The Effect Of Biliary Tract External Drainage In Intra-abdominal Hypertension Induced Multiple Organ Dysfunction Syndrome

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are commonly found in critical ill patients, and are often characterized by quickly deterioration of clinical situations, multiple organ dysfunction syndrome (MODS), leading to high rates of mortality and morbidity. The majority of current researches on I AH/ACS are focusing on the adverse outcomes of vital organs, such as cardiovascular system, respiratory system, renal and gastrointestinal system, or technical issues, such as organ function supporting, reduction of intra-abdominal pressure, reconstruction of abdominal wall, etc. However, the mechanism of IAH-induced MODS is still not completely clear. Moreover, in clinical practice, even with powerful organ function supporting, such as fluid resuscitation, ventilator support, continuous renal replacement therapy (CRRT), vasoactive drugs for anti-shock therapy, the overall mortality is still in a high level.Biliary tract is often be neglected by most of the clinicians when 1AH/ACS develops. Mounting evidences proves that biliary tract plays an important role in hepatic pathophysiologic process. In our daily clinical practice, IAH/ACS patients are often complicated with not only elevated hepatic enzymes and bilirubin, but also inflammation changes in imaging tests, such as cholestasis, peri-gallbladder effusion, etc. If left untreated, these lesions may aggravate the IAH-leaded systemic inflammation response syndrome (SIRS), which may induce or deteriorate MODS. Furthermore, some researchers found, in LPS-induced sepsis rat model, the tumor necrosis factor a (TNFa) concentration in the bile was 30 times higher than it was in the serum and the histopathology damage degree was ameliorated by biliary tract external drainage (BTED). Thus, we made an assumption that IAH-leaded biliary tract injury may paly important role in the development and progression of MODS.In this thesis, IAH+BTED pig model was made by injecting nitrogen into the abdominal cavity and indwelling catheter into the common bile duct. With this animal model, we firstly observed the effects of different degree of IAH on inflammation cytokines in bile and serum and pathophysiological changes of the vital organs, and based on that we innovatively explored the protective significance of BTED in IAH-leaded MODS. This study may further reveal and complement the mechanism of IAH-leaded MODS. Moreover, this study may also provide a new way for clinician in the prevention and treatment of IAH caused MODS. This thesis could be divided into 2 parts:PART 1. Effects of intra-abdominal hypertension on inflammation cytokines in bile and serum and changes of vital organsObjective:We aimed to observe the effects of IAH on the inflammation cytokines in both bile and serum and the pathophysiological changes of vital organs.Methods:12 pigs were used in this study. Animal models were made by injecting nitrogen into the abdominal cavity and then were randomly divided into 3 groups: control group; IAH 15mmHg group and IAH 25mmHg group. Blood gas analysis was performed every 3 hours and samples of serum and bile were collected at the same time points, during the experiment vital signs were recorded every 30 minutes. Animals were sacrificed after 9 hours from the beginning of the experiment and lung, liver, kidney and intestinal tissue samples were obtained for pathological study.Result:Animal models were successfully induced in all animals. Compared with control group, mean artery pressure, heart rate, tidal volume and urine output together with blood gas parameters including partial pressure of oxygen and lactic acid deteriorated rapidly and significantly in IAH groups, and was characterized by higher level of IAH resulting in worsen outcomes. For inflammation cytokines measurements, IAH groups showed higher concentration of TNFa and sTREM-1 in both serum and bile sample (serum sTREM-19h:130.79±15.21,382.07±48.74, 545.85±46.17 respectively; bile sTREM-19h:197.43±25.12,552.29±54.32, 796.00±38.12 respectively, P<0.05 for both). Meanwhile, bile concentration was significantly higher than serum in both IAH groups (P<0.05). Moreover, IAH groups also showed more deteriorated liver and kidney function indicators in addition with more serious pathological injury, and 25mmHg group showed significantly more serious injury than 15mmHg.Conclusion:IAH can significantly deteriorate the vital signs and blood gas parameters, leading to severe inflammation response and deteriorated organ function.PART 2. The role of biliary tract external drainage in intra-abdominal hypertension induced MODSObjective:To explore the role of biliary tract external drainage (BTED) in intra-abdominal hypertension induced MODS.Methods:12 pigs used in this study were randomly divided into 3 groups:control group; BTED group and None-BTED) group. Animal models was made by injecting nitrogen into the abdominal cavity and indwelling catheter into the common bile duct. Blood gas analysis was performed every 3 hours and samples of serum and bile were collected at the same time points, during the experiment vital signs were recorded every 30 minutes. Animals were sacrificed after 9 hours with lung, liver, kidney and intestinal tissue samples were obtained for pathological study.Result:Compared with control group, mean artery pressure, heart rate, tidal volume and urine output together with blood gas parameters including partial pressure of oxygen and lactic acid deteriorated rapidly and significantly in IAH groups. However, compare with None-BTED group, BTED could not prominently ameliorate any of these parameters, and simple BTED could not protect lung, kidney and intestinal from IAH leaded pathological injury, but could ameliorate denaturation and putrescence of hepatocytes and could decrease the level of liver and kidney function indicators at the ending point (AST:187.50±30.01,232.50±31.53, P=0.047; Cre:96.97±14.44, 156.92±14.02, P=0.004). Meanwhile, for inflammation cytokines measurements, compare with None-BTED group, BTED significantly reduced the concentration of TNFa and sTREM-1 in both bile and serum at the ending point (serum sTREM-1: 352.89±31.72 vs.545.85±46.17, P=0.010; bile sTREM-1:525.76±49.89 vs. 796.00±38.12 respectively, P=0.006).Conclusion:BTED can play a protective role in a certain scope but could not totally reverse the pathophysiological changes in IAH.