Plasma platelet-activating factor acetylhydrolase activity in critically ill patients.
OBJECTIVE
Platelet-activating factor (PAF) is a potent proinflammatory mediator in systemic inflammation and sepsis and is inactivated by the enzyme PAF-acetylhydrolase (PAF-AH). Recently, a large phase III clinical trial using recombinant PAF-AH to treat patients with severe sepsis was performed but failed to reduce 28-day mortality rate. To get more information on the activity of PAF-AH in sepsis, we repeatedly measured its activity in plasma in critically ill patients compared with healthy controls.


METHODS
Retrospective cohort study.


METHODS
Intensive care unit.


METHODS
Two hundred thirty-one patients who were admitted to an operative intensive care unit within 1 yr were enrolled and evaluated daily for American College of Chest Physicians/Society of Critical Care Medicine criteria. PAF-AH activity was measured as the release of [H]-acetate from [H]-acetyl-PAF.


METHODS
Analysis of plasma samples.


RESULTS
At the day of admission, PAF-AH activity of patients was below controls but markedly increased over time. Higher activities were seen in patients with severe sepsis or septic shock compared with those without organ failure. With respect to the clinical outcome, lower values were found in nonsurvivors only as long as they had not developed organ failure. In severe sepsis/septic shock, values of nonsurvivors exceeded those of survivors. PAF-AH activity was positively correlated with plasma levels of inflammatory mediators such as neopterine and tumor necrosis factor-alpha but not with acute phase reactants such as C-reactive protein, interleukin-6, or PCT. In addition, parenteral nutrition with lipid emulsions was seemingly associated with low PAF-AH activity compared with enteral nutrition.


CONCLUSIONS
The data indicate severity- and time-dependent changes in PAF-AH activity and may help to explain the failure of recombinant PAF-AH treatment strategies that were not based on activity measurements.
Claus
Ralf A
RA
Department for Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany.
Russwurm
Stefan
S
Dohrn
Barbara
B
Bauer
Michael
M
Lösche
Wolfgang
W
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018805:Sepsis / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D012772:Shock, Septic / Q000201:enzymology / Q000401:mortality / Q000503:physiopathology; D018746:Systemic Inflammatory Response Syndrome / Q000201:enzymology / Q000401:mortality / Q000503:physiopathology
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase