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Evaluation of tris-hydroxymethylaminomethane on reversing coagulation abnormalities caused by acidosis in pigs*

Martini, Wenjun Z. PhD; Dubick, Michael A. PhD; Wade, Charles E. PhD; Holcomb, John B. MD

doi: 10.1097/01.CCM.0000266682.74602.6A
Laboratory Investigations

Objective: To investigate the effect of tris-hydroxymethylaminomethane (THAM) pH neutralization on reversing coagulation abnormalities caused by acidosis.

Design: Random and controlled study.

Setting: Animal research facility and laboratory.

Subjects: Yorkshire swine (n = 18).

Interventions: 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).

Measurements and Main 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 [α], 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%, α 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, α, 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.

From the U.S. Army Institute of Surgical Research, Ft. Sam Houston, TX.

Supported by the U.S. Army Medical Research and Medical Command.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense (AR 360-5).

The authors have not disclosed any potential conflicts of interest.

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© 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins