Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia

Abstract

BackgroundTrauma and sepsis are individually two of the leading causes of death worldwide. When combined, the mortality is greater than 50%. Thus, it is imperative to have a reproducible and reliable animal model to study the effects of polytrauma and sepsis and test novel treatment options. Porcine models are more translatable to humans than rodent models due to the similarities in anatomy and physiological response. We embarked on a study to develop a reproducible model of lethal polytrauma and intra-abdominal sepsis, which was lethal, though potentially salvageable with treatment.MethodsOur laboratory has a well-established porcine model that was used as the foundation. Animals were subjected to a rectus crush injury, long bone fracture, liver and spleen laceration, traumatic brain injury and hemorrhage that was used as a foundation. We tested various colon injuries to create intra-abdominal sepsis. All animals underwent injuries followed by a period of shock, then subsequent resuscitation.ResultsAll animals had blood culture-proven sepsis. Attempts at long-term survival of animals after injury were ceased because of poor appetite and energy. We shifted to an 8-hour endpoint. The polytrauma injury pattern remained constant and the colon injury pattern changed with the intention of creating a model that was ultimately lethal but potentially salvageable with a therapeutic drug. An uncontrolled cecal injury (n=4) group resulted in very early deaths. A controlled cecal injury (CCI; n=4) group had prolonged time prior to mortality with one surviving to the endpoint. The sigmoid injury (n=5) produced a similar survival curve to CCI but no animals surviving to the endpoint.ConclusionWe have described a porcine model of polytrauma and sepsis that is reproducible and may be used to investigate novel treatments for trauma and sepsis.Level of evidenceNot applicable. Animal study.

A combat casualty relevant dismounted complex blast injury model in swine

“…Cho et al 24 also showed increasing PT and declining MA in their multicenter polytrauma swine model; however, their use of normal saline (NS) creates a dilutional coagulopathy. Other previous military-relevant polytrauma models utilized NS; 23,25 however, we avoided NS to prevent dilutional coagulopathy and instead evaluate iatrogenic TIC. Thus, the increasing PT and decreasing MA levels are significantly correlated with greater blood loss and deeper shock leading to TIC.…”

“…Previously described military relevant polytrauma models include a noncompressible torso hemorrhage model, 23 a multicenter lethal triad model (consisting of acidosis, hypothermia, and dilutional coagulopathy), 24 and an intra-abdominal sepsis model incorporating TBI. 25 Our newly created model focuses on DCBI with TBI, TI, and HS; thus incorporating additional challenges that TBI contributes to shock resuscitation and vice versa. Secondary insults such as hypotension, hypoxia, and inflammation lead to additional neurological injury and worsen secondary Figure 3.…”

“…Animal models are essential to evaluate HS-induced TIC and TBI resuscitation strategies, but few models have employed polytrauma (TI and hypoperfusion), and fewer incorporate TBI. Previously described military relevant polytrauma models include a noncompressible torso hemorrhage model, 23 a multicenter lethal triad model (consisting of acidosis, hypothermia, and dilutional coagulopathy), 24 and an intra-abdominal sepsis model incorporating TBI 25 . Our newly created model focuses on DCBI with TBI, TI, and HS; thus incorporating additional challenges that TBI contributes to shock resuscitation and vice versa.…”

Defining Endotheliopathy in Murine Polytrauma Models

“…Mice underwent a 1 inch long midline laparotomy with bilateral abdominal rectus muscle crush injury. After entry to the abdomen was achieved bilateral hemostat clamps were placed onto the abdominal rectus muscles for 30 s. Methods utilized here were adapted from those previously described in a porcine model (21,22). After laparotomy and crush the abdomen was closed and animals were recovered in warmed recovery area.…”