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Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease
P Brandtzaeg1, P Kierulf, P Gaustad
1Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway.
Abstract:
We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.
Insights
High levels of circulating endotoxin (lipooligosaccharides [LOSs]) in patients with systemic meningococcal disease (SMD) strongly predict severe illness, organ failure, and death. LOS quantitation offers crucial prognostic information.
Area of Science:
- Microbiology
- Immunology
- Critical Care Medicine
Background:
- Systemic meningococcal disease (SMD) can lead to severe complications, including multiple organ failure and death.
- The role of circulating endotoxins, specifically lipooligosaccharides (LOSs), in the pathogenesis of severe SMD requires further elucidation.
Purpose of the Study:
- To prospectively investigate the quantitative relationship between circulating lipooligosaccharides (LOSs) and the development of multiple organ failure and mortality in patients with bacteriologically verified systemic meningococcal disease (SMD).
Main Methods:
- Prospective study of 45 consecutively admitted patients with confirmed SMD.
- Quantitative measurement of plasma lipooligosaccharides (LOSs) using the limulus amebocyte lysate assay with a chromogenic substrate.
- Correlation analysis between initial plasma LOS levels and clinical outcomes, including severe septic shock, adult respiratory distress syndrome, elevated serum creatinine, and death.
Main Results:
- Plasma LOS levels greater than 700 ng/L significantly correlated with severe septic shock, adult respiratory distress syndrome, elevated serum creatinine, and death (P < .0001).
- Fatality rates increased progressively with initial plasma LOS levels: 0% (<25 ng/L), 14% (25-700 ng/L), 27% (700-10,000 ng/L), and 86% (>10,000 ng/L).
- The half-life of LOS after antibiotic initiation was short (1-3 hours), with no observed increase in plasma LOS levels during treatment.
Conclusions:
- Quantitative assessment of plasma lipooligosaccharides (LOSs) via the limulus amebocyte lysate assay provides critical prognostic information in systemic meningococcal disease (SMD).
- LOS levels are a key determinant of disease severity and patient outcomes, offering insights into the pathophysiology of SMD.
- This assay may aid in risk stratification and management of patients with severe meningococcal infections.