Microdialysate concentration changes do not provide sufficient information to evaluate metabolic effects of lactate supplementation in brain-injured patients

Abstract

Cerebral microdialysis is a widely used clinical tool for monitoring extracellular concentrations of selected metabolites after brain injury and to guide neurocritical care. Extracellular glucose levels and lactate/pyruvate ratios have high diagnostic value because they can detect hypoglycemia and deficits in oxidative metabolism, respectively. In addition, patterns of metabolite concentrations can distinguish between ischemia and mitochondrial dysfunction, and are helpful to choose and evaluate therapy. Increased intracranial pressure can be life-threatening after brain injury, and hypertonic solutions are commonly used for pressure reduction. Recent reports have advocated use of hypertonic sodium lactate, based on claims that it is glucose sparing and provides an oxidative fuel for injured brain. However, changes in extracellular concentrations in microdialysate are not evidence that a rise in extracellular glucose level is beneficial or that lactate is metabolized and improves neuroenergetics. The increase in glucose concentration may reflect inhibition of glycolysis, glycogenolysis, and pentose phosphate shunt pathway fluxes by lactate flooding in patients with mitochondrial dysfunction. In such cases, lactate will not be metabolizable and lactate flooding may be harmful. More rigorous approaches are required to evaluate metabolic and physiological effects of administration of hypertonic sodium lactate to brain-injured patients.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury

“…10 The significance of such extracellular lactate elevation after TBI under treatment remained unclear, as it could reflect aerobic glycolysis 30 [i.e. the conversion of lactate to pyruvate to be utilised in aerobic conditions (lactate oxidation) with concomitant increase of cerebral microdialysis lactate and pyruvate concentrations], or the inability of injured brain cells to utilise exogenous lactate 13 that is caused by insufficient oxygen availability and reduced Krebs cycle metabolism of pyruvate. In order to clarify this issue, we used in vivo 1 H-MRS to assess intracellular lactate metabolism.…”

“…11,12 Such a notion would imply a benefit of such lactate flooding on mitochondrial function in injured brain tissue, a hypothesis that remains unexplored. 13 Alternatively, the cerebral effects of HSL may be caused by lactate-related vasodilator effects, 14,15 and hyper-osmotic and anti-oedematous effects leading to a reduction in intracranial pressure. 10,16,17 In order to clarify the exact role of HSL as a whole solution in brain injury, we compared HSL vs isotonic saline solution in injured and normal brain.…”

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

“…CMD glucose or KB levels do not provide a dynamic value of cerebral metabolic rate as other measurements such as positron emission tomography do, 46 and might provide only a partial information on brain energy metabolism. 47 Finally, due to the sample size, this study did not explore possible relationships between ketone metabolism and different nutritional products with patient prognosis, which will require further investigation.…”

The Correlation between Cerebral Blood Flow Measured by Bedside Xenon-CT and Brain Chemistry Monitored by Microdialysis in the Acute Phase following Subarachnoid Hemorrhage

“…However, high lactate levels may also indicate hyperglycolysis ( 21 , 22 ), explaining its rather low specificity as a biomarker of ischemia ( 9 ). Consequently, additional parameters such as L/P-ratio, pyruvate, and CBF should be evaluated to distinguish between ischemia, hyperglycolysis, and mitochondrial dysfunction ( 5 , 23 – 25 ). In the current study, there was a significant negative correlation between CBF and lactate.…”