The Investigation Of Portable Extracorporeal Life Support System Development And Its Potential In Thoracic Explosive Injury Treatment Under Deep Hypothermia With Hypoperfusion

In today’s multi-polar world,explosive weapons are mainly used in local wars and terrorist attacks.For these reasons,the incident rate of explosive injuries in peacetime and wartime is increasing day by day.In all types of injuries,chest injury is serious,difficult to treat and has a high mortality rate.In this case,the lung,which is the most sensitive to overpressure,becomes the most vulnerable organ.The special battlefield environment is different from the conventional one.The characteristics of the type of war injuries,trauma types and features of injuries are very specific.Cold region of north China is a typical representative of an extreme battlefield environment.Its perennial temperature difference is large and the environment is harsh.Permafrost,snows,ice,complex terrain and the pathogenic factors are all its features.It is worth noting that,low temperatures and other environment disadvantages often aggravate the initial trauma.The mortality of war injuries in the cold regions is very high if the wounded couldn’t get timely treatment or get improper treatment measures.At the same time,there are a lot of inconveniences in medical evacuation of the wounded in the cold regions,which lead to the excessive combat casualty and non-battle casualty.Some injuries can be treated surgically after blast damages occur on a cold battlefield.However,the data shows that more than half of the trauma patients in recent military conflicts died because of limited medical care before they could receive the surgical treat.Thus,an effective and aggressive solution to transport combat trauma patients,particularly potentially survivable patients,to well-equipped medical treatment hospitals or more advanced hospitals is badly needed.Extracorporeal life system(ECLS)is such an effective solution that it can provide basic life support during the evacuation period,especially for the wounded of heart,lung and great vessels problems and it also plays a key role in improving survival rates.In recent years,ECLS becomes an emerging medical technology in cardiac surgery.It has been proved to be effective in improving the quality of patient care in acute.However,due to its large size,high environmental requirements and other limitations,it is difficult to be applied to the treatment of patients in extreme environmental battlefields.Therefore,miniaturization of the devices necessary for cardiac and pulmonary support becomes more and more popular among the researchers.Based on this present situation,portable extracorporeal life support system(PELS)seems like a new solution.Appling PELS developed by ourselves independently for the treatment of thoracic blast injury can win more valuable time for the transfer to deliver the patients,so as to improve both the survival rate and the treatment success rate of such patients through subsequent effective treatment.So,this paper mainly researches the investigation of PELS development and its potential in thoracic explosive injury treatment under deep hypothermia with hypoperfusion.Part1.Independently development for Portable external life support systemObjective: 1.Developing Portable external life support system independently;2.Testing the application of PELS which is developed by us;3.Testing the runnability of PELS which is developed by us with experimental animal models.Methods: 1.In vitro,PELS was tested for stable assessment of speed,flow and pressure;2.PELS was tested for stable assessment in realistic low temperature environment;3.PELS was tested with 8 animal experimental models.8 male Bama minipigs were randomized into 2 groups: Group A(4000r/min in PELS,n=4)and Group B(2000r/min in PELS,n=4).CPB was repectively established with PELS in two ways.One was with PELS under 1L/min of flow and 2000r/min for 6 hours,the other was with PELS under 4L/min of flow and 4000r/min for 6 hours.The plasma free hemoglobin and platelet activation were evaluated before initial of CPB,every 2 hours in CPB and after terminated CPB.Results: 1.In vitro,portable PELS was stable in speed,flow and pressure;2.CPB was used in animal experimental models with PELS,and the detected indexes were safe.Conclusion: The PELS conducts stable and reliable performance in experimental animal models for CPB.Part2.Establishment of hypothermia explosive injury model and investigation of the potential of PELS for early treatment strategies in reality hypothermia environmentObjective: 1.To establish hypothermia thoracic explosive injury model in Bama minipigs;2.Preliminary application of PELS in reality hypothermia environment;investigating the feasibility of early CPB treatment strategies for experiment animals with PELS.Methods: Totally 36 healthy Bama minipigs(weight: 37kg-56 kg,regardless male or female)were randomly divided into 9 groups according to the different equivalent explosive effects and whether there is early treatment with PELS or with routine ECMO: Group A(PELS group,n =4;routine ECMO group,n=4;control group,n = 4),detonators ×1.0.Group B(PELS group,n =4;routine ECMO group,n=4;control group,n = 4),detonators × 1.5.Group C(PELS group,n =4;routine ECMO group,n=4;control group,n = 4),detonators × 2.0.The experimental group was given PELS or routine ECMO with CPB,but control group was no treatment.After explosion,the injured animals were sent to the field medical station quickly and carried out early treatment with PELS.Dynamically monitor basic vital signs and characteristics of injury of all experimental animals.Results: The experimental animals in Group A suffered the least injury: PELS group all survived,with the death status(0/4);routine ECMO group all survived,with the death status(0/4);control group all survived,with the death status(0/4).The degree of injury in Group B was significantly higher than that in Group A: 1 animal died in PELS group,with the death status(1/4);1 animal died in routine ECMO group,with the death status(1/4);2 animals died in the control group,with the death status(2/4).Heavy injury and difficult treatment in group C: 3 animals died in PELS group,with the death status(3/4);4 animals died in conventional ECMO group,with the death status(4/4);4 animals died in control group,with the death status(4/4).Conclusion:1.Thoracic blast injury is more common with multiple injuries and complex wound leading to high early mortality rate.2.The establishment of the model of chest blast injury under low temperature environment was successful.Group B proved to be used as the most suitable model group of the hypothermia thoracic explosive injury because the degree of injury of the in Group B was in the middle and it could reflect the change characteristics of the condition of chest blast injury with good controllability and repeatability.3.The experiment showed that PELS could work normally in China’ cold region,and it could intervene and treat the thoracic detonation injury of early experimental animal models.Part3.Feasibility analysis of PELS to treat traumatic hemorrhage animal models in an induced hypothermia circumstancesObjective: 1.To explore the feasibility of using PELS to treat traumatic hemorrhage animal models in an induced deep hypothermia environment;2.Preliminarily to determine the safe use time range of PELS under the condition of induced hypothermia and low flow circumstances wasMethods: The common carotid artery and internal jugular vein were intubated in 9 small Bama minipigs to establish extracorporeal circulation.A constant volume hemorrhagic shock model was adopted by rapidly release 40%-45% of the blood volume(calculated according to the body mass of 30 ml /kg)through the lateral hole of femoral artery intubation.PELS on application flow,when induced experimental animals to 15 ℃ lower rectal temperature,low flow perfusion circulation 90 minutes(Set a time for the attempt for 90 min)attempt to set back to normal.After the rectal temperature was restored to the preoperative level,CPB was stopped,and the ventilator continued to assist ventilation until the patient left the machine for spontaneous breathing.The index of vital signs and survival of the experimental animal were observed.Results: Of 9 experimental animals which hearts were automatically re-beat and safely recover from ventilator,7 animals was observed hemodynamic stability after off-line within 2h and 2 animals died after CPB within 2h.Conclusion: 1.Applying PELS under the induced hypothermia circumstances to treat traumatic hemorrhage animal models is feasible and safe.2.When PELS was used on the traumatic hemorrhage animal models under induced hypothermia with low-flow perfusion,the duration of safety operation time should be kept around 90 minutes except induction time and recovery.Brief summary: 1.PELS was effective in the intervention of lung blast injury in the low temperature environment.2.It is effective in the treatment of trauma model under the condition of artificially induced deep and low temperature.3.Is PELS effective for lung blast injury under the condition of artificially induced deep hypothermia and low flow? Can it play a positive role in lung treatment?Part4.Feasibility study on the treatment of PELS in animal models of thoracic blast injury under hypothermia with low-flow perfusionObjective: To explore the safety and feasibility of PELS in the treatment of animal models of thoracic blast injury under hypothermia with low-flow perfusion.Methods: 24 Bama minipigs were randomized into three groups: Group A: treatment group with PELS(n=8),Group B: conventional experimental group with heart-lung machine(n=8)and C group: control group(n=8).All the Bama minipigs were established as a thoracic explosive injury model.Group A were established extracorporeal circulation with PELS through which the vein end quickly was added ice viscera protection fluid,inducing hypothermia in experimental animals(rectal temperature 15 ℃ lowest).After CPB with deep hypothermia and low-flow perfusion,the experimental animals were gradually re-warmed and resuscitated.In Group B,heart-lung machine was used instead of PELS to finish the same operation process like what has been done in Group A.There was no treatment in the control group except cannula.The lung static compliance,Interleukin 8(IL-8),Interleukin 10(IL-10),and Tumor necrosis factor-a(TNF-a),as well as body temperature,heart rate,and K+ were measured before and after CPB in the three groups to evaluate the safety of applying PELS after thoracic blast injury.The inspiratory pause pressure,tidal volume,Pa O2 and Fi O2 were measured,and the pulmonary static compliance(Cstat)and Pa O2/Fi O2 were calculated.Results: 22 animals of all 24 experimental Bama minipigs were established as a thoracic explosive injury model successfully.The other 2 died instantaneously after modeling.One death was caused by a blunt aortic injury in the heart and the other one was caused by an acute aortic injury in the lung.The values of the temperature,heart rate,K+ in group A and group B were respectively(A vs B): 37.97℃±0.85 vs 38.04±0.76℃,103.25±17.76 /min vs 102.57±18.88/min,4.71±0.591 mmol/L vs 4.76±0.58mmol/L before CPB and 36.97±0.504℃ vs 37.25±0.75℃,119.63±13.81/min vs 120.29±13.17/min,6.40±1.07 vs 6.26 mmol/L±1.11mmol/Loff after CPB.Group C caused more significant decrement of pulmonary static compliance after CPB than treatment Group A and Group B(A vs B: 4.86±0.63 vs 4.76±0.84,P>0.05;A vs C: 4.86±0.63 VS 4.06±0.28,P<0.05;B vs C: 4.76±0.84 vs 4.06±0.28,P<0.05).Arterial blood oxygen partial pressure to inspired oxygen fraction decreased more significantly after CPB in Group C than treatment Group A and Group B(A vs B:355.0±23.60 mm Hg vs 355.7±18.01 mm Hg,P>0.05;A vs C:355.0±23.60 mm Hg vs 288.2±29.001 mm Hg,P<0.05;B vs C: 355.7±18.01 mm Hg vs 288.2±29.001 mm Hg,P<0.05).According to statistical analysis before CPB,there was no significant difference in IL-8,IL-10 and TNF-a values treatment among three groups: IL-8: A vs B 1.01±0.015 vs 0.98±0.051,P>0.05;A vs C 1.01±0.015 vs 0.99±0.016,P>0.05;B vs C 0.98±0.051 vs 0.99±0.016,P>0.05.IL-10: A vs B 0.94±0.047 vs 0.95±0.061,P>0.05;A vs C 0.94±0.047 vs 0.98±0.027,P>0.05;B vs C 0.95±0.061 vs 0.98±0.027,P>0.05.TNF-a: A vs B 1.02±0.032 vs 0.99±0.043,P>0.05;A vs C 1.02±0.032 vs 0.99±0.29,P>0.05;B vs C 0.99±0.043 vs 0.99±0.29,P>0.05).After CPB,there was no statistically significant difference in IL-8,IL-10 and TNF-a values between Group A and Group B respectively(A vs B): IL-8:1.28±0.114 vs 1.23±0.889,P>0.05;IL-10:1.31±0.045 v.30±0.145,P>0.05;TNF-a: 1.37±0.126 vs 1.33±0.143,P>0.05.There were statistically significant differences in IL-8,IL-10 and TNF-a values between Group A and Group C(A vs C): IL-8:1.28±0.114 vs 1.49±0.226,P<0.05;IL-10:1.31±0.045 v.63±0.238,P<0.05;TNF-a:1.37±0.126 vs 1.52±0.127,P<0.05.There also were statistically significant differences in IL-8,IL-10 and TNF-a values between Group B and Group C(B vs C): IL-8:1.23±0.889 vs 1.49±0.226,P<0.05;IL-10:1.30±0.145 v.63±0.238,P<0.05;TNFa:1.33±0.143 vs 1.52±0.127,P<0.05.Conclusions: 1.Using PELS to treat experimental animal models after thoracic explosive injury is feasible,safe and effective.2.PELS will play a protective role in the treatment of thoracic explosive injury,providing conditions and opportunities to gain prime first aid and transport time on the battlefield.