Evaluation of a novel hydrogel intravascular embolization agent in a swine model of fatal uncontrolled solid organ hemorrhage and coagulopathy.

INTRODUCTION: Current agents for the intravascular embolization of traumatic hemorrhage are used off-label and have been minimally studied with respect to their performance under differing coagulation conditions. We studied the hemorrhage control efficacy of a novel, liquid, polyethylene glycol-based hydrogel delivered as two liquid precursors that polymerize within the target vessel in a unique animal model of severe solid organ injury with and without dilutional coagulopathy. METHODS: Anesthetized swine (n = 36, 45 ± 3 kg) had laparotomy and splenic externalization. Half underwent 50% isovolemic hemodilution with 6% hetastarch and cooling to 33°C-35°C (coagulopathic group). All animals had controlled 20 mL/kg hemorrhage and endovascular proximal splenic artery access with a 4F catheter via a right femoral sheath. Splenic transection and 5-minute free bleeding were followed by treatment (n = 5/group) with 5 mL of gelfoam slurry, three 6-mm coils, up to 6 mL of hydrogel, or no treatment (n = 3, control). Animals received 15 mL/kg plasma and were monitored for 6 hours with continuous blood loss measurement. RESULTS: Coagulopathy was successfully established, with coagulopathic animals having greater pretreatment blood loss and earlier mean time to death regardless of the treatment group. All control animals died within 100 minutes. Overall survival without coagulopathy was 5/5 for hydrogel, 4/5 for coil, and 3/5 for gelfoam. With coagulopathy, one hydrogel animal survived to the end of the experiment, with 2/4 hydrogel deaths occurring in the final hour of observation. In noncoagulopathic animals, hydrogel demonstrated improved survival time (P < .01) and post-treatment blood loss (1.46 ± 0.8 mL/kg) over controls (18.8 ± 0.7, P = .001), gelfoam (4.7 ± 1.3, P > .05), and coils (4.6 ± 1.5, P > .05). In coagulopathic animals, hydrogel had improved survival time (P = .003) and decreased blood loss (4.2 ± 0.8 mL/kg) compared with control (20.4 ± 4.2, P = .003). CONCLUSIONS: The hydrogel demonstrated equivalent hemorrhage control performance to standard treatments under noncoagulopathic conditions and improved performance in the face of dilutional coagulopathy. This agent should be explored as a potential preferable treatment for the embolization of traumatic solid organ and other injuries. (JVS-Vascular Science 2021;2:43-51.). CLINICAL RELEVANCE: In a translational model of severe solid organ injury hemorrhage with and without coagulopathy, a novel hydrogel transarterial embolization agent demonstrated equivalent hemorrhage control performance to standard agents under noncoagulopathic conditions and improved performance in the face of dilutional coagulopathy. This agent represents a promising future treatment for the embolization of traumatic solid organ and other injuries.

Endovascular Embolization Techniques in a Novel Swine Model of Fatal Uncontrolled Solid Organ Hemorrhage and Coagulopathy.

BACKGROUND: Endovascular embolization is increasingly used in treating traumatic hemorrhage and other applications. No endovascular-capable translational large animal models exist and coagulopathy's effect on embolization techniques is unknown. We developed a coagulation-adaptable solid organ hemorrhage model in swine for investigation of embolization techniques. METHODS: Anesthetized swine (n = 26, 45 ± 3 kg) had laparotomy and splenic externalization. Half underwent 50% isovolemic hemodilution with 6% hetastarch and cooling to 33-35°C (COAG group). All had controlled 20 mL/kg hemorrhage and endovascular access to the proximal splenic artery with a 4F catheter via a right femoral sheath. Splenic transection and 5 min free bleeding were followed by treatment (n = 5/group) with 5 mL gelfoam slurry, three 6-mm coils, or no treatment (n = 3, control). Animals received 15 mL/kg plasma resuscitation and were monitored for 6 hr. Splenic blood loss was continuously measured and angiograms were performed at specified times. RESULTS: Coagulopathy was successfully established in COAG animals. Pre-treatment blood loss was greater in COAG (11 ± 6 mL/kg) than non-COAG (7 ± 3 mL/kg, P = 0.04) animals. Splenic hemorrhage was universally fatal without treatment. Non-COAG coil survival was 4/5 (326 ± 75 min) and non-COAG Gelfoam 3/5 (311 ± 67 min) versus non-COAG Control 0/3 (82 ± 18 min, P < 0.05 for both). Neither COAG Coil (0/5, 195 ± 117 min) nor COAG Gelfoam (0/5, 125 ± 32 min) treatment improved survival over COAG Control (0/3, 56 ± 19 min). Post-treatment blood loss was 4.6 ± 3.4 mL/kg in non-COAG Coil and 4.6 ± 2.9 mL/kg in non-COAG Gelfoam, both lower than non-COAG Control (18 ± 1.3 mL/kg, P = 0.05). Neither COAG Coil (8.4 ± 5.4 mL/kg) nor COAG Gelfoam (15 ± 11 ml/kg) had significantly less blood loss than COAG Control (20 ± 1.2 mL/kg). Both non-COAG treatment groups had minimal blood loss during observation, while COAG groups had ongoing slow blood loss. In the COAG Gelfoam group, there was an increase in hemorrhage between 30 and 60 min following treatment. CONCLUSIONS: A swine model of coagulation-adaptable fatal splenic hemorrhage suitable for endovascular treatment was developed. Coagulopathy had profound negative effects on coil and gelfoam efficacy in controlling bleeding, with implications for trauma and elective embolization procedures.

Abdominal aortic and junctional tourniquet versus zone III resuscitative endovascular balloon occlusion of the aorta in a swine junctional hemorrhage model.

BACKGROUND: Junctional hemorrhage is a leading contributor to battlefield mortality. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infrarenal (zone III) resuscitative endovascular balloon occlusion of the aorta (REBOA) are emerging strategies for controlling junctional hemorrhage, with AAJT currently available in select forward deployed settings and increasing interest in applying REBOA in the military prehospital environment. This study compared the hemostatic, hemodynamic, and metabolic effects of these devices used for junctional hemorrhage control. METHODS: Shock was induced in anesthetized, mechanically ventilated swine with a controlled hemorrhage (20 mL/kg) and closed femur fracture followed by uncontrolled hemorrhage from a partial femoral artery transection (40% total hemorrhage volume). Residual femoral hemorrhage was recorded during 60-minute AAJT (n = 10) or zone III REBOA (n = 10) deployment, and the arterial injury was repaired subsequently. Animals were resuscitated with 15 mL/kg autologous whole blood and observed for 6 hours. RESULTS: One animal in each group died during observation. Both devices achieved hemostasis with mean residual femoral blood loss in the AAJT and REBOA groups of 0.38 ± 0.59 mL/kg and 0.10 ± 0.07 mL/kg (p = 0.16), respectively, during the 60-minute intervention. The AAJT and REBOA augmented proximal blood pressure equally with AAJT allowing higher distal pressure than REBOA during intervention (p < 0.01). Following device deflation, AAJT animals had transiently lower mean arterial blood pressure than REBOA pigs (39 ± 6 vs. 54 ± 11 mm Hg p = 0.01). Both interventions resulted in similar degrees of lactic acidemia which resolved during observation. Similar cardiac and renal effects were observed between AAJT and REBOA. CONCLUSION: The AAJT and REBOA produced similar hemostatic, resuscitative, and metabolic effects in this model of severe shock with junctional hemorrhage. Both interventions may have utility in future military medical operations.

Should Albumin be Considered for Prehospital Resuscitation in Austere Environments? A Prospective Randomized Survival Study in Rabbits.

BACKGROUND: The new guidelines for prehospital care of combat casualties in shock recommend administration of whole blood or blood components to increase blood pressure to a permissible hypotensive level (i.e., hypotensive resuscitation [HR]). We investigated if 2 h of HR using limited volumes of whole blood, plasma, or albumin would lead to full recovery and long-term survival of rabbits subjected to severe hemorrhagic shock (HS). METHODS: Following instrumentation, laparotomy was performed on IV-anesthetized spontaneously breathing New Zealand white rabbits (3.0 kg -3.5 kg). Next, ∼40% of rabbits' blood volume was removed producing HS (mean arterial pressure [MAP]∼20 mm Hg). Fifteen minutes later, rabbits were resuscitated with a limited volume (12.5 mL/kg) of rabbit whole blood (fresh whole blood [FWB]), rabbit fresh frozen plasma (FFP), or 5% human albumin (ALB) to a target pressure (MAP) of 60 mm Hg (n=8/grp) and monitored for 2 h. Liver bleeding time was measured at baseline and 10 min after HR. Subsequently, animals were fully resuscitated (blood + lactated Ringer [LR]), surgically repaired, and recovered for 8 days. An untreated group (n = 6) was also included. RESULTS: Following HS, lactate and base deficit levels were increased to 8.2 ±â€Š1.6 and 12.9 ±â€Š3.1 mM respectively with no difference among groups. A lower volume of FWB volume was required to reach the target MAP (P < 0.05 vs. ALB) but MAP declined during the HR period (P < 0.01 vs. ALB). FWB provided higher hematocrit and platelets but it did not reduce lactate level faster than other fluids. Beside higher fibrinogen, no differences were found in hemostatic or resuscitative effects of FFP versus ALB. Bleeding time was prolonged with ALB and FFP fluids but unchanged with FWB. Untreated rabbits died during shock or shortly after. All treated rabbits except one recovered and lived for 8 days with normal blood tests and similar tissue histology. CONCLUSIONS: Two hours of HR using a limited volume of FWB, FFP, or ALB led to full recovery and long-term survival of rabbits subjected to HS. Apart from bleeding time, no clinically significant differences were found among the three fluids. Five percent human albumin solutions are isotonic, iso-oncotic, ready-to-use, stable, and compatible with all blood types and should be considered for prehospital resuscitation where blood products are not available or not accepted.

Differing Resuscitation With Aortic Occlusion in a Swine Junctional Hemorrhage Polytrauma Model.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) and Abdominal Aortic and Junctional Tourniquet (AAJT) have received much attention in recent as methods for temporary control of junctional hemorrhage. Previous studies typically used the animal's shed blood for resuscitation. With current interest in moving REBOA to prehospital environment, this study aimed to evaluate the hemodynamic and metabolic responses to different resuscitation fluids used with these devices. METHODS: In swine (Sus scrofa), shock was induced using a controlled hemorrhage, femur fracture, and uncontrolled hemorrhage from the femoral artery. Infrarenal REBOA or AAJT was deployed for 60 min during which the arterial injury was repaired. Animals were resuscitated with 15 mL/kg of shed whole blood (SWB) or fresh frozen plasma (FFP) or 30 mL/kg of a balanced crystalloid (PlasmaLyte). RESULTS: Animals in the AAJT and REBOA groups did not show any measurable differences in hemodynamics, metabolic responses, or survival with AAJT or REBOA treatment; hence, the data are pooled and analyzed among the three resuscitative fluids. SWB, FFP, and PlasmaLyte groups did not have a difference in survival time or overall survival. The animals in the SWB and FFP groups maintained higher blood pressure after resuscitation, (P < 0.001) and required significantly less norepinephrine to maintain blood pressure than those in the PlasmaLyte group (P < 0.001). The PlasmaLyte resuscitation prolonged prothrombin time and decreased thromboelastography maximum amplitude. CONCLUSIONS: After 60 min, infrarenal REBOA or AAJT aortic occlusion SWB and FFP resuscitation provided better blood pressure support with half of the resuscitative volume of PlasmaLyte. Swine resuscitated with SWB and FFP also had a more favorable coagulation profile. These data suggest that whole blood or component therapy should be used for resuscitation in conjunction with REBOA or AAJT, and administration of these fluids should be considered if prehospital device use is pursued.

Effect of partial and complete aortic balloon occlusion on survival and shock in a swine model of uncontrolled splenic hemorrhage with delayed resuscitation.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is accepted as a resuscitation adjunct and bridge to definitive hemostasis. The ischemic burden of REBOA may be mitigated by a partial REBOA (P-REBOA) strategy permitting longer occlusion times and military use for combat trauma. We evaluated REBOA and P-REBOA in a swine multiple trauma model with uncontrolled solid organ hemorrhage and delayed resuscitation and surgical hemostasis. METHODS: Anesthetized swine (51.9 ± 2.2 kg) had 20 mL/kg hemorrhage and closed femur fracture. Splenic transection was performed and free bleeding permitted for 10 minutes. Controls (n = 5) were hemorrhaged but had no REBOA, REBOA (n = 8) had 60 minutes complete zone 1 occlusion, P-REBOA (n = 8) had 15 minutes complete occlusion and 45 minutes 50% occlusion. Splenectomy was performed and plasma (15 mL/kg) resuscitation initiated 5 minutes prior to deflation. Resuscitation goal was 80 mm Hg systolic with epinephrine as needed. Animals were monitored for 6 hours. RESULTS: An initial study with 120-minute occlusion had universal fatality in three REBOA (upon deflation) and three P-REBOA animals (after 60 minutes inflation). With 60-minute occlusion, mortality was 100%, 62.5%, and 12.5% in the control, REBOA, and P-REBOA groups, respectively (p < 0.05). Survival time was shorter in controls (120 ± 89 minutes) than REBOA and P-REBOA groups (241 ± 139, 336 ± 69 minutes). Complete REBOA hemorrhaged less during inflation (1.1 ± 0.5 mL/kg) than Control (5.6 ± 1.5) and P-REBOA (4.3 ± 1.4), which were similar. Lactate was higher in the REBOA group compared with the P-REBOA group after balloon deflation, remaining elevated. Potassium increased in REBOA after deflation but returned to similar levels as P-REBOA by 120 minutes. CONCLUSION: In a military relevant model of severe uncontrolled solid organ hemorrhage 1-hour P-REBOA improved survival and mitigated hemodynamic and metabolic shock. Two hours of partial aortic occlusion was not survivable using this protocol due to ongoing hemorrhage during inflation. There is potential role for P-REBOA as part of an integrated minimally invasive field-expedient hemorrhage control and resuscitation strategy.

Long-term consequences of abdominal aortic and junctional tourniquet for hemorrhage control.

BACKGROUND: Specialized tourniquets have been deployed to the battlefield for the control of junctional/pelvic hemorrhage despite limited knowledge concerning their safety and duration of use. This study investigated long-term effects of abdominal application of the abdominal aortic and junctional tourniquet (AAJT) in a swine survival model. METHODS: Anesthetized spontaneously air-breathing swine were subjected to bilateral femoral artery injuries and subsequent 40% hemorrhage. Further hemorrhage was controlled by applying the AAJT on the lower abdomen for 0 h (n = 2, controls), 1 h (n = 6), 1.5 h (n = 6), or 2 h (n = 3). Before tourniquet release, arterial injuries were repaired, and mechanical ventilation and rapid crystalloid fluid were provided for at least 5 min. Additional fluid and 500 mL autologous blood were transfused after restoring blood flow. Animals were recovered and their mobility and health monitored up to 2 wk. RESULTS: AAJT application occluded the infrarenal abdominal aorta and stopped bilateral groin hemorrhage with rapid reversal of hemorrhagic shock and improved cranial blood pressure. All animals including controls recovered overnight but regaining hind leg function varied among AAJT-treated groups. In contrast to 1 h AAJT-treated swine that recovered full mobility in 1 wk, 2 h animals developed persistent hind leg paraplegia concurrent with urinary retention and ischemic necrosis of lumber muscles and had to be euthanized 3 d after surgery. Half of the 1.5-h group also had to be euthanized early due to paraplegia, whereas the other half recovered motor function within 2 wk. CONCLUSIONS: The results of this animal study indicated that ischemic reperfusion injuries associated with abdominal application of the AAJT were time-dependent. To avoid permanent injuries, AAJT application on the abdomen to control a groin hemorrhage could not be longer than 1 h. This was consistent with recent instructions for application of this tourniquet on the abdomen in patients.

Management of Suspected Tension Pneumothorax in Tactical Combat Casualty Care: TCCC Guidelines Change 17-02.

This change to the Tactical Combat Casualty Care (TCCC) Guidelines that updates the recommendations for management of suspected tension pneumothorax for combat casualties in the prehospital setting does the following things: (1) Continues the aggressive approach to suspecting and treating tension pneumothorax based on mechanism of injury and respiratory distress that TCCC has advocated for in the past, as opposed to waiting until shock develops as a result of the tension pneumothorax before treating. The new wording does, however, emphasize that shock and cardiac arrest may ensue if the tension pneumothorax is not treated promptly. (2) Adds additional emphasis to the importance of the current TCCC recommendation to perform needle decompression (NDC) on both sides of the chest on a combat casualty with torso trauma who suffers a traumatic cardiac arrest before reaching a medical treatment facility. (3) Adds a 10-gauge, 3.25-in needle/ catheter unit as an alternative to the previously recommended 14-gauge, 3.25-in needle/catheter unit as recommended devices for needle decompression. (4) Designates the location at which NDC should be performed as either the lateral site (fifth intercostal space [ICS] at the anterior axillary line [AAL]) or the anterior site (second ICS at the midclavicular line [MCL]). For the reasons enumerated in the body of the change report, participants on the 14 December 2017 TCCC Working Group teleconference favored including both potential sites for NDC without specifying a preferred site. (5) Adds two key elements to the description of the NDC procedure: insert the needle/ catheter unit at a perpendicular angle to the chest wall all the way to the hub, then hold the needle/catheter unit in place for 5 to 10 seconds before removing the needle in order to allow for full decompression of the pleural space to occur. (6) Defines what constitutes a successful NDC, using specific metrics such as: an observed hiss of air escaping from the chest during the NDC procedure; a decrease in respiratory distress; an increase in hemoglobin oxygen saturation; and/or an improvement in signs of shock that may be present. (7) Recommends that only two needle decompressions be attempted before continuing on to the "Circulation" portion of the TCCC Guidelines. After two NDCs have been performed, the combat medical provider should proceed to the fourth element in the "MARCH" algorithm and evaluate/treat the casualty for shock as outlined in the Circulation section of the TCCC Guidelines. Eastridge's landmark 2012 report documented that noncompressible hemorrhage caused many more combat fatalities than tension pneumothorax.1 Since the manifestations of hemorrhagic shock and shock from tension pneumothorax may be similar, the TCCC Guidelines now recommend proceeding to treatment for hemorrhagic shock (when present) after two NDCs have been performed. (8) Adds a paragraph to the end of the Circulation section of the TCCC Guidelines that calls for consideration of untreated tension pneumothorax as a potential cause for shock that has not responded to fluid resuscitation. This is an important aspect of treating shock in combat casualties that was not presently addressed in the TCCC Guidelines. (9) Adds finger thoracostomy (simple thoracostomy) and chest tubes as additional treatment options to treat suspected tension pneumothorax when further treatment is deemed necessary after two unsuccessful NDC attempts-if the combat medical provider has the skills, experience, and authorizations to perform these advanced interventions and the casualty is in shock. These two more invasive procedures are recommended only when the casualty is in refractory shock, not as the initial treatment.

Diagnostic accuracy of a novel software technology for detecting pneumothorax in a porcine model.

INTRODUCTION: Our objective was to measure the diagnostic accuracy of a novel software technology to detect pneumothorax on Brightness (B) mode and Motion (M) mode ultrasonography. METHODS: Ultrasonography fellowship-trained emergency physicians performed thoracic ultrasonography at baseline and after surgically creating a pneumothorax in eight intubated, spontaneously breathing porcine subjects. Prior to pneumothorax induction, we captured sagittal M-mode still images and B-mode videos of each intercostal space with a linear array transducer at 4cm of depth. After collection of baseline images, we placed a chest tube, injected air into the pleural space in 250mL increments, and repeated the ultrasonography for pneumothorax volumes of 250mL, 500mL, 750mL, and 1000mL. We confirmed pneumothorax with intrapleural digital manometry and ultrasound by expert sonographers. We exported collected images for interpretation by the software. We treated each individual scan as a single test for interpretation by the software. RESULTS: Excluding indeterminate results, we collected 338M-mode images for which the software demonstrated a sensitivity of 98% (95% confidence interval [CI] 92-99%), specificity of 95% (95% CI 86-99), positive likelihood ratio (LR+) of 21.6 (95% CI 7.1-65), and negative likelihood ratio (LR-) of 0.02 (95% CI 0.008-0.046). Among 364 B-mode videos, the software demonstrated a sensitivity of 86% (95% CI 81-90%), specificity of 85% (81-91%), LR+ of 5.7 (95% CI 3.2-10.2), and LR- of 0.17 (95% CI 0.12-0.22). CONCLUSIONS: This novel technology has potential as a useful adjunct to diagnose pneumothorax on thoracic ultrasonography.

Physiological Consequences of Abdominal Aortic and Junctional Tourniquet (AAJT) Application to Control Hemorrhage in a Swine Model.

INTRODUCTION: Specialized tourniquets such as Abdominal Aortic and Junctional Tourniquet (AAJT) have been deployed for control of junctional hemorrhage with limited information concerning their efficacy and safety. We examined physiological effects of a 2-h abdominal application of AAJT to control groin hemorrhage in a swine model. METHODS: Anesthetized pigs were subjected to 25% controlled hemorrhage and a groin arterial injury. Resulting hemorrhage from the groin wound was controlled for 2 h by applying AAJT on each pig's abdomen. After AAJT removal, the artery was repaired and blood flow was fully restored for 1 h. CT angiography and blood analyses were done and tissues collected for histology. Experiments were conducted in three groups of pigs (n = 6/group): mechanically ventilated (MV); spontaneously breathing (SB); and spontaneously breathing during AAJT application but transitioned to mechanical ventilation (SB-MV) before AAJT release. RESULTS: AAJT application produced sharp increases in blood pressure and heart rate. SB animals experienced labored and rapid respiration, but their PaO2 and PaCO2 were unaffected. Their respiration suddenly stopped when the AAJT was released requiring manual respiratory assistance. However, three pigs in SB group eventually died from cardiac and respiratory arrests, which coincided with hyperkalemia and metabolic acidosis that occurred after reflow. These changes were less severe in other groups. Other measures including increased hematocrit, tissue injury biomarkers, and kidney function indicators were similar in all groups. Histological changes were mild and reversible. CONCLUSION: The ischemia-induced hyperkalemia and metabolic acidosis associated with AAJT application are life-threatening in spontaneously breathing subjects. Cardiopulmonary resuscitation appears necessary when AAJT is released to prevent life-threatening consequences.

Management of External Hemorrhage in Tactical Combat Casualty Care: The Adjunctive Use of XStat™ Compressed Hemostatic Sponges: TCCC Guidelines Change 15-03.

Exsanguination from wounds in the so-called junctional regions of the body (i.e., the neck, the axilla, and the groin) was responsible for 19% of the combat fatalities who died from potentially survivable wounds sustained in Afghanistan or Iraq during 2001 to 2011. The development of improved techniques and technology to manage junctional hemorrhage has been identified in the past as a high-priority item by the Committee on Tactical Combat Casualty Care (CoTCCC) and the Army Surgeon General's Dismounted Complex Blast Injury (DCBI) Task Force. Additionally, prehospital care providers have had limited options with which to manage hemorrhage resulting from deep, narrow-track, penetrating trauma. XStat™ is a new product recently approved by the US Food and Drug Administration as a hemostatic adjunct to aid in the control of bleeding from junctional wounds in the groin or axilla. XStat has now been recommended by the CoTCCC as another tool for the combat medical provider to use in the management of junctional hemorrhage. The evidence that supports adding XStat to the TCCC Guidelines for the treatment of external hemorrhage is summarized in this paper.

Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding.

BACKGROUND: Reports of survival benefits of early transfusion of plasma with red blood cells (1:1 ratio) in trauma patients suggest that plasma may be a better fluid to replace Hextend for battlefield resuscitation. We studied possible advantages of prehospital resuscitation with plasma compared with Hextend or albumin in a model of uncontrolled hemorrhage. METHODS: Male New Zealand white rabbits (3.3 ± 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Ten minutes after injury (mean arterial pressure [MAP] < 40 mm Hg), the rabbits received small and equal volumes (15 mL/kg) of rabbit plasma (n = 10), Hextend (n = 10), or 5% human albumin (n = 9) or no fluid. Fluids were administered in two bolus injections (20 minutes apart) and targeted to a MAP of 65 mm Hg. Animals were monitored for 2.5 hours or until death, and their blood losses were measured. Arterial blood samples were collected at different times and analyzed for ABG, CBC, and coagulation tests. RESULTS: There were no differences in baseline measures among groups. Splenic injury caused similar hemorrhages (9.1 ± 0.4 mL/kg at 10 minutes) and decreased MAP in all subjects. Subsequent resuscitation initiated additional bleeding. At 60 minutes after injury (20 minutes after resuscitation), longer activated partial thromboplastin time and lower fibrinogen concentrations were apparent compared with baseline values with differences among groups. Thrombelastography analysis indicated faster and stronger clot formation with plasma and albumin resuscitation than with Hextend use. Shock indices were increased in all groups, but smaller changes were measured in the albumin group. Total blood loss did not differ among resuscitated rabbits but was higher (p < 0.05) than among nonresuscitated animals. Survival rates were 11% (untreated), 40% (Hextend and plasma), and 89% (albumin, p < 0.05). CONCLUSION: Resuscitation with plasma or albumin better preserved coagulation function than did Hextend. However, despite these improvements, plasma resuscitation did not reduce blood loss or improve survival, while albumin administration seemed beneficial.

Performance of Junctional Tourniquets in Normal Human Volunteers.

BACKGROUND: Inguinal bleeding is a common and preventable cause of death on the battlefield. Four FDA-cleared junctional tourniquets (Combat Ready Clamp [CRoC], Abdominal Aortic and Junctional Tourniquet [AAJT], Junctional Emergency Treatment Tool [JETT], and SAM Junctional Tourniquet [SJT]) were assessed in a laboratory on volunteers in order to describe differential performance of models. OBJECTIVE: To examine safety and effectiveness of junctional tourniquets in order to inform the discussions of device selection for possible fielding to military units. METHODS: The experiment measured safety and effectiveness parameters over timed, repeated applications. Lower extremity pulses were measured in 10 volunteers before and after junctional tourniquet application aimed at stopping the distal pulse assessed by Doppler auscultation. Safety was determined as the absence of adverse events during the time of application. RESULTS: The CRoC, SJT, and JETT were most effective; their effectiveness did not differ (p > 0.05). All tourniquets were applied safely and successfully in at least one instance each, but pain varied by model. Subjects assessed the CRoC as most tolerable. The CRoC and SJT were the fastest to apply. Users ranked CRoC and SJT equally as performing best. CONCLUSION: The CRoC and SJT were the best-performing junctional tourniquets using this model.

Management of External Hemorrhage in Tactical Combat Casualty Care: Chitosan-Based Hemostatic Gauze Dressings--TCCC Guidelines-Change 13-05.

Hemorrhage remains the leading cause of combat death and a major cause of death from potentially survivable injuries. Great strides have been made in controlling extremity hemorrhage with tourniquets, but not all injuries are amenable to tourniquet application. Topical hemostatic agents and dressings have also contributed to success in controlling extremity and compressible junctional hemorrhage, and their efficacy continues to increase as enhanced products are developed. Since the addition of Combat Gauze™ (Z-Medica Corporation, Wallingford, CT, USA; http://www.z-medica.com/) in April 2008 to the Tactical Combat Casualty Care (TCCC) Guidelines, there are consistent data from animal studies of severe hemorrhage that chitosan-based hemostatic gauze dressings developed for battlefield application are, at least, equally efficacious as Combat Gauze. Successful outcomes are also reported using newer chitosan-based dressings in civilian hospital-based surgical case reports and prehospital (battlefield) case reports and series. Additionally, there have been no noted complications or safety concerns in these cases or across many years of chitosan-based hemostatic dressing use in both the military and civilian prehospital sectors. Consequently, after a decade of clinical use, there is added benefit and a good safety record for using chitosan-based gauze dressings. For these reasons, many specific US military Special Operations Forces, NATO militaries, and emergency medical services (EMS) and law enforcement agencies have already implemented the widespread use of these new recommended chitosan-based hemostatic dressings. Based on the past battlefield success, this report proposes to keep Combat Gauze as the hemostatic dressing of choice along with the new addition of Celox™ Gauze (Medtrade Products Ltd., Crewe, UK; http://www.celoxmedical.com/usa/products /celox-gauze/) and ChitoGauze® (HemCon Medical Technologies, Portland, OR, USA; http://www.hemcon.com/) to the TCCC Guidelines.

Testing of junctional tourniquets by military medics to control simulated groin hemorrhage.

BACKGROUND: Junctional hemorrhage is a common cause of death on the battlefield, but there is no documented direct comparison for the use of junctional tourniquet models by US medics. The purpose of this testing is to assess military medic experience with the use of junctional tourniquets in simulated out-of-hospital trauma care. METHODS: Nine medics (seven men and two women) used four different junctional tourniquets: Combat Ready Clamp™ (CRoC™; http://www.combatmedicalsystems .com), Abdominal Aortic and Junctional Tourniquet™ (AAJT™; http://www.compressionworks.net), Junctional Emergency Treatment Tool (JETT™; http://www.narescue .com), and SAM Junctional Tourniquet® (SJT®; http://www.sammedical.com/products). These medics also acted as simulated casualties. Effectiveness percentages, as measured by stopped distal pulse by Doppler auscultation, and time to effectiveness were recorded in two tests per tourniquet (72 total tests). Tourniquet users ranked their preference of model by answering the question: "If you had to go to war today and you could only choose one, which tourniquet would you choose to bring?" RESULTS: All tourniquets used were safe under the conditions of this study. Both the SJT and the CRoC had high effectiveness percentages; their rate difference was not statistically significant. The SJT and the CRoC had fast times to effectiveness; their time difference was not statistically significant. Users preferred the SJT and the CRoC; their ranked difference was not statistically significant. CONCLUSION: The SJT and the CRoC were equally effective and fast and were preferred by the participants.

Long-term effects of Combat Ready Clamp application to control junctional hemorrhage in swine.

BACKGROUND: Groin application of Combat Ready Clamp (CRoC) in pigs elicits an acute inflammation in underlying ischemic tissues. This study examined functional recovery of pigs' hind leg(s) following 2 hours of CRoC application. METHODS: Left femoral arteries were isolated and injured in anesthetized pigs. Following 25% hemorrhage, CRoC was applied on the inguen for 2 hours (n = 6), and wounds were covered with combat gauze (CG). Bleeding was treated in the control animals (n = 5) with CG only. Next, CRoC and CG were removed, arteries were repaired and reflowed, and animals were recovered. The legs' mobility was scored daily, and their neuromuscular functions were measured on Days 7 and 14. Computed tomographic angiography and blood analysis were performed on Days 0, 2, 7, and 14. Pigs were then euthanized, and tissues were collected for histology. Umbilicus application of CRoC was also tested in four pilot experiments. RESULTS: Inguinal application of CRoC with 524 ± 12 mm Hg pressure occluded iliac arteries and collateral circulation. Following surgical repair, blood flow to the arteries was restored, and five of six CRoC-applied legs recovered full mobility within 9 days. Control-treated legs recovered full function in 3 days (p = 0.001). At 2 weeks, muscle strength of CRoC-applied legs was diminished (p < 0.05 vs. baselines or controls). Injury biomarkers in the CRoC group increased severalfold compared with the controls on Day 2 but returned to baseline afterward. Histologic changes were mostly mild and indicative of ischemia in the CRoC group. Umbilical application of CRoC required higher pressure (625 ± 8 mm Hg) and caused gross ischemic necrosis of lumbar muscles with significant disabilities. CONCLUSION: Two-hour inguinal application of CRoC caused mild and reversible ischemic injuries, which delayed full recovery of the limb function by a few days. In contrast, 2-hour umbilicus application of CRoC resulted in extensive muscle necrosis with functional disabilities. While CRoC seems safe and effective for inguinal application, other tourniquets should be evaluated for treating bilateral junctional bleeding.

Management of Junctional Hemorrhage in Tactical Combat Casualty Care: TCCC Guidelines?Proposed Change 13-03.

The vast majority of combat casualties who die from their injuries do so prior to reaching a medical treatment facility. Although most of these deaths result from nonsurvivable injuries, efforts to mitigate combat deaths can still be directed toward primary prevention through modification of techniques, tactics, and procedures and secondary prevention through improvement and use of personal protective equipment. For deaths that result from potentially survivable injuries, mitigation efforts should be directed toward primary and secondary prevention as well as tertiary prevention through medical care with an emphasis toward prehospital care as dictated by the fact that the preponderance of casualties die in the prehospital environment. Since the majority of casualties with potentially survivable injuries died from hemorrhage, priority must be placed on interventions, procedures, and training that mitigate death from truncal, junctional, and extremity exsanguination. In response to this need, multiple novel and effective junctional tourniquets have recently been developed.