title: High-dose tranexamic acid is related to increased risk of generalized seizures after aortic valve replacement.
abstract: OBJECTIVE
  To investigate the incidence of postoperative generalized seizures in patients undergoing aortic valve replacement (AVR) under extracorporeal circulation, who received either high-dose tranexamic acid (TXA) or epsilon aminocaproic acid (EACA) as an antifibrinolytic agent.
  
  
  METHODS
  This retrospective analysis comprised 682 consecutive patients undergoing AVR with or without simultaneous coronary artery bypass surgery. Patients operated on before March 2008 were treated intra-operatively with TXA (100 mg kg⁻¹; n = 341), patients operated on after March 2008 received EACA (50 mg kg⁻¹ loading dose, followed by 25 mg kg⁻¹ h⁻¹, and an additional 5 g in the extracorporeal circuit; n = 341).
  
  
  RESULTS
  Clinically diagnosed generalized seizures were observed within the first 24h postoperatively, more frequently in patients receiving TXA compared with EACA (6.4% vs 0.6%, p < 0.001, difference = 5.8%, 95% confidence interval 3.1-8.5%). Besides the antifibrinolytic agent, three other variables differed significantly between patients with and without postoperative seizures: age (mean (SD), 77.0 (5.9) years vs 73.2 (9.0) years, p = 0.039), preoperative creatinine clearance (55.4 (16.5)ml min⁻¹ vs 72.6 (28.5)ml min⁻¹, p = 0.002), and administration of recombinant activated factor VIIa (3 out of 24 patients (12.5%) vs 8 out of 658 patients (1.2%), p = 0.005). Logistic regression analysis demonstrated a significant impact of the antifibrinolytic drug, creatinine clearance, and the application of recombinant activated factor VIIa on the occurrence of generalized seizures.
  
  
  CONCLUSIONS
  Our results indicate that high-dose TXA is associated with an increased incidence of postoperative generalized seizures in patients undergoing AVR compared with EACA, especially when suffering from renal impairment. A possible association between recombinant activated factor VIIa and the occurrence of postoperative seizures needs further investigation.
authors.affiliation: Department of Anesthesiology, Heart Center Bad Krozingen, Bad Krozingen, Germany. cornelius.keyl@herzzentrum.de
authors.forename: Cornelius
authors.initials: C
authors.lastname: Keyl
authors.forename: Reiner
authors.initials: R
authors.lastname: Uhl
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Susanne
authors.initials: S
authors.lastname: Stampf
authors.forename: Cornelius
authors.initials: C
authors.lastname: Lehane
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiesenack
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015119:Aminocaproic Acid / Q000009:adverse effects; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001021:Aortic Valve / Q000601:surgery*; D004334:Drug Administration Schedule; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D012189:Retrospective Studies; D012640:Seizures / Q000139:chemically induced* / Q000209:etiology; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D015119:Aminocaproic Acid