Application Of Limited Fluid Resuscitation In Uncontrolled Hemorrhagic Shock Which Simulated Abdominal Trauma In Battlefield And Its Mechanism Of Mesenteric Lymph

Traumatic hemorrhagic shock and its complications are the leading causes of death in modern battlefield. Uncontrolled hemorrhagic shock (UHS) is the major type of shock. Liquid resuscitation is an important method which can decrease the mortality at early stage and following-up MODS morbidity in UHS. A new method called limited fluid resuscitation was recommended recently. But this method is still open to controversial. And the patho-physiologic mechanism of limited resuscitation in UHS is unclear, too. The mesenteric lymphatic system plays an important role in shock and MODS. Some researchers found that the mesenteric lymph fluid circulation in shock was abnormal. The structure of lymphatic vessel was damaged and the components of lymph fluid were changed in shock. It was the mesenteric lymph fluid that causes MODS in shock. The mesenteric lymph circulation could be improved by fluid resuscitation. However, all studies of the mesenteric lymph in shock were carried out in controlled hemorrhagic shock (CHS). The situation of mesenteric lymph in uncontrolled hemorrhagic shock is unknown. We presumed that the changes of mesenteric lymph fluid circulation must be an important event in UHS as that in CHS. Improvement of the mesenteric lymph fluid circulation and reduction of the mesenteric "lymph-induced" organ damage may be important mechanisms of limited resuscitation in UHS. In our experiments, an abdominal traumatic uncontrolled hemorrhagic shock model which simulated abdominal aorta injury in battlefield was established and the effects of different liquid resuscitation methods at early stage were tested. In pathophysiologic study, the changes of the mesenteric lymph fluid circulation were tested and the effects of limited resuscitation in UHS on mesenteric lymph were examed, too.Objectives1. To establish a practical uncontrolled hemorrhagic shock model which simulate abdominal aorta injury in battlefield.2. To test the effects of different liquid resuscitation methods at early stage in abdominal traumatic UHS.3. To identify the changes of mesenteric lymph fluid in UHS and the effects of limited resuscitation in UHS on mesenteric lymph.MethodsThe study was carried out in 3 experiments.1. Establishment of an uncontrolled hemorrhagic shock model which simulated abdominal aorta injury in battlefield38 Sprague-Dawley rats were canulated with PE 50 catheters and introduced into the left ventricle, femoral artery and femoral vein. Catheters were connected to pressure transducers for MAP, CVR Blood samples were analyzed for lactic acid, ALT and Cr. Animals were subjected to vascular injury leading to UHS by piercing through the infra-renal aorta with a 22G, 25G or 28G needle. After aorta injury, the models were divided into 4 stages: early injured stage, "field aid" stage, "hospital" stage and observation stage. The animals were treated with different methods according practical field condition e.g. transfusion, operation and so on.2. Early fluid resuscitation in simulated abdominal traumatic uncontrolled hemorrhagic shock in battlefield60 Sprague-Dawley rats were canulated with catheters and were subjected to vascular injury leading to uncontrolled hemorrhagic shock by piercing though the infra-renal aorta with a 25G needle. The animals were divided into 4 stages as described in experiment 1 and assigned to 5 groups: (1) Control group: No fluid resuscitation at any stage but had bleeding controlled "in hospital" by operation. (2) Only resuscitation "in hospital" group: No fluid resuscitation "pre-hospital" but resuscitated "in hospital" with Ringer's solution which was 3 times of abdominal blood loss. Bleeding was controlled "in hospital" too. (3) Aggressive resuscitation "pre-hospital" group: Resuscitation "pre-hospital" with Ringer's solution at the speed of 3mL/kg·min. And fluid resuscitation and bleeding controlled "in hospital" as group (2). (4) Limited resuscitation "pre-hospital" group: Resuscitation "pre-hospital" with Ringer's solution at the speed of 1mL/kg·min. And fluid resuscitation and bleeding controlled "in hospital" as group (2), too. (5) Sham: Operation but no bleeding and no fluid resuscitation. The MAP, CVP, lactic acid, HCT, alanine amino-transferase and carnine were tested. The volume of blood loss and survival time was recorded, too.3. The pattern of mesenteric lymph fluid in uncontrolled hemorrhagic shock and the effects of limited fluid resuscitation60 SD rats were canulated and were subjected to vascular injury leading to uncontrolled hemorrhagic shock by piercing though the infra-renal aorta with a 25G needle and was divided into 4 stages as described in experiment 1. A self-made steel catheter was inserted into the main mesenteric lymph duct and the mesenteric lymph fluid was collected continuously. The rats were divided into 5 groups and resuscitated as described in experiment 2. The MAP, CVP, volume of mesenteric lymph fluid was recorded. And the protein concentration, MDA and endotoxin content, TNF-αlevel of mesenteric lymph fluid were examined, too. The tissues of lung, intestine, liver and kidney were examined for histology, water content, blood flow and MPO. Results1. In the model of UHS, the MAP and CVP decreased remarkably after aorta injury and reached to the lowest within 5 min then increased slowly. The lactic acid increased and reached 3-4 time of baseline at 4 h after injury. The ALT and Cr increased significantly at later stages. The blood loss in abdomen was increased with the increase of needle's thickness. The median survival time of 22G, 25G and 28G was 7 min,50 min and 3860 min respectively.2. In the fluid resuscitation study, we found that: (1) The MAP increased quickly after Aggressive resuscitation then decreased quickly. But it increased slowly and continuously in Limited resuscitation group. (2) Except for temporary rose in Aggressive resuscitation group, CVP didn't increase significantly in other groups after resuscitation. (3) Dp/dt max, LVSP, and HR decreased but t(dp/dt max) increased significantly in UHS. There were not significant improvement of dp/dt max, LVSP, HR and t(dp/dt max) in Aggressive resuscitation group and Only resuscitation "in hospital" group but improved significantly in Limited resuscitation group. (4) The HCT was decreased after Aggressive resuscitation but still unchanged after Limited resuscitation. (5) Lactic acid, alanine amino-transferase and carnine were increased in Control, Only resuscitation "in hospital" group and Aggressive resuscitation group but not significantly increased in Limited resuscitation group in 4 h. (6) The blood loss in ab domen increased in Aggressive resuscitation group but not in others. (7) The median survival time in Control, Only resuscitation "in hospital" group, Aggressive resuscitation group and Limited resuscitation group was 76 min, 907 min, 846 min and 2968 min. And the mortalities of them in 72 h were 100%, 90.1%, 90.1% and 36.4%, respectively.3. In the mesenteric lymph research, we found that: (1) The mesenteric lymph fluid was 1.50±0.22 mL/kg·h and decreased remarkably in UHS. It's below to 1/4 of normal (p<0.01). After aggressive resuscitation, it increased quickly and decreased soon. However, it increased persistently and reached to 4.79±0.15 mL/kg·h in Limited resuscitation group. There's more than 3 times of normal (p<0.01). (2) The protein content in lymph fluid was not different significantly in UHS but decreased after aggressive fluid resuscitation. The lymphatic protein output was increased after resuscitation and decreased soon except Limited resuscitation group. (3) The endotoxin in lymph fluid increased more than 3 times (p<0.01) at 4 hour in UHS but remained normal (p>0.05) in portal vein in all groups. The endotoxin in lymph fluid in Limited resuscitation group was decreased significantly than others. (4) The MDA content in mesenteric lymph was increased in UHS and increased more significantly after aggressive resuscitation. However, it did not increased significantly in Limited resuscitation group. So did the MDA content in plasma. (5) The TNF-αlevel increased significantly in mesenteric lymph in UHS and decreased in Limited resuscitation group but not in others. So did the TNF-αin plasma. (6) Pathomorphology study showed the villus breakage and exposure of blood capillary of small intestine in UHS. And the historic morphology improved more after Limited resuscitation group than other groups, too. (7) The water content was not increased significantly in UHS. And it was increased significantly in Aggressive resuscitation group than the others. (8) The blood flow of small intestine decreased from 2.75±0.67 mL/min·g to 1.18±0.51 mL/min·g (p<0.01). It was 2.47±0.67mL/min·g in Limited resuscitation group, which was significantly different from the other groups (p<0.05 or p<0.01). (9) The MPO activity in lung and small intestine was increased significantly in UHS. And it was at high level persistently in Aggressive resuscitation group and No resuscitation group at early stage but at low level in Limited resuscitation group.Conclusions1. Being similar to battlefield bullet injury and easy duplicated, the staged UHS model which is made by piecing through the infra-renal aorta with a 25G needle is feasible. 2. If not resuscitated pre-hospital, it is not so effective to resuscitate in hospital for UHS. So, fluid resuscitation pre-hospital is necessary.3. In UHS, aggressive resuscitation pre-hospital cannot increase the live time but decreases the HCT, increases abdominal blood loss and liquid usage.4. Although limited resuscitation pre-hospital in UHS cannot increase the blood pressure and circulation blood volume to normal, it can reduce the level of blood lactic acid and maintain the heart dynamic function, liver and renal function. In addition, it cannot increase blood loss significantly. The live time and the survival rate can be increased by this method.5. The mesenteric lymph fluid circulation is abnormal in UHS: The volume and protein output of mesenteric lymph fluid decrease. And the endotoxin and proinflammatory mediator in lymph fluid increase, too.6. Aggressive resuscitation pre-hospital or only resuscitated in hospital in UHS cannot improve the mesenteric lymph fluid circulation.7. Limited resuscitation pre-hospital in UHS can reduce the bacterial/endotoxin translocation from the mesenteric lymph fluid, reduce the lipid peroxidation in mesenteric lymph, reduce the PMN sequestration, increase the blood volume in organ and reduce the intestinal damage.8. The improvement of mesenteric fluid circulation is an important event of limited resuscitation which can reduce the early mortality and following-up MODS morbidity in UHS.