Validation Of Efficacy And Safety Of Two Axillary Junctional Site Tourniquets

Objective: Axillary junctional site hemorrhage remains an important issue in combat care.As the anatomical structures are certainly different in the axillary sites compared to the better-understood inguinal area.A valid animal model is highly desirable.This study details the development of an axillary artery hemorrhage model based on swine and validated the efficacy and safety of a junctional tourniquet on the model.Methods:1.Quantitative hemostasis device controlling axillary artery hemorrhage in swine modelTwenty male Yorkshire swine,aged 4 month old and weighing 50-60 kg,were randomized equally into three groups,with 4 in each.Group Ⅰ,Ⅱ,and Ⅲ first received Volume-Controlled Blood Loss（VCBL）through the right femoral artery to 10%,20%,and 30%of Effective Circulating Volume（ECV）,respectively,to simulate the hemorrhagic shock,which was induced by rapid blood loss of artery injury before hemostatic measures were adopted.An axillary hemorrhage model was achieved by cutting a 2-mm（1/3 of the vessel’s circumference）incision.Then,Free Blood Loss（FBL）through the pre-cut of the axillary artery was achieved by releasing the pre-set vascular blocking bands.During the FBL phase,a mechanical arm with a hemostatic balloon was used to simulate the external compression action in pre-hospital settings.Five sheets of gauze were pre-packed in the wound to calculate the Free Blood Loss（FBL）.Hemodynamic parameters were monitored every 10 mins for 90 mins.2.The effect of SAM^? Junctional Tourniquet when applied in the axilla,a swine model studyEighteen male Yorkshire swine,aged 6-month-old and weighing 55-72 kg,were randomized into three groups,with 6 in each.An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery.Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of30% of total blood volume.Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied.In Group Ⅰ,the swine spontaneously breathed,while SJT was applied for 2 h with a pressure of 210 mm Hg.In Group Ⅱ,the swine were mechanically ventilated,and SJT was applied for the same duration and pressure as Group Ⅰ.In Group Ⅲ,the swine spontaneously breathed,but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression.The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands.After then,a temporary vascular shunt was performed in the three groups to achieve resuscitation.Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 m L of autologous whole blood and 500 m L of lactated ringer solution.Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock,respectively.T30,T60,T90 and T120,denote 30,60,90,and 120 min after T0（hemostasis period）,while T150,and T180 denote 150 and 180 min after T0（resuscitation period）.The mean arterial pressure（MAP）and heart rate（HR）were monitored through the right carotid artery catheter.Blood samples were collected at each time point for the analysis of blood gas,complete cell count,serum chemistry,standard coagulation tests,etc.,and thromboelastography was conducted subsequently.Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration.Data were presented as mean ± standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method.All statistical analyses were processed using Graph Pad Prism software.Results:1.All the 12 experimental animals survived at the endpoint of the experiment.There was no statistical significance in Body Weight（BW）,and ECV of the three groups（p>0.05）.Volume-Controlled Blood Loss ratio（VCBLr）reached 10%,20%,and 30% in Group Ⅰ,Ⅱ,and Ⅲ successfully.The free hemorrhage through the pre-cut of the axillary artery in three groups was all effectively stopped by the external compression device with average Compression Pressure（CP）of 211±1.89 mm Hg,209.20±0.70 mm Hg,194.80±12.59 mm Hg respectively.No statistical significance was found in FBL and Free Blood Loss ratio（FBLr）among the three groups（p >0.05）.The Total Blood Loss ratio（TBLr）of the three groups was13.09±1.16%,25.04±1.79%,and 34.18±0.35%,respectively.2.Group Ⅰ and Ⅱ can successfully stop bleeding at 209-210 mm Hg pressure when SJT is used,and the average inflating time is 33.33 seconds.Free Blood Loss in groups I,Ⅱ and Ⅲ was less than 55 ml in T0-T120（Group Ⅰ: 54.70±16.30 ml vs.Group Ⅱ: 54.75±16.42 ml vs.Group Ⅲ: 54.74±16.42 ml,p > 0.05）,there was no statistical difference.There was no significant difference in installation time among the groups（Group Ⅰ: 32.98±7.94 s vs.Group Ⅱ: 33.01±7.92 s vs.Group Ⅲ: 33.01±3.24 s,p > 0.05）.Compared to Tb,a significant increase in the left hemidiaphragm movement at T0 was detected in Groups I and Ⅱ.In Group Ⅲ,the left hemidiaphragm movement remained unchanged（Group Ⅰ: 1.180±0.130 cm vs.1.980±0.130 cm,p<0.001;Group Ⅱ: 1.420±0.010 cm vs.1.720±0.020 cm,p<0.001;Group Ⅲ:1.150 ± 0.080 cm vs.1.170 ± 0.110 cm,p=0.660）.Compared to Group Ⅰ,mechanical ventilation in Group Ⅱ significantly alleviated the effect of SJT application on the left hemidiaphragm movement（Group Ⅱ: 1.72±0.02 cm vs.Group Ⅰ: 1.98±0.13 cm,p<0.001）.Compared to Tb,MAP（Group Ⅰ: 101.33±2.30 mm Hg vs.64.00±2.90 mm Hg,p<0.001;Group Ⅱ: 95.33±2.88 mm Hg vs.65.00±2.88 mm Hg,p<0.001;Group Ⅲ: 107.00±1.30 mm Hg vs.70.00±1.20 mm Hg,p<0.001）and HR（Group Ⅰ: 182.30±15.30 bpm vs.178.25±10.60 bpm,p<0.001;Group Ⅱ: 207.0±13.5 bpm vs.168.5±22.0 bpm,p<0.001;Group Ⅲ: 167.3±12.6 bpm vs.150.0±11.9 bpm,p<0.001）significantly increased at T0 in the three groups.When SJT was released,respiratory arrest suddenly occurred in 2 swine in Group Ⅰ,which required immediate manual respiratory assistance.When SJT was released,Pa O2 in Group Ⅰ decreased significantly,accompanied by increased Pa CO2（both p < 0.001 vs.other groups）.Other biochemical metabolic changes were similar in all groups.However,in all three groups,lactate（Group Ⅰ: 14.32±0.4 mmol/L vs.8.71±0.60 mmol/L,p<0.001;Group Ⅱ: 12.38±0.38 mmol/L vs.9.44±0.38 mmol/L,p<0.001;Group Ⅲ: 12.36±0.40mmol/L vs.9.34±0.45 mmol/L,p<0.001）and potassium（Group Ⅰ: 7.61±0.32 mmol/L vs.4.65±0.12 mmol/L,p<0.001;Group Ⅱ: 6.75±0.19 mmol/L vs.4.90±0.14 mmol/L,p<0.001;Group Ⅲ: 6.00 ± 0.23 mmol/L vs.4.64 ± 0.24 mmol/L,p < 0.001）increased immediately after 1 min of resuscitation concurrent with a drop in p H（Group Ⅰ: 6.97±0.16 vs.7.35±0.14,p<0.001;Group Ⅱ: 7.12±0.02 vs.7.41±0.05,p<0.001;Group Ⅲ: 7.17±0.09 vs.7.35±0.09,p<0.001）.The experimental animals in Group Ⅰ have the most severe hyperkalemia and metabolic acidosis（both p < 0.001 vs.other groups）.The coagulation function test did not show statistically significant differences among groups.However,after60 min of resuscitation,D-dimer measurements showed a greater than 16-fold increase in all three groups.The clot strength（Group Ⅰ: 75.42±1.42 mm vs.71.32±1.50 mm,p<0.001;Group Ⅱ: 73.62±2.38 mm vs.70.37±1.16 mm,p<0.001;Group Ⅲ: 73.40±1.24 mm vs.69.32±1.32 mm,p<0.001）also increased significantly during T0-T60,concomitant with a decrease in the clotting index（Group Ⅰ: 3.09±0.21 vs.4.32±0.23,p<0.001;Group Ⅱ:3.11±0.12 vs.4.20±0.32,p<0.001;Group Ⅲ: 3.21±0.12 vs.4.16±0.21,p<0.001）.Conclusions:1.A quantitative evaluation model for the axillary junctional site hemorrhage was successfully established by the combination of volume-controlled hemorrhage and free hemorrhage under the external compression device.The model can be used for quantitative analysis and research to verify the effectiveness of pre-hospital hemostatic material and devices for junctional hemorrhage.2.SJT could control axillary hemorrhage in the swine model through spontaneous breathing and mechanical ventilation.When SJT was used in the state of spontaneous respiration,hyperkalacidosis was more obvious after the removal of the device,and the compensatory movement of the diaphragm increased after the restriction of thoracic movement.Mechanical ventilation could alleviate the influence of SJT compression on respiratory function,and did not affect the hemostatic effect.