Elevated Lactate Levels Research Articles

Hyperlactataemia and acid–base disturbances in normotensive patients with acute heart failure

Acute heart failure (AHF) may be associated with low-tissue perfusion and/or hypoxaemia leading to increased lactate levels and acid-base perturbations. Few data are available on the clinical significance of elevated lactate levels and primary acid-base disorders in the setting of AHF. Arterial blood gas was obtained at admission in 4012 normotensive (systolic blood pressure ≥ 90 mmHg) patients with AHF. The association between lactate levels and acid-base status and in-hospital mortality was determined using multivariable logistic regression. Hyperlactataemia (>2 mmol/L) was present in 38.0% of patients and was strongly associated with markers of sympathetic activation, such as hyperglycaemia. Hyperlactataemia was present in 31.0%, 43.7%, and 42.0% of patients with normal pH, acidosis, and alkalosis, respectively. In-hospital mortality occurred in 16.4% and 11.1% of patients with and without hyperlactataemia [adjusted odds ratio (OR) 1.49; 95% confidence interval (CI) 1.22-1.82, P < 0.0001]. Compared with normal pH, the OR for in-hospital mortality was 2.48 (95% CI 1.95-3.16, P < 0.0001) in patients with acidosis and 1.77 (95% CI 1.32-2.26, P < 0.0001) in patients with alkalosis. The risk for in-hospital mortality was high with acidosis (18.1%) or alkalosis (10.4%) even with normal lactate. The most common primary acid-base disturbances included metabolic acidosis, respiratory acidosis, and metabolic alkalosis with respiratory acidosis having the highest risk for in-hospital mortality. Hyperlactataemia was common in patients without hypotension and was associated with increased risk for in-hospital mortality. Hyperlactataemia is not associated with any specific acid-base disorder. Acute heart failure patients also present with diverse acid-base disorders portending increased in-hospital mortality.

Rev1 deficiency induces replication stress to cause metabolic dysfunction differently in males and females.

DNA damage responses compete for cellular resources with metabolic pathways, but little is known about the metabolic consequences of impaired DNA replication, a process called replication stress. Here we characterized the metabolic consequences of DNA replication stress at endogenous DNA lesions by using mice with a disruption of Rev1, a translesion DNA polymerase specialized in the mutagenic replication of damaged DNA. Male and female Rev1 knockout (KO) mice were compared with wild-type (WT) mice and followed over time to study the natural course of body weight gain and glucose tolerance. Follow-up measurements were performed in female mice for in-depth metabolic characterization. Body weight and fat mass were only increased in female KO mice versus WT mice, whereas glucose intolerance and a reduction in lean mass were observed in both sexes. Female KO mice showed reduced locomotor activity while male KO mice showed increased activity as compared with their WT littermates. Further characterization of female mice revealed that lipid handling was unaffected by Rev1 deletion. An increased respiratory exchange ratio, combined with elevated plasma lactate levels and increased hepatic gluconeogenesis indicated problems with aerobic oxidation and increased reliance on anaerobic glycolysis. Supplementation with the NAD+ precursor nicotinamide riboside to stimulate aerobic respiration failed to restore the metabolic phenotype. In conclusion, replication stress at endogenous DNA lesions induces a complex metabolic phenotype, most likely initiated by muscular metabolic dysfunction and increased dependence on anaerobic glycolysis. Nicotinamide riboside supplementation after the onset of the metabolic impairment did not rescue this phenotype.NEW & NOTEWORTHY An increasing number of DNA lesions interferes with cellular replication leading to metabolic inflexibility. We utilized Rev1 knockout mice as a model for replication stress, and show a sex-dependent metabolic phenotype, with a pronounced reduction of lean mass and glucose tolerance. These data indicate that in obesity, we may end up in an infinite loop where metabolic disturbance promotes the formation of DNA lesions, which in turn interferes with cellular replication causing further metabolic disturbances.

Antiplatelet Therapy in Acute Myocardial Infarction and Cardiogenic Shock: Insights From the National Cardiogenic Shock Initiative.

Patients presenting with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) are at high risk for impaired antiplatelet activity secondary to malabsorption, systemic hypoperfusion, hypothermia, need for mechanical ventilation, and high use of analgesics. The use of antiplatelet therapy in these high-risk patients is not well studied. Using the National Cardiogenic Shock Initiative database, we analyzed patients who presented with AMI-CS at 60 hospitals from March 2018 to December 2020. All patients were treated using a standard shock protocol. Herein, the patterns of antiplatelet use are described. A total of 204 patients were included in the analysis, of which 174 (85.3%) presented with ST-segment elevation myocardial infarction (STEMI). The majority (84.3%) received antiplatelet therapy before percutaneous coronary intervention (PCI); of those who received antiplatelets, 77.9% received aspirin, 55.2% received an oral P2Y12 inhibitor, and 19.2% received intravenous (IV) antiplatelet therapy. Ticagrelor was the most common P2Y12 inhibitor administered (41.9%), followed by clopidogrel (12.2%) and prasugrel (1.2%). Only 18.6% of oral antiplatelet agents were crushed. Baseline characteristics of patients who received IV vs non-IV antiplatelet agents were similar. Thrombolysis in Myocardial Infarction (TIMI) 0 flow was present in 69.6% of patients before PCI and aspiration thrombectomy was performed in 24.5% of patients. The presence of STEMI, cardiac arrest, cardiopulmonary resuscitation, hypothermia, vasopressor use, elevated lactate levels, or number of vessels treated did not influence the use of IV antiplatelet agents. The use of crushed and IV antiplatelet agents in AMI-CS is low. Further studies are needed in this high-risk population to assess whether more potent antiplatelet inhibition will improve outcomes.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis

PurposeThe question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors.Methods297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted.ResultsPatients had a median age of 56 (IQR 44–65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1–32.4%). Low platelet count (HR 0.997, 95% CI 0.996–0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012–1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081–3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044–2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO.ConclusionThe overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

Lactate and Lactate-to-Pyruvate Ratio in Critically Ill COVID-19 Patients: A Pilot Study.

A limited number of coronavirus disease-19 (COVID-19) cases may require treatment in an intensive care unit (ICU). Arterial blood lactate levels are routinely measured in the ICU to estimate disease severity, predict poor outcomes, and monitor therapeutic handlings. A number of studies have suggested that, simultaneously with lactate, pyruvate should also be measured, providing augmented prognostic ability, and a better understanding of the underlying metabolic alterations in ICU patients. Hence, the aim of the present study was to elucidate the relationship between lactate levels and the lactate-to-pyruvate (LP) ratio with the clinical outcome in mechanically ventilated COVID-19 patients. Lactate and pyruvate were serially measured during the first 24 h of ICU stay. A group of ICU non-COVID-19 patients was used as a comparison group. The majority of COVID-19 patients (82.5%) had normal lactate levels and a normal LP ratio on ICU admission (normal metabolic pattern). A small, yet significant, percentage of patients had either elevated lactate levels or a high LP ratio (abnormal metabolic pattern); these patients exhibited a significantly higher risk of ICU mortality compared to the patients with a normal metabolic pattern (72.7% vs. 34.6%, p = 0.04). In our critically ill COVID-19 patients, elevated lactate levels or high LP ratios on admission to the ICU could be associated with poor clinical outcome.

PID controls: the forgotten bioprocess parameters

The ambr250 high-throughput bioreactor platform was adopted to provide a highly-controlled environment for a project investigating genome instability in Chinese hamster ovary (CHO) cells, where genome instability leads to lower protein productivity. Development of the baseline (control) and stressed process conditions highlighted the need to control critical process parameters, including the proportional, integral, and derivative (PID) control loops. Process parameters that are often considered scale-independent, include dissolved oxygen (DO) and pH; however, these parameters were observed to be sensitive to PID settings. For many bioreactors, control loops are cascaded such that the manipulated variables are adjusted concurrently. Conversely, for the ambr250 bioreactor system, the control levels are segmented and implemented sequentially. Consequently, each control level must be tuned independently, as the PID settings are independent by control level. For the CHO cell studies, it was observed that initial PID settings did not resulted in a robust process, which was observed as elevated lactate levels; which was caused by the pH being above the setpoint most of the experiment. After several PID tuning iterations, new PID settings were found that could respond appropriately to routine feed and antifoam additions. Furthermore, these new PID settings resulted in more robust cell growth and increased protein productivity. This work highlights the need to describe PID gains and manipulated variable ranges, as profoundly different outcomes can result from the same feeding protocol. Additionally, improved process models are needed to allow process simulations and tuning. Thus, these tuning experiments support the idea that PID settings should be fully described in bioreactor publications to allow for better reproducibility of results.

Clinical observations of Leber hereditary optic neuropathy with and without neurological symptoms

Three case studies of adults with Leber hereditary optic neuropathy with and without neurological symptoms are presented. An elevated blood lactate level and changes in the activity of the mitochondrial enzymes in peripheral blood lymphocytes were noted. Mutations in the mitochondrial DNA (G3460A in one patient and G11778A in two patients) were found. The patient with a G3460A mutation, in addition to reduced visual acuity, was diagnosed with a cerebellar disorder due to cerebellar vermis hypoplasia. These changes are indications for prescribing energotropic drugs (idebenone, carnitine); carnosine can also be prescribed. These case studies show that patients with optic nerve atrophy should be assessed for Leber hereditary optic neuropathy. Differential diagnosis with multiple sclerosis should be performed, since this condition often presents as optic neuropathy.

Serum Lactate for Predicting Cardiac Arrest in the Emergency Department.

Objectives: Early recognition and prevention of in-hospital cardiac arrest (IHCA) play an increasingly important role in the Chain of Survival. However, clinical tools for predicting IHCA in the emergency department (ED) are scanty. We sought to evaluate the role of serum lactate in predicting ED-based IHCA. Methods: Data were retrieved from 733,398 ED visits over a 7-year period in a tertiary medical centre. We selected one ED visit per person and excluded out-of-hospital cardiac arrest, children, or those without lactate measurements. Patient demographics, computerised triage information, and serum lactate levels were extracted. The initial serum lactate levels were grouped into normal (≤2 mmol/L), moderately elevated (2 < lactate ≤ 4), and highly elevated (>4 mmol/L) categories. The primary outcome was ED-based IHCA. Results: A total of 17,392 adult patients were included. Of them, 342 (2%) developed IHCA. About 50% of the lactate levels were normal, 30% were moderately elevated, and 20% were highly elevated. In multivariable analysis, the group with highly elevated lactate had an 18-fold increased risk of IHCA (adjusted odds ratio [OR], 18.0; 95% confidence interval [CI], 11.5–28.2), compared with the normal lactate group. In subgroup analysis, the poor lactate-clearance group (<2.5%/h) was associated with a 7.5-fold higher risk of IHCA (adjusted OR, 7.5; 95%CI, 3.7–15.1) compared with the normal clearance group. Conclusions: Elevated lactate levels and poor lactate clearance were strongly associated with a higher risk of ED-based IHCA. Clinicians may consider a more liberal sampling of lactate in patients at higher risk of IHCA with follow-up of abnormal levels.

Prognostication of haemato-biochemical, electrolyte and blood gas parameters in canine parvoviral enteritis

Canine parvovirus (CPV) infection remains as a major threat to canine practitioners as well as pet owners as it requires intensive care for at least seven days and is associated with a high rate of fatality. This study conducted on 40 dogs with diarrhoea revealed a prevalence of 35 per cent (14/40) for CPV infection in Thissur, Kerala. Aetiology was confirmed by polymerase chain reaction (PCR) targeting the VP2 gene of CPV to get amplicon of approximately 583 bp length. Alterations in various blood parameters like blood gases, electrolytes, metabolites, haematological parameters and serum biochemical parameters are analysed and accessed as prognostic markers. Notable variations could be detected in the levels of pCO2, pO2, pSO2, HCO3-, base deficit, per cent of granulocytes, total erythrocyte count (TEC), haemoglobin (Hb), volume of packed red cells (VPRC), total protein, albumin, blood urea nitrogen (BUN) and alkaline phosphate (ALP). Mortality was associated with major decrease in the levels of HCO3- and a greater base deficit as evidenced from the blood gas analysis values. No correlation could be obtained for hypokalaemia and elevated levels of lactate in relation with mortality.

Tear Lactate Levels as a Surrogate Marker of Oxidative Stress in Myopia: A Case-control Study

Introduction: Myopia is most common refractive error leading to visual dysfunctions worldwide. Oxygen deficit due to environmental stress leads to increase in anaerobic glycolysis which results in lactate production. Increase in Reactive Oxygen Species (ROS) and inability of defense system to eliminate them is also responsible for alteration of regulatory pathways. The patient with elevated lactate levels are at significant risk of morbidity and hence, require a prompt treatment. Aim: To estimate and study the lactate levels in tear in various degree of myopia. Materials and Methods: This case-control study was conducted in tertiary care center, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India. Twenty five patients each with low, medium, high myopia, age and sex matched healthy controls (i.e, Group 1-4). Diagnosis was established with help of detailed history, clinical and ocular examination. Lactate levels were estimated in tear samples by enzymatic method on autoanalyzer within 30 minutes of collection. Independent Student’s t-test was used to determine the significance between myopia and controls. Results: Out of total 100 subjects, 68% were males and 32% were females. The mean±SD age was 24.56±6.35, 24.12±5.45, and 23.24±5.17, 21.69±3.95 in the Group 1, Group 2, Group 3 and Group 4 respectively in the control group, group with low, medium and high myopia respectively which was statistically not significant. The results of this study showed that lactate levels in tears were significantly higher (p-value=0.013) in myopia patients as compared to controls (1.34±0.46 versus 1.06±0.50). Additionally, the lactate levels increased with the progression of degree of myopia. Conclusion: Increase in the level of lactate in tear was directly proportional to the degree of myopia. Tear lactate levels can be used as a non invasive method to study oxidative stress in individuals. Further studies with more oxidative markers in tears can also be compared with blood values in larger groups of patients with long-term follow-up to validate the finding.

Spectrum of magnetic resonance abnormalities in leigh syndrome with emphasis on correlation of diffusion-weighted imaging findings with clinical presentation.

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy/early childhood secondary to mitochondrial dysfunction. Imaging plays a pivotal role in the diagnosis of LS with certain typical magnetic resonance imaging (MRI) findings considered as a part of diagnostic criteria. We appraised various MRI findings on conventional MRI sequences and also assessed potential correlation between diffusion abnormalities and patient's clinical presentation. Our aim was to describe various patterns of central nervous system involvement in LS and to assess the correlation of diffusion-weighted imaging abnormalities with clinical presentation. The design of the study was retrospective comprising 8 children with LS who had MRI between years 2014 and 2019. Eight children between the age group of 4 months 8 years with LS based on clinical presentation, elevated lactate levels in CSF/Blood, and typical MRI findings were included in the study. Brainstem was involved all (100%) patients while basal ganglia was affected in 5 (62.5%) children. Cerebral white matter involvement was present in 3 (37.5%) children, cerebellar in 2 (25%) children while spinal, corpus callosum, and thalamic involvement were observed in one (12.5%) patient each. Diffusion restriction was observed in 6 children, all of them presented with altered sensorium. Conventional MRI serves as an excellent tool for the diagnosis of LS in children with clinical suspicion. Acute encephalopathy frequently presents with diffusion restriction corresponding to active lesions. Hence, diffusion restriction on MRI predicts the activity of lesions in patients with LS.

Lactate modulates cardiac gene expression in mice during acute physical exercise.

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

Time dependency of CSF cell count, lactate and blood-CSF barrier dysfunction after epileptic seizures and status epilepticus

BackgroundThis retrospective observational study was conducted to examine the temporal relationship between increased cell count, lactate concentration in cerebrospinal fluid (CSF) and blood-CSF barrier dysfunction and the onset of a seizure event. MethodsPatients with a seizure event who underwent lumbar puncture for CSF analysis during diagnostic work-up (interindividual analysis) and those with at least one follow-up CSF analysis (intraindividual analysis) were studied. Pathologically altered parameters, such as cell count, lactate concentration, and blood-CSF barrier dysfunction as indicated by the albumin quotient (QAlb=CSF albumin/serum albumin), were examined with regard to the changes over time after seizure onset. ResultsAn increased CSF cell count (>4/µl) was shown in 3% of our patients, whereas pathological lactate concentrations were found in 24% after single seizures and 28% after status epilepticus (SE)/recurring seizures. However, lactate levels showed a marked decrease with increasing time after an isolated seizure (p<0.0001) but not after SE/recurring seizures. Lactate levels were most frequently and significantly elevated within the first six hours after a single seizure (p<0.0001). Blood-CSF barrier dysfunction was detected in 34% after isolated seizures and in 47% after SE/recurrent seizures. Blood-CSF barrier dysfunction showed no association with latency between seizure onset and time of CSF collection. ConclusionsChanges in lactate and CSF protein concentrations are common after epileptic seizures. In contrast, CSF pleocytosis is uncommon and should prompt careful investigation for the presence of intrathecal infection or autoimmune CNS disease. Elevated lactate levels more than 6 h after the seizure event may indicate ongoing epileptic activity.

Diagnostic Values of Venous Peak Lactate, Lactate-to-pyruvate Ratio, and Fold Increase in Lactate from Baseline in Aerobic Exercise Tests in Patients with Mitochondrial Diseases.

Objective Although aerobic exercise tests on cycle ergometry have long been used for initial assessments of cases of suspected mitochondrial disease, the test parameters in patients with final diagnoses of other diseases via the widely used 15 W for 15 minutes exercise protocol have not been fully characterized. Methods We retrospectively reviewed all patients who underwent the test at our institution. We classified the patients with genetic diagnoses or those who met previously reported clinical criteria as having mitochondrial diseases and those with a final diagnosis of another disease as having other diseases. Results were available from 6 patients with mitochondrial disease and 15 with other diseases. Results During the test, elevated venous peak lactate above the upper normal limit of healthy controls at rest [19.2 mg/dL (2.13 mM)] was observed in 3 patients with mitochondrial diseases (50.0%) and 5 with other diseases (33.3%). In the group of patients with elevated venous peak lactate, a lactate-to-pyruvate ratio of >20 was observed in all 3 patients with mitochondrial disease but in only 1 of the 5 with other diseases. More than a 2-fold increase in venous lactate from baseline was observed in 4 patients with mitochondrial disease (66.7%) and 1 with another disease (6.7%). Conclusion Elevated venous peak lactate levels were observed in patients with final diagnoses of other diseases, even under a low 15-minute workload at 15 W. The lactate-to-pyruvate ratio and increase in lactate level from baseline may add diagnostic value to venous peak lactate levels alone.

Extracellular Lactate Acts as a Metabolic Checkpoint and Shapes Monocyte Function Time Dependently.

Elevated blood lactate levels are frequently found in critically ill patients and thought to result from tissue hypoperfusion and cellular oxygen shortage. Considering the close relationship between immune cell function and intracellular metabolism, lactate is more than a glycolytic waste molecule but able to regulate the immune response. Our aim was to elucidate the temporal and mechanistic effect of extracellular lactate on monocytes. To this end, primary human monocytes and the human monocytic cell line MonoMac6 were stimulated with various toll-like-receptor agonists after priming with Na-L-lactate under constant pH conditions. As readout, cytokine production was measured, real-time assessment of intracellular energy pathways was performed, and intracellular metabolite concentrations were determined. Irrespective of the immunogenic stimulus, short-term Na-lactate-priming strongly reduced cytokine production capacity. Lactate and hexoses accumulated intracellularly and, together with a decreased glycolytic flux, indicate a lactate-triggered impairment of glycolysis. To counteract intracellular hyperglycemia, glucose is shunted into the branching polyol pathway, leading to sorbitol accumulation. In contrast, long-term priming with Na-L-lactate induced cellular adaption and abolished the suppressive effect. This lactate tolerance is characterized by a decreased cellular respiration due to a reduced complex-I activity. Our results indicate that exogenous lactate shapes monocyte function by altering the intracellular energy metabolism and acts as a metabolic checkpoint of monocyte activation.

Serum Lactate Level as a Predictor for Blood Transfusion in Postpartum Hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. At present, there are no reliable clinical or laboratory indicators to identify which patients might require blood transfusions during a PPH. Serum lactate has long been used as an early biomarker of tissue hypoperfusion in trauma settings. The aim of this study is to understand serum lactate's role in the management of obstetric hemorrhage. A retrospective chart review was performed of women who delivered between 2016 and 2019 at our institution and experienced a PPH. The patients were divided into two groups: those with a normal serum lactate level, defined as ≤2 mmol/L, and those with an abnormal serum lactate level, defined as >2 mmol/L. Need for packed red blood cell transfusion, as part of the resuscitation, was assessed for both groups. During the study period, 938 women experienced PPH. Of these, 108 (11.5%) had a normal serum lactate, ≤2 mmol/L, and 830 (88.5%) had an abnormal lactate, >2 mmol/L. Women with elevated lactate levels were more likely to receive a blood transfusion versus those with a normal lactate level (57.0 vs. 46.3%, p = 0.035, respectively). Additionally, the average number of blood transfusions administered was significantly higher in the abnormal lactate group versus in the normal lactate group (1.34 vs. 0.97, respectively, p = 0.004). In a multivariable linear regression model, increasing serum lactate levels were found to be predictive of requiring more than 1 unit of blood (p < 0.001). Women with elevated serum lactate levels were more likely to require blood transfusions during a PPH versus those with a normal serum lactate level. Thus, serum lactate levels are useful as an early indicator of requirement for blood transfusion in the management of obstetric hemorrhage. · Lactate is a biomarker for blood transfusion in trauma.. · Lactate's role in PPH is unknown.. · Elevated lactate predicts receiving more blood transfusions..

Glucose tolerance in fibromyalgia.

Objectives:Fibromyalgia (FM) patients have an increased risk for glucose metabolism disturbances, and impaired glucose tolerance may be associated with symptom severity. Elevated levels of plasma lactate have been detected in FM patients. Both pyruvate and lactate are produced in glucose metabolism and reflect oxidative metabolism. The objective of our study was to analyse disturbances in glucose, pyruvate, or lactate metabolism in FM patients.Methods:We measured plasma levels of glucose, pyruvate, and lactate during an oral glucose tolerance test in 40 non-diabetic, female FM patients and 30 age- and gender-matched healthy controls.Results:FM patients showed a higher glycaemic response to the glucose load at 1 hour (F [1,68] = 10.4, P = .006) and 2 hours (F [1,68] = 7.80, P = .02), and higher glucose area under the curve (13.8 [SD 2.92] vs 11.6 [SD 2.31], P < .01), than healthy controls. Group differences were explained by higher body mass index and percentage of smokers among the FM patients. Pyruvate and lactate levels were similar in both groups.Discussion:Impaired glucose regulation in FM patients is likely not due to FM itself, but to associated lifestyle factors. Our results highlight the importance of assessing the glucose regulation status and the lifestyle factors affecting glucose regulation in FM patients for prevention or early treatment of diabetes and associated complications.Trial Registration:ClinicalTrials.gov (NCT03300635)

Abstract 17034: Acute Ventricular Septal Rupture Management By The Cardiac Intensivist

Case Presentation: A 59-year-old male presented with chest pain and electrocardiogram showed convex ST elevations in the inferior leads. He underwent emergent coronary angiography revealing a 99% mid-distal right coronary artery thrombotic occlusion followed by placement of a drug-eluting stent. Transthoracic echocardiogram (TTE) revealed a 2.5 cm muscular ventricular septal rupture (VSR) with a calculated pulmonary-systemic flow ratio (Qp/Qs) of 2.4 in the setting of normal right and left ventricular systolic function. In the intensive care unit, he still had nausea and chest discomfort, along with acute kidney injury and elevated lactate levels. A trial of aggressive medical management was pursued to avoid emergent cardiac surgery. We placed an arterial line and initiated afterload reduction with sodium nitroprusside, utilizing serial bedside TTEs to monitor his Qp/Qs, which trended down to 1.8 over the subsequent 12 hours followed by normalization of lactate and kidney function. His symptoms resolved and he remained stable while transitioning to oral vasodilators. After four weeks of medical therapy, he underwent timely surgical repair of his VSR and discharged home. Discussion: Ventricular septal rupture is a serious complication of inferior myocardial infarctions (MI). From a cardiac intensivist perspective, we maintained the patient at a euvolemic state while using systemic vasodilators to divert the left-to-right shunt flow and augment his systemic flow. We want to highlight the utility of serial bedside TTEs to guide therapy for VSR (Figure 1). Fortunately, our patient did not require mechanical circulatory support to maintain his hemodynamics. We also discussed with our cardiothoracic surgeons about the optimal timing for surgical repair. The guidelines suggest urgent VSR repair following an MI; however, the exact timing is debatable given the fragility of the inflamed post-MI myocardium and better surgical outcomes with maturation of the VSR.

Abstract 11328: Risk Analytics and Clinical Decision Support System Role in Identifying Elevated Serum Lactate Level for Pediatric Cardiac Patients

Introduction: Pediatric patients with congenital heart defect are predisposed for low cardiac output syndrome (LCOS). Serum lactate is a well-defined marker of LCOS. To improve the quality and safety of care, new tools that are less invasive, more sensitive and specific are needed. Hypothesis: We hypothesize that analytics algorithms can compute risk indices that are associated with elevated lactate. Methods: Quality improvement project in tertiary pediatric cardiac intensive care unit. Data used were collected retrospectively throughout 6/2019-8/2020. The risk analytics algorithm uses a model of patient physiology with vitals and lab data to compute probability density curves for various physiologic variables in real-time. These densities are used to calculate the Hyperlactatemia Index (HLA) and Inadequate Delivery of Oxygen Index (IDO2) [Etiometry Inc., Boston, MA]. HLA and IDO2 represent the integrated probabilities that the current lactate is greater than 4 mmol/L and that the current SvO2 is less than 40% respectively. The minimum data required to calculate HLA and IDO2 is heart rate every 60 seconds, oxygen saturation via pulse oximetry, blood pressures every ten minutes, and at least one lactate lab per day (HLA only). The reported lactates were categorized in four groups. We subdivided the preceding three hours period before the lactate into 30 minutes windows. Subsequently, we calculated the mean IDO2 and HLA and compared the positive predictive value (PPV) of lactate &gt; 4 for both. Results: We included 484 patients in our analysis, 20% of which were neonates. The median patient age was 7.7 months (IQR:2,46). IDO2 and HLA trended higher when lactate levels were elevated, especially in the 30 minutes immediately preceding the lactate check. When the individual probability &gt; 50%, lactate was &gt; 4 in 44% ( + 10%) for HLA and 3% for IDO2. Conclusions: HLA shows a strong association with lactate and is superior to IDO2 across all time points. Performance of the indices was better in the 30min prior to the elevated lactate. Future studies validating this new tool prospectively are critical before its usage in the clinical setting.

Elevated serum lactate levels and age are associated with an increased risk for severe injury in trauma team activation due to trauma mechanism.

The identification of risk factors for severe injury is crucial in trauma triage and trauma team activation (TTA) depends on a sufficient triage. The aim of this study was to determine whether or not elevated serum lactate levels and age are risk factors for severe injury in TTA due to trauma mechanism. We conducted a retrospective cohort study in a single level one trauma center between September 2019 and May 2021 and analysed every TTA due to trauma mechanism. Primary endpoint of interest was the association of serum lactate as well as age with injury severity assessed by the injury severity score (ISS). During the study period, we included 250 patients. Mean age was 43.3years (Min.: 11, Max.: 90, SD: 18.7) and the initial lactate level was 1.7mmol/L (SD: 0.95) with a mean ISS of 8.4 (SD: 8.99). The adjusted odds ratio (OR) for age > 65 being associated with an ISS > 16 is 9.7 (p < 0.001; 95% CI 4.01-25.58) and for lactate > 2.2mmol/L being associated with an ISS > 16 is 6.29 (p < 0.001; 95% CI 2.93-13.48). A lactate level of > 4mmol/L results in a 36-fold higher risk of severe injury with an ISS > 16 (OR 36.06; 95% CI 4-324.29). This study identifies age (> 65) and lactate (> 2.2mmol/L) as independent risk factors for severe injury in a TTA due to trauma mechanism. Existing triage protocols might benefit from congruous amendments.