Elevated glutamate and lactate predict brain death after severe head trauma

Abstract

ObjectiveClinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.MethodsThis cross‐sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, n = 6) or survival (survival, n = 14), within 3 days after hospital admission. CSF levels of brain‐derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed.ResultsGlutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55–98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55–98.08%). BDNF and GDNF did not discriminate poor outcome.InterpretationThis early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI.

Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers

“…These biochemical and metabolomic alterations first appear in the brain tissue and then, by crossing a number of barriers, manifest in biofluids such as cerebrospinal fluid (CSF), blood, saliva and urine [1][2][3][4][5][6][7][8][9][10][11][12]. Therefore, biofluids contain valuable information about the occurrence and progression of TBI and thus recently have been explored as a source for potential biomarkers to diagnose TBI, as well as to assess its severity, monitor its progression, predict patient outcomes, and determine the effectiveness of therapeutic interventions [1,4,5,[9][10][11][13][14][15][16][17][18][19]. The use of serum biomarkers has greatly contributed to improved diagnostic and therapeutic methods in fields such as hematology, cardiology, oncology, and infectious disease [10].…”

“…Over the last few years, several biofluid biomarkers such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), S100β, glial fibrillary acidic protein (GFAP), neurofilament light chain (e.g., NF-L) and tau have been studied as diagnostic and prognostic markers of TBI [1,13,15,22,23]. In addition to these biomarkers that are directly associated with primary neuronal, glial, or axonal damage due to TBI, the concentration levels of amino acids and other metabolite markers in CSF, serum, and even urine, have been shown to be significantly different in patients with TBI in comparison to non-TBI subjects in clinical studies [5,8,12,16,19] and are altered following TBI in comparison to pre-injury conditions in pre-clinical studies [3,[6][7][8]. The metabolite biomarkers have been shown to be related to secondary injury and associated with acute to chronic neuropathological sequelae, neurodegeneration, cognitive impairments, as well as energy deficits and damages in the brain tissue following TBI [8,19].…”

“…The metabolite biomarkers have been shown to be related to secondary injury and associated with acute to chronic neuropathological sequelae, neurodegeneration, cognitive impairments, as well as energy deficits and damages in the brain tissue following TBI [8,19]. Studies suggested that metabolite changes have great potential to be used as diagnostic and prognostic biomarkers for TBI and TBI-induced neurodegeneration [1][2][3]8,16,17,19,24,25].…”

A Precision Medicine Approach to Cerebral Edema and Intracranial Hypertension after Severe Traumatic Brain Injury: Quo Vadis?

“…The concept of longitudinal patterns appears to be a consistent theme, observed for ICP trajectories and other biomarkers (Sur1) [26]. A recent human TBI study ( n = 20) correlated CSF glutamate and lactate levels with 3-day mortality; however, prediction on ICP or cerebral edema measures was not performed [130]. …”

Lactate Albumin Ratio is Associated with Mortality in Patients with Moderate to Severe Traumatic Brain Injury

“…The serum lactate level, a widely acknowledged indicator of tissue hypoperfusion, has been con rmed associated with organ failure and mortality in many clinical settings such as sepsis, trauma, pediatric critical Illness [4][5][6][7][8]. And several studies have been conducted to explore the prognostic value of serum lactate level in TBI patients [9][10][11]. Most of these studies showed that higher serum lactate was associated with worse injury severity and poor outcome in TBI patients.…”