Interaction between Brain Chemistry and Physiology after Traumatic Brain Injury: Impact of Autoregulation and Microdialysis Catheter Location

Abstract

Bedside monitoring of cerebral metabolism in traumatic brain injury (TBI) with microdialysis is gaining wider clinical acceptance. The objective of this study was to examine the relationship between the fundamental physiological neuromonitoring modalities intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (P bt O 2 ), and cerebrovascular pressure reactivity index (PRx), and cerebral chemistry assessed with microdialysis, with particular focus on the lactate/pyruvate (LP) ratio as a marker of energy metabolism. Prospectively collected observational neuromonitoring data from 97 patients with TBI, requiring neurointensive care management and invasive cerebral monitoring, were analyzed. A linear mixed model analysis was used to account for individual patient differences. Perilesional tissue chemistry exhibited a significant independent relationship with ICP, P bt O 2 and CPP thresholds, with increasing LP ratio in response to decrease in P bt O 2 and CPP, and increase in ICP. The relationship between CPP and chemistry depended upon the state of PRx. Within the studied physiological range, tissue chemistry only changed in response to increasing ICP or drop in P bt O 2 < 1.33 kPa (10 mmHg). In agreement with previous studies, significantly higher levels of cerebral lactate ( p < 0.001), glycerol ( p = 0.013), LP ratio ( p < 0.001) and lactate/glucose (LG) ratio ( p = 0.003) were found in perilesional tissue, compared to ''normal'' brain tissue (Mann-Whitney test). These differences remained significant following adjustment for the influences of other important physiological parameters (ICP, CPP, P bt O 2 , P bt CO 2 , PRx, and brain temperature; mixed linear model), suggesting that they may reflect inherent tissue properties related to the initial injury. Despite inherent biochemical differences between less-injured brain and ''perilesional'' cerebral tissue, both tissue types exhibited relationships between established physiological variables and biochemistry. Decreases in perfusion and oxygenation were associated with deteriorating neurochemistry and these effects were more pronounced in perilesional tissue and when cerebrovascular reactivity was impaired.

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

“…[7][8][9][10] Probe Site Microdialysis catheter location is important, e.g., in gray or white matter ipsilateral or contralateral to the injury because metabolite level changes are larger in lesioned or penumbral zones compared with distant 'normal' tissue. [10][11][12] Also, gray and white matter exhibit different magnitudes and time courses of responses (i) to hypoxia for lactate and pyruvate in immature brain, 13 and (ii) to ischemia and reperfusion for the decline in direct current potential and levels of extracellular [Ca 2+ ], adenosine, inosine, hypoxanthine, glutamate, and GABA in adult brain, with white matter being usually less negatively affected. [14][15][16] Because white matter has approximately two-to fourfold lower metabolic and blood flow rates than gray matter, synaptic activity and excitatory neurotransmission (and excitotoxic damage) predominate in neuropil, and white matter is enriched with axons and oligodendroglia, caution must be applied when extrapolating data derived from small extracellular fluid volumes sampled by microdialysis (frequently placed in 'normal' white matter) to other brain regions.…”

“…45 Discordance between cited ANL-supportive studies and relevant uncited literature requires a more balanced presentation. Because (i) the magnitude of ANL shuttling has never been established and proven to be significant in vivo, and (ii) model predictions do not match experimentally established characteristics of brain activation in vivo, 23 statements such as the following by Bouzat et al 38 are very misleading: "However, emerging evidence demonstrated that in patients with TBI increased lactate seems predominantly non-hypoxic/ischemic and rather the consequence of increased cerebral glycolysis [2,12,13]. Lactate formed under such glycolytic conditions is shuttled from one lactate-producing cell (astrocyte) to another lactate-consuming cell (neuron) (astrocyte-neuron lactate shuttle) [14,15]."…”

Cerebral haemodynamics during experimental intracranial hypertension

“…1 Such an intracranial hypertension is universally detrimental; it impairs cerebral blood flow (CBF), 2 electrical activity 3 and metabolism. 4,5 Given these pathophysiological sequelae of intracranial hypertension, it is not surprising that active control of ICP plays a pivotal role in the management of neurological disorders including TBI. 6 The haemodynamic response to raised ICP is, however, incompletely described.…”

Multimodal brain monitoring in neurocritical care practice

“…Cerebral microdyalisis detects early hypoxia and ischemia and increases the therapeutic window to avoid secondary lesion. However, remains to be established if treatment-related improvement in biochemistry translates into better outcome after acute brain injury [31].…”