Manifold beneficial effects of acetyl salicylic acid and nonsteroidal anti-inflammatory drugs on sepsis

Abstract

Acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) may have potential as adjunctive agents for sepsis. This review considers the large body of literature that indicates a basis for sepsis therapy with ASA and suggests an agenda for future intervention studies in sepsis prevention and treatment. ASA and NSAIDs have beneficial effects in numerous experimental models of sepsis. Low doses of ASA of 100 mg/day or less trigger synthesis of lipoxins that are anti-inflammatory and aid in resolution of inflammation. Higher doses of ASA and NSAIDs act to reduce NF-κB stimulation and inhibit numerous septic pathways. While a previous randomised controlled trial of ibuprofen failed to show a reduction in mortality in sepsis, it did reduce clinical manifestations of sepsis. More recent observational studies have shown reduction in sepsis or acute lung injury leading to lower mortality in ICU patients treated with ASA. Low-dose ASA appears to be beneficial in the prevention and treatment of sepsis and SIRS. If proven, this intervention would have a major, cost-effective impact on sepsis care.