Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury

OBJECT: Severe traumatic brain injury (TBI) imposes a huge metabolic load on brain tissue, which can be summarized initially as a state of hypermetabolism and hyperglycolysis. In experiments O2 consumption has been shown to increase early after trauma, especially in the presence of high lactate levels and forced O2 availability. In recent clinical studies the effect of increasing O2 availability on brain metabolism has been analyzed. By their nature, however, clinical trauma models suffer from a heterogeneous injury distribution. The aim of this study was to analyze, in a standardized diffuse brain injury model, the effect of increasing the fraction of inspired O2 on brain glucose and lactate levels, and to compare this effect with the metabolism of the noninjured sham-operated brain. METHODS: A diffuse severe TBI model developed by Foda and Maramarou, et al., in which a 420-g weight is dropped from a height of 2 m was used in this study. Forty-one male Wistar rats each weighing approximately 300 g were included. Anesthesized rats were monitored by placing a femoral arterial line for blood pressure and blood was drawn for a blood gas analysis. Two time periods were defined: Period A was defined as preinjury and Period B as postinjury. During Period B two levels of fraction of inspired oxygen (FiO2) were studied: air (FiO2 0.21) and oxygen (FiO2 1). Four groups were studied including sham-operated animals: air-air-sham (AAS); air-O2-sham (AOS); air-air-trauma (AAT); and air-O2-trauma (AOT). In six rats the effect of increasing the FiO2 on serum glucose and lactate was analyzed. During Period B lactate values in the brain determined using microdialysis were significantly lower (p < 0.05) in the AOT group than in the AAT group and glucose values in the brain determined using microdialysis were significantly higher (p < 0.04). No differences were demonstrated in the other groups. Increasing the FiO2 had no significant effect on the serum levels of glucose and lactate. CONCLUSIONS: Increasing the FiO2 influences dialysate glucose and lactate levels in injured brain tissue. Using an FiO2 of 1 influences brain metabolism in such a way that lactate is significantly reduced and glucose significantly increased. No changes in dialysate glucose and lactate values were found in the noninjured brain.

Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury

OBJECTIVE: The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. METHODS: In a prospective, observational study 20 patients suffering severe head injury (GCS< or =8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (F IO2 1.0) ( Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge ( Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. RESULTS: F IO2 was positively correlated with PtiO2 (p < 0.0001) over the whole study period. PtiO2 was significantly higher (p < 0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p < 0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p = 0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. CONCLUSION: PtiO2 is significantly positively correlated with F IO2, meaning that PtiO2 can be improved by the simple manipulation of increasing F IO2 and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure.

Influence of inspired oxygen on glucose-lactate dynamics after subdural hematoma in the rat

The mechanisms causing brain damage after acute subdural hematoma (SDH) are poorly understood. A decrease in cerebral blood flow develops immediately after the hematoma forms, thus reducing cerebral oxygenation. This in turn may activate mitochondrial failure and tissue damage leading to ionic imbalance and possibly to cellular breakdown. The purpose of this study was to test whether a simple therapeutic measure, namely increased fraction of inspired oxygen (FiO2 100), and hence increased arterial and brain tissue oxygen tension, can influence brain glucose and lactate dynamics acutely after subdural hematoma in the rat. Twenty-five male Sprague-Dawley anesthetized rats were studied before, during and after induction of the SDH in two separate groups. The Oxygen group (n = 10) was ventilated with 100% oxygen immediately after induction of the SDH. The Air group (n = 10) was ventilated during the entire study with 21% oxygen. Brain microdialysate samples were analyzed for glucose and lactate. All rats were monitored with femoral arterial blood pressure catheters, arterial blood gas analysis, arterial glucose, lactate and end tidal CO2 (EtCO2). Five male Sprague-Dawley rats were sham operated to measure the effect of oxygen challenge on glucose-lactate dynamics without injury. Arterial oxygen tension in the Oxygen group was 371 +/- 30 mmHg and was associated with significantly greater increase in dialysate lactate in the first 30 min after induction of SDH. Dialysate glucose initially dropped in both groups, after SDH, but then reverted significantly faster to values above baseline in the Oxygen group. Changes in ventilatory parameters had no significant effect on dialysate glucose and lactate parameters in the sham group. Extracellular dialysate lactate and glucose are influenced by administration of 100% O2 after SDH. Dialysate glucose normalizes significantly quicker upon 100% oxygen ventilation. We hypothesize that increased neural tissue oxygen tension, in presence of reduced regional CBF, and possibly compromised mitochondrial function, after acute SDH results in upregulation of rate-limiting enzyme systems responsible for both glycolytic and aerobic metabolism. Similar changes have been seen in severe human head injury, and suggest that a simple therapeutic measure, such as early ventilation with 100% O2, may improve cerebral energy metabolism, early after SDH. Further studies to measure the generation of adenosine triphosphate (ATP) are needed to validate the hypothesis.

Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury

OBJECT: Early impairment of cerebral blood flow in patients with severe head injury correlates with poor brain tissue O2 delivery and may be an important cause of ischemic brain damage. The purpose of this study was to measure cerebral tissue PO2, lactate, and glucose in patients after severe head injury to determine the effect of increased tissue O2 achieved by increasing the fraction of inspired oxygen (FiO2). METHODS: In addition to standard monitoring of intracranial pressure and cerebral perfusion pressure, the authors continuously measured brain tissue PO2, PCO2, pH, and temperature in 22 patients with severe head injury. Microdialysis was performed to analyze lactate and glucose levels. In one cohort of 12 patients, the PaO2 was increased to 441+/-88 mm Hg over a period of 6 hours by raising the FiO2 from 35+/-5% to 100% in two stages. The results were analyzed and compared with the findings in a control cohort of 12 patients who received standard respiratory therapy (mean PaO2 136.4+/-22.1 mm Hg). The mean brain PO2 levels increased in the O2-treated patients up to 359+/-39% of the baseline level during the 6-hour FiO2 enhancement period, whereas the mean dialysate lactate levels decreased by 40% (p < 0.05). During this O2 enhancement period, glucose levels in brain tissue demonstrated a heterogeneous course. None of the monitored parameters in the control cohort showed significant variations during the entire observation period. CONCLUSIONS: Markedly elevated lactate levels in brain tissue are common after severe head injury. Increasing PaO2 to higher levels than necessary to saturate hemoglobin, as performed in the O2-treated cohort, appears to improve the O2 supply in brain tissue. During the early period after severe head injury, increased lactate levels in brain tissue were reduced by increasing FiO2. This may imply a shift to aerobic metabolism.

The Effect of Respirator Wear on Blood Lactate During Maximal Exertion

The impact of a filtering half-face respirator and a half-face supplied air respirator use on blood lactate production was assessed during maximal exertion to determine if anaerobic strain increased compared to no respirator use. Twenty-eight participants performed a 30 second cycling Wingate anaerobic test (WAnT) wearing a half-face respirator. Blood lactate production was measured to evaluate if there was an increase in anaerobic strain from wearing a tight fitting half-face respirator compared to wearing no respirator. A supplied air respirator WAnT was then performed using 18 participants from the first experiment to evaluate if supplied air decreased anaerobic strain. Data from both experiments were compared to evaluate differences in the physiological effects due to respirator use during maximal exertion. A survey was administered following the second WAnT experiment to measure the participants' perception of acceptability and impact of supplied air respirator use in workplace. The blood lactate levels measured directly after the WAnT yielded lower overall mean values during the half-mask respirator trial (12.1 mmollL) and supplied air respirator trial (12.2 mmollL) than the no respirator trial (13.1 mmoI/L). However, differences in blood lactate levels were not statistically significant (p =0.597). Participants reported an average acceptability of 92.3% to wearing the supplied air respirator while performing light work. However, the average acceptability decreased as the exertion increased to moderate (78.8%) and heavy (46.6%) workloads. The supplied air respirator used provided no significant reduction in anaerobic strain within this study group compared to either the filtering half-face respirator or the no respirator condition. However, there were differences in physiological effects of respirators on each gender identified in this study. Further assessment of the anaerobic impact of respirators on each gender should be conducted.

Early serum procalcitonin, interleukin-6, and 24-hour lactate clearance: useful indicators of septic infections in severely traumatized patients

BACKGROUND: Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients. METHODS: A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS) > 16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72 h of admission (24.5%), late admission > 12 h after injury (16%), and age < 16 years (0.5%). Data are stated as the median (range). RESULTS: Altogether, 1032 trauma patients (76.2% male) with an average age of 38 years, a median ISS of 29 (16-75), and an Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score of 14 (0-40) were evaluated. The in-hospital mortality (>3 days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p < 0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5. CONCLUSIONS: This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortality.

Serial lactate and admission SOFA scores in trauma: an analysis of predictive value in 724 patients with and without traumatic brain injury

Objective Arterial lactate, base excess (BE), lactate clearance, and Sequential Organ Failure Assessment (SOFA) score have been shown to correlate with outcome in severely injured patients. The goal of the present study was to separately assess their predictive value in patients suffering from traumatic brain injury (TBI) as opposed to patients suffering from injuries not related to the brain. Materials and methods A total of 724 adult trauma patients with an Injury Severity Score (ISS) ≥ 16 were grouped into patients without TBI (non-TBI), patients with isolated TBI (isolated TBI), and patients with a combination of TBI and non-TBI injuries (combined injuries). The predictive value of the above parameters was then analyzed using both uni- and multivariate analyses. Results The mean age of the patients was 39 years (77 % males), with a mean ISS of 32 (range 16–75). Mortality ranged from 14 % (non-TBI) to 24 % (combined injuries). Admission and serial lactate/BE values were higher in non-survivors of all groups (all p < 0.01), but not in patients with isolated TBI. Admission SOFA scores were highest in non-survivors of all groups (p = 0.023); subsequently septic patients also showed elevated SOFA scores (p < 0.01), except those with isolated TBI. In this group, SOFA score was the only parameter which showed significant differences between survivors and non-survivors. Receiver operating characteristic (ROC) analysis revealed lactate to be the best overall predictor for increased mortality and further septic complications, irrespective of the leading injury. Conclusion Lactate showed the best performance in predicting sepsis or death in all trauma patients except those with isolated TBI, and the differences were greatest in patients with substantial bleeding. Following isolated TBI, SOFA score was the only parameter which could differentiate survivors from non-survivors on admission, although the SOFA score, too, was not an independent predictor of death following multivariate analysis.

Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery.

The value of cerebrospinal fluid (CSF) lactate level and CSF/blood glucose ratio for the identification of bacterial meningitis following neurosurgery was assessed in a retrospective study. During a 3-year period, 73 patients fulfilled the inclusion criteria and could be grouped by preset criteria in one of three categories: proven bacterial meningitis (n = 12), presumed bacterial meningitis (n = 14), and nonbacterial meningeal syndrome (n = 47). Of 73 patients analyzed, 45% were treated with antibiotics and 33% with steroids at the time of first lumbar puncture. CSF lactate values (cutoff, 4 mmol/L), in comparison with CSF/blood glucose ratios (cutoff, 0.4), were associated with higher sensitivity (0.88 vs. 0.77), specificity (0.98 vs. 0.87), and positive (0.96 vs. 0.77) and negative (0.94 vs. 0.87) predictive values. In conclusion, determination of the CSF lactate value is a quick, sensitive, and specific test to identify patients with bacterial meningitis after neurosurgery.

Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis

Diagnosis of osteoarthritis (OA) is based upon the clinical orthopaedic examination and the radiographic assessment, both of which can be non-specific and insensitive in early joint disease. The aim of our study was to investigate if there is an increase in serum levels of C-reactive protein (CRP) in degenerative joint disease (DJD) and if CRP could be used to help diagnose OA. We also wished to investigate whether it was possible to distinguish a joint with clinically and radiographically confirmed OA from a healthy joint by comparing lactate dehydrogenase (LDH) levels within the synovial fluid and the serum. We have shown a difference in synovial LDH levels between diseased and healthy joints (P<0.0001). There was also a significant difference between LDH in arthritic synovial fluid and serum, with no correlation between the values. Despite the fact that the values of our clinical patients tended to be higher than the values of our control group (P=0.05) all measured values were within the normal limits of previous publications. From these data, we conclude that single measurements of serum CRP do not permit detection of OA in clinical patients and that serum LDH is not a reliable marker for osteoarthritis. LDH levels in the synovial fluid could be of diagnostic value for identifying osteoarthritis.

The value of serial serum lactate measurements in predicting the extent of ischemic bowel and outcome of patients suffering acute mesenteric ischemia

BACKGROUND Acute mesenteric ischemia (AMI) is an emergency with a mortality rate up to 50 %. Detecting AMI continues to be a major challenge. This study assed the correlation of repeated preoperative serum lactate with bowel necrosis and to identify risk factors for a lethal outcome in patients with AMI. METHODS A retrospective study of 91 patients with clinically and pathologically confirmed AMI from January 2006 to December 2012 was performed. RESULTS In-hospital mortality rate was 42.9 %. Two hundred nine preoperative lactate measurements were analyzed (2.3 ± 1.1 values per patient). Less than or equal to six hours prior to surgery, the mean serum lactate level was significantly higher (4.97 ± 4.21 vs. 3.24 ± 3.05 mmol/L, p = 0.006) and the mean pH significantly lower (7.28 ± 0.12 vs. 7.37 ± 0.08, p = 0.001) compared to >6 h before surgery. Thirty-four patients had at least two lactate measurements within 24 h prior to surgery. In this subgroup, 17 patients (50 %) exhibited an increase, 17 patients (50 %) a decrease in lactate levels. Forward logistic regression analysis showed that length of necrotic bowel and the highest lactate value 24 h prior to surgery were independent risk factors for mortality (r (2)  = 0.329). CONCLUSION The value of serial lactate and pH measurements to predict the length of necrotic bowel is very limited. Length of necrotic bowel and lactate values are independent risk factors for mortality.

Insulin, CCAAT/enhancer-binding proteins and lactate regulate the human 11β-hydroxysteroid dehydrogenase type 2 gene expression in colon cancer cell lines.

11β-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid receptor transactivation by glucocorticoids and regulate access to the glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess. As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity. In the present study we show that insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT-29) at the transcriptional level, in a time and dose dependent manner. The downregulation was reversible and required new protein synthesis. Pathway analysis using mRNA profiling revealed that insulin treatment modified the expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding proteins) but also of glycolysis related enzymes. Western blot and real time PCR confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression regulation. In addition, secretion of lactate, a byproduct of glycolysis, was shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we demonstrate that insulin downregulates HSD11B2 through increased LIP expression and augmented lactate secretion. Such mechanisms are of interest and potential significance for sodium reabsorption in the colon.

Lactate dehydrogenase concentration in nasal wash fluid indicates severity of rhinovirus-induced wheezy bronchitis in preschool children.

The clinical course of rhinovirus (RV)-associated wheezing illnesses is difficult to predict. We measured lactate dehydrogenase concentrations, RV load, antiviral and proinflammatory cytokines in nasal washes obtained from 126 preschool children with RV wheezy bronchitis. lactate dehydrogenase values were inversely associated with subsequent need for oxygen therapy. lactate dehydrogenase may be a useful biomarker predicting disease severity in RV wheezy bronchitis.