• Christian Schoergenhofer, Eva-Luise Hobl, Michael Schwameis, Georg Gelbenegger, Thomas Staudinger, Gottfried Heinz, Walter S Speidl, Christian Zauner, Birgit Reiter, Irene Lang, and Bernd Jilma.
• Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
• Eur. J. Clin. Invest. 2017 Jul 1; 47 (7): 504-512.

BackgroundDespite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid (ASA) in critically ill patients remain ill-defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness.DesignA cross-sectional study and a randomized, parallel-group trial were performed. Critically ill patients under chronic oral ASA treatment (100 mg enteric-coated) were screened for high 'on-treatment' platelet reactivity (HTPR) according to arachidonic acid-induced whole-blood aggregometry. Thirty patients with HTPR were randomized to receive 100 mg ASA intravenously, 100 mg enteric-coated ASA bid (bis in die) or 81 mg chewable ASA (n = 10 per group). Serum thromboxane B2 (TXB2) levels, ASA and salicylic acid levels were quantified.ResultsOf 66 patients, 85% (95% confidence intervals 74-93%) had HTPR. Compared to baseline infusion of 100 mg, ASA significantly reduced platelet aggregation after 24 h to median 80% (Quartiles: 66-84%). Intake of 81 mg chewable ASA significantly reduced platelet aggregation to 75% (54-86%) after four hours, but increased it to 117% after 24 h (81-163%). Treatment with 100 mg enteric-coated ASA bid decreased platelet aggregation after 24 h to median 56% (52-113%). Baseline TXB2 levels were median 0·35 ng/mL (0·07-0·94). Infusion of ASA or intake of 100 mg ASA bid reduced TXB2 levels to 0·07-0·18 ng/mL after 24 h, respectively. Chewable ASA reduced TXB2 levels only transiently. Pharmacokinetic analysis revealed highly variable absorption patterns of oral ASA formulations.ConclusionThere is a very high prevalence of HTPR in critically ill patients on peroral ASA therapy, caused by an incomplete suppression of TXB2 and/or by impaired absorption of ASA.© 2017 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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