To the Editor:
We appreciate the comments by Sarridou et al.  regarding our article , since they highlight the importance of “drug safety” in anesthesia. With respect to etomidate-induced convulsive seizures (CS), it is noteworthy that they occasionally appear immediately after administration of the induction dose, persist for only a few minutes , and are not routinely assessed. Tranexamic acid (TXA)—associated CS, however, are usually observed in the intensive care unit, at a time when TXA concentrations in the cerebral fluid reach a maximum . Since etomidate is associated with more stable hemodynamics than its competitors without increasing adverse outcomes , it is difficult to replace etomidate as an induction agent in cardiac surgery.
We agree with Sarridou et al. that our study was probably underpowered for the detection of an interaction between history of stroke and risk of CS. Nevertheless, it is also important to note that even in our large cohort of cardiac surgical patients no statistical evidence could be provided that history of stroke is a contraindication for TXA use.
The effect of renal impairment on the TXA-induced risk of CS is indeed well-known and in patients with chronic kidney disease even a single bolus dose of 1 g TXA (equivalent to about 10–15 mg/kg body weight) was associated with a higher risk of CS than in patients without renal impairment . However, this latter data are limited by the small number of patients with chronic kidney disease and further supportive studies are thus required. A recent meta-analysis on the efficacy and safety of TXA, which focused on CS for safety, suggested a cumulative dose of approximately 15 mg/kg body weight for a bolus plus continuous infusion regimen and 20 mg/kg body weight for a bolus-only regimen . In our opinion, these are values that should be commonly considered in clinical practice.
Sarridou DG, Boutou A, Mouratoglou SA. TXA and stroke in seizure activity in valvular surgery. J Anesth. 2021. https://doi.org/10.1007/s00540-021-02956-2.
Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery. J Anesth. 2021;35(3):451–4. https://doi.org/10.1007/s00540-021-02924-w.
Rainess RA, Patel V, Stander E. Etomidate induced seizure: adverse drug event case report. J Pharm Pract. 2020;14: 897190020958243. https://doi.org/10.1177/0897190020958243.
Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid-associated seizures: causes and treatment. Ann Neurol. 2016;79(1):18–26. https://doi.org/10.1002/ana.24558.
Yao YT, He LX, Fang NX, Ma J. Anesthetic induction with etomidate in cardiac surgical patients: a PRISMA-compliant systematic review and meta-analysis. J Cardiothorac Vasc Anesth. 2021;35(4):1073–85. https://doi.org/10.1053/j.jvca.2020.11.068.
Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Tranexamic acid and convulsive seizures after off-pump coronary artery bypass surgery: the role of renal insufficiency. Interact Cardiovasc Thorac Surg. 2019;29(6):852–4. https://doi.org/10.1093/icvts/ivz188.
Zufferey PJ, Lanoiselée J, Graouch B, Vieille B, Delavenne X, Ollier E. Exposure-response relationship of tranexamic acid in cardiac surgery. Anesthesiology. 2021;134(2):165–78. https://doi.org/10.1097/ALN.0000000000003633.
Open Access funding enabled and organized by Projekt DEAL.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Koster, A., Hulde, N. & Zittermann, A. Reply to Sarridou et al.. J Anesth 35, 769–770 (2021). https://doi.org/10.1007/s00540-021-02964-2
- Renal dysfunction
- Tranexamic acid