Identifying physiological determinants of 800 m running performance using post-exercise blood lactate kinetics.

PURPOSE: The aims of the present study were to investigate blood lactate kinetics following high intensity exercise and identify the physiological determinants of 800 m running performance. METHODS: Fourteen competitive 800 m runners performed two running tests. First, participants performed a multistage graded exercise test to determine physiological indicators related to endurance performance. Second, participants performed four to six 30-s high intensity running bouts to determine post-exercise blood lactate kinetics. Using a biexponential time function, lactate exchange ability (γ1), lactate removal ability (γ2), and the quantity of lactate accumulated (QLaA) were calculated from individual blood lactate recovery data. RESULTS: 800 m running performance was significantly correlated with peak oxygen consumption (r = -0.794), γ1 and γ2 at 800 m race pace (r = -0.604 and -0.845, respectively), and QLaA at maximal running speed (r = -0.657). V ˙ O2peak and γ2 at 800 m race pace explained 83% of the variance in 800 m running performance. CONCLUSION: Our results indicate that (1) a high capacity to exchange and remove lactate, (2) a high capacity for short-term lactate accumulation and, (3) peak oxygen consumption, are critical elements of 800 m running performance. Accordingly, while lactate has primarily been utilized as a performance indicator for long-distance running, post-exercise lactate kinetics may also prove valuable as a performance determinant in middle-distance running.

V ˙ Lamax: determining the optimal test duration for maximal lactate formation rate during all-out sprint cycle ergometry.

PURPOSE: This study aimed to ascertain the optimal test duration to elicit the highest maximal lactate formation rate ( V ˙ Lamax), whilst exploring the underpinning energetics, and identifying the optimal blood lactate sampling period. METHODS: Fifteen trained to well-trained males (age 27 ± 6 years; peak power: 1134 ± 174 W) participated in a randomised cross-over design completing three all-out sprint cycling tests of differing test durations (10, 15, and 30 s). Peak and mean power output (W and W.kg-1), oxygen uptake, and blood lactate concentrations were measured. V ˙ Lamax and energetic contributions (phosphagen, glycolytic, and oxidative) were determined using these parameters. RESULTS: The shortest test duration of 10 s elicited a significantly (p = 0.003; p < 0.001) higher V ˙ Lamax (0.86 ± 0.17 mmol.L-1.s-1; 95% CI 0.802-0.974) compared with both 15 s (0.68 ± 0.18 mmol.L-1.s-1; 95% CI 0.596-0.794) and 30 s (0.45 ± 0.07 mmol.L-1.s-1; 95% CI 0.410-0.487). Differences in V ˙ Lamax were associated with large effect sizes (d = 1.07, d = 3.15). We observed 81% of the PCr and 53% of the glycolytic work completed over the 30 s sprint duration was attained after 10 s. BLamaxpost were achieved at 5 ± 2 min (ttest 10 s), 6 ± 2 min (ttest 15 s), and 7 ± 2 min (ttest 30 s), respectively. CONCLUSION: Our findings demonstrated a 10 s test duration elicited the highest V ˙ Lamax. Furthermore, the 10 s test duration mitigated the influence of the oxidative metabolism during all-out cycling. The optimal sample time to determine peak blood lactate concentration following 10 s was 5 ± 2 min.

Can lactate levels and lactate kinetics predict mortality in patients with COVID-19 with using qCSI scoring system?

INTRODUCTION: In this study, we aimed to investigate the relationship between blood lactate levels and lactate kinetics (lactate clearance and Δ lactate) for predicting mortality in patients with COVID-19 admitted to the emergency department. METHODS: This study was performed as a retrospective study that included patients admitted to the emergency department between March 1st, 2020, and January 1st, 2022. Lactate levels were recorded at the first admission (0 h lactate) and the highest blood lactate levels in the first 24 h of follow-up (2nd highest lactate). Lactate kinetics were calculated. Clinical severity was determined according to the quick COVID Severity Index (qCSI). RESULTS: 300 patients were included in the study. Lactate levels at admission were similar in groups with or without mortality, but 2nd highest lactate levels were found to be significantly higher in the group with mortality (p < 0.001). Lactate clearance and ∆ lactate levels were also found to be lower in the mortality group (p < 0.001). Lactate kinetics in patients in the clinically low severity group were lower in the mortality group (p = 0.02 and p = 0.039, respectively). In the low-intermediate and high-intermediate groups, 0-h lactate and 2nd highest lactate levels were found to be higher in the mortality group, and lactate kinetics were similar in the groups with and without mortality. In the group with high clinical severity, 2nd highest lactate levels were found to be higher in the group with mortality (p = 0.010). Lactate kinetics were also found to be significantly lower in the mortality group (p < 0.001). In the high qCSI group, based on ROC analysis, the AUC for 2nd highest lactate levels predicting mortality was 0.642 (95% CI: 0.548-0.728). The optimal cut-off value for mortality was greater than >2.4 mmol/L (60.6% sensitivity, 67.4% specificity). The AUC for lactate clearance was 0.748 (95% CI: 0.659-0.824). The lactate clearance cut-off value was ≤ -177.78% (49.3% sensitivity, 100% specificity). The AUC for ∆ lactate was 0.707 (95% CI: 0.616-0.787). The optimal ∆ lactate cut-off was ≤ -2 mmol/L (45.1% sensitivity, 93.5% specificity). CONCLUSION: In COVID-19, 2nd highest blood lactate and lactate kinetics were found to be prognostic indicators of the disease. High 2nd highest lactate levels and low lactate kinetics in patients with high clinical severity were guiding physicians regarding the outcome of the disease.

Study of Significance of Serum Lactate Kinetics in Sepsis as Mortality Predictor.

Introduction: Sepsis is one of the leading causes of death worldwide. Serum lactate is being used in sepsis for diagnostic and prognostic purposes for years now. In this study, we shed light over a novel use of lactate in form of various clearance parameters to determine mortality in septic patients at the 28th day. Materials and methods: In our study, 200 patients with sepsis were included using quick sequential organ failure assessment (qSOFA) score and their lactate levels were measured at the time of admission (0 hour) and 24 hours after admission. Lactate clearance parameters (absolute and relative lactate clearance, lactate clearance rate) were calculated. All patients were followed up for a period of 28 days to determine the outcome, and data analysis was done accordingly. Results and conclusion: Our study showed that higher SOFA score, qSOFA score, and serum lactate levels were associated with increased 28th-day mortality. Low absolute, relative lactate clearance and lactate clearance rate were also associated with poor outcomes. The best cutoffs to predict poor outcomes were serum lactate level at 24 hours ≥4 mmol/L and relative lactate clearance ≤40.3% with good sensitivity and specificity. How to cite this article: Chaudhari M, Agarwal N. Study of Significance of Serum Lactate Kinetics in Sepsis as Mortality Predictor. Indian J Crit Care Med 2022;26(5):591-595.

Lactate Measurements and Their Association With Mortality in Pediatric Severe Sepsis in India: Evidence That 6-Hour Level Performs Best.

PURPOSE: To investigate association of static and dynamic lactate indices with early mortality (within 48 hours of admission), as well as need for vasopressors and mechanical ventilation in pediatric severe sepsis/shock. To explore optimal cutoffs of lactate indices. We hypothesized that dynamic indices are superior to static indices in predicting early mortality. METHODS: This prospective cohort study involved children (aged <14 years) admitted in emergency department, tertiary care teaching hospital in North India with severe sepsis/shock (2015-2016). Arterial lactate was measured at admission (X0) and after 6 hours (X6). Primary outcome of the measurement was early mortality. Association between lactate indices- lactate at 0 hours (Lac0), lactate after 6 hours (Lac6), time-weighted average (LacTW), delta (ΔLac), clearance (LacCl%) and early mortality, need for vasopressors, and mechanical ventilation-was assessed using Student t test/Mann-Whitney test. Area under the receiver operating characteristic curve (AUROC) for early mortality deduced for all lactate indices and compared with reference (Lac0). Optimal cutoffs (maximizing both sensitivity and specificity) and their positive predictive value (PPV) and negative predictive value (NPV) were determined. RESULTS: During the study period, 116 children were assessed. Septic shock was present at admission in 56.9% children; 50% of children died during the next 48 hours. Lac0, Lac6, and LacTW were significantly higher, and LacCl% was lower in nonsurvivors versus survivors (all P < .001). Lac6 (0.837 [0.76-0.91]) had significantly higher AUROC (95% confidence interval) than Lac0 (0.77; P = .03). Abnormal lactate metrics (higher Lac0, Lac6, LacTW, and lower LacCl%) were associated with vasopressors need and mechanical ventilation. On logistic regression, Lac6 emerged as an independent predictor of early mortality as well as vasopressor and mechanical ventilation need. The optimal cutoff of Lac6 for identifying early mortality with good sensitivity, specificity, PPV, and NPV was ≥2.65 (76, 85, 83, 78). CONCLUSIONS: Lactate6 is the best marker associated with early mortality and higher level of care in severe sepsis/septic shock in resource-poor regions.

Stepwise lactate kinetics in critically ill patients: prognostic, influencing factors, and clinical phenotype.

BACKGROUND: To investigate the optimal target e of lactate kinetics at different time during the resuscitation, the factors that influence whether the kinetics achieve the goals, and the clinical implications of different clinical phenotypes. METHODS: Patients with hyperlactatemia between May 1, 2013 and December 31, 2018 were retrospectively analyzed. Demographic data, basic organ function, hemodynamic parameters at ICU admission (T0) and at 6 h, 12 h, 24 h, 48 h, and 72 h, arterial blood lactate and blood glucose levels, cumulative clinical treatment conditions at different time points and final patient outcomes were collected. RESULTS: A total of 3298 patients were enrolled, and the mortality rate was 12.2%. The cutoff values of lactate kinetics for prognosis at 6 h, 12 h, 24 h, 48 h, and 72 h were 21%, 40%, 57%, 66%, and 72%. The APACHE II score, SOFA score, heart rate (HR), and blood glucose were risk factors that correlated with whether the lactate kinetics attained the target goal. Based on the pattens of the lactate kinetics, eight clinical phenotypes were proposed. The odds ratios of death for clinical phenotypes VIII, IV, and II were 4.39, 4.2, and 5.27-fold of those of clinical phenotype I, respectively. CONCLUSION: Stepwise recovery of lactate kinetics is an important resuscitation target for patients with hyperlactatemia. The APACHE II score, SOFA score, HR, and blood glucose were independent risk factors that influenced achievement of lactate kinetic targets. The cinical phenotypes of stepwise lactate kinetics are closely related to the prognosis.

Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate.

BACKGROUND: Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied. AIM: To establish and validate a feasible method to study lactate kinetics in critically ill patients. METHODS: Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 µmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (Ra) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10). RESULTS: Ra for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 µmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques. CONCLUSION: This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients. TRIAL REGISTRATION: ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true.

Mathematical Modeling of Substrates Fluxes and Tumor Growth in the Brain.

The aim of this article is to show how a tumor can modify energy substrates fluxes in the brain to support its own growth. To address this question we use a modeling approach to explain brain nutrient kinetics. In particular we set up a system of 17 equations for oxygen, lactate, glucose concentrations and cells number in the brain. We prove the existence and uniqueness of nonnegative solutions and give bounds on the solutions. We also provide numerical simulations.

Use of stepwise lactate kinetics-oriented hemodynamic therapy could improve the clinical outcomes of patients with sepsis-associated hyperlactatemia.

BACKGROUND: Setting lactate kinetics at >30% might improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. The aim of this study was to explore the outcome benefits of stepwise lactate kinetics vs central venous oxygen saturation (ScvO2)-oriented hemodynamic therapy at 6 h as the protocol goal during early resuscitation. METHODS: The relevant parameters and adverse events after different targets in 360 randomly assigned patients with sepsis-associated hyperlactatemia were recorded and compared. RESULTS: Heart rate (HR) at 48 h in the ScvO2 group was higher than in the lactate kinetics group (105 ± 19 bpm vs 99 ± 20 bpm, P = 0.040). The liquid balance at 4 h, 12 h, and 24 h in the lactate kinetics group was larger than in the ScvO2 group (1535 (1271-1778) ml vs 826 (631-1219) ml, P < 0.001; 1688 (1173-1923) ml vs 1277 (962 - 1588) ml, P <0.001; and 1510 (904-2087) ml vs 1236 (740-1808) ml, P = 0.005), respectively. Mortality was higher in the ScvO2 group (27.9% vs 18.3%, P = 0.033), but there was no significant difference between the two groups in the length of stay in the ICU or mechanical ventilation. In terms of new onset organ dysfunction, there was a significant difference between the two groups in total bilirubin at 48 h and 72 h. Based on the 60-day survival curves, there was significantly more mortality in the ScvO2 group than in the lactate kinetics group (X 2 = 4.133, P = 0.042). In addition, fewer adverse events occurred in the lactate kinetics group. CONCLUSIONS: Stepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry, NCT02566460 . Registered on 26 September 2015.

Time course of blood lactate levels, inflammation, and mitochondrial function in experimental sepsis.

BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if <10% or increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and mitochondrial function were compared between groups. In a second group of animals with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal regional Lac exchange was measured, and animals were categorized according to the decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in the Lac ≥10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In cohort 1, systemic hemodynamics were similar in the Lac ≥10% (n = 13) and Lac <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated sepsis and decreased during resusciation in both groups, but they were lower at study end in the Lac ≥10% group (p = 0.047). Complexes I and II maximal (state 3) and resting (state 4) isolated brain mitochondrial respiration at study end was higher in the Lac ≥10% group than in the Lac <10% group, whereas hepatic, myocardial, and skeletal muscle mitochondrial respiration was similar in both groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end was higher in the Lac ≥10% group (n = 7) than in the Lac <10% group (n = 9), despite similar cardiac output. Hepatic lactate influx and uptake in the Lac ≥10% group were approximately 1.5 and 3 times higher, respectively, than in the Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac.

New potential for an old kid on the block: Impact of premorbid metformin use on lactate kinetics, kidney injury and mortality in sepsis and septic shock, an observational study.

INTRODUCTION: Sepsis and septic shock cause significant mortality worldwide, with no targeted molecular therapies available. Metformin has pleomorphic effects that may be beneficial in sepsis, but at present, the impact of metformin exposure on sepsis remains controversial. Metformin might alter lactate metabolism, but little is known about its influence on lactate kinetics. We therefore investigated the impact of preadmission metformin use on lactate kinetics, acute kidney injury (AKI) and mortality in sepsis. MATERIALS AND METHODS: We retrospectively analysed all ICU admissions with sepsis and septic shock between January 2013 and September 2020, identifying 77 users and 390 nonusers (subdivided in diabetics, n = 48 and nondiabetics, n = 342). RESULTS: (Sub)groups did not differ in illness severity or sepsis aetiology. Admission lactate levels were similar, but evolution in lactate over the first 24 h showed a larger decrease in users vs nonusers (median - 53% vs. -36%, p = .010). No difference in AKI or renal replacement therapy was found. Mortality was lower in users vs nonusers in case of septic shock (21.9% (n = 7) vs. 42.7% (n = 61) for 90d mortality, p = .029, OR 0.38 [95% CI: 0.15-0.93]), but showed no significant differences in the combined sepsis and septic shock population. CONCLUSIONS: In our data, preadmission metformin use is associated with a significantly larger decrease in lactate after admission with sepsis or septic shock and with reduced mortality in septic shock. This underscores the need for further studies investigating the interplay between metformin, lactate and sepsis, thereby exploring the potential use of metformin or its pathways in sepsis.

Relationship between Blood Volume, Blood Lactate Quantity, and Lactate Concentrations during Exercise.

We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake (V·O2max), lactate concentrations ([La-]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V·O2max and maximum power (Pmax) ranged between 32 and 62 mL·min-1·kg-1 and 2.3 and 5.5 W·kg-1, respectively. BV ranged between 81 and 121 mL·kg-1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La-] was significantly correlated to the systemic lactate quantity (La-, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = -0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La- have a major influence on the resulting [La-] during dynamic exercise. Moreover, the blood La- transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La-] during a cardio-pulmonary exercise test.

The Effects of L-Citrulline on Blood-Lactate Removal Kinetics Following Maximal-Effort Exercise.

The accumulation of lactate in muscle and blood during high-intensity exercise is negatively correlated with the duration exercise can be sustained. Removal of lactate is a key component of acute recovery between consecutive bouts of such exercise. Low-intensity exercise enhances recovery by accelerating lactate turnover in metabolically active tissues, largely mediated by blood flow to these tissues. Therefore, the purpose of this research was to clarify if L-citrulline, a nutritional supplement purported to promote vasodilation via enhanced nitric oxide availability, would augment the removal of blood lactate during active recovery (AR). L-citrulline ingestion will augment the rate of blood lactate concentration decrease during AR, reduce the oxygen-cost of submaximal exercise, and increase time-to-exhaustion and peak oxygen uptake (V̇O2peak) during a test of maximal aerobic power. Healthy university students (five males & five females) participated in this double-blind, randomized, placebo-controlled study. Participants exercised on a cycle ergometer at submaximal steady-state intensities followed by progressively increasing intensity to exhaustion, 10 min of AR, and then supramaximal intensity exercise to exhaustion. Oxygen uptake was measured throughout the trial and blood lactate was sampled repeatedly during AR. The protocol elicited very high peak blood lactate concentrations after exercise (11.3 + 1.3 mmol/L). L-citrulline supplementation did not significantly alter blood lactate kinetics during AR, the oxygen cost of exercise, V̇O2peak, or time-to-exhaustion. Despite a strong theoretical basis by which L-citrulline could augment lactate removal from the blood, L-citrulline supplementation showed no effect as an exercise-recovery supplement.

Prognosis of Hypothermic Patients Undergoing ECLS Rewarming-Do Alterations in Biochemical Parameters Matter?

BACKGROUND: While ECLS is a highly invasive procedure, the identification of patients with a potentially good prognosis is of high importance. The aim of this study was to analyse changes in the acid-base balance parameters and lactate kinetics during the early stages of ECLS rewarming to determine predictors of clinical outcome. METHODS: This single-centre retrospective study was conducted at the Severe Hypothermia Treatment Centre at John Paul II Hospital in Krakow, Poland. Patients ≥18 years old who had a core temperature (Tc) < 30 °C and were rewarmed with ECLS between December 2013 and August 2018 were included. Acid-base balance parameters were measured at ECLS implantation, at Tc 30 °C, and at 2 and 4 h after Tc 30 °C. The alteration in blood lactate kinetics was calculated as the percent change in serum lactate concentration relative to the baseline. RESULTS: We included 50 patients, of which 36 (72%) were in cardiac arrest. The mean age was 56 ± 15 years old, and the mean Tc was 24.5 ± 12.6 °C. Twenty-one patients (42%) died. Lactate concentrations in the survivors group were significantly lower than in the non-survivors at all time points. In the survivors group, the mean lactate concentration decreased -2.42 ± 4.49 mmol/L from time of ECLS implantation until 4 h after reaching Tc 30 °C, while in the non-survivors' group (p = 0.024), it increased 1.44 ± 6.41 mmol/L. CONCLUSIONS: Our results indicate that high lactate concentration is associated with a poor prognosis for hypothermic patients undergoing ECLS rewarming. A decreased value of lactate kinetics at 4 h after reaching 30 °C is also associated with a poor prognosis.

Resistance Index of the Superior Mesenteric Artery: Correlation With Lactate Concentration and Kinetics Prediction After Cardiac Surgery.

Objective: This study aimed to measure blood flow changes in the superior mesenteric artery (SMA), using Doppler ultrasound, in post-cardiac surgery patients, to evaluate the correlation between the SMA resistance index (SMA-RI) and lactate concentrations. Methods: The patients' basic hemodynamics, blood gas parameters and lactate concentration were collected at admission. Simultaneously, the SMA blood flow parameters were collected using Doppler ultrasound with the patients in the supine position. The lactate concentrations were measured again at 2, 6, and 12-h time points after the first test. The length of intensive care unit stays and prognoses continued to be monitored. Results: A total of 67 patients were included. The SMA-RI correlated with the admission (r = 0.3117, P = 0.0102), 2-h (r = 0.5091, P < 0.0001), 6-h (r = 0.5061, P < 0.0001), and 12-h (r = 0.2483, P = 0.0428) lactate concentrations. The SMA-RI could predict the 2-h 10% [area under the curve (AUC) = 0.8294, P < 0.0001] and 6-h 40% lactate kinetics (AUC = 0.7708, P = 0.0012). The cut-off value was 0.83. When the SMA-RI was <0.83, the specificity and sensitivity were 86.38 and 75.56%, respectively for the prediction of the 2-h >10% lactate kinetics, and 64.71 and 75.00%, respectively, for the prediction of the 6-h >40% lactate kinetics. The lactate concentrations at admission, 2 and 6-h points were higher in the high-RI group (RI ≥ 0.83) and the intensive care unit stays were significantly longer than in the low-RI group (P = 0.0005). Conclusions: The increase in SMA-RI was associated with higher lactate concentrations and worse lactate kinetics in post-cardiac surgery patients. This may be related to intestinal hypoperfusion. The SMA-RI may be one of the indicators that should be monitored to guide resuscitation in these patients.

Partial differential model of lactate neuro-energetics: analytic results and numerical simulations.

Interfaces play a key role on diseases development because they dictate the energy inflow of nutrients from the surrounding tissues. What is underestimated by existing mathematical models is the biological fact that cells are able to use different resources through nonlinear mechanisms. Among all nutrients, lactate appears to be a sensitive metabolic when talking about brain tumours or neurodegenerative diseases. Here we present a partial differential model to investigate the lactate exchanges between cells and the vascular network in the brain. By extending an existing kinetic model for lactate neuro-energetics, we first provide analytical proofs of the uniqueness and the derivation of precise bounds on the solutions of the problem including diffusion of lactate in a representative volume element comprising the interface between a capillary and cells. We further perform finite element simulations of the model in two test cases, discussing the relevant physical parameters governing the lactate dynamics.

Blood lactate and lactate kinetics as treatment and prognosis markers for tissue hypoperfusion.

Objective: Blood lactate concentration (L) and lactate kinetic (LK) over time might be a helpful marker of the shock severity. The purpose of this study is to analyze whether the L and LK could correlate with the outcome and the therapy of patients with different types of shock.Methods: Design: A 3.5-year retrospective observational study. Patients: Eighteen years of age or older, diagnosed with shock were included. Arterial L measurements were performed upon admission and approximatively 3 and 6 h later. The evolution of lactate over this period of time was correlated with the outcome and therapy. Interventions: Univariate and multivariable statistical tests were performed to examine the relation between the initial L/LK and the in-hospital mortality, total mortality, length of stay (LOS), the LOS at the intensive care unit and the administered therapy. The optimal cut-off point of the LK over time to predict the mortality was calculated.Results: The initial L and the 6 h LK were significantly associated with the outcome. The higher the initial L and lower the LK, the higher the risk of mortality in the hospital or within 6 months. Moreover, the higher the initial L and lower the 6 h LK, the longer was the LOS. A relation between the initial L/LK and the required therapy was found. The optimal cut-off for the 6-h LK is 38.1%. Patients with a 6 h LK >38.1% had a significantly higher chance of survival.Conclusions: A significant relationship between the L/6-h LK and the outcome and treatment was found. The optimal survival cut-off point of 6 h LK in our study was 38.1%.

Regional venous-arterial CO2 to arterial-venous O2 content difference ratio in experimental circulatory shock and hypoxia.

BACKGROUND: Venous-arterial carbon dioxide (CO2) to arterial-venous oxygen (O2) content difference ratio (Cv-aCO2/Ca-vO2) > 1 is supposed to be both sensitive and specific for anaerobic metabolism. What regional hemodynamic and metabolic parameters determine the ratio has not been clarified. OBJECTIVES: To address determinants of systemic and renal, spleen, gut and liver Cv-aCO2/Ca-vO2. METHODS: Post hoc analysis of original data from published experimental studies aimed to address effects of different fluid resuscitation strategies on oxygen transport, lactate metabolism and organ dysfunction in fecal peritonitis and endotoxin infusion, and from animals in cardiac tamponade or hypoxic hypoxia. Systemic and regional hemodynamics, blood flow, lactate uptake, carbon dioxide and oxygen-derived variables were determined. Generalized estimating equations (GEE) were fit to assess contributors to systemic and regional Cv-aCO2/Ca-vO2. RESULTS: Median (range) of pooled systemic Cv-aCO2/Ca-vO2 in 64 pigs was 1.02 (0.02 to 3.84). While parameters reflecting regional lactate exchange were variably associated with the respective regional Cv-aCO2/Ca-vO2 ratios, only regional ratios were independently correlated with systemic ratio: renal Cv-aCO2 /Ca-vO2 (ß = 0.148, 95% CI 0.062 to 0.234; p = 0.001), spleen Cv-aCO2/Ca-vO2 (ß = 0.065, 95% CI 0.002 to 0.127; p = 0.042), gut Cv-aCO2/Ca-vO2 (ß = 0.117, 95% CI 0.025 to 0.209; p = 0.013), liver Cv-aCO2/Ca-vO2 (ß = - 0.159, 95% CI - 0.297 to - 0.022; p = 0.023), hepatosplanchnic Cv-aCO2/Ca-vO2 (ß = 0.495, 95% CI 0.205 to 0.786; p = 0.001). CONCLUSION: In a mixed set of animals in different shock forms or during hypoxic injury, hepatosplanchnic Cv-aCO2/Ca-vO2 ratio had the strongest independent association with systemic Cv-aCO2/Ca-vO2, while no independent association was demonstrated for lactate or hemodynamic variables.

Maximal Lactate Steady State and Lactate Thresholds in the Cross-Country Skiing Sub-Technique Double Poling.

The response of blood lactate concentration (BLC) to exercise is a commonly used approach to set training intensities and to determine the anaerobic threshold, which are important in evaluation of endurance exercise performance. The maximal lactate steady state (MLSS) is defined as the highest workload or BLC that can be maintained without continual lactate accumulation over time. The aim of this study was to investigate MLSS in the cross-country skiing sub-technique double poling and to assess the validity of a fixed blood lactate threshold (OBLA and the 45° tangent of the lactate curve). Eight well-trained cross-country skiers (age = 27.6±8.8 years [mean±SD], body mass = 73.9±6.2 kg, height = 179.3±7.0 cm) performed an incremental test to determine OBLA and Individual Anaerobic Threshold (IAnT) and several constant workload tests of 30 min to determine the MLSS. Lactate concentration at MLSS in double poling was 6.7±1.3 mmol ·L-1 which was significantly higher compared to OBLA (p<0.001) and IAnT (p<0.01). Despite significant correlations in velocities between MLSS-IAnT and MLSS-OBLA (r=0.95/0.95, p<0.001), significant (p<0.01) differences between MLSS (21.4±2.8 km ·h-1) versus IAnT (20.6±3.6 km ·h-1) and OBLA (19.9±3.0 km ·h-1) was observed. It was concluded that both OBLA and IAnT underestimate MLSS in double poling. A fixed value of 7 mmol ·L-1 would be more appropriate in lactate testing of cross-country skiers using the double poling technique, yet dissuaded because of intra-individual variations. Direct determination of MLSS is the recommended approach for useful exercise thresholds, important for training interventions in elite cross-country skiers.

A Lactate Kinetics Method for Assessing the Maximal Lactate Steady State Workload.

During a continuously increasing exercise workload (WL) a point will be reached at which arterial lactate accumulates rapidly. This so-called lactate threshold (LT) is associated with the maximal lactate steady state workload (MLSSW), the highest WL, at which arterial lactate concentration [LA] does not change. However, the physiological range in which the LT and the MLSSW occur has not been demonstrated directly. We used minor WL variations in the MLSSW range to assess arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise tests. At a certain workload, minimal further increment of running speed (0.1-0.15 m/s) or cycling power (7-10 W) caused a steep elevation of [LA] (0.9 ± 0.43 mM, maximum increase 2.4 mM), indicating LT achievement. This sharp [LA] increase was more pronounced when higher WL increments were used (0.1 vs. 0.30 m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15 W, P = 0.002; 10 vs. 15 W, P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA] increase indicating MLSSW realization. LT based determination of running speed (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001), valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned regulation of exercise-related lactate metabolism, which can be reliably captured by assessing lactate kinetics at the MLSSW.