EudraCT number: 2010-024104-99.

This study sought to compare the effect of tranexamic acid (TXA) administration on cardiopulmonary bypass-induced platelet dysfunction in patients who received preoperative aspirin or not. We performed a prospective, randomized, double-blind pilot study, including patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Patients without aspirin interruption were enrolled in the 'group ASPIRIN' (n = 18) and those who had never been treated with aspirin were included in the 'group NO ASPIRIN' (n = 10). Patients were then randomized to receive either TXA or the same infusion of normal saline. Multiple electrode aggregometry was used to assess platelet function at the different time points throughout the surgery: baseline, post-TXA loading dose, aortic unclamping (End CPB), and 5 min after protamine (Protamine). Compared to those included in the group NO ASPIRIN, patients included in the group ASPIRIN presented a decreased baseline platelet function measured by ASP test (P < 0.01) and collagen test (P < 0.01). In the group NO ASPIRIN, treatment group (TXA vs. placebo) significantly influenced the results for ADP test (P < 0.01), thrombin receptor-activating peptide test (P = 0.01), and ASP test (P = 0.01). We observed that TXA improved platelet function, as measured using multiple electrode aggregometry on ADP test, thrombin receptor-activating peptide test, and ASP test, at the end of CPB (P < 0.05). TXA might decrease the magnitude of platelet dysfunction in aspirin-free patients undergoing cardiac surgery. Further studies are needed to confirm these results and assess a potential relationship with clinical endpoints.

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Background: Cardiac output (CO) is a physiological variable that should be monitored during cardiac surgery. The purpose of this study was to assess the trending ability of two CO monitors, esCCO (Nihon Kohden™, Tokyo, Japan) and Volume View (VV) (Edwards Lifesciences, Irvine, USA). Methods: A total of 19 patients were included in the study. Before cardiopulmonary bypass (CPB), CO was measured simultaneously using both esCCO and VV devices before and after three CO-modifying manoeuvres (passive leg raise [PLR], the end expiratory occlusion test [EEOT] and positive end expiratory pressure [PEEP] at 10 cm H 2 O). Five CO values for esCCO and three for VV were averaged and compared during a one-minute period of time before and after each manoeuvre. Results: A total of 114 paired readings were collected. Median CO values were 4.3 L min -1 (IQR: 3.8; 5.2) and 3.8 L min -1 (IQR: 3.5; 4.5) for esCCO and VV, respectively. The precision error was 1.4% (95% CI:1.0-1.7) for esCCO and 2.2% (95% CI: 1.8-2.7) for VV. The bias between esCCO and VV values was normally distributed (P = 0.0596). Between esCCO and VV, the mean bias was +0.6 L min -1 with a Limit of Agreement (LOA) of -1.8 L min -1 and +3.0 L min -1 . The concordance rate was 43% (95% CI: 29-58) between esCCO and VV. Conclusion: Both single and trended measurements of CO using esCCO and VV were not in agreement. This large discrepancy leads one to the conclusion that any outcome study conducted with one of these devices cannot be applied to the other.

Antifibrinolytic agents are often used in different clinical situations, especially in cardiac surgery. During several years, aprotinin was the drug of choice because more than antifibrinolytic properties, aprotinin offers a direct effect on kallikrein and inflammatory pathways. In 2008, The Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) initiated a discussion about real risks associated with aprotinin administration. Tranexamic acid and epsilon-aminocaproic acid appear to be interesting alternatives in our daily practice. The exact mechanism of action, the pharmacokinetic parameters, the efficacy, and the safety profile need to be clarified for lysine analogs. In this review, the different antifibrinolytics will be described with a special interest into the route of work, and recent patents. Current studies about the pharmacokinetic and the pharmacodynamic profile will be described, and finally the benefit-to-risk balance in patients undergoing cardiac surgery with cardiopulmonary bypass will be discussed.

To the Editor:I read with interest the recent article of Shimizu et al. [1]. First, I congratulate the authors for their work and their wish to improve our knowledge about the use of tranexamic acid (TXA) in congenital heart surgery (CHS). It appears more and more evident that if TXA could reduce blood loss, the clinical benefit of this drug does not appear so evident. Indeed, if we analyze the available literature comparing TXA to placebo in terms of blood loss but also transfusion requirement, the results of the analysis indicate that TXA marginally decreases blood-product transfusion compared with placebo in the pediatric population. The results obtained for postoperative blood loss and other outcomes, such as re-exploration, are generally too heterogeneous, and no clear results could be interpreted [2]. As the authors wrote, the variability in the dosage schemes used in the different studies is striking. Moreover, the choice of TXA dosage was not based on pharmacokinetic (PK) data regarding the fibrinolytic inhibiting activity of the drug; instead, dosage choice was empirical based on its effects on blood loss. In fact, no pharmacological data on TXA are available in the pediatric cardiac surgery population. PK data have been determined in adults, and suggest the administration of a loading dose of 12.5 mg/kg given over 30 min, a maintenance infusion of 6.5 mg/kg/h, and a cardiopulmonary bypass (CPB) priming dose of 1 mg/kg to maintain TXA concentration in blood [345 lM/ml [3]. This dosage scheme is clearly smaller than those used in the different pediatric trials. Another lack of evidence in the use of TXA is the pharmacodynamic (PD) evaluation. Indeed, no randomized controlled trials have evaluated the effect of CPB on fibrinolysis activation with the currently available monitoring (thromboelastography, rotation thromboelastometry, or standard biological tests). What is the exact frequency rate of hyperfibrinolysis during CPB in CHS? What is the minimal effective concentration of TXA require to inhibit this fibrinolysis? Does TXA mechanism of action only work by fibrinolysis inhibition or by a combination with inflammatory pathway inhibition, and/or platelet function improvement [4]?In the pediatric population, side effects related to TXA administration are not well established. Most of the studies available have evaluated the effect on bleeding and bloodproduct requirements, but none were designed to evaluate postoperative outcomes in the population. Actually, only two retrospective cohort studies reported side effects related to TXA administration during pediatric cardiac surgery [5]. They found 9.6% renal injury, 1.8% renal failure, 3.5% seizure, and 2.6% other neurological events. According to their results, more than 500 patients per group are needed to evaluate side effects related to TXA administration.In conclusion, the article by Shimizu et al. offers another study and another reason to believe that we need more evaluations! We need to describe the PK in the pediatric population; we need to evaluat...

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