Lactate Measurements Research Articles

Point of care lactate for differentiating septic shock from hypovolemic shock in non-ICU settings: a prospective observational study

BackgroundSeptic shock and hypovolemic shock are life-threatening illnesses that necessitate immediate recognition and intervention, as they can result in deadly consequences. While the underlying processes may vary, both entities can exhibit hypotension and organ dysfunction. No studies have been conducted on bedside testing to differentiate between these illnesses. Lactate measurement has been established as a viable option for early detection of septic shock. However, its role in diagnosing hypovolemic shock has yet to be evaluated. The aim of the study was to investigate alterations in lactate levels among diarrheal patients with septic shock and hypovolemic shock following the administration of first fluid resuscitation. MethodsWe conducted a prospective observational study in critically ill diarrheal adults aged ≥18 years in the emergency ward in Dhaka Hospital of icddr,b from 21st October 2021 to 31st May 2023 (total 19 months). The enrollment process was operational between 8:30 AM and 5:00 PM. Diarrheal adults with a diagnosis of sepsis with shock featured with poor peripheral perfusion (characterized by cold periphery and weak or absent pulse and capillary refill time >3 sec) or hypotension (characterized by mean arterial pressure <65 mm-Hg) were enrolled as cases and consecutive diarrheal patients without any obvious features of sepsis with hypovolemic shock (due to severe dehydration) comprised the comparison group.POC lactate test was done at hours 0, 1st and 6th by StatStrip Lactate meters (Nova Biomedical, US) to all enrolled patients. For comparison of POC lactate levels, we used paired t-test for comparing the lactate samples drawn at hour 0, hour 1 and 6 with the septic shock and hypovolemic shock group. Odds ratio (OR) and their 95% confidence intervals (CIs) were used to demonstrate the strength of association. The study was registered at Clinicaltrials.gov (NCT05108467) and received institutional ethical approval (PR-21097). FindingsOf 435 patients, 135 had septic shock and 141 had hypovolemic shock, rest 41 patient responded with fluid bolus. 25% (34/135) of the people in the septic shock group died whereas there is no mortality in the hypovolemic shock group. The number of patients visiting from outside Dhaka city had more septic shock than from inside were higher in comparison with (55% vs. 28%; p <0.001). Statistically significant difference was observed between septic shock and hypovolemic shock group for a median POC lactate in 0, 1st and 6th hours with an OR of 1.07 (95% CI: 0.99, 1.17; p=0.039); 1.48, (95% CI: 1.28, 1.70; p<0.001) and 2.36 (95% CI: 1.85, 3.00; p<0.001), respectively. The gradient of 1st to 2nd sample between septic shock and hypovolemic shock was found to be significantly different (OR:0.74, 95% CI: 0.64, 0.85; p<0.001). InterpretationPOC lactate test can detect septic shock by differentiating hypovolemic shock in diarrheal patients. By providing quick, reliable and accurate result this test can help clinicians quickly diagnose and treat time-sensitive condition, like septic shock. FundingThe study was funded by Global Affairs of Canada (GR-01726). The donors had no role in the design, implementation, analysis, data interpretation or writing manuscript, or decision to publish. The corresponding author had access to all data and takes responsibility for the final approval and submission of the manuscript.

Scalable enzymatic lactate sensor for continuous monitoring in interstitial fluid

Abstract Elevated lactate levels have been shown to be an indicator of poor outcome in cardiovascular patients [1]. Moreover, continuous monitoring of lactate may be more clinically valuable than the absolute value of lactate for risk stratification [2]. A promising approach involves the implementation of a lactate monitoring system inspired by advanced continuous glucose monitoring [3] to provide real-time measurements of lactate in interstitial fluid (ISF) based on miniaturized lactate sensors with submillimeter dimensions. The proposed amperometric lactate sensor employs Pt electrodes (WE = 0.785 mm²) on which the enzyme lactate oxidase is immobilized to selectively detect lactate. The sensing mechanism, shown in Fig. 1a, is based on the conversion of lactate to hydrogen peroxide, which then undergoes oxidation at the electrode surface, generating a current proportional to the concentration of lactate. Amperometric measurements are performed with an applied potential of 0.5 V, a sample volume of 2 µL and a flow rate of 1 µL/min, respecting real-life conditions. The response of the sensor towards lactate is shown in Fig. 1c, demonstrating excellent reversibility, long-term stability over 8 hours and negligible cross sensitivity to glucose (G), ascorbic acid (AA) and uric acid (UA). In addition, the sensor linear range can be extended by 10x by incorporating an outer Nafion layer, acting as a diffusion-limiter. As shown in Fig. 1d, by adjusting the thickness of Nafion layer, the linear range increases up to 20 mM lactate, as per ICU specifications. The physiological challenges associated with ISF extraction prompted us to develop a minimally invasive, submillimeter-sized sensor for direct placement inside the body. To address the most critical step of miniaturization, we have successfully fabricated a three-electrode platform on a Si ribbon measuring 300x1500 µm² and a thickness of 100 µm (Fig. 2a). The sensor is also drastically scaled down, with smallest design having a total sensing area of 200x500 µm² (WE = 0.026 mm², Fig. 2b). Its response to lactate is displayed in Fig. 2c, confirming a reliable functionality. Fig. 2d presents the calibration curves obtained from sensors with different sizes, indicating that the reduction in size does not affect the sensitivity. The developed lactate sensor demonstrates excellent performance: high sensitivity, excellent reversibility, and high stability. In addition, the linear range of the sensor is tunable by integrating an outer Nafion membrane. Finally, we demonstrate the successful fabrication and characterization of submillimeter-sized sensors, opening up their potential for minimally invasive in-vivo measurements.Working principle and characterizationCharacterization miniaturized sensors

B-004 Method Validation of Lactate in the Plasma of Rats

Abstract Background The objective of this study is to validate Lactate (LAC) measurement in rat plasma using the ADVIA 1800 analyzer. Methods LAC was validated in rat plasma using the ADVIA 1800 analyzer. Validation testing included intra-assay and inter-assay precision, accuracy, linearity of dilution, limit of quantitation (LOQ), limit of detection (LOD), reference interval, carry-over, correlation, recovery, and stability. Samples were collected into tubes containing sodium fluoride. Intra-assay precision was determined by analyzing two biological samples and the two quality control levels of Bio-Rad Lyphochek Assayed Chemistry Control 10 consecutive times. Inter-assay precision was determined by analyzing the two quality control levels in duplicate for six days over a 10-day period. Accuracy was calculated using the data obtained from the inter-assay precision testing. For linearity of dilution, Audit MicroControl General Chemistry Linearity Kit and biological samples were diluted and analyzed in duplicate. The LOQ was determined by diluting the calibrator material to produce a value at the low end of the reportable range. Diluted material was tested six times. The LOD was determined by assaying the appropriate blank 10 times. The reference interval was determined by analyzing 21 plasma samples. Correlation between the two ADVIA 1800 analyzers was determined by assaying 10 samples on both analyzers once. The carry-over of the assay was determined by analyzing the high-level quality control material followed by the low-level quality control material. Recovery was determined by analyzing a pair of test samples in duplicate that have been spiked and diluted. The proportional error between the two test samples was calculated. Stability of plasma samples was tested on wet ice, refrigerated, and frozen (at -70°C) for various durations of storage. Results Measurement of LAC in rat plasma met the acceptance criteria for precision, accuracy, linearity of dilution, limit of quantitation, carry-over, recovery, and stability. For intra-assay precision in specimen and control material, the %CV was within ±20%. The inter-assay precision %CV was within ±20%. The total error observed (TEobs) was within ±20% for accuracy and the obtained mean of the control material was within the manufacturer’s acceptable range. For linearity of dilution, the coefficient of determination was ≥ 0.9000, the slope was within 1.00 ± 0.25, and TEobs for each plasma and linearity kit dilution was ≤20%. The LOQ was set at the lowest concentration for which the TEobs was within ±20%. The LOD was calculated by adding the mean concentration obtained and three times the standard deviation. The reference interval was set to the 2.5th to 97.5th percentile interval using Excel software. The carry-over was acceptable at ≤2%. Correlation between the two ADVIA 1800 analyzers was determined to describe any bias in result interpretation. Recovery was acceptable as the proportional error was within ±20%. Stability at all storage conditions was found to be acceptable with a mean %difference within ±20%. Conclusions LAC in rat plasma met the acceptance criteria for all required validation parameters. The ADVIA 1800 analyzer can be used for preclinical studies to test LAC in rat plasma.

Physiological Profiles: Speed Reserve Ratio, Skeletal Muscle Oxygenation, And Lactate Measurements In Middle-distance Runners

Physiological Profiles: Speed Reserve Ratio, Skeletal Muscle Oxygenation, And Lactate Measurements In Middle-distance Runners

Arterial to jugular-bulb lactate difference in patients undergoing elective brain tumor craniotomy.

Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular-bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular-bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed-effects model with jugular-bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular-bulb concentrations. The slope of the regression line between arterial and jugular-bulb lactate was 0.95 (95% CI 0.93-0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57-5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor-craniotomy patients probably does not originate from the brain.

A Rapid Increase in Serum Lactate Levels after Cardiovascular Surgery Is Associated with Postoperative Serious Adverse Events: A Single Center Retrospective Study.

Hyperlactatemia is a common predictive factor for poor post-cardiovascular surgery outcomes. However, it is not well understood whether the rapid postoperative lactate level elevation in a short period of time is associated with patient outcomes. Herein, we investigated the relationship between the degree of change in serum lactate levels and postoperative serious adverse events (PSAEs), including mortality, within 24 h of cardiovascular surgery. In this retrospective study, we evaluated the relationship between a rapid serum lactate level increase and PSAEs after open-heart and major vascular surgery. We divided the patients into those with and without PSAEs. Univariate and multivariate analyses were performed to evaluate the association between PSAEs and rapid lactate level increases. We enrolled 445 patients; 16% (n = 71) had PSAEs. The peak lactate levels during the first 24 h of intensive care unit (ICU) stay were higher in patients with PSAEs than in those without. The maximum change in lactate levels between two consecutive lactate measurements during the first 24 h after ICU admission was higher in patients with PSAEs than in those without. A multivariate logistic regression analysis revealed that changes in lactate levels of 2 mmol/L or more between two consecutive lactate measurements were associated with PSAEs. ICU peak lactate levels of 3 mmol/L or more were not associated with PSAEs. Rapid serum lactate level increases of 2 mmol/L or more during the first 24 h of ICU admission post-cardiovascular surgery are associated with PSAEs.

Impact of Point-of-Care Lactate Testing for Sepsis on Bundle Adherence and Clinical Outcomes in the Emergency Department: A Pre-Post Observational Study.

Background: The early diagnosis and prompt treatment of sepsis can enhance clinical outcomes. This study aimed to assess the relationship between point-of-care testing (POCT) for lactate levels and both adherence to the Surviving Sepsis Campaign (SSC) guidelines and mortality rates among sepsis patients in the emergency department (ED). We hypothesized that bedside lactate POCT would lead to better clinical outcomes. Methods: We conducted a pre-post observational study utilizing data from a prospectively collected sepsis registry. Following the introduction of lactate POCT, lactate levels were determined using both the central laboratory pathway and a POCT device. We then compared the characteristics and clinical outcomes between the periods before and after the introduction of POCT lactate measurement. Results: The analysis included a total of 1191 patients. The introduction of bedside lactate POCT led to a significant reduction in the time taken to obtain lactate results (from 53 to 33 min) and an increase in the rate of subsequent lactate measurements (from 82.1% to 88.2%). Lactate POCT did not significantly affect adherence to the overall SSC guidelines bundle (47.5% vs. 45.0%) or reduce 30-day mortality rates (31.1% vs. 31.4%). However, bedside lactate POCT could decrease extremely delayed lactate measurements. Conclusions: Bedside lactate POCT successfully reduced the time to obtain lactate results. Although lactate POCT did not lead to improved adherence to the overall SSC guidelines bundle or affect short-term mortality rates in sepsis patients, it may have an advantage in a specific situation such as overcrowded ED where there are subsequent or multiple measurements required.

Surveillance fœtale : limites actuelles et nouvelles pistes basées sur l’analyse du système nerveux autonome fœtal

ObjectiveCurrently, fetal monitoring during labor is based on visual analysis of the fetal heart rate (FHR). This test is imperfect, with high intra- and inter-observer variability and a moderate to poor prediction of the occurrence of neonatal acidosis or anoxic-ischaemic encephalopathy. In situations where there is an intermediate risk of acidosis, it is possible to use second-line tests such as blood scalp sampling (with pH or lactate measurement) or ST segment analysis of the fetal ECG. However, these invasive tests have many limitations and their place is debated. Some authors suggest a more physiological approach to FHR assessment. The main actor in maintaining fetal homeostasis is the autonomic nervous system (ANS). Its activity can be assessed by analysing heart rate variability (HRV). The aim is to assess whether HRV can be used to identify situations at risk of acidosis. Materials and methodsOur team has developed an index, the Fetal Stress Index, to measure HRV. To test it in a situation of acidosis, we used a pregnant ewe model. We also developed in parallel a human fetal ECG recording system. ResultsIn our experimental model, we have shown that this index reflects variations in the parasympathetic system and correlates with the onset of acidosis. As its use in clinical practice requires the acquisition of a beat-to-beat FHR signal, we have also developed an abdominal patch that allows highly accurate analysis of the fetal ECG. ConclusionThe future is therefore to validate the FSI as a marker of acidosis in a prospective cohort using the signal obtained from our patch. This could be a new tool for fetal monitoring during labor.

Comparison of lactate measurements from earlobe and fingertip capillary blood using Biosen S-Line and lactate scout analyzers.

This study aimed to compare variations between the earlobe and fingertip sampling sites in exercises dominated by upper body muscle exertion. It also sought to investigate capillary blood lactate differences between Lactate Scout 4 (LS4) and a bench-top analyzer (Biosen S-Line analyzer, BSL) during Double Poling. Blood samples were collected from the earlobe and fingertip immediately before exercise, at the end of each of five stages, and at 1-, 3-, 5-, and 7-min post-exercise. Forty healthy university students participated as volunteers. During the study, they performed double poling on a ski ergometer with progressively increasing load. Lactate levels were measured using both the BSL and LS4 analyzers. Fingertip Bla values were significantly higher than earlobe values, with a mean bias of -0.66mmol/L, reaching -0.86mmol/L in the 4-8mmol/L range. At the earlobe, the highest CCC between BSL and LS4-a was 0.84 (> 8mmol/L), and for BSL and LS4-b, it was 0.85 (> 8mmol/L). At the fingertip, the highest CCC between BSL and LS4-c was 0.68 (> 8mmol/L), and for BSL and LS4-d, it was 0.52 (> 8mmol/L). Comparing LS4-a and LS4-b at the earlobe, the highest CCC was 0.83 (0-4mmol/L). At the fingertip, comparing LS4-c and LS4-d, the highest CCC was 0.68 (> 8mmol/L). Blood lactate concentrations are higher at the fingertip than the earlobe during SkiErg double poling. The LS4 is less reliable, especially at the fingertip, so using the earlobe with the BSL analyzer is recommended for accurate measurements.

Effect of ZCRB1 on the glycolysis via PKM2-HIF1α axis and promotion of immune tolerance in nasopharyngeal carcinoma.

130 Background: Nasopharyngeal carcinoma (NPC) is characterized by abundant lymphocyte infiltration. The failure of immune checkpoint inhibitors in NPC may be related to immune tolerance. Methods: Bioinformatics analysis was performed to identify the correlation between the ZCRB1 mRNA level and immune cell infiltration in NPC tissues. Quantitative real time PCR and immunoblotting were used to determine the mRNA and protein expression, respectively. Functional experiments (CCK8, colony formation assay, cell migration assay and tumor xenograft) were used to explore the effect of ZCRB1 on the malignant phenotype in NPC cells. Glucose and lactate measurement assays as well as Seahorse XF glycolysis stress assay, were conducted to investigate the effects of ZCRB1 on glycolysis in NPC cells. RNA sequencing, QPCR and minigene analysis were used to confirm the splicing switch between PKM1 and PKM2. Luciferase assay was performed to detect the transcription activity of HIF1-α. Finally, correlation analysis between the ZCRB1 expression and glycolysis level was performed to in NPC samples. Results: The expression of ZCRB1 was negatively correlated with checkpoint-related genes and immune regulation-related gene sets in head and neck cancer. Likewise, in NPC, the expression of ZCRB1 was negatively correlated with lymphocyte infiltration, tumor immune microenvironment score and tumor-infiltrating CD4+ T cells, CD8+ T cells, and dendritic cells. Low expression of ZCRB1 was associated with better prognosis. Functional assays demonstrated that ZCRB1 significantly promoted NPC cells growth, clonogenicity, migratory capacity and glycolysis. Mechanistically, ZCRB1 was mainly involved in the hypoxic signaling pathway. Cells with ZCRB1 downregulation downregulated glycolysis-related genes and significantly reduced the transcriptional activity of HIF-1α. Moreover, minigene assays showed that the intron 9 region spliced by PKM in cells with ZCRB1 downregulation. Finally, bioinformatics analysis showed that the mRNA expression of ZCRB1 was positively correlated with the immune infiltration score significantly during glycolysis. Conclusions: ZCRB1 promotes the growth and migration of nasopharyngeal carcinoma cells and is associated with immune tolerance. Further, ZCRB1 accelerates the glycolysis via enhancing the transcriptional activity of HIF-1α through increasing PKM2 isoform splicing, providing a scientific basis for tumor metabolic reprogramming to reshape the immune microenvironment.

A wearable nanozyme–enzyme electrochemical biosensor for sweat lactate monitoring

In this study, we developed a wearable nanozyme–enzyme electrochemical biosensor that enablies sweat lactate monitoring. The biosensor comprises a flexible electrode system prepared on a polyimide (PI) film and the Janus textile for unidirectional sweat transport. We obtained favorable electrochemical activities for hydrogen peroxide reduction by modifying the laser-scribed graphene (LSG) electrode with cerium dioxide (CeO2)–molybdenum disulphide (MoS2) nanozyme and gold nanoparticles (AuNPs). By further immobilisation of lactate oxidase (LOx), the proposed biosensor achieves chronoamperometric lactate detection in artificial sweat within a range of 0.1–50.0 mM, a high sensitivity of 25.58 μA mM−1cm−2 and a limit of detection (LoD) down to 0.135 mM, which fully meets the requirements of clinical diagnostics. We demonstrated accurate lactate measurements in spiked artificial sweat, which is consistent with standard ELISA results. To monitor the sweat produced by volunteers while exercising, we conducted on-body tests, showcasing the wearable biosensor's ability to provide clinical sweat lactate diagnosis for medical treatment and sports management.

Sepsis Alert Systems, Mortality, and Adherence in Emergency Departments

Early detection and management of sepsis are crucial for patient survival. Emergency departments (EDs) play a key role in sepsis management but face challenges in timely response due to high patient volumes. Sepsis alert systems are proposed to expedite diagnosis and treatment initiation per the Surviving Sepsis Campaign guidelines. To review and analyze the association of sepsis alert systems in EDs with patient outcomes. A thorough search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1, 2004, to November 19, 2023. Studies that evaluated sepsis alert systems specifically designed for adult ED patients were evaluated. Inclusion criteria focused on peer-reviewed, full-text articles in English that reported on mortality, ICU admissions, hospital stay duration, and sepsis management adherence. Exclusion criteria included studies that lacked a control group or quantitative reports. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Two independent reviewers conducted the data extraction using a standardized form. Any disagreements were resolved through discussion. The data were synthesized using a random-effects model due to the expected heterogeneity among the included studies. Key outcomes included mortality, intensive care unit admissions, hospital stay duration, and adherence to the sepsis bundle. Of 3281 initially identified studies, 22 (0.67%) met inclusion criteria, encompassing 19 580 patients. Sepsis alert systems were associated with reduced mortality risk (risk ratio [RR], 0.81; 95% CI, 0.71 to 0.91) and length of hospital stay (standardized mean difference [SMD], -0.15; 95% CI, -0.20 to -0.11). These systems were also associated with better adherence to sepsis bundle elements, notably in terms of shorter time to fluid administration (SMD, -0.42; 95% CI, -0.52 to -0.32), blood culture (SMD, -0.31; 95% CI, -0.40 to -0.21), antibiotic administration (SMD, -0.34; 95% CI, -0.39 to -0.29), and lactate measurement (SMD, -0.15; 95% CI, -0.22 to -0.08). Electronic alerts were particularly associated with reduced mortality (RR, 0.78; 95% CI, 0.67 to 0.92) and adherence with blood culture guidelines (RR, 1.14; 95% CI, 1.03 to 1.27). These findings suggest that sepsis alert systems in EDs were associated with better patient outcomes along with better adherence to sepsis management protocols. These systems hold promise for enhancing ED responses to sepsis, potentially leading to better patient outcomes.

Operational stability study of lactate biosensors: modeling, parameter identification, and stability analysis.

This paper investigates the operational stability of lactate biosensors, crucial devices in various biomedical and biotechnological applications. We detail the construction of an amperometric transducer tailored for lactate measurement and outline the experimental setup used for empirical validation. The modeling framework incorporates Brown and Michaelis-Menten kinetics, integrating both distributed and discrete delays to capture the intricate dynamics of lactate sensing. To ascertain model parameters, we propose a nonlinear optimization method, leveraging initial approximations from the Brown model's delay values for the subsequent model with discrete delays. Stability analysis forms a cornerstone of our investigation, centering on linearization around equilibrium states and scrutinizing the real parts of quasi-polynomials. Notably, our findings reveal that the discrete delay model manifests marginal stability, occupying a delicate balance between asymptotic stability and instability. We introduce criteria for verifying marginal stability based on characteristic quasi-polynomial roots, offering practical insights into system behavior. Qalitative examination of the model elucidates the influence of delay on dynamic behavior. We observe a transition from stable focus to limit cycle and period-doubling phenomena with increasing delay values, as evidenced by phase plots and bifurcation diagrams employing Poincaré sections. Additionally, we identify limitations in model applicability, notably the loss of solution positivity with growing delays, underscoring the necessity for cautious interpretation when employing delayed exponential function formulations. This comprehensive study provides valuable insights into the design and operational characteristics of lactate biosensors, offering a robust framework for understanding and optimizing their performance in diverse settings.

The absolute lactate levels versus clearance for prognostication of post-cardiotomy patients on veno-arterial ECMO.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving procedure for supporting patients with cardiogenic shock after cardiac surgery. This work aimed to analyse the impact of changes in blood lactate levels on the survival of patients on post-cardiotomy ECMO (PC-ECMO) and whether lactate clearance (LC) performs better than absolute lactate levels. We retrospectively analysed the data of adult patients who received PC-ECMO at our centre between 2016 and 2022. The primary outcome was the in-hospital mortality rate. Arterial lactate levels were measured at ECMO initiation, peak and 12 and 24h after VA-ECMO support. LC was calculated at 12 and 24h. Out of 2368 patients who received cardiac surgeries, 152 (median age, 48years; 57.9% of them were men) received PC-ECMO. Of them, 48 (31.6%) survived and were discharged, while 104 (68.4%) died during the index hospitalization. Non-survivors had higher frequencies of atrial fibrillation (41.35% vs. 12.5%, P<0.001), chronic kidney disease (26.9% vs. 6.3%, P=0.004), prolonged cardiopulmonary bypass (237 vs. 192min, P=0.016) and aortic cross-clamping times (160 vs. 124min, P=0.04) than survivors. Non-survivors had a significantly higher median Sequential Organ Failure Assessment (SOFA) score at ECMO initiation (13.5 vs. 9, P<0.001) and a lower median Survival After Veno-arterial ECMO (SAVE) score (-3 vs. 3, P<0.001) with higher SAVE classes (P<0.001) than survivors. After 12h of VA-ECMO support, the blood lactate level was negatively correlated with LC in survivors (r=-0.755, P<0.001) and non-survivors (r=-0.601, P<0.001). After 24h, the same negative correlation was identified between survivors (r=-0.764, P<0.001) and non-survivors (r=-0.847, P<0.001). Blood lactate levels measured at 12h to determine hospital mortality [>8.2mmol/L, area under the receiver operating characteristic curve (AUROC): 0.868] and 24h (>2.6mmol/L, AUROC: 0.896) had the best performance, followed by LC-T12 (<21.94%, AUROC: 0.807), LC-T24 (<40.3%, AUROC: 0.839) and peak blood lactate (>14.35mmol/L, AUROC: 0.828). The initial pre-ECMO blood lactate (>6.25mmol/L, AUROC: 0.731) had an acceptable ability to discriminate mortality but was less than the following measurements and clearance. Kaplan-Meier curves demonstrated that LC of <21.94% at T12h and <40.3% at T24h was associated with decreased survival (log-rank P<0.001). Cox proportional hazards regression analysis for mortality revealed that LC of <21.94% at T12h had an adjusted hazard ratio (HR) of 2.73 [95% confidence interval (CI): 1.64-5.762, P<0.001] and LC of <40.3% at T24h had an adjusted HR of 1.98 (95% CI: 1.46-4.173, P<0.001). The predictors of hospital mortality after PC-ECMO were the lactate level at 12h [odds ratio (OR): 1.67, 95% CI: 1.121-2.181, P=0.001], initial SOFA score (OR: 1.593, 95% CI: 1.15-2.73, P<0.001), initial blood lactate (OR: 1.21, 95% CI: 1.016-1.721, P=0.032) and atrial fibrillation (OR: 6.17, 95% CI: 2.37-57.214, P=0.003). Bivariate models using lactate levels and clearance at the same points revealed that blood lactate levels performed better than the clearance percentage. Serial measurements of arterial blood lactate and LC help in obtaining early prognostic guidance in adult patients supported by VA-ECMO after cardiac surgery. Absolute lactate levels, compared with LC at the same time points, demonstrated better performance in differentiating mortality.

The Role of Serum Lactate Values as a Predictor of Morbidity in Preterm Infants

Abstract Background Early hemodynamic assessment of critically ill newborns requires mostly invasive measurements in neonatal intensive care unit. Base deficit and serum lactate concentrations may be important prognostic indicators in preterm infants. Aim and Objectives to investigate the relationship between serum lactate levels and adverse outcome in preterm infants who were admitted to NICU of Ain Shams University Hospital. Subjects and Methods This study is prospective cohort study, that included 90 preterm patients that were admitted to neonatal intensive care unit during a period of 6 months, all the neonates had the level of serum lactate been evaluated by ELISA (at 6, 12, 18 and 24 hours of birth) and correlated with the incidence of intracranial hemorrhage as diagnosed by cranial ultrasonography. Result: The initial serum lactate level was compared with the follow up readings at 12, 18 and 24 hours and showed statistically significant reduction of serum lactate in follow up recordings (p-value &amp;lt;0.05), Serum lactate was statistically significant predictors of death with increase serum lactate at 12hrs., at 18hrs. and at 24hrs, with p-value (p &amp;lt; 0.05). Serum lactate had no statistically significant association with intracranial hemorrhage as detected by transcranial ultrasonography. Conclusion Serial lactate measurements greater than 5.6 mmol/l predict adverse outcome and may aid the clinician in bedside decision making.

Prognostic Value of Systemic Arterial Lactate Levels in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abstract Background Acute myocardial infarction is the most severe manifestation of coronary artery disease, which causes more than 2.4 million deaths in the USA, more than 4 million deaths in Europe and northern Asia, and more than a third of deaths in developed nations annually. Objective To assess the prognostic value of systemic arterial lactate levels in patients with ST segment elevation myocardial infarction undergoing primary PCI and correlate with the results of primary PCI and 30 days MACE follow up. Patients and Methods This study included 300 patients who presented with documented STEMI and underwent reperfusion by successful primary PCI in Ain Shams University hospitals. Results There was statistically significant positive correlation found between serum lactate and (WBCs) count, (HbA1C) level and cardiac enzymes (CKtotal - CKmb – troponin) and negative correlation found between serum lactate and ejection fraction in echocardiography. Also, we found that other parameters were associated with MACE follow up in 30 days such as Killip class at admission, ST segment elevation resolution, heart block in ECG, lower ejection fraction, dyslipidemia, post-procedure TIMI flow, peri-procedural time intervals and occurrence of complications. Conclusion The value of an early lactate measurement in patients with STEMI is to be a part of the risk stratification of these patients and intensified medical care should be considered to patients with strongly elevated lactate levels. Also, increasing arterial lactate levels were associated with occurrence of MACE in 30 days, worse hemodynamics, lower ejection fraction in echocardiography, higher HbA1C level, large infarct area (cardiac biomarkers peak level), poor post-procedure TIMI flow and thrombus grade.

Effects of acute beetroot juice intake on performance, maximal oxygen uptake, and ventilatory efficiency in well-trained master rowers: a randomized, double-blinded crossover study.

Beetroot juice (BRJ) intake has been considered a practical nutritional strategy among well-trained athletes. This study aimed to assess the effects of BRJ intake on performance, cardiorespiratory and metabolic variables during a simulated 2000-meter rowing ergometer test in well-trained master rowers. Ten well-trained male master rowers (30-48 years) participated in a randomized, double-blind, crossover design for 3 weeks. In the first week, a researcher explained all the experimental procedures to the participants. In the next two weeks, the participants were tested in 2 rowing ergometer sessions, separated from each other by a 7-day washout period. In both strictly identical sessions, the participants randomly drank BRJ or placebo (PL) 3 hours before the start of the tests. Subsequently, the participants carried out the 2000-meter rowing ergometer tests. Oxygen saturation and blood lactate measurements were performed before starting (pretest) and at the end of the test (posttest). Performance parameters and cardiorespiratory variables were recorded during the rowing ergometer test. An improvement in time trial performance was observed, with a mean difference of 4 seconds (90% confidence limits ± 3.10; p ≤ 0.05) compared to PL. Relative and absolute increased (mean difference of 2.10 mL·kg-1·min-1, 90% confidence limits ± 1.80; mean difference of 0.16 L·min-1 90% confidence limits ± 0.11, respectively; p ≤ 0.05) compared to PL. No ergogenic effect was observed on ventilatory efficiency and blood lactate concentrations after BRJ intake. Acute BRJ intake may improve time trial performance as well as in well-trained master rowers. However, BRJ does not appear to improve ventilatory efficiency.

Identifying high-risk undifferentiated emergency department patients with hyperlactatemia: Predictors of 30-day in-hospital mortality.

Hyperlactatemia has been recognized as a significant prognostic indicator in critically ill patients. Nonetheless, there remains a gap in understanding the specific risk factors contributing to increased mortality among undifferentiated emergency department (ED) patients presenting with elevated lactate levels. The objective of the study is to investigate potential risk factors for 30-day in-hospital mortality in ED patients with hyperlactatemia. All nontraumatic adult presentations to the ED who had a lactate level of ≥2.5 mmol/L were included. Comorbidities, vital signs, lactate levels, lactate clearance, lactate normalization, and final diagnosis were compared with 30-day in-hospital mortality. A 30-day in-hospital mortality rate of 10.4% was observed in 979 patients. The mortality rate was higher in hypotensive patients (odds ratio [OR] 4.973), in nursing home patients (OR 5.689), and bedridden patients (OR 3.879). The area under the curve for the second lactate level (0.804) was higher than the first lactate level (0.691), and lactate clearance (0.747) for in-hospital mortality. A second lactate level >3.15 mmol/l had a sensitivity of 81.3% in predicting in-hospital mortality. The OR for mortality was 6.679 in patients without lactate normalization. A higher mortality rate was observed in patients with acute renal failure (OR 4.305), septic shock (OR 4.110), and acute coronary syndrome (OR 2.303). A second lactate measurement more accurately predicts in-hospital mortality than lactate clearance and the first lactate level in ED patients. Nursing home patients, bed-ridden patients, hypotensive patients on initial ED presentation, patients without lactate normalization, and patients with a final diagnosis of acute renal failure, septic shock, and acute coronary syndrome had a higher mortality rate.

Trends in Empiric Broad-Spectrum Antibiotic Use for Suspected Community-Onset Sepsis in US Hospitals

Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time. To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis. This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission. Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use. Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics. Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13). In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial.

The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30mL/kg crystalloid fluid for hypotension or lactate ≥ 4mmol/L, remains controversial. We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2mmol/L were eligible. The intervention was theimplementation of the 1-h sepsis bundle.The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24h, acute heart failure at 24h, SOFA score at 72h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40min in the intervention group vs 113min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.