the integration of multiple signals from different sources to try to understand the physiological states giving rise to them. We have previously published several computational models to assist with such interpretation. Like many models in the realm of Systems Biology, these are complex and dependent on many parameters that can be difficult or impossible to measure precisely. Taking one such model, BrainSignals, as a starting point, we have developed several variant models in which specific regions of complexity are substituted with much simpler linear approximations. We demonstrate that model behaviour can be maintained whilst achieving a significant reduction in complexity, provided that the linearity assumptions hold. The simplified models have been tested for applicability with simulated data and experimental data from healthy adults undergoing a hypercapnia challenge, but relevance to different physiological and pathophysiological conditions will require specific testing. In conditions where the simplified models are applicable, their greater efficiency has potential to allow their use at the bedside to help interpret clinical data in near real-time

Treatment threshold for intra-operative hypotension in clinical practice-a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin

The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin

Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data

In diffuse optical tomography (DOT), overlapping and multidistance measurements are required to reconstruct depth-resolved images of oxy- ([Formula: see text]) and deoxy- (HHb) hemoglobin concentration changes occurring in the brain. These can be considered an indirect measure of brain activity, under the assumption of intact neurovascular coupling. Broadband systems also allow changes in the redox state of cytochrome c oxidase (oxCCO) to be measured, which can be an important biomarker when neurovascular coupling is impaired. We used DOT to reconstruct images of [Formula: see text], [Formula: see text], and [Formula: see text] from data acquired with a broadband system. Four healthy volunteers were measured while performing a visual stimulation task (4-Hz inverting checkerboard). The broadband system was configured to allow multidistance and overlapping measurements of the participants' visual cortex with 32 channels. A multispectral approach was employed to reconstruct changes in concentration of the three chromophores during the visual stimulation. A clear and focused activation was reconstructed in the left occipital cortex of all participants. The difference between the residuals of the three-chromophore model and of the two-chromophore model (recovering only [Formula: see text] and [Formula: see text]) exhibits a spectrum similar to that of oxCCO. These results form a basis for further studies aimed to further optimize image reconstruction of [Formula: see text]

Normobaric hyperoxia does not change optical scattering or pathlength but does increase oxidised cytochrome C oxidase concentration in patients with brain injury.

We report the use of a novel hybrid near-infrared spectrometer for the measurement of optical scattering, pathlength and chromophore concentration in critically ill patients with brain injury. Ten mechanically ventilated patients with acute brain injury were studied. In addition to standard neurointensive care monitoring, middle cerebral artery flow velocity, brain lactate-pyruvate ratio (LPR) and brain tissue oxygen tension were monitored. The patients were subjected to graded normobaric hyperoxia (NBH), with the inspired fraction of oxygen increased from baseline to 60% then 100%. NBH induced significant changes in the concentrations of oxyhaemoglobin, deoxyhaemoglobin and oxidised-reduced cytochrome c oxidase; these were accompanied by a corresponding reduction in brain LPR and increase in brain tissue oxygen tension. No significant change in optical scattering or pathlength was observed. These results suggest that the measurement of chromophore concentration in the injured brain is not confounded by changes in optical scattering or pathlength and that NBH induces an increase in cerebral aerobic metabolism

Treatment threshold for intra‐operative hypotension in clinical practice—a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

Learning to become an online editor: the editathon as a learning environment

This study explores Wikipedia as a site for learning. In particular it traces how people learn to become Wikipedia editors through engagement in an editathon, a training event for people who want to become a volunteer editor. The study is original in its emphasis on the various types of knowledge editors acquire as they develop expertise. Determining the knowledge needed to contribute to Wikipedia is significant in terms of understanding Wikipedia as a site for learning. Data was gathered from nine participants who took part in an ‘editathon’ event on the theme of the Edinburgh Seven. The study used a rigorous methodology, combining quantitative social network analysis, documenting the online activity of participants as they created and edited Wikipedia pages, with qualitative interviews, which recorded participants reflections on their participation in the editathon. A key finding is that conceptual and procedural knowledge are representative of the foundational knowledge needed to contribute to Wikipedia actively as an editor. However, this knowledge on its own is not sufficient. Editors also develop socio-cultural and relational knowledge forms of knowledge to enable them to operate and problem-solve effectively. The relationship between the physical and the digital is important, since socio-cultural and relational knowledge are developed through active experimentation as the editathon engage with physical objects to create the online wiki pages