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Plasma platelet-activating factor acetylhydrolase activity in critically ill patients
Ralf A Claus1, Stefan Russwurm, Barbara Dohrn
1Department for Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany.
Critical Care Medicine
|June 9, 2005
Summary
Platelet-activating factor-acetylhydrolase (PAF-AH) activity in sepsis patients increases over time and differs between survivors and non-survivors. These findings may explain why recombinant PAF-AH failed in clinical trials.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Platelet-activating factor (PAF) is a key mediator in systemic inflammation and sepsis.
- PAF-acetylhydrolase (PAF-AH) inactivates PAF.
- A recent clinical trial using recombinant PAF-AH for severe sepsis did not reduce mortality.
Purpose of the Study:
- To investigate PAF-AH activity in critically ill patients with sepsis.
- To compare PAF-AH activity between patients and healthy controls.
- To explore the relationship between PAF-AH activity and sepsis severity and outcomes.
Main Methods:
- Retrospective cohort study of 231 intensive care unit patients.
- Daily measurement of plasma PAF-AH activity using a radiolabeled substrate.
- Comparison of activity levels based on sepsis severity, organ failure, and survival status.
Main Results:
- On admission, PAF-AH activity was lower in patients than controls but increased over time.
- Higher PAF-AH activity was observed in patients with severe sepsis/septic shock and organ failure.
- Lower PAF-AH activity was associated with non-survival only before organ failure development; in severe sepsis, non-survivors had higher activity than survivors.
- PAF-AH activity correlated positively with neopterin and TNF-alpha, but not CRP, IL-6, or PCT.
- Parenteral nutrition with lipid emulsions was associated with lower PAF-AH activity compared to enteral nutrition.
Conclusions:
- PAF-AH activity exhibits severity- and time-dependent changes in sepsis.
- These dynamic changes in PAF-AH activity may explain the limited efficacy of previous recombinant PAF-AH treatment strategies.
- Future therapeutic strategies should consider the evolving activity of PAF-AH in sepsis.