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Robbins E, Wong B, Pwint MY, Salavatian S, Mahajan A, Cui XT. Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt. ACS APPLIED MATERIALS & INTERFACES 2024; 16:40570-40580. [PMID: 39078097 PMCID: PMC11310907 DOI: 10.1021/acsami.4c06692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 07/24/2024] [Accepted: 07/24/2024] [Indexed: 07/31/2024]
Abstract
In vivo glutamate sensing has provided valuable insight into the physiology and pathology of the brain. Electrochemical glutamate biosensors, constructed by cross-linking glutamate oxidase onto an electrode and oxidizing H2O2 as a proxy for glutamate, are the gold standard for in vivo glutamate measurements for many applications. While glutamate sensors have been employed ubiquitously for acute measurements, there are almost no reports of long-term, chronic glutamate sensing in vivo, despite demonstrations of glutamate sensors lasting for weeks in vitro. To address this, we utilized a platinum electrode with nanometer-scale roughness (nanoPt) to improve the glutamate sensors' sensitivity and longevity. NanoPt improved the GLU sensitivity by 67.4% and the sensors were stable in vitro for 3 weeks. In vivo, nanoPt glutamate sensors had a measurable signal above a control electrode on the same array for 7 days. We demonstrate the utility of the nanoPt sensors by studying the effect of traumatic brain injury on glutamate in the rat striatum with a flexible electrode array and report measurements of glutamate taken during the injury itself. We also show the flexibility of the nanoPt platform to be applied to other oxidase enzyme-based biosensors by measuring γ-aminobutyric acid in the porcine spinal cord. NanoPt is a simple, effective way to build high sensitivity, robust biosensors harnessing enzymes to detect neurotransmitters in vivo.
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Affiliation(s)
- Elaine
M. Robbins
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Benjamin Wong
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Department
of Anesthesiology & Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States
| | - May Yoon Pwint
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Center
for Neural Basis of Cognition, University
of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Siamak Salavatian
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Department
of Anesthesiology & Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States
| | - Aman Mahajan
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Department
of Anesthesiology & Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States
| | - Xinyan Tracy Cui
- Department
of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Center
for Neural Basis of Cognition, University
of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- McGowan
Institute for Regenerative Medicine, University
of Pittsburgh, Pittsburgh, Pennsylvania 15261, United
States
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Yan A, Torpey A, Morrisroe E, Andraous W, Costa A, Bergese S. Clinical Management in Traumatic Brain Injury. Biomedicines 2024; 12:781. [PMID: 38672137 PMCID: PMC11048642 DOI: 10.3390/biomedicines12040781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/06/2024] [Accepted: 03/14/2024] [Indexed: 04/28/2024] Open
Abstract
Traumatic brain injury is one of the leading causes of morbidity and mortality worldwide and is one of the major public healthcare burdens in the US, with millions of patients suffering from the traumatic brain injury itself (approximately 1.6 million/year) or its repercussions (2-6 million patients with disabilities). The severity of traumatic brain injury can range from mild transient neurological dysfunction or impairment to severe profound disability that leaves patients completely non-functional. Indications for treatment differ based on the injury's severity, but one of the goals of early treatment is to prevent secondary brain injury. Hemodynamic stability, monitoring and treatment of intracranial pressure, maintenance of cerebral perfusion pressure, support of adequate oxygenation and ventilation, administration of hyperosmolar agents and/or sedatives, nutritional support, and seizure prophylaxis are the mainstays of medical treatment for severe traumatic brain injury. Surgical management options include decompressive craniectomy or cerebrospinal fluid drainage via the insertion of an external ventricular drain. Several emerging treatment modalities are being investigated, such as anti-excitotoxic agents, anti-ischemic and cerebral dysregulation agents, S100B protein, erythropoietin, endogenous neuroprotectors, anti-inflammatory agents, and stem cell and neuronal restoration agents, among others.
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Affiliation(s)
- Amy Yan
- Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.Y.); (A.T.); (W.A.); (A.C.)
| | - Andrew Torpey
- Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.Y.); (A.T.); (W.A.); (A.C.)
| | - Erin Morrisroe
- Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA;
| | - Wesam Andraous
- Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.Y.); (A.T.); (W.A.); (A.C.)
| | - Ana Costa
- Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.Y.); (A.T.); (W.A.); (A.C.)
| | - Sergio Bergese
- Department of Anesthesiology and Neurological Surgery, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
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3
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Riviere-Cazaux C, Rajani K, Rahman M, Oh J, Brown DA, White JF, Himes BT, Jusue-Torres I, Rodriguez M, Warrington AE, Kizilbash SH, Elmquist WF, Burns TC. Methodological and analytical considerations for intra-operative microdialysis. Fluids Barriers CNS 2023; 20:94. [PMID: 38115038 PMCID: PMC10729367 DOI: 10.1186/s12987-023-00497-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 12/01/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations. METHODS Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry. RESULTS Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed. CONCLUSIONS Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT04047264.
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Affiliation(s)
- Cecile Riviere-Cazaux
- Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Karishma Rajani
- Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Masum Rahman
- Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Juhee Oh
- Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Desmond A Brown
- Neurosurgical Oncology Unit, Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Jaclyn F White
- Department of Neurological Surgery, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Benjamin T Himes
- Department of Neurological Surgery, Montefiore/Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ignacio Jusue-Torres
- Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | | | - Arthur E Warrington
- Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | | | - William F Elmquist
- Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Terry C Burns
- Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
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Stovell MG, Howe DJ, Thelin EP, Jalloh I, Helmy A, Guilfoyle MR, Grice P, Mason A, Giorgi-Coll S, Gallagher CN, Murphy MP, Menon DK, Carpenter TA, Hutchinson PJ, Carpenter KLH. High-physiological and supra-physiological 1,2- 13C 2 glucose focal supplementation to the traumatised human brain. J Cereb Blood Flow Metab 2023; 43:1685-1701. [PMID: 37157814 PMCID: PMC10581237 DOI: 10.1177/0271678x231173584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 03/12/2023] [Accepted: 04/02/2023] [Indexed: 05/10/2023]
Abstract
How to optimise glucose metabolism in the traumatised human brain remains unclear, including whether injured brain can metabolise additional glucose when supplied. We studied the effect of microdialysis-delivered 1,2-13C2 glucose at 4 and 8 mmol/L on brain extracellular chemistry using bedside ISCUSflex, and the fate of the 13C label in the 8 mmol/L group using high-resolution NMR of recovered microdialysates, in 20 patients. Compared with unsupplemented perfusion, 4 mmol/L glucose increased extracellular concentrations of pyruvate (17%, p = 0.04) and lactate (19%, p = 0.01), with a small increase in lactate/pyruvate ratio (5%, p = 0.007). Perfusion with 8 mmol/L glucose did not significantly influence extracellular chemistry measured with ISCUSflex, compared to unsupplemented perfusion. These extracellular chemistry changes appeared influenced by the underlying metabolic states of patients' traumatised brains, and the presence of relative neuroglycopaenia. Despite abundant 13C glucose supplementation, NMR revealed only 16.7% 13C enrichment of recovered extracellular lactate; the majority being glycolytic in origin. Furthermore, no 13C enrichment of TCA cycle-derived extracellular glutamine was detected. These findings indicate that a large proportion of extracellular lactate does not originate from local glucose metabolism, and taken together with our earlier studies, suggest that extracellular lactate is an important transitional step in the brain's production of glutamine.
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Affiliation(s)
- Matthew G Stovell
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Department of Neurosurgery, The Walton Centre, Liverpool, UK
| | - Duncan J Howe
- Department of Chemistry, University of Cambridge, Cambridge, UK
| | - Eric P Thelin
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
| | - Ibrahim Jalloh
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Adel Helmy
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Mathew R Guilfoyle
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Peter Grice
- Department of Chemistry, University of Cambridge, Cambridge, UK
| | - Andrew Mason
- Department of Chemistry, University of Cambridge, Cambridge, UK
| | - Susan Giorgi-Coll
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Clare N Gallagher
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
| | - Michael P Murphy
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK
| | - David K Menon
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - T Adrian Carpenter
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Peter J Hutchinson
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Keri LH Carpenter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
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5
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Poblete RA, Yaceczko S, Aliakbar R, Saini P, Hazany S, Breit H, Louie SG, Lyden PD, Partikian A. Optimization of Nutrition after Brain Injury: Mechanistic and Therapeutic Considerations. Biomedicines 2023; 11:2551. [PMID: 37760993 PMCID: PMC10526443 DOI: 10.3390/biomedicines11092551] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 09/13/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Emerging science continues to establish the detrimental effects of malnutrition in acute neurological diseases such as traumatic brain injury, stroke, status epilepticus and anoxic brain injury. The primary pathological pathways responsible for secondary brain injury include neuroinflammation, catabolism, immune suppression and metabolic failure, and these are exacerbated by malnutrition. Given this, there is growing interest in novel nutritional interventions to promote neurological recovery after acute brain injury. In this review, we will describe how malnutrition impacts the biomolecular mechanisms of secondary brain injury in acute neurological disorders, and how nutritional status can be optimized in both pediatric and adult populations. We will further highlight emerging therapeutic approaches, including specialized diets that aim to resolve neuroinflammation, immunodeficiency and metabolic crisis, by providing pre-clinical and clinical evidence that their use promotes neurologic recovery. Using nutrition as a targeted treatment is appealing for several reasons that will be discussed. Given the high mortality and both short- and long-term morbidity associated with acute brain injuries, novel translational and clinical approaches are needed.
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Affiliation(s)
- Roy A. Poblete
- Department of Neurology, Keck School of Medicine, The University of Southern California, 1540 Alcazar Street, Suite 215, Los Angeles, CA 90033, USA; (R.A.); (P.S.); (H.B.)
| | - Shelby Yaceczko
- UCLA Health, University of California, 100 Medical Plaza, Suite 345, Los Angeles, CA 90024, USA;
| | - Raya Aliakbar
- Department of Neurology, Keck School of Medicine, The University of Southern California, 1540 Alcazar Street, Suite 215, Los Angeles, CA 90033, USA; (R.A.); (P.S.); (H.B.)
| | - Pravesh Saini
- Department of Neurology, Keck School of Medicine, The University of Southern California, 1540 Alcazar Street, Suite 215, Los Angeles, CA 90033, USA; (R.A.); (P.S.); (H.B.)
| | - Saman Hazany
- Department of Radiology, Keck School of Medicine, The University of Southern California, 1500 San Pablo Street, Los Angeles, CA 90033, USA;
| | - Hannah Breit
- Department of Neurology, Keck School of Medicine, The University of Southern California, 1540 Alcazar Street, Suite 215, Los Angeles, CA 90033, USA; (R.A.); (P.S.); (H.B.)
| | - Stan G. Louie
- Department of Clinical Pharmacy, School of Pharmacy, The University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA;
| | - Patrick D. Lyden
- Department of Neurology, Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, The University of Southern California, 1540 Alcazar Street, Suite 215, Los Angeles, CA 90033, USA;
| | - Arthur Partikian
- Department of Neurology, Department of Pediatrics, Keck School of Medicine, The University of Southern California, 2010 Zonal Avenue, Building B, 3P61, Los Angeles, CA 90033, USA;
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Albers D, Sirlanci M, Levine M, Claassen J, Nigoghossian CD, Hripcsak G. Interpretable physiological forecasting in the ICU using constrained data assimilation and electronic health record data. J Biomed Inform 2023; 145:104477. [PMID: 37604272 DOI: 10.1016/j.jbi.2023.104477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 08/08/2023] [Accepted: 08/18/2023] [Indexed: 08/23/2023]
Abstract
OBJECTIVE Prediction of physiological mechanics are important in medical practice because interventions are guided by predicted impacts of interventions. But prediction is difficult in medicine because medicine is complex and difficult to understand from data alone, and the data are sparse relative to the complexity of the generating processes. Computational methods can increase prediction accuracy, but prediction with clinical data is difficult because the data are sparse, noisy and nonstationary. This paper focuses on predicting physiological processes given sparse, non-stationary, electronic health record data in the intensive care unit using data assimilation (DA), a broad collection of methods that pair mechanistic models with inference methods. METHODS A methodological pipeline embedding a glucose-insulin model into a new DA framework, the constrained ensemble Kalman filter (CEnKF) to forecast blood glucose was developed. The data include tube-fed patients whose nutrition, blood glucose, administered insulins and medications were extracted by hand due to their complexity and to ensure accuracy. The model was estimated using an individual's data as if they arrived in real-time, and the estimated model was run forward producing a forecast. Both constrained and unconstrained ensemble Kalman filters were estimated to compare the impact of constraints. Constraint boundaries, model parameter sets estimated, and data used to estimate the models were varied to investigate their influence on forecasting accuracy. Forecasting accuracy was evaluated according to mean squared error between the model-forecasted glucose and the measurements and by comparing distributions of measured glucose and forecast ensemble means. RESULTS The novel CEnKF produced substantial gains in robustness and accuracy while minimizing the data requirements compared to the unconstrained ensemble Kalman filters. Administered insulin and tube-nutrition were important for accurate forecasting, but including glucose in IV medication delivery did not increase forecast accuracy. Model flexibility, controlled by constraint boundaries and estimated parameters, did influence forecasting accuracy. CONCLUSION Accurate and robust physiological forecasting with sparse clinical data is possible with DA. Introducing constrained inference, particularly on unmeasured states and parameters, reduced forecast error and data requirements. The results are not particularly sensitive to model flexibility such as constraint boundaries, but over or under constraining increased forecasting errors.
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Affiliation(s)
- David Albers
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA; Department of Biomedical Engineering, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA; Department of Biomedical Informatics, Columbia University, New York, 10032, NY, USA.
| | - Melike Sirlanci
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA
| | - Matthew Levine
- Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena, 91125, CA, USA
| | - Jan Claassen
- Division of Critical Care Neurology, Department of Neurology, Columbia University, New York, 10032, NY, USA
| | | | - George Hripcsak
- Department of Biomedical Informatics, Columbia University, New York, 10032, NY, USA
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Robbins EM, Jaquins-Gerstl AS, Okonkwo DO, Boutelle MG, Michael AC. Dexamethasone-Enhanced Continuous Online Microdialysis for Neuromonitoring of O 2 after Brain Injury. ACS Chem Neurosci 2023. [PMID: 37369003 PMCID: PMC10360069 DOI: 10.1021/acschemneuro.2c00703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023] Open
Abstract
Traumatic brain injury (TBI) is a major public health crisis in many regions of the world. Severe TBI may cause a primary brain lesion with a surrounding penumbra of tissue that is vulnerable to secondary injury. Secondary injury presents as progressive expansion of the lesion, possibly leading to severe disability, a persistent vegetive state, or death. Real time neuromonitoring to detect and monitor secondary injury is urgently needed. Dexamethasone-enhanced continuous online microdialysis (Dex-enhanced coMD) is an emerging paradigm for chronic neuromonitoring after brain injury. The present study employed Dex-enhanced coMD to monitor brain K+ and O2 during manually induced spreading depolarization in the cortex of anesthetized rats and after controlled cortical impact, a widely used rodent model of TBI, in behaving rats. Consistent with prior reports on glucose, O2 exhibited a variety of responses to spreading depolarization and a prolonged, essentially permanent decline in the days after controlled cortical impact. These findings confirm that Dex-enhanced coMD delivers valuable information regarding the impact of spreading depolarization and controlled cortical impact on O2 levels in the rat cortex.
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Affiliation(s)
- Elaine M Robbins
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Andrea S Jaquins-Gerstl
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - David O Okonkwo
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, United States
| | - Martyn G Boutelle
- Department of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
| | - Adrian C Michael
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
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8
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Fenger AW, Olsen MH, Fabritius ML, Riberholt CG, Møller K. Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review. Acta Anaesthesiol Scand 2023; 67:240-247. [PMID: 36310523 PMCID: PMC10099998 DOI: 10.1111/aas.14166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 10/27/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury. METHODS We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/, http://www. CLINICALTRIALS gov/, www.eudraCT.com, http://centerwatch.com/, The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. DISCUSSION The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.
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Affiliation(s)
- Anne‐Sophie Worm Fenger
- Department of Neuroanaesthesiology, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
| | - Markus Harboe Olsen
- Department of Neuroanaesthesiology, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
| | - Maria Louise Fabritius
- Department of Neuroanaesthesiology, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
| | - Christian Gunge Riberholt
- Department of Neuroanaesthesiology, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
- Department of Neurorehabilitation, Traumatic Brain Injury, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
| | - Kirsten Møller
- Department of Neuroanaesthesiology, The Neuroscience CentreCopenhagen University Hospital—RigshospitaletCopenhagenDenmark
- Department of Clinical Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
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9
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Sharma H, McGinnis JP, Kabotyanski KE, Gopinath SP, Goodman JC, Robertson C, Cruz Navarro J. Cerebral microdialysis and glucopenia in traumatic brain injury: A review. Front Neurol 2023; 14:1017290. [PMID: 36779054 PMCID: PMC9911651 DOI: 10.3389/fneur.2023.1017290] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 01/09/2023] [Indexed: 01/28/2023] Open
Abstract
Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such measurements of cellular metabolism can yield critical missing information about a patient's physiologic state and help limit secondary damage. Glucose management in traumatic brain injury is still an unresolved question. As cerebral glucose metabolism may be uncoupled from systemic glucose levels due to the metabolic dysfunction, measurement of cerebral extracellular glucose concentrations could provide more predictive information and prove to be a better biomarker to avoid secondary injury of at-risk brain tissue. Based on data obtained from cerebral microdialysis, specific interventions such as ICP-directed therapy, blood glucose increment, seizure control, and/or brain oxygen optimization can be instituted to minimize or prevent secondary insults. Thus, microdialysis measurements of parenchymal metabolic function provides clinically valuable information that cannot be obtained by other monitoring adjuncts in the standard ICU setting.
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Affiliation(s)
- Himanshu Sharma
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States,*Correspondence: Himanshu Sharma ✉
| | - John P. McGinnis
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | | | - Shankar P. Gopinath
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Jerry C. Goodman
- Department of Pathology, Baylor College of Medicine, Houston, TX, United States
| | - Claudia Robertson
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Jovany Cruz Navarro
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States,Department of Anesthesiology, Baylor College of Medicine, Houston, TX, United States
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10
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Godoy DA, Murillo-Cabezas F, Suarez JI, Badenes R, Pelosi P, Robba C. "THE MANTLE" bundle for minimizing cerebral hypoxia in severe traumatic brain injury. Crit Care 2023; 27:13. [PMID: 36635711 PMCID: PMC9835224 DOI: 10.1186/s13054-022-04242-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 11/12/2022] [Indexed: 01/13/2023] Open
Abstract
To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.
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Affiliation(s)
- Daniel Agustin Godoy
- Departamento Medicina Critica. Unidad de Cuidados Neurointensivos, Sanatorio Pasteur, Catamarca, Argentina
| | | | - Jose Ignacio Suarez
- Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, USA
| | - Rafael Badenes
- Anesthesiology and Surgical-Trauma Intensive Care, University Clinic Hospital, Valencia, Spain
- Department of Surgery, University of Valencia, Valencia, Spain
- INCLIVA Research Medical Institute, Valencia, Spain
| | - Paolo Pelosi
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Chiara Robba
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
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11
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Falcone JA, Chen JW. Technical notes on the placement of cerebral microdialysis: A single center experience. Front Neurol 2023; 13:1041952. [PMID: 36698903 PMCID: PMC9868911 DOI: 10.3389/fneur.2022.1041952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Background Cerebral microdialysis enables monitoring of brain metabolism and can be an important part of multimodal monitoring strategies in a variety of brain injuries. Microdialysis catheters can be placed in brain parenchyma through a burr hole, a cranial bolt, or directly at the time of an open craniotomy or craniectomy. The location of catheters in relation to brain pathology is important to the interpretation of data and guidance of interventions. Methods Here we retrospectively review the use of cerebral microdialysis at a US Regional Medical Center between March 2018 and February 2022 and provide detailed descriptions and technical nuances of the different methods to place microdialysis catheters. Results Eighty two unique microdialysis catheters were utilized in 52 patients. 35 (42.68%) were placed via a quad-lumen bolt and 47 (57.32%) were placed through craniotomies. 27 catheters (32.93%) were placed in a perilesional location, 50 (60.98%) were located in healthy tissue, and 6 (7.32%) were mispositioned. No significant difference was seen between placement by bolt or craniotomy in regard to perilesional location, mispositioning, or complications. Conclusion With careful planning and thoughtful execution, cerebral microdialysis catheters can be successfully placed though a variety of strategies to optimize and individualize brain monitoring in different clinical settings. This paper provides a detailed guide for the various methods of catheter placement to help providers begin or expand their use of cerebral microdialysis.
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12
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Gomez-Pinilla F. Editorial to special issue of BBADIS: Brain-gut interaction and cognitive control. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166396. [PMID: 35306166 DOI: 10.1016/j.bbadis.2022.166396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Fernando Gomez-Pinilla
- Department of Integrative Biology & Physiology, UCLA, Los Angeles, USA; Department of Neurosurgery, UCLA Brain Injury Research Center, Los Angeles, USA.
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13
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Elliott E, Shoykhet M, Bell MJ, Wai K. Nutritional Support for Pediatric Severe Traumatic Brain Injury. Front Pediatr 2022; 10:904654. [PMID: 35656382 PMCID: PMC9152222 DOI: 10.3389/fped.2022.904654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
In critically ill children with severe traumatic brain injury (sTBI), nutrition may help facilitate optimal recovery. There is ongoing research regarding nutritional practices in the pediatric intensive care unit (PICU). These are focused on identifying a patient's most appropriate energy goal, the mode and timing of nutrient delivery that results in improved outcomes, as well as balancing these goals against inherent risks associated with nutrition therapy. Within the PICU population, children with sTBI experience complex physiologic derangements in the acute post-injury period that may alter metabolic demand, leading to nutritional needs that may differ from those in other critically ill patients. Currently, there are relatively few studies examining nutrition practices in PICU patients, and even fewer studies that focus on pediatric sTBI patients. Available data suggest that contemporary neurocritical care practices may largely blunt the expected hypermetabolic state after sTBI, and that early enteral nutrition may be associated with lower morbidity and mortality. In concordance with these data, the most recent guidelines for the management of pediatric sTBI released by the Brain Trauma Foundation recommend initiation of enteral nutrition within 72 h to improve outcome (Level 3 evidence). In this review, we will summarize available literature on nutrition therapy for children with sTBI and identify gaps for future research.
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Affiliation(s)
- Elizabeth Elliott
- Critical Care Medicine, Children's National Hospital, Washington, DC, United States
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14
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Casault C, Couillard P, Kromm J, Rosenthal E, Kramer A, Brindley P. Multimodal brain monitoring following traumatic brain injury: A primer for intensive care practitioners. J Intensive Care Soc 2022; 23:191-202. [PMID: 35615230 PMCID: PMC9125434 DOI: 10.1177/1751143720980273] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2023] Open
Abstract
Traumatic brain injury (TBI) is common and potentially devastating. Traditional examination-based patient monitoring following TBI may be inadequate for frontline clinicians to reduce secondary brain injury through individualized therapy. Multimodal neurologic monitoring (MMM) offers great potential for detecting early injury and improving outcomes. By assessing cerebral oxygenation, autoregulation and metabolism, clinicians may be able to understand neurophysiology during acute brain injury, and offer therapies better suited to each patient and each stage of injury. Hence, we offer this primer on brain tissue oxygen monitoring, pressure reactivity index monitoring and cerebral microdialysis. This narrative review serves as an introductory guide to the latest clinically-relevant evidence regarding key neuromonitoring techniques.
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Affiliation(s)
- Colin Casault
- Department of Critical Care
Medicine, University of Calgary, Calgary, Canada
| | - Philippe Couillard
- Department of Critical Care
Medicine, University of Calgary, Calgary, Canada
- Department of Clinical
Neurosciences, University of Calgary, Calgary, Canada
| | - Julie Kromm
- Department of Critical Care
Medicine, University of Calgary, Calgary, Canada
- Department of Clinical
Neurosciences, University of Calgary, Calgary, Canada
| | - Eric Rosenthal
- Department of Critical Care
Medicine, University of Alberta, Edmonton, Canada
| | - Andreas Kramer
- Department of Critical Care
Medicine, University of Calgary, Calgary, Canada
- Department of Clinical
Neurosciences, University of Calgary, Calgary, Canada
| | - Peter Brindley
- Department of Neurology, Harvard
University, Boston, MA, USA
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15
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Zimphango C, Alimagham FC, Carpenter KLH, Hutchinson PJ, Hutter T. Monitoring Neurochemistry in Traumatic Brain Injury Patients Using Microdialysis Integrated with Biosensors: A Review. Metabolites 2022; 12:metabo12050393. [PMID: 35629896 PMCID: PMC9146878 DOI: 10.3390/metabo12050393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/14/2022] [Accepted: 04/20/2022] [Indexed: 02/04/2023] Open
Abstract
In a traumatically injured brain, the cerebral microdialysis technique allows continuous sampling of fluid from the brain’s extracellular space. The retrieved brain fluid contains useful metabolites that indicate the brain’s energy state. Assessment of these metabolites along with other parameters, such as intracranial pressure, brain tissue oxygenation, and cerebral perfusion pressure, may help inform clinical decision making, guide medical treatments, and aid in the prognostication of patient outcomes. Currently, brain metabolites are assayed on bedside analysers and results can only be achieved hourly. This is a major drawback because critical information within each hour is lost. To address this, recent advances have focussed on developing biosensing techniques for integration with microdialysis to achieve continuous online monitoring. In this review, we discuss progress in this field, focusing on various types of sensing devices and their ability to quantify specific cerebral metabolites at clinically relevant concentrations. Important points that require further investigation are highlighted, and comments on future perspectives are provided.
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Affiliation(s)
- Chisomo Zimphango
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK; (F.C.A.); (K.L.H.C.); (P.J.H.); (T.H.)
- Correspondence:
| | - Farah C. Alimagham
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK; (F.C.A.); (K.L.H.C.); (P.J.H.); (T.H.)
| | - Keri L. H. Carpenter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK; (F.C.A.); (K.L.H.C.); (P.J.H.); (T.H.)
| | - Peter J. Hutchinson
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK; (F.C.A.); (K.L.H.C.); (P.J.H.); (T.H.)
| | - Tanya Hutter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK; (F.C.A.); (K.L.H.C.); (P.J.H.); (T.H.)
- Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
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16
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Godoy DA, Robba C, Paiva WS, Rabinstein AA. Acute Intracranial Hypertension During Pregnancy: Special Considerations and Management Adjustments. Neurocrit Care 2022; 36:302-316. [PMID: 34494211 PMCID: PMC8423073 DOI: 10.1007/s12028-021-01333-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 08/12/2021] [Indexed: 12/19/2022]
Abstract
Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.
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Affiliation(s)
- Daniel Agustin Godoy
- Neurointensive Care Unit, Sanatorio Pasteur, Catamarca, Argentina.
- Intensive Care, Hospital Carlos Malbran, Catamarca, Argentina.
| | - Chiara Robba
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, Investigational Research for Critical Care for Oncology and Neurosciences, Genoa, Italy
| | - Wellingson Silva Paiva
- Division of Neurological Surgery, University of Sao Paulo Medical School, Sao Paulo, Brazil
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17
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Gifford EK, Robbins EM, Jaquins-Gerstl A, Rerick MT, Nwachuku EL, Weber SG, Boutelle MG, Okonkwo DO, Puccio AM, Michael AC. Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury. ACS Chem Neurosci 2021; 12:3588-3597. [PMID: 34506125 DOI: 10.1021/acschemneuro.1c00231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Traumatic brain injury (TBI) induces a pathophysiologic state that can be worsened by secondary injury. Monitoring brain metabolism with intracranial microdialysis can provide clinical insights to limit secondary injury in the days following TBI. Recent enhancements to microdialysis include the implementation of continuously operating electrochemical biosensors for monitoring the dialysate sample stream in real time and dexamethasone retrodialysis to mitigate the tissue response to probe insertion. Dexamethasone-enhanced continuous-online microdialysis (Dex-enhanced coMD) records long-lasting declines of glucose after controlled cortical impact in rats and TBI in patients. The present study employed retrodialysis and fluorescence microscopy to investigate the mechanism responsible for the decline of dialysate glucose after injury of the rat cortex. Findings confirm the long-term functionality of Dex-enhanced coMD for monitoring brain glucose after injury, demonstrate that intracranial glucose microdialysis is coupled to glucose utilization in the tissues surrounding the probes, and validate the conclusion that aberrant glucose utilization drives the postinjury glucose decline.
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Affiliation(s)
- Emily K. Gifford
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Elaine M. Robbins
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Andrea Jaquins-Gerstl
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Michael T. Rerick
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Enyinna L. Nwachuku
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, United States
| | - Stephen G. Weber
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
| | - Martyn G. Boutelle
- Department of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
| | - David O. Okonkwo
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, United States
| | - Ava M. Puccio
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, United States
| | - Adrian C. Michael
- Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States
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18
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Zhang W, Hong J, Zheng W, Liu A, Yang Y. High glucose exacerbates neuroinflammation and apoptosis at the intermediate stage after post-traumatic brain injury. Aging (Albany NY) 2021; 13:16088-16104. [PMID: 34176788 PMCID: PMC8266309 DOI: 10.18632/aging.203136] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/19/2021] [Indexed: 12/12/2022]
Abstract
Traumatic brain injury (TBI) is a highly lethal event with a poor prognosis. Recovering residual neuronal function in the intermediate stage of TBI is important for treatment; however, neuroinflammation and neuronal apoptosis impede residual neuronal repair processes. Considering that hyperglycemia influences inflammatory processes and neuronal survival, we examined the effects of high glucose on neuroinflammation and neuronal death during the intermediate phase of TBI. Rat models of type 2 diabetes mellitus and/or TBI were developed and behaviorally assessed. Neurological function and cognitive abilities were impaired in TBI rats and worsened by type 2 diabetes mellitus. Histopathological staining and analyses of serum and hippocampal mRNA and protein levels indicated that neuroinflammation and apoptosis were induced in TBI rats and exacerbated by hyperglycemia. Hyperglycemia inhibited hippocampal mitogen-activated protein kinase kinase 5 (MEK5) phosphorylation in TBI rats. In vitro assays were used to assess inflammatory factor expression, apoptotic protein levels and neuronal survival after MEK5 activation in TBI- and/or high-glucose-treated neurons. MEK5/extracellular signal-regulated kinase 5 (ERK5) pathway activation reduced the inflammation, cleaved caspase-3 expression, Bax/Bcl-2 ratio and apoptosis of TBI neurons, even under high-glucose conditions. Thus, high glucose exacerbated neuroinflammation and apoptosis in the intermediate stage post-TBI by inhibiting the MEK5/ERK5 pathway.
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Affiliation(s)
- Wenqian Zhang
- Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- Hebei Institute of Head Trauma, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
| | - Jun Hong
- Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- Hebei Institute of Head Trauma, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
| | - Wencheng Zheng
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
| | - Aijun Liu
- Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- Hebei Institute of Head Trauma, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
| | - Ying Yang
- Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
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19
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Lu P, Cui L, Wang Y, Kang K, Gu H, Li Z, Liu L, Wang Y, Zhao X. Relationship Between Glycosylated Hemoglobin and Short-Term Mortality of Spontaneous Intracerebral Hemorrhage. Front Neurol 2021; 12:648907. [PMID: 33935947 PMCID: PMC8085396 DOI: 10.3389/fneur.2021.648907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 03/15/2021] [Indexed: 11/13/2022] Open
Abstract
Background: The relationship between glycosylated hemoglobin (HbA1c) and prognosis of spontaneous intracerebral hemorrhage (SICH) patients has not been fully elucidated. This study aimed to reveal the relationship between HbA1c levels and short-term mortality after patient admission with SICH. Methods: It was a large-scale, multicenter, cross-sectional study. From August 1, 2015, to July 31, 2019, a total of 41910 SICH patients were included in the study from the Chinese Stroke Center Alliance (CSCA) program. Finally, we comprehensively analyzed the data from 21,116 patients with SICH. HbA1c was categorized into four groups by quartile. Univariate and multivariate logistic regression analyses were used to assess the association between HbA1c levels and short-term mortality in SICH patients. Results: The average age of the 21,116 patients was 62.8 ± 13.2 years; 13,052 (61.8%) of them were male, and 507 (2.4%) of them died. Compared to the higher three quartiles of HbA1c, the lowest quartile (≤5.10%) had higher short-term mortality. In subgroup analysis with or without diabetes mellitus (DM) patients, the mortality of the Q3 group at 5.60-6.10% was significantly lower than that of the Q1 group at ≤5.10%. After adjustment for potential influencing factors, the ROC curve of HbA1c can better predict the short-term mortality of patients with SICH (AUC = 0.6286 P < 0.001). Conclusions: Therefore, we concluded that low or extremely low HbA1c levels (≤5.10%) after stroke were associated with higher short-term mortality in SICH patients, with or without DM.
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Affiliation(s)
- Ping Lu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Lingyun Cui
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yu Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Kaijiang Kang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Hongqiu Gu
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Zixiao Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Liping Liu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yilong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China
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20
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Svedung Wettervik TM, Lewén A, Enblad P. Fine Tuning of Traumatic Brain Injury Management in Neurointensive Care-Indicative Observations and Future Perspectives. Front Neurol 2021; 12:638132. [PMID: 33716941 PMCID: PMC7943830 DOI: 10.3389/fneur.2021.638132] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 01/20/2021] [Indexed: 01/01/2023] Open
Abstract
Neurointensive care (NIC) has contributed to great improvements in clinical outcomes for patients with severe traumatic brain injury (TBI) by preventing, detecting, and treating secondary insults and thereby reducing secondary brain injury. Traditional NIC management has mainly focused on generally applicable escalated treatment protocols to avoid high intracranial pressure (ICP) and to keep the cerebral perfusion pressure (CPP) at sufficiently high levels. However, TBI is a very heterogeneous disease regarding the type of injury, age, comorbidity, secondary injury mechanisms, etc. In recent years, the introduction of multimodality monitoring, including, e.g., pressure autoregulation, brain tissue oxygenation, and cerebral energy metabolism, in addition to ICP and CPP, has increased the understanding of the complex pathophysiology and the physiological effects of treatments in this condition. In this article, we will present some potential future approaches for more individualized patient management and fine-tuning of NIC, taking advantage of multimodal monitoring to further improve outcome after severe TBI.
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Affiliation(s)
| | - Anders Lewén
- Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
| | - Per Enblad
- Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
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21
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Guilfoyle MR, Helmy A, Donnelly J, Stovell MG, Timofeev I, Pickard JD, Czosnyka M, Smielewski P, Menon DK, Carpenter KLH, Hutchinson PJ. Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients. PLoS One 2021; 16:e0260291. [PMID: 34914701 PMCID: PMC8675704 DOI: 10.1371/journal.pone.0260291] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 11/05/2021] [Indexed: 11/29/2022] Open
Abstract
Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p<0.05). Significant non-linear associations were observed between LPR and cerebral glucose, CPP, and PRx (p<0.001 to p<0.05). GAMM models suggested improved cerebral metabolism (i.e. reduced LPR with CPP >70mmHg, PRx <0.1, PbtO2 >18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.
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Affiliation(s)
- Mathew R. Guilfoyle
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
- * E-mail:
| | - Adel Helmy
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Joseph Donnelly
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Matthew G. Stovell
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Ivan Timofeev
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - John D. Pickard
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Marek Czosnyka
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Peter Smielewski
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - David K. Menon
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Keri L. H. Carpenter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Peter J. Hutchinson
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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22
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High Arterial Glucose is Associated with Poor Pressure Autoregulation, High Cerebral Lactate/Pyruvate Ratio and Poor Outcome Following Traumatic Brain Injury. Neurocrit Care 2020; 31:526-533. [PMID: 31123993 PMCID: PMC6872512 DOI: 10.1007/s12028-019-00743-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Background Arterial hyperglycemia is associated with poor outcome in traumatic brain injury (TBI), but the pathophysiology is not completely understood. Previous preclinical and clinical studies have indicated that arterial glucose worsens pressure autoregulation. The aim of this study was to evaluate the relationship of arterial glucose to both pressure reactivity and cerebral energy metabolism. Method This retrospective study was based on 120 patients with severe TBI treated at the Uppsala University hospital, Sweden, 2008–2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial glucose, and pressure reactivity index (PRx55-15) were analyzed the first 3 days post-injury. Results High arterial glucose was associated with poor outcome/Glasgow Outcome Scale-Extended at 6-month follow-up (r = − 0.201, p value = 0.004) and showed a positive correlation with both PRx55-15 (r = 0.308, p = 0.001) and cerebral lactate/pyruvate ratio (LPR) days 1–3 (r = 0. 244, p = 0.014). Cerebral lactate-to-pyruvate ratio and PRx55-15 had a positive association day 2 (r = 0.219, p = 0.048). Multivariate linear regression analysis showed that high arterial glucose predicted poor pressure autoregulation on days 1 and 2. Conclusions High arterial glucose was associated with poor outcome, poor pressure autoregulation, and cerebral energy metabolic disturbances. The latter two suggest a pathophysiological mechanism for the negative effect of arterial hyperglycemia, although further studies are needed to elucidate if the correlations are causal or confounded by other factors.
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Kurtz P, Rocha EEM. Nutrition Therapy, Glucose Control, and Brain Metabolism in Traumatic Brain Injury: A Multimodal Monitoring Approach. Front Neurosci 2020; 14:190. [PMID: 32265626 PMCID: PMC7105880 DOI: 10.3389/fnins.2020.00190] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 02/21/2020] [Indexed: 12/19/2022] Open
Abstract
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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Affiliation(s)
- Pedro Kurtz
- Department of Neurointensive Care, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.,Department of Intensive Care Medicine, Hospital Copa Star, Rio de Janeiro, Brazil
| | - Eduardo E M Rocha
- Department of Intensive Care Medicine, Hospital Copa Star, Rio de Janeiro, Brazil
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Drabek T, Kochanek PM. Is there a role for therapeutic hypothermia in critical care? EVIDENCE-BASED PRACTICE OF CRITICAL CARE 2020:179-185.e1. [DOI: 10.1016/b978-0-323-64068-8.00035-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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25
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Högstedt A, Iredahl F, Tesselaar E, Farnebo S. Effect of N G -monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load. Microcirculation 2019; 27:e12597. [PMID: 31628700 DOI: 10.1111/micc.12597] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 09/09/2019] [Accepted: 10/16/2019] [Indexed: 12/28/2022]
Abstract
OBJECTIVE The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor NG -monomethyl l-arginine using microdialysis. METHODS Microdialysis catheters, perfused with NG -monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. RESULTS After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the NG -monomethyl l-arginine catheter compared to the control catheter (urea clearance: P < .006, glucose dialysate concentration: P < .035). No significant effect of NG -monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). CONCLUSION Local delivery of NG -monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.
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Affiliation(s)
- Alexandra Högstedt
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Fredrik Iredahl
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Erik Tesselaar
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Medical Radiation Physics, Linköping University, Linköping, Sweden
| | - Simon Farnebo
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Hand Surgery, Plastic Surgery and Burns, Linköping University, Linköping, Sweden
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Mandalaywala MD, Crawford KM, Pinto SM. Management of Traumatic Brain Injury: Special Considerations for Older Adults. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2019. [DOI: 10.1007/s40141-019-00239-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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27
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Intracranial Monitoring in the Neurocritical Care Unit. Neurocrit Care 2019. [DOI: 10.1017/9781107587908.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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28
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Management of Head Trauma in the Neurocritical Care Unit. Neurocrit Care 2019. [DOI: 10.1017/9781107587908.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Stocker RA. Intensive Care in Traumatic Brain Injury Including Multi-Modal Monitoring and Neuroprotection. Med Sci (Basel) 2019; 7:medsci7030037. [PMID: 30813644 PMCID: PMC6473302 DOI: 10.3390/medsci7030037] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 02/01/2019] [Accepted: 02/14/2019] [Indexed: 12/20/2022] Open
Abstract
Moderate to severe traumatic brain injuries (TBI) require treatment in an intensive care unit (ICU) in close collaboration of a multidisciplinary team consisting of different medical specialists such as intensivists, neurosurgeons, neurologists, as well as ICU nurses, physiotherapists, and ergo-/logotherapists. Major goals include all measurements to prevent secondary brain injury due to secondary brain insults and to optimize frame conditions for recovery and early rehabilitation. The distinction between moderate and severe is frequently done based on the Glascow Coma Scale and therefore often is just a snapshot at the early time of assessment. Due to its pathophysiological pathways, an initially as moderate classified TBI may need the same sophisticated surveillance, monitoring, and treatment as a severe form or might even progress to a severe and difficult to treat affection. As traumatic brain injury is rather a syndrome comprising a range of different affections to the brain and as, e.g., age-related comorbidities and treatments additionally may have a great impact, individual and tailored treatment approaches based on monitoring and findings in imaging and respecting pre-injury comorbidities and their therapies are warranted.
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Affiliation(s)
- Reto A Stocker
- Institute for Anesthesiology and Intensive Care Medicine, Klinik Hirslanden, CH-8032 Zurich, Switzerland.
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30
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The Evaluation and Management of the Blood Glucose for the Intracranial Disease. Neurocrit Care 2019. [DOI: 10.1007/978-981-13-7272-8_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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31
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Li D, Sun H, Ru X, Sun D, Guo X, Jiang B, Luo Y, Tao L, Fu J, Wang W. The Gaps Between Current Management of Intracerebral Hemorrhage and Evidence-Based Practice Guidelines in Beijing, China. Front Neurol 2018; 9:1091. [PMID: 30619050 PMCID: PMC6297270 DOI: 10.3389/fneur.2018.01091] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 11/28/2018] [Indexed: 12/11/2022] Open
Abstract
Background: The leading cause of death in China is stroke, a condition that also contributes heavily to the disease burden. Nontraumatic intracerebral hemorrhage (ICH) is the second most common cause of stroke. Compared to Western countries, in China the proportion of ICH is significantly higher. Standardized treatment based on evidence-based medicine can help reduce ICH's burden. In the present study we aimed to explore the agreement between the management strategies during ICH's acute phase and Class I recommendations in current international practice guidelines in Beijing (China), and to elucidate the reasons underlying any inconsistencies found. Method: We retrospectively collected in-hospital data from 1,355 ICH patients from 15 hospitals in Beijing between January and December 2012. Furthermore, a total of 75 standardized questionnaires focusing on ICH's clinical management were distributed to 15 cooperative hospitals. Each hospital randomly selected five doctors responsible for treating ICH patients to complete the questionnaires. Results: Numerous approaches were in line with Class I recommendations, as follows: upon admission, all patients underwent radiographic examination, about 93% of the survivors received health education and 84.5% of those diagnosed with hypertension were prescribed antihypertensive treatment at discharge, in-hospital antiepileptic drugs were administered to 91.8% of the patients presenting with seizures, and continuous monitoring was performed for 88% of the patients with hyperglycemia on admission. However, several aspects were inconsistent with the guidelines, as follows: only 14.2% of the patients were initially managed in the neurological intensive care unit and 22.3% of the bedridden patients received preventive treatment for deep vein thrombosis (DVT) within 48 h after onset. The questionnaire results showed that imaging examination, blood glucose monitoring, and secondary prevention of ICH were useful to more clinicians. However, the opposite occurred for the neurological intensive care unit requirement. Regarding the guidelines' recognition, no significant differences among the 3 education subgroups were observed (p > 0.05). Conclusions: Doctors have recognized most of ICH's evidence-based practice guidelines. However, there are still large gaps between the management of ICH and the evidence-based practice guidelines in Beijing (China). Retraining doctors is required, including focusing on preventing DVT providing a value from the National Institutes of Health Stroke Scale and Glasgow Coma Scalescores at the time of admission.
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Affiliation(s)
- Di Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Haixin Sun
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Xiaojuan Ru
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Dongling Sun
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Xiuhua Guo
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
- School of Public Health, Capital Medical University, Beijing, China
| | - Bin Jiang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Yanxia Luo
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
- School of Public Health, Capital Medical University, Beijing, China
| | - Lixin Tao
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
- School of Public Health, Capital Medical University, Beijing, China
| | - Jie Fu
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Wenzhi Wang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
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Kongwad LI, Hegde A, Menon G, Nair R. Influence of Admission Blood Glucose in Predicting Outcome in Patients With Spontaneous Intracerebral Hematoma. Front Neurol 2018; 9:725. [PMID: 30210444 PMCID: PMC6121104 DOI: 10.3389/fneur.2018.00725] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 08/09/2018] [Indexed: 01/08/2023] Open
Abstract
Background and Aims: Hyperglycemia or elevated blood glucose levels have been associated with poor outcomes in patients with ischemic stroke yet control of hyperglycemia has not resulted in good outcomes. High admission blood glucose (ABG) values have been mitigated by other poor prognosticators like large hematoma volume, intraventricular extension (IVE) of hematoma and poor GCS. The aim of this study was to evaluate the effects of blood glucose levels at admission, on mortality and functional outcomes at discharge and 3 months follow up. Methods: This was a retrospective observational study conducted at a tertiary care. Patients with spontaneous SICH were enrolled from a prospective SICH register maintained at our hospital. Blood glucose values were recorded on admission. Patients with traumatic hematomas, vascular malformations, aneurysms, and coagulation abnormalities were excluded from our study. Results: A total of 510 patients were included in the study. We dichotomised our cohort into two groups, group A with ABG>160 mg/dl and group B with ABG<160 mg/dl. Mean blood glucose levels in these two groups were 220.73 mg/dl and 124.37 mg/dl respectively, with group A having twice the mortality. mRS at discharge and 3 months was better in Group B (p ≤ 0.001) as compared to Group A. Age, GCS, volume of hematoma, ABG, IVE and Hydrocephalus were significant predictors of mortality and poor outcome on univariate analysis with a p < 0.05. The relationship between ABG and mortality (P = 0.249, 95% CI 0.948-1.006) and outcome (P = 0.538, 95% CI 0.997-1.005) failed to reach statistical significance on multivariate logistic regression. Age, Volume of hematoma and GCS were stronger predictors of mortality and morbidity. Conclusion: Admission blood glucose levels was not an independent predictor of mortality in our study when adjusted with age, GCS, and hematoma volume. The effect of high ABG on SICH outcome is probably multifactorial and warrants further research.
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Affiliation(s)
| | - Ajay Hegde
- Department of Neurosurgery, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
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Farrell D, Bendo AA. Perioperative Management of Severe Traumatic Brain Injury: What Is New? CURRENT ANESTHESIOLOGY REPORTS 2018; 8:279-289. [PMID: 30147453 PMCID: PMC6096919 DOI: 10.1007/s40140-018-0286-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF THE REVIEW Severe traumatic brain injury (TBI) continues to represent a global public health issue, and mortality and morbidity in TBI patients remain substantial. There are ongoing international collaborations to provide guidelines for perioperative care and management of severe TBI patients. In addition, new pharmacologic agents are being tested along with cognitive rehabilitation to improve functional independence and outcome in TBI patients. This review will discuss the current updates in the guidelines for the perioperative management of TBI patients and describe potential new therapies to improve functional outcomes. RECENT FINDINGS In the most recent guidelines published by The Brain Trauma Foundation, therapeutic options were reviewed based on new and revised evidence or lack of evidence. For example, changes and/or updates were made to the recommendations for the use of sedation and hypothermia in TBI patients, and new evidence was provided for the use of cerebrospinal fluid drainage as a first-line treatment for increased intracranial pressure (ICP). In addition to the guidelines, new 'multi-potential' agents that can target several mechanisms are being tested along with cognitive rehabilitation. SUMMARY The major goal of perioperative management of TBI patients is to prevent secondary damage. Therapeutic measures based on established guidelines and recommendations must be instituted promptly throughout the perioperative course to reduce morbidity and mortality.
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Affiliation(s)
- Deacon Farrell
- Downstate Medical Center, State University of New York (SUNY), 450 Clarkson Avenue, Box 6, Brooklyn, New York 11203 USA
| | - Audrée A. Bendo
- Downstate Medical Center, State University of New York (SUNY), 450 Clarkson Avenue, Box 6, Brooklyn, New York 11203 USA
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Al-Mufti F, Thabet AM, Singh T, El-Ghanem M, Amuluru K, Gandhi CD. Clinical and Radiographic Predictors of Intracerebral Hemorrhage Outcome. INTERVENTIONAL NEUROLOGY 2018; 7:118-136. [PMID: 29628951 PMCID: PMC5881146 DOI: 10.1159/000484571] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Intracerebral hemorrhage (ICH) represents 10-15% of all stroke cases in the US annually. Fewer than 40% of these patients ever reach long-term functional independence, and mortality rate is roughly 40% at 1 month. Due to the high morbidity and mortality rates after ICH, early detection of high-risk patients would be beneficial in directing the management course and goals of care. This review aims to discuss relevant clinical and radiographic characteristics that can serve as predictors of poor prognosis and examine their efficacy in predicting patient outcomes after ICH. SUMMARY A literature review was conducted on various clinical and radiographic factors. They were examined for their predictive value in relation to ICH outcome. Studies that focused on each of these factors were included, and their results analyzed for trends with regard to incidence, patient outcome, and mortality rate. KEY MESSAGE In this review, we examined clinical and radiographic characteristics that have been found to be significantly associated to a varying degree with poor outcome. Clinical and radiographic predictors of poor patient outcome are invaluable when it comes to identifying high-risk patients and triaging accordingly as well as guiding decision-making.
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Affiliation(s)
- Fawaz Al-Mufti
- Department of Neurology, Neurosurgery, and Radiology, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- Department of Neurosurgery, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA
| | - Ahmad M. Thabet
- Department of Neurology, Neurosurgery, and Radiology, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Tarundeep Singh
- Department of Neurology, Neurosurgery, and Radiology, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Mohammad El-Ghanem
- Department of Neurology, Neurosurgery, and Radiology, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- Department of Neurosurgery, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA
| | - Krishna Amuluru
- Department of Neurosurgery, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA
- Department of Interventional Neuroradiology, University of Pittsburgh Medical Center Hamot, Erie, Pennsylvania, USA
| | - Chirag D. Gandhi
- Westchester Medical Center, New York College of Medicine, Valhalla, New York, USA
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Crémillieux Y, Salvati R, Dumont U, Pinaud N, Bouchaud V, Sanchez S, Glöggler S, Wong A. Online 1 H-MRS measurements of time-varying lactate production in an animal model of glioma during administration of an anti-tumoral drug. NMR IN BIOMEDICINE 2018; 31:e3861. [PMID: 29193406 DOI: 10.1002/nbm.3861] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 10/15/2017] [Accepted: 10/16/2017] [Indexed: 06/07/2023]
Abstract
The aims of this study were to implement a magnetic resonance spectroscopy (MRS) protocol for the online profiling of subnanomolar quantities of metabolites sampled from the extracellular fluid using implanted microdialysis and to apply this protocol in glioma-bearing rats for the quantification of lactate concentration and the measurement of time-varying lactate concentration during drug administration. MRS acquisitions on the brain microdialysate were performed using a home-built, proton-tuned, microsolenoid with an active volume of 2 μL. The microcoil was placed at the outlet of the microdialysis probe inside a preclinical magnetic resonance imaging (MRI) scanner. C6-bearing rats were implanted with microdialysis probes perfused with artificial cerebrospinal fluid solution and the lactate dehydrogenase (LDH) inhibitor oxamate. Microcoil magnetic resonance spectra were continuously updated using a single-pulse sequence. Localized in vivo spectra and high-resolution spectra on the dialysate were also acquired. The limit of detection and limit of quantification per unit time of the lactate methyl peak were determined as 0.37 nmol/√min and 1.23 nmol/√min, respectively. Signal-to-noise ratios (SNRs) of the lactate methyl peak above 120 were obtained from brain tumor microdialysate in an acquisition time of 4 min. On average, the lactate methyl peak amplitude measured in vivo using the nuclear magnetic resonance (NMR) microcoil was 193 ± 46% higher in tumor dialysate relative to healthy brain dialysate. A similar ratio was obtained from high-resolution NMR spectra performed on the collected dialysate. Following oxamate addition in the perfusate, a monotonic decrease in the lactate peaks was observed in all animals with an average time constant of 4.6 min. In the absence of overlapping NMR peaks, robust profiling of extracellular lactate can be obtained online using a dedicated sensitive NMR microcoil. MRS measurements of the dynamic changes in lactate production induced by anti-tumoral drugs can be assessed accurately with temporal resolutions on the order of minutes. The MRS protocol can be readily transferred to the clinical environment with the use of suitable clinical microdialysis probes.
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Affiliation(s)
- Yannick Crémillieux
- Institut des Sciences Moléculaires, Université de Bordeaux, Bordeaux, France
| | - Roberto Salvati
- Institut des Sciences Moléculaires, Université de Bordeaux, Bordeaux, France
| | - Ursule Dumont
- Institut des Sciences Moléculaires, Université de Bordeaux, Bordeaux, France
| | - Noël Pinaud
- Institut des Sciences Moléculaires, Université de Bordeaux, Bordeaux, France
| | - Véronique Bouchaud
- Centre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, Bordeaux, France
| | - Stéphane Sanchez
- Centre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, Bordeaux, France
| | - Stefan Glöggler
- Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany
| | - Alan Wong
- NIMBE, CEA-Saclay, Gif-sur-Yvette, France
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Iredahl F, Högstedt A, Henricson J, Sjöberg F, Tesselaar E, Farnebo S. Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load. Microcirculation 2018; 23:597-605. [PMID: 27681957 DOI: 10.1111/micc.12325] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 09/20/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. METHODS Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). RESULTS Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. CONCLUSION Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.
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Affiliation(s)
- Fredrik Iredahl
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
| | - Alexandra Högstedt
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Joakim Henricson
- Department of Dermatology and Venerology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Folke Sjöberg
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Hand Surgery, Plastic Surgery, and Burns, Linköping University, Linköping, Sweden
| | - Erik Tesselaar
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Radiation Physics, Linköping University, Linköping, Sweden
| | - Simon Farnebo
- Department of Hand Surgery, Plastic Surgery, and Burns, Linköping University, Linköping, Sweden
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Plummer MP, Notkina N, Timofeev I, Hutchinson PJ, Finnis ME, Gupta AK. Cerebral metabolic effects of strict versus conventional glycaemic targets following severe traumatic brain injury. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2018; 22:16. [PMID: 29368635 PMCID: PMC5784688 DOI: 10.1186/s13054-017-1933-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/27/2017] [Indexed: 01/04/2023]
Abstract
Background Optimal glycaemic targets for patients with severe traumatic brain injury remain unclear. The primary objective of this microdialysis study was to compare cerebral metabolism with strict versus conventional glycaemic control. Methods We performed a prospective single-centre randomised controlled within-subject crossover study of 20 adult patients admitted to an academic neurointensive care unit with severe traumatic brain injury. Patients underwent randomised, consecutive 24-h periods of strict (4–7 mmol/L; 72–126 mg/dl) and conventional (<10 mmol/L; 180 mg/dl) glycaemic control with microdialysis measurements performed hourly. The first 12 h of each study period was designated as a ‘washout’ period, with the subsequent 12 h being the period of interest. Results Cerebral glucose was lower during strict glycaemia than with conventional control (mean 1.05 [95% CI 0.58–1.51] mmol/L versus 1.28 [0.81–1.74] mmol/L; P = 0.03), as was lactate (3.07 [2.44–3.70] versus 3.56 [2.81–4.30]; P < 0.001). There were no significant differences in pyruvate or the lactate/pyruvate ratio between treatment phases. Strict glycaemia increased the frequency of low cerebral glucose (< 0.8 mmol/L; OR 1.91 [95% CI 1.01–3.65]; P < 0.05); however, there were no differences in the frequency of critically low glucose (< 0.2 mmol/L) or critically elevated lactate/pyruvate ratio between phases. Conclusions Compared with conventional glycaemic targets, strict blood glucose control was associated with lower mean levels of cerebral glucose and an increased frequency of abnormally low glucose levels. These data support conventional glycaemic targets following traumatic brain injury. Trial registration ISRCTN, ISRCTN19146279. Retrospectively registered on 2 May 2014. Electronic supplementary material The online version of this article (10.1186/s13054-017-1933-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Mark P Plummer
- Neurosciences Critical Care Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - Natalia Notkina
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - Ivan Timofeev
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - Peter J Hutchinson
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - Mark E Finnis
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, 5000, Australia
| | - Arun K Gupta
- Neurosciences Critical Care Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. .,Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
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Hermanides J, Plummer MP, Finnis M, Deane AM, Coles JP, Menon DK. Glycaemic control targets after traumatic brain injury: a systematic review and meta-analysis. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2018; 22:11. [PMID: 29351760 PMCID: PMC5775599 DOI: 10.1186/s13054-017-1883-y] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Accepted: 10/31/2017] [Indexed: 01/04/2023]
Abstract
Background Optimal glycaemic targets in traumatic brain injury (TBI) remain unclear. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing intensive with conventional glycaemic control in TBI requiring admission to an intensive care unit (ICU). Methods We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to November 2016. Outcomes of interest included ICU and in-hospital mortality, poor neurological outcome, the incidence of hypoglycaemia and infective complications. Data were analysed by pairwise random effects models with secondary analysis of differing levels of conventional glycaemic control. Results Ten RCTs, involving 1066 TBI patients were included. Three studies were conducted exclusively in a TBI population, whereas in seven trials, the TBI population was a sub-cohort of a mixed neurocritical or general ICU population. Glycaemic targets with intensive control ranged from 4.4 to 6.7 mmol/L, while conventional targets aimed to keep glucose levels below thresholds of 8.4–12 mmol/L. Conventional versus intensive control showed no association with ICU or hospital mortality (relative risk (RR) (95% CI) 0.93 (0.68–1.27), P = 0.64 and 1.07 (0.84–1.36), P = 0.62, respectively). The risk of a poor neurological outcome was higher with conventional control (RR (95% CI) = 1.10 (1.001–1.24), P = 0.047). However, severe hypoglycaemia occurred less frequently with conventional control (RR (95% CI) = 0.22 (0.09–0.52), P = 0.001). Conclusions This meta-analysis of intensive glycaemic control shows no association with reduced mortality in TBI. Intensive glucose control showed a borderline significant reduction in the risk of poor neurological outcome, but markedly increased the risk of hypoglycaemia. These contradictory findings should motivate further research. Electronic supplementary material The online version of this article (10.1186/s13054-017-1883-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jeroen Hermanides
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. .,Department of Anesthesiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Mark P Plummer
- Neurosciences Critical Care Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - Mark Finnis
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, 5000, Australia
| | - Adam M Deane
- Intensive Care Unit, Royal Melbourne Hospital, Melbourne, 3050, Australia
| | - Jonathan P Coles
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
| | - David K Menon
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
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Tu TW, Ibrahim WG, Jikaria N, Munasinghe JP, Witko JA, Hammoud DA, Frank JA. On the detection of cerebral metabolic depression in experimental traumatic brain injury using Chemical Exchange Saturation Transfer (CEST)-weighted MRI. Sci Rep 2018; 8:669. [PMID: 29330386 PMCID: PMC5766554 DOI: 10.1038/s41598-017-19094-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 12/21/2017] [Indexed: 12/13/2022] Open
Abstract
Metabolic abnormalities are commonly observed in traumatic brain injury (TBI) patients exhibiting long-term neurological deficits. This study investigated the feasibility and reproducibility of using chemical exchange saturation transfer (CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the selective saturation for enhancing the endogenous contrast-weighting of the proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in the resting rat brain. The optimized glucoCEST-weighted imaging was performed on a closed-head model of diffuse TBI in rats with 2-deoxy-D-[14C]-glucose (2DG) autoradiography validation. The results demonstrated that saturation duration of 1‒2 seconds at pulse powers 1.5‒2µT resulted in an improved contrast-to-noise ratio between the gray and white matter comparable to 2DG autoradiographs. The intrasubject (n = 4) and intersubject (n = 3) coefficient of variations for repeated glucoCEST acquisitions (n = 4) ranged between 8‒16%. Optimization for the TBI study revealed that glucoCEST-weighted images with 1.5μT power and 1 s saturation duration revealed the greatest changes in contrast before and after TBI, and positively correlated with 2DG autoradiograph (r = 0.78, p < 0.01, n = 6) observations. These results demonstrate that glucoCEST-weighted imaging may be useful in detecting metabolic abnormalities following TBI.
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Affiliation(s)
- Tsang-Wei Tu
- Frank Laboratory, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States. .,Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United States. .,Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington, DC, United States.
| | - Wael G Ibrahim
- Center for Infectious Disease Imaging, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States
| | - Neekita Jikaria
- Frank Laboratory, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States.,Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United States.,Acute Stroke Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Jeeva P Munasinghe
- Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Jaclyn A Witko
- Frank Laboratory, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States.,Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United States
| | - Dima A Hammoud
- Center for Infectious Disease Imaging, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States
| | - Joseph A Frank
- Frank Laboratory, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States.,National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, United States
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Geeraerts T, Velly L, Abdennour L, Asehnoune K, Audibert G, Bouzat P, Bruder N, Carrillon R, Cottenceau V, Cotton F, Courtil-Teyssedre S, Dahyot-Fizelier C, Dailler F, David JS, Engrand N, Fletcher D, Francony G, Gergelé L, Ichai C, Javouhey É, Leblanc PE, Lieutaud T, Meyer P, Mirek S, Orliaguet G, Proust F, Quintard H, Ract C, Srairi M, Tazarourte K, Vigué B, Payen JF. Management of severe traumatic brain injury (first 24hours). Anaesth Crit Care Pain Med 2017; 37:171-186. [PMID: 29288841 DOI: 10.1016/j.accpm.2017.12.001] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The latest French Guidelines for the management in the first 24hours of patients with severe traumatic brain injury (TBI) were published in 1998. Due to recent changes (intracerebral monitoring, cerebral perfusion pressure management, treatment of raised intracranial pressure), an update was required. Our objective has been to specify the significant developments since 1998. These guidelines were conducted by a group of experts for the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie et de réanimation [SFAR]) in partnership with the Association de neuro-anesthésie-réanimation de langue française (ANARLF), The French Society of Emergency Medicine (Société française de médecine d'urgence (SFMU), the Société française de neurochirurgie (SFN), the Groupe francophone de réanimation et d'urgences pédiatriques (GFRUP) and the Association des anesthésistes-réanimateurs pédiatriques d'expression française (ADARPEF). The method used to elaborate these guidelines was the Grade® method. After two Delphi rounds, 32 recommendations were formally developed by the experts focusing on the evaluation the initial severity of traumatic brain injury, the modalities of prehospital management, imaging strategies, indications for neurosurgical interventions, sedation and analgesia, indications and modalities of cerebral monitoring, medical management of raised intracranial pressure, management of multiple trauma with severe traumatic brain injury, detection and prevention of post-traumatic epilepsia, biological homeostasis (osmolarity, glycaemia, adrenal axis) and paediatric specificities.
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Affiliation(s)
- Thomas Geeraerts
- Pôle anesthésie-réanimation, Inserm, UMR 1214, Toulouse neuroimaging center, ToNIC, université Toulouse 3-Paul Sabatier, CHU de Toulouse, 31059 Toulouse, France.
| | - Lionel Velly
- Service d'anesthésie-réanimation, Aix-Marseille université, CHU Timone, Assistance publique-Hôpitaux de Marseille, 13005 Marseille, France
| | - Lamine Abdennour
- Département d'anesthésie-réanimation, groupe hospitalier Pitié-Salpêtrière, AP-HP, 75013 Paris, France
| | - Karim Asehnoune
- Service d'anesthésie et de réanimation chirurgicale, Hôtel-Dieu, CHU de Nantes, 44093 Nantes cedex 1, France
| | - Gérard Audibert
- Département d'anesthésie-réanimation, hôpital Central, CHU de Nancy, 54000 Nancy, France
| | - Pierre Bouzat
- Pôle anesthésie-réanimation, CHU Grenoble-Alpes, 38043 Grenoble cedex 9, France
| | - Nicolas Bruder
- Service d'anesthésie-réanimation, Aix-Marseille université, CHU Timone, Assistance publique-Hôpitaux de Marseille, 13005 Marseille, France
| | - Romain Carrillon
- Service d'anesthésie-réanimation, hôpital neurologique Pierre-Wertheimer, groupement hospitalier Est, hospices civils de Lyon, 69677 Bron, France
| | - Vincent Cottenceau
- Service de réanimation chirurgicale et traumatologique, SAR 1, hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
| | - François Cotton
- Service d'imagerie, centre hospitalier Lyon Sud, hospices civils de Lyon, 69495 Pierre-Bénite cedex, France
| | - Sonia Courtil-Teyssedre
- Service de réanimation pédiatrique, hôpital Femme-Mère-Enfant, hospices civils de Lyon, 69677 Bron, France
| | | | - Frédéric Dailler
- Service d'anesthésie-réanimation, hôpital neurologique Pierre-Wertheimer, groupement hospitalier Est, hospices civils de Lyon, 69677 Bron, France
| | - Jean-Stéphane David
- Service d'anesthésie réanimation, centre hospitalier Lyon Sud, hospices civils de Lyon, 69495 Pierre-Bénite, France
| | - Nicolas Engrand
- Service d'anesthésie-réanimation, Fondation ophtalmologique Adolphe de Rothschild, 75940 Paris cedex 19, France
| | - Dominique Fletcher
- Service d'anesthésie réanimation chirurgicale, hôpital Raymond-Poincaré, université de Versailles Saint-Quentin, AP-HP, Garches, France
| | - Gilles Francony
- Pôle anesthésie-réanimation, CHU Grenoble-Alpes, 38043 Grenoble cedex 9, France
| | - Laurent Gergelé
- Département d'anesthésie-réanimation, CHU de Saint-Étienne, 42055 Saint-Étienne, France
| | - Carole Ichai
- Service de réanimation médicochirurgicale, UMR 7275, CNRS, Sophia Antipolis, hôpital Pasteur, CHU de Nice, 06000 Nice, France
| | - Étienne Javouhey
- Service de réanimation pédiatrique, hôpital Femme-Mère-Enfant, hospices civils de Lyon, 69677 Bron, France
| | - Pierre-Etienne Leblanc
- Département d'anesthésie-réanimation, hôpital de Bicêtre, hôpitaux universitaires Paris-Sud, AP-HP, Le Kremlin-Bicêtre, France; Équipe TIGER, CNRS 1072-Inserm 5288, service d'anesthésie, centre hospitalier de Bourg en Bresse, centre de recherche en neurosciences, Lyon, France
| | - Thomas Lieutaud
- UMRESTTE, UMR-T9405, IFSTTAR, université Claude-Bernard de Lyon, Lyon, France; Service d'anesthésie-réanimation, hôpital universitaire Necker-Enfants-Malades, université Paris Descartes, AP-HP, Paris, France
| | - Philippe Meyer
- EA 08 Paris-Descartes, service de pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte, 75743 Paris cedex 15, France
| | - Sébastien Mirek
- Service d'anesthésie-réanimation, CHU de Dijon, Dijon, France
| | - Gilles Orliaguet
- EA 08 Paris-Descartes, service de pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte, 75743 Paris cedex 15, France
| | - François Proust
- Service de neurochirurgie, hôpital Hautepierre, CHU de Strasbourg, 67098 Strasbourg, France
| | - Hervé Quintard
- Service de réanimation médicochirurgicale, UMR 7275, CNRS, Sophia Antipolis, hôpital Pasteur, CHU de Nice, 06000 Nice, France
| | - Catherine Ract
- Département d'anesthésie-réanimation, hôpital de Bicêtre, hôpitaux universitaires Paris-Sud, AP-HP, Le Kremlin-Bicêtre, France; Équipe TIGER, CNRS 1072-Inserm 5288, service d'anesthésie, centre hospitalier de Bourg en Bresse, centre de recherche en neurosciences, Lyon, France
| | - Mohamed Srairi
- Pôle anesthésie-réanimation, Inserm, UMR 1214, Toulouse neuroimaging center, ToNIC, université Toulouse 3-Paul Sabatier, CHU de Toulouse, 31059 Toulouse, France
| | - Karim Tazarourte
- SAMU/SMUR, service des urgences, hospices civils de Lyon, hôpital Édouard-Herriot, 69437 Lyon cedex 03, France
| | - Bernard Vigué
- Département d'anesthésie-réanimation, hôpital de Bicêtre, hôpitaux universitaires Paris-Sud, AP-HP, Le Kremlin-Bicêtre, France; Équipe TIGER, CNRS 1072-Inserm 5288, service d'anesthésie, centre hospitalier de Bourg en Bresse, centre de recherche en neurosciences, Lyon, France
| | - Jean-François Payen
- Pôle anesthésie-réanimation, CHU Grenoble-Alpes, 38043 Grenoble cedex 9, France
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Figaji AA. Anatomical and Physiological Differences between Children and Adults Relevant to Traumatic Brain Injury and the Implications for Clinical Assessment and Care. Front Neurol 2017; 8:685. [PMID: 29312119 PMCID: PMC5735372 DOI: 10.3389/fneur.2017.00685] [Citation(s) in RCA: 117] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 11/30/2017] [Indexed: 01/08/2023] Open
Abstract
General and central nervous system anatomy and physiology in children is different to that of adults and this is relevant to traumatic brain injury (TBI) and spinal cord injury. The controversies and uncertainties in adult neurotrauma are magnified by these differences, the lack of normative data for children, the scarcity of pediatric studies, and inappropriate generalization from adult studies. Cerebral metabolism develops rapidly in the early years, driven by cortical development, synaptogenesis, and rapid myelination, followed by equally dramatic changes in baseline and stimulated cerebral blood flow. Therefore, adult values for cerebral hemodynamics do not apply to children, and children cannot be easily approached as a homogenous group, especially given the marked changes between birth and age 8. Their cranial and spinal anatomy undergoes many changes, from the presence and disappearance of the fontanels, the presence and closure of cranial sutures, the thickness and pliability of the cranium, anatomy of the vertebra, and the maturity of the cervical ligaments and muscles. Moreover, their systemic anatomy changes over time. The head is relatively large in young children, the airway is easily compromised, the chest is poorly protected, the abdominal organs are large. Physiology changes—blood volume is small by comparison, hypothermia develops easily, intracranial pressure (ICP) is lower, and blood pressure normograms are considerably different at different ages, with potentially important implications for cerebral perfusion pressure (CPP) thresholds. Mechanisms and pathologies also differ—diffuse injuries are common in accidental injury, and growing fractures, non-accidental injury and spinal cord injury without radiographic abnormality are unique to the pediatric population. Despite these clear differences and the vulnerability of children, the amount of pediatric-specific data in TBI is surprisingly weak. There are no robust guidelines for even basics aspects of care in children, such as ICP and CPP management. This is particularly alarming given that TBI is a leading cause of death in children. To address this, there is an urgent need for pediatric-specific clinical research. If this goal is to be achieved, any clinician or researcher interested in pediatric neurotrauma must be familiar with its unique pathophysiological characteristics.
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Affiliation(s)
- Anthony A Figaji
- Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Red Cross Children's Hospital, Rondebosch, Cape Town, South Africa
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Carteron L, Bouzat P, Oddo M. Cerebral Microdialysis Monitoring to Improve Individualized Neurointensive Care Therapy: An Update of Recent Clinical Data. Front Neurol 2017; 8:601. [PMID: 29180981 PMCID: PMC5693841 DOI: 10.3389/fneur.2017.00601] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 10/27/2017] [Indexed: 01/04/2023] Open
Abstract
Cerebral microdialysis (CMD) allows bedside semicontinuous monitoring of patient brain extracellular fluid. Clinical indications of CMD monitoring are focused on the management of secondary cerebral and systemic insults in acute brain injury (ABI) patients [mainly, traumatic brain injury (TBI), subarachnoid hemorrhage, and intracerebral hemorrhage (ICH)], specifically to tailor several routine interventions—such as optimization of cerebral perfusion pressure, blood transfusion, glycemic control and oxygen therapy—in the individual patient. Using CMD as clinical research tool has greatly contributed to identify and better understand important post-injury mechanisms—such as energy dysfunction, posttraumatic glycolysis, post-aneurysmal early brain injury, cortical spreading depressions, and subclinical seizures. Main CMD metabolites (namely, lactate/pyruvate ratio, and glucose) can be used to monitor the brain response to specific interventions, to assess the extent of injury, and to inform about prognosis. Recent consensus statements have provided guidelines and recommendations for CMD monitoring in neurocritical care. Here, we summarize recent clinical investigation conducted in ABI patients, specifically focusing on the role of CMD to guide individualized intensive care therapy and to improve our understanding of the complex disease mechanisms occurring in the immediate phase following ABI. Promising brain biomarkers will also be described.
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Affiliation(s)
- Laurent Carteron
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Besançon, University of Bourgogne - Franche-Comté, Besançon, France
| | - Pierre Bouzat
- Department of Anesthesiology and Critical Care, University Hospital Grenoble, Grenoble, France
| | - Mauro Oddo
- Department of Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland
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Abstract
Traumatic brain injury is the number one cause of death and disability among the pediatric population in the USA. The heterogeneity of the pediatric population is reflected by both the normal cerebral maturation and the age differences in the causes of TBI, which generate unique age-related pathophysiology responses and recovery profiles. This review will address the normal changes in cerebral glucose metabolism throughout developmental phases and how TBI alters glucose metabolism. Evidence has shown that TBI disrupts the biochemical processing of glucose to energy. This brings to question, "What is the optimal substrate to manage a pediatric TBI patient?" Issues related to glycemic control and alternative substrate metabolism are addressed specifically in regard to pediatric TBI. Research into pediatric glucose metabolism after TBI is limited, and understanding these age-related differences within the pediatric population have great potential to improve support for the injured younger brain.
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Griffiths H, Goyal MS, Pineda JA. Brain metabolism and severe pediatric traumatic brain injury. Childs Nerv Syst 2017; 33:1719-1726. [PMID: 29149384 DOI: 10.1007/s00381-017-3514-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Accepted: 06/27/2017] [Indexed: 01/30/2023]
Abstract
Age-dependent changes in brain metabolism may influence the response to and tolerance of secondary insults, potentially affecting outcomes. More complete characterization of brain metabolism across the clinical trajectory of severe pediatric TBI is needed to improve our ability to measure and better mitigate the impact of secondary insults. Better management of secondary insults will impact clinical care and the probability of success of future neuroprotective clinical trials. Improved bedside monitoring and imaging technologies will be required to achieve these goals. Effective and sustained integration of brain metabolism information into the pediatric critical care setting will be equally challenging and important.
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Affiliation(s)
- Heidi Griffiths
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Manu S Goyal
- Department of Neuroradiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jose A Pineda
- Department of Pediatrics and Neurology, Washington University School of Medicine, St. Louis, MO, USA.
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Figaji AA, Graham Fieggen A, Mankahla N, Enslin N, Rohlwink UK. Targeted treatment in severe traumatic brain injury in the age of precision medicine. Childs Nerv Syst 2017; 33:1651-1661. [PMID: 28808845 DOI: 10.1007/s00381-017-3562-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 07/27/2017] [Indexed: 11/28/2022]
Abstract
In recent years, much progress has been made in our understanding of traumatic brain injury (TBI). Clinical outcomes have progressively improved, but evidence-based guidelines for how we manage patients remain surprisingly weak. The problem is that the many interventions and strategies that have been investigated in randomized controlled trials have all disappointed. These include many concepts that had become standard care in TBI. And that is just for adult TBI; in children, the situation is even worse. Not only is pediatric care more difficult than adult care because physiological norms change with age, but also there is less evidence for clinical practice. In this article, we discuss the heterogeneity inherent in TBI and why so many clinical trials have failed. We submit that a key goal for the future is to appreciate important clinical differences between patients in their pathophysiology and their responses to treatment. The challenge that faces us is how to rationally apply therapies based on the specific needs of an individual patient. In doing so, we may be able to apply the principles of precision medicine approaches to the patients we treat.
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Affiliation(s)
- Anthony A Figaji
- Division of Neurosurgery and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
| | - A Graham Fieggen
- Division of Neurosurgery and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
| | - Ncedile Mankahla
- Division of Neurosurgery, University of Cape Town, Cape Town, South Africa
| | - Nico Enslin
- Division of Neurosurgery, University of Cape Town, Cape Town, South Africa
| | - Ursula K Rohlwink
- Division of Neurosurgery and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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48
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Krinsley JS, Chase JG, Gunst J, Martensson J, Schultz MJ, Taccone FS, Wernerman J, Bohe J, De Block C, Desaive T, Kalfon P, Preiser JC. Continuous glucose monitoring in the ICU: clinical considerations and consensus. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2017; 21:197. [PMID: 28756769 PMCID: PMC5535285 DOI: 10.1186/s13054-017-1784-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.
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Affiliation(s)
- James S Krinsley
- Division of Critical Care, Department of Medicine, Stamford Hospital, Columbia University College of Physicians and Surgeons, Stamford, CT, 06902, USA
| | - J Geoffrey Chase
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Christchurch, 8140, New Zealand
| | - Jan Gunst
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000, Leuven, Belgium
| | - Johan Martensson
- Department of Intensive Care, Austin Hospital, Heidelberg, 3084, VIC, Australia.,Department of Anesthesia and Intensive Care Medicine, Karolinska University Hospital, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden
| | - Marcus J Schultz
- Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.,Department of Intensive Care, Laboratory of Experimental Intensive Care and Anesthesia (L E I C A), Faculty of Tropical Medicine, Mahidol University, Mahidol-Oxford Research Unit (MORU), Bangkok, Thailand
| | - Fabio S Taccone
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium
| | - Jan Wernerman
- Karolinska University Hospital Huddinge & Karolinska Institutet, K32 14186, Stockholm, Sweden
| | - Julien Bohe
- Medical Intensive Care Unit, University Hospital of Lyon, Lyon, France
| | - Christophe De Block
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, B-2650, Edegem, Belgium
| | - Thomas Desaive
- GIGA-In Silico Medicine, Université de Liège, B4000, Liège, Belgium
| | - Pierre Kalfon
- Service de Réanimation polyvalente, Hôpital Louis Pasteur, CH de Chartres, 28000, Chartres, France
| | - Jean-Charles Preiser
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium.
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49
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Chen S, Zhao B, Wang W, Shi L, Reis C, Zhang J. Predictors of hematoma expansion predictors after intracerebral hemorrhage. Oncotarget 2017; 8:89348-89363. [PMID: 29179524 PMCID: PMC5687694 DOI: 10.18632/oncotarget.19366] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 06/19/2017] [Indexed: 01/04/2023] Open
Abstract
Despite years of effort, intracerebral hemorrhage (ICH) remains the most devastating form of stroke with more than 40% 30-day mortality worldwide. Hematoma expansion (HE), which occurs in one third of ICH patients, is strongly predictive of worse prognosis and potentially preventable if high-risk patients were identified in the early phase of ICH. In this review, we summarize data from recent studies on HE prediction and classify those potential indicators into four categories: clinical (severity of consciousness disturbance; blood pressure; blood glucose at and after admission); laboratory (hematologic parameters of coagulation, inflammation and microvascular integrity status), radiographic (interval time from ICH onset; baseline volume, shape and density of hematoma; intraventricular hemorrhage; especially the spot sign and modified spot sign) and integrated predictors (9-point or 24-point clinical prediction algorithm and PREDICT A/B). We discuss those predictors’ underlying pathophysiology in HE and present opportunities to develop future therapeutic strategies.
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Affiliation(s)
- Sheng Chen
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
| | - Binjie Zhao
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
| | - Wei Wang
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
| | - Ligen Shi
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
| | - Cesar Reis
- Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, USA.,Department of Preventive Medicine, Loma Linda University, Loma Linda, California, USA
| | - Jianmin Zhang
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
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50
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Wolahan SM, Prins ML, McArthur DL, Real CR, Hovda DA, Martin NA, Vespa PM, Glenn TC. Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury. Neurocrit Care 2017; 26:239-246. [PMID: 27761730 PMCID: PMC5336412 DOI: 10.1007/s12028-016-0313-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults. METHODS The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed. RESULTS Fifteen patients completed the crossover study. Total ketones were increased 81 μM ([38 135], p < 0.001) when blood glucose was targeted to tight (4.4-6.1 mM) compared with loose glycemic control (6.7-8.3 mM), corresponding to a 60 % increase. There was a significant decrease in total nutritional provisions (p = 0.006) and a significant increase in insulin dose (p = 0.008). CONCLUSIONS Permissive underfeeding was tolerated when targeting tight glycemic control, but total nutritional support is an important factor when treating hyperglycemia.
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Affiliation(s)
- Stephanie M Wolahan
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA.
| | - Mayumi L Prins
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
| | - David L McArthur
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
| | - Courtney R Real
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
| | - David A Hovda
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
- Department of Molecular and Medical Pharmacology, University of California - Los Angeles, Los Angeles, CA, USA
| | - Neil A Martin
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
| | - Paul M Vespa
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
| | - Thomas C Glenn
- Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, University of California - Los Angeles, Los Angeles, CA, USA
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