Objective: Serial lactate concentrations can be used to examine disease severity in the intensive care unit. This study examines the clinical utility of the lactate clearance before intensive care unit admission (during the most proximal period of disease presentation) as an indicator of outcome in severe sepsis and septic shock. We hypothesize that a high lactate clearance in 6 hrs is associated with decreased mortality rate. Design: Prospective observational study. Setting: An urban emergency department and intensive care unit over a 1-yr period. Patients: A convenience cohort of patients with severe sepsis or septic shock. Interventions: Therapy was initiated in the emergency department and continued in the intensive care unit, including central venous and arterial catheterization, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, and inotropes when appropriate. Measurements and Main Results: Vital signs, laboratory values, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were obtained at hour 0 (emergency department presentation), hour 6, and over the first 72 hrs of hospitalization. Therapy given in the emergency department and intensive care unit was recorded. Lactate clearance was defined as the percent decrease in lactate from emergency department presentation to hour 6. Logistic regression analysis was performed to determine independent variables associated with mortality. One hundred and eleven patients were enrolled with mean age 64.9 16.7 yrs, emergency department length of stay 6.3 3.2 hrs, and overall in-hospital mortality rate 42.3%. Baseline APACHE II score was 20.2 6.8 and lactate 6.9 4.6 mmol/L. Survivors compared with nonsurvivors had a lactate clearance of 38.1 34.6 vs. 12.0 51.6%, respectively (p .005). Multivariate logistic regression analysis of statistically significant univariate variables showed lactate clearance to have a significant inverse relationship with mortality (p .04). There was an approximately 11% decrease likelihood of mortality for each 10% increase in lactate clearance. Patients with a lactate clearance >10%, relative to patients with a lactate clearance <10%, had a greater decrease in APACHE II score over the 72-hr study period and a lower 60-day mortality rate (p .007). Conclusions: Lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance. (Crit Care Med 2004; 32:1637‐1642)

http://www.urgentools.com/wp-content/uploads/2015/08/Early-lactate-Clearance-assosciated-with-improved-outcome-in-severe-sepsis-and-shock.pdf

Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.

Background Despite successful initial resuscitation, septic shock frequently evolves into multiple system organ failure (MSOF) and death. Since blood lactate levels can reflect the degree of cellular derangements, we examined the relation between serial blood lactate levels and the development of MSOF, or mortality, in patients with septic shock. Patients and methods In 87 patients with a first episode of septic shock, we measured initial lactate (at onset of septic shock), final lactate (before recovery or death), "lactime" (time during which blood lactate was >2.0 mmol/L), and the area under the curve (AUC) for abnormal values (above 2.0 mmol/L). These measurements were correlated with survival and organ failure and scored for four systems (ie, respiratory, renal, hepatic, and coagulation), adding to a maximal score of 8. Results Thirty-three (38%) patients survived. Of the 54 (62%) nonsurvivors, the 13 patients who died during the first 24 hours of septic shock had higher initial blood lactate levels than those who died later (mean ± standard deviation 9.6 ± 5.3 mmol/L versus 5.6 ± 3.7 mmol/L, P The 74 patients who survived the first 24 hours of shock were studied in more detail. On presentation, survivors had a significantly higher mean arterial pressure (76 ± 12 mm Hg versus 63 ± 20 mm Hg, P P R 2 = 0.266, P Conclusions In patients with septic shock, serial determinations of blood lactate levels are good predictors of the development of MSOF and death. In this respect, the duration of lactic acidosis is more important than the initial lactate value. Although a number of factors may contribute to hyperlactatemia, these observations are compatible with a direct role of prolonged tissue hypoxia in the development of complications following septic shock.

Serial blood lactate levels can predict the development of multiple organ failure following septic shock

Laboratory models of sepsis and septic shock

Sepsis is characterized by a severe inflammatory response to infection, and its complications, including acute kidney injury, can be fatal. Animal models that correctly mimic human disease are extremely valuable because they hasten the development of clinically useful therapeutics. Too often, however, animal models do not properly mimic human disease. In this Review, we outline a bedside-to-bench-to-bedside approach that has resulted in improved animal models for the study of sepsis — a complex disease for which preventive and therapeutic strategies are unfortunately lacking. We also highlight a few of the promising avenues for therapeutic advances and biomarkers for sepsis and sepsis-induced acute kidney injury. Finally, we review how the study of drug targets and biomarkers are affected by and in turn have influenced these evolving animal models.

/pdf/animal-models-of-sepsis-and-sepsis-induced-kidney-injury-3kwa2ipc9j.pdf

Animal models of sepsis and sepsis-induced kidney injury

Objectives: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. Design: A prospective, intervention, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: 30 patients with a cardiac index (CI) > 3.5 l · min–1· m–2 and a mean arterial pressure (MAP) ≤ 60 mmHg after volume loading and dopamine 20 μg/kg per min and either oliguria or hyperlactatemia. Interventions: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Measurements and main results: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 ± 1.5 to 5.9 ± 1.0 mmol/l; p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 ± 1.5 to 2.7 ± 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 ± 5.4 to 21 ± 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 ± 5 to 14 ± 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 ± 0.11 to 7.16 ± 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2– arterial PCO2) increased (from 10 ± 2.7 to 14 ± 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 ± 0.11 to 7.35 ± 0.07) and the PCO2 gap (from 10 ± 3.0 to 4 ± 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. Conclusions: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

/pdf/comparison-of-norepinephrine-and-dobutamine-to-epinephrine-3hgvpkdzid.pdf

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study.

The effect of chronic sepsis on the concentration of active pyruvate dehydrogenase complex has been investigated in liver and skeletal muscle of normal, sterile inflammatory, and chronic septic (small and large abscess) animals. Hyperdynamic sepsis was induced by the intraperitoneal introduction of a rat fecal-agar pellet of known size and bacterial composition (Escherichia coli + Bacteroides fragilis). Total pyruvate dehydrogenase complex activity was not altered in either liver or skeletal muscle in any of the conditions studied. In hepatic tissue, sterile inflammation increased the proportion of active complex 2.5-fold compared with control. The same increase in the concentration of active complex was observed in animals with a small abscess. When the abscess size was increased (large abscess), the concentration of active complex was decreased relative to sterile inflammatory or small abscess septic animals. In contrast to liver, sterile inflammation did not alter the proportion of active complex in skeletal muscle. Sepsis (either small or large septic abscess) resulted in threefold decrease in the concentration of active complex relative to control or sterile inflammatory animals. Changes in the concentration of active complex did not appear to be dependent on the ATP/ADP concentration ratio or tissue pyruvate levels but were consistent with changes in the acetyl-coenzyme A-to-coenzyme A concentration ratio. The mechanism responsible for altered concentration of active complex may be mediated through changes in the activity of the pyruvate dehydrogenase kinase, secondary to alterations in the effector concentration ratios.

Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver.

Hepatic cellular injury following lethal Escherichia coli bacteremia in rats.

A single, uniform abscess was formed in 100% of the animals inoculated with a fecal pellet made of sterile rat feces, agar, and a known number and strain of bacteria. The effects of monoclonal Escherichia coli abscess (83 rats) were compared to those of sterile abscess (34 rats) and sham operation (35 rats without abscess). Bacteroides fragilis was added to the sterile pellet to study the effect of an anaerobic monoclonal abscess (16 rats) or of a biclonal abscess containing both aerobes and anaerobes (32 rats). After inoculation, a peritonitis stage with leucopenia, hypoglycemia, body weight loss, and slight fever was followed by the abscess stage with leucocytosis and a slight hyperglycemia. Mild hepatic energy charge deficiency and hepatic lactic acidosis were observed in sterile abscess rats, and slightly enhanced energy charge was seen in monoclonal E. coli abscess rats. The addition of B. fragilis to the sterile pellet, alone or together with E. coli, produced hepatic energy charge deficiency and hepatic lactic acidosis, which were significantly enhanced compared with the monoclonal E. coli abscess rats. The greatest effect was seen in the biclonal E. coli plus B. fragilis abscess, suggesting that anaerobic or combined aerobe and anaerobe abscesses may produce a greater hepatic injury than an aerobic organism abscess alone. This may account for the apparent synergic interaction between aerobic and anaerobic organisms.

Hepatic and systemic metabolic responses to aerobic and anaerobic intra-abdominal abscesses in a highly reproducible chronic rat model

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.

A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection.

In acute renal failure in man following shock and trauma, an amazing discrepancy was found between the complete breakdown of renal function and the very modest histological and ultrastructural changes in "immediate autopsy" patients, even in those who sustained septic shock. Although, from this limited number of studies no satisfactory interpretation of the pathogenesis of acute renal failure can be deduced from the structural changes found, the findings do indicate that hypoxia plays a key role in aggravating the structural changes that induce permanent cell damage in man following shock of various etiologies including septic shock.

Ultrastructural study on kidney cell injury following various types of shock in 26 immediate autopsy patients.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Sato T

Author Tools

Chat about Author