Prognostic value of hyperlactatemia and lactate clearance in septic patients with hematological malignancies.

BACKGROUND: The coexistence of sepsis and hematological malignancies increases patient vulnerability, revealing the need for precise prognostic markers. This study explores the prognostic significance of lactate levels and clearance in septic patients with hematological malignancies. MATERIALS AND METHODS: A retrospective cohort study from January 2016 to December 2019 in a tertiary hematological intensive care unit (ICU) included 167 adults with hematological malignancies and sepsis. The relationship between lactate levels, hyperlactatemia, lactate clearance, and ICU outcomes was investigated. ICU survivors and non-survivors were compared to identify the factors affecting ICU mortality. RESULTS: Patients were primarily with lymphoma and acute leukemia (66%) and had frequent hyperlactatemia (64%) on ICU admission. ICU non-survivors demonstrated higher lactate levels and hyperlactatemia frequency at various time points (0, 6, and 12 h) than survivors. Lactate clearance and liver function tests did not differ significantly between the two groups. Invasive mechanical ventilation [OR (95% confidence interval-CI): 20.4 (2.4-79.8), p < 0.01], requirement of vasopressors [OR (95% CI): 5.6 (1.3-24.5), p < 0.01], lactate level at the 6th hour [OR (95% CI): 1.51 (1.1-2.07), p = 0.01], and APACHE II score (OR (95% CI): 1.16 (1.01-1.34), p = 0.05) were independent risk factors for ICU mortality. The Area Under the Curve for APACHE II score and lactate level at the 6th hour were 0.774 (95% CI: 0.682-0.866) and 0.703 (95% CI: 0.602-0.804), respectively. CONCLUSION: While elevated lactate levels correlate with mortality rate and lactate level at the 6th hour is an independent risk factor for mortality, the absence of a significant difference in lactate clearance challenges traditional assumptions. These results question the commonly accepted perspective regarding lactate dynamics in sepsis among individuals with hematological malignancies. ORAL PRESENTATION: Inci K, et al. "Hyperlactatemia, lactate clearance and outcome in critically ill patients with hematological malignancies," 22nd international intensive care symposium, 2019.

Prognostic Significance of Lactate Clearance in Cardiogenic Pulmonary Edema in the Emergency Department.

Background and Objectives: Acute cardiorespiratory failure disrupts the delicate balance of energy supply, demand, and consumption, with elevated lactate levels and decreased blood pH serving as crucial indicators. Acute cardiogenic pulmonary edema (ACPO), a common cause of acute respiratory failure, poses a substantial mortality risk. Lactate, a byproduct of pyruvate reduction, is a pertinent marker in perfusion assessment. Lactate clearance (LC) has proven prognostic efficacy in various conditions but lacks consensus on its predictive power in acute cardiogenic pulmonary edema. Materials and Methods: This prospective observational study, conducted in a metropolitan area's third-level emergency department, involved patients with cardiogenic pulmonary edema from May 2021 to August 2023. The inclusion criteria specified acute cardiogenic pulmonary edema, excluding patients with incomplete data or other respiratory conditions. Lactate clearance, calculated at presentation and after 6 h, served as the primary outcome predictor. Our data analysis employed logistic regression, the ROC curve, and statistical tests. Results: The cohort of 106 patients revealed that a lactate clearance below 14.29% was significantly associated with mortality. While 51.6% of survivors were discharged, LC's predictive success for discharge was inconclusive. Logistic regression underscored the significance of lactate clearance, with a one-unit increase yielding a 5.55-fold probability of survival. The AUC for LC was 0.759. Conclusions: This study pioneers the exploration of lactate clearance in patients with acute cardiogenic pulmonary edema. LC below 14.29% signifies a poor prognosis, emphasizing its potential as an early treatment initiation marker. While acknowledging this study's limitations, we advocate for further multicenter research to refine the understanding of lactate clearance in this context.

Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility?

How to cite this article: Angadi VM, Jindal A. Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility? Indian J Crit Care Med 2024;28(1):89.

Author Response.

How to cite this article: Rajbanshi LK, Arjyal B. Author Response. Indian J Crit Care Med 2024;28(1):90-91.

Viability assessment of livers donated after circulatory determination of death during normothermic regional perfusion.

BACKGROUND: Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP. METHODS: To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. RESULTS: Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2 ) and VO2 . Lactate clearance was correlated to transaminase levels and DO2 -normalized lactate clearance was the parameter best discriminating between study groups. CONCLUSIONS: DO2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP.

Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study.

BACKGROUND: High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia. METHODS: This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline. RESULTS: The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 - 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 - 20.2] vs. 8.8% [IQR: 2.9 - 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 - 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02). CONCLUSIONS: In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.

The role of cardiac power and lactate clearance as an indicator of resuscitation success among pediatric patients with shock in the intensive care unit of Cipto Mangunkusumo Hospital.

BACKGROUND: Shock in children remains the primary cause of mortality and morbidity worldwide. Furthermore, its management outcome is improved using many hemodynamic parameters, such as cardiac power (CP) and lactate clearance (LC). Cardiac power is a contractility index based on the measurement of flow and pressure, and it is a relatively new hemodynamic parameter with limited studies. In contrast, LC has been proven useful as a target outcome in shock resuscitation. This study aims to explore the values of CP and LC in pediatric shock and their association with clinical outcomes. METHODS: This prospective observational study was conducted on children (1 month-18 years old) with shock at Cipto Mangunkusumo Hospital, Indonesia, from April to October 2021. We measured CP using ultrasonic cardiac output monitoring (USCOM®) and serum lactate levels at 0, 1, 6, and 24 h post-initial resuscitation. Subsequently, the variables were described and analyzed with the resuscitation success, length of stay, and mortality. RESULTS: A total of 44 children were analyzed. There were 27 (61.4%), 7 (15.9%), 4 (9.1%), 4 (9.1%), and 2 (4.5%) cases of septic, hypovolemic, cardiogenic, distributive, and obstructive shock, respectively. Within the first 24 h post-initial resuscitation, CP and LC had an increasing trend. Compared to children who had successful resuscitation, those who did not have successful resuscitation had similar CP at all time points (p > 0.05) and lower LC at 1 and 24 h post-initial resuscitation (p < 0.05). Lactate clearance was an acceptable predictor of resuscitation success (area under the curve: 0.795 [95% CI: 0.660-0.931]). An LC of 7.5% had a sensitivity, specificity, positive predictive value, and negative predictive value of 75.00%, 87.5%, 96.43%, and 43.75%, respectively. Lactate clearance in the first hour post-initial resuscitation had a weak correlation (r=-0.362, p < 0.05) with hospital length of stay. We found no difference in CP and LC among survivors compared to nonsurvivors. CONCLUSIONS: We found no evidence that CP was associated with resuscitation success, length of stay, or mortality. Meanwhile, higher LC was associated with successful resuscitation and shorter length of stay at the hospital, but not mortality.

Exercise and emersion in air, and recovery in seawater in the green crab (Carcinus maenas): metabolic, acid-base, cardio-ventilatory and ionoregulatory responses.

In nature, the green crab exhibits emersion and terrestrial activity at low tide. Treadmill exercise in air (20-23°C) of crabs acclimated to 32 ppt seawater (13°C) revealed an inverse relationship between velocity and duration: 2.0 body lengths (BL) s-1 was sustainable for several minutes, and 0.25 BL s-1 was sustainable for long periods. Fatigue was not due to dehydration. Physiological responses over an 18 h recovery in seawater after near-exhaustive exercise (0.25 BL s-1, 1 h) in air were compared with responses after quiet emersion (1 h) in air. Exercising crabs exhibited transient scaphognathite slowing and progressive increases in heart rate, whereas emersed crabs exhibited persistent inhibition of ventilation and transient heart slowing. Upon return to seawater, all these rates increased above both control and treatment levels. Post-exercise disturbances were more marked and/or longer lasting (e.g. EPOC, hyperventilation, tachycardia, metabolic acidosis, lactate elevation, ionic disturbances) than those after simple air exposure. However, an increase in net acidic equivalent excretion to the environment occurred after emersion but not after exercise. Instead, post-exercise crabs relied on carapace buffering, signalled by elevated haemolymph Ca2+ and Mg2+. Prolonged lowering of haemolymph PCO2 associated with hyperventilation also played a key role in acid-base recovery. EPOC after exercise was 3-fold greater than after emersion, sufficient to support resting MO2 for >14 h. This reflected clearance of a large lactate load, likely by glycogen re-synthesis rather than oxidation. We conclude that the amphibious green crab uses a combination of aquatic and terrestrial strategies to support exercise in air, emersion in air and recovery in seawater.

Establishment of MELD-lactate clearance scoring system in predicting death risk of critically ill cirrhotic patients.

BACKGROUND: To develop a scoring system related to the lactate clearance (ΔLA) to predict the mortality risk (MELD-ΔLA) for critically ill cirrhotic patients. METHODS: In this retrospective cohort study, 881 critically ill cirrhotic patients from the Medical Information Mart for Intensive Care (MIMIC-III) database were included eventually. The outcomes of our study were defined as ICU death, 28-day, 90-day and 1-year mortality. Predictors were identified by multivariate Cox analysis to develop the predictive scoring system. The C-index and area under the curve (AUC) of receiver operator characteristic curve (ROC) were used to identify the predicting performance of the MELD-ΔLA, sequential organ failure assessment (SOFA), chronic liver failure-sequential organ failure assessment (CLIF-SOFA), the model for end-stage liver disease (MELD), Child-Pugh, chronic liver failure consortium acute-on-chronic liver failure (CLIF-C ACLF), chronic liver failure consortium-acute decompensation (CLIF-C AD) and MELD-Na scoring systems. Additionally, subgroup analysis was also performed based on whether critically ill cirrhotic patients underwent liver transplantation. RESULTS: Creatinine, bilirubin, international normalized ratio (INR), lactate first, ΔLA and vasopressors were closely associated with ICU death of liver critically ill cirrhotic patients. The C-index of the MELD-ΔLA in ICU death was 0.768 (95% CI 0.736-0.799) and the AUC for the MELD-ΔLA scoring system in predicting 28-day, 90-day, and 1-year mortality were 0.774 (95% CI 0.743-0.804), 0.765 (95% CI 0.735-0.796), and 0.757 (95% CI 0.726-0.788), suggested that MELD-ΔLA scoring system has a good predictive value than SOFA, CLIF-SOFA, MELD, Child-Pugh, CLIF-C ACLF, CLIF-C AD) and MELD-Na scoring systems. Additionally, the study also confirmed the good predictive value of MELD-ΔLA scoring system for critically ill cirrhotic patients regardless of undergoing liver transplantation. CONCLUSION: The developed MELD-ΔLA score is a simple scoring system in predicting the risk of ICU death, 28-day, 90-day and 1-year mortality for critically ill cirrhotic patients, which may have a good predictive performance.

The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically Ill patients: a retrospective cohort study.

BACKGROUND: The mortality rate is high in critically ill patients due to the difficulty of diagnosis and treatment. Thus, it is very important to explore the predictive value of different indicators related to prognosis in critically ill patients. METHODS: This was a retrospective cohort study of patients in the intensive care unit (ICU) of the Sixth People's Hospital in Shanghai, China. A total of 1465 ICU patients had lactate values > 2.1 mmol/L at least once within 24 h of ICU admission, and arterial blood gas was monitored more than twice during the ICU stay. RESULTS: The predictive value of lactate clearance at 24 h was not high, and the sensitivity and specificity were lower. The predictive value of the lactate level at baseline and the APACHE II score was higher than that of lactate clearance at 24 h in critically ill patients. The predictive value of the lactate level at baseline combined with the APACHE II score was higher than that of the lactate level at baseline or the APACHE II score alone. In addition, the predictive value of lactate clearance at 24 h combined with the APACHE II score was also significantly higher than that of lactate clearance at 24 h or the APACHE II score alone. In particular, the area under the ROC curve reached 0.900, the predictive value was markedly higher than that of the ROC alone, and the sensitivity and specificity were better when these three indicators were combined. CONCLUSIONS: The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically ill patients.

Could lactate clearance be a marker of mortality in pediatric intensive care unit?

BACKGROUND: Hyperlactatemia is a common finding in critically ill patients and has significant prognostic implications. However, a single lactate measurement has not been correlated to mortality consistently. In this study, we aimed to correlate the clinical efficacy of lactate clearance for the prediction of mortality in pediatric intensive care unit patients. METHODS: This retrospective observational study was performed in the pediatric intensive care unit in patients with lactate level >3 mmol/lt. Initial, 6th h, and 24th h lactate levels were recorded and lactate clearance was calculated using these values (lactate level at admission - level 6 h later × 100/lactate level at admission). RESULTS: A total of 172 patients were included in the study. Forty-four out of 172 patients died. Median (IQR) lactate (mmol/L) at admission was low in those who survived in comparison to nonsurvivors 4.4 (3.1) vs. 5.75 (7.7) (p = 0.002). Clearance at 6th h was significantly lower in those who died (11.7%) than those who survived (36.7) (p = 0.001). 6th h lactate clearance level <20.7% predicted mortality with a sensitivity of 63.6% and specificity of 69.5% along with a positive predictive value of 41.8 and a negative predictive value of 84.8 (p = 0.004). Both lactate levels and lactate clearance values were significantly predictive factors for mortality (p < 0.05). Only a positive moderate correlation was found between the percentage of PRISM-IV % and 6th h lactate level. DISCUSSION: The present study revealed that lactate clearance is a simple and rapid risk-stratification tool holding to be a potential biomarker of managing the treatment efficacy of children in the pediatric intensive care unit.

Study of Significance of Serum Lactate Kinetics in Sepsis as Mortality Predictor.

Introduction: Sepsis is one of the leading causes of death worldwide. Serum lactate is being used in sepsis for diagnostic and prognostic purposes for years now. In this study, we shed light over a novel use of lactate in form of various clearance parameters to determine mortality in septic patients at the 28th day. Materials and methods: In our study, 200 patients with sepsis were included using quick sequential organ failure assessment (qSOFA) score and their lactate levels were measured at the time of admission (0 hour) and 24 hours after admission. Lactate clearance parameters (absolute and relative lactate clearance, lactate clearance rate) were calculated. All patients were followed up for a period of 28 days to determine the outcome, and data analysis was done accordingly. Results and conclusion: Our study showed that higher SOFA score, qSOFA score, and serum lactate levels were associated with increased 28th-day mortality. Low absolute, relative lactate clearance and lactate clearance rate were also associated with poor outcomes. The best cutoffs to predict poor outcomes were serum lactate level at 24 hours ≥4 mmol/L and relative lactate clearance ≤40.3% with good sensitivity and specificity. How to cite this article: Chaudhari M, Agarwal N. Study of Significance of Serum Lactate Kinetics in Sepsis as Mortality Predictor. Indian J Crit Care Med 2022;26(5):591-595.

The anaerobic threshold: 50+ years of controversy.

The anaerobic threshold (AT) remains a widely recognized, and contentious, concept in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT coalesced the increase of blood lactate concentration ([La- ]), during a progressive exercise test, with an excess pulmonary carbon dioxide output ( V̇CO2 ). Its principal tenets were: limiting oxygen (O2 ) delivery to exercising muscle→increased glycolysis, La- and H+ production→decreased muscle and blood pH→with increased H+ buffered by blood [HCO3- ]→increased CO2 release from blood→increased V̇CO2 and pulmonary ventilation. This schema stimulated scientific scrutiny which challenged the fundamental premise that muscle anoxia was requisite for increased muscle and blood [La- ]. It is now recognized that insufficient O2 is not the primary basis for lactataemia. Increased production and utilization of La- represent the response to increased glycolytic flux elicited by increasing work rate, and determine the oxygen uptake ( V̇O2 ) at which La- accumulates in the arterial blood (the lactate threshold; LT). However, the threshold for a sustained non-oxidative contribution to exercise energetics is the critical power, which occurs at a metabolic rate often far above the LT and separates heavy from very heavy/severe-intensity exercise. Lactate is now appreciated as a crucial energy source, major gluconeogenic precursor and signalling molecule but there is no ipso facto evidence for muscle dysoxia or anoxia. Non-invasive estimation of LT using the gas exchange threshold (non-linear increase of V̇CO2 versus V̇O2 ) remains important in exercise training and in the clinic, but its conceptual basis should now be understood in light of lactate shuttle biology.

Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance.

BACKGROUND & AIMS: Lactate has recently been reported to accumulate in the livers of patients progressing from simple steatosis to non-alcoholic steatohepatitis (NASH). However, the underlying mechanism(s) of lactate accumulation and the role of lactate in the progression of non-alcoholic fatty liver disease (NAFLD) are essentially unknown. METHODS: We compared the acetylome in liver samples taken from healthy individuals, patients with simple steatosis and patients with NASH to identify potential targets of acetylation with a role in lactate metabolism. Interactions between the acetylated target and acetyltransferases were measured in multiple cell lines. An acetyltransferase inhibitor was injected into high-fat diet (HFD)-fed mice to determine the role of lactate on NAFLD progression in vivo. RESULTS: Hyperacetylation of lactate dehydrogenase B (LDHB) was found to be associated with lactate accumulation in NAFL and NASH livers in humans and mice. P300/CBP-associated factor (PCAF)-mediated acetylation of LDHB K82 was found to significantly decrease LDHB activity and impair hepatic lactate clearance, resulting in lactate accumulation. Acetylated LDHB induced lactate accumulation which exacerbated lipid deposition and inflammatory responses by activating histone hyperacetylation in HFD-induced NASH. The administration of embelin, a PCAF inhibitor, and the generation of an acetylation-deficient mutant of LDHB ameliorated NASH. CONCLUSION: PCAF-dependent LDHB acetylation plays a key role in hepatic lipid accumulation and inflammatory responses by impairing lactate clearance; this process might be a potential therapeutic target for the treatment of NASH. LAY SUMMARY: Lactate is known to accumulate in the livers of patients during the progression of non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism(s) of this accumulation and its importance in disease progression are unknown. Herein, we show that the acetylation of an enzyme involved in lactate metabolism leads to impaired lactate clearance and exacerbates NAFLD progression.

Inhaled Albuterol Use and Impaired Lactate Clearance in Patients With Sepsis: A Retrospective Cohort Study.

BACKGROUND: Lactate clearance has become important in the management of sepsis. However, factors unrelated to sepsis-induced hyperlactatemia, including ß-2 adrenergic agonists, can interfere with lactate clearance. OBJECTIVES: To investigate the association of inhaled albuterol with lactate clearance in patients with sepsis. METHODS: This was a single-center retrospective cohort study. Adult patients with sepsis diagnosed in the emergency department from May 2015 to May 2016 with initial lactate levels >2 mmol/L and serial lactate measurements 2 to 6 hours apart were included. Patients were divided into 2 groups based on whether they received inhaled albuterol between lactate measurements. The primary end point was lactate clearance of 10%. Secondary end points included intensive care unit (ICU) consultation and in-hospital mortality. A multivariate logistic regression analysis was performed to assess the effect of inhaled albuterol on lactate clearance. RESULTS: Of 269 patients included, 58 (22%) received inhaled albuterol between lactate measurements. This group had a significantly higher prevalence of pulmonary disease and a lower initial lactate compared to those who did not receive inhaled albuterol. They had a significantly lower rate of lactate clearance (45% vs 77%, P < .001); however, ICU consultation (71% vs 57%, P = .066) and in-hospital mortality (19% vs 22%, P = .64) were not significantly different. A multivariate logistic regression analysis adjusting for age, sex, chronic kidney disease, cirrhosis, cancer, septic shock or severe sepsis, and the amount of intravenous fluids received showed that inhaled albuterol was independently associated with impaired lactate clearance (adjusted odds ratio: 0.26, 95% confidence interval: 0.14-0.50, P < .001). CONCLUSIONS: Inhaled albuterol in patients with sepsis was associated with impaired lactate clearance without an increase in ICU consultation or in-hospital mortality. Impaired lactate clearance in patients with sepsis who receive inhaled albuterol should be interpreted with caution.

Lactate Measurements and Their Association With Mortality in Pediatric Severe Sepsis in India: Evidence That 6-Hour Level Performs Best.

PURPOSE: To investigate association of static and dynamic lactate indices with early mortality (within 48 hours of admission), as well as need for vasopressors and mechanical ventilation in pediatric severe sepsis/shock. To explore optimal cutoffs of lactate indices. We hypothesized that dynamic indices are superior to static indices in predicting early mortality. METHODS: This prospective cohort study involved children (aged <14 years) admitted in emergency department, tertiary care teaching hospital in North India with severe sepsis/shock (2015-2016). Arterial lactate was measured at admission (X0) and after 6 hours (X6). Primary outcome of the measurement was early mortality. Association between lactate indices- lactate at 0 hours (Lac0), lactate after 6 hours (Lac6), time-weighted average (LacTW), delta (ΔLac), clearance (LacCl%) and early mortality, need for vasopressors, and mechanical ventilation-was assessed using Student t test/Mann-Whitney test. Area under the receiver operating characteristic curve (AUROC) for early mortality deduced for all lactate indices and compared with reference (Lac0). Optimal cutoffs (maximizing both sensitivity and specificity) and their positive predictive value (PPV) and negative predictive value (NPV) were determined. RESULTS: During the study period, 116 children were assessed. Septic shock was present at admission in 56.9% children; 50% of children died during the next 48 hours. Lac0, Lac6, and LacTW were significantly higher, and LacCl% was lower in nonsurvivors versus survivors (all P < .001). Lac6 (0.837 [0.76-0.91]) had significantly higher AUROC (95% confidence interval) than Lac0 (0.77; P = .03). Abnormal lactate metrics (higher Lac0, Lac6, LacTW, and lower LacCl%) were associated with vasopressors need and mechanical ventilation. On logistic regression, Lac6 emerged as an independent predictor of early mortality as well as vasopressor and mechanical ventilation need. The optimal cutoff of Lac6 for identifying early mortality with good sensitivity, specificity, PPV, and NPV was ≥2.65 (76, 85, 83, 78). CONCLUSIONS: Lactate6 is the best marker associated with early mortality and higher level of care in severe sepsis/septic shock in resource-poor regions.

The prognostic value of early lactate clearance for survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication of survival after out-of-hospital cardiac arrest (OHCA) remains challenging with current guidelines recommending the prognostication no earlier than 72 h after return of spontaneous circulation (ROSC). Prognostic factors that could be used earlier after ROSC, like lactate clearance, are still being studied. OBJECTIVES: This paper aims to investigate the prognostic strength of early lactate clearance for survival after OHCA. METHODS: This retrospective observational single-center study focuses on patients for whom ROSC was achieved after OHCA. Patients ≥18 years admitted between September 2012 and January 2019, for which arterial serum lactate measurements were available immediately at and 3 h after hospital admission (T0 and T3), were included. RESULTS: 192 patients were included. Lactate clearance at T3 (p < 0.001) was identified as an independent predictor for 24 h, 48 h and 72 h survival. Witnessed arrest, bystander CPR and initial shockable rhythm were independent significant predictors for long term survival after ROSC (1 month, 3 months and 1 year; p < 0.05), but not for 24 h survival. Age (above or below 65 years) was not significant for predicting survival. Upon combination of witnessed arrest, bystander CPR and initial shockable rhythm in a multivariate logistic regression model for long term survival, the initial rhythm was the dominant factor in the combined model, making witnessed arrest and bystander CPR redundant. CONCLUSION: Lactate clearance at T3 after ROSC is associated with 24 h, 48 h and 72 h survival. Further research is needed to determine how to incorporate lactate clearance as part of a clinically useful tool to predict long term survival.

Transcutaneous oxygen pressure-related variables as noninvasive indicators of low lactate clearance in sepsis patients after resuscitation.

The transcutaneous oxygen challenge test (OCT) is associated with central venous oxygen saturation and cardiac output index, and has predictive value for prognosis. Whether the change of transcutaneous oxygen pressure (PtcO2)-related variables can reflect lactate clearance in sepsis patients is worth studying. We conducted a prospective observational study of 79 patients with sepsis or septic shock in the ICU. Immediately after enrollment, PtcO2 monitoring was continuously performed for 6 h. The OCT was performed at enrollment (T0) and the sixth hour (T6). The correlation between lactate clearance and PtcO2-related variables such as PtcO2 at T6, ΔPtcO2 (PtcO2 at T6 - PtcO2 at T0), ΔPtcO2 index (PtcO2/PaO2 at T6 - PtcO2/PaO2 at T0), 10 OCT [(PtcO2 after 10 min on FiO2 of 1.0) - (PtcO2 at baseline)], Δ10 OCT (10 OCT at T6 - 10 OCT at T0) was analyzed. The difference of PtcO2-related variables was compared between the high and low lactate clearance groups. PtcO2 at T6 (r = 0.477, p < 0.001), ΔPtcO2 (r = 0.592, p < 0.001), ΔPtcO2 index (r = 0.553, p < 0.001) and Δ10 OCT (r = 0.379, p = 0.001) were significantly correlated with the lactate clearance. To discriminate low lactate clearance, the area under the ROC curve was largest for ΔPtcO2, which was 0.804. PtcO2 at T6, PtcO2 index, ΔPtcO2, ΔPtcO2 index and Δ10 OCT were significantly different between the two different lactate clearance groups. Low lactate clearance in the initial 6 h of resuscitation of septic shock was associated to lower improvements in PtcO2-related variables.

Non-invasive tools for guiding hemodynamic resuscitation in septic shock: the perfusion vs metabolic issue.

Transcutaneous oxygen pressure reflects the balance between cardiac output, arterial oxygenation, and the metabolic rate of the tissue. In septic shock, it allows a real time assessment of the adequacy of tissue perfusion, and therefore it has been proposed as a non-invasive tool to guide the hemodynamic resuscitation process. However, its value is limited in those situations where cardiac output has been optimized, but tissue dysoxia persists as results of an impairment in oxygen utilization.