Diagnostic Potential of Endotoxin Scattering Photometry for Sepsis and Septic Shock

Abstract

Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Endotoxemia in End‐Stage Kidney Disease

“…This assay uses a light‐scattering photometer to detect the formation of coagulin particles which are precursor gel clots formed during the early stages of the LAL coagulation cascade. Its predictive power in diagnosing intra‐abdominal sepsis is superior to the conventional kinetic turbidimetric LAL assay . Recently, genetically engineered recombinant factor C , an intracellular serine protease zymogen that initiates the coagulation cascade system in response to endotoxins has been developed for use as an endotoxin detection system.…”

Anti-endotoxin Properties of Polymyxin B-immobilized Fibers

“…The ESP method allows for more rapid and sensitive detection of endotoxin compared with the turbidimetric LAL method. Furthermore, ESP is able to discriminate between patients with sepsis and those with septic shock undergoing gastrointestinal emergency surgery compared with the standard turbidimetric LAL assay [35]. After undergoing PMX therapy for a longer-duration (> 2 h), the hemodynamic condition of patients with septic shock due to intra-abdominal infection improved, and the reduction in plasma endotoxin concentration could be detected via ESP but not through the standard turbidimetric method.…”

Outstanding Contributions of LAL Technology to Pharmaceutical and Medical Science: Review of Methods, Progress, Challenges, and Future Perspectives in Early Detection and Management of Bacterial Infections and Invasive Fungal Diseases

“…ESP is characterized by the method based on the same principle of turbidimetric assay; however, ESP can detect very small particles in a fluid generated in the reaction, which is the first appearance of LAL cascade triggered by endotoxin. Shimizu et al showed that the ESP assay was even more useful than previous tests for detecting endotoxin, depending on the severity of septic patients [ 35 ]; nevertheless, this technique has not been authorized by MHLW for widespread use. Furthermore, chromogenic LAL coupled with a bioluminescence technique has been newly developed using mutant firefly luciferase (Luminutes-ET; DKK-TOA, Tokyo, Japan) [ 36 ].…”