Lactate and the Lactate-to-Pyruvate Molar Ratio Cannot Be Used as Independent Biomarkers for Monitoring Brain Energetic Metabolism: A Microdialysis Study in Patients with Traumatic Brain Injuries

Abstract

BackgroundFor decades, lactate has been considered an excellent biomarker for oxygen limitation and therefore of organ ischemia. The aim of the present study was to evaluate the frequency of increased brain lactate levels and the LP ratio (LPR) in a cohort of patients with severe or moderate traumatic brain injury (TBI) subjected to brain microdialysis monitoring to analyze the agreement between these two biomarkers and to indicate brain energy metabolism dysfunction.MethodsForty-six patients with an admission Glasgow coma scale score of ≤13 after resuscitation admitted to a dedicated 10-bed Neurotraumatology Intensive Care Unit were included, and 5305 verified samples of good microdialysis data were analyzed.ResultsLactate levels were above 2.5 mmol/L in 56.9% of the samples. The relationships between lactate and the LPR could not be adequately modeled by any linear or non-linear model. Neither Cohen’s kappa nor Gwet’s statistic showed an acceptable agreement between both biomarkers to classify the samples in regard to normal or abnormal metabolism. The dataset was divided into four patterns defined by the lactate concentrations and the LPR. A potential interpretation for these patterns is suggested and discussed. Pattern 4 (low pyruvate levels) was found in 10.7% of the samples and was characterized by a significantly low concentration of brain glucose compared with the other groups.ConclusionsOur study shows that metabolic abnormalities are frequent in the macroscopically normal brain in patients with traumatic brain injuries and a very poor agreement between lactate and the LPR when classifying metabolism. The concentration of lactate in the dialysates must be interpreted while taking into consideration the LPR to distinguish between anaerobic metabolism and aerobic hyperglycolysis.

Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain

“…At 0.3 mL/min, we found a lower pyruvate limit of 39 mmol/L in anesthetized patients, corresponding to a true [Pyr] brain of $55 mmol/L. This value was similar to the lower limit obtained by Reinstrup et al 10 Our upper limit for the LP ratio was 34.2 at a perfusion rate of 0.3 mL/min, and it was 39.2 when using the ZFM data (Table 4); this corresponds to a LP ratio that is above [35][36][37][38][39][40], as suggested by the 2014 microdialysis consensus conference. 20 Therefore, the limit of 25 we suggested in a previous paper is likely too low to indicate ischemic or non-ischemic brain hypoxia or mitochondrial dysfunction.…”

“…As we discussed in a previous paper, the best available estimate for upper brain lactate levels derives from studies of CSF and from a few studies of patients operated on in neurosurgical procedures in whom brain MD were monitored under general anesthesia and using different anesthetic management techniques. 36 These studies and others-conducted in severe TBI and patients with SAH-found that certain lactate thresholds were related to poor clinical outcomes, and the upper limit for brain lactate most widely used in neurocritical patients is extremely variable (range: 1.50 to 5.10). 11,13,16,17,37 The 2014 cerebral microdialysis consensus statement recommended 4 mmol/L as the upper reference limit.…”

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

“…Similarly, while TNF signaling is detrimental to CNS homeostasis, transforming growth factor-β (TGF-β) is strongly neuroprotective as signaling acts to reduce inflammation, excitotoxicity and apoptosis, and to enhance neuronal regeneration [for review, see (31)]. The trend toward increased lactate release in females is also intriguing, as lactate levels are increased during several types of brain injury and are thought to both indicate and enhance tissue damage (63,102). Thus, alcohol-induced astrocyte dysfunction in females is predicted to accelerate alcohol-induced neurotoxicity in a sexually dimorphic fashion.…”

Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats

“…30,31 In addition, ''metabolic crisis,'' defined by a high lactate/pyruvate ratio (L/P), was associated with poor prognosis. 32,33 Metabolic crisis was further dichotomized based on brain lactate concentration ([Lac]b), rCBF, and PbtO 2 : type 1 (ischemic) displays high [Lac]b whereas type 2 (nonischemic) displays normal to low [Lac]b. 32,33 By contrast, ''aerobic hyperglycolysis,'' defined as high [Lac]b and low L/P with rCBF and PbtO 2 within physiological ranges, was associated with good prognosis.…”