title: Evaluation of tris-hydroxymethylaminomethane on reversing coagulation abnormalities caused by acidosis in pigs.
abstract: OBJECTIVE
  To investigate the effect of tris-hydroxymethylaminomethane (THAM) pH neutralization on reversing coagulation abnormalities caused by acidosis.
  
  
  METHODS
  Random and controlled study.
  
  
  METHODS
  Animal research facility and laboratory.
  
  
  METHODS
  Yorkshire swine (n = 18).
  
  
  METHODS
  Acidosis was induced in 12 pigs by infusing 0.2 M hydrochloric acid (HCl). When the target pH of 7.1 was achieved, the pigs were infused with either 0.3 M THAM to achieve pH of 7.4 (intervention group) or an equal volume of lactated Ringer's solution (acid control group).
  
  
  RESULTS
  Blood samples were taken at baseline, 15 mins after reaching pH of 7.1, and 15 mins after THAM pH neutralization. Coagulation function was assessed by thrombin generation, prothrombin time, activated partial thromboplastin time, activated clotting time, and thromboelastography (maximum clot formation time [R+K], clotting rapidity [alpha], and clot strength [maximum amplitude]). An additional six pigs (sham group) were infused with THAM, and an equal volume of fluid as the 12 coagulopathic pigs was given to assess effects of THAM and hemodilution. Comparisons were made using a mixed model analysis of variance. No change in any indexes of coagulation was observed in sham pigs. Compared with baseline, acidosis of pH 7.1 decreased base excess from 6.6 +/- 0.5 mM to -12.4 +/- 0.5 mM; reduced fibrinogen levels to 72% +/- 2%, platelet counts to 53% +/- 3%, thrombin generation to 58% +/- 4%, alpha to 84% +/- 2%, and maximum amplitude to 75% +/- 3%; and prolonged prothrombin time to 113% +/- 2%, partial thromboplastin time to 122% +/- 4%, activated clotting time to 124% +/- 3%, and R + K to 119% +/- 3% (all p < .05). THAM infusion corrected pH to 7.40 +/- 0.02 and base excess to 2.6 +/- 0.9 mM (p < .05). However, there were no differences in thrombin generation, prothrombin time, partial thromboplastin time, activated clotting time, R+K, alpha, or maximum amplitude between the groups with or without pH correction.
  
  
  CONCLUSIONS
  Acidosis impaired coagulation by depleting clotting factors, inhibiting thrombin generation, and affecting clot strength and stability. THAM corrected acid-base deficit but did not acutely reverse the coagulation abnormalities in the model.
authors: U.S. Army Institute of Surgical Research, Ft. Sam Houston, TX, USA. wenjun.martini@amedd.army.mil
authors: Wenjun Z
authors: WZ
authors: Martini
authors: Michael A
authors: MA
authors: Dubick
authors: Charles E
authors: CE
authors: Wade
authors: John B
authors: JB
authors: Holcomb
mesh_terms: D000138:Acidosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000517:prevention & control*; D001780:Blood Coagulation Tests; D002021:Buffers; D005340:Fibrinogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D011897:Random Allocation; D013552:Swine; D013917:Thrombin / Q000096:biosynthesis; D014325:Tromethamine / Q000627:therapeutic use*
chemical_list: D002021:Buffers; D014325:Tromethamine; D005340:Fibrinogen; D013917:Thrombin