Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain.

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.