Lactate Clearance Research Articles

Effect of Continuous Infusion Therapy With Low-dose Terlipressin Combined With Norepinephrine on Hemodynamics, Inflammatory Markers, and Prognosis in Patients With Severe Septic Shock.

The present study investigated the impact of continuous infusion therapy with low-dose terlipressin (TP) combined with norepinephrine on hemodynamics, inflammatory markers, and prognosis in patients with severe septic shock. Seventy-four patients with severe septic shock were randomly assigned to either a control group (n = 37) or an observation group (n = 37). Patients in the control group received norepinephrine alone, while those in the observation group received a continuous infusion of low-dose TP in addition to norepinephrine. To assess the effect of treatment, a set of clinical parameters was evaluated in both groups before and after treatment. These parameters included hemodynamic indicators (heart rate [HR], mean arterial pressure [MAP], central venous pressure [CVP], cardiac index [CI], and systemic vascular resistance index [SVRI]), levels of serum inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitivity C-reactive protein [hs-CRP]), renal function indicators (blood urea nitrogen [BUN], serum creatinine [SCr], and cystatin C [Cys-C]), serum procalcitonin (PCT), and lactate, as well as lactate clearance rate (LCR). Additionally, the acute physiology and chronic health evaluation II (APACHE II) score, 28-day mortality rate, multiple organ dysfunction syndrome (MODS) incidence rate, and adverse reaction incidence were also determined. Compared to baseline values, MAP, CVP, CI, SVRI, and LCR increased in both groups after treatment, while HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate all decreased. Additionally, APACHE II scores also decreased. Furthermore, the observation group exhibited higher MAP, CVP, CI, SVRI, and LCR, along with lower HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate than the control group after treatment. The observation group also had lower APACHE II score, 28-day mortality rate, MODS incidence rate, and adverse reaction incidence than the control group after treatment (P < .05). Continuous infusion therapy with low-dose TP combined with norepinephrine was effective in treating patients with severe septic shock, improving hemodynamic parameters, reducing the levels of inflammatory markers, promoting renal function recovery, and reducing the mortality rate.

Serum Lactate Clearance as a Predictive Biomarker for Optimal Graft Perfusion in Living Donor Liver Transplantation

BackgroundThe optimal balance between the graft volume (GV) and portal venous flow (PVF) in living donor liver transplantation (LDLT) is unclear. As lactate is mainly metabolized in the liver, perioperative lactate levels are reportedly a useful biomarker for early graft dysfunction (EGD). The present study analyzed perioperative lactate levels according to the PVF. MethodsThe PVF/GV (mL/min per 100 g GV) of 97 recipients from 1996 to 2022 was retrospectively classified as low (LPVF; PVF/GV ≤ 100, N = 29), moderate (MPVF; PVF/GV 100–250, N = 40), or high (HPVF; PVF/GV > 250, N = 28). Lactate levels were obtained preoperatively (L0), immediately after graft reperfusion (L1), 4 h after reperfusion (L2), and on postoperative day 3 (L3). The lactate clearances were then calculated. ResultsThe lower the PVF/GV ratio, the younger the age at LDLT and the higher the graft-to-recipient weight ratio. The median L2 and L3 in the HPVF group were significantly higher than those in the other groups (p = 0.019 and p = 0.003, respectively). The median ΔL1 in the HPVF group was lower than that in the LPVF and MPVF groups (0.23 vs. 0.50, p < 0.0001 and 0.23 vs. 0.41, p = 0.011, respectively). ΔL1 was negatively correlated with the PVF/GV. Although no patient had EGD, three patients with HPVF with low ΔL1 developed small-for-size syndrome. ConclusionsGraft hyperperfusion may delay the recovery of the graft function and result in poor lactate clearance. The combination of the PVF/GV and lactate clearance may be useful as a prognostic marker for optimal graft perfusion in LDLT. Level of evidenceIV.

Comparison of clinical features of septic shock in children with hematological malignancies versus children without malignant tumors

Objective: To investigate the clinical features of septic shock in children with hematological malignancies compared with those without malignant tumor in the pediatric intensive care unit (PICU). Methods: This retrospective study enrolled children with septic shock at the PICU of Capital Institute of Pediatrics' Children's Hospital from June 2015 to July 2022. According to the presence of hematological malignancies, patients were divided into the hematological malignancies group and without malignant tumor group. Clinical data were compared between the two groups, and logistic regression analysis was used to identify related factors for mortality. Results: A total of 164 children (97 males and 67 females) with a median age of 3.6 (interquartile range 0.8, 7.8) years were enrolled, including 75 (45.7%) patients with hematological malignancies and 89 (54.3%) patients without malignant tumors. Patients in the hematological malignancies group were older [6.0(3.6, 9.4) years vs 1.2 (0.4, 4.3) years, P<0.001] and more experienced hospital-acquired infections [48.0%(36/75) vs 21.3%(19/89),P=0.001], compared with patients without malignant tumors. Surgical emergencies were more frequent in patients without malignant tumors (32.6% vs 14.7%, P=0.013). Patients with hematological malignancies mainly had blood stream infections (58.7%), with Gram-negative bacilli (46.7%), meanwhile, patients without malignant tumors more experienced Gram-positive cocci infections (22.5%) of the respiratory system (40.4%) or digestive system (28.1%). There were significant differences regarding the infection sites (P<0.001) and pathogens (P=0.001). The types of antibacterial agents (P<0.001) and the frequency of noradrenaline (P=0.013) used in patients with hematological malignancies were significantly higher than those without malignant tumors. Patients with hematological malignancies had a higher incidence of multiple organ dysfunction (MODS) [100.0%(75/75) vs 80.9%(72/89), P<0.001] and higher 28-day mortality [34.8%(23/66) vs 19.0%(15/79),P=0.048]. Multivariate logistic regression analysis showed that Pediatric Critical Illness Score (PCIS) was an independent factor for death (odds ratio, OR=1.387, 95%CI: 1.161-1.657, P<0.001) in patients with hematological malignancies, and PCIS (OR=1.419, 95%CI: 1.140-1.767, P=0.002) and the 6-hour lactate clearance rate (OR=65.857, 95%CI: 2.953-1 468.638, P=0.008) were independent factors for death in patients without malignant tumors. Conclusions: Children with hematological malignancies were older, more frequently experienced bloodstream infections, and had a higher incidence of MODS and higher 28-day mortality. PCIS is related to poor prognosis of septic shock in children.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation

PurposeIn an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications.MethodsaNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range.ResultsThe liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301–451) µg/kg/h versus those who did not 105 (70–158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = − 0.755) and aspartate transaminase (AST; R = − 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346–453) µg/kg/h) from those who were discarded (155 (87–206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels.ConclusionsThis study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients.

Effects of Chlorich®EnergyBoost on Enhancing Physical Performance and Anti-Fatigue Properties in Mice.

Chlorich®EnergyBoost, a water extract obtained from Chlorella sorokiniana, has been proposed to enhance physical performance and provide anti-fatigue effects. This study assessed the impact of Chlorich®EnergyBoost supplementation on physical performance and its anti-fatigue properties. Twenty-four mice were allocated into four groups: (1) the control group receiving only water,;(2) the 1X group (49.2 mg/kg/day); (3) the 2X group (98.4 g/kg/day); and (4) the 5X group (246 g/kg/day). All groups were orally administered the supplements for four consecutive weeks. The evaluation included grip strength, swimming endurance, an exhaustion test, and serum biochemistry analysis. Additionally, the study examined the bioactive peptides through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and conducted bacterial reverse mutation and acute oral toxicity tests for safety assessment. The findings indicated that Chlorich®EnergyBoost supplementation led to a significant reduction in serum lactate levels by 14.08% to 22.54% and blood urea nitrogen levels by 12.23% to 16.76%, an increase in the lactate clearance rate by 0.28 to 0.35, an enhancement of muscle glycogen storage by 1.10 to 1.44-fold, and hepatic glycogen storage by 1.41 to 1.47-fold. These results demonstrated dose-dependent effects. MALDI-TOF analysis revealed the expression of dihydrolipoamide dehydrogenase and superoxide dismutase. Both the bacterial reverse mutation and acute oral toxicity tests showed no adverse effects.

Clinical characteristics of extracorporeal cardiopulmonary resuscitation in China: a multicenter retrospective study

PurposeExtracorporeal cardiopulmonary resuscitation (ECPR) might markedly increase the survival of selected patients with refractory cardiac arrest. But the application situation and indications remained unclear.Materials and methodsWe respectively reviwed all adult patients who underwent ECPR from January 2017 to March 2021. Patient characteristics, initiation and management of ECMO, complications, and outcomes were collected and compared between the survivors and nonsurvivors. LASSO regression was used to screen risk factors. Multivariate logistic regression was performed with several parameters screened by LASSO regression.ResultsData were reported from 42 ECMO centers covering 19 provinces of China. A total of 648 patients were included in the study, including 491 (75.8%) males. There were 11 ECPR centers in 2017, and the number increased to 42 in 2020. The number of patients received ECPR increased from 33 in 2017 to 274 in 2020, and the survival rate increased from 24.2% to 33.6%. Neurological complications, renal replacement therapy, epinephrine dosage after ECMO, recovery of spontaneous circulation before ECMO, lactate clearance and shockable rhythm were risk factors independently associated with outcomes of whole process. Sex, recovery of spontaneous circulation before ECMO, lactate, shockable rhythm and causes of arrest were pre-ECMO risk factors independently affecting outcomes.ConclusionsFrom January 2017 to March 2021, the numbers of ECPR centers and cases in mainland China increased gradually over time, as well as the survival rate. Pre-ECMO risk factors, especially recovery of spontaneous circulation before ECMO, shockable rhythm and lactate, are as important as post-ECMO management,. Neurological complications are vital risk factors after ECMO that deserved close attention.Trial registrationNCT04158479, registered on 2019/11/08. https://clinicaltrials.gov/NCT04158479

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.

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.

Associations of serum lactate and lactate clearance with delirium in the early stage of ICU: a retrospective cohort study of the MIMIC-IV database.

This study aimed to investigate the associations of serum lactate level [within and after 24 h of the intensive care unit (ICU) admission] and lactate clearance rate with delirium and assess associations of lactate and lactate clearance rate with 30-day mortality in delirium patients. Data in this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database in 2012-2019. The associations of lactate and lactate clearance rate with delirium were explored through univariable and multivariable logistic regression analyses, whereas the associations of lactate and lactate clearance rate with 30-day mortality in delirium patients were investigated using univariable and multivariable Cox regression analyses. Subgroup analysis was performed for age, gender, sepsis, hypertension, sedative drug, ventilation, antibiotic drug, vasopressors, and the Sequential Organ Failure Assessment (SOFA) score. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). Among 7,812 (14.58%) eligible participants, 4,338 (8.19%) had delirium and 1,903 (24.36%) died within 30 days. After adjusting for covariates, patients with lactic acidosis (lactate level > 5 mmol/L and PH < 7.35) at T0 (within 24 h of the ICU admission) had higher odds of delirium (OR = 1.235, 95%CI: 1.105-1.382). Hyperlactatemia (lactate level 2-5 mmol/L and PH > 7.35) at T1 (after 24 h of the ICU admission) was also associated with higher odds of delirium (OR = 1.277, 95%CI: 1.126-1.447). Lactate clearance rate > 50% was linked to lower odds of delirium (OR = 0.705, 95%CI: 0.613-0.811), and this relationship was also observed in ≥65 years old, female, male, non-sepsis, sepsis, non-hypertension, non-sedative drug use, sedative drug use, ventilation, antibiotic drug use, use of vasopressors, and different SOFA score subgroups (all p < 0.05). Additionally, hyperlactatemia and lactic acidosis (whether at T0 or T1) may be potential risk factors for 30-day mortality in delirium patients, whereas lactate clearance rate ≥ 0 had a potential protective effect on 30-day mortality (all p < 0.05). Higher serum lactate levels in the early stage of the ICU were associated with a higher risk of delirium and subsequent mortality. Measures taken to increase the lactate clearance rate are necessary to reduce potential delirium or mortality risk in clinical settings. However, more evidence from prospective studies is needed to verify these findings.

Unveiling the Deadly Dance of Hypocalcemia and Lactic Acidosis in a 59-Year-Old Woman with B-Cell Lymphoma.

Lactic acidosis in B-cell lymphoma can be multifactorial. Contributing factors include inability of liver lactate clearance, tumor cell metabolism or impaired oxygenation.Patients with B-cell lymphoma may have hypocalcemia secondary to tumor lysis syndrome, paraneoplastic syndrome, or secondary to treatment.These reversible causes should always be considered in cardiac arrest in cancer patients.

Exploring the Influence of Acid-Base Status on Athletic Performance during Simulated Three-Day 400 m Race.

This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups-one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)-performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes' ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.

4-week stretching program after submaximal strength exercise affects performance but not heart rate variability and lactate clearance. An exploratory study.

Previous research has demonstrated that stretching can enhance athletic performance and induce cardiovascular adaptations. This study aims to assess whether a 4-week preventative stretching routine can enhance heart rate variability and heart rate recovery, faster blood lactate clearance, and improve performance following submaximal strength exercises. Twenty-four healthy adults were recruited and randomly allocated to either the experimental group or the control group. Both groups engaged in submaximal strength exercises (5 sets to voluntary failure at 60% of 1RM) comprising bench press and back squat exercises under baseline conditions and after stretching protocol. The experimental group followed the Stretching Protocol, while the control group adhered to their regular training routine. ANOVA analysis revealed a significant pre-post interaction effect between groups in the variable of squat repetitions, although no notable pre- or post-differences were observed in heart rate variability, heart rate recovery, blood lactate concentration, or bench repetitions in either group. A 4-week preventative stretching program does not appear adequate to enhance lactate clearance and cardiovascular adaptation after submaximal strength exercises in resistance-trained individuals compared to the control group. However, it is plausible that such a stretching routine may mitigate muscle fatigue, though further investigation is warranted to substantiate this hypothesis.

Defatting of donor transplant livers during normothermic perfusion—a randomised clinical trial: study protocol for the DeFat study

BackgroundLiver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes.MethodsIn the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months).DiscussionThis study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths.Trial registrationISRCTN ISRCTN14957538. Registered in October 2022.

Enhancing SAPS-3 Predictive Accuracy with Initial, Peak, and Last Lactate Measurements in Septic Shock.

Background/Objectives: Septic shock is a severe condition with high mortality necessitating precise prognostic tools for improved patient outcomes. This study aimed to evaluate the collective predictive value of the Simplified Acute Physiology Score 3 (SAPS-3) and lactate measurements (initial, peak, last, and clearance rates within the first 24 h) in patients with septic shock. Specifically, it sought to determine how these markers enhance predictive accuracy for 28-day mortality beyond SAPS-3 alone. Methods: This retrospective cohort study analyzed data from 66 septic shock patients at two ICUs of Vienna General Hospital (2017-2019). SAPS-3 and lactate levels (initial, peak, last measurement within 24 h, and 24 h clearance) were obtained from electronic health records. Logistic regression models were constructed to identify predictors of 28-day mortality, and receiver operating characteristic (ROC) curves assessed predictive accuracy. Results: Among 66 patients, 36 (55%) died within 28 days. SAPS-3 scores significantly differed between survivors and non-survivors (76 vs. 85 points; p = 0.016). First, last, and peak lactate were significantly higher in non-survivors compared to survivors (all p < 0.001). The combination of SAPS-3 and first lactate produced the highest predictive accuracy (AUC = 80.6%). However, 24 h lactate clearance was not predictive of mortality. Conclusions: Integrating SAPS-3 with lactate measurements, particularly first lactate, improves predictive accuracy for 28-day mortality in septic shock patients. First lactate serves as an early, robust prognostic marker, providing crucial information for clinical decision-making and care prioritization. Further large-scale studies are needed to refine these predictive tools and validate their efficacy in guiding treatment strategies.

Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Lactate clearance as a predictor of 24-hour mortality in sepsis patients

Lactate clearance as a predictor of 24-hour mortality in sepsis patients

4-h mean lactate clearance as a good predictor of adverse outcome in acute cardiogenic pulmonary edema: a pilot study

Abstract Objectives This pilot study aimed to evaluate the efficacy of the 4-h mean lactate clearance (LACclr) level as a predictive factor for in-hospital outcomes, 30-day mortality, and treatment success in patients with acute cardiogenic pulmonary edema (ACPE), a significant clinical form of acute heart failure (AHF). Methods A total of 44 patients diagnosed with acute pulmonary edema were included in the study. The patients were divided into two groups based on lactate levels and negative outcomes, and lactate and LACclr levels and negative outcomes were analyzed using statistical tests such as Fisher’s exact test, Student’s t-test, Mann-Whitney U test, and Receiver operating characteristic (ROC) analysis. Results The results indicated a statistically significant difference in the total hospitalization length of stay according to whether the patients had a negative outcome (intubation and in-hospital mortality) (p=0.033). Additionally, the area under the curve (AUC) value for 4-h mean LACclr was 0.795 in all patients, which was statistically significant in predicting 30-day mortality (p=0.033). The optimal cut-off value for the 4-h mean LACclr in predicting 30-day mortality was found to be 5.57 %, with 80 % sensitivity and 66.7 % specificity. The threshold to rule out 30-day mortality for all patients was 18.85 with 100 % sensitivity and 30.2 % specificity (AUC, 0.795 95 % CI [0.546–1.000], p=0.033). Conclusions These findings suggest that the 4-h LACclr level, calculated within 4 h of emergency department (ED) presentation, can be used as a predictive indicator for needing intubation, in-hospital mortality, and 30-day mortality and to identify patients at higher risk for adverse outcomes.

Lactate Profile Assessment-A Good Predictor of Prognosis in Patients with COVID-19 and Septic Shock Requiring Continuous Renal Therapy.

Lactate is a useful prognostic marker, as its level increases in hypoxic tissue and/or during accelerated aerobic glycolysis due to excessive beta-adrenergic stimulation and decreased lactate clearance. The Surviving Sepsis Campaign Bundle 2018 Update suggests premeasurement of lactate within 2-4 h so that physicians perform, assist, administer, and introduce lactate-guided resuscitation to reduce mortality due to sepsis. A total of 108 patients with septic shock who underwent continuous renal replacement therapy (CRRT) for acute kidney injury were enrolled in this observational study. Demographic, clinical, and laboratory data were collected, and patients were divided into two groups: survivors and non-survivors. Multivariate analysis demonstrated that lactate levels at 24 h after initiation of CRRT treatment, but not lactate levels at intensive care unit (ICU) admission, were associated with mortality. Lactate clearance was associated with lower mortality among the survivors (OR = 0.140) at 6 h after ICU admission and late mortality (OR = 0.260) after 24 h. The area under the ROC curves for mortality was 0.682 for initial lactate; 0.797 for lactate at 24 h; and 0.816 for lactate clearance at 24 h. Our result reinforces that the determination of lactate dynamics represents a good predictor for mortality, and serial lactate measurements may be more useful prognostic markers than initial lactate in patients with septic shock.

Role of lactate and lactate metabolism in liver diseases (Review).

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study

BackgroundSepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock.MethodsThe current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome.ResultsA total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan–Meier survival curve analysis.ConclusionsThis study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.