Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery.
Research article published in Anesthesiology (2021)
Abstract
BACKGROUND: It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug. METHODS: Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure-response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models. RESULTS: Sixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery. CONCLUSIONS: In cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug.
Por qué esto importa para la hirudoterapia
Este metaanálisis basado en modelos agrupó 64 RCT y 18 estudios observacionales (49,817 pacientes) utilizando un modelo farmacocinético poblacional para caracterizar la relación exposición-respuesta del antifibrinolítico ácido tranexámico en cirugía cardíaca, hallando una reducción máxima de la pérdida hemática posoperatoria de aproximadamente el 40%, con regímenes de dosis bajas que ya se aproximan a un efecto casi máximo (la pérdida hemática acumulada predicha difirió en solo 58 mL entre los regímenes de dosis bajas y altas, con una diferencia absoluta del 2% en la tasa de transfusión de eritrocitos), mientras que la dosis alta duplicó aproximadamente el riesgo de convulsiones frente a un incremento de 1.2 veces para la dosis baja, lo que respalda los regímenes de dosis bajas. Para la hirudoterapia, esto es relevante como un caso de contraste en el eje sangrado frente a fibrinólisis: el ácido tranexámico suprime la fibrinólisis para reducir el sangrado, el polo opuesto a las moléculas del secretoma de la sanguijuela (como la destabilasa y la hirudin) que promueven la anticoagulación y la degradación del coágulo, ilustrando cuán finamente la dosis y la exposición gobiernan el equilibrio hemostático que la terapia con sanguijuelas también perturba. Advertencia: los autores advierten explícitamente que los resultados derivan de modelos y son parcialmente observacionales, con exposiciones farmacológicas predichas (no medidas), y que el estudio se refiere a un antifibrinolítico sintético en cirugía, sin contenido de sanguijuelas o hirudoterapia.
Citación
Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery.
Zufferey PJ et al. · Anesthesiology, 2021
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026