Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/24834
Title: Cytokine and lipid metabolome effects of low-dose acetylsalicylic acid in critically ill patients with systemic inflammation: a pilot, feasibility, multicentre, randomised, placebo-controlled trial.
Austin Authors: Cioccari, Luca;Luethi, Nora;Duong, Thy;Ryan, Eileen;Cutuli, Salvatore L ;Lloyd-Donald, Patryck ;Eastwood, Glenn M ;Peck, Leah ;Young, Helen ;Vaara, Suvi T;French, Craig J;Orford, Neil;Dwivedi, Jyotsna;Lankadeva, Yugeesh R;Bailey, Michael;Reid, Gavin E;Bellomo, Rinaldo 
Affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Vic, Australia
Intensive Care
Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic, Australia
Department of Intensive Care, Bankstown Hospital, Sydney, NSW, Australia
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia
School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Vic, Australia
Issue Date: Sep-2020
Date: 2020-09
Publication information: Critical Care and Resuscitation 2020; 22(3): 227-236
Abstract: The 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). Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial. Four interdisciplinary intensive care units (ICUs) in Australia. Critically ill patients with SIRS. ASA 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. Interleukin-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. The 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. In 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. Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).
URI: https://ahro.austin.org.au/austinjspui/handle/1/24834
Journal: Critical Care and Resuscitation
PubMed URL: 32900329
ISSN: 1441-2772
Type: Journal Article
Appears in Collections:Journal articles

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