The Effect Of Sustained Intra Abdominal Hypertension Combined With Severe Acute Pancreatitis On Pancreatic Damage And Organ Functions

The incidence rate of intra abdominal hypertension(IAH) ranges from60%to80%in patients with severe acute pancreatitis(SAP). During different phases of SAP, IAH has different causes such as inflammation, capillary leakage and abdominal wall swelling in the acute phase and abdominal infection, septic shock and intestinal dysfunction in the latter phase. There are several previous studies regarding the different outcome between SAP patients with or without IAH, but the results are quite confusing due to different standards of IAH and different methods for measuring intra abdominal pressure. Therefore, the risk factors of IAH in SAP patients and the effect of different levels of IAH on the outcome of SAP need to be further studied according to the standards established by the World Society of Abdominal Compartment Syndrome(WSACS). Additionally, the optimal timing and indication of surgical decompression remains unknown, hence animals studies are warranted to address these issues.In our serial studies, we retrospectively reviewed the clinical data of SAP patients admitted in the acute phase to explore the risk factors and outcome of SAP patients in combination with IAH. On the basis of clinical results, we set up a brand new animal model to assess the effect of sustained different levels of IAH combined with SAP on global hemodynamics, systemic oxygenation and organ functions. Furthermore, we also studied the effect of decompression at different time point in a porcine model of25mmHg IAH incorporating SAP to help optimize the timing for surgical intervention in this special patient population. Part I:Risk factors and Outcome of Intra Abdominal Hypertension in Patients with Severe Acute PancreatitisObjective:Intra-abdominal hypertension(IAH) is common in patients with severe acute pancreatitis(SAP). The aim of this study was to investigate the risk factors of IAH in SAP patients and assess the prognosis of SAP combined with IAH.Methods:To analyze the data from patients with SAP, both univariate and multivariate logistic regression analyses were applied, using16indices including age, gender, Acute Physiology and Chronic Health Evaluation Ⅱ scores(APACHE Ⅱ),24-hour fluid balance, hematocrit, serum calcium level and so on. Clinical prognosis such as mortality, hospital duration, etc. of SAP patients with or without IAH was also compared.Results:First24-hour fluid balance (OR,1.003;95%CI,1.001-1.006), number of fluid collections(OR,1.652;95%CI,1.023-2.956) and serum calcium level(OR,0.132;95%CI,0.012-0.775) were found to be independent risk factors for IAH in patients with SAP. Moreover, patients with SAP and IAH had significantly longer average length of hospital and intensive care unit duration, higher rates of systemic and local complications and more invasive treatments.Conclusion:The significant risk factors for IAH in patients with SAP include24-hour fluid balance (first day), number of fluid collections and serum calcium level. Additionally, IAH is associated with extremely bad prognosis evidenced by high rates of death, complications and invasive interventions. Part II:The effect of different intra-abdominal pressures (IAP) on pancreatic necrosis, organ function, hemodynamics and oxygen metabolism in severe acute pancreatitis porcine modelObjective:The deterioration of severe acute pancreatitis (SAP) is associated with abdominal bleeding, formation of microthrombus and intra-abdominal hypertension (IAH). Abdominal compartment syndrome (ACS) and IAH are common complications in patients with SAP. However, the effects of different degrees of IAH on pancreatic necrosis, organ function including heart, lung and kidney are unclear. Our research is aimed to evaluate the effects of different degrees of IAH on pancreatic necrosis and organ function in severe acute pancreatitis in a porcine model.Methods:24swine were divided into4groups randomly as follows (N=6):A) IAP=15mmHg for12hours with SAP, B) IAP=25mmHg for12hours with SAP, C) IAP=30mmHg for12hours with SAP, D) no IAH with SAP. The swine were anaesthetized, endotracheally intubated and placed on mechanical ventilation. SAP was induced by retrograde infusion of5%sodium taurocholate and0.5%trypsin solution via pancreatic duct with a dose of1ml/kg. IAP is raised by intraperitoneal insufflation with N2. An artery catheter and a Swan-Ganz catheter were placed to monitor mean arterial pressure (MAP), cardiac output (CO), central vein pressure (CVP). Arterial blood was also collected via the artery catheter for blood gas measurement. At different time points, blood sample was collected for determination of aspartate aminotransferase (AST), amylase, lactic acid (Lac) and serum creatinine. At the end of the experiment, pancreas, liver and lung tissue were harvested. The tissue samples were immediately transferred into10%phosphate-buffered saline (PBS) buffered formalin and embedded in paraffin. Sections measuring4um in thickness were cut, placed on glass slides, and stained with hematoxylin and eosin (H&E). Images were obtained using a light microscope and analyzed by pathologist.Results:One swine in30mmHg group died after11hours, while other23swine were alive during the12-hour experiment period. The results of group B and C were significantly changed due to the IAH. Comparing with group A, the histological appearance demonstrated pancreatic acinus necrosis, bleeding, formation of microthrombus and alveolar collapse, interstitial bleeding and inflammatory cells infiltration after3,6and12hours. The heart rate, CVP were increased while CO and MAP were decreased significantly after12hours (P<0.05). The blood gas measurements manifested that blood pH, PaO2were decreased while blood Lac and PaCO2were increased significantly in group B and C (P<0.05).Conclusions:ACS has detrimental effect on SAP in a porcine model, including pancreatic lesion, circulation and respiratory function. Relief of ACS is one of the key strategies in the treatment of SAP. PART Ⅲ:Effect of decompression in different time on pancreatic necrosis, organ function and hemodynamics of porcine model with severe acute pancreatitis combined intra-abdominal hypertensionObjective:The aim of this study was to assess the effect of decompression in different time on systemic hemodynamics and oxygen metabolism in a24h lasting porcine model of severe acute pancreatitis incorporating intra-abdominal hypertension(IAH).Methods:Following baseline registrations, SAP was induced in all32animals. We used a N2pneumoperitoneum to increase the intra-abdominal pressure (IAP) to25mmHg in24of32SAP animals (n=8). After6hours, we applied decompression in8of these pigs and the other16animals received decompression at9h and12h respectively since the induction of IAH. For decompression, the nitrogen gas was pumped out slowly to avoid sudden drop of abdominal pressure which could lead to acute cardiac failure due to sudden increase of venous return. The investigation period was24h. Heart rate (HR), cardiac output (CO) and mean arterial pressure (MAP) were continuously recorded with the aid of Swan-Ganz catheter and electrocardiography monitor; Oxygen partial pressure of artery (PaO2) was measured by blood-gas analysis. Besides that, the level of serum TNF-α and IL-6were taken every6h; Plasma samples were frozen at-70℃degrees for later measurements. Serum cytokine concentrations(TNF-α and IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) with commercial kit (R&D Systems, Munich, Germany under the same experimental conditions.The urine output was recorded every1h。 At different time points, blood sample was collected for determination of aspartate aminotransferase (AST), lactic acid (Lac) and serum creatinine. At the end of the experiment, pancreas and lung tissue were harvested. The tissue samples were immediately transferred into10%phosphate-buffered saline (PBS) buffered formalin and embedded in paraffin. Sections measuring4um in thickness were cut, placed on glass slides, and stained with hematoxylin and eosin (H&E). Images were obtained using a light microscope and analyzed by pathologist.Results:After induction of IAH+SAP, CO in all three study groups was much more significantly reduced than SAP group in the first a few hours. Decompression could increase CO remarkably in both6h and9h groups but slightly in the12h group. In the latter phase of observation, the SAP group as well as6h group showed higher CO when compared with9h and12h groups, although very few statistical differences were reached. MAP in all groups decreased gradually over time, but no significant between-group difference could be detected throughout the experiment. Similar to CO, HR dropped more profoundly in6h and9h group than12h group after abdominal decompression and statistical differences could hardly be seen during the second half as well. Blood gas results showed that arterial PO2in the SAP group ranged without significant differences in the first6hours and decreased gradually thereafter. Differently, the combination of IAH decreased PO2more significantly in other3groups and decompression especially early intervention could help PO2back to a higher level which is still lower than the baseline value but similar to SAP group. The induction of IAH also led to much higher lactate levels in3study groups, although SAP animals showed an upbeat trend as well. Decompression could slow down or even slightly reverse the increase of lactate evidenced by that6h group and SAP group presented very similar levels of lactate during the last9hours. The application of SAP+IAH dramatically decreased UO over time and decompression at6h could regain the UO to a level similar to the SAP group. Regarding the9h and12h groups, although UO increased substantially after decompression, the levels of these two groups were still lower than other2groups during the rest of the observation. After induction of SAP and IAH, concentration of plasma cytokines increased significantly and reached peak at different time points (6h for6h,9h and SAP group,12h for12h group) and different levels. Early decompression resulted in statistically lower levels of both TNF-a and IL-6during the second half of experiment. Indicators of liver and kidney injury, including AST and creatinine increased more significantly in IAH groups compared with SAP alone animals.Compared with the6h group and9h group, the survival time of animals in12h group was significantly reduced(P=0.037vs.9h and P=0.008vs.6h).Conclusions:There were remarkable and relatively irreversible effects on global hemodynamics and oxygen metabolism in response to the decompression in different time after sustained25mmHg IAH with the underlying condition of SAP.The results of this study are in favor of a decompression in SAP with IAH in an early time.