Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Abstract

Object: Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors' objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value.

Methods: A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score < or = 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO(2), jugular venous O(2) saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded.

Results: One hundred sixty-five patients were included in the study. Initially high glutamate values were predictive of a poor outcome. The mortality rate was 30.3% among patients with glutamate levels > 20 micromol/L, compared with 18% among those with levels < or = 20 micromol/L. Two general patterns were recognized: Pattern 1, glutamate levels tended to normalize over the monitoring period (120 hours); and Pattern 2, glutamate levels tended to increase with time or remain abnormally elevated. Patients showing Pattern 1 had a lower mortality rate (17.1 vs 39.6%) and a better 6-month functional outcome among survivors (41.2 vs 20.7%).

Conclusions: Glutamate levels measured by microdialysis appear to have an important role in TBI. Data in this study suggest that glutamate levels are correlated with the mortality rate and 6-month functional outcome.

Conflict of interest statement

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Figures

Fig. 1

Two patterns were identified regarding the changes of glutamate levels over the monitoring period. In Pattern 1 (left), the glutamate levels tend to normalize over time. Two trends represent subgroups of this pattern: in the first, levels are initially low and remain low; in the second, they are initially high but decrease over time. In Pattern 2 (right), the glutamate levels tend to increase over time or remain abnormally elevated. Three trends are identified as subgroups of this pattern: in the first, levels are initially low but increase over time; in the second, they are initially high, and although they decrease over time, they remain abnormally elevated; and in the third, they are initially high and continue to increase for several days before decreasing.

Fig. 2

This 40-year-old man, who presented to the emergency department after an aggravated assault, had a GCS score of 6. A: Head CT scan without contrast showing a right acute subdural hematoma with midline shift. The patient underwent emergency surgery for evacuation of the hematoma, and ICP monitor, microdialysis catheter, and SjvO2 catheters were inserted intraoperatively. B: Intracranial pressure traces showing initially well-controlled (~ 24 hours) ICP; however, ICP increased later and was refractory to maximal medical management. C: Graph depicting initially low (for ~ 80 hours) glutamate levels; later, however, a significant increase was recorded. This patient was severely disabled at the 1-month follow-up and died 6 months after surgery.

Fig. 3

This 36-year-old man, who presented to the emergency department after an aggravated assault, had a GCS score of 7. A: Head CT scan showing a right temporal epidural hematoma as well as bilateral multiple contusions and evidence of traumatic subarachnoid hemorrhage. The patient underwent emergency surgery for evacuation of the hematoma, and an ICP monitor, microdialysis catheter, and brain tissue PO2 and SjvO2 catheters were inserted intraoperatively. B: Intracranial pressure traces indicating that despite evacuation of the hematoma and maximal medical management, this patient’s ICP was persistently high. C: Graph demonstrating that his glutamate level was initially high. A moderate decrease was noted after 24 hours, but later a significant increase was recorded. D: Graph showing a progressive decrease in the SjvO2 values over the monitoring period. E: Graph depicting a progressive decline in brain tissue PO2 (PbO2) values over the monitoring period.