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Coagulopathy is an important contributor to morbidity and mortality in trauma patients. Acidosis contributes to coagulopathy. Acidosis can be neutralized with intravascular bicarbonate, but it is unclear if the coagulation defect is rapidly reversed. The effects of acidosis and bicarbonate neutralization on coagulation function were investigated in vivo.Acidosis was induced in 12 pigs by infusing 0.2 mol/L HCl to pH 7.1. Pigs were then infused with either LR to maintain a pH of 7.1 (A-LR, n = 6) or 0.3 mol/L bicarbonate to a pH of 7.4 (A-Bi, n = 6). Blood samples were taken at baseline, 15 minutes after acidosis induction, and 15 minutes after bicarbonate neutralization. Coagulation function was assessed by prothrombin time (PT), partial thromboplastin time (PTT), thrombin generation, initial clot formation time (R), clotting rapidity (α), and clot strength (MA).Compared with baseline values, acidosis reduced fibrinogen concentration to 66% ± 2% in A-LR and to 71% ± 3% in A-Bi, and decreased platelet counts to 49% ± 4% in A-LR and to 53% ± 4% in A-Bi. Thrombin generation decreased to 60% ± 4% in A-LR and to 53% ± 7% in A-Bi. Acidosis prolonged PT and PTT about 20% and decreased α and MA. After pH neutralization, fibrinogen and platelet levels remained depleted and no reversal of acidosis-induced changes in thrombin generation, PT, PTT, α, and MA were observed.Acidosis impaired coagulation by depleting fibrinogen and platelets and by inhibiting clotting kinetics. The deficit associated with acidosis was not reversed with bicarbonate pH neutralization.