Cerebral Microdialysis in the Traumatic Brain Injury Patient Population


While microdialysis was first introduced in 1960, it was not until 1992 that the first microdialysis catheter was placed in a human brain.1 Since then, our understanding of the cerebral molecular environment has grown tremendously and with it the potential clinical application of the data gathered by microdialysis catheters. Here, we briefly review the concept behind cerebral microdialysis (CMD), its characterization of the cerebral microenvironment and its usefulness as a clinical tool in treatment of traumatic brain injury (TBI).

Currently, the only FDA-approved CMD catheter in the United States is the 10mm 20 kD probe at a flow rate of 0.3 m/min, though clinical trials in Europe are investigating the 100 kD probe.1 The monitoring device utilizes a double-lumen dialysis probe that is implanted in brain parenchyma, with the goal of indirectly sampling extracellular fluid (ECF). Molecules, such as glucose, pyruvate, lactate, glycerol and glutamate at high concentrations in the ECF, pass through the semi-permeable dialysis membrane with minimal passage of water, allowing for indirect sampling of ECF. It is worth noting that concentrations in the dialysate vary based on location, i.e. normal brain parenchyma versus perihematomal, and by individual patient; consequently, the literature proposes that trends in CMD are equally, if not more, important to evaluate than absolute values.2-4

Several CMD parameters have shown promise in evaluating outcomes in TBI patients. Glucose, the primary energy substrate of the brain, is one of the most widely measured parameters. When consumed through the aerobic pathway, glucose undergoes glycolysis and is converted to pyruvate and subsequently ATP. However, in the absence of oxygen, it is converted to ATP through the anaerobic pathway with lactate as a metabolic end-product. Decreased neuronal concentrations of glucose are indicative of decreased cerebral perfusion and subsequent reduction in oxidative metabolism, a common sequela of secondary injury in the TBI population. Multiple studies have demonstrated significant evidence that low cerebral glucose concentrations are associated with unfavorable outcomes. Several investigators suggest that CMD glucose levels less than 0.8mmol/L is associated with metabolic crisis and decreased Glasgow Coma Score (GCS) at three and six months.5 Measurement of lactate and pyruvate, as well as the lactate/pyruvate ratio (LPR), has also proven to be sensitive to tissue ischemic changes and a high LPR is associated with unfavorable outcome. In a systemic review of 25 studies measuring LPR, all studies demonstrated significantly worse outcomes in GCS at three and six months for elevated LPR, with most studies quoting a LPR between 25 and 40 as the cutoff for metabolic crisis or ischemia.6 Importantly, elevated LPR can be an indicator of either ischemia or of neuronal mitochondrial dysfunction and must be evaluated in the context of oxygenation. As noted in Hutchinson et al, an increase in LPR in the presence of low pyruvate and low oxygen is indicative of ischemia, while an elevated LPR with normal pyruvate or oxygen indicates mitochondrial dysfunction.3 Interestingly, one study found that elevated LPR predicted increases in ICPs in the following three hours, suggesting that CMD is predictive of changes at the molecular level that become apparent at the tissue level in a delayed fashion.1

Neuronal injury also releases excitatory neurotransmitters, such as glutamate, into the surrounding ECF, making glutamate an attractive target for monitoring. Most studies have demonstrated a correlation between glutamate and ischemia following TBI and it may be useful in estimating prognosis.3 Similarly, glycerol acts as a marker of cell membrane breakdown and, as a result, a surrogate for oxidative stress, but no definitive relationship between glycerol or outcome has been established at this time.3 Still, CMD poses significant promise in predicting TBI outcomes. Hlatky and colleagues evaluated 33 patients with intracranial monitoring following severe TBI and found that in the 11 patients with an uneventful clinical course and good outcomes, there were no changes in CMD numbers, while the five patients with fatal refractory intracranial hypertension demonstrated a typical pattern of changes in CMD values along with increased intracranial pressure (ICP).7 Another study noted that the addition of CMD to their multimodal monitoring model improved the predictive value from 78% to 90%.1

Although there is significant evidence that CMD predicts outcomes in TBI patients, it is worth noting that a wide variation of reference values was reported across studies, making it a difficult tool to implement systematically. Additionally, Nelson and colleagues noted that CMD values only weakly correlated to changes in ICP or cerebral perfusion pressure, suggesting long-term perturbances to cerebral tissue not related to pressure influenced molecular changes seen through CMD.8 Consequently, despite growing evidence that CMD has useful clinical applications in the TBI patient population, further investigation is necessary to better systematically characterize absolute and relative thresholds for intervention and to gain a more comprehensive understanding of the local and regional cellular changes that occur following brain injury. As such, CMD at this time should be used as a tool only in the presence of additional multimodal monitoring and in the context of clinical judgement, while offering great potential as a target for future research.


1. Kitagawa, R., Yokobori, S., Mazzeo, A. T., & Bullock, R. (2013). Microdialysis in the Neurocritical Care Unit. Neurosurgery Clinics of North America, 24(3), 417–426.

2. Tisdall, M., and Smith, M. (2006). Cerebral microdialysis: research technique or clinical tool. British Journal of Anaesthesia, 97(1), 18–25.

3. Hutchinson, P. J., Jalloh, I., Helmy, A., Carpenter, K. L. H., Rostami, E., Bellander, B.-M., … Ungerstedt, U. (2015). Consensus statement from the 2014 International Microdialysis Forum. Intensive Care Medicine, 41(9), 1517–1528.

4. Helmy, A., & Hutchinson, P. (2012). Is cerebral microdialysis a clinical tool? Acta Neurochirurgica, 155(2), 355–356.

5. Makarenko, S., Griesdale, D. E., Gooderham, P., & Sekhon, M. S. (2016). Multimodal neuromonitoring for traumatic brain injury: A shift towards individualized therapy. Journal of Clinical Neuroscience, 26, 8–13.

6. Zeiler, F. A., Thelin, E. P., Helmy, A., Czosnyka, M., Hutchinson, P. J. A., & Menon, D. K. (2017). A systematic review of cerebral microdialysis and outcomes in TBI: relationships to patient functional outcome, neurophysiologic measures, and tissue outcome. Acta Neurochirurgica, 159(12), 2245–2273.

7. Hlatky, R., Valadka, A. B., Goodman, J. C., Contant, C. F., & Robertson, C. S. (2004). Patterns of Energy Substrates during Ischemia Measured in the Brain by Microdialysis. Journal of Neurotrauma, 21(7), 894–906.

8. Nelson, D. W., Thornquist, B., Maccallum, R. M., Nyström, H., Holst, A., Rudehill, A., … Weitzberg, E. (2011). Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement. BMC Medicine, 9(1).