title: Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery.
abstract: OBJECTIVE
  To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB).
  
  
  BACKGROUND
  CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs.
  
  
  METHODS
  One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded.
  
  
  RESULTS
  The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P < .05), and the plasma TNF-α and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (P < .05). The plasma t-PA, α2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (P < .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (P < .05) at T2 and T3. The plasma α2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (P < .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (P < .05).
  
  
  CONCLUSIONS
  Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.
authors: Department of Cardiovascular Surgery, Chinese PLA General Hospital, Beijing, China.
authors: Ting-Ting
authors: TT
authors: Chen
authors: Jiandong-Liu
authors: Gang
authors: G
authors: Wang
authors: Sheng-Li
authors: SL
authors: Jiang
authors: Li-Bing
authors: LB
authors: Li
authors: Chang-Qing
authors: CQ
authors: Gao
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000933:Antifibrinolytic Agents / Q000008:administration & dosage; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D004359:Drug Therapy, Combination / Q000379:methods; D006023:Glycoproteins / Q000008:administration & dosage*; D019918:Heart Valve Prosthesis Implantation / Q000706:statistics & numerical data*; D006801:Humans; D007249:Inflammation / Q000453:epidemiology* / Q000517:prevention & control*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology* / Q000517:prevention & control*; D015995:Prevalence; D018570:Risk Assessment; D014148:Tranexamic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000008:administration & dosage
chemical_list: D000893:Anti-Inflammatory Agents; D000933:Antifibrinolytic Agents; D006023:Glycoproteins; D014361:Trypsin Inhibitors; D014148:Tranexamic Acid; C028665:urinastatin