Understanding and monitoring brain injury: the role of cerebral microdialysis

Oddo, Mauro; Hutchinson, Peter J.

doi:10.1007/s00134-017-5031-6

Cited by 15 publications

(12 citation statements)

References 16 publications

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“…Lactate/pyruvate ratio (27 [17-44] vs. 27 vs. 28 ), brain tissue PO 2 (29 [19-39] vs. 29.5 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] vs. 29 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] mm Hg) and ICP (10 [3-20] vs. 11 [5][6][7][8][9][10][11][12][13][14][15][16][17] (Figure 3(a)), representing a median 4.7-fold decrease of blood KB from fasting to stable nutrition state. Median individual plasma/brain KB ratio was 11.…”

Section: Modulation Of Cerebral Ketone Metabolism By Nutritional Statementioning

confidence: 99%

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Bernini

Masoodi

Solari

et al. 2018

J Cereb Blood Flow Metab

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Adaptive metabolic response to injury includes the utilization of alternative energy substrates -such as ketone bodies (KB) -to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n ¼ 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and b-hydroxybutyrate). Nutrition -from fasting vs. stable nutrition state -was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] mmol/L vs. 13.1 [6.5-64.3] mmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] mmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p ¼ 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.

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Section: Modulation Of Cerebral Ketone Metabolism By Nutritional Statementioning

confidence: 99%

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Bernini

Masoodi

Solari

et al. 2018

J Cereb Blood Flow Metab

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“…Cerebral metabolic sampling also allows the calculation of the lactate/pyruvate ratio, to assess brain cell redox state, and the sampling of other molecules, such as glutamate, as a marker of brain excitotoxicity [11]. CMD is therefore well suited to monitor the cerebral metabolic state at the acute phase of TBI in humans [12].…”

Section: Introductionmentioning

confidence: 99%

Discovery and validation of temporal patterns involved in human brain ketometabolism in cerebral microdialysis fluids of traumatic brain injury patients

Eiden¹,

Christinat

Chakrabarti

et al. 2019

eBioMedicine

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Background Traumatic brain injury (TBI) is recognized as a metabolic disease, characterized by acute cerebral glucose hypo-metabolism. Adaptive metabolic responses to TBI involve the utilization of alternative energy substrates, such as ketone bodies. Cerebral microdialysis (CMD) has evolved as an accurate technique allowing continuous sampling of brain extracellular fluid and assessment of regional cerebral metabolism. We present the successful application of a combined hypothesis- and data-driven metabolomics approach using repeated CMD sampling obtained routinely at patient bedside. Investigating two patient cohorts ( n = 26 and n = 12), we identified clinically relevant metabolic patterns at the acute post-TBI critical care phase. Methods Clinical and CMD metabolomics data were integrated and analysed using in silico and data modelling approaches. We used both unsupervised and supervised multivariate analysis techniques to investigate structures within the time series and associations with patient outcome. Findings The multivariate metabolite time series exhibited two characteristic brain metabolic states that were attributed to changes in key metabolites: valine, 4-methyl-2-oxovaleric acid (4-MOV), isobeta-hydroxybutyrate (iso-bHB), tyrosyine, and 2-ketoisovaleric acid (2-KIV). These identified cerebral metabolic states differed significantly with respect to standard clinical values. We validated our findings in a second cohort using a classification model trained on the cerebral metabolic states. We demonstrated that short-term (therapeutic intensity level (TIL)) and mid-term patient outcome (6-month Glasgow Outcome Score (GOS)) can be predicted from the time series characteristics. Interpretation We identified two specific cerebral metabolic patterns that are closely linked to ketometabolism and were associated with both TIL and GOS. Our findings support the view that advanced metabolomics approaches combined with CMD may be applied in real-time to predict short-term treatment intensity and long-term patient outcome.

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“…Analysis of hourly measures of brain glucose, lactate, pyruvate, and glutamate permits a better understating of pathophysiological processes leading to imbalances in supply and demand. Early recognition of these patterns and imbalances, especially when analyzed in combination with other multimodal monitoring parameters such as intracranial pressure (ICP), brain tissue oxygen (PtiO2) and electroencephalography (EEG), may create a window of opportunity for clinical interventions that prevent definite secondary brain injury (Stocchetti et al, 2013;Citerio et al, 2015;Hutchinson et al, 2015;Oddo and Hutchinson, 2018).…”

Section: Brain Metabolism and Multimodal Monitoring The Role Of Cerebmentioning

confidence: 99%

“…This observation has led to the early identification of patients at higher risk that deserve more aggressive treatment. Furthermore, CMD has allowed the improvement of our understanding of novel mechanisms involved in brain metabolism and future treatment approaches (Quintard et al, 2016;Patet et al, 2016;Carteron et al, 2017Carteron et al, , 2018Bernini et al, 2018;Oddo and Hutchinson, 2018).…”

Section: Brain Metabolism and Multimodal Monitoring The Role Of Cerebmentioning

confidence: 99%

Nutrition Therapy, Glucose Control, and Brain Metabolism in Traumatic Brain Injury: A Multimodal Monitoring Approach

Kurtz

Rocha²

2020

Front. Neurosci.

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The goal of neurocritical care in patients with traumatic brain injury (TBI) is to prevent secondary brain damage. Pathophysiological mechanisms lead to loss of body mass, negative nitrogen balance, dysglycemia, and cerebral metabolic dysfunction. All of these complications have been shown to impact outcomes. Therapeutic options are available that prevent or mitigate their negative impact. Nutrition therapy, glucose control, and multimodality monitoring with cerebral microdialysis (CMD) can be applied as an integrated approach to optimize systemic immune and organ function as well as adequate substrate delivery to the brain. CMD allows real-time bedside monitoring of aspects of brain energy metabolism, by measuring specific metabolites in the extracellular fluid of brain tissue. Sequential monitoring of brain glucose and lactate/pyruvate ratio may reveal pathologic processes that lead to imbalances in supply and demand. Early recognition of these patterns may help individualize cerebral perfusion targets and systemic glucose control following TBI. In this direction, recent consensus statements have provided guidelines and recommendations for CMD applications in neurocritical care. In this review, we summarize data from clinical research on patients with severe TBI focused on a multimodal approach to evaluate aspects of nutrition therapy, such as timing and route; aspects of systemic glucose management, such as intensive vs. moderate control; and finally, aspects of cerebral metabolism. Research and clinical applications of CMD to better understand the interplay between substrate supply, glycemic variations, insulin therapy, and their effects on the brain metabolic profile were also reviewed. Novel mechanistic hypotheses in the interpretation of brain biomarkers were also discussed. Finally, we offer an integrated approach that includes nutritional and brain metabolic monitoring to manage severe TBI patients.

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Understanding and monitoring brain injury: the role of cerebral microdialysis

Cited by 15 publications

References 16 publications

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Discovery and validation of temporal patterns involved in human brain ketometabolism in cerebral microdialysis fluids of traumatic brain injury patients

Nutrition Therapy, Glucose Control, and Brain Metabolism in Traumatic Brain Injury: A Multimodal Monitoring Approach

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