Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients

Abstract

Secondary insults can adversely influence outcome following severe traumatic brain injury. Monitoring of cerebral extracellular chemistry with microdialysis has the potential for early detection of metabolic derangements associated with such events. The objective of this study was to determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury. Prospectively collected observational neuromonitoring data from 223 patients were analysed. Monitoring modalities included digitally recorded intracranial pressure, cerebral perfusion pressure, cerebrovascular pressure reactivity index and microdialysis markers glucose, lactate, pyruvate, glutamate, glycerol and the lactate/pyruvate ratio. Outcome was assessed using the Glasgow Outcome Scale at 6 months post-injury. Patient-averaged values of parameters were used in statistical analysis, which included univariate non-parametric methods and multivariate logistic regression. Monitoring with microdialysis commenced on median (interquartile range) Day 1 (1-2) from injury and median (interquartile range) duration of monitoring was 4 (2-7) days. Averaged over the total monitoring period levels of glutamate (P = 0.048), lactate/pyruvate ratio (P = 0.044), intracranial pressure (P = 0.006) and cerebrovascular pressure reactivity index (P = 0.01) were significantly higher in patients who died. During the initial 72 h of monitoring, median glycerol levels were also higher in the mortality group (P = 0.014) and median lactate/pyruvate ratio (P = 0.026) and lactate (P = 0.033) levels were significantly lower in patients with favourable outcome. In a multivariate logistic regression model (P < 0.0001), which employed data averaged over the whole monitoring period, significant independent positive predictors of mortality were glucose (P = 0.024), lactate/pyruvate ratio (P = 0.016), intracranial pressure (P = 0.029), cerebrovascular pressure reactivity index (P = 0.036) and age (P = 0.003), while pyruvate was a significant independent negative predictor of mortality (P = 0.004). The results of this study suggest that extracellular metabolic markers are independently associated with outcome following traumatic brain injury. Whether treatment-related improvement in biochemistry translates into better outcome remains to be established.

Elevated glutamate and lactate predict brain death after severe head trauma

“…Moreover, there is strong evidence showing that impaired cerebrovascular pressure reactivity, and decreased brain perfusion and oxygenation, are forces driving metabolic abnormalities related to lactate/pyruvate ratio. However, this oxygen deficiency is more pronounced in the perilesional tissue26, 30 and apparently does not explain the metabolic alterations in the whole brain after a TBI. Indeed, increased lactate production in the injured brain seems to be independent of oxygen availability, and therefore cannot be considered as a direct ischemic and hypoxic metabolic marker30.…”

“…However, the majority of clinical studies indicate that increased brain extracellular glutamate levels in association with comorbidities may predict poor functional outcomes and brain death 11, 12, 13, 14. For instance, secondary mechanisms associated with the brain tissue deformation including global ischemia, sustained increased intracranial pressure and focal contusions11, 13, and spontaneous brain hypothermia (<36°C)26 have been implicated in the increase in glutamate levels and acute neuronal death. Also, increased extracellular brain glutamate concentration after TBI is also influenced by decreased astrocytic glutamate uptake 27.…”

Intracranial pressure and its surrogates

“…The correlation between clinical deterioration and ICP is not a robust one: because the brain is anatomically compartmentalized, fatal herniation syndromes may occur without associated changes in ICP, for example, after posterior fossa hemorrhage or infarction. Studies conducted in TBI patients with parenchymal oxygen or microdialysis probes demonstrate that brain tissue hypoxia and metabolic distress can occur independently of ICP or CPP [9,10], perhaps superseding the latter in terms of prognostic significance [11]. Evidence that cerebral pressure autoregulation is globally or regionally impaired following severe TBI means that ischemia can occur at apparently adequate CPP levels [12,13]-a serious challenge to the current recommendation of a single CPP target in all patients [14].…”

Microdialysis to Optimize Cord Perfusion and Drug Delivery in Spinal Cord Injury

“…Low glucose, high lactate, high lactate-topyruvate ratio (LPR) and high lactate-to-glucose ratio (LGR) indicate metabolic derangement [13][14][15] . Glutamate is released during ischemia and causes neuronal death (excitotoxicity) whereas glycerol is a marker for cell membrane lipid degradation 12 .…”