Lower Lactate Levels Research Articles

Systematic Innominate Artery Cannulation Strategy in Acute Type A Aortic Dissection: Better Perfusion, Better Results.

(1) Background: Arterial cannulation in type A acute aortic dissection (TAAAD) is still subject to debate. We describe a systematic approach of using the innominate artery for arterial perfusion (2) Methods: The hospital records of 110 consecutive patients with acute TAAAD operated on between January 2014 and December 2022 were retrospectively analyzed. The effect of the cannulation site on early and late mortality, as well as on cardio-pulmonary perfusion indices (lactate and base excess levels, and cooling and rewarming speed) were investigated. (3) Results: There was a significant difference in early mortality (8.82% vs. 40.79%, p < 0.01) but no difference in long-term survival beyond the first 30 days. Using the innominate artery enabled the use of approximately 20% higher CPB flows (2.73 ± 0.1 vs. 2.42 ± 0.06 L/min/m2 BSA, p < 0.01), which resulted in more rapid cooling (1.89 ± 0.77 vs. 3.13 ± 1.62 min/°C/m2 BSA, p < 0.01), rewarming (2.84 ± 1.36 vs. 4.22 ± 2.23, p < 0.01), lower mean base excess levels during CPB (-5.01 ± 2.99 mEq/L vs. -6.66 ± 3.37 mEq/L, p = 0.01) and lower lactate levels at the end of the procedure (4.02 ± 2.48 mmol/L vs. 6.63 ± 4.17 mmol/L, p < 0.01). Postoperative permanent neurologic insult (3.12% vs. 20%, p = 0.02) and acute kidney injury (3.12% vs. 32.81%, p < 0.01) were significantly reduced. (4) Conclusions: systematic use of the innominate artery enables better perfusion and superior results in TAAAD repair.

Autosomal Recessively Inherited Glucose Transporter-1 Deficiency Syndrome with Acanthocytosis: A Case Report

AbstractGlucose transporter-1 deficiency syndrome (GLUT-1DS) is a rare, autosomal dominantly inherited disorder due to a heterozygous mutation in the gene solute channel 2A1 (SLC2A1).This gene encodes the glucose transporter protein-1. Autosomal recessive inheritance is extremely rare. Similarly, only very few reports are found in the literature of hematological manifestations in this syndrome. We report an autosomal recessively inherited GLUT-1DS, due to a de novo mutation, with the classical infantile presentation associated with concomitant acanthocytosis. In this case report, the second child born to consanguineous parents with initial refractory neonatal seizures and subsequent poorly controlled epilepsy and developmental regression is discussed. The most notable investigation findings supportive of his underlying diagnosis were very low cerebrospinal fluid (CSF) glucose and CSF lactate levels. His CSF:plasma glucose ratio was 1:7.6. He was anemic with a hemoglobin of 8.8 g/dL with his blood film showing marked acanthocytosis. His elder brother who also had refractory epilepsy and developmental regression had similar hypoglycorrhachia, low CSF:plasma glucose ratio, and mild anemia with acanthocytosis, and he died before establishment of a diagnosis. Our patient was diagnosed to have a novel mutation SLC2A1 c.184A &gt; G p.(Thr62Ala), for which both parents were heterozygous, confirming autosomal recessive inheritance. Commencement of a ketogenic diet resulted in improvement of his seizures and slow gain in development. It also resulted in gradual disappearance of acanthocytes from his peripheral blood. This case describes a rare case of classical GLUT-1DS, autosomal recessively inherited, due to a novel mutation. The acanthocytosis in his blood smear is another rare association minimally reported in GLUT-1DS. The cause of his abnormal red blood cell morphology is unclear. It is possibly related to cation leakage reported in some rare mutations of the SLC2A1 gene needs reference.

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that belongs to the serine protease inhibitor (serpin) family. An increase in PEDF activity has been shown to be a potent inhibitor of tumour progression and proliferation, suggesting a possible therapeutic target. There is still a great deal to learn about how PEDF controls metabolic pathways in breast cancer and its metastatic form. Given this, the primary purpose of this study was to use a metabolomics approach to gain a better understanding of the mechanisms driving the reprogramming of metabolic events involved in breast cancer pertaining to PEDF under various glycaemic loads. We employed gas chromatography-quadrupole mass spectrometry (GC-Q-MS) to investigate metabolic changes in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 treated with PEDF under glycaemic loading. Multivariate and univariate analyses were carried out as indicative tools via MetaboAnalyst (V.5.0) and R packages to identify the significantly altered metabolites in the MDA-MB-231 cell line after PEDF exposure under glycaemic loading. A total of 61 metabolites were found, of which nine were selected to be distinctively expressed in MDA-MB-231 cells under glycaemic conditions and exhibited differential responses to PEDF (p < 0.05, VIP > 1). Abnormalities in amino acid metabolism pathways were observed. In particular, glutamic acid, glutamine, and phenylalanine showed different levels of expression across different treatment groups. The lactate and glucose-6-phosphate production significantly increased in high-glucose vs. normal conditions while it decreased when the cells were exposed to PEDF, confirming the positive influence on the Warburg effect. The TCA cycle intermediates, including malate and citric acid, showed different patterns of expression. This is an important finding in understanding the link of PEDF with metabolic perturbation in TNBC cells in response to glycaemic conditions. Our findings suggest that PEDF significantly influenced the Warburg effect (as evidenced by the significantly lower levels of lactate), one of the well-known metabolic reprogramming pathways in cancer cells that may be responsive to metabolic-targeted therapeutic strategies. Moreover, our results demonstrated that GC-MS-based metabolomics is an effective tool for identifying metabolic changes in breast cancer cells after glycaemic stress or in response to PEDF treatment.

Abstract 14039: The Cardioprotective and Anti-Inflammatory Effect of Inhaled Nitric Oxide During Fontan Surgery: A Prospective Randomized Study

Introduction: Open heart surgery that requires cardiopulmonary by-pass (CPB) evokes tremendous stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although part of this reaction triggers protective and anti-inflammatory phenomena, it is harmful, particularly in patients with single ventricle congenital heart defects during Fontan surgery. Unfortunately, there is no perfect anti-inflammatory and stress defence strategy despite decades of research. Hypothesis: This study aimed to investigate the influence of nitric oxide (NO) inhaled directly into the oxygenator during CPB on a proteome profile of inflammatory cytokines, metabolic response markers, heart and lung protection indicators, and the early clinical outcomes. Methods: The study involved 115 patients randomized to the Fontan-NO group, receiving NO inhalation (n=48) and the Fontan group, not receiving NO (n=49). Eighteen patients were excluded from the study. The clinical data were prospectively analyzed. Proteome profiler essays were used for repeated measurements of investigated analytes. Results: Fontan-NO patients had significantly lower levels of lactate (p=0.04) and glucose (p=0.02), lower pulmonary artery pressure (p=0.03) and catecholamine index (p=0.042), shorter ventilatory support time (p=0.03) and ICU stay (p=0.04). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, tissue inhibitor of metalloproteinase, prolactin, and angiopoietin and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, granulocyte-macrophage colony-stimulating factor, pentraxin, matrix metalloproteinase-8, troponin-I, CK-MB, and insulin in Fontan-NO group. Multiple regression analysis revealed the influence of Il-6 and Il-8 on respiratory support time and ICU stay and the relationship between catecholamine index, duration of effusions, and indicators of myocardial damage. Conclusions: NO inhaled into the oxygenator during CPB can alleviate the inflammatory response, improve myocardial and lung protection, and reduce metabolic stress in patients with a single ventricle undergoing Fontan surgery. The observed effects can influence short-term clinical outcomes.

Temporary Right Ventricular Assist Device Support for Acute Right Heart Failure: A Single-Center Experience

IntroductionSevere right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs. MethodsWe conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan–Meier method and multivariable Cox proportional hazards regression models. ResultsFrom 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P < 0.01) and the lactic acidosis was less (P < 0.01). ConclusionsIn conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

Comparison of the predictive ability of lactate and central venous blood gas in pediatric venoarterial mode extracorporeal membrane oxygenation outcome.

This study aims to compare lactate and central venous blood gas in the prediction of outcome in pediatric venoarterial mode extracorporeal membrane oxygenation (V-A ECMO). This was a retrospective observational study conducted on patients undergoing V-A ECMO care in the pediatric intensive care unit of a tertiary medical center in Taiwan. Patients under 18 years of age undergoing V-A ECMO from January 2009 to April 2019 were included in this study. This study consisted of 47 children who received V-A ECMO with an overall weaning rate of 66.0%. The mean age was 5.5 years and mean ECMO duration was 11.6 days. Successful weaning group had significantly lower lactate levels at initial (58.7±47.0 mg/dL vs. 108.0±55.3 mg/dL, p = 0.003), 0-12 h (37.8±29.0 mg/dL vs. 83.5±60.0 mg/dL, p Z 0.001), and 12-24 h (29.4±26.9 mg/dL vs. 69.1±59.1 mg/dL, p = 0.003) after ECMO initiation; however, the central venous blood gas including pH, HCO3, CO2, base excess (BE), and O2 saturation showed no significant difference. The favorable outcome group had significantly lower lactate levels at 0-12 h (32.8±26.3 mg/dL vs. 71.3±53.3 mg/dL, p = 0.005), and 12-24h (20.7±10.2 mg/dL vs. 61.9±53.5 mg/dL, p = 0.002); however, the HCO3 levels (26.2±4.5 mmol/L vs. 22.9±6.8 mmol/L, p = 0.042) and BE (2.2±5.4 vs. 2.2±8.5, p = 0.047) were significantly higher at 12-24 h. In multivariate logistic regression, 12-24 h lactate value was an independent factor for unfavorable outcomes (p = 0.015, odds ratio [OR] = 1.1) with the best cut-off value of 48.6 mg/dL (sensitivity 48%, specificity 100%). Lactate has better outcome prediction than central venous blood gas in pediatric V-A ECMO. The lactate value 12-24 h after ECMO initiation was an independent factor for unfavorable outcomes.

Experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: intraoperative indicators

Background/Aim: Intraoperative extracorporeal membrane oxygenation (ECMO) is being used with increasing frequency in lung transplantation. However, the factors associated with the use of intraoperative ECMO in lung transplant patients are not yet conclusive. In this study, we aimed to determine the effective factors for providing intraoperative ECMO support in patients undergoing lung transplantation. In addition, we aimed to evaluate the effect of ECMO support on morbidity and mortality. Methods: In this retrospective cohort study evaluating lung transplant patients, patients were divided into two groups: those who received intraoperative ECMO support and those who did not. Demographic data, the lung allocation score (LAS) and pulmonary arterial pressure (PAP), intraoperative data, postoperative complications, duration of mechanical ventilation (MV), length of stay (LOS) in intensive care and hospital, and mortality rates were recorded for both groups. Factors affecting entry to ECMO were analyzed by Multivariate Logistic Regression. Results: In this period, 51.9% of 87 patients who underwent lung transplantation required intraoperative ECMO. The mean age, LAS, and PAP of the ECMO group were significantly higher than the non-ECMO group (P = 0.043, P = 0.007, and P = 0.007, respectively). In multivariate analysis, it was found that lower MAP averages were a predictive parameter in intraoperative ECMO requirements (OR: 1.091; CI: 1.009-1.179; P = 0.028). The ECMO group’s mechanical ventilation time and hospital mortality were significantly higher than the other group (P = 0.004 and P = 0.025, respectively). Conclusion: Preoperative indicators of intraoperative ECMO support were determined as age, LAS, and PAP elevation. In addition, low MAP levels and high lactate levels were always determined as intraoperative indicators in lung transplantation until the transition to ECMO support.

The predictors of mortality in patients with methyl alcohol intoxication

Aim: Methanol intoxication is a worldwide public health problem. Mortality rates are quite high unless there is early intervention and diagnosis. The aim of this study was to investigate the predictors of mortality in patients with methyl alcohol intoxication. Material and Method: The study included 18 patients admitted to emergency department of our hospital in 2019-2020, who were diagnosed with methanol intoxication. Laboratory parameters and basic features of the patients were recorded. According to the criteria of 2012 Clinical Practice Guideline for Acute Kidney Injury (AKI), patients were diagnosed with AKI. Results: The mean age of the patients was 45.7±15.21 years and 72.2% of those were male. The mortality and AKI rate were 38.9% and 44.4%, respectively. In regression analyses, delay in admission to hospital, low Glasgow coma scale score, AKI development and high lactate level were independent predictors of mortality. According to ROC analyses when lactate level was more than 5.75 mmol/L, mortality rate increased more rapidly. Conclusion: Mortality rate is very high in methanol intoxication. Patients with AKI and high lactate levels should be intervened faster.

A quick Sequential Organ Failure Assessment-negative result at triage is associated with low compliance with sepsis bundles: a retrospective analysis of a multicenter prospective registry.

ObjectiveWe investigated the effects of a quick Sequential Organ Failure Assessment (qSOFA)–negative result (qSOFA score <2 points) at triage on the compliance with sepsis bundles among patients with sepsis who presented to the emergency department (ED).MethodsProspective sepsis registry data from 11 urban tertiary hospital EDs between October 2015 and April 2018 were retrospectively reviewed. Patients who met the Third International Consensus Definitions for Sepsis and Septic Shock criteria were included. Primary exposure was defined as a qSOFA score ≥2 points at ED triage. The primary outcome was defined as 3-hour bundle compliance, including lactate measurement, blood culture, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration. Multivariate logistic regression analysis to predict 3-hour bundle compliance was performed.ResultsAmong the 2,250 patients enrolled in the registry, 2,087 fulfilled the sepsis criteria. Only 31.4% (656/2,087) of the sepsis patients had qSOFA scores ≥2 points at triage. Patients with qSOFA scores <2 points had lower lactate levels, lower SOFA scores, and a lower 28-day mortality rate. Rates of compliance with lactate measurement (adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.29–0.75), antibiotics administration (aOR, 0.64; 95% CI, 0.52–0.78), and 30 mL/kg crystalloid administration (aOR, 0.62; 95% CI, 0.49–0.77) within 3 hours from triage were significantly lower in patients with qSOFA scores <2 points. However, the rate of compliance with blood culture within 3 hours from triage (aOR, 1.66; 95% CI, 1.33–2.08) was higher in patients with qSOFA scores <2 points.ConclusionA qSOFA-negative result at ED triage is associated with low compliance with lactate measurement, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration within 3 hours in sepsis patients.

P-225 Positive effects of low-lactate culture medium on embryo development and blastocyst ploidy status: a 3.5-year multi-clinic retrospective review

Abstract Study question Can lower concentrations of lactate in culture medium have a positive effect on day 5 and day 6 blastocyst ploidy determined by PGT-A? Summary answer Embryos cultured to the blastocyst stage in medium containing 1mM concentration of lactate vs. 6mM or 10mM are significantly more likely to be euploid. What is known already Extended culture to the blastocyst stage is required for PGT-A analysis following trophectoderm biopsy. Although there are many published studies which debate the use of a single-step culture media vs. sequential culture media, very few studies address the importance of culture conditions and media component concentrations as it relates to ploidy of the resulting embryo. Previous media validation studies do support the benefits of lower lactate levels in culture media with an increase in the total number of usable blastocysts, particularly in older patients. Study design, size, duration A multi-lab retrospective review with the first lab using high lactate (6mM) continuous culture system (January 2016 through December 2017) compared to a low lactate continuous culture system, January 2018 through July 2021, (&amp;gt;13,000 embryos). In another lab, a retrospective review was undertaken to compare their sequential culture system in a high lactate concentration (10mM) (January 2016 through October 2017) with a low lactate continuous culture system from October 2017 through July 2021 (&amp;gt;12,000 embryos). Participants/materials, setting, methods The entire patient population in the timeframes reviewed were included with no allowances given to demographics in two separate private IVF clinics in different regions of the country. Analysis included the ploidy status of the embryos as well as the usable blastocyst rate. Ploidy status was determined by trophectoderm biopsy/PGT-A analysis on Day 5 and 6. Usable blastocysts were determined by any blastocyst that was of a quality to be transferred or vitrified. Main results and the role of chance Our data indicates that the lower level of lactate concentration in Continuous Single Culture Medium-NX (1mM) supports a significant increase in euploidy in day 5 and day 6 blastocysts compared to higher lactate concentrations, both 6mM (Continuous Single Culture Medium) and 10mM (Sequential G1/G2). The euploid rate of day 5 blastocysts cultured in 1mM vs. 6mM lactate was 58.4% compared to 52.1% (p &amp;lt; 0.001) and 51.0% vs. 41.4% (p &amp;lt; 0.001) for day 6 blastocysts. The percentage of day 5 euploid blastocysts in 1mM vs. 10mM was 54.3% vs. 50.0% (p &amp;lt; 0.05) and 41.3% vs. 39.4% (not significant) respectively for day 6 blastocysts. The euploidy rate in 1mM vs 10mM lactate concentration, as a function of the blastocyst utilization rate, results in a 3.3% increase in total normal blastocysts (p &amp;lt; 0.001) on day 5 and a 1.4% increase of the same on day 6 (p &amp;lt; 0.05). Interestingly, when the total number of chromosomally normal blastocysts is similarly compared in 1mM vs 6mM, there is only a 0.8% increase in the 6mM group vs the 1mM group (p &amp;lt; 0.05); However, on day 6, 1mM results in an increase of 1.3% over 6mM (p &amp;lt; 0.01). Limitations, reasons for caution As patient age is the strongest predictor for blastocyst development and embryonic aneuploidy, additional analysis is being conducted to stratify the data by maternal age in order to identify if low-lactate culture media provides a more suitable metabolic environment for specific age groups. Wider implications of the findings Although the specific mechanism involved in the alteration of the cytogenetic composition of embryos cultured in higher lactate medium are unknown at this time, these findings support the importance and need to further investigate the epigenetic effects of culture media components and concentrations on the developing embryo. Trial registration number not applicable

Acute Cardiovascular and Metabolic Effects of Different Warm-Up Protocols on Dynamic Apnea.

The aim of this study was to evaluate the acute physiological response to different warm-up protocols on the dynamic apnea performance. The traditional approach, including a series of short-mid dives in water (WET warm-up), was compared to a more recent strategy, consisting in exercises performed outside the water (DRY warm-up). Nine athletes were tested in two different sessions, in which the only difference was the warm-up executed before 75m of dynamic apnea. Heart rate variability, baroreflex sensitivity, hemoglobin, blood lactate and the rate of perceived exertion were recorded and analyzed. With respect to WET condition, DRY showed lower lactate level before the dive (1.93 vs. 2.60 mmol/L, p = 0.006), higher autonomic indices and lower heart rate during the subsequent dynamic apnea. A significant correlation between lactate produced during WET with the duration of the subsequent dynamic apnea, suggests that higher lactate levels could affect the dive performance (72 vs. 70 sec, p = 0.028). The hemoglobin concentration and the rate of perceived exertion did not show significant differences between conditions. The present findings partially support the claims of freediving athletes who adopt the DRY warm-up, since it induces a more pronounced diving response, avoiding higher lactate levels and reducing the dive time of a dynamic apnea.

Levosimendan's effect on venoarterial extracorporeal membrane oxygenation weaning.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides temporary haemodynamic support in refractory cardiogenic shock. Recent retrospective studies on levosimendan on V-A ECMO weaning had conflicting results. This study aimed to determine the association between levosimendan on V-A ECMO weaning success in a tertiary centre in Hong Kong. This retrospective study was conducted in an intensive care unit in Hong Kong. All adult patients requiring V-A ECMO from January 2016 to September 2020 were included. Patients who were given levosimendan were compared to patients who were not, on rates of successful V-A ECMO weaning. The groups were also compared after propensity matching based on covariates closely associated with the use of levosimendan. A total of 119 patients were included in the study, with 38 in the levosimendan group and 81 in the non-levosimendan group. Patients treated with levosimendan trended towards improved weaning success, but the difference was not statistically significant (63% vs 53%, p = 0.404). In the propensity-matched groups, there was no difference in weaning success (odds ratio 1.00, 95% CI 0.23-8.00). The levosimendan group was associated with lower vasopressor requirement, lower lactate levels, and more significant drop in lactate in the first 2 days of V-A ECMO. The levosimendan group had longer ECMO duration. There was no difference in other secondary outcomes including mortality, length of stay in ICU and hospital and duration of mechanical ventilation. There was no difference in the rate of ventricular arrhythmias. Levosimendan did not improve V-A ECMO weaning success in our cohort with refractory cardiogenic shock.

Goal-Directed Fluid Therapy Enhances Gastrointestinal Recovery after Laparoscopic Surgery: A Systematic Review and Meta-Analysis.

(1) Background: Whether goal-directed fluid therapy (GDFT) provides any outcome benefit as compared to non-goal-directed fluid therapy (N-GDFT) in elective abdominal laparoscopic surgery has not been determined yet. (2) Methods: A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Web of Science, and Scopus. The main outcomes were length of hospital stay (LOHS), time to first flatus and stool, intraoperative fluid and vasopressor requirements, serum lactate levels, and urinary output. Pooled risks ratios (RRs) with 95% confidence intervals (CI) were calculated for dichotomous outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. (3) Results: Eleven studies were included in the quantitative, and fifteen in the qualitative synthesis. LOHS (WMD: −1.18 days, 95% CI: −1.84 to −0.53) and time to first stool (WMD: −9.8 h; CI −12.7 to −7.0) were significantly shorter in the GDFT group. GDFT resulted in significantly less intraoperative fluid administration (WMD: −441 mL, 95% CI: −790 to −92) and lower lactate levels at the end of the operation: WMD: −0.25 mmol L−1; 95% CI: −0.36 to −0.14. (4) Conclusions: GDFT resulted in enhanced recovery of the gastrointestinal function and shorter LOHS as compared to N-GDFT.

The mesoionic compound MI-D changes energy metabolism and induces apoptosis in T98G glioma cells

The mesoionic compound 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride (MI-D) impairs mitochondrial oxidative phosphorylation and has a significant antitumour effect against hepatocarcinoma and melanoma. This study evaluated the cytotoxic effect of MI-D on T98G glioblastoma cells and investigated whether the impairment of oxidative phosphorylation promoted by MI-D is relevant to its cytotoxic effect. The effects of MI-D on T98G cells cultured in high glucose Dulbecco's modified Eagle's medium (DMEM) HG (glycolysis-dependent) and galactose plus glutamine-supplemented Dulbecco's modified Eagle's medium (DMEM) GAL (oxidative phosphorylation-dependent) were compared. T98G cells grown in DMEM GAL medium exhibited higher respiration rates and citrate synthase activity and lower lactate levels, confirming the metabolic shift to oxidative phosphorylation in these cells. MI-D significantly decreased the cell viability in a dose-dependent manner in both media; however, T98G cells cultured in DMEM GAL medium were more susceptible. The mesoionic significantly inhibited mitochondrial oxidative phosphorylation of glioma cells in both media. At the same time, lactate levels were not altered, indicating an absence of compensatory glycolysis activation. Additionally, MI-D increased the citrate synthase activity of cells in both media, which in DMEM HG-cultivated cells was followed by citrate accumulation. Apoptosis dependent on caspase-3 mediated the toxicity of MI-D on T98G cells. The higher susceptibility of glioma cells cultured in DMEM GAL medium to MI-D indicates that the impairment of mitochondrial functions is involved in mesoionic cytotoxicity. The results of this study indicate the potential use of MI-D for glioblastoma treatment.

Prognostic value of lactate in out-of-hospital cardiac arrest: a prospective cohort study

Background: The prognostic role of lactate in out-of-hospital cardiac arrest (OHCA) remains unclear. Aims: To explore serum lactate as a predictor of return of spontaneous circulation in patients experiencing OHCA after arrival at hospital. Methods: This 13-month prospective observational cohort study involved patients aged ≥18 years. Serum lactate levels were measured during cardiopulmonary resuscitation before ROSC. Patients were divided into two groups by lactate level: Group 1, low (≤9.9 mmol/l) and Group 2, high (≥10 mmol/l). Findings: 105 patients were included, 50 in group 1 and 55 group 2. Median lactate were 7.4 mmol/l and 14.2 mmol/l respectively. More patients in group 1 were found with ventricular fibrillation (40% versus 14.5%; P≤0.01), obtained ROSC more quickly (37 minutes 38 seconds versus 39 minutes 13 seconds; P=0.79) and achieved short-term survival (survived &gt;24 hours) (40% versus 23.5%; P=0.32), versus group 2; prediction of survival did not reach statistical significance. Conclusion: Lower lactate levels in OHCA appear to be associated with better short-term outcomes but the cut-off points regarding survival remain unclear.

Dynamic and Static Cardiac Function Measurements During Sepsis.

Dynamic and Static Cardiac Function Measurements During Sepsis.

Effect of lidocaine infusion compared to dexmedetomidine infusion on proinflammatory cytokines and stress response in pelvi–abdominal cancer surgeries: a randomized clinical trial

Background &amp; Objectives: Stress response to extensive surgeries in cancer patients results in an imbalance between the pro-inflammatory and anti-inflammatory cytokines, besides activating an inflammatory cascade. We investigated the comparative effects of intravenous infusion of dexmedetomidine and lidocaine on proinflammatory cytokines and the stress reaction.&#x0D; Methodology: A prospective randomized double blind trial was performed in National Cancer Institute. 54 patients scheduled for pelvi–abdominal cancer surgery under general anesthesia were randomly allocated to three equal groups. Lidocaine group: patients received 1.5 mg/kg loading dose of lidocaine followed by 1.5 mg/kg/h infusion; Dexmedetomidine group: received a loading dose of dexmedetomidine 1 µg/kg followed by infusion of 0.5 µg/kg/h; or Saline group: received 50 ml of normal saline followed by infusion at a rate of 10 ml/h till the end of the surgery. The primary outcome was a postoperative target level of IL–6 after 24 h.&#x0D; Results: Immediate and 24 h postoperative IL–6 and TNFα were significantly lower in both dexmedetomidine and lidocaine groups compared to the control group (P &lt; 0.001). Dexmedetomidine group had a significantly lower IL–6 and TNFα levels compared to lidocaine group at immediate postoperative and 24 h postoperative period (P &lt; 0.001). Dexmedetomidine and lidocaine groups had a significantly lower lactate and insulin levels compared to the control group immediately postoperatively as well as 24 h postoperatively (P &lt; 0.001). The dexmedetomidine group had a significantly lower lactate levels compared to the lidocaine group immediately postoperatively only. The lidocaine group had lower insulin level than the control group regarding immediate postoperative period only.&#x0D; Conclusion: Intraoperative infusion of dexmedetomidine or lidocaine, both attenuate the postoperative levels of proinflammatory cytokines and stress response in patients undergoing pelvi–abdominal cancer surgeries.&#x0D; Clinical trial registration: The study was registered at clinicaltrials.gov (NCT 04148599).&#x0D; Key words: Lidocaine; Dexmedetomidine; Interleukins; Tumor necrosis factor-α; Stress response; Pelvi–abdominal cancer; Surgery&#x0D; Abbreviations: TNF - Tumor necrosis factor; IL – Interleukins;&#x0D; Citation: Hassan MM, Saleh RG, Abdalla NO, Radwan NH, Abdelghfar EM. Effect of lidocaine infusion compared to dexmedetomidine infusion on proinflammatory cytokines and stress response in pelvi–abdominal cancer surgeries: a randomized clinical trial. Anaesth. pain intensive care 2021;26 (1):44-52.&#x0D; DOI: 10.35975/apic.v26i1.1765&#x0D; Received: February 15, 2021, Reviewed: December 02, 2021, Accepted: December 05, 2021

Comparative Analysis of Patient Characteristics in Cardiogenic Shock Studies

This study sought to evaluate the differences in cardiogenic shock patient characteristics in trial patients and real-life patients.Cardiogenic shock (CS) is a leading cause of mortality in patients presenting with acute myocardial infarction (AMI). However, the enrollment of patients into clinical trials is challenging and may not be representative of real-world patients.We performed a systematic review of studies in patients presenting with AMI-related CS and compared patient characteristics of those enrolled into randomized controlled trials (RCTs) with those in registries.We included 14 RCTs (n = 2,154) and 12 registries (n = 133,617). RCTs included more men (73% vs 67.7%, P < 0.001) compared with registries. Patients enrolled in RCTs had fewer comorbidities, including less hypertension (61.6% vs 65.9%, P < 0.001), dyslipidemia (36.4% vs 53.6%, P < 0.001), a history of stroke or transient ischemic attack (7.1% vs 10.7%, P < 0.001), and prior coronary artery bypass graft surgery (5.4% vs 7.5%, P < 0.001). Patients enrolled in RCTs also had lower lactate levels (4.7 ± 2.3 mmol/L vs 5.9 ± 1.9 mmol/L, P < 0.001) and higher mean arterial pressure (73.0 ± 8.8 mm Hg vs 62.5 ± 12.2 mm Hg, P < 0.001). Percutaneous coronary intervention (97.5% vs 58.4%, P < 0.001) and extracorporeal membrane oxygenation (11.6% vs 3.4%, P < 0.001) were used more often in RCTs. The in-hospital mortality (23.9% vs 38.4%, P < 0.001) and 30-day mortality (39.9% vs 45.9%, P < 0.001) were lower in RCT patients.RCTs in AMI-related CS tend to enroll fewer women and lower-risk patients compared with registries. Patients enrolled in RCTs are more likely to receive aggressive treatment with percutaneous coronary intervention and extracorporeal membrane oxygenation and have lower in-hospital and 30-day mortality.

Predialysis serum lactate levels could predict dialysis withdrawal in Type 1 cardiorenal syndrome patients.

SummaryBackgroundRenal replacement therapy (RRT) is an effective rescue therapy for Type 1 cardiorenal syndrome (CRS). Previous studies have demonstrated that type 1 CRS patients with severe renal dysfunction were susceptible to sepsis, and that serum lactate has been correlated with the risk of mortality in patients with sepsis. However, the association between serum lactate level and the prognosis of type 1 CRS patients requiring RRT is unknown.MethodsAn inception cohort of 500 type 1 CRS patients who received RRT in a tertiary-care referral hospital in Taiwan from August 2011 to January 2018 were enrolled. The outcomes of interest were dialysis withdrawal and 90-day mortality. The results were further externally validated using sampling data of type 1 CRS patients requiring dialysis from multiple tertiary-care centers.FindingsThe 90-day mortality rate was 52.8% and the incidence rate of dialysis withdrawal was 34.8%. Lower pre-dialysis lactate was correlated with a higher rate of dialysis withdrawal and lower rate of mortality. Generalized additive model showed that 4.2 mmol/L was an adequate cut-off value of lactate to predict mortality. Taking mortality as a competing risk, Fine-Gray subdistribution hazard analysis further indicated that a low lactate level (≦ 4.2 mmol/L) was an independent predictor for the possibility of dialysis withdrawal, as also shown in external validation. The interaction of quick Sequential Organ Failure Assessment score and lactate was associated with dialysis dependence in a disease severity-dependent manner. Furthermore, the associations between hyperlactatemia and dialysis dependence were consistent in the patients with and without sepsis.InterpretationSerum lactate level is accurate and capable of forecasting the prognosis along with qSOFA severity for clinical decision-making for treating type 1 CRS patients. Further studies are needed to validate our results.FundingThis study was supported by grants from Taiwan National Science Council [104–2314-B-002–125-MY3,106–2314-B-002–166-MY3,107–2314-B-002–026-MY3], National Taiwan University Hospital [106-FTN20,106-P02,UN106–014,106-S3582,107-S3809,107-T02,PC1246,VN109–09,109-S4634,UN109–041], Ministry of Science and Technology of the Republic of China [MOST106–2321-B-182–002,106-2314-B-182A-064,MOST107–2321-B-182–004,MOST107-2314-B-182A-138, MOST108–2321-B-182–003,MOST109–2321-B-182–001, MOST108-2314-B-182A-027], Chang Gung Memorial Hospital [CMRPG-2G0361,CMRPG-2H0161,CMRPG-2J0261, CMRPG-2K0091], and Ministry of Health and Welfare of the Republic of China [PMRPG-2L0011].

Comparison of β-endorphin, Lactate and Cortisol Concentrations in Winning and Losing Racehorses

Understanding the physiological and biochemical changes in racehorses can be invaluable. Accurate information in this area could result in better understanding of needs of sport horses. The aim of this study was to prove the hypothesis that biochemical changes could influence the outcome of competitions. In this study, β-endorphin was evaluated as an indicator of analgesia, lactate as an indicator of fatigue and cortisol as an indicator of stress in the first two horses and the last ones that cross the finish line. This study was performed on 44 horses participating in the 1000-meter national championship. In Group 1, 22 winners and second place horses were included; for Group 2, 22 last and penultimate horses were included. Blood samples were obtained in the doping room after race (T0) and 20 minutes after finishing (T20). Results for beta endorphin at T0 and T20 were higher (P > 0.05) for Group 1 compared to Group 2; on the contrary, lactate concentration was lower (P > 0.05) for Group 1 than Group 2 at T0 and T20. However, differences (P < 0.05) were obtained within groups at T0 and T20 for beta endorphin and lactate concentrations. No significant differences were found for cortisol concentration.The results of this study showed that winning horses had higher levels of β-endorphin and lower levels of lactate than losers. Further and deeper experimental studies are needed to prove the hypothesis that biochemical changes could influence the outcome of competitions.