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
Department of Intensive Care, Austin Hospital, Melbourne, Vic, Australia.
Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Vic, Australia.
Crit Care Resusc. 2020 Sep;22(3):227-236. doi: 10.1016/S1441-2772(23)00390-3.
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).
全身炎症反应综合征（SIRS）是一种失调的反应，可导致危重病。辅助使用乙酰水杨酸（ASA）治疗可能通过增加特异性促分解介质（多不饱和脂肪酸衍生脂质介质的一个子集）的合成而产生有益效果。
试点、可行性、多中心、双盲、随机、安慰剂对照试验。
澳大利亚的四个跨学科重症监护病房（ICU）。
患有SIRS的危重病患者。
ASA 100毫克，每12小时一次或安慰剂，在入住ICU后24小时内给药，并持续至ICU第7天、出院或死亡（以先发生者为准）。
随机分组后48小时的白细胞介素-6（IL-6）血清浓度，以及在预先指定的患者亚组中，通过质谱法测量的血清脂质介质浓度。
由于入组缓慢，在纳入48例患者后，该试验于2017年12月停止。与安慰剂相比，ASA在48小时时并未降低IL-6血清浓度。在32例进行脂质介质分析的患者中，低剂量ASA增加了脂氧素A4的促分解前体15-羟基二十碳四烯酸的浓度，并降低了促炎细胞色素P依赖性介质17-羟基二十碳四烯酸（HETE）、18-HETE和20-HETE的浓度。在二十碳五烯酸途径中，ASA显著增加了抗炎介质17,18-二羟基二十碳四烯酸（DiHETE）和14,15-DiHETE的浓度。
在患有SIRS的ICU患者中，低剂量ASA并未显著改变血清IL-6浓度，但确实影响了某些脂质介质的血浆浓度。在临床样本中测量脂质介质以及监测ASA对其水平的影响的能力，开启了危重症生物学研究的一个潜在领域。
澳大利亚新西兰临床试验注册中心（ACTRN 12614001165673）。
