EFFECTS OF HEMORRHAGE AND LACTATED RINGER'S (LR) RESUSCITATION ON COAGULATION AND FIBRINOGEN METABOLISM IN PIGS

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Objective: Hemorrhagic coagulopathy is a significant complication following traumatic injury and much of the underlying mechanism remains unclear. We investigated changes in fibrinogen metabolism and coagulation following a moderate hemorrhage and resuscitation. Methods: Pigs of either sex (40 ± 1 kg) were anesthetized and instrumented with arterial and venous catheters, and a thermodilution cardiac output (CO) catheter. Pigs were randomized into control (C; n = 6), hemorrhage (H, n = 6), and hemorrhage and resuscitation (H-LR, n = 6) groups. Hemorrhage was induced by bleeding 35% of total blood volume in 30 min in H and H-LR. Resuscitation was performed using LR at 3 times the bled volume over 30 min in H-LR. Fibrinogen metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (phe, 6h) and d5-phe (4h) and subsequent analysis by gas chromatograph mass spectrometry, together with measurements of hemodynamics and coagulation (by TEG). Results: Hemorrhage caused decreases in mean arterial pressure, CO, pH and BE, as well as an increase in lactate content. Resuscitation corrected these changes toward normal. Clotting R time was unchanged in C, and shortened to 93 ± 3% in H and to 91 ± 1% in H-LR (both p <0.05, compare to baseline). Fibrinogen level was unchanged in C and decreased to 76 ± 4% in H and to 73 ± 3% in H-LR (both p <0.05, compare to baseline). Fibrinogen breakdown was increased from 3.0 ± 0.4 mg/kg/h in C to 5.4 ± 0.6 mg/kg/h in H and to 5.6 ± 0.5 mg/kg/h in H-LR (both p <0.05, compare to control), but synthesis was unchanged. Conclusion: Hemorrhage shock caused accelerated fibrinogen breakdown and coagulation. LR resuscitation reduced tissue hypoxia indices but did not affect the changes in fibrinogen metabolism and coagulation from hemorrhage. Thus, effective treatment of hemorrhage should include combining standard of care resuscitation with interventions to correct alterations in coagulation.