title: Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain.
abstract: Cerebral microdialysis is widely used in neurocritical care units. The goal of this study was to establish the reference interval for the interstitial fluid concentrations of energy metabolites and glycerol by using the extrapolation to zero-flow methodology in anesthetized patients and by constant perfusion at 0.3 µL/min in awake patients. A CMA-71 probe was implanted during surgery in normal white matter of patients with posterior fossa or supratentorial lesions, and the perfusion flow rate was randomized to 0.1, 0.3, 0.6, 1.2, and 2.4 µL/min. Within 24 h of surgery, perfusion was restarted at a constant 0.3 µL/min in fully awake patients. The actual interstitial fluid metabolite concentrations were calculated using the zero-flow methodology. In vitro experiments were also conducted to evaluate the reproducibility of the in vivo methodology. Nineteen patients (seven males) with a median age of 44 years (range: 21-69) were included in the in vivo study. The median (lower-upper) reference interval values were 1.57 (1.15-4.13 mmol/L) for glucose, 2.01 (1.30-5.31 mmol/L) for lactate, 80.0 (54.4-197.0 µmol/L) for pyruvate, and 49.9 (23.6-227.3 µmol/L) for glycerol. The reference intervals reported raises the need to reconsider traditional definitions of brain metabolic disturbances and emphasize the importance of using different thresholds for awake patients and patients under anesthesia.
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Sánchez-Guerrero
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Mur-Bonet
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Vidal-Jorge
authors.affiliation: 2 Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: Gándara-Sabatini
authors.affiliation: 3 Department of Anesthesiology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Ivette
authors.initials: I
authors.lastname: Chocrón
authors.affiliation: 2 Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Cordero
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.|2 Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Maria-Antonia
authors.initials: MA
authors.lastname: Poca
authors.affiliation: 4 Department of Statistics, UCLA, Los Angeles, CA, USA.
authors.forename: Katharine
authors.initials: K
authors.lastname: Mullen
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.|2 Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sahuquillo
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000601:surgery; D004734:Energy Metabolism / Q000502:physiology*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods*; D011446:Prospective Studies; D019289:Pyruvic Acid / Q000378:metabolism; D012016:Reference Values; D014851:Wakefulness; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D005990:Glycerol
keywords: Brain metabolism; cerebral microdialysis; lactate; reference intervals; traumatic brain injury