Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients.
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.
Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
Ivan
I
Timofeev
Keri L H
KL
Carpenter
Jürgens
J
Nortje
Pippa G
PG
Al-Rawi
Mark T
MT
O'Connell
Marek
M
Czosnyka
Peter
P
Smielewski
John D
JD
Pickard
David K
DK
Menon
Peter J
PJ
Kirkpatrick
Arun K
AK
Gupta
Peter J
PJ
Hutchinson
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism* / Q000401:mortality; D002540:Cerebral Cortex / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry*; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged; D019289:Pyruvic Acid / Q000378:metabolism
D015415:Biomarkers; D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid; D005947:Glucose; D005990:Glycerol