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.

Cerebral Microdialysis Monitoring to Improve Individualized Neurointensive Care Therapy: An Update of Recent Clinical Data

“…As for reference values, L/P ratio >25 is considered abnormal (impaired cerebral oxidative metabolism), while L/P ratio >40 is the critical level above which brain energy crisis is defined. The reference level for CMD glucose is still debated, but probably lies at 1 (±0.15) mmol/L ( 17 ).…”

Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

“…While MD is relatively safe, it is a highly invasive technique and is, therefore, intrinsically unsuitable for use in mild TBI. For similar reasons, it is difficult to obtain normative data from truly “normal” brain that limits our physiological understanding although MD has been applied to patients who have undergone elective neurosurgery in an attempt to obtain better reference ranges ( 14 ).…”

Surgically Treated Intracerebral Haemorrhage : Pathophysiology and Clinical Aspects

“…The patients were then monitored with microdialysis during surgery, anaesthesia and a wakeful post-operative period (190). The results of this study, which were recently validated (191), constitute the entire basis for what is referred to as normal baseline values in the literature ( Table 2.2). Consensus on levels of low-molecular-weight metabolites considered clearly pathological, signalling metabolic distress in the sampled tissue, are glucose <0.2 mmol/mL, and LPR >40, whereas a glucose <0.8 mmol/mL and LPR >25 are considered warning signals ( Table 2.2) (16).…”