Lactate-pyruvate Ratio Research Articles

Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.

Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury

Traumatic brain injury (TBI) generates regional alterations in cerebral metabolism, leading to the potential evolution of persistent metabolic dysfunction. In the case of penetrating, firearm-related TBI, the pathophysiological mechanisms underlying these acute-phase metabolic derangements are not entirely understood-hindering the potential effectiveness of therapeutic intervention. The use of cerebral microdialysis to monitor biochemical alterations that occur, post-TBI, provides critical insight into the events that perpetuate neurological deterioration. Cerebral microdialysis was used to monitor alterations in the brain tissue chemistry of a 22-year-old female patient who sustained a penetrating gunshot wound to the head. Extracellular glucose, lactate, pyruvate, and lactate pyruvate ratio (LPR) were monitored over the course of the first-week post-injury. Analysis of the microdialysate revealed sustained elevations in LPR with peaks in excess of those seen in patients who have sustained permanent ischemic injury. This interval of persistently elevated LPR was followed by a spontaneous reduction of values, to levels below the defined threshold for metabolic crisis, over a period of several days. Microdialysis studies may significantly improve the understanding of the metabolic alterations that occur in patients who sustain a variety of forms of neurotrauma. Ultimately, monitoring these variations in brain tissue chemistry will improve the insight into the neuropathological mechanisms underlying penetrating traumatic brain injury, and enhance the therapeutic approach of these patients.

Changes in myocardial lactate, pyruvate and lactate-pyruvate ratio during cardiopulmonary bypass for elective adult cardiac surgery: Early indicator of morbidity

Background:Myocardial lactate assays have been established as a standard method to compare various myocardial protection strategies. This study was designed to test whether coronary sinus (CS) lactates, pyruvate and lactate-pyruvate (LP) ratio correlates with myocardial dysfunction and predict postoperative outcomes.Materials and Methods:This prospective observational study was conducted on 40 adult patients undergoing elective cardiac surgery with the aid of cardiopulmonary bypass (CPB). CS blood sampling was done for estimation of myocardial lactate (ML), pyruvate (MP) and lactate-pyruvate ratio (MLPR) namely: pre-CPB (T1), after removal of aortic cross clamp (T2) and 30 minutes post-CPB (T3).Results:Baseline myocardial LPR strongly correlated with Troponin-I at T1 (σ: 0.6). Patients were sub grouped according to the median value of myocardial lactate (2.9) at baseline T1 into low myocardial lactate (LML) group, mean (2.39±0.4 mmol/l), n=19 and a high myocardial lactate (HML) group, mean (3.65±0.9 mmol/l), n = 21. A significant increase in PL, ML, MLPR and TropI occurred in both groups as compared to baseline. Patients in HML group had significant longer period of ICU stay. Patients with higher inotrope score had significantly higher ML (T2, T3). ML with a baseline value of 2.9 mmol/l had 70.83% sensitivity and 62.5% specificity (ROC area: 0.7109 Std error: 0.09) while myocardial pyruvate with a baseline value of 0.07 mmol/l has 79.17% sensitivity and 68.75% specificity (ROC area: 0.7852, Std error: 0.0765) for predicting inotrope requirement after CPB.Conclusion:CS lactate, pyruvate and LP ratio correlate with myocardial function and can predict postoperative outcome.

Electrocautery causes more ischemic peritoneal tissue damage than ultrasonic dissection

BackgroundMinimizing peritoneal tissue injury during abdominal surgery has the benefit of reducing postoperative inflammatory response, pain, and adhesion formation. Ultrasonic dissection seems to reduce tissue damage. This study aimed to compare electrocautery and ultrasonic dissection in terms of peritoneal tissue ischemia measured by microdialysis.MethodsIn this study, 18 Wistar rats underwent a median laparotomy and had a peritoneal microdialysis catheter implanted in the left lateral sidewall. The animals were randomly assigned to receive two standard peritoneal incisions parallel to the catheter by either ultrasonic dissection or electrocautery. After the operation, samples of microdialysis dialysate were taken every 2 h until 72 h postoperatively for measurements of pyruvate, lactate, glucose, and glycerol, and ratios were calculated.ResultsThe mean lactate–pyruvate ratio (LPR), lactate–glucose ratio (LGR), and glycerol concentration were significantly higher in the electrocautery group than in the ultrasonic dissection group until respectively 34, 48, and 48 h after surgery. The mean areas under the curve (AUC) of LPR, LGR, and glycerol concentration also were higher in the electrocautery group than in the ultrasonic dissection group (4,387 vs. 1,639, P = 0.011; 59 vs. 21, P = 0.008; 7,438 vs. 4,169, P = 0.008, respectively).ConclusionElectrosurgery causes more ischemic peritoneal tissue damage than ultrasonic dissection.

Effect of mannitol on brain metabolism and tissue oxygenation in severe haemorrhagic stroke

BackgroundThe impact of osmotic therapies on brain metabolism has not been extensively studied in humans. The authors examined if mannitol treatment of raised intracranial pressure will result in an improvement...

Relevance of Cerebral Interleukin-6 After Aneurysmal Subarachnoid Hemorrhage

This study examines the inflammatory response via interleukin-6 (IL-6) in aneurysmal subarachnoid hemorrhage (aSAH) patients and its association with their clinical course (occurrence of acute focal neurological deficits, AFND; and delayed cerebral ischemia, DCI). A total of 38 consecutive aSAH patients were studied prospectively within 14 days after admission and classified as asymptomatic (n = 9; WFNS grade 1 (1-2), median and quartiles) and symptomatic (n = 29; WFNS grade 4 (2-5)); the latter presenting with AFND (n = 13), DCI (n = 10) or both (n = 6). Levels of pro-inflammatory cytokine IL-6 were determined in cerebral extracellular fluid (ECF, using cerebral microdialysis), cerebrospinal fluid (CSF) and plasma for 10 days after aSAH. Additionally, C-reactive protein (CRP) levels were measured in plasma. High IL-6 levels in CSF, ECF and plasma were found in all patients, reflecting a pronounced local inflammatory response after aSAH, followed only in symptomatic patients by a delayed systemic inflammation (CRP P < 0.025, days 7-9 after aSAH). In all compartments, IL-6 levels appeared to be higher in symptomatic patients, accompanied also by a higher ECF lactate-pyruvate ratio (P = 0.04). Cerebral, but not plasma IL-6, levels were indicative of the development of DCI in symptomatic patients (ECF P = 0.003; CSF P = 0.001). A pronounced initial cerebral inflammatory state was observed in patients of all WFNS grades, suggesting that IL-6 elevations are not necessarily detrimental. Cerebral, but not plasma IL-6, levels were predictive of the development of delayed ischemic deficits in symptomatic patients, suggesting that CSF or ECF are the best sampling media for future studies.

Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively). In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 μM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured. The hypoxanthine concentration was 23.0 ± 12 μM in early samples and 11.7 ± 6.8 μM in late samples (normal level ~2.0 μM). The inosine concentration was 7.2 ± 7.1 μM and 2.8 ± 1.6 μM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8). This study shows that the high cerebral LP ratio correlates to the hypoxanthine level in patients with acute liver failure. However, these metabolic alterations were not related to the development of intracranial hypertension.

Metabolic Crisis After Traumatic Brain Injury is Associated with a Novel Microdialysis Proteome

To examine if the metabolic distress after traumatic brain injury (TBI) is associated with a unique proteome. Patients with severe TBI prospectively underwent cerebral microdialysis for the initial 96 h after injury. Hourly sampling of metabolism was performed and patients were categorized as having normal or abnormal metabolism as evidenced by the lactate/pyruvate ratio (LPR) threshold of 40. The microdialysate was frozen for proteomic batch processing retrospectively. We employed two different routes of proteomic techniques utilizing mass spectrometry (MS) and categorized as diagnostic and biomarker identification approaches. The diagnostic approach was aimed at finding a signature of MS peaks which can differentiate these two groups. We did this by enriching for intact peptides followed by MALDI-MS analysis. For the biomarker identification approach, we applied classical bottom-up (trypsin digestion followed by LC-MS/MS) proteomic methodologies. Five patients were studied, 3 of whom had abnormal metabolism and 2 who had normal metabolism. By comparison, the abnormal group had higher LPR (1609 +/- 3691 vs. 15.5 +/- 6.8, P < 0.001), higher glutamate (157 +/- 84 vs. 1.8 +/- 1.4 microM, P < 0.001), and lower glucose (0.27 +/- 0.35 vs. 1.8 +/- 1.1 mmol/l, P < 0.001). The abnormal group demonstrated 13 unique proteins as compared with the normal group in the microdialysate. These proteins consisted of cytoarchitectural proteins, as well as blood breakdown proteins, and a few mitochondrial proteins. A unique as yet to be characterized peptide was found at m/z (mass/charge) 4733.5, which may represent a novel biomarker of metabolic distress. Metabolic distress after TBI is associated with a differential proteome that indicates cellular destruction during the acute phase of illness. This suggests that metabolic distress has immediate cellular consequences after TBI.

Systemic Glucose and Brain Energy Metabolism after Subarachnoid Hemorrhage

Brain energy metabolic crisis (MC) and lactate-pyruvate ratio (LPR) elevations have been linked to poor outcome in comatose patients. We sought to determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are associated with acute reductions in serum glucose. Twenty-eight consecutive comatose SAH patients that underwent multimodality monitoring with intracranial pressure and microdialysis were studied. MC was defined as lactate/pyruvate ratio (LPR) > or = 40 and brain glucose < 0.7 mmol/l. Time-series data were analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. Multimodality monitoring included 3,178 h of observation (mean 114 +/- 65 h per patient). In exploratory analysis, serum glucose significantly decreased from 8.2 +/- 1.8 mmol/l (148 mg/dl) 2 h before to 6.9 +/- 1.9 mmol/l (124 mg/dl) at the onset of MC (P < 0.001). Reductions in serum glucose of 25% or more were significantly associated with new onset MC (adjusted odds ratio [OR] 3.6, 95% confidence interval [CI] 2.2-6.0). Acute reductions in serum glucose of 25% or more were also significantly associated with an LPR rise of 25% or more (adjusted OR 1.6, 95% CI 1.1-2.4). All analyses were adjusted for significant covariates including Glasgow Coma Scale and cerebral perfusion pressure. Acute reductions in serum glucose, even to levels within the normal range, may be associated with brain energy metabolic crisis and LPR elevation in poor-grade SAH patients.

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

Objective TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 h and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 h of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels ( β = 0.066, p < 0.02), intraventricular hemorrhage ( β = 0.085, p < 0.021), and aneurysm size > 6 mm ( β = 0.14, p < 0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate–pyruvate ratio. Interpretation Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels.

Effect of packed red blood cell transfusion on cerebral oxygenation and metabolism after subarachnoid hemorrhage

Background Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH. Methods This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO2) was tested using univariate and multivariable analyses. Results PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after

Microdialysis of paraspinal muscle in healthy volunteers and patients underwent posterior lumbar fusion surgery

Paraspinal muscle damage is inevitable during conventional posterior lumbar fusion surgery. Minimal invasive surgery is postulated to result in less muscle damage and better outcome. The aim of this study was to monitor metabolic changes of the paraspinal muscle and to evaluate paraspinal muscle damage during surgery using microdialysis (MD). The basic interstitial metabolisms of the paraspinal muscle and the deltoid muscle were monitored using the MD technique in eight patients, who underwent posterior lumbar fusion surgery (six male and two female, median age 57.7 years, range 37-74) and eight healthy individuals for different positions (five male and three female, age 24.1 +/- 0.8 years). Concentrations of glucose, glycerol, and lactate pyruvate ratio (L/P) in both tissues were compared. In the healthy group, the glucose and glycerol concentrations and L/P were unchanged in the paraspinal muscle when the body position changed from prone to supine. The glucose concentration and L/P were stable in the paraspinal muscle during the surgery. Glycerol concentrations increased significantly to 243.0 +/- 144.1 microM in the paraspinal muscle and 118.9 +/- 79.8 microM in the deltoid muscle in the surgery group. Mean glycerol concentration difference (GCD) between the paraspinal muscle and the deltoid tissue was 124.1 microM (P = 0.003, with 95% confidence interval 83.4-164.9 microM). The key metabolism of paraspinal muscle can be monitored by MD during the conventional posterior lumbar fusion surgery. The glycerol concentration in the paraspinal muscle is markedly increased compared with the deltoid muscle during the surgery. It is proposed that GCD can be used to evaluate surgery related paraspinal muscle damage. Changing body position did not affect the paraspinal muscle metabolism in the healthy subjects.

Microdialysis: is it ready for prime time?

This review highlights recent advances in cerebral microdialysis for investigational and clinical neurochemical monitoring in patients with critical neurological conditions. Use of microdialysis with other methods, including PET, electrophysiological monitoring and brain tissue oximetry in traumatic brain injury, subarachnoid hemorrhage with vasospasm, and infarction with refractory increased intracranial pressure have been reported. Potentially adverse neurochemical effects of nonconvulsive status epilepticus and cortical slow depolarization waves, both of which are increasingly recognized in traumatic brain injury and stroke patients, have been reported. The explosive growth in the use of cerebral oximetry with targeted management of brain tissue oxygen levels is leading to greater understanding of derangements of cerebral bioenergetics in the critically ill brain, but there remain unresolved basic issues. Understanding of the analytes that are measurable at the bedside - glucose, lactate, pyruvate, glutamate and glycerol - continues to evolve with glucose, lactate, pyruvate and the lactate-pyruvate ratio taking center stage. Analytes including inflammatory biomarkers such as cytokines and metabolites of nitric oxide are presently investigational, but hold promise for future application in advancing our understanding of basic pathophysiology, therapeutic target selection and prognostication. Growing consensus on indications for use of clinical microdialysis and advances in commercially available equipment continue to make microdialysis increasingly 'ready for prime time.' Cerebral microdialysis is an established tool for neurochemical research in the ICU. This technique cannot be fruitfully used in isolation, but when combined with other monitoring methods provides unique insights into the biochemical and physiological derangements in the injured brain.

The effect of red blood cell transfusion on cerebral oxygenation and metabolism after severe traumatic brain injury*

There is evidence to suggest that anemia after severe traumatic brain injury (sTBI) is detrimental. However, there is a paucity of evidence supporting the use of transfusion of packed red blood cells in patients with sTBI. To understand the acute effect of packed red blood cell transfusion on cerebral oxygenation and metabolism in patients with sTBI. Prospective clinical study. Addenbrooke's Neurosciences Critical Care Unit, a 21-bed tertiary academic unit. Thirty patients with sTBI. Patients were randomized by computer random number generator to one of three transfusion thresholds: 8, 9, or 10 g/dL. When the patients' hemoglobin concentration fell below their assigned threshold, two units of packed red blood cells were transfused over 2 hours. A 1-hour period of stabilization was observed before final data collection. The primary outcome was change in brain tissue oxygen (Pbto2). Secondary outcomes included dependence of baseline hemoglobin concentration and baseline Pbto2 on the relationship of transfusion and Pbto2, and the effect of transfusion on lactate pyruvate ratio (LPR) and brain pH as markers of cerebral metabolic state. Fifty-seven percent of patients experienced an increase in Pbto2 during the course of the study, whereas in 43% of patients, Pbto2 either did not change or decreased. Multivariable generalized estimating equation analysis revealed change in hemoglobin concentration to significantly and positively associated with change in Pbto2 [0.10 kPa/(g/dL) 95% confidence interval 0.03-0.17, p = 0.003]. Improvement in Pbto2 was not associated with baseline hemoglobin concentration or low Pbto2 (<1 kPa). Fifty-six percent of patients experienced an increase in LPR. No significant relationship between change in LPR or transfusion on pHbt and change in hemoglobin could be demonstrated. Transfusion of packed red blood cells acutely results in improved brain tissue oxygen without appreciable effect on cerebral metabolism. ISRCTN89085577.

Induced Normothermia Attenuates Cerebral Metabolic Distress in Patients With Aneurysmal Subarachnoid Hemorrhage and Refractory Fever

The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Prostacyclin Treatment in Severe Traumatic Brain Injury: A Microdialysis and Outcome Study

Prostacyclin (PGI(2)) is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation. In trauma the balance between PGI(2) and thromboxane A(2) (TXA(2)) is shifted towards TXA(2). Externally provided PGI(2) would, from a theoretical and experimental point of view, improve the microcirculation in injured brain tissue. This study is a prospective consecutive double-blinded randomized study on the effect of PGI(2) versus placebo in severe traumatic brain injury (sTBI). All patients with sTBI were eligible. verified sTBI, Glasgow Coma Score (GCS) at intubation and sedation of <or=8, age 15-70 years, a first-recorded cerebral perfusion pressure (CPP) of >or=10 mm Hg, and arrival within 24 h of trauma. All subjects received an intracranial pressure (ICP) measuring device, bilateral intracerebral microdialysis catheters, and a microdialysis catheter in the abdominal subcutaneous adipose tissue. Subjects were treated according to an ICP-targeted therapy based on the Lund concept. 48 patients (mean age of 35.5 years and a median GCS of 6 [3-8]) were included. We found no significant effect of prostacyclin (epoprostenol, Flolan) on either the lactate-pyruvate ratio (L/P) at 24 h or the brain glucose levels. There was no significant difference in clinical outcome between the two groups. The median Glasgow Outcome Score (GOS) at 3 months was 4, and mortality was 12.5%. The favorable outcome (GOS 4-5) was 52%. The initial L/P did not prognosticate for outcome. Thus our results indicate that there is no effect of PGI(2) at a dose of 0.5 ng/kg/min on brain L/P, brain glucose levels, or outcome at 3 months.

The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis

Ischemia-reperfusion injury induced by the Pringle maneuver is a well-known problem after liver surgery. The aim of this study was to monitor metabolic changes in the pig liver during warm ischemia and the following reperfusion preceded by ischemic preconditioning (IPC). Eight Landrace pigs underwent laparotomy. Two microdialysis catheters were inserted in the liver, one in the left lobe and another in the right lobe. A reference catheter was inserted in the right biceps femoris muscle. Microdialysis samples were collected every 30 min during the study. After 2 h of baseline measurement, IPC was performed by subjecting pigs to 10 min of ischemia, followed by 10 min of reperfusion. Total ischemia for 60 min was followed by 3 h of reperfusion. The samples were analyzed for glucose, lactate, pyruvate, and glycerol. Blood samples were drawn three times to determine standard liver parameters. All parameters remained stable during baseline. Glycerol and glucose levels increased significantly during ischemia, followed by a decrease from the start of reperfusion. During the ischemic period, lactate levels increased significantly and decreased during reperfusion. The lactate-pyruvate ratio increased significantly during ischemia and decreased rapidly during reperfusion. Only minor changes were observed in standard liver parameters. The present study demonstrated profound metabolic changes before, during, and after warm liver ischemia under the influence of IPC. Compared with a similar study without IPC, the metabolic changes seem to be unaffected by preconditioning.

Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury*

To determine whether persistent metabolic dysfunction in normal-appearing frontal lobe tissue is correlated with long-term tissue atrophy. Prospective monitoring with retrospective data analysis. Single-center academic neurointensive care unit. Fifteen patients with moderate to severe traumatic brain injury (Glasgow Coma Scale score 3-12). None. Hourly cerebral microdialysis was performed for the initial 96 hrs after trauma to determine extracellular levels of glucose, glutamate, glycerol, lactate, and pyruvate in normal appearing frontal lobes. Six months after injury, the anatomical outcome was assessed by measures of global and regional cerebral atrophy using volumetric brain magnetic resonance imaging. The lactate/pyruvate ratio was elevated >40 after traumatic brain injury in most patients, with a mean percent time of 32 +/- 29% of hours monitored. At 6 months after traumatic brain injury, there was a mean frontal lobe atrophy of 12 +/- 11% and global brain atrophy of 8.5 +/- 4.5%. The percentage of time of elevated lactate/pyruvate ratio correlated with the extent of frontal lobe brain atrophy (r = -.56, p < 0.01), but not global brain atrophy (r = -.31, p = 0.20). The predictive effect of lactate/pyruvate ratio was independent of patient age, Glasgow Coma Scale score, and volume of frontal lobe contusion. Persistent metabolic crisis, as reflected by an elevated lactate/pyruvate ratio, in normal appearing posttraumatic frontal lobe, is predictive of the degree of tissue atrophy at 6 months.

Increase in cerebral aerobic metabolism by normobaric hyperoxia after traumatic brain injury

Traumatic brain injury (TBI) is associated with depressed aerobic metabolism and mitochondrial dysfunction. Normobaric hyperoxia (NBH) has been suggested as a treatment for TBI, but studies in humans have produced equivocal results. In this study the authors used brain tissue O(2) tension measurement, cerebral microdialysis, and near-infrared spectroscopy to study the effects of NBH after TBI. They investigated the effects on cellular and mitochondrial redox states measured by the brain tissue lactate/pyruvate ratio (LPR) and the change in oxidized cytochrome c oxidase (CCO) concentration, respectively. The authors studied 8 adults with TBI within the first 48 hours postinjury. Inspired oxygen percentage at normobaric pressure was increased from baseline to 60% for 60 minutes and then to 100% for 60 minutes before being returned to baseline for 30 minutes. The results are presented as the median with the interquartile range in parentheses. During the 100% inspired oxygen percentage phase, brain tissue O2 tension increased by 7.2 kPa (range 4.5-9.6 kPa) (p < 0.0001), microdialysate lactate concentration decreased by 0.26 mmol/L (range 0.0-0.45 mmol/L) (p = 0.01), microdialysate LPR decreased by 1.6 (range 1.0-2.3) (p = 0.02), and change in oxidized CCO concentration increased by 0.21 mumol/L (0.13-0.38 micromol/L) (p = 0.0003). There were no significant changes in intracranial pressure or arterial or microdialysate glucose concentration. The change in oxidized CCO concentration correlated with changes in brain tissue O(2) tension (r(s)= 0.57, p = 0.005) and in LPR (r(s)= -0.53, p = 0.006). The authors have demonstrated oxidation in cerebral cellular and mitochondrial redox states during NBH in adults with TBI. These findings are consistent with increased aerobic metabolism and suggest that NBH has the potential to improve outcome after TBI. Further studies are warranted.

Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study

Cerebral microdialysis (MD) is able to detect markers of tissue damage and cerebral ischaemia and can be used to monitor the biochemical changes subsequent to head injury. In this prospective, observational study we analysed the correlation between microdialysis markers of metabolic impairment and intracranial pressure (ICP) and investigated whether changes in biomarker concentration precede rises in ICP. MD and ICP monitoring was carried out in twenty-five patients with severe TBI in Neurointensive care. MD samples were analysed hourly for lactate:pyruvate (LP) ratio, glutamate and glycerol. Abnormal values of microdialysis variables in presence of normal ICP were used to calculate the risk of intracranial hypertension developing within the next 3 h. An LP ratio >25 and glycerol >100 micromol/L, but not glutamate >12 micromol/L, were associated with significantly higher risk of imminent intracranial hypertension (odds ratio: 9.8, CI 5.8-16.1; 2.2, CI 1.6-3.8; 1.7, CI 0.6-3, respectively). An abnormal LP ratio could predict an ICP rise above normal levels in 89% of cases, whereas glycerol and glutamate had a poorer predictive value. Changes in the compound concentrations in microdialysate are a useful tool to describe molecular events triggered by TBI. These changes can occur before the onset of intracranial hypertension, suggesting that biochemical impairment can be present before low cerebral perfusion pressure is detectable. This early warning could be exploited to expand the window for therapeutic intervention.