Bench-to-bedside review: Clinical experience with the endotoxin activity assay

Romaschin, Alexander D.; Klein, David J.; Marshall, John C.

doi:10.1186/cc11495

Cited by 59 publications

(55 citation statements)

References 20 publications

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“…Patients from 31 hospitals with severe sepsis and septic shock sepsis originating in the abdominal cavity or otherwise supported by high activity levels of endotoxin (EAA >0.6) [5,6] measured by chemiluminescence in whole blood and accompanied by severe sepsis or septic shock received up to two PMX-DHP hemoperfusions (the second cycle for EAA >0.6 coming 24 h after the first). All patients were intended to be managed by applying standard protocols of intensive care, following current guidelines and recommendations.…”

Section: Methodsmentioning

confidence: 99%

Polymyxin B Hemoperfusion in Clinical Practice: The Picture from an Unbound Collaborative Registry

Antonelli¹

2014

Blood Purif

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After the publication of the EUPHAS trial, the clinical use of polymyxin B hemoperfusion (Toraymyxin®) increased significantly in Italy. Nevertheless, no structured data collections have been carried out to underline the characteristics of treated patients. Therefore, a collaborative registry of clinical data was promoted among users in order to better define the structure of the prospective data collection named the EUPHAS2 project. Neither inclusion criteria nor therapeutic constraints were imposed, highlighting adherence to clinical evidence provided by previous randomized controlled trials, and also unusual or borderline practice in the selection of patients for polymyxin B-based cartridges (PMX-DHP). This first retrospective phase of data collection included patients with severe sepsis and septic shock treated with Toraymyxin over the last 3 years, up to July 2013. Thirty-one hospitals participated in the EUPHAS2 study, collecting data on 306 patients. Enrolled patients were grouped according to the main source of sepsis: abdominal (41.8%) and nonabdominal (58.2%). The abdominal patients had characteristics well matching those selected for the EUPHAS randomized controlled trial in terms of time-to-enrolment, severity of the illness, 28-day mortality and in-hospital mortality. Their 28-day mortality rate was 35% with a significant reduction of the Sequential Organ Failure Assessment Score (SOFA) score after 72 h of treatment (p < 0.001). Patients with nonabdominal sepsis were heterogeneous and only a few of them had their endotoxin activity tested in a manner not allowing a reliable evaluation of the real efficacy of the treatment and organ dysfunction control. Their 28-day mortality rate was 49% and the SOFA score did not significantly change before and after treatment. In conclusion, clinical experience confirms the results of the original EUPHAS randomized trial in terms of outcome for patients with abdominal severe sepsis. Specific studies focused on a population of patients with Gram-negative infections of nonabdominal origin are needed before recommending treatment with Toraymyxin as an effective therapy.

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Section: Methodsmentioning

confidence: 99%

Polymyxin B Hemoperfusion in Clinical Practice: The Picture from an Unbound Collaborative Registry

Antonelli¹

2014

Blood Purif

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“…The EAA™ normalises endotoxin induced neutrophil chemilumiescence against a maximal control tube spiked with exogenous endotoxin levels to simulate sepsis. Romaschin et al in their review of the EAA™ assay report the most sensitive part of the dose response curve (change in EU per LPS dose) in the revised calibration using WHO standardised LPS (200 pg/EU) was greatest in the range of 0.1 to 0.3EU, yet these results remain unpublished [30]. It is therefore plausible that manipulation of the EAA™ protocol through decreasing the endotoxin concentration within the maximum response tube may yield an assay that can accurately measure endotoxin activity in a "low range" metabolic endotoxemia context [31].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the use of the Endotoxin Activity Assay (EAA™) to Quantify Non-septic Exposure of Metabolic Endotoxemia

McPhee¹,

Tremellen²,

Pearce³

2017

J Med Diagn Meth

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Objective: Endotoxin, also known as lipopolysaccharide (LPS), is a potent immune stimulant. Low levels of endotoxin exposure (metabolic endotoxemia) play a pivotal role in metabolic disorders. However, there is no robust clinical assay to directly quantify metabolic endotoxemia. We aimed to validate the whole blood Endotoxin Activity Assay (EAA™) as a novel, rapid method to quantify low grade metabolic endotoxemia against the well-established lipopolysaccharide binging protein assay (LBP), a robust surrogate marker of endotoxaemia.Methods: 67 women and 47 men aged 21 to 47 years (35.4 ± 5.5 years, 34.5 ±7.2 years respectively) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), endotoxin levels (LBP, EAA™) and inflammatory status (serum CRP, IL-6, IL-8).Results: There was no direct relationship between EAA™ and LBP measures for quantitating metabolic endotoxemia for either women or men (R=0.146, p=0.284; R=0.283 p=0.09 respectively). In women, the traditional indirect marker of endotoxemia LBP correlated significantly with CRP and IL-6, measures of generalised immune activation and inflammation (R=0.664, p<0.001, R=0.296, p=0.028 respectively), but not with EAA™ assed endotoxemia. Supporting this relationship, LBP correlated with BMI and body fat percentage (R=0.306, p=0.022; R=0.301, p=0.024 respectively). However, the EAA™ only correlated with body fat percentage (R=0.382, p=0.014). In men, LBP was significantly related to CRP and IL-6 (R=0.345, p=0.046; R=0.421, p=0.009 respectively), but no relationship was observed between these inflammatory markers and EAA™ assed metabolic endotoxemia (R=0.206, p=0.243; R=0.280, p=0.093 respectively). There was no relationship between EAA ™ or LBP and any of the three measures of adiposity. Conclusion:In conclusion, the existing rapid whole blood EAA™ method of analysis was not suitable to detect low levels of endotoxemia known to be present in the obese state, while the results suggest LBP indirect analysis remains the superior tool for measuring low grade endotoxemia in this population.

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“…Taking into account the recommendations of several other authors [6,8,][28], the dynamics of the endotoxin load were assessed before the procedures and within 12 h after the end of treatment because the ‘re-equilibration' of endotoxin concentrations requires a long period of time.…”

Section: Discussionmentioning

confidence: 99%

“…It activates macrophages leading for example to the release of acute-phase proteins, cytokines, chemokines and complement factors [4]. High endotoxin levels in the blood in the perioperative period are associated with an increased risk of infectious complications and multiple organ dysfunction syndrome development [5,6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

Combined Extracorporeal Therapy for Severe Sepsis in Patients after Cardiac Surgery

Yaroustovsky¹,

Abramyan²,

Кротенко³

et al. 2014

Blood Purif

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Introduction: Sepsis still represents an obstacle in modern medicine. The aim of this study was to evaluate the effectiveness and safety of the combined use of lipopolysaccharide adsorption and haemodialysis (HD) with high cut-off haemofilters as part of the complex intensive care of patients with severe sepsis after cardiac surgery. Methods: The study group included 26 patients, 57 (48-62) years of age, with severe sepsis. The inclusion criteria were clinical signs of severe sepsis (systemic inflammatory response syndrome + infection site + failure of two or more organs) together with endotoxin activity assay (EAA) ≥0.6 and procalcitonin (PCT) levels ≥2 ng/ml. Antimicrobial therapy was initiated in the first hour after the diagnosis of severe sepsis and extracorporeal therapy was initiated within 24 h. All of the patients in the study group received standard therapy. Additionally, they received treatment consisting of two LPS adsorption procedures and HD procedures with high cut-off haemofilters in a single circuit. For the control group, 30 comparable patients, 57 (51-61) years of age, were selected and received only standard therapy. Results: After the last HD procedure within the extracorporeal therapy, we noted an increase in the mean arterial pressure from 76 to 90 mm Hg, p < 0.01, and oxygenation index (from 226 to 291, p < 0.02), in addition to decreases in the LPS concentration according to EAA (from 0.73 to 0.59, p < 0.01) and the Limulus amebocyte lysate test (from 1.44 to 0.36 IU/ml, p < 0.01); PCT falls from 8.19 to 2.44 ng/ml, p < 0.01, and sepsis-related organ failure assessment scores decreases from 13 to 10, p = 0.007. When we compared the data between the study group the day after the procedures and the control group 3 days after the start of intensive care, we discovered that there were statistically significant differences in mean arterial pressure (90 vs. 81 mm Hg, p = 0.0004), oxygenation index (291 vs. 229, p = 0.01), and EAA levels (0.59 vs. 0.67, p = 0.05). Differences in the PCT were not significant (2.44 vs. 3.41, p = 0.15). The 28-day survival rate in the study group was higher than that in the control group (65.4 vs. 33.3%, p = 0.03). Conclusion: The combined use of LPS adsorption and HD with high cut-off haemofilters in conjunction with standard therapy is a safe, effective method for treating patients who have severe sepsis.

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Bench-to-bedside review: Clinical experience with the endotoxin activity assay

Cited by 59 publications

References 20 publications

Polymyxin B Hemoperfusion in Clinical Practice: The Picture from an Unbound Collaborative Registry

Polymyxin B Hemoperfusion in Clinical Practice: The Picture from an Unbound Collaborative Registry

Evaluation of the use of the Endotoxin Activity Assay (EAA™) to Quantify Non-septic Exposure of Metabolic Endotoxemia

Combined Extracorporeal Therapy for Severe Sepsis in Patients after Cardiac Surgery

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