Cerebral microdialysis and glucopenia in traumatic brain injury: A review

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.

Keywords: cerebral microdialysis; glucopenia; glucose; lactate-to-pyruvate ratio; traumatic brain injury.

Figure 1

Schematic representation of the physiologic concept behind cerebral microdialysis.

Figure 2

Glucose, which is the major fuel in the brain, is transported across the cell membranes by facilitated diffusion mediated by glucose transporter proteins (GLUT). Two types of glucose transporters (sodium dependent and facilitative transporters) are localized in the membranes of neurons, astrocytes and brain endothelial cells. Of these, GLUT-1 and GLUT-3 represent the two most important transporters in the brain. Under normal conditions, pyruvate is formed from glucose after entering the glycolytic process generating two molecules of ATP. Subsequently, it enters the citric acid cycle if oxygen is available, yielding 32 ATP molecules. During a state of cerebral hypoxia and low glucose (e.g., intracranial hypertension) the production of ATP from the citric acid cycle decreases. Then, cells attempt to compensate for the decrease in ATP production by increasing the turnover of glucose in the anaerobic part of the glycolysis. During this process it is necessary to regenerate NAD+ from NADH, which facilitates maintenance of glycolysis. The NAD+ regeneration causes an increase in lactate and the lactate/pyruvate ratio. The ratio is essentially the same in all tissues (i.e., about 20). A ratio above 25 is considered as an early warning of beginning metabolic crises.