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euthanasia, the external dressings were checked for evidence   Strengths
          of any blood, then removed, and the Celox hemostatics also   The aim of the study, to ascertain whether Celox topical he-
          checked and removed. The area surrounding the wound was   mostatic dressing would be effective in an extended field care
          inspected for any evidence of adverse reaction.    model, was met in full. The strengths of the study are various.
                                                             It was done using the Kheirabadi model  for testing hemostat-
                                                                                           13
                                                             ics, which is the standard for conducting preclinical experimen-
          Results
                                                             tation on topical hemostatics. With similarities in physiology
          Throughout the 8-hour period, hemostasis was maintained by   and anatomy to human beings, as well as because of results in
          the dressings, with no blood soaking through to the external   previous preclinical evidence on hemostatics, it is fair to say
          dressings. The animal’s vital signs remained largely normal   that the porcine response to hemostatics is very similar to that
          throughout the study until euthanasia, with no concerns from   of humans, thus making them excellent animal test subjects.
          the veterinary anesthetist. There was some variation in blood   Outcomes were defined in advance, and the swine was treated
          pressure, but this was attributed to the large volumes of anes-  in accordance with battlefield medical protocols, making the
          thetic agents used during the study.               study rigorous within the confines of practicality of animal and
                                                             laboratory testing. Additionally, the bilateral wounding effec-
          On removal of the external dressings, the hemostatic dressings   tively doubles the results of the study, with two separate hem-
          were still intact and the external surfaces were clean. There was   orrhage sites being effectively controlled by  Celox dressing.
          no evidence of adverse reaction around the site of the wounds
          or in the blood vessels or the skin surrounding the wound. A   To our knowledge this is the longest documented use of a he-
          rudimentary autopsy was carried out to assess for any bleeding   mostatic available in the literature and adds to the body of
          from the previous study carried out within the animal’s tho-  evidence for their effectiveness as adjuncts in the treatment
          racic cavity, and no evidence of hemorrhage or other adverse   of major hemorrhage. Although this study is a useful proof
          effects was found.                                 of principle, further research is needed to prove conclusively
                                                             that hemostatics are effective in extended use, particularly in
                                                             the context of remote battlefield evacuation. Large-scale con-
          Discussion
                                                             trolled  testing  of  various  hemostatic  agents  against  a  gauze
          To our knowledge, this is the first study to show that Celox,   control, preferably with a simulated evacuation and surgical
          a first-line treatment for junctional hemorrhage,  is effective   follow-up, would be the ideal method to assess this effective-
                                                14
          over an extended period for the maintenance of hemostasis. As   ness. An analysis demonstrating how long a hemostatic would
          NATO military forces switch from large scale to contingency   be expected, or needed, to maintain hemostasis, and then test-
          operations, there is an increased chance of casualties in loca-  ing of this duration, would also add to the current body of
          tions away from Role 3 hospitals with the capability to defin-  evidence.
          itively treat arterial hemorrhage. Therefore, the capability of
          hemostatics to maintain hemostasis will be crucial to prevent
          exsanguination in the medium term, before and during evac-  Conclusion
          uation. Some hemostatics come with suggestions for duration   This study provides preclinical evidence that topical hemostat-
          of use (e.g., “can be left in place for 48 hours”).  It is unclear   ics, specifically Celox in this instance, are effective in maintain-
                                               15
          what the basis is for these recommendations, if any. There   ing hemostasis over an extended period. The evidence from
          have been no adverse effects reported with the current genera-  previous porcine studies seems to indicate that the findings
          tion of hemostatic dressings.                      may be transferable to human beings, although less-forgiving
                                                             battlefield or prehospital conditions may present more of a
          Weaknesses                                         challenge to the products used.
          This was a single experimental model on one animal with var-
          ious factors that were not in keeping with simulation of the   Further testing is needed, but in the absence of other evidence,
          remote battlefield environment. The animal was not moved   it seems that topical hemostatics will be an effective adjunct to
          after the arteriotomy wounds were created; there were no con-  the maintenance of hemostasis in extended field care. Celox
          taminants, such as dirt or sand; and the experiment was for 8   topical hemostatic dressing has proven to be effective in this
          hours’ duration only. A remote field evacuation to definitive   extended field care model and should be considered for use
          care could take considerably longer than this, but logistical   in hemorrhage where evacuation and definitive care may be
          constraints meant that the study was time limited. Thoracic   delayed.
          surgery had previously been carried out on the swine, but
          because the hemostatic was tested in the femoral area, it   Author Contributions
          is unlikely that this affected the outcome of the study. The   MW and JB are joint first authors; they conducted the exper-
          postevacuation surgical and long-term ramifications of having   iment and drafted the study. AP and CW reviewed the study,
          the hemostatics in place for this period were also not evalu-  made additions and corrections, and formatted the paper in a
          ated. The lack of a control subject is another limitation that   scientific style.
          could be considered in further experimentation; here it was
          felt that performing the intervention bilaterally, effectively   Ethical Approval Information
          doubling the subject number of the study, was more informa-  The  study  was  carried  out  under  Institutional  Animal  Care
          tive than use of a control subject. Thromboelastography was   and Use Committee (IACUC) certificate number 52-R-0114,
          not performed because of a lack of the requisite equipment,   approved by the University of Manchester (UK), as part of
          although this would have been a useful adjunct to allow mon-  a wider body of research. It took place in a veterinary prac-
          itoring of the efficiency of the animal’s coagulation.  tice in Virginia, with support from a veterinarian, a veterinary



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