Effect of Recombinant FVIIa in Hypothermic, Coagulopathic Pigs with Liver Injuries
| Autor: | Michael R. Scherer, Allen P. Burke, Jennifer Wojtaszczyk, Kathy L. Ryan, John B. Holcomb, Anthony E. Pusateri, Ángel V. Delgado, John M. Uscilowicz, Joseph M Macaitis, Heather Currier, Suzanne Christensen, Rodolpho DeGuzman, Douglas S Cortez, Jason Bliss, Harold G. Klemcke |
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| Rok vydání: | 2005 |
| Předmět: |
Resuscitation
Swine Drug Evaluation Preclinical Hemorrhage Factor VIIa Critical Care and Intensive Care Medicine Bolus (medicine) Hypothermia Induced Animals Medicine Hetastarch Liver injury Disseminated intravascular coagulation Prothrombin time Analysis of Variance biology medicine.diagnostic_test business.industry Blood Coagulation Disorders Factor VII medicine.disease Survival Analysis Recombinant Proteins Disease Models Animal Liver Recombinant factor VIIa Anesthesia Prothrombin Time biology.protein Partial Thromboplastin Time Surgery business Partial thromboplastin time |
| Zdroj: | The Journal of Trauma: Injury, Infection, and Critical Care. 59:155-161 |
| ISSN: | 0022-5282 |
| Popis: | BACKGROUND Previous experiments with diverse pig models to evaluate the ability of rFVIIa to reduce hemorrhage have provided divergent results. The current study was conducted to address concerns related to previous work by using larger sample sizes, and an extended observational period of 4 hours post-injury. The objectives were to evaluate further the hemostatic efficacy and safety of rFVIIa administration after traumatic, uncontrolled hemorrhage. METHODS Anesthetized, splenectomized pigs (36.6 +/- 0.3 kg; n = 18/group) underwent an approximately 50% isovolemic blood exchange with 33 degrees C 6% hetastarch, and body temperature was adjusted to 32.5 +/- 0.5 degrees C. Subsequently, a Grade V liver injury was inflicted. After 30 seconds, either vehicle or treatment (180 microg/kg or 720 microg/kg rFVIIa) was administered intravenously as a bolus. Concomitantly, laparotomy pads were packed around the liver. Resuscitation with 33 degrees C lactated Ringer's solution (260 mL/min) was initiated and pigs were monitored for 4 hour post-injury or until death. Tissues were collected and examined histologically to assess the presence of disseminated intravascular coagulation (DIC). RESULTS Liver injuries were comparable among all groups (p = 0.89). Measures associated with in vitro coagulation (prothrombin time, activated partial thromboplastin time, thromboelastographic split-point and R times) were enhanced by rFVIIa administration (p < 0.05). However, neither percent survival (p = 0.82), survival time (p = 0.56), nor blood loss (p = 0.63) were affected by treatment. DIC was not evident in lung or kidney tissue. CONCLUSIONS These data indicate an inability of rFVIIa at these doses to reduce blood loss, or to increase survival time or percent survival in this pig model. Absence of DIC provides evidence for safe use of rFVIIa under conditions specific to this study. |
| Databáze: | OpenAIRE |
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