• Luca Cioccari, Nora Luethi, Thy Duong, Eileen Ryan, Salvatore L Cutuli, Patryck Lloyd-Donald, Glenn M Eastwood, Leah Peck, Helen Young, Suvi T Vaara, Craig J French, Neil Orford, Jyotsna Dwivedi, Yugeesh R Lankadeva, Michael Bailey, Gavin E Reid, and Rinaldo Bellomo.
• Department of Intensive Care, Austin Hospital, Melbourne, Vic, Australia. luca.cioccari@insel.ch.
• Crit Care Resusc. 2020 Sep 1; 22 (3): 227236227-236.

ObjectiveThe systemic inflammatory response syndrome (SIRS) is a dysregulated response that contributes to critical illness. Adjunctive acetylsalicylic acid (ASA) treatment may offer beneficial effects by increasing the synthesis of specialised proresolving mediators (a subset of polyunsaturated fatty acid-derived lipid mediators).DesignPilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial.SettingFour interdisciplinary intensive care units (ICUs) in Australia.ParticipantsCritically ill patients with SIRS.InterventionsASA 100 mg 12-hourly or placebo, administered within 24 hours of ICU admission and continued until ICU day 7, discharge or death, whichever came first.Main Outcome MeasuresInterleukin-6 (IL-6) serum concentration at 48 hours after randomisation and, in a prespecified subgroup of patients, serum lipid mediator concentrations measured by mass spectrometry.ResultsThe trial was discontinued in December 2017 due to slow recruitment and after the inclusion of 48 patients. Compared with placebo, ASA did not decrease IL-6 serum concentration at 48 hours. In the 32 patients with analysis of lipid mediators, low-dose ASA increased the concentration of 15-hydroxyeicosatetraenoic acid, a proresolving precursor of lipoxin A4, and reduced the concentration of the proinflammatory cytochrome P-dependent mediators 17-HETE (hydroxyeicosatetraenoic acid), 18-HETE and 20-HETE. In the eicosapentaenoic acid pathway, ASA significantly increased the concentration of the anti-inflammatory mediators 17,18-DiHETE (dihydroxyeicosatetraenoic acid) and 14,15-DiHETE.ConclusionsIn ICU patients with SIRS, low-dose ASA did not significantly alter serum IL-6 concentrations, but it did affect plasma concentrations of certain lipid mediators. The ability to measure lipid mediators in clinical samples and to monitor the effect of ASA on their levels unlocks a potential area of biological investigation in critical care.Trial RegistrationAustralian New Zealand Clinical Trials Registry (ACTRN 12614001165673).

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