title: Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies.
abstract: BACKGROUND
  The aim of this meta-analysis was to assess whether tranexamic acid (TXA) therapy for adult cardiac surgery is associated with an increase in the risk of seizures, and we performed a meta-analysis of randomized controlled trials (RCTs) and non-randomized observational studies.
  
  
  METHODS
  MEDLINE and EMBASE were searched through December 2016 using PubMed and OVID. Eligible studies were RCTs and non-randomized observational studies on TXA versus control (no TXA, placebo, or active control such as low-dose TXA, aprotinin, and epsilon aminocaproic acid) enrolling adult patients undergoing cardiac surgery and reporting the postoperative incidence of seizures as an outcome. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic odds ratios (ORs) in the random-effects model.
  
  
  RESULTS
  Of 90 potentially relevant articles screened initially, 16 reports of eligible studies were identified and included. A pooled analysis of all 16 studies (enrolling 45,235 patients) demonstrated that TXA therapy was associated with a statistically significant increase in the seizures incidence (OR=4.13; 95% CI: 2.59 to 6.57; P<0.00001). A subgroup analysis indicated a statistically significant increase in the seizures incidence with TXA therapy in all subgroups of 5 RCTs, 5 adjusted observational studies, and 6 unadjusted observational studies with no statistically significant subgroup differences (P=0.36; I2=1.5%).
  
  
  CONCLUSIONS
  The results of the present meta-analysis of 16 studies enrolling 45,235 patients confirmed that TXA therapy for adult cardiac surgery is associated with a 4.1-fold increase in the risk of seizure.
authors.affiliation: Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan - kfgth973@ybb.ne.jp.
authors.forename: Hisato
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Cardiology, Detroit Medical Center, Detroit, MI, USA.
authors.forename: Tomo
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Umemoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000009:adverse effects*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012640:Seizures / Q000139:chemically induced*; D014148:Tranexamic Acid / Q000009:adverse effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid