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

Background Trauma 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. Porcin...

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Autores principales: Ben E Biesterveld, Umar F Bhatti, Aaron M Williams, Yongqing Li, Hasan B Alam, Michael T Kemp, Rachel L O'Connell, Glenn K Wakam, Ali Siddiqui, Nathan Graham, Kiril Chtraklin, Alizeh Shamshad
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spelling oai:doaj.org-article:5bdfe70f8fc2480882ba381daa2394432021-11-11T10:30:08ZDevelopment of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia10.1136/tsaco-2020-0006362397-5776https://doaj.org/article/5bdfe70f8fc2480882ba381daa2394432021-11-01T00:00:00Zhttps://tsaco.bmj.com/content/6/1/e000636.fullhttps://doaj.org/toc/2397-5776Background Trauma 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.Methods Our 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.Results All 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.Conclusion We 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 evidence Not applicable. Animal study.Ben E BiesterveldUmar F BhattiAaron M WilliamsYongqing LiHasan B AlamMichael T KempRachel L O'ConnellGlenn K WakamAli SiddiquiNathan GrahamKiril ChtraklinAlizeh ShamshadBMJ Publishing GrouparticleSurgeryRD1-811Medical emergencies. Critical care. Intensive care. First aidRC86-88.9ENTrauma Surgery & Acute Care Open, Vol 6, Iss 1 (2021)
institution DOAJ
collection DOAJ
language EN
topic Surgery
RD1-811
Medical emergencies. Critical care. Intensive care. First aid
RC86-88.9
spellingShingle Surgery
RD1-811
Medical emergencies. Critical care. Intensive care. First aid
RC86-88.9
Ben E Biesterveld
Umar F Bhatti
Aaron M Williams
Yongqing Li
Hasan B Alam
Michael T Kemp
Rachel L O'Connell
Glenn K Wakam
Ali Siddiqui
Nathan Graham
Kiril Chtraklin
Alizeh Shamshad
Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
description Background Trauma 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.Methods Our 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.Results All 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.Conclusion We 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 evidence Not applicable. Animal study.
format article
author Ben E Biesterveld
Umar F Bhatti
Aaron M Williams
Yongqing Li
Hasan B Alam
Michael T Kemp
Rachel L O'Connell
Glenn K Wakam
Ali Siddiqui
Nathan Graham
Kiril Chtraklin
Alizeh Shamshad
author_facet Ben E Biesterveld
Umar F Bhatti
Aaron M Williams
Yongqing Li
Hasan B Alam
Michael T Kemp
Rachel L O'Connell
Glenn K Wakam
Ali Siddiqui
Nathan Graham
Kiril Chtraklin
Alizeh Shamshad
author_sort Ben E Biesterveld
title Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
title_short Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
title_full Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
title_fullStr Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
title_full_unstemmed Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
title_sort development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia
publisher BMJ Publishing Group
publishDate 2021
url https://doaj.org/article/5bdfe70f8fc2480882ba381daa239443
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