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Transexamic acid (TXA) is an antifibrinolytic that has been used successfully to prevent blood loss during major surgery. However, as its usage has increased, there have been growing reports of postsurgical seizure events in cardiac surgery patients. In this issue of the JCI, Lecker et at explore this connection and suggest that TXA-mediated inhibition of glycine receptors may underlie the effect. This finding prompted the authors to explore the preclinical efficacy of common anesthetics that function by reducing the TXA-mediated inhibition to prevent or modify postsurgical seizures.
Introduction
Translation from clinical bedside to laborarory bench and back is the holy grail of medicine. In this issue, Lecker et al. (1) undertake just such a translation. In an elegant set of studies, the authors investigate the neuronal mechanisms that underlie seizures occurring as side effects in patients receiving transexamic acid (TXA) to reduce blood loss during major cardiovascular surgery. Given the structural similarity between the antifibrinolytic drug TXA and inhibitory neurotransmitter-gated Cl· channel glycine receptors, the authors tested the hypothesis that TXA inhibits glycine receptor action as a possible mechanism underlying the seizures. After demonstrating that TXA inhibits glycine receptors, they then proposed that anesthetic agents with glycine receptor agonist properties may be uniquely suited to prevent such seizures. The studies presented are of high quality, based on an impressive range of laboratory data and models. However, they may be premature in recommending specific clinical actions to prevent seizures based on the limited clinical data. To place these interesting and provocative translational findings in context, we review use of antifibrinolytics in major cardiovascular surgery; this is followed by a brief overview of mechanisms of general anesthesia recognized to date and how anesthetic agents may play a role in treating seizures generally rather than specifically. We conclude by suggesting how the work of Lecker et al moves the field forward, and where further work is still needed.
Antifibrinolytic agents and major cardiovascular surgery
Excessive perioperative bleeding remains a complication of cardiac surgery employing cardiopulmonary bypass, with blood transfusions considered a major contributor to subsequent morbidity and mortality (2). Despite serious efforts to achieve perioperative blood conservation by multimodal approaches (e.g., point-of-care monitoring paired with institution-specific blood transfusion algorithms and applied pharmacologic strategies), cardiac surgery patients continue...