Hemodynamic and Lactate Response to Exhaustive Exercise with L-Arginine Supplementation

Introduction: To further understand the effects of L-arginine on both its ability to enhance lactate clearance and increase overall blood flow before, during, and after exhaustive anaerobic exercise. Methods: Twelve healthy male subjects between the ages of 18-25 first completed an initial visit where baseline data was recorded. Subjects completed three additional visits, in which they ingested either a placebo, two-gram or four-gram dose of L-arginine. Blood flow (BF) and lactate were recorded before ingestion of the treatment, 5 and 15-minutes post-ingestion prior to performing a push-up test to volitional fatigue. Immediately following the push-up test, BF and lactate were assessed and again 15-minutes post exercise. Results: Blood lactate did not differ across condition (p=0.569). Lactate clearance was not influenced by L-arginine when analyzing the Area Under Curve. Blood flow increased with ingestion of the four-gram dose while at rest (the 15-minute mark). Blood flow was also enhanced in the four-gram dose immediately after exercise at the 25-minute mark. Conclusions: The data suggests that a four-gram dose of L-arginine plays a more significant role in blood flow than the clearance of lactate after exercise compared to a two-gram dose or placebo.

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.

High-intensity interval resistance training (HIIRT) improves liver gluconeogenesis from lactate in Swiss mice

High-intensity physical exercise favors anaerobic glycolysis and increases lactatemia. Lactate is converted back to glucose in the liver, so that the lactate threshold, an indicator of physical performance, must be related to the gluconeogenic capacity of the liver. This research assessed the effect of a high-intensity interval resistance training (HIIRT) on liver gluconeogenesis from lactate. Swiss mice were trained (groups T) on vertical ladder with overload of 90% of their maximal load. Control animals remained untrained (groups C0 and C8). In situ liver perfusion with lactate and adrenaline was performed in rested mice after six hours of food deprivation. There were larger outputs of glucose (T6 71.90%, T8 54.53%) and pyruvate (T8 129.28%) (representative values for 4 mM lactate) in the groups trained for six or eight weeks (T6 and T8), and of glucose in the presence of adrenaline in group T8 (280%). The content of PEPCK, an important regulatory enzyme of the gluconeogenic pathway, was 69.13% higher in group T8 than in the age-matched untrained animals (C8). HIIRT augmented liver gluconeogenesis from lactate and this might improve the lactate threshold. Bullet points: The liver metabolizes lactate from muscle into glucose. Physical training may enhance the gluconeogenic capacity of the liver. As lactate clearance by the liver improves, lactate threshold is displaced to higher exercise intensities.

Analysis of Prognostic Risk Factors of Sepsis Patients in Intensive Care Unit Based on Data Analysis

In this paper, a data-enabled analysis of the prognostic risk factors of sepsis patients in the intensive care unit is presented. For this purpose, we have selected 220 sepsis patients, preferably those admitted to the intensive care unit for treatment in a tertiary a hospital in Tianjin from June 2018 to June 2019 and received complete data as the research objects, to explore the prognostic risk factors of sepsis patients in the intensive care unit. All patients met the SSC sepsis diagnosis guidelines and recorded the patients’ age, gender, underlying disease, and infection site. Laboratory indicators, such as blood routine, electrolytes, arterial blood gas, liver function, and renal function, were collected within 24 hours of admission. Furthermore, the corresponding specimens were cultured for pathogenic microorganisms according to the site of infection. The LAC value was measured at admission and 24 h after admission, and the 24 h lactate clearance rate was calculated. The Acute Physiological and Chronic Health Status Score II (APACHE-II) and SOFA score were calculated, which were based on the worst value of the index within 24 hours after admission. According to the prognosis of patients during hospitalization, they are divided into two groups: (i) survival group and (ii) death group. We entered all the data into Excel and used SPSS21.0 statistical software for data analysis and processing. Quantitative data are tested for normality. Quantitative data for normal distribution are expressed as mean ± standard deviation, and normal distribution and uniform variance are measured. The factors affecting the prognosis of patients with sepsis were first subjected to a single-factor logistic regression analysis, and a multiple logistic regression analysis was performed on the basis of the significance of the single-factor analysis. The results found that the prognosis of patients with sepsis in the ICU is affected by multiple factors such as underlying diseases, infectious microorganisms, comorbidities, and interventional therapy. APACHE-II score, 24 h lactate clearance rate, ARDS, and DIC are independent risk factors that affect the prognosis of ICU patients.

Norepinephrine Dosage Is Associated With Lactate Clearance After Resuscitation in Patients With Septic Shock

Background: Some septic shock patients have persistent hyperlactacidemia despite a normal systemic hemodynamics after resuscitation. Central venous oxygen saturation (ScvO2), mean arterial pressure (MAP), and central venous pressure (CVP) cannot be target in subsequent hemodynamic treatments. Vasoplegia is considered to be one of the main causes of oxygen metabolism abnormalities in septic shock patients, and norepinephrine (NE) is the first-line vasopressor in septic shock treatment; its dosage represents the severity of vasoplegia. This study was performed to determine whether vasoplegia, as assessed by NE dosage, can indicate patients' lactate clearance after the completion of resuscitation.Methods: A retrospective study was performed, and 106 patients with septic shock in an intensive care unit were analyzed. Laboratory values and hemodynamic variables were obtained upon completion of resuscitation (H 0) and 6 h after (H 6). Lactate clearance was defined as the percent decrease in lactate from H 0 to H 6. Student's t-test, Mann-Whitney U-test, Chi-square or Fisher's exact tests, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis.Results: Patients with a mean age of 63.7 ± 13.8 years, baseline APACHE II score of 21.0 ± 5.1, and SOFA score of 12.7 ± 2.7 were enrolled. The study found that after 6-h of resuscitation, lactate clearance (LC) was &lt;10% in 33 patients (31.1%). Patients with 6-h LC &lt;10% compared with 6-h LC ≥ 10% had a higher NE dose (μg·kg−1·min−1) (0.55 [0.36–0.84] vs. 0.25 [0.18–0.41], p &lt; 0.001). Multivariate logistic regression analysis of statistically significant univariate variables showed that NE dose had a significant inverse relationship with 6-h LC &lt; 10%. The cutoff for NE was ≥ 0.32 μg·kg−1·min−1 for predicting 6-h lactate clearance after resuscitation, with a sensitivity of 75.76% and a specificity of 70.00%. Septic shock patients with an NE dose ≥ 0.32 μg·kg−1·min−1, relative to patients with an NE dose &lt; 0.32 μg·kg−1·min−1, had a greater 30-day mortality rate (69.8% vs. 26.4% p &lt; 0.001).Conclusion: Some patients with septic shock had persistent oxygen metabolism disorders after hemodynamic resuscitation. NE dose may indicate vasoplegia and oxygen metabolism disorder. After resuscitation, septic shock patients with high-dose NE have lower lactate clearance and a greater 30-day mortality rate than those with low-dose NE.

A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

Effect of Glucose-Insulin-Potassium Infusion on Hemodynamics in Patients with Septic Shock

BACKGROUND: Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. AIM: The aim of this study was to assess role of GIK infusion in improving hemodynamics in patients with septic shock in addition to its role in myocardial protection and preventing occurrence of sepsis-induced myocardial dysfunction and sepsis-induced arrhythmias. METHODS: This study was conducted on 75 patients admitted to the Critical Care Department in Cairo University Hospital with the diagnosis of septic shock during the period from January 2019 to December 2019. Patients were divided into two groups; first group was managed according to the last guidelines of surviving sepsis campaign and was subjected to the GIK infusion protocol while second group was managed following the last guidelines of surviving sepsis campaign only without adding GIK infusion. RESULTS: Patients in the GIK group showed better lactate clearance (50% vs. 46.7%) and less time needed for successful weaning of vasopressors than the control group (3.57±1.16 vs. 3.6±1.45 days) thought not reaching statistical significance. There was no statistically significant difference between both groups regarding development of septic-induced cardiomyopathy (16.7% in the control group vs. 13.3% in the GIK group); however, patients with hypodynamic septic shock showed better improvement in hemodynamic profile in the GIK group. Sepsis-induced arrhythmias occurred more in patients of the control group than in patients of the GIK group with no statistically significant difference between both groups (33.3% vs. 20%, p = 0.243). Few side effects were developed as a result of using GIK infusion protocol. CONCLUSIONS: GIK may help in improving hemodynamics and weaning of vasopressors in patients with refractory septic shock and those with septic induced cardiomyopathy. The use of GIK was well tolerated with minimal adverse reactions.

The impact of lactate clearance on outcomes according to infection sites in patients with sepsis: a retrospective observational study

Whether lactate clearance (LC) influences outcomes differently depending on the infection site in sepsis cases is not fully elucidated. Herein, we analyzed LC’s clinical utility as a predictor of patient outcomes according to infection site. This retrospective study, conducted at two tertiary emergency critical care medical centers in Japan, included patients with sepsis or septic shock. The associations between infection site (lungs vs. other organs) and in-hospital mortality and ventilator-free days (VFDs) were evaluated using univariable and multivariate analyses. We assessed LC’s ability to predict in-hospital mortality using the area under the receiver operating characteristic curve. Among 369 patients with sepsis, infection sites were as follows: lungs, 186 (50.4%); urinary tract, 45 (12.2%); abdomen, 102 (27.6%); and other, 36 (9.8%). Patients were divided into a pneumonia group or non-pneumonia group depending on their infection site. The pneumonia group displayed a higher in-hospital mortality than the non-pneumonia group (24.2% vs. 15.8%, p = 0.051). In the multivariate analysis, lower LC was associated with higher in-hospital mortality [adjusted odds ratio (AOR), 0.97; 95% confidence interval (CI) 0.96–0.98; p < 0.001] and fewer VFD [adjusted difference p value (AD), − 1.23; 95% CI − 2.42 to − 0.09; p = 0.025] in the non-pneumonia group. Conversely, LC did not affect in-hospital mortality (AOR 0.99; 95% CI 0.99–1.00; p = 0.134) and VFD (AD − 0.08; 95% CI − 2.06 to 1.91; p = 0.854) in the pneumonia group. Given the differences in the impact of LC on outcomes between the pneumonia and non-pneumonia groups, this study suggests that optimal treatment strategies might improve outcomes. Further studies are warranted to validate our results and develop optimal therapeutic strategies for sepsis patients.

Abstract 10522: Early Lactate Clearance is Associated With Survival in a National Cohort of Refractory Out-of-Hospital Cardiac Arrest Patients Managed With Extracorporeal Cardiopulmonary Resuscitation

Introduction: In refractory out-of-hospital cardiac arrest (OHCA), prolonged whole-body ischemia with global tissue injury proceeds even after achievement of reperfusion with extracorporeal cardiopulmonary resuscitation (eCPR). Hypothesis: Biomarkers reflecting ischemia and inflammation may be used for prognostication of refractory OHCA managed with eCPR. Methods: This nationwide retrospective study included patients (≥18 years) with refractory OHCA managed with eCPR in Denmark (2011 to 2020). Biomarker levels at admission, at 24 hours (lactate, leukocytes, and platelets), and repeated measures of lactate after eCPR initiation were analyzed. Lactate clearance was calculated as (admission lactate - post eCPR lactate) / admission lactate x100%. Results: Two hundred eighteen patients (80% male; age 52±12yrs) were included. Primary cause of OHCA was acute myocardial infarction (63%), 69% had shockable primary rhythm and 86% witnessed OHCA with a median low-flow time of 105 minutes (Q1-Q3: 86-124 min.). Fifty-three (24%) survived to hospital discharge. Survivors had a significantly lower lactate level at admission (13.1 vs. 15.4 mmol/l, p=0.004) and after 24 hours (2.8 vs. 5.0, p=0.001), and a significantly higher admission platelet level (181 vs. 153 x10 9 /l, p=0.03). No difference in admission levels of leukocytes nor leukocytes and platelets after 24 hours were found between survivors and non-survivors. Lactate clearance was available for 68% and 79% of patients alive after 8 and 24 hours, respectively. All survivors had a lactate level less than admission lactate at 8 hours (lactate clearance >0%) and had cleared >25% of admission lactate at 24 hours after eCPR initiation. There was a significant difference in survival between quartiles of lactate clearance at 8 hours after eCPR initiation (Figure 1). Conclusion: In conclusion, early lactate clearance after eCPR initiation was associated with survival to discharge in refractory OHCA-patients.