Safe and effective use of aspirin in intensive care patients.

This proposal will examine the impact of aspirin on 15-epi-lipoxin A4 biosynthesis in severely ill patients for the first time. Low doses of aspirin have been clearly demonstrated to modulate this anti-inflammatory pathway. We will define the pharmacokinetics of low doses of aspirin in SIRS/sepsis patients providing critical information for future large-scale use of this agent in this population. Focusing on aspirin triggered lipoxins (ATL), we will explore the pharmacodynamics of low dose aspirin’s effects in SIRS/sepsis patients. This will extend previous measurements of beneficial impacts on nitric oxide, PMN apoptosis and TNF secretion by systematically analysing adaptive and innate immunological processes. The clinical trial is designed to be definitive and provide a clear answer on the basis with which to proceed to large-scale intervention trials.