title: Topical tranexamic Acid does not affect electrophysiologic or neurovascular sciatic nerve markers in an animal model.
abstract: BACKGROUND
  Tranexamic acid is a safe and effective antifibrinolytic agent used systemically and topically to reduce blood loss and transfusion rate in patients having TKA or THA. As the hip does not have a defined capsule, topical application of tranexamic acid may entirely envelop the sciatic nerve during THA. Accidental application of tranexamic acid onto the spinal cord in spinal anesthesia has been shown to produce seizures; therefore, we sought to investigate if topical application of tranexamic acid on the sciatic nerve has a deleterious effect.
  
  
  OBJECTIVE
  We explored whether there were any short- or long-term alterations in (1) electrophysiologic measures, (2) macrophage recruitment, or (3) blood-nerve barrier permeability. Our hypothesis was that local application of tranexamic acid would have a transient effect or no effect on histologic features and function of the sciatic nerve.
  
  
  METHODS
  We used a rat protocol to model sciatic nerve exposure in THA to determine the effects of tranexamic acid on neural histologic features and function. We evaluated 35 rats by the dorsal gluteal splitting approach to expose the sciatic nerve for topical use of control and tranexamic acid. We evaluated EMG changes (distal latency, amplitude, nerve conduction velocity), histologic signs of nerve injury via macrophage recruitment, and changes in blood-nerve barrier permeability at early (4 days) and late (1 month) times after surgery, after application of subtherapeutic (1 mg/kg body weight [1.6 mg]), therapeutic (10 mg/kg [16 mg]), and supratherapeutic (100 mg/kg [160 mg]) concentrations of tranexamic acid. Differences in blood-nerve barrier permeability, macrophage recruitment, and EMG between normal and tranexamic acid-treated nerves were calculated using one-way ANOVA, with Newman-Keuls post hoc analyses, at each time. A post hoc power calculation showed that with the numbers available, we had 16% power to detect a 50% difference in EMG changes between the control, 1 mg/kg group, 10 mg/kg group, and 100 mg/kg group.
  
  
  RESULTS
  At the early and late times, with the numbers available, there were no differences in EMG except for distal latency at 4 days, macrophage recruitment, or changes in blood-nerve barrier between control rats and those with tranexamic acid-treated nerves. The distal latency in the 1 mg tranexamic acid-treated animals at 4 days was 1.06 ± 0.15 ms (p = 0.0036 versus all other groups, 95% CI, 0.89-1.25), whereas the distal latencies in the control, the 10 mg/kg, and 100 mg/kg tranexamic acid-treated animals were 0.83 ± 0.11, 0.89 ± 0.05, and 0.87 ± 0.13, respectively. Distal latencies were not increased in any of the groups at 1 month with the numbers available (0.81 ± 0.10, 0.89 ± 0.03, 0.81 ± 0.06, and 0.83 ± 0.08 ms, respectively, for controls; 1 mg/kg, 10 mg/kg, and 100 mg/kg for the tranexamic acid-treated groups).
  
  
  CONCLUSIONS
  In our in vivo rat model study, tranexamic acid did not appear to have any clinically relevant effect on the sciatic nerve resulting from topical administration up to 1 month. However, because our statistical power was low, these data should be considered hypothesis-generating pilot data for larger, more-definitive studies.
  
  
  CONCLUSIONS
  Topical tranexamic acid is effective in decreasing patient blood loss during THA, and results from our in vivo rat model study suggest there may be no electrophysiologic and histologic effects on the sciatic nerve, with the numbers available, up to 1 month.
authors.affiliation: Department of Orthopaedic Surgery, University of California, Irvine, 101 The City Drive S, Pavillion III, Orange, CA, 92868, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Schwarzkopf
authors.forename: Phuc
authors.initials: P
authors.lastname: Dang
authors.forename: Michele
authors.initials: M
authors.lastname: Luu
authors.forename: Tahseen
authors.initials: T
authors.lastname: Mozaffar
authors.forename: Ranjan
authors.initials: R
authors.lastname: Gupta
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects*; D014148:Tranexamic Acid / Q000008:administration & dosage*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid