Hai-bin Ni

The Effect of Intra-Abdominal Hypertension Incorporating Severe Acute Pancreatitis in a Porcine Model

Introduction Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model. Measurements and Methods Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group): SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP) and sham-operated group. We used a N2 pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP), urine output, oxygenation parameters(e.g., SvO2, PO2, PaCO2), peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine) were recorded. Histological examination of liver, intestine, pancreas, and lung was performed. Main Results Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in SvO2. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP. Conclusions Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH/ACS-induced exacerbation and to optimize the treatment strategies for counteracting the development of organ dysfunction.

Percutaneous catheter drainage for infective pancreatic necrosis: is it always the first choice for all patients?

Objective To learn the clinical outcome of percutaneous catheter drainage (PCD) for patients with infective pancreatic necrosis and the possible influencing factors. Methods A retrospective review of medical records of patients with infective pancreatic necrosis who received PCD as the first choice for treatment in the recent 2 years. The patients were divided into 2 groups: (1) PCD success group and (2) PCD alteration group. Characteristics, complications, and PCD process were compared. Results In this study, 19 of 34 patients were cured by PCD alone (55.9%), whereas open necrosectomy were needed for 15 patients (44.1%). Between these 2 groups, most baseline and clinical characteristics did not show any statistical difference, including the number and size of catheter used and the bacterial culture result. The PCD alteration group had higher mean computed tomographic density (P = 0.012) and larger distribution range of infected pancreatic necrosis (4.53 ± 1.35 vs 5.93 ± 1.62; P = 0.009) than the PCD success group (P < 0.01). The logistic regression analysis revealed the same facts. Conclusion The mean computed tomographic density and distribution range of infective pancreatic necrosis could significantly influence the success rate of PCD; higher values of them indicate less appropriate for PCD; thus, it should be considered seriously before the treatment decision.

The importance of timing of decompression in severe acute pancreatitis combined with abdominal compartment syndrome.

BACKGROUND Surgical decompression is widely considered as an important treatment in patients with severe acute pancreatitis (SAP) and abdominal compartment syndrome (ACS). Until now, the indication and optimal time of decompression remain unknown, and no experimental data exist, although extremely high mortality has been repeatedly reported in these patients. The aim of this study was to evaluate the effects of three different time points for decompression in a 24-hour lasting porcine model. METHODS Following baseline registrations, 32 animals were divided into four groups (8 animals each group) as follows: one SAP-alone group and three SAP + ACS groups, which received decompression at 6, 9, and 12 hours. We used a N2 pneumoperitoneum to increase the intra-abdominal pressure to 25 mm Hg and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and serum biochemical parameters of the animals were studied. At the end of the experiment, histologic examination of the intestine and lung was performed. RESULTS The survival time of the 12-hour group was significantly shortened (p = 0.037 vs. 9 hours and p = 0.008 vs. 6 hours). In SAP + ACS animals, decompression at 6 hours restored systemic hemodynamics, oxygen-derived parameters, organ function, and inflammatory intensity to a level comparable with that of the SAP-alone group. In contrast, animals in the 9 hours and 12 hours developed more severe hemodynamic and organ dysfunction. The histopathologic analyses also revealed higher grade injury of the intestine and lung in animals receiving delayed decompression. CONCLUSION Well-timed decompression in a porcine model of SAP incorporating 25-mm Hg intra-abdominal hypertension/ACS was associated with significantly reduced mortality, improved systemic hemodynamics and organ function, as well as alleviated histologic injury and inflammatory intensity. According to our results and previous reports, both too early and too late decompression should be avoided owing to significant morbidity for the former and unfavorable outcomes for the latter.

Codonopsis pilosula polysaccharide attenuates cecal ligation and puncture sepsis via circuiting regulatory T cells in mice.

ABSTRACT Background: Codonopsis pilosula polysaccharide (CPPS) isolated from one of the Chinese herbs is known to have a variety of immunomodulatory activities. However, it is not clear whether CPPS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of CPPS on the immune function of peripheral blood Tregs in sepsis induced by cecal ligation and puncture (CLP). Methodology and Principal Findings: BALB/c mice were randomly divided into five groups: sham group, CLP group, CLP with CPPS (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3, and 4 after CLP, respectively, with eight animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4+ T cells. Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed by flow cytometry, and coculture medium cytokines levels were determined with enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3 in the Treg from CLP group were markedly increased in comparison to the sham group. Administration of CPPS could significantly decrease the TLR4 level and inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time, proliferative activity and expression of interleukin 2 and interleukin 2R&agr; on CD4+ T cells were restored. In contrast, anti-TLR4 antibody could block the effect of CPPS on Treg immune function. Conclusions: Codonopsis pilosula polysaccharide might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and trigger a shift of TH2 to TH1 with activation of CD4+ T cells in sepsis induced by CLP.

Efficacy of continuous regional arterial infusion with low-molecular-weight heparin for severe acute pancreatitis in a porcine model.

ABSTRACT Objective: Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. Methods: Following baseline measurements, 18 animals were divided into three groups: CRAI group (LMWH infused through placed arterial catheter), venous group (LMWH infused through central venous catheter), and SAP control group. We used retrograde intraductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and inflammatory and serum biochemical parameters of the animals were studied. At the end of the experiment, histological examination of pancreas, intestine, and lung was performed. Results: Continuous regional arterial infusion with LMWH remarkably stabilized hemodynamic profiles, improved systemic oxygenation and peripheral perfusion, alleviated histological injury of pancreas (especially for the necrosis scale), and downregulated inflammatory response when compared with the other two groups. Moreover, serum D-dimer level also decreased most significantly in the CRAI group (474 ± 144 vs. 664 ± 155 µg/L in the venous group and 945 ± 351 µg/L in the controls at the end), partly indicating ameliorated coagulation disorders in the study group. No bleeding complication was observed in the CRAI group, whereas two animals in the venous group presented gastrointestinal hemorrhage. Conclusions: Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.

Acute cholecystitis in the late phase of severe acute pancreatitis: a neglected problem.

Objective This study aimed to evaluate the incidence and risk factors for acute cholecystitis (AC) in the late phase of severe acute pancreatitis (SAP). Methods A review of patients with SAP from January 2008 to December 2009 was performed. Clinical characteristics were compared between patients with AC in the late phase and those without. Risk factors for AC were analyzed using a logistic regression analysis. Receiver operating characteristic curve was used to estimate the predictive value of the risk factors. Results A total of 269 cases were included. Twenty-seven episodes of AC in the late phase were identified. Patients with AC had higher computed tomography severity index and Acute Physiology and Chronic Health Evaluation (APACHE) II score, as well as higher rate of intraabdominal hypertension, infective pancreatic necrosis (IPN) of the pancreas head, fistula, abdominal bleeding, mechanical ventilation, and prolonged enteral nutrition (EN) via jejunal tube. Independent risk factors for AC, based on the results of logistic regression analysis, included higher APACHE II score, prolonged EN via jejunal tube, and IPN of the pancreas head. Conclusions Approximately 10% of patients with SAP will develop AC in the late phase. Risk factors include higher APACHE II score, prolonged EN via jejunal tube, and IPN of the pancreas head.

Beneficial effect of hypertonic saline resuscitation in a porcine model of severe acute pancreatitis.

Objective Hypertonic saline (HTS) solution resuscitation has been used in a variety of clinical settings. The aim of this study was to assess the effect of HTS resuscitation on hemodynamics, systemic oxygenation, and organ damage in a porcine model of severe acute pancreatitis. Methods Eighteen anesthetized and mechanically ventilated pigs were divided into 3 groups: HTS group, lactated Ringer solution (LR) group, and sham-operated group. Severe acute pancreatitis was induced in the first 2 groups by injecting 5% sodium taurocholate into the pancreatic duct, and the investigation period was 12 hours. Hemodynamic parameters, urine output, oxygenation parameters, and serum parameters were recorded consecutively. Finally, histologic examinations of the kidney, intestine, pancreas, and lung were performed. Results In the HTS group, cardiac output decreased less significantly compared with the LR group. Furthermore, aspartate aminotransferase, creatinine, and lactate levels increased significantly in all animals with severe acute pancreatitis, but the increasing tendency was slower in the HTS group. Nevertheless, the histopathologic analysis revealed similar injuries of the kidney, intestine, pancreas, and lung between the HTS and LR groups. Conclusions Early administration of HTS generally improves hemodynamics and peripheral oxygenation. Despite these normalized parameters, organ damage could not be diminished to a significant degree during observation.

Response to Letter to the Editor: Intra-abdominal Pressure and Abdominal Perfusion Pressure Early in Severe Acute Pancreatitis Miss the Forest for the Trees

To the Editor: Thanks to Dr. Mirandas recent letter and thoughtful comments regarding our article. We really appreciate and agree with his suggestion that the cutoff level of intra-abdominal pressure (IAP, 15 mmHg for the maximal value and 12 mmHg for the mean value) demonstrated from the ROC curves 1 should be cautiously used; however, there are several important issues that need to be clarified. We agree with Dr. Mirandas statement that pancreatic infection could not be adequately detected 72 h after admission. In fact, secondary pancreatic infections we mentioned in this study were mostly diagnosed 2 weeks after the onset of severe acute pancreatitis (SAP), which is in accordance with previous studies and the natural course of SAP. 2 Moreover, we have stated our standards for the diagnosis of pancreatic infection in the Methods section, which is “positive findings in bacterial culture of abdominal fluid and temperature increased consistently.” The samples were obtained through imaging-guided aspiration or drainage, and/or imaging-guided fine needle aspiration, and/or surgical drainage. Consistently increased temperature was confirmed in patients whose body temperatures were greater than 38°C for three consecutive days. In the article, we did not describe the criteria in detail for concision. It is really true that a prospective controlled trial with a large sample size will make great sense. Actually, there were several studies regarding the different outcomes between SAP patients with or without raised IAP like what Dr. Miranda suggested in the letter had been published, some of which used the reference level (15 mmHg) we demonstrated in our article. 3,4 However, these studies including ours were all single-center ones with limited sample size. We do agree that causality between increased IAP and the onset of infection or other important complications need to be further confirmed by a large, multi-center, prospective study.