title: Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and fibrinogen metabolism in swine.
abstract: Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in fibrinogen metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and instrumented with arterial and venous catheters and a thermodilution cardiac output 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 for 30 min in H and H-LR groups. Resuscitation in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the bled volume for 30 min. Fibrinogen metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and subsequent analysis by gas chromatograph-mass spectrometry, together with measurements of hemodynamics (hourly) and coagulation by thromboelastography (at baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases in arterial pH and base excess, and an increase in arterial lactate content. Fluid resuscitation corrected these changes toward normal levels. Fibrinogen level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR (both P<0.05, compared with baseline) after hemorrhage and resuscitation. Fibrinogen breakdown was increased from 3.0+/-0.4 mg kg-1 h-1 in C to 5.4+/-0.6 mg kg-1 h-1 in H and to 5.6+/-0.5 mg kg-1 h-1 in H-LR (both P<0.05, compared with control), but synthesis was unchanged. The clotting reaction time was unchanged in C and shortened to 93%+/-3% in H and to 91%+/-1% in H-LR (both P<0.05, compared with baseline). We conclude that hemorrhagic shock caused accelerated fibrinogen breakdown and coagulation. The LR resuscitation reduced tissue hypoxia indexes 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.
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA. wenjun.martini@amedd.army.mil
authors.forename: Wenjun Z
authors.initials: WZ
authors.lastname: Martini
authors.forename: David L
authors.initials: DL
authors.lastname: Chinkes
authors.forename: Jill
authors.initials: J
authors.lastname: Sondeen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism*; D006405:Hematology; D006470:Hemorrhage / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000627:therapeutic use*; D019344:Lactic Acid / Q000627:therapeutic use*; D012151:Resuscitation; D000077331:Ringer's Solution; D013552:Swine
chemical_list: D007552:Isotonic Solutions; D019344:Lactic Acid; D000077331:Ringer's Solution; D005340:Fibrinogen