Comparison of trauma-dosed tranexamic acid versus aminocaproic acid in cardiac surgery in the setting of drug shortage.

BACKGROUND: Antifibrinolytic agents, tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), are often used during cardiac surgery to decrease the number of allogenic blood transfusions and to prevent perioperative bleeding. Weight-based TXA dosing regimens have been compared to fixed-dose regimens of EACA with variable outcomes in perioperative blood product transfusions and chest tube output. Serious adverse events, including seizures, have been reported with higher doses of TXA. Fixed-dose TXA regimens have been evaluated in trauma and orthopedic surgery but there is a paucity of evidence in the cardiac surgery population. AIMS OF THE STUDY: To compare the safety and efficacy of fixed-dose TXA versus EACA in patients undergoing cardiac surgery. METHODS: A single-center, retrospective chart review was conducted at a 793-bed tertiary care academic teaching hospital comparing cardiac surgery patients receiving either fixed-dose TXA 1000 mg followed by a 500-1000 mg infusion or EACA-7.5 g intravenous boluses followed by a 1-1.25 g/h infusion for the duration of the surgery. The major endpoint included chest tube output at 12 h, 24 h, and 7 days postoperatively. Minor endpoints included quantity and incidence of blood product transfusions and reported safety events. RESULTS: There were 1544 patients included. Chest tube output was similar between groups and the TXA group required more intraoperative blood product transfusions (22.7% vs. 18.2%, p = .03). There were no differences in the median quantity of total blood products administered postoperatively at 24 h or at 7 days. Reported safety events were similar between groups. CONCLUSION: Both fixed-dose TXA and EACA may be considered safe and effective options for antifibrinolytic therapy in cardiac surgery patients.

Development and characterization of rat duodenal organoids for ADME and toxicology applications.

Many in vitro gastrointestinal models have been developed with the hope that they will continue to improve in their similarity to the organs from which they were isolated. Intestinal organoids isolated from various species are now being used to investigate physiology and pathophysiology. In this study, intestinal stem cells were isolated from adult rat duodenum and culture conditions were optimized to promote the growth, differentiation and development of 3D organoids. We optimized and characterized rat duodenal organoids with light and electron microscopy, immunofluorescence and notably, global mRNA expression. The metabolic capacity of these cultures was investigated using probe substrates for multiple phase I and phase II drug metabolizing enzymes and found to be in line with previous results from intestinal primary cultures and a significant improvement over immortalized cell lines. Over the course of differentiation, the gene expression profiles of the rat duodenal organoids were consistent with expected trends in differentiation to various cell lineages reflecting the duodenum in vivo. Further, incubations of these cultures with naproxen and celecoxib resulted in cytotoxicity consistent with the direct cytotoxic effects of these drugs to duodenum in vivo. Based on these characteristics, the rat duodenal organoids described herein will provide a novel platform for investigating a wide variety of mechanistic questions.