title: Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis.
abstract: BACKGROUND
  The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the efficacy and safety of combined topical with intravenous tranexamic acid (TXA) versus topical, intravenous TXA alone or control for reducing blood loss after a total knee arthroplasty (TKA).
  
  
  METHODS
  In May 2016, a systematic computer-based search was conducted in the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Wanfang database. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. Only patients prepared for primary TKA that administration combined topical with intravenous TXA with topical TXA, intravenous (IV) TXA, or control group for reducing blood loss were included. Eligible criteria were published RCTs about combined topical with intravenous TXA with topical alone or intravenous alone. The primary endpoint was the total blood loss and need for transfusion. The complications of deep venous thrombosis (DVT) were also compiled to assess the safety of combined topical TXA with intravenous TXA. Relative risks (RRs) with 95% CIs were estimated for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. The Cochrane risk of bias tool was used to appraise a risk of bias. Stata 12.0 software was used for meta-analysis.
  
  
  RESULTS
  Fifteen studies involving 1495 patients met the inclusion criteria. The pooled meta-analysis indicated that combined topical TXA with intravenous TXA can reduce the total blood loss compared with placebo with a mean of 458.66 mL and the difference is statistically significant (MD = -458.66, 95% CI: -655.40 to 261.91, P < 0.001). Compared with intravenous TXA, combined administrated TXA can decrease the total blood loss, and the difference is statistically significant (MD = -554.03, 95% CI: -1066.21 to -41.85, P = 0.034). Compared with the topical administration TXA, the pooled meta-analysis indicated that combined TXA can decrease the amount of total blood loss with mean 107.65 mL with statistically significant(MD = -107.65, 95% CI: -525.55 to -239.9141.85, P = 0.001). The pooled results indicated that combined topical with intravenous TXA can decrease the need for transfusion (RR = 0.34, 95% CI: 0.23-0.50, P < 0.001). There is no significant difference between combined topical with intravenous TXA with topical or intravenous TXA (P > 0.05) in terms of need for transfusion and the occurrence of DVT.
  
  
  CONCLUSIONS
  Compared with topical, intravenous TXA alone or control group, combined topical with TXA, can decrease the total blood loss and subsequent need for transfusion without increasing the occurrence of DVT. The dose and timing to administration TXA is different, and more randomized controlled trials are warranted to clarify the optimal dosing and time to administration TXA.
authors.affiliation: Department of Orthopedic Nursing, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Lin
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Jie
authors.forename: Hong-Biao
authors.initials: HB
authors.lastname: Li
authors.forename: Xi-Cheng
authors.initials: XC
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.forename: Xin-Qiang
authors.initials: XQ
authors.lastname: Jiang
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Ma
mesh_terms: D061605:Administration, Intravenous; D000287:Administration, Topical; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000379:methods; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006801:Humans; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid