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Objective: 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)., Design: Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial., Setting: Four interdisciplinary intensive care units (ICUs) in Australia., Participants: Critically ill patients with SIRS., Interventions: 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., Main Outcome Measures: 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., Results: 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., Conclusions: 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., Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).

Background: Normal saline (NS) is the most commonly used crystalloid solution worldwide but contains an excess of chloride and may cause metabolic acidosis and hyperchloraemia. Such abnormalities may be attenuated by the use of a balanced solution such as Plasma-Lyte 148 (PL-148)., Objective: To assess the feasibility, safety and biochemical and physiological effects of resuscitation with NS versus PL-148 in critically ill patients., Design, Setting and Participants: An exploratory, multicentre, doubleblind, randomised controlled trial involving patients aged ≥ 18 years who were prescribed crystalloid fluid resuscitation by the treating clinician between 16 July and 22 October 2015, in three multidisciplinary intensive care units in Melbourne, Victoria, Australia., Methods: Random allocation of NS or PL-148 was concealed, and all fluids were delivered in indistinguishable bags., Intervention: NS or PL-148 was administered for all fluid resuscitation and for all subsequent crystalloid fluid therapy until Day 4 of ICU admission. The treating intensivist determined the rate and frequency of fluid administration., Main Outcome Measures: Primary outcome was daily base excess (BE). Relevant secondary outcomes included the incidence of acute kidney injury (AKI), change in serum creatinine and serum chloride levels, and mortality., Results: Seventy patients were recruited, with 34 in the NS group and 33 in the PL-148 group available for analysis. Baseline characteristics of study patients were well balanced; the mean ages were 64 and 62 years, respectively, and nearly two-thirds of the patients in each group were men. The median Acute Physiology and Chronic Health Evaluation III scores were 64 for the NS group (interquartile range [IQR], 48-73) and 55 for the PL-148 group (IQR, 44-81). After treatment, there was no significant difference in the worst (most negative) median BE between the NS and PL-148 groups (-4 mEq/L [IQR, -7 to -2 mEq/L] v -3 mEq/L [IQR, -7 to 2 mEq/L]; P = 0.42). Chloride levels were significantly higher with NS therapy (median, 111 mmol/L [IQR, 108-116 mmol/L] v 108 mmol/L [IQR, 106-110 mmol/L]; P = 0.01). There was no significant difference in the incidence of AKI (P = 0.48), peak creatinine levels (P = 0.92) or ICU or hospital mortality between the two groups., Conclusions: In our exploratory, double-blind, randomised controlled trial, when compared with NS, PL-148 did not significantly increase BE values in critically ill patients requiring fluid resuscitation, but decreased peak chloride concentrations.